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    16

    Uploaded by

    Carlos Hernández
    w

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    © All Rights Reserved
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    of 214

    var title_f0_16_256="Communicating hydrocele";

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    " </div>",
    " <div class=\"lgnd\">",
    " A narrowly patent processus vaginalis that only permits passage of peritoneal
    fluid results in a communicating hydrocele.",
    " <div class=\"footnotes\">",
    " </div>",
    " <div class=\"reference\">",
    " Adapted from Paidas, C. Inguinal hernia. In: Oski's Pediatrics. Principles
    and Practice, 3rd ed, McMillan, JA, DeAngelis, CD, Feigin, RD, et al (Eds),
    Lippincott Williams &amp;Wilkins, Philadelphia 1999. p.1640.",
    " </div>",
    " </div>",
    " </div>",
    " </div>",
    "</div>"].join("\n");
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    var outline_f0_16_256=null;
    var title_f0_16_257="Abd and inguinal intertrigo";
    var content_f0_16_257=[" <div id=\"graphicsToolbar\">",
    " <div id=\"graphicsCopy\">",
    " &copy;2013 UpToDate",
    " <sup>",
    " &reg;",
    " </sup>",
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    " <a class=\"etacLink\" href=\"#\">",
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    " </div>",
    " </div>",
    " <div class=\"graphic\">",
    " <div class=\"figure\" style=\"width: 473px\">",
    " <div class=\"ttl\">",
    " Intertrigo",
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    " </div>",
    " <div class=\"lgnd\">",
    " Severe intertrigo of the abdominal and inguinal folds in an elderly patient.",
    " <div class=\"footnotes\">",
    " </div>",
    " <div class=\"reference\">",
    " Courtsey of Eva Rawlings Parker, MD.",
    " </div>",
    " </div>",
    " </div>",
    " </div>",
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    var outline_f0_16_257=null;
    var title_f0_16_258="Fasciolopsiasis adult worm";
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    " &copy;2013 UpToDate",
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    " &reg;",
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    " </a>",
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    " <div class=\"graphic\">",
    " <div class=\"figure\" style=\"width: 604px\">",
    " <div class=\"ttl\">",
    " Fasciolopsiasis adult worm",
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    ooxnHFFFFAH//2Q==);\">",
    " </div>",
    " <div class=\"lgnd\">",
    " (A, B) Adult fluke of",
    " <em>",
    " F. buski",
    " </em>",
    " .",
    " <div class=\"footnotes\">",
    " </div>",
    " <div class=\"reference\">",
    " Reproduced from: Centers for Disease Control and Prevention. Parasites and
    Health: Fasciolopsiasis. Available at:",
    " <a href=\"file://dpd.cdc.gov/dpdx/html/Fasciolopsiasis.htm\"
    target=\"_blank\">",
    " file://dpd.cdc.gov/dpdx/html/Fasciolopsiasis.htm",
    " </a>",
    " .",
    " </div>",
    " </div>",
    " </div>",
    " </div>",
    "</div>"].join("\n");
    var script_f0_16_258=[""].join("\n");
    var outline_f0_16_258=null;
    var title_f0_16_259="Eosinophilic fasciitis biopsy 2";
    var content_f0_16_259=[" <div id=\"graphicsToolbar\">",
    " <div id=\"graphicsCopy\">",
    " &copy;2013 UpToDate",
    " <sup>",
    " &reg;",
    " </sup>",
    " </div>",
    " <div id=\"graphicsLinks\">",
    " <a href=\"?imageKey=RHEUM
    %2F76113&amp;source=image_view&amp;view=print&amp;elapsedTimeMs=1\" onclick=\"\">",
    " <img alt=\"Print this page\" src=\"./../images/icn_print.myextg\"
    title=\"Print this page\"/>",
    " </a>",
    " <a class=\"icontxt textLink\" href=\"?imageKey=RHEUM
    %2F76113&amp;source=image_view&amp;view=print&amp;elapsedTimeMs=1\" onclick=\"\"
    title=\"Print this page\">",
    " Print",
    " </a>",
    " <a class=\"etacLink\" href=\"#\">",
    " <img alt=\"Email graphic(s)\" src=\"./../images/icn_email.myextg\"
    title=\"Email graphic(s)\"/>",
    " </a>",
    " <a class=\"icontxt textLink etacLink\" href=\"#\" title=\"Email graphic(s)\">",
    " Email",
    " </a>",
    " </div>",
    " </div>",
    " <div class=\"graphic\">",
    " <div class=\"figure\" style=\"width: 470px\">",
    " <div class=\"ttl\">",
    " Eosinophilic fasciitis",
    " </div>",
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    " </div>",
    " <div class=\"lgnd\">",
    " This high power view of a hematoxylin and eosin stained skin biopsy from a
    patient with eosinophilic fasciitis shows marked accumulation of eosinophils in
    close proximity to collagen bundles in the fascia.",
    " <div class=\"footnotes\">",
    " </div>",
    " <div class=\"reference\">",
    " Courtesy of John Varga, MD.",
    " </div>",
    " </div>",
    " </div>",
    " </div>",
    "</div>"].join("\n");
    var script_f0_16_259=[""].join("\n");
    var outline_f0_16_259=null;
    var title_f0_16_260="Folic acid, cyanocobalamin, and pyridoxine: Patient drug
    information";
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    " <div id=\"topicContent\">",
    " <div id=\"disclaimer\">",
    " The content on the UpToDate website is not intended nor recommended as a
    substitute",
    "for medical advice, diagnosis, or treatment. Always seek the advice of your own
    physician or",
    "other qualified health care professional regarding any medical questions or
    conditions. The",
    "use of this website is governed by the",
    " <a href=\"/home/terms-use\" target=\"_blank\">",
    " UpToDate Terms of Use",
    " </a>",
    " &copy;2013 UpToDate, Inc.",
    " </div>",
    " <div id=\"drugTitle\">",
    " Folic acid, cyanocobalamin, and pyridoxine: Patient drug information",
    " </div>",
    " <div id=\"lexiTitleImg\">",
    " <img height=\"17\" src=\"./../images/lexiComp/Lexicomp_2012_71x17.myextg\"
    width=\"71\"/>",
    " </div>",
    " <div class=\"clear\">",
    " </div>",
    " <div id=\"drugCopy\">",
    " Copyright 1978-2013 Lexicomp, Inc. All rights reserved.",
    " </div>",
    " <div id=\"topicText\">",
    " <p>",
    " (For additional information",
    " <a class=\"drug drug_general\" href=\"UTD.htm?31/41/32403?source=see_link\">",
    " see \"Folic acid, cyanocobalamin, and pyridoxine: Drug information\"",
    " </a>",
    " )",
    " </p>",
    " <div class=\"list ubnlist drugH1Div drugBrandNames\" id=\"F173848\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Brand Names: U.S.",
    " </span>",
    " <ul>",
    " <li>",
    " FaBB;",
    " </li>",
    " <li>",
    " Folastin;",
    " </li>",
    " <li>",
    " Folbee&reg;;",
    " </li>",
    " <li>",
    " Folbic&trade;;",
    " </li>",
    " <li>",
    " Folcaps&trade;;",
    " </li>",
    " <li>",
    " Folgard RX&reg;;",
    " </li>",
    " <li>",
    " Folgard&reg; [OTC] [DSC];",
    " </li>",
    " <li>",
    " Folplex 2.2;",
    " </li>",
    " <li>",
    " Foltabs&trade; 800 [OTC];",
    " </li>",
    " <li>",
    " Foltx&reg; [DSC];",
    " </li>",
    " <li>",
    " Homocysteine Guard [OTC];",
    " </li>",
    " <li>",
    " Lev-Tov [OTC];",
    " </li>",
    " <li>",
    " Tri-B&reg; [OTC];",
    " </li>",
    " <li>",
    " Tricardio B;",
    " </li>",
    " <li>",
    " Virt-Vite Forte;",
    " </li>",
    " <li>",
    " Vita-Respa&reg;",
    " </li>",
    " </ul>",
    " </div>",
    " <div class=\"ord-stmt war-os drugH1Div\" id=\"F10019390\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Warning",
    " </span>",
    " <ul class=\"statements\" style=\"list-style-type:none;\">",
    " <li class=\"statement\">",
    " <span class=\"attributes\" style=\"display:none;\">",
    " <span class=\"entity\">",
    " &bull;",
    " </span>",
    " <span class=\"link\">",
    " urn:lims:b498:s2700602",
    " </span>",
    " </span>",
    " <span class=\"content\">",
    " Sometimes drugs are not safe when you take them with certain other drugs.
    Taking them together can cause bad side effects. This is one of those drugs. Be
    sure to talk to your doctor about all the drugs you take.",
    " </span>",
    " </li>",
    " </ul>",
    " </div>",
    " <div class=\"ord-stmt yya-os drugH1Div\" id=\"F10019392\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " What is this drug used for?",
    " </span>",
    " <ul class=\"statements\" style=\"list-style-type:none;\">",
    " <li class=\"statement\">",
    " <span class=\"attributes\" style=\"display:none;\">",
    " <span class=\"entity\">",
    " &bull;",
    " </span>",
    " <span class=\"link\">",
    " urn:lims:b498:s2691572",
    " </span>",
    " </span>",
    " <span class=\"content\">",
    " It is used to help growth and good health.",
    " </span>",
    " </li>",
    " </ul>",
    " </div>",
    " <div class=\"ord-stmt coi-os drugH1Div\" id=\"F10019391\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " What do I need to tell my doctor before I take this drug?",
    " </span>",
    " <ul class=\"statements\" style=\"list-style-type:none;\">",
    " <li class=\"statement\">",
    " <span class=\"attributes\" style=\"display:none;\">",
    " <span class=\"entity\">",
    " &bull;",
    " </span>",
    " <span class=\"link\">",
    " urn:lims:b498:s2702157",
    " </span>",
    " </span>",
    " <span class=\"content\">",
    " If you have an allergy to folic acid, cyanocobalamin, pyridoxine, or any
    other part of this drug.",
    " </span>",
    " </li>",
    " <li class=\"statement\">",
    " <span class=\"attributes\" style=\"display:none;\">",
    " <span class=\"entity\">",
    " &bull;",
    " </span>",
    " <span class=\"link\">",
    " urn:lims:b498:s2705171",
    " </span>",
    " </span>",
    " <span class=\"content\">",
    " If you are allergic to any drugs, foods, or other substances. Tell your
    doctor about the allergy and what signs you had, like rash; hives; itching;
    shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or
    any other signs.",
    " </span>",
    " </li>",
    " </ul>",
    " </div>",
    " <div class=\"ord-stmt yye-os drugH1Div\" id=\"F10019396\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " What are some things I need to know or do while I take this drug?",
    " </span>",
    " <ul class=\"statements\" style=\"list-style-type:none;\">",
    " <li class=\"statement\">",
    " <span class=\"attributes\" style=\"display:none;\">",
    " <span class=\"entity\">",
    " &bull;",
    " </span>",
    " <span class=\"link\">",
    " urn:lims:b498:s2699677",
    " </span>",
    " </span>",
    " <span class=\"content\">",
    " Keep a list of all your drugs (prescription, natural products, vitamins,
    OTC) with you. Give this list to your doctor.",
    " </span>",
    " </li>",
    " <li class=\"statement\">",
    " <span class=\"attributes\" style=\"display:none;\">",
    " <span class=\"entity\">",
    " &bull;",
    " </span>",
    " <span class=\"link\">",
    " urn:lims:b498:s2696717",
    " </span>",
    " </span>",
    " <span class=\"content\">",
    " Check all drugs you are taking with your doctor. This drug may not mix well
    with some other drugs.",
    " </span>",
    " </li>",
    " <li class=\"statement\">",
    " <span class=\"attributes\" style=\"display:none;\">",
    " <span class=\"entity\">",
    " &bull;",
    " </span>",
    " <span class=\"link\">",
    " urn:lims:b498:s2697641",
    " </span>",
    " </span>",
    " <span class=\"content\">",
    " Tell your doctor if you are pregnant or plan on getting pregnant. You will
    need to talk about the benefits and risks of using this drug while you are
    pregnant.",
    " </span>",
    " </li>",
    " <li class=\"statement\">",
    " <span class=\"attributes\" style=\"display:none;\">",
    " <span class=\"entity\">",
    " &bull;",
    " </span>",
    " <span class=\"link\">",
    " urn:lims:b498:s2697636",
    " </span>",
    " </span>",
    " <span class=\"content\">",
    " Tell your doctor if you are breast-feeding. You will need to talk about any
    risks to your baby.",
    " </span>",
    " </li>",
    " </ul>",
    " </div>",
    " <div class=\"ord-stmt yyf-os drugH1Div\" id=\"F10019397\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " What are some side effects of this drug?",
    " </span>",
    " <ul class=\"statements\" style=\"list-style-type:none;\">",
    " <li class=\"statement\">",
    " <span class=\"attributes\" style=\"display:none;\">",
    " <span class=\"entity\">",
    " &bull;",
    " </span>",
    " <span class=\"link\">",
    " urn:lims:b498:s2698272",
    " </span>",
    " </span>",
    " <span class=\"content\">",
    " Upset stomach or throwing up. Many small meals, good mouth care, sucking
    hard, sugar-free candy, or chewing sugar-free gum may help.",
    " </span>",
    " </li>",
    " <li class=\"statement\">",
    " <span class=\"attributes\" style=\"display:none;\">",
    " <span class=\"entity\">",
    " &bull;",
    " </span>",
    " <span class=\"link\">",
    " urn:lims:b498:s2697998",
    " </span>",
    " </span>",
    " <span class=\"content\">",
    " Loose stools (diarrhea).",
    " </span>",
    " </li>",
    " </ul>",
    " </div>",
    " <div class=\"ord-stmt yyh-os drugH1Div\" id=\"F10019399\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " What are some side effects that I need to call my doctor about right away?",
    " </span>",
    " <ul class=\"statements\" style=\"list-style-type:none;\">",
    " <li class=\"statement\">",
    " <span class=\"attributes\" style=\"display:none;\">",
    " <span class=\"entity\">",
    " &bull;",
    " </span>",
    " <span class=\"link\">",
    " urn:lims:b498:s2698721",
    " </span>",
    " </span>",
    " <span class=\"content\">",
    " If you think there has been an overdose, call 1-800-222-1222 (the American
    Association of Poison Control Centers), your local poison control center
    (file://www.aapcc.org), or emergency room (ER) right away.",
    " </span>",
    " </li>",
    " <li class=\"statement\">",
    " <span class=\"attributes\" style=\"display:none;\">",
    " <span class=\"entity\">",
    " &bull;",
    " </span>",
    " <span class=\"link\">",
    " urn:lims:b498:s2699066",
    " </span>",
    " </span>",
    " <span class=\"content\">",
    " Signs of an allergic reaction, like rash; hives; itching; red, swollen,
    blistered, or peeling skin with or without fever; wheezing; tightness in the chest
    or throat; trouble breathing or talking; unusual hoarseness; or swelling of the
    mouth, face, lips, tongue, or throat.",
    " </span>",
    " </li>",
    " <li class=\"statement\">",
    " <span class=\"attributes\" style=\"display:none;\">",
    " <span class=\"entity\">",
    " &bull;",
    " </span>",
    " <span class=\"link\">",
    " urn:lims:b498:s2699042",
    " </span>",
    " </span>",
    " <span class=\"content\">",
    " Very upset stomach or throwing up.",
    " </span>",
    " </li>",
    " <li class=\"statement\">",
    " <span class=\"attributes\" style=\"display:none;\">",
    " <span class=\"entity\">",
    " &bull;",
    " </span>",
    " <span class=\"link\">",
    " urn:lims:b498:s2699019",
    " </span>",
    " </span>",
    " <span class=\"content\">",
    " Very loose stools (diarrhea).",
    " </span>",
    " </li>",
    " <li class=\"statement\">",
    " <span class=\"attributes\" style=\"display:none;\">",
    " <span class=\"entity\">",
    " &bull;",
    " </span>",
    " <span class=\"link\">",
    " urn:lims:b498:s2698603",
    " </span>",
    " </span>",
    " <span class=\"content\">",
    " Any rash.",
    " </span>",
    " </li>",
    " <li class=\"statement\">",
    " <span class=\"attributes\" style=\"display:none;\">",
    " <span class=\"entity\">",
    " &bull;",
    " </span>",
    " <span class=\"link\">",
    " urn:lims:b498:s2698977",
    " </span>",
    " </span>",
    " <span class=\"content\">",
    " Side effect or health problem is not better or you are feeling worse.",
    " </span>",
    " </li>",
    " </ul>",
    " </div>",
    " <div class=\"ord-stmt yyc-os drugH1Div\" id=\"F10019394\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " How is this drug best taken?",
    " </span>",
    " <ul class=\"statements\" style=\"list-style-type:none;\">",
    " <li class=\"statement\">",
    " <span class=\"attributes\" style=\"display:none;\">",
    " <span class=\"entity\">",
    " &bull;",
    " </span>",
    " <span class=\"link\">",
    " urn:lims:b498:s2696130",
    " </span>",
    " </span>",
    " <span class=\"content\">",
    " To gain the most benefit, do not miss doses.",
    " </span>",
    " </li>",
    " <li class=\"statement\">",
    " <span class=\"attributes\" style=\"display:none;\">",
    " <span class=\"entity\">",
    " &bull;",
    " </span>",
    " <span class=\"link\">",
    " urn:lims:b498:s2695914",
    " </span>",
    " </span>",
    " <span class=\"content\">",
    " Take with or without food. Take with food if it causes an upset stomach.",
    " </span>",
    " </li>",
    " </ul>",
    " </div>",
    " <div class=\"ord-stmt yyd-os drugH1Div\" id=\"F10019395\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " What do I do if I miss a dose?",
    " </span>",
    " <ul class=\"statements\" style=\"list-style-type:none;\">",
    " <li class=\"statement\">",
    " <span class=\"attributes\" style=\"display:none;\">",
    " <span class=\"entity\">",
    " &bull;",
    " </span>",
    " <span class=\"link\">",
    " urn:lims:b498:s2696563",
    " </span>",
    " </span>",
    " <span class=\"content\">",
    " Take a missed dose as soon as you think about it.",
    " </span>",
    " </li>",
    " <li class=\"statement\">",
    " <span class=\"attributes\" style=\"display:none;\">",
    " <span class=\"entity\">",
    " &bull;",
    " </span>",
    " <span class=\"link\">",
    " urn:lims:b498:s2696496",
    " </span>",
    " </span>",
    " <span class=\"content\">",
    " If it is close to the time for your next dose, skip the missed dose and go
    back to your normal time.",
    " </span>",
    " </li>",
    " <li class=\"statement\">",
    " <span class=\"attributes\" style=\"display:none;\">",
    " <span class=\"entity\">",
    " &bull;",
    " </span>",
    " <span class=\"link\">",
    " urn:lims:b498:s2696475",
    " </span>",
    " </span>",
    " <span class=\"content\">",
    " Do not take 2 doses at the same time or extra doses.",
    " </span>",
    " </li>",
    " </ul>",
    " </div>",
    " <div class=\"ord-stmt yyi-os drugH1Div\" id=\"F10019400\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " How do I store and/or throw out this drug?",
    " </span>",
    " <ul class=\"statements\" style=\"list-style-type:none;\">",
    " <li class=\"statement\">",
    " <span class=\"attributes\" style=\"display:none;\">",
    " <span class=\"entity\">",
    " &bull;",
    " </span>",
    " <span class=\"link\">",
    " urn:lims:b498:s2699336",
    " </span>",
    " </span>",
    " <span class=\"content\">",
    " Store at room temperature.",
    " </span>",
    " </li>",
    " <li class=\"statement\">",
    " <span class=\"attributes\" style=\"display:none;\">",
    " <span class=\"entity\">",
    " &bull;",
    " </span>",
    " <span class=\"link\">",
    " urn:lims:b498:s2699264",
    " </span>",
    " </span>",
    " <span class=\"content\">",
    " Protect from light.",
    " </span>",
    " </li>",
    " <li class=\"statement\">",
    " <span class=\"attributes\" style=\"display:none;\">",
    " <span class=\"entity\">",
    " &bull;",
    " </span>",
    " <span class=\"link\">",
    " urn:lims:b498:s2699266",
    " </span>",
    " </span>",
    " <span class=\"content\">",
    " Store in a dry place. Do not store in a bathroom.",
    " </span>",
    " </li>",
    " </ul>",
    " </div>",
    " <div class=\"ord-stmt yyj-os drugH1Div\" id=\"F10019401\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " General drug facts",
    " </span>",
    " <ul class=\"statements\" style=\"list-style-type:none;\">",
    " <li class=\"statement\">",
    " <span class=\"attributes\" style=\"display:none;\">",
    " <span class=\"entity\">",
    " &bull;",
    " </span>",
    " <span class=\"link\">",
    " urn:lims:b259:s2699675",
    " </span>",
    " </span>",
    " <span class=\"content\">",
    " If your symptoms or health problems do not get better or if they become
    worse, call your doctor.",
    " </span>",
    " </li>",
    " <li class=\"statement\">",
    " <span class=\"attributes\" style=\"display:none;\">",
    " <span class=\"entity\">",
    " &bull;",
    " </span>",
    " <span class=\"link\">",
    " urn:lims:b259:s2699673",
    " </span>",
    " </span>",
    " <span class=\"content\">",
    " Do not share your drugs with others and do not take anyone else's drugs.",
    " </span>",
    " </li>",
    " <li class=\"statement\">",
    " <span class=\"attributes\" style=\"display:none;\">",
    " <span class=\"entity\">",
    " &bull;",
    " </span>",
    " <span class=\"link\">",
    " urn:lims:b259:s2699678",
    " </span>",
    " </span>",
    " <span class=\"content\">",
    " Keep all drugs out of the reach of children and pets.",
    " </span>",
    " </li>",
    " <li class=\"statement\">",
    " <span class=\"attributes\" style=\"display:none;\">",
    " <span class=\"entity\">",
    " &bull;",
    " </span>",
    " <span class=\"link\">",
    " urn:lims:b259:s2699709",
    " </span>",
    " </span>",
    " <span class=\"content\">",
    " If you have any questions about this drug, please talk with your doctor,
    pharmacist, or other health care provider.",
    " </span>",
    " </li>",
    " <li class=\"statement\">",
    " <span class=\"attributes\" style=\"display:none;\">",
    " <span class=\"entity\">",
    " &bull;",
    " </span>",
    " <span class=\"link\">",
    " urn:lims:b259:s3302581",
    " </span>",
    " </span>",
    " <span class=\"content\">",
    " In Canada, take any unused drugs to the pharmacy. Also, visit
    file://www.hc-sc.gc.ca/hl-vs/iyh-vsv/med/disposal-defaire-eng.php#th to learn about
    the right way to get rid of unused drugs.",
    " </span>",
    " </li>",
    " <li class=\"statement\">",
    " <span class=\"attributes\" style=\"display:none;\">",
    " <span class=\"entity\">",
    " &bull;",
    " </span>",
    " <span class=\"link\">",
    " urn:lims:b259:s2699677",
    " </span>",
    " </span>",
    " <span class=\"content\">",
    " Keep a list of all your drugs (prescription, natural products, vitamins,
    OTC) with you. Give this list to your doctor.",
    " </span>",
    " </li>",
    " <li class=\"statement\">",
    " <span class=\"attributes\" style=\"display:none;\">",
    " <span class=\"entity\">",
    " &bull;",
    " </span>",
    " <span class=\"link\">",
    " urn:lims:b259:s2699671",
    " </span>",
    " </span>",
    " <span class=\"content\">",
    " These are not all of the side effects that may occur. If you have questions
    about side effects, call your doctor. Call your doctor for medical advice about
    side effects.",
    " </span>",
    " </li>",
    " <li class=\"statement\">",
    " <span class=\"attributes\" style=\"display:none;\">",
    " <span class=\"entity\">",
    " &bull;",
    " </span>",
    " <span class=\"link\">",
    " urn:lims:b259:s2699683",
    " </span>",
    " </span>",
    " <span class=\"content\">",
    " Talk with the doctor before starting any new drug, including prescription
    or OTC, natural products, or vitamins.",
    " </span>",
    " </li>",
    " </ul>",
    " </div>",
    " </div>",
    " <div id=\"topicAgreement\">",
    " Use of UpToDate is subject to the",
    " <a class=\"licenseLink\" href=\"./license\" id=\"sla_in_page\"
    target=\"_blank\">",
    " Subscription and License Agreement",
    " </a>",
    " .",
    " </div>",
    " <div id=\"topicVersionRevision\">",
    " Topic 11020 Version 39.0",
    " </div>",
    " </div>",
    " <div id=\"footer\">",
    " <div id=\"supportFooter\">",
    " <span class=\"sfInfo\">",
    " &copy; 2013 UpToDate, Inc. All rights reserved.",
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    " |",
    " </span>",
    " <a class=\"licenseLink\" href=\"./license\" id=\"sla_footer\">",
    " Subscription and License Agreement",
    " </a>",
    " <span class=\"sfInfo\">",
    " <span class=\"pipeSpace\">",
    " |",
    " </span>",
    " Release: 21.6- C21.56",
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    " <br/>",
    " <span class=\"sfInfo\">",
    " Licensed to:",
    " <span class=\"emphasis\">",
    " AsanBook Dig. Med. Lib.",
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    " |",
    " </span>",
    " Support Tag: [1104-61.234.146.186-C5FDE4D645-S244013.14]",
    " <br/>",
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    " </div>",
    " </div>",
    "</div>"].join("\n");
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    var outline_f0_16_260=[" <div id=\"toggleOutline\">",
    " <a href=\"#\" title=\"Collapse Topic Outline\">",
    " <img alt=\"\" src=\"./../images/orange_arrow_left.myextg\"/>",
    " </a>",
    " </div>",
    " <div id=\"innerOutline\">",
    " <h1>",
    " TOPIC OUTLINE",
    " </h1>",
    " <div id=\"outline\">",
    " <ul>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F173848\">",
    " Brand Names: U.S.",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F10019390\">",
    " Warning",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F10019392\">",
    " What is this drug used for?",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F10019391\">",
    " What do I need to tell my doctor before I take this drug?",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F10019396\">",
    " What are some things I need to know or do while I take this drug?",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F10019397\">",
    " What are some side effects of this drug?",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F10019399\">",
    " What are some side effects that I need to call my doctor about right away?",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F10019394\">",
    " How is this drug best taken?",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F10019395\">",
    " What do I do if I miss a dose?",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F10019400\">",
    " How do I store and/or throw out this drug?",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F10019401\">",
    " General drug facts",
    " </a>",
    " </li>",
    " </ul>",
    " </div>",
    " <h1>",
    " RELATED TOPICS",
    " </h1>",
    " <div id=\"relatedTopics\">",
    " <ul>",
    " <li class=\"plainItem\">",
    " <a class=\"drug drug_general\" href=\"UTD.htm?31/41/32403?
    source=related_link\">",
    " Folic acid, cyanocobalamin, and pyridoxine: Drug information",
    " </a>",
    " </li>",
    " </ul>",
    " </div>",
    " </div>"].join("\n");
    var title_f0_16_261="Atrial fibrillation";
    var content_f0_16_261=[" <h1 id=\"patTopicTitle\">",
    " Patient information: Atrial fibrillation (Beyond the Basics)",
    " </h1>",
    " <div id=\"patTopicContributors\">",
    " <div class=\"rcTop\">",
    " <div>",
    " </div>",
    " </div>",
    " <div class=\"rcContent\">",
    " <table>",
    " <tr>",
    " <td>",
    " <a class=\"contributor contributor_credentials patTopicContributorsType\"
    href=\"UTD.htm?0/16/261/contributors\">",
    " Author",
    " </a>",
    " <a class=\"contributor contributor_credentials\" href=\"UTD.htm?
    0/16/261/contributors\" id=\"au4322\">",
    " Leonard I Ganz, MD, FHRS, FACC",
    " </a>",
    " </td>",
    " <td>",
    " <a class=\"contributor contributor_credentials patTopicContributorsType\"
    href=\"UTD.htm?0/16/261/contributors\">",
    " Section Editor",
    " </a>",
    " <a class=\"contributor contributor_credentials\" href=\"UTD.htm?
    0/16/261/contributors\" id=\"se6340\">",
    " Bradley P Knight, MD, FACC",
    " </a>",
    " </td>",
    " <td>",
    " <a class=\"contributor contributor_credentials patTopicContributorsType\"
    href=\"UTD.htm?0/16/261/contributors\">",
    " Deputy Editor",
    " </a>",
    " <a class=\"contributor contributor_credentials\" href=\"UTD.htm?
    0/16/261/contributors\" id=\"de1101\">",
    " Gordon M Saperia, MD, FACC",
    " </a>",
    " </td>",
    " </tr>",
    " </table>",
    " </div>",
    " <div class=\"rcBottom\">",
    " <div>",
    " </div>",
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    " <div id=\"topicText\">",
    " <p class=\"headingAnchor\" id=\"H1\">",
    " <span class=\"h1\">",
    " ATRIAL FIBRILLATION OVERVIEW",
    " </span>",
    " </p>",
    " <p>",
    " Atrial fibrillation (also called AF or a-fib) is an abnormal rhythm of the
    heart. It is relatively common, affecting 2.3 million adults in the United States.
    Most people who develop atrial fibrillation are over 65 years of age. Atrial
    fibrillation is more frequent in men than women, and in whites than blacks.",
    " </p>",
    " <p>",
    " There are two forms of this abnormal heart rhythm:",
    " </p>",
    " <p>",
    " <ul class=\"bullet-block\">",
    " <li>",
    " Intermittent (paroxysmal) atrial fibrillation, which is characterized by
    episodes that occur with varying frequency and last for a variable period of time
    before spontaneously stopping.",
    " </li>",
    " <li>",
    " Chronic or persistent atrial fibrillation, which is sustained and does not
    usually stop spontaneously.",
    " </li>",
    " </ul>",
    " </p>",
    " <p>",
    " The purpose of this review is to describe the symptoms of atrial
    fibrillation, its risks, and to review current treatments.",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H2\">",
    " <span class=\"h1\">",
    " WHAT IS ATRIAL FIBRILLATION?",
    " </span>",
    " </p>",
    " <p>",
    " In atrial fibrillation, part of the heart (the upper chambers, or atria) does
    not work correctly because of abnormal electrical activity. This means that blood
    is not forcefully moved out of these chambers. The blood that remains in the atria
    becomes \"sluggish\" or static, which allows blood clots to form (see",
    " <a class=\"local\" href=\"#H5\">",
    " 'Risk of stroke'",
    " </a>",
    " below). Atrial fibrillation can be intermittent and stop on its own
    (paroxysmal), continue for several days and require treatment (persistent), or be
    present all the time (permanent).",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H3\">",
    " <span class=\"h1\">",
    " ATRIAL FIBRILLATION CAUSES",
    " </span>",
    " </p>",
    " <p>",
    " Atrial fibrillation increases in frequency with aging and typically occurs in
    people who have underlying heart disease. Almost any heart disease can increase the
    risk of this abnormal rhythm, but the most common causes are:",
    " </p>",
    " <p>",
    " <ul class=\"bullet-block\">",
    " <li>",
    " Hypertensive heart disease due to chronic high blood pressure.",
    " </li>",
    " <li>",
    " A heart attack (myocardial infarction, or MI)",
    " </li>",
    " <li>",
    " Heart failure",
    " </li>",
    " <li>",
    " Heart valve disease, such as mitral regurgitation or mitral stenosis.
    (See",
    " <a class=\"medical medical_patient\" href=\"UTD.htm?26/59/27575?
    source=see_link\">",
    " \"Patient information: Mitral regurgitation (Beyond the Basics)\"",
    " </a>",
    " .)",
    " </li>",
    " <li>",
    " After heart surgery and, less often, after other types of surgery",
    " </li>",
    " </ul>",
    " </p>",
    " <p>",
    " Atrial fibrillation can also be seen with other medical problems. These
    include:",
    " </p>",
    " <p>",
    " <ul class=\"bullet-block\">",
    " <li>",
    " Alcohol and binge drinking &mdash; Binge drinkers can develop atrial
    fibrillation that is usually transient. This often occurs over weekends or holidays
    when alcohol intake is excessive. It is called \"holiday heart syndrome.\"",
    " </li>",
    " <li>",
    " Hyperthyroidism &mdash; Atrial fibrillation occurs in about 13 percent of
    all people with an overactive thyroid gland (called hyperthyroidism). It has been
    estimated that hyperthyroidism accounts for 5 percent of cases of atrial
    fibrillation. Thus, blood testing for this disorder is recommended in anyone with
    AF since hyperthyroidism is treatable. (See",
    " <a class=\"medical medical_patient\" href=\"UTD.htm?3/6/3172?
    source=see_link\">",
    " \"Patient information: Hyperthyroidism (overactive thyroid) (Beyond the
    Basics)\"",
    " </a>",
    " .)",
    " </li>",
    " <li>",
    " Medications &mdash; Drugs that stimulate the heart can contribute to the
    development of atrial fibrillation. These include theophylline (used in the
    treatment of asthma or chronic lung disease) and caffeine.",
    " </li>",
    " <li>",
    " Sleep apnea &mdash; Atrial fibrillation can be caused by sleep apnea, a
    condition where patients stop breathing for prolonged periods of time while
    sleeping. Patients with atrial fibrillation who are overweight, or have a history
    of snoring or excessive sleepiness during the daytime, should be evaluated with a
    sleep study. Treatment for sleep apnea can eliminate atrial fibrillation in some
    patients. (See",
    " <a class=\"medical medical_patient\" href=\"UTD.htm?25/25/26003?
    source=see_link\">",
    " \"Patient information: Sleep apnea in adults (Beyond the Basics)\"",
    " </a>",
    " .)",
    " </li>",
    " <li>",
    " A variety of chronic lung diseases, particularly emphysema.",
    " </li>",
    " </ul>",
    " </p>",
    " <p>",
    " Some people with atrial fibrillation have no apparent cause. When this occurs
    in people under age 60 to &nbsp;risk of blood clots is much lower than it is in
    people who are older or who have known causes of atrial fibrillation.",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H4\">",
    " <span class=\"h1\">",
    " ATRIAL FIBRILLATION SYMPTOMS",
    " </span>",
    " </p>",
    " <p>",
    " Some people have no symptoms at all while others have a variety of symptoms.
    Mild symptoms include:",
    " </p>",
    " <p>",
    " <ul class=\"bulletCompact-block\">",
    " <li>",
    " Unpleasant palpitations or irregularity of the heart beat",
    " </li>",
    " <li>",
    " Mild chest discomfort (sensation of tightness) or pain",
    " </li>",
    " <li>",
    " A sense of the heart racing",
    " </li>",
    " <li>",
    " Lightheadedness",
    " </li>",
    " <li>",
    " Mild shortness of breath and fatigue that limit the ability to exercise",
    " </li>",
    " </ul>",
    " </p>",
    " <p>",
    " Some patients report severe symptoms:",
    " </p>",
    " <p>",
    " <ul class=\"bulletCompact-block\">",
    " <li>",
    " Difficulty breathing",
    " </li>",
    " <li>",
    " Shortness of breath with exertion",
    " </li>",
    " <li>",
    " Fainting, or near fainting, due to a reduction in blood flow to the brain",
    " </li>",
    " <li>",
    " Confusion, due to a reduction in blood supply to the brain",
    " </li>",
    " <li>",
    " Chest discomfort",
    " </li>",
    " <li>",
    " Fatigue",
    " </li>",
    " </ul>",
    " </p>",
    " <p>",
    " Chest discomfort generally results from inadequate blood flow to meet the
    needs of the heart (called angina); this can be due to an increase in the heart's
    need for oxygen",
    " <span class=\"nowrap\">",
    " and/or",
    " </span>",
    " a decrease in the heart's supply of blood and oxygen. In some cases, chest
    pain is due to the rapid heart rate itself or perhaps due to stretching of the
    heart's chambers. Chest discomfort can also result from worsening heart failure.",
    " </p>",
    " <p class=\"headingAnchor2\" id=\"H5\">",
    " <span class=\"h2\">",
    " Risk of stroke",
    " </span>",
    " &nbsp;&mdash;&nbsp;A serious complication associated with atrial fibrillation
    is stroke, which can lead to permanent brain damage. A stroke can occur if a blood
    clot forms in the left atrium because of sluggish blood flow and a piece of the
    clot (called an embolus) breaks off. The embolus enters the blood circulation and
    can block a small blood vessel. If this happens in the brain, a stroke can occur.
    The embolus may also travel to the eye, kidneys, spine, or important arteries of
    the arms or legs. When the symptoms of a stroke resolve completely within 24 hours,
    it is called a transient ischemic attack (TIA); many patients refer to this as a
    &ldquo;mini-stroke.&rdquo; (See",
    " <a class=\"medical medical_patient\" href=\"UTD.htm?37/37/38484?
    source=see_link\">",
    " \"Patient information: Stroke symptoms and diagnosis (Beyond the Basics)\"",
    " </a>",
    " .) Like atrial fibrillation, the risk of stroke increases with age. Without
    preventive treatment (eg, blood thinners), stroke occurs in approximately 1.3
    percent of people with AF who are 50 to 59 years each year and increases gradually
    to 5 percent each year for people 80 to 89 years. The other risk factors for stroke
    include diabetes, high blood pressure, congestive heart failure, or prior stroke or
    embolus.",
    " </p>",
    " <p>",
    " Taking a blood thinner lowers the risk of stroke (see",
    " <a class=\"local\" href=\"#H16\">",
    " 'Treatment to prevent blood clots'",
    " </a>",
    " below). Blood thinners used in this setting include warfarin (Coumadin&reg;),
    aspirin, or a new agent called dabigatran (Pradaxa&reg;).",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H6\">",
    " <span class=\"h1\">",
    " ATRIAL FIBRILLATION DIAGNOSIS",
    " </span>",
    " </p>",
    " <p>",
    " Atrial fibrillation is diagnosed with an electrocardiogram (ECG or EKG),
    which records the heart's electrical activity. Other tests, such as an
    echocardiogram (ultrasound), may be performed to look for heart failure or heart
    valve problems. Blood tests may be used to screen for thyroid disorders.
    Occasionally, sleep studies and lung function tests are sometimes used to look for
    sleep apnea or underlying lung disease.",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H7\">",
    " <span class=\"h1\">",
    " ATRIAL FIBRILLATION TREATMENT",
    " </span>",
    " </p>",
    " <p class=\"headingAnchor2\" id=\"H8\">",
    " <span class=\"h2\">",
    " Electrical cardioversion",
    " </span>",
    " &nbsp;&mdash;&nbsp;Electrical cardioversion involves the use of an electrical
    shock from a cardioverter, delivered by paddles placed on the chest, to \"reset\"
    the heart rhythm. Urgent cardioversion is usually performed if AF is interfering
    with heart's ability to supply blood and oxygen to vital organs. (See",
    " <a class=\"medical medical_patient\" href=\"UTD.htm?24/10/24738?
    source=see_link\">",
    " \"Patient information: Cardioversion (Beyond the Basics)\"",
    " </a>",
    " .)",
    " </p>",
    " <p>",
    " Some people with newly diagnosed AF can undergo electrical or medical
    cardioversion (using an antiarrhythmic drug) immediately. However, due to the risk
    of stroke from blood clots lodged in the left atrium, many people are advised to
    delay cardioversion until starting treatment with a blood thinner. This medication,
    (usually warfarin [Coumadin&reg;]) is given for three to four weeks, which allows
    most preexisting blood clots in the left atrium to resolve.",
    " </p>",
    " <p class=\"headingAnchor2\" id=\"H9\">",
    " <span class=\"h3\">",
    " Transesophageal echocardiogram",
    " </span>",
    " &nbsp;&mdash;&nbsp;Use of a procedure called transesophageal echocardiogram
    (TEE) is an alternative to delaying cardioversion while starting a blood thinner.
    The TEE avoids the need for delaying cardioversion until three to four weeks after
    starting warfarin, but it is still important that the blood is thinned at the time
    of the cardioversion. The blood can be thinned with either warfarin, or the blood
    thinner heparin that is administered subcutaneously (under the skin) or
    intravenously (by vein). A TEE uses a small ultrasound device that is swallowed.
    The device allows the physician to see the left atrium and look for evidence of
    blood clots. If there is no evidence of blood clot, cardioversion can be performed
    safely without three to four weeks of warfarin pretreatment. Although there is
    still a risk that cardioversion could result in a stroke even when a clot that is
    not seen on the TEE, the risk is quite small. Following cardioversion, a blood
    thinner must be continued for at least a month, assuming normal rhythm is
    maintained.",
    " </p>",
    " <p class=\"headingAnchor2\" id=\"H10\">",
    " <span class=\"h2\">",
    " Long-term treatment",
    " </span>",
    " &nbsp;&mdash;&nbsp;For people with intermittent or chronic atrial
    fibrillation, there are two long-term treatment options: rhythm control and rate
    control.",
    " </p>",
    " <p class=\"headingAnchor2\" id=\"H11\">",
    " <span class=\"h3\">",
    " Rhythm control",
    " </span>",
    " &nbsp;&mdash;&nbsp;Rhythm control refers to electrical or medical
    cardioversion followed by an antiarrhythmic drug to lower the risk of recurrent AF.
    After successful conversion to normal sinus rhythm, only 20 to 30 percent of people
    are in sinus rhythm after one year. This can be increased to between 40 and 80
    percent by adding an antiarrhythmic drug.",
    " </p>",
    " <p>",
    " The advantages to rhythm control include improved cardiac function and, for
    some people, reduced symptoms. Selected people who maintain a normal rhythm are
    allowed to stop blood thinning medications. However, rhythm control is more likely
    to reduce the frequency of AF than eliminate it entirely. Thus, many people treated
    with antiarrhythmic medications continue some form of blood thinning medications
    indefinitely.",
    " </p>",
    " <p>",
    " The disadvantages of rhythm control are the high rate of recurrent AF and
    side effects associated with antiarrhythmic drugs, including the development of new
    abnormal heart rhythms.",
    " </p>",
    " <p class=\"headingAnchor2\" id=\"H12\">",
    " <span class=\"h3\">",
    " Rate control",
    " </span>",
    " &nbsp;&mdash;&nbsp;People who are treated with rate control continue to have
    AF. However, the person uses a medication (a beta blocker, a calcium channel
    blocker, or digoxin) to slow conduction through the AV node, thereby keeping the
    rate of the lower pumping chambers (ventricles) in the normal range. People who use
    this treatment require treatment with a blood thinner since there is a risk of
    blood clot formation and possible stroke. (See",
    " <a class=\"local\" href=\"#H16\">",
    " 'Treatment to prevent blood clots'",
    " </a>",
    " below.)",
    " </p>",
    " <p>",
    " The major disadvantage of the rate control strategy is sometimes it is
    difficult to adequately control the rate and relieve symptoms.",
    " </p>",
    " <p>",
    " Either a rate control or a rhythm control strategy, along with a treatment to
    prevent blood clots, may be appropriate. You should discuss the risks and benefits
    of each type of treatment with your doctor or nurse.",
    " </p>",
    " <p class=\"headingAnchor2\" id=\"H13\">",
    " <span class=\"h2\">",
    " Nonpharmacologic treatments",
    " </span>",
    " &nbsp;&mdash;&nbsp;There are alternate ways to achieve rhythm or rate
    control, including radiofrequency catheter ablation, use of a pacemaker or
    implantable atrial defibrillator, and several surgical treatments. &nbsp;(See",
    " <a class=\"medical medical_patient\" href=\"UTD.htm?20/16/20741?
    source=see_link\">",
    " \"Patient information: Pacemakers (Beyond the Basics)\"",
    " </a>",
    " and",
    " <a class=\"medical medical_patient\" href=\"UTD.htm?11/20/11589?
    source=see_link\">",
    " \"Patient information: Implantable cardioverter-defibrillators (Beyond the
    Basics)\"",
    " </a>",
    " .)",
    " </p>",
    " <p class=\"headingAnchor2\" id=\"H14\">",
    " <span class=\"h3\">",
    " Radiofrequency ablation",
    " </span>",
    " &nbsp;&mdash;&nbsp;Radiofrequency ablation is a procedure that can sometimes
    cure atrial fibrillation. The technique, however, is still evolving, and there is a
    small but real risk of serious complications, even with an experienced physician.
    (See",
    " <a class=\"medical medical_patient\" href=\"UTD.htm?14/31/14834?
    source=see_link\">",
    " \"Patient information: Radiofrequency catheter ablation for the heart
    (Beyond the Basics)\"",
    " </a>",
    " .)",
    " </p>",
    " <p>",
    " Increasingly, this therapy is being considered an initial option in young
    people who have symptoms of AF who do not wish to take long-term medications. It is
    also being used increasingly in patients who are having recurrent atrial
    fibrillation despite using one or more antiarrhythmic drug. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?39/62/40938?
    source=see_link\">",
    " \"Radiofrequency catheter ablation to prevent recurrent atrial
    fibrillation\"",
    " </a>",
    " .)",
    " </p>",
    " <p class=\"headingAnchor2\" id=\"H15\">",
    " <span class=\"h3\">",
    " Surgical procedures",
    " </span>",
    " &nbsp;&mdash;&nbsp;Surgical procedures, including the complete maze procedure
    and the less invasive alternative surgeries, may be considered in some people with
    AF, especially those who must undergo open-heart surgery for other reasons. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?36/45/37591?
    source=see_link\">",
    " \"Surgical approaches to prevent recurrent atrial fibrillation\"",
    " </a>",
    " .)",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H16\">",
    " <span class=\"h1\">",
    " TREATMENT TO PREVENT BLOOD CLOTS",
    " </span>",
    " </p>",
    " <p>",
    " People with atrial fibrillation have an increased risk of stroke as a result
    of blood clots that can form in the heart. As a result, most people are advised to
    use a treatment to reduce the risk of developing blood clots. The most commonly
    used treatments include anticoagulants (also called blood thinners) or antiplatelet
    drugs (such as aspirin).",
    " </p>",
    " <p class=\"headingAnchor2\" id=\"H17\">",
    " <span class=\"h2\">",
    " Anticoagulant drugs",
    " </span>",
    " &nbsp;&mdash;&nbsp;Taking an anticoagulant (blood thinner) can reduce the
    risk of having a stroke by approximately 50 to 70 percent. (See",
    " <a class=\"medical medical_patient\" href=\"UTD.htm?21/15/21747?
    source=see_link\">",
    " \"Patient information: Warfarin (Coumadin) (Beyond the Basics)\"",
    " </a>",
    " .)",
    " </p>",
    " <p>",
    " Warfarin is an anticoagulant that has been used for many years, but a major
    problem with it is that it increases the risk of bleeding. The most serious type of
    bleeding is bleeding into the brain. However, the benefit of preventing strokes is
    greater than the small risk of bleeding into the brain in most cases. If you take
    warfarin, you will need careful monitoring with periodic blood tests to be sure you
    are taking the right dose of warfarin.",
    " </p>",
    " <p>",
    " Dabigatran, apixaban, and rivaroxaban are newer anticoagulants that work as
    well as warfarin, and are as safe, but don&rsquo;t require periodic blood tests.
    Patients should discuss with their doctors whether one of these newer agents is
    better for them than warfarin. Further information about dabigatran is available at
    the following website:",
    " <a class=\"external\"
    href=\"file://circ.ahajournals.org/content/124/8/e209.full\">",
    " file://circ.ahajournals.org/content/124/8/e209.full",
    " </a>",
    " .",
    " </p>",
    " <p class=\"headingAnchor2\" id=\"H18\">",
    " <span class=\"h2\">",
    " Antiplatelet drugs",
    " </span>",
    " &nbsp;&mdash;&nbsp;Anticoagulants are the most effective treatment for
    preventing blood clots in patients at high-risk of stroke. However, treatment with
    antiplatelet drugs is a reasonable option in certain people. Aspirin is the most
    frequently used of this kind.",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H19\">",
    " <span class=\"h1\">",
    " WHERE TO GET MORE INFORMATION",
    " </span>",
    " </p>",
    " <p>",
    " Your healthcare provider is the best source of information for questions and
    concerns related to your medical problem.",
    " </p>",
    " <p>",
    " This article will be updated as needed on our web site (",
    " <a class=\"external\" href=\"file://www.uptodate.com/patients\">",
    " www.uptodate.com/patients",
    " </a>",
    " ). Related topics for patients, as well as selected articles written for
    healthcare professionals, are also available. Some of the most relevant are listed
    below.",
    " </p>",
    " <p class=\"headingAnchor2\" id=\"H191\">",
    " <span class=\"h2\">",
    " Patient level information",
    " </span>",
    " &nbsp;&mdash;&nbsp;UpToDate offers two types of patient education
    materials.",
    " </p>",
    " <p class=\"headingAnchor2\" id=\"H5394522\">",
    " <span class=\"h3\">",
    " The Basics",
    " </span>",
    " &nbsp;&mdash;&nbsp;The Basics patient education pieces answer the four or
    five key questions a patient might have about a given condition. These articles are
    best for patients who want a general overview and who prefer short, easy-to-read
    materials.",
    " </p>",
    " <p>",
    " <a class=\"medical medical_basics\" href=\"UTD.htm?20/32/20994?
    source=see_link\">",
    " Patient information: Atrial fibrillation (The Basics)",
    " </a>",
    " <br/>",
    " <a class=\"medical medical_basics\" href=\"UTD.htm?37/60/38850?
    source=see_link\">",
    " Patient information: Implantable cardioverter-defibrillators (The Basics)",
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    " Patient information: ECG and stress test (The Basics)",
    " </a>",
    " <br/>",
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    " Patient information: Heart failure and atrial fibrillation (The Basics)",
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    " <br/>",
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    source=see_link\">",
    " Patient information: Tachycardia (The Basics)",
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    source=see_link\">",
    " Patient information: Atrial flutter (The Basics)",
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    " Patient information: Mitral stenosis in adults (The Basics)",
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    " Patient information: Supraventricular tachycardia (SVT) (The Basics)",
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    " <a class=\"medical medical_basics\" href=\"UTD.htm?17/36/17986?
    source=see_link\">",
    " Patient information: Medicines for atrial fibrillation (The Basics)",
    " </a>",
    " </p>",
    " <p class=\"headingAnchor2\" id=\"H5394530\">",
    " <span class=\"h3\">",
    " Beyond the Basics",
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    source=see_link\">",
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    source=see_link\">",
    " Patient information: Implantable cardioverter-defibrillators (Beyond the
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    " </a>",
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    " Patient information: Radiofrequency catheter ablation for the heart (Beyond
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    source=see_link\">",
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    " </a>",
    " <br/>",
    " </p>",
    " <p class=\"headingAnchor2\" id=\"H21\">",
    " <span class=\"h2\">",
    " Professional level information",
    " </span>",
    " &nbsp;&mdash;&nbsp;Professional level articles are designed to keep doctors
    and other health professionals up-to-date on the latest medical findings. These
    articles are thorough, long, and complex, and they contain multiple references to
    the research on which they are based. Professional level articles are best for
    people who are comfortable with a lot of medical terminology and who want to read
    the same materials their doctors are reading.",
    " </p>",
    " <p>",
    " <a class=\"medical medical_review\" href=\"UTD.htm?20/28/20938?
    source=see_link\">",
    " Antiarrhythmic drugs to maintain sinus rhythm in patients with atrial
    fibrillation: Recommendations",
    " </a>",
    " <br/>",
    " <a class=\"medical medical_review\" href=\"UTD.htm?34/27/35257?
    source=see_link\">",
    " Anticoagulation prior to and after restoration of sinus rhythm in atrial
    fibrillation",
    " </a>",
    " <br/>",
    " <a class=\"medical medical_review\" href=\"UTD.htm?41/32/42506?
    source=see_link\">",
    " Antithrombotic therapy to prevent embolization in atrial fibrillation",
    " </a>",
    " <br/>",
    " <a class=\"medical medical_review\" href=\"UTD.htm?23/53/24408?
    source=see_link\">",
    " Control of ventricular rate in atrial fibrillation: Nonpharmacologic
    therapy",
    " </a>",
    " <br/>",
    " <a class=\"medical medical_review\" href=\"UTD.htm?11/50/12074?
    source=see_link\">",
    " Control of ventricular rate in atrial fibrillation: Pharmacologic therapy",
    " </a>",
    " <br/>",
    " <a class=\"medical medical_review\" href=\"UTD.htm?27/54/28522?
    source=see_link\">",
    " Epidemiology of and risk factors for atrial fibrillation",
    " </a>",
    " <br/>",
    " <a class=\"medical medical_review\" href=\"UTD.htm?23/50/24362?
    source=see_link\">",
    " General principles of the implantable cardioverter-defibrillator",
    " </a>",
    " <br/>",
    " <a class=\"medical medical_review\" href=\"UTD.htm?0/22/361?
    source=see_link\">",
    " Overview of atrial fibrillation",
    " </a>",
    " <br/>",
    " <a class=\"medical medical_review\" href=\"UTD.htm?30/41/31384?
    source=see_link\">",
    " Paroxysmal atrial fibrillation",
    " </a>",
    " <br/>",
    " <a class=\"medical medical_review\" href=\"UTD.htm?39/62/40938?
    source=see_link\">",
    " Radiofrequency catheter ablation to prevent recurrent atrial fibrillation",
    " </a>",
    " <br/>",
    " <a class=\"medical medical_review\" href=\"UTD.htm?21/57/22426?
    source=see_link\">",
    " Restoration of sinus rhythm in atrial fibrillation",
    " </a>",
    " <br/>",
    " <a class=\"medical medical_review\" href=\"UTD.htm?5/43/5817?
    source=see_link\">",
    " Rhythm control versus rate control in atrial fibrillation",
    " </a>",
    " <br/>",
    " <a class=\"medical medical_review\" href=\"UTD.htm?2/50/2856?
    source=see_link\">",
    " Role of echocardiography in atrial fibrillation",
    " </a>",
    " <br/>",
    " <a class=\"medical medical_review\" href=\"UTD.htm?36/45/37591?
    source=see_link\">",
    " Surgical approaches to prevent recurrent atrial fibrillation",
    " </a>",
    " <br/>",
    " <br/>",
    " The following organizations also provide reliable health information.",
    " </p>",
    " <p>",
    " <ul class=\"bullet-block\">",
    " <li>",
    " National Library of Medicine",
    " </li>",
    " </ul>",
    " </p>",
    " <p>",
    " &nbsp; &nbsp; &nbsp;(",
    " <a class=\"external\"
    href=\"file://www.nlm.nih.gov/medlineplus/healthtopics.html\">",
    " www.nlm.nih.gov/medlineplus/healthtopics.html",
    " </a>",
    " )",
    " </p>",
    " <p>",
    " <ul class=\"bullet-block\">",
    " <li>",
    " National Heart, Lung, and Blood Institute",
    " </li>",
    " </ul>",
    " </p>",
    " <p>",
    " &nbsp; &nbsp; &nbsp;(",
    " <a class=\"external\" href=\"file://www.nhlbi.nih.gov/\">",
    " www.nhlbi.nih.gov/",
    " </a>",
    " )",
    " </p>",
    " <p>",
    " <ul class=\"bullet-block\">",
    " <li>",
    " American Heart Association",
    " </li>",
    " </ul>",
    " </p>",
    " <p>",
    " &nbsp; &nbsp; &nbsp;(",
    " <a class=\"external\" href=\"file://www.americanheart.org/\">",
    " www.americanheart.org",
    " </a>",
    " )",
    " </p>",
    " <p>",
    " <ul class=\"bullet-block\">",
    " <li>",
    " Harvard Center for Cancer Prevention",
    " </li>",
    " </ul>",
    " </p>",
    " <p>",
    " &nbsp; &nbsp; &nbsp;(",
    " <a class=\"external\" href=\"file://www.yourdiseaserisk.harvard.edu/\">",
    " www.yourdiseaserisk.harvard.edu/",
    " </a>",
    " )",
    " </p>",
    " <p>",
    " &nbsp; &nbsp; &nbsp;Includes a calculator for estimating the risk of stroke",
    " </p>",
    " <p>",
    " <ul class=\"bullet-block\">",
    " <li>",
    " Heart Rhythm Society",
    " </li>",
    " </ul>",
    " </p>",
    " <p>",
    " &nbsp; &nbsp; &nbsp;(",
    " <a class=\"external\" href=\"file://www.hrsonline.org/\">",
    " www.hrsonline.org",
    " </a>",
    " )",
    " </p>",
    " <p>",
    " [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/261/abstract/1-8\">",
    " 1-8",
    " </a>",
    " ]",
    " </p>",
    " </div>",
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    " <ol id=\"reference\">",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/16/261/abstract/1\">",
    " Silverman DI, Manning WJ. Strategies for cardioversion of atrial
    fibrillation--time for a change? N Engl J Med 2001; 344:1468.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/16/261/abstract/2\">",
    " Weigner MJ, Caulfield TA, Danias PG, et al. Risk for clinical
    thromboembolism associated with conversion to sinus rhythm in patients with atrial
    fibrillation lasting less than 48 hours. Ann Intern Med 1997; 126:615.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/16/261/abstract/3\">",
    " Go AS, Hylek EM, Chang Y, et al. Anticoagulation therapy for stroke
    prevention in atrial fibrillation: how well do randomized trials translate into
    clinical practice? JAMA 2003; 290:2685.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/16/261/abstract/4\">",
    " van Walraven C, Hart RG, Singer DE, et al. Oral anticoagulants vs aspirin in
    nonvalvular atrial fibrillation: an individual patient meta-analysis. JAMA 2002;
    288:2441.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/16/261/abstract/5\">",
    " Klein AL, Grimm RA, Murray RD, et al. Use of transesophageal
    echocardiography to guide cardioversion in patients with atrial fibrillation. N
    Engl J Med 2001; 344:1411.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/16/261/abstract/6\">",
    " Wyse DG, Waldo AL, DiMarco JP, et al. A comparison of rate control and
    rhythm control in patients with atrial fibrillation. N Engl J Med 2002; 347:1825.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/16/261/abstract/7\">",
    " Van Gelder IC, Hagens VE, Bosker HA, et al. A comparison of rate control and
    rhythm control in patients with recurrent persistent atrial fibrillation. N Engl J
    Med 2002; 347:1834.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/16/261/abstract/8\">",
    " Snow V, Weiss KB, LeFevre M, et al. Management of newly detected atrial
    fibrillation: a clinical practice guideline from the American Academy of Family
    Physicians and the American College of Physicians. Ann Intern Med 2003; 139:1009.",
    " </a>",
    " </li>",
    " </ol>",
    " </div>",
    " </div>",
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    var outline_f0_16_261=[" <div class=\"patTopicFancyTop\">",
    " <div class=\"rcTop\">",
    " <div>",
    " </div>",
    " </div>",
    " <div class=\"rcContent\">",
    " <p>",
    " Contents of this article",
    " </p>",
    " </div>",
    " </div>",
    " <div class=\"patTopicFancySpacer\">",
    " </div>",
    " <div class=\"patTopicOutline\">",
    " <div class=\"rcbBottom\">",
    " <div class=\"rcbLeft\">",
    " <div class=\"rcbRight\">",
    " <div class=\"rcbBottomLeft\">",
    " <div class=\"rcbBottomRight rcbBottomRightBottomOnly\">",
    " <div id=\"outline\">",
    " <ul>",
    " <li class=\"plainItem\">",
    " <a href=\"#H1\">",
    " ATRIAL FIBRILLATION OVERVIEW",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a href=\"#H2\">",
    " WHAT IS ATRIAL FIBRILLATION?",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a href=\"#H3\">",
    " ATRIAL FIBRILLATION CAUSES",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a href=\"#H4\">",
    " ATRIAL FIBRILLATION SYMPTOMS",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a href=\"#H6\">",
    " ATRIAL FIBRILLATION DIAGNOSIS",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a href=\"#H7\">",
    " ATRIAL FIBRILLATION TREATMENT",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a href=\"#H16\">",
    " TREATMENT TO PREVENT BLOOD CLOTS",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a href=\"#H19\">",
    " WHERE TO GET MORE INFORMATION",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a href=\"#references\">",
    " REFERENCES",
    " </a>",
    " </li>",
    " </ul>",
    " </div>",
    " </div>",
    " </div>",
    " </div>",
    " </div>",
    " </div>",
    " </div>"].join("\n");
    var title_f0_16_262="Basic principles of electrocardiographic interpretation";
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    " <div id=\"topicContent\">",
    " <div id=\"topicTitle\">",
    " Basic principles of electrocardiographic interpretation",
    " </div>",
    " <div id=\"topicContributors\">",
    " <div>",
    " <a id=\"authors\">",
    " </a>",
    " <a class=\"contributor contributor_credentials contributorType\"
    href=\"UTD.htm?0/16/262/contributors\">",
    " Author",
    " </a>",
    " <br/>",
    " <a class=\"contributor contributor_credentials\" href=\"UTD.htm?
    0/16/262/contributors\">",
    " Ary L Goldberger, MD",
    " </a>",
    " <br/>",
    " </div>",
    " <div>",
    " <a class=\"contributor contributor_credentials contributorType\"
    href=\"UTD.htm?0/16/262/contributors\">",
    " Section Editor",
    " </a>",
    " <br/>",
    " <a class=\"contributor contributor_credentials\" href=\"UTD.htm?
    0/16/262/contributors\">",
    " David M Mirvis, MD",
    " </a>",
    " <br/>",
    " </div>",
    " <div>",
    " <a class=\"contributor contributor_credentials contributorType\"
    href=\"UTD.htm?0/16/262/contributors\">",
    " Deputy Editor",
    " </a>",
    " <br/>",
    " <a class=\"contributor contributor_credentials\" href=\"UTD.htm?
    0/16/262/contributors\">",
    " Gordon M Saperia, MD, FACC",
    " </a>",
    " <br/>",
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    " <div id=\"literatureReviewDate\">",
    " <span class=\"emphasis\">",
    " Literature review current through:",
    " </span>",
    " Oct 2013.",
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    " |",
    " </span>",
    " <span class=\"emphasis\">",
    " This topic last updated:",
    " </span>",
    " Mar 14, 2012.",
    " </div>",
    " <div id=\"topicText\">",
    " <p class=\"headingAnchor\" id=\"H1\">",
    " <span class=\"h1\">",
    " INTRODUCTION",
    " </span>",
    " &nbsp;&mdash;&nbsp;The electrocardiogram (ECG) is a graphical record of
    electric potentials generated by the heart muscle during each cardiac cycle. These
    potentials are detected on the surface of the body using electrodes attached to the
    extremities and chest wall, and are then amplified by the electrocardiograph
    machine and displayed on special graph paper.",
    " </p>",
    " <p>",
    " This topic will review the basic aspects of ECG interpretation, including:",
    " </p>",
    " <p>",
    " <ul class=\"bulletCompact-block\">",
    " <li>",
    " The cardiac electrical cycle",
    " </li>",
    " <li>",
    " ECG waveforms and intervals",
    " </li>",
    " <li>",
    " ECG leads",
    " </li>",
    " <li>",
    " Genesis of the normal ECG",
    " </li>",
    " </ul>",
    " </p>",
    " <p>",
    " Each of these issues is discussed in greater detail in published reviews [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/262/abstract/1-3\">",
    " 1-3",
    " </a>",
    " ].",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H2\">",
    " <span class=\"h1\">",
    " THE CARDIAC ELECTRICAL CYCLE",
    " </span>",
    " &nbsp;&mdash;&nbsp;The initiating event for cardiac contraction is the spread
    of depolarizing electrical currents through the heart. These currents are produced
    by three types of cells: cardiac pacemaker cells; specialized conduction tissue;
    and the heart muscle itself. The surface ECG, however, only records the
    depolarization and repolarization potentials generated by the \"working\" atrial
    and ventricular myocardial fibers.",
    " </p>",
    " <p>",
    " The depolarization stimulus for the heartbeat normally begins in the
    sinoatrial (SA) or sinus node, a collection of pacemaker cells with spontaneous
    automaticity (",
    " <a class=\"graphic graphic_figure graphicRef63340 \" href=\"UTD.htm?
    42/52/43841\">",
    " figure 1",
    " </a>",
    " ). (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?6/29/6614?
    source=see_link\">",
    " \"Anatomy and electrophysiology of the sinoatrial node\"",
    " </a>",
    " .) The initial phase of cardiac electrical activation consists of the spread
    of the depolarization wave through the right and left atria, resulting in atrial
    contraction. As the impulse reaches the base of the intraatrial septum, it also
    stimulates pacemaker and specialized conduction tissues in the atrioventricular
    (AV) nodal and His-bundle areas. Together, these two regions constitute the AV
    junction.",
    " </p>",
    " <p>",
    " The bundle of His splits into two main branches, the right and the left
    bundles. The main left bundle bifurcates into two primary subdivisions: a left
    anterior fascicle; and a left posterior fascicle. The bundle branches and fascicles
    rapidly transmit depolarization wavefronts to the myocardium by way of Purkinje
    fibers that penetrate the ventricular walls to excite the working ventricular
    myocardial cells. The depolarization wavefronts spread through the ventricular
    wall, from endocardium (inner layer) to epicardium (outer layer), triggering
    intracellular calcium release and myofilament contraction (electromechanical
    coupling).",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H3\">",
    " <span class=\"h1\">",
    " ECG ELECTRODES AND LEADS",
    " </span>",
    " &nbsp;&mdash;&nbsp;Electrodes are the sites at which an electrical potential
    is measured, while ECG leads record the difference in potentials between two
    electrodes.",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H4\">",
    " <span class=\"h2\">",
    " Electrodes",
    " </span>",
    " &nbsp;&mdash;&nbsp;Standard surface electrodes (right and left arm, right and
    left leg, and the six precordial electrodes) measure the electrical potential at a
    site.",
    " </p>",
    " <p>",
    " In addition, a reference site, the central terminal of Wilson, is calculated
    from the average voltage of the limb leads. This idealized site is meant to
    represent a reference at the center of Einthoven's triangle where total current is
    zero. The central terminal is referred to as the reference or indifferent
    electrode. Unipolar ECG leads are derived from the difference between the measured
    voltage at a surface electrode and the calculated voltage at this central reference
    point.",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H5\">",
    " <span class=\"h2\">",
    " ECG leads",
    " </span>",
    " &nbsp;&mdash;&nbsp;The 12 conventional ECG leads record differences in
    electrical potentials, either between two surface electrodes (bipolar leads), or
    between a surface electrode and the central terminal of Wilson (unipolar leads).",
    " </p>",
    " <p>",
    " ECG leads are divided into two groups: six extremity (limb) leads and six
    chest (precordial) leads. The extremity leads record potentials transmitted onto
    the frontal plane and the chest leads record potentials transmitted onto the
    horizontal plane (",
    " <a class=\"graphic graphic_figure graphicRef65700 \" href=\"UTD.htm?
    17/31/17904\">",
    " figure 2",
    " </a>",
    " ).",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H6\">",
    " <span class=\"h3\">",
    " Limb leads",
    " </span>",
    " &nbsp;&mdash;&nbsp;The six extremity, or limb, leads are further subdivided
    into three bipolar leads (I, II and III) and three unipolar leads (aVR, aVL and
    aVF). Each bipolar lead measures the difference in potential between electrodes at
    two extremities, with one electrode connected to the positive pole and the other to
    the negative pole of the voltmeter:",
    " </p>",
    " <p>",
    " <ul class=\"bulletCompact-block\">",
    " <li>",
    " Lead I records the difference between potential sensed by the electrode
    placed on the left arm (the positive pole) and one placed on the right arm
    (negative pole).",
    " </li>",
    " <li>",
    " Lead II records the difference between electrodes on the left leg (positive)
    and the right arm (negative).",
    " </li>",
    " <li>",
    " Lead III records the difference between electrodes on the left leg
    (positive) and the left arm (negative).",
    " </li>",
    " </ul>",
    " </p>",
    " <p>",
    " These were the leads of the original string galvanometer, the forerunner of
    the modern electrocardiograph introduced by the Dutch physiologist, Dr. Willem
    Einthoven at the beginning of the 20th century.",
    " </p>",
    " <p>",
    " The \"unipolar\" limb leads, in comparison, measure the cardiac voltage (V) at
    one site relative to the central terminal, which has approximately zero potential.
    Thus:",
    " </p>",
    " <p>",
    " <ul class=\"bulletCompact-block\">",
    " <li>",
    " Lead aVR records right arm potentials",
    " </li>",
    " <li>",
    " Lead aVL records left arm potentials",
    " </li>",
    " <li>",
    " Lead aVF records left leg (foot) potentials.",
    " </li>",
    " </ul>",
    " </p>",
    " <p>",
    " The lower case \"a\" indicates that these potentials are augmented by 50
    percent. The right leg electrode functions as a ground.",
    " </p>",
    " <p>",
    " The spatial orientation and polarity of the six frontal plane leads is
    represented on the hexaxial diagram (",
    " <a class=\"graphic graphic_figure graphicRef65292 \" href=\"UTD.htm?
    27/60/28622\">",
    " figure 3",
    " </a>",
    " ). As examples, lead I is primarily a left-right lead, while aVF is an
    inferior-superior lead.",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H7\">",
    " <span class=\"h3\">",
    " Precordial leads",
    " </span>",
    " &nbsp;&mdash;&nbsp;The six chest, or precordial, leads are also unipolar
    recordings. They represent the voltage difference between the central terminal and
    electrodes placed in the following positions (",
    " <a class=\"graphic graphic_figure graphicRef75588 \" href=\"UTD.htm?
    6/48/6912\">",
    " figure 4",
    " </a>",
    " ):",
    " </p>",
    " <p>",
    " <ul class=\"bulletCompact-block\">",
    " <li>",
    " V1 &mdash; 4th intercostal space (ICS), just to the right of the sternum",
    " </li>",
    " <li>",
    " V2 &mdash; 4th ICS, just to the left of the sternum",
    " </li>",
    " <li>",
    " V3 &mdash; midway between V2 and V4",
    " </li>",
    " <li>",
    " V4 &mdash; 5th ICS in the mid-clavicular line",
    " </li>",
    " <li>",
    " V5 &mdash; anterior axillary line, same level as V4",
    " </li>",
    " <li>",
    " V6 &mdash; mid-axillary line, same level as V4 and V5",
    " </li>",
    " </ul>",
    " </p>",
    " <p>",
    " Inadvertent misplacement of chest leads is quite common and can lead to
    considerable diagnostic confusion.",
    " </p>",
    " <p>",
    " The ECG leads are designed so that a positive (upright) deflection will be
    recorded in a lead if a wave of depolarization spreads toward the positive pole of
    that lead. A negative deflection will be recorded if the wave of depolarization
    spreads toward the negative pole of any lead (ie, away from the positive role). As
    an example, depolarization spreading to the left and posterior will produce a
    positive deflection in lead I (a left-right lead) and a negative deflection in lead
    V1 (an anterior-posterior lead). If, however, the mean orientation of the
    depolarization vector (or electrical axis) is at right angles to a given lead axis,
    a small biphasic (equally positive and negative) deflection will be recorded.",
    " </p>",
    " <p>",
    " Together, the frontal and horizontal plane electrodes provide a three-
    dimensional report of cardiac electrical activity. Each lead can be likened to a
    different video camera angle \"looking\" at the same dynamic events &mdash; atrial
    and ventricular depolarization and repolarization &mdash; from different spatial
    orientations. The standard 12 lead ECG can be supplemented with additional leads
    under special circumstances. For example, right precordial leads, such as V3R and
    V4R are useful in detecting acute right ventricular ischemia or infarction. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?0/57/922?
    source=see_link\">",
    " \"Right ventricular myocardial infarction\"",
    " </a>",
    " .)",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H8\">",
    " <span class=\"h1\">",
    " ECG WAVEFORMS AND INTERVALS",
    " </span>",
    " &nbsp;&mdash;&nbsp;ECG waves are labeled alphabetically starting with the P
    wave which represents atrial depolarization (",
    " <a class=\"graphic graphic_figure graphicRef76390 \" href=\"UTD.htm?
    30/21/31069\">",
    " figure 5",
    " </a>",
    " ). The QRS complex represents ventricular depolarization and the ST-T-U
    complex (ST segment, T wave and U wave) represents ventricular repolarization. The
    J point is the junction between the end of the QRS and beginning of the ST segment.
    (Atrial repolarization occurs during the PR segment and QRS complex but is usually
    of too low an amplitude to be detected, but may become apparent in conditions such
    as acute pericarditis or atrial infarction.)",
    " </p>",
    " <p>",
    " The QRS-T waveforms on the surface ECG correspond in a general way to the
    different phases of simultaneously obtained ventricular action potentials, the
    intracellular recordings from single myocardial fibers (",
    " <a class=\"graphic graphic_figure graphicRef78354 \" href=\"UTD.htm?
    33/3/33852\">",
    " figure 6",
    " </a>",
    " ). (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?37/33/38422?
    source=see_link\">",
    " \"Myocardial action potential and action of antiarrhythmic drugs\"",
    " </a>",
    " .):",
    " </p>",
    " <p>",
    " <ul class=\"bullet-block\">",
    " <li>",
    " QRS onset corresponds to the rapid upstroke (phase 0) of the action
    potential.",
    " </li>",
    " <li>",
    " The isoelectric ST segment corresponds to phase 2 of the action potential
    (plateau phase), during which myocardial fibers normally achieve about the same
    potential.",
    " </li>",
    " <li>",
    " The T wave corresponds to phase 3 of the action potential (active
    repolarization).",
    " </li>",
    " <li>",
    " The isoelectric segment between the end of the T wave and the next
    depolarization corresponds to phase 4 of the action potential (recovery).",
    " </li>",
    " </ul>",
    " </p>",
    " <p>",
    " Factors that decrease the slope of phase 0 by, for example, impairing the
    influx of sodium tend to increase QRS duration (eg, severe hyperkalemia or drugs
    such as",
    " <a class=\"drug drug_general\" href=\"UTD.htm?0/48/777?source=see_link\">",
    " quinidine",
    " </a>",
    " ,",
    " <a class=\"drug drug_general\" href=\"UTD.htm?29/30/30182?source=see_link\">",
    " flecainide",
    " </a>",
    " , or",
    " <a class=\"drug drug_general\" href=\"UTD.htm?25/51/26423?source=see_link\">",
    " propafenone",
    " </a>",
    " ). On the other hand, factors that prolong phase 2 (eg, hypocalcemia or drugs
    such as",
    " <a class=\"drug drug_general\" href=\"UTD.htm?22/58/23466?source=see_link\">",
    " amiodarone",
    " </a>",
    " ,",
    " <a class=\"drug drug_general\" href=\"UTD.htm?5/3/5176?source=see_link\">",
    " dronedarone",
    " </a>",
    " , or",
    " <a class=\"drug drug_general\" href=\"UTD.htm?21/13/21721?source=see_link\">",
    " sotalol",
    " </a>",
    " ) increase the QT interval. In contrast, factors such as digitalis and
    hypercalcemia shorten ventricular repolarization (phase 2) and abbreviate the ST
    segment.",
    " </p>",
    " <p>",
    " The ECG waves are recorded on special graph paper which is divided into 1 mm",
    " <sup>",
    " 2",
    " </sup>",
    " grid-like boxes. The ECG paper speed is ordinarily 25",
    " <span class=\"nowrap\">",
    " mm/sec.",
    " </span>",
    " As a result, each 1 mm horizontal box corresponds to 0.04 second (40 ms), with
    heavier lines at larger 0.20 sec (200 ms) intervals. Vertically, the ECG graph
    measures the height (amplitude) of a given wave or deflection, as 10 mm equals 1 mV
    with standard calibration.",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H9\">",
    " <span class=\"h2\">",
    " ECG intervals",
    " </span>",
    " &nbsp;&mdash;&nbsp;There are four major ECG intervals: R-R (inversely related
    to the heart rate), PR, QRS, and",
    " <span class=\"nowrap\">",
    " QT/QTc",
    " </span>",
    " (",
    " <a class=\"graphic graphic_figure graphicRef76390 \" href=\"UTD.htm?
    30/21/31069\">",
    " figure 5",
    " </a>",
    " ). The heart rate",
    " <span class=\"nowrap\">",
    " (beats/min)",
    " </span>",
    " can be readily computed from the interbeat (R-R) interval by dividing the
    number of large (0.20 sec) time units between consecutive R waves into 300 or, for
    more precise measurement, the number of small (0.04 sec) units into 1500.",
    " </p>",
    " <p>",
    " The PR interval measures the time (normally 0.12 to 0.20 sec; 3 to 5 small
    boxes) between the onset of atrial and ventricular depolarization. This includes
    the physiologic delay imposed by stimulation of cells in the AV junction area.",
    " </p>",
    " <p>",
    " The QRS interval (normally &le;0.10 sec; 2",
    " <span class=\"nowrap\">",
    " 1/2",
    " </span>",
    " small boxes) is a measure of the duration of ventricular depolarization. The
    QRS complex is subdivided into specific deflections or waves. If the initial QRS
    deflection in a given lead is negative, it is termed a Q wave. The first positive
    deflection is termed an R wave. A negative deflection after an R wave is called an
    S wave. Subsequent positive or negative waves are labeled R' or S', respectively.
    Lower case letters (q, r, or s) are used for relatively small amplitude waves of
    less than 0.5 mV (less than 5 mm with standard calibration). An entirely negative
    QRS complex is called a QS wave.",
    " </p>",
    " <p>",
    " The QT interval begins with the onset of the QRS complex and ends at the end
    of the T-wave, subtends both ventricular depolarization and repolarization times,
    and varies inversely with the heart rate. A rate-related (or corrected) QT interval
    (QTc) can be calculated from:",
    " </p>",
    " <p>",
    " &nbsp;QTc &nbsp; = &nbsp; QT interval &nbsp;&divide; &nbsp;square root of the
    RR interval",
    " </p>",
    " <p>",
    " The upper limit of the normal value for the QTc is approximately 0.44.",
    " </p>",
    " <p>",
    " A number of other formulas have also been suggested for correcting the QT for
    heart rate. However, there is no consensus on an optimal way to do this
    correction.",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H10\">",
    " <span class=\"h1\">",
    " GENESIS OF THE NORMAL ECG",
    " </span>",
    " &nbsp;&mdash;&nbsp;The direction and magnitude of the ECG waveform reflects
    the sequential vectors of atrial and ventricular depolarization and
    repolarization.",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H11\">",
    " <span class=\"h2\">",
    " P wave",
    " </span>",
    " &nbsp;&mdash;&nbsp;The wave of atrial depolarization normally travels downward
    and toward the subject's left, reflecting the spread of the depolarization stimulus
    from the sinus node to the right and left atrial muscle and the AV junction. This
    downward and left vector points toward the positive pole of lead II and the
    negative pole of lead aVR (",
    " <a class=\"graphic graphic_figure graphicRef55410 \" href=\"UTD.htm?
    43/12/44224\">",
    " figure 7",
    " </a>",
    " ). As a result, the normal sinus P wave is positive (upright) in lead II and
    negative (downward) in lead aVR. In contrast, activation of the atria from an
    ectopic pacemaker in the lower part of either atrium or in the AV junction region
    may produce retrograde P waves moving upward and to the right. This will produce P
    waves that are negative in lead II and positive in lead aVR.",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H12\">",
    " <span class=\"h2\">",
    " QRS complex",
    " </span>",
    " &nbsp;&mdash;&nbsp;Normal ventricular depolarization can be divided into two
    major, sequential phases. Each phase can be represented by a mean vector (",
    " <a class=\"graphic graphic_figure graphicRef63074 \" href=\"UTD.htm?
    42/14/43247\">",
    " figure 8",
    " </a>",
    " ).",
    " </p>",
    " <p>",
    " <ul class=\"bullet-block\">",
    " <li>",
    " The first phase is depolarization of the interventricular septum from left
    to right (vector 1).",
    " </li>",
    " <li>",
    " The second phase is simultaneous depolarization of the main mass of the
    right and left ventricles. This second phase is normally dominated by the more
    massive left ventricle so that vector 2 points leftward and posteriorly.",
    " </li>",
    " </ul>",
    " </p>",
    " <p>",
    " Thus, a right precordial lead like V1 will record this biphasic depolarization
    process with a small positive deflection (septal r wave) followed by a larger
    negative deflection (S wave). In contrast, a left precordial lead such as V6 will
    record the same sequence with a small negative deflection (septal q wave) followed
    by a relatively tall positive deflection (R wave). Intermediate precordial leads
    show a relative increase in R wave amplitude and a decrease in S wave amplitude
    progressing across the chest from right to left (",
    " <a class=\"graphic graphic_waveform graphicRef58149 \" href=\"UTD.htm?
    36/55/37751\">",
    " waveform 1",
    " </a>",
    " ). This normal R wave progression in the precordial leads is a reflection of
    the progressively more leftward orientation of these leads. The precordial lead
    where the R wave and S wave are of about equal amplitude is referred to as the
    transition zone (usually lead V3 or V4).",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H13\">",
    " <span class=\"h2\">",
    " QRS axis",
    " </span>",
    " &nbsp;&mdash;&nbsp;The electrical axis describes the overall orientation of
    the QRS vector with reference to the six frontal plane leads. The QRS pattern in
    the extremity leads may vary considerably from one normal subject to another
    depending upon the electrical axis of the QRS complex.",
    " </p>",
    " <p>",
    " The normal QRS axis in adults ranges from about -30&ordm; to + 100&ordm; (",
    " <a class=\"graphic graphic_figure graphicRef65292 \" href=\"UTD.htm?
    27/60/28622\">",
    " figure 3",
    " </a>",
    " ). An axis more negative than -30&ordm; is referred to as left axis deviation
    (LAD), while an axis more positive than +100&ordm; is referred to as right axis
    deviation (RAD).",
    " </p>",
    " <p>",
    " Left axis deviation can occur as a normal variant, but is most commonly
    associated with a more pronounced leftward QRS vector due to left ventricular
    hypertrophy, a block in the anterior fascicle of the left bundle system (left
    anterior fascicular block or hemiblock) or inferior myocardial infarction. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?16/31/16886?
    source=see_link\">",
    " \"Left anterior fascicular block\"",
    " </a>",
    " .)",
    " </p>",
    " <p>",
    " Right axis deviation can also occur as a normal variant (particularly in
    children and young adults), as a spurious finding due to reversal of the left and
    right arm electrodes, or in such conditions such as right ventricular overload
    syndromes (acute or chronic), apicolateral wall infarction of the left ventricle,
    dextrocardia, left pneumothorax, or left posterior fascicular block. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?16/2/16420?
    source=see_link\">",
    " \"Left posterior fascicular block\"",
    " </a>",
    " .)",
    " </p>",
    " <p>",
    " The QRS axis can be estimated as being at right angles to the positive pole of
    any extremity lead in which the positive and negative deflections are of roughly
    equal magnitude. With lead II, for example, the positive pole is at +60&ordm; (",
    " <a class=\"graphic graphic_figure graphicRef65292 \" href=\"UTD.htm?
    27/60/28622\">",
    " figure 3",
    " </a>",
    " ); as a result, the axis must be either -30&ordm; (borderline LAD) or
    +150&ordm; (RAD) if the QRS complex has positive and negative waves of roughly
    equal magnitude in that lead. These two possibilities can be readily distinguished
    by looking at another lead such as lead I (positive pole at +0&ordm;), which will
    be have a net positive deflection with LAD and negative deflection with RAD.",
    " </p>",
    " <p>",
    " In general, you can usually determine whether the QRS electrical axis is
    normal, leftward or rightward from simple inspection of leads I and II (",
    " <a class=\"graphic graphic_figure graphicRef57151 \" href=\"UTD.htm?
    42/10/43182\">",
    " figure 9",
    " </a>",
    " ):",
    " </p>",
    " <p>",
    " <ul class=\"bulletCompact-block\">",
    " <li>",
    " Normal QRS axis: Net QRS area positive in I and II.",
    " </li>",
    " <li>",
    " Left axis deviation: Net QRS positive in I, negative in II.",
    " </li>",
    " <li>",
    " Right axis deviation: Net QRS negative in I, positive in II.",
    " </li>",
    " </ul>",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H14\">",
    " <span class=\"h2\">",
    " T and U waves",
    " </span>",
    " &nbsp;&mdash;&nbsp;In the normal ECG, the orientation of the mean T wave
    vector is roughly the same as the mean QRS vector. Since depolarization and
    repolarization are electrically opposite processes, this physiologic QRS-T wave
    vector concordance indicates that repolarization must normally proceed in the
    reverse direction from depolarization (ie, from epicardium to endocardium or from
    cardiac apex to base).",
    " </p>",
    " <p>",
    " The normal U wave is a small rounded deflection (&le;1 mm) following the T
    wave, which usually has the same polarity of the T wave. An abnormal increase in U
    wave amplitude is most commonly due to drugs (such as",
    " <a class=\"drug drug_general\" href=\"UTD.htm?13/32/13829?source=see_link\">",
    " ibutilide",
    " </a>",
    " ,",
    " <a class=\"drug drug_general\" href=\"UTD.htm?6/2/6183?source=see_link\">",
    " dofetilide",
    " </a>",
    " ,",
    " <a class=\"drug drug_general\" href=\"UTD.htm?21/13/21721?source=see_link\">",
    " sotalol",
    " </a>",
    " ,",
    " <a class=\"drug drug_general\" href=\"UTD.htm?0/48/777?source=see_link\">",
    " quinidine",
    " </a>",
    " ,",
    " <a class=\"drug drug_general\" href=\"UTD.htm?35/34/36391?source=see_link\">",
    " procainamide",
    " </a>",
    " , or",
    " <a class=\"drug drug_general\" href=\"UTD.htm?34/49/35607?source=see_link\">",
    " disopyramide",
    " </a>",
    " ) or hypokalemia. Very prominent U waves with prolonged ventricular
    repolarization (long QT interval) are associated with increased susceptibility to
    torsades de pointes, a type of polymorphic ventricular tachycardia. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?22/55/23418?
    source=see_link\">",
    " \"Acquired long QT syndrome\"",
    " </a>",
    " and",
    " <a class=\"medical medical_review\" href=\"UTD.htm?36/48/37641?
    source=see_link\">",
    " \"Catecholaminergic polymorphic ventricular tachycardia and other polymorphic
    ventricular tachycardias with a normal QT interval\"",
    " </a>",
    " .)",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H9241824\">",
    " <span class=\"h1\">",
    " SUMMARY",
    " </span>",
    " </p>",
    " <p>",
    " <ul class=\"bullet-block\">",
    " <li>",
    " The electrocardiogram (ECG) is a graphical record that sums the electric
    potentials generated by the heart muscle during each cardiac cycle. (See",
    " <a class=\"local\" href=\"#H1\">",
    " 'Introduction'",
    " </a>",
    " above.)",
    " </li>",
    " <li>",
    " The conventional ECG is recorded using 12 leads, applied to the arms, legs,
    and chest, that represent the difference in electrical potentials in the frontal
    and horizontal planes of the body. (See",
    " <a class=\"local\" href=\"#H3\">",
    " 'ECG electrodes and leads'",
    " </a>",
    " above.)",
    " </li>",
    " <li>",
    " ECG waves are labeled alphabetically starting with the P wave, which
    represents atrial depolarization. The QRS complex represents ventricular
    depolarization and the ST-T-U complex (ST segment, T wave and U wave) represents
    ventricular repolarization. The J point is the junction between the end of the QRS
    and beginning of the ST segment. (See",
    " <a class=\"local\" href=\"#H8\">",
    " 'ECG waveforms and intervals'",
    " </a>",
    " above.)",
    " </li>",
    " <li>",
    " There are four major ECG intervals: R-R (inversely related to the heart
    rate), PR, QRS, and",
    " <span class=\"nowrap\">",
    " QT/QTc.",
    " </span>",
    " (See",
    " <a class=\"local\" href=\"#H8\">",
    " 'ECG waveforms and intervals'",
    " </a>",
    " above.)",
    " </li>",
    " <li>",
    " The ECG can be conceptualized in terms of vectors (arrows with magnitude and
    direction) that represent the orientation and balance of cardiac depolarization and
    repolarization forces projected onto the ECG leads. (See",
    " <a class=\"local\" href=\"#H10\">",
    " 'Genesis of the normal ECG'",
    " </a>",
    " above.)",
    " </li>",
    " </ul>",
    " </p>",
    " </div>",
    " <div id=\"topicAgreement\">",
    " Use of UpToDate is subject to the",
    " <a class=\"licenseLink\" href=\"./license\" id=\"sla_in_page\"
    target=\"_blank\">",
    " Subscription and License Agreement",
    " </a>",
    " .",
    " </div>",
    " <div class=\"headingAnchor\" id=\"references\">",
    " <h1>",
    " REFERENCES",
    " </h1>",
    " <ol id=\"reference\">",
    " <li>",
    " Goldberger, AL, Goldberger, E. Clinical Electrocardiography: A Simplified
    Approach, 7th ed, Elsevier/Mosby, Inc, St. Louis 2006.",
    " </li>",
    " <li>",
    " Mirvis, DM, Goldberger, AL. Electrocardiography. In: Braunwald's Heart
    Disease: A Textbook of Cardiovascular Medicine, 9th ed, Bonow, RO, Mann, DL, Zipes,
    DP, Libby, P (Eds), W.B. Saunders Company, Philadelphia 2011.",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/16/262/abstract/3\">",
    " Kligfield P, Gettes LS, Bailey JJ, et al. Recommendations for the
    standardization and interpretation of the electrocardiogram. Part I: The
    electrocardiogram and its technology. A scientific statement from the American
    Heart Association Electrocardiography and Arrhythmias Committee, Council on
    Clinical Cardiology; the American College of Cardiology Foundation; and the Heart
    Rhythm Society. Heart Rhythm 2007; 4:394.",
    " </a>",
    " </li>",
    " </ol>",
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    " Topic 2098 Version 6.0",
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    var outline_f0_16_262=[" <div id=\"toggleOutline\">",
    " <a href=\"#\" title=\"Collapse Topic Outline\">",
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    " <h1>",
    " TOPIC OUTLINE",
    " </h1>",
    " <div id=\"outline\">",
    " <ul>",
    " <li>",
    " <a class=\"sr_button\" href=\"#H9241824\" id=\"summRecButton\">",
    " <span>",
    " SUMMARY",
    " </span>",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#H1\">",
    " INTRODUCTION",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#H2\">",
    " THE CARDIAC ELECTRICAL CYCLE",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#H3\">",
    " ECG ELECTRODES AND LEADS",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H4\">",
    " Electrodes",
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    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H5\">",
    " ECG leads",
    " </a>",
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    " <li class=\"dashItem\">",
    " <a class=\"outlineLink\" href=\"#H6\">",
    " - Limb leads",
    " </a>",
    " </li>",
    " <li class=\"dashItem\">",
    " <a class=\"outlineLink\" href=\"#H7\">",
    " - Precordial leads",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#H8\">",
    " ECG WAVEFORMS AND INTERVALS",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H9\">",
    " ECG intervals",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#H10\">",
    " GENESIS OF THE NORMAL ECG",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H11\">",
    " P wave",
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    " QRS complex",
    " </a>",
    " </li>",
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    " <a class=\"outlineLink\" href=\"#H13\">",
    " QRS axis",
    " </a>",
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    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H14\">",
    " T and U waves",
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    " SUMMARY",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a href=\"#references\">",
    " REFERENCES",
    " </a>",
    " </li>",
    " </ul>",
    " </div>",
    " <h1>",
    " <div class=\"openRelatedGraphics\" id=\"CARD/2098\" rel=\"outline_link\">",
    " GRAPHICS",
    " <a class=\"graphics_icon\" href=\"#\" title=\"View All Related Graphics\">",
    " View All",
    " </a>",
    " </div>",
    " </h1>",
    " <div id=\"relatedGraphics\">",
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    " <li class=\"plainItem\">",
    " <div class=\"openRelatedGraphics\" id=\"CARD/2098|FIG\">",
    " <a href=\"#\" title=\"FIGURES\">",
    " FIGURES",
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    " </div>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"graphic graphic_figure\" href=\"UTD.htm?42/52/43841\"
    title=\"figure 1\">",
    " Normal conduction system",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"graphic graphic_figure\" href=\"UTD.htm?17/31/17904\"
    title=\"figure 2\">",
    " Activity of ECG leads",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"graphic graphic_figure\" href=\"UTD.htm?27/60/28622\"
    title=\"figure 3\">",
    " Electrical axis of ECG leads",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"graphic graphic_figure\" href=\"UTD.htm?6/48/6912\" title=\"figure
    4\">",
    " Placement of precordial leads",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"graphic graphic_figure\" href=\"UTD.htm?30/21/31069\"
    title=\"figure 5\">",
    " Generation of ECG",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"graphic graphic_figure\" href=\"UTD.htm?33/3/33852\"
    title=\"figure 6\">",
    " ECG and action potential",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"graphic graphic_figure\" href=\"UTD.htm?43/12/44224\"
    title=\"figure 7\">",
    " Generation of the P wave",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"graphic graphic_figure\" href=\"UTD.htm?42/14/43247\"
    title=\"figure 8\">",
    " Generation of the QRS complex",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"graphic graphic_figure\" href=\"UTD.htm?42/10/43182\"
    title=\"figure 9\">",
    " Left and right axis deviation",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <div class=\"openRelatedGraphics\" id=\"CARD/2098|Waveform\">",
    " <a href=\"#\" title=\"WAVEFORMS\">",
    " WAVEFORMS",
    " </a>",
    " </div>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"graphic graphic_waveform\" href=\"UTD.htm?36/55/37751\"
    title=\"waveform 1\">",
    " ECG of sinus rhythm",
    " </a>",
    " </li>",
    " </ul>",
    " </div>",
    " <h1>",
    " RELATED TOPICS",
    " </h1>",
    " <div id=\"relatedTopics\">",
    " <ul>",
    " <li class=\"plainItem\">",
    " <a class=\"medical medical_review\" href=\"UTD.htm?22/55/23418?
    source=related_link\">",
    " Acquired long QT syndrome",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"medical medical_review\" href=\"UTD.htm?6/29/6614?
    source=related_link\">",
    " Anatomy and electrophysiology of the sinoatrial node",
    " </a>",
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    " <li class=\"plainItem\">",
    " <a class=\"medical medical_review\" href=\"UTD.htm?36/48/37641?
    source=related_link\">",
    " Catecholaminergic polymorphic ventricular tachycardia and other polymorphic
    ventricular tachycardias with a normal QT interval",
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    " </li>",
    " <li class=\"plainItem\">",
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    " Myocardial action potential and action of antiarrhythmic drugs",
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    " </div>",
    " </div>"].join("\n");
    var title_f0_16_263="Dehydroepiandrosterone and its sulfate";
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    " <div id=\"topicContent\">",
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    " Dehydroepiandrosterone and its sulfate",
    " </div>",
    " <div id=\"topicContributors\">",
    " <div>",
    " <a id=\"authors\">",
    " </a>",
    " <a class=\"contributor contributor_credentials contributorType\"
    href=\"UTD.htm?0/16/263/contributors\">",
    " Author",
    " </a>",
    " <br/>",
    " <a class=\"contributor contributor_credentials\" href=\"UTD.htm?
    0/16/263/contributors\">",
    " George P Chrousos, MD",
    " </a>",
    " <br/>",
    " </div>",
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    " <a class=\"contributor contributor_credentials contributorType\"
    href=\"UTD.htm?0/16/263/contributors\">",
    " Section Editor",
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    " <br/>",
    " <a class=\"contributor contributor_credentials\" href=\"UTD.htm?
    0/16/263/contributors\">",
    " Andre Lacroix, MD",
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    " <br/>",
    " </div>",
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    " <a class=\"contributor contributor_credentials contributorType\"
    href=\"UTD.htm?0/16/263/contributors\">",
    " Deputy Editor",
    " </a>",
    " <br/>",
    " <a class=\"contributor contributor_credentials\" href=\"UTD.htm?
    0/16/263/contributors\">",
    " Kathryn A Martin, MD",
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    " <span class=\"emphasis\">",
    " Literature review current through:",
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    " Oct 2013.",
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    " This topic last updated:",
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    " Apr 17, 2012.",
    " </div>",
    " <div id=\"topicText\">",
    " <p class=\"headingAnchor\" id=\"H1\">",
    " <span class=\"h1\">",
    " INTRODUCTION",
    " </span>",
    " &nbsp;&mdash;&nbsp;Adrenal production of dehydroepiandrosterone (DHEA) and
    dehydroepiandrosterone sulfate (DHEA sulfate or DHEA-S) is substantial in both men
    and women. The production of both is greatest among young adults, and it declines
    progressively with age. At their peak at age 25 years, serum DHEA concentrations
    range from 0.2 to 0.9",
    " <span class=\"nowrap\">",
    " mcg/dL",
    " </span>",
    " (7 to 31",
    " <span class=\"nowrap\">",
    " nmol/L),",
    " </span>",
    " 10-fold lower than those of cortisol, and serum DHEA-S concentrations range
    from 75 to 370",
    " <span class=\"nowrap\">",
    " mcg/dL",
    " </span>",
    " (2 to 10",
    " <span class=\"nowrap\">",
    " &micro;mol/L),",
    " </span>",
    " 20-fold higher than those of cortisol. By age 80 years, the concentrations are
    only about 20 percent of those at age 25 years [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/263/abstract/1-3\">",
    " 1-3",
    " </a>",
    " ].",
    " </p>",
    " <p>",
    " DHEA is converted to DHEA-S in the adrenal and liver, both of which contain a
    sulfotransferase. The former is produced from the latter in peripheral tissues that
    contain a sulfatase. In the adrenal glands and peripheral tissues such as hair
    follicles, prostate, external genitalia, and adipose tissue, small amounts of DHEA
    and DHEA-S are converted to more active androgens such as androstenedione,
    androstenediol, testosterone, and 5-dihydrotestosterone, and estrogens such as
    estradiol and estrone. These hormones then exert their usual androgenic and
    estrogenic effects via the androgen and estrogen receptors, respectively. In women,
    adrenal production of DHEA and DHEA-S contributes substantially to overall androgen
    production and effects; in men the adrenal contribution is very small.",
    " </p>",
    " <p>",
    " DHEA has been proposed to have many actions, including vasodilatory, anti-
    aging, anti-inflammatory, anti-atherosclerotic actions and anti-depressant, and it
    is widely available in stores that sell health foods and nutritional supplements.
    However, quality control of these products has been shown to be quite poor [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/263/abstract/4,5\">",
    " 4,5",
    " </a>",
    " ].",
    " </p>",
    " <p>",
    " The possible sites of action and clinical uses of DHEA are reviewed here.
    Measurements of adrenal androgens and the causes and effects of excess endogenous
    production of DHEA and DHEA-S are discussed separately. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?20/60/21445?
    source=see_link\">",
    " \"Measurement of adrenal androgens\"",
    " </a>",
    " and",
    " <a class=\"medical medical_review\" href=\"UTD.htm?39/8/40071?
    source=see_link\">",
    " \"Adrenal hyperandrogenism\"",
    " </a>",
    " .)",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H2\">",
    " <span class=\"h1\">",
    " POSSIBLE SITES OF ACTION",
    " </span>",
    " &nbsp;&mdash;&nbsp;DHEA and DHEA-S act, after conversion to androgens and
    estrogens, by activating androgen and estrogen receptors, respectively, as noted
    above.",
    " </p>",
    " <p>",
    " In addition, there are five receptors other than the androgen and estrogen
    receptor with which DHEA and DHEA-S may interact in vitro, but the clinical
    importance of these interactions is not known. They are:",
    " </p>",
    " <p>",
    " <ul class=\"bullet-block\">",
    " <li>",
    " The gamma-aminobutyric acid",
    " <span class=\"nowrap\">",
    " (GABA)-A/benzodiazepine",
    " </span>",
    " receptor complex, via which DHEA and DHEA-S may antagonize the effects of
    GABA [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/263/abstract/6\">",
    " 6",
    " </a>",
    " ]",
    " </li>",
    " <li>",
    " N-methyl-aspartate excitatory amino acid receptors, where DHEA may
    potentiate the effects of glutamate [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/263/abstract/7\">",
    " 7",
    " </a>",
    " ]",
    " </li>",
    " <li>",
    " A novel nuclear hormone-type receptor called CAR, for which reduced
    metabolites of DHEA may be the natural ligands [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/263/abstract/8\">",
    " 8",
    " </a>",
    " ]",
    " </li>",
    " <li>",
    " A cell-surface receptor in vascular endothelial cells that binds DHEA (but
    not DHEA-S) and is functionally coupled to G-proteins and nitric oxide synthase [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/263/abstract/9\">",
    " 9",
    " </a>",
    " ]",
    " </li>",
    " <li>",
    " The sigma-1 receptor binds neurosteroids, including DHEA and DHEA-S, which
    have antidepressant-like effects in animal models of depression [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/263/abstract/10\">",
    " 10",
    " </a>",
    " ]",
    " </li>",
    " </ul>",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H3\">",
    " <span class=\"h1\">",
    " USE IN ADRENAL INSUFFICIENCY",
    " </span>",
    " &nbsp;&mdash;&nbsp;In women, the adrenal cortex is the primary source of
    androgen in the form of DHEA and DHEA-S. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?39/8/40071?
    source=see_link\">",
    " \"Adrenal hyperandrogenism\"",
    " </a>",
    " and",
    " <a class=\"medical medical_review\" href=\"UTD.htm?19/45/20184?
    source=see_link\">",
    " \"Androgen production and therapy in women\"",
    " </a>",
    " .) DHEA and DHEA-S production is low in patients with primary or secondary
    adrenal insufficiency, resulting in androgen deficiency, particularly in women. The
    physiological role of these androgens in women is not known, and replacement of
    them has not historically been part of the treatment regimen for patients with
    adrenal insufficiency. Clinical trial data suggest that androgen replacement
    therapy (DHEA) in women with primary or secondary adrenal insufficiency may be
    beneficial.",
    " </p>",
    " <p>",
    " In the United States, the use of DHEA is severely limited by the lack of
    product quality control, as DHEA is considered to be a diet supplement rather than
    a hormone preparation. Therefore, DHEA supplements available commercially may not
    actually contain the advertised dose. This topic is discussed in detail separately.
    (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?41/47/42745?
    source=see_link\">",
    " \"Treatment of adrenal insufficiency in adults\"",
    " </a>",
    " .)",
    " </p>",
    " <p>",
    " The role of adrenal androgen replacement has been evaluated in several studies
    of patients with adrenal insufficiency:",
    " </p>",
    " <p>",
    " <ul class=\"bullet-block\">",
    " <li>",
    " In a study of 24 women with primary adrenal insufficiency who were receiving
    adequate glucocorticoid and mineralocorticoid therapy, administration of DHEA in a
    dose of 50 mg daily for four months increased serum androgen concentrations into
    the normal range [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/263/abstract/11\">",
    " 11",
    " </a>",
    " ]. General and psychological well-being and sexuality increased, and scores
    on tests of depression and anxiety were lower after treatment with DHEA as compared
    with placebo. Most of the women had only transient, mild, skin-related androgenic
    side effects, but five had more pronounced effects.",
    " <br/>",
    " <br/>",
    " In the same study, DHEA replacement had no effect on carbohydrate
    metabolism, body composition, or exercise capacity [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/263/abstract/12\">",
    " 12",
    " </a>",
    " ].",
    " </li>",
    " <li>",
    " In a second, randomized, double-blind study of 15 men and 24 women with
    primary adrenal insufficiency, DHEA (50 mg daily) improved self-esteem and overall
    sense of well-being in both sexes, with less fatigue and improved mood in the
    evening [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/263/abstract/13\">",
    " 13",
    " </a>",
    " ]. The beneficial effects in men suggest that DHEA may act directly on the
    brain.",
    " </li>",
    " <li>",
    " Results were somewhat different in a 12-month trial in 106 men and women
    with primary adrenal insufficiency. DHEA (50",
    " <span class=\"nowrap\">",
    " mg/day)",
    " </span>",
    " prevented bone loss at the femoral neck (but not other sites), and increased
    total body and truncal lean body mass with no change in fat mass. There was no
    significant benefit of DHEA on fatigue, cognitive function, or sexual function, and
    only minimal effect on psychological well-being [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/263/abstract/14\">",
    " 14",
    " </a>",
    " ].",
    " </li>",
    " <li>",
    " Higher doses of DHEA (200",
    " <span class=\"nowrap\">",
    " mg/day)",
    " </span>",
    " did not appear to cause more severe side effects, but provided no additional
    clinical benefit [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/263/abstract/15\">",
    " 15",
    " </a>",
    " ].",
    " </li>",
    " <li>",
    " Doses lower than 50 mg may not be effective. In a nine-month study of 39
    women with adrenal insufficiency, 25 mg DHEA was no more effective than placebo in
    increasing well-being and sexuality, and 89 percent of the women given DHEA had
    side effects [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/263/abstract/16\">",
    " 16",
    " </a>",
    " ].",
    " </li>",
    " <li>",
    " DHEA (50",
    " <span class=\"nowrap\">",
    " mg/day",
    " </span>",
    " for 12 weeks) improved insulin sensitivity (as measured by hyperinsulinemic-
    euglycemic clamp studies in a placebo-controlled trial) in 28 women with primary
    adrenal insufficiency [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/263/abstract/17\">",
    " 17",
    " </a>",
    " ]. DHEA also reduced serum total cholesterol, triglyceride, and LDL
    concentrations, however, HDL concentrations decreased as well.",
    " </li>",
    " </ul>",
    " </p>",
    " <p>",
    " Lower doses of DHEA may be effective in women with ACTH deficiency (secondary
    adrenal insufficiency). In a study of 38 women with hypopituitarism, administration
    of DHEA (20 to 30",
    " <span class=\"nowrap\">",
    " mg/day",
    " </span>",
    " for six months) resulted in increases in serum androgens, axillary and pubic
    hair, and energy, but no increase in sexual interest or activity [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/263/abstract/18\">",
    " 18",
    " </a>",
    " ]. In a second trial of DHEA in men and women with panhypopituitarism (ACTH
    and gonadotropin deficiency), modest and minor improvements were seen in
    psychological well-being in the women and men, respectively [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/263/abstract/19\">",
    " 19",
    " </a>",
    " ].",
    " </p>",
    " <p>",
    " In a published placebo-controlled double blind study of adolescent girls with
    central adrenal insufficiency, daily replacement with 25mg DHEA orally was
    beneficial: atrichia pubis vanished, and psychological well-being improved
    significantly [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/263/abstract/20\">",
    " 20",
    " </a>",
    " ].",
    " </p>",
    " <p>",
    " Other effects of DHEA in patients with adrenal insufficiency and a meta-
    analysis of its efficacy for depression and quality of life are reviewed in detail
    separately. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?41/47/42745?
    source=see_link&amp;anchor=H13#H13\">",
    " \"Treatment of adrenal insufficiency in adults\", section on 'Androgen
    replacement (DHEA)'",
    " </a>",
    " .)",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H4\">",
    " <span class=\"h1\">",
    " OTHER PROPOSED USES",
    " </span>",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H5\">",
    " <span class=\"h2\">",
    " Athletic performance",
    " </span>",
    " &nbsp;&mdash;&nbsp;DHEA has been given to trained athletes in an attempt to
    improve performance. The effect of DHEA on muscle strength is unclear as results
    from clinical trials have been conflicting. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?20/35/21050?
    source=see_link&amp;anchor=H7#H7\">",
    " \"Use of androgens and other hormones to enhance athletic performance\",
    section on 'Androgen precursors'",
    " </a>",
    " .)",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H6\">",
    " <span class=\"h2\">",
    " Systemic lupus erythematosus",
    " </span>",
    " &nbsp;&mdash;&nbsp;Women with systemic lupus erythematosus (SLE) have low
    serum DHEA and DHEA-S concentrations, even prior to initiating chronic
    glucocorticoid therapy [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/263/abstract/21\">",
    " 21",
    " </a>",
    " ]. The possible beneficial and adverse effects of DHEA when used in patients
    with SLE are discussed in more detail elsewhere. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?40/38/41578?
    source=see_link\">",
    " \"Overview of the therapy and prognosis of systemic lupus erythematosus in
    adults\"",
    " </a>",
    " .)",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H7\">",
    " <span class=\"h2\">",
    " Fibromyalgia",
    " </span>",
    " &nbsp;&mdash;&nbsp;DHEA appears to be ineffective for the treatment of
    fibromyalgia. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?14/15/14586?
    source=see_link\">",
    " \"Initial treatment of fibromyalgia in adults\"",
    " </a>",
    " .)",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H8\">",
    " <span class=\"h2\">",
    " Sj&ouml;gren's syndrome",
    " </span>",
    " &nbsp;&mdash;&nbsp;Disease manifestations in primary Sj&ouml;gren's syndrome
    are associated with low sex hormone levels: dry mouth symptoms with low androgens
    and dry eyes with low estrogens. In a double blind placebo-controlled study, oral
    exogenous DHEA at the dose of",
    " <span class=\"nowrap\">",
    " 50mg/day",
    " </span>",
    " was preferentially transformed into androgens rather than estrogens and its
    administration was associated with some improvement of dry mouth [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/263/abstract/22\">",
    " 22",
    " </a>",
    " ].",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H9\">",
    " <span class=\"h2\">",
    " Depression",
    " </span>",
    " &nbsp;&mdash;&nbsp;DHEA may also be more effective than placebo for the
    treatment of depression. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?39/8/40074?
    source=see_link&amp;anchor=H35#H35\">",
    " \"Initial treatment of depression in adults\", section on 'DHEA'",
    " </a>",
    " .)",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H10\">",
    " <span class=\"h2\">",
    " Perimenopause",
    " </span>",
    " &nbsp;&mdash;&nbsp;DHEA does not appear to be effective for perimenopausal
    symptoms. This was illustrated in a trial of 60 symptomatic perimenopausal women in
    whom DHEA 50",
    " <span class=\"nowrap\">",
    " mg/day,",
    " </span>",
    " when compared to placebo, did not result in significantly greater improvements
    in the severity of perimenopausal symptoms, mood, dysphoria, libido, cognition,
    memory, or well-being [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/263/abstract/23\">",
    " 23",
    " </a>",
    " ].",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H11\">",
    " <span class=\"h2\">",
    " Anti-aging",
    " </span>",
    " &nbsp;&mdash;&nbsp;It had been thought that DHEA might have antiaging effects,
    with possible beneficial effects on well-being, cognitive function, and body
    compositions. However, most data suggest that this is not the case.",
    " </p>",
    " <p>",
    " In postmenopausal women and older men, in whom serum DHEA and DHEA-S
    concentrations are considerably lower than in younger subjects, administration of
    DHEA in doses of 50 to 100 mg daily for 3 to 24 months raises serum DHEA and DHEA-S
    concentrations to values comparable to those in young subjects [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/263/abstract/24-30\">",
    " 24-30",
    " </a>",
    " ]. Small increases in serum testosterone and estradiol have also been observed
    in women [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/263/abstract/29\">",
    " 29",
    " </a>",
    " ]. Although physiologic serum concentrations of DHEA may be achieved, the
    clinical benefits observed are inconsistent as illustrated by the following
    findings:",
    " </p>",
    " <p>",
    " <ul class=\"bullet-block\">",
    " <li>",
    " In one trial of aging women and men, DHEA improved psychological well-being
    [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/263/abstract/24\">",
    " 24",
    " </a>",
    " ]. However, most trials have not seen improvements in sense of well-being on
    quality-of-life measures with DHEA administration [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/263/abstract/26,27,29\">",
    " 26,27,29",
    " </a>",
    " ].",
    " </li>",
    " <li>",
    " DHEA has had no effect on either muscle size or strength in most trials of
    elderly subjects [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/263/abstract/29-31\">",
    " 29-31",
    " </a>",
    " ].",
    " </li>",
    " <li>",
    " Administration of DHEA reduces visceral fat accumulation in obese rats and
    mice [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/263/abstract/32\">",
    " 32",
    " </a>",
    " ]. In humans, the effects of DHEA on body composition have been
    inconsistent. One small trial reported a significant decrease in abdominal visceral
    and subcutaneous fat [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/263/abstract/33\">",
    " 33",
    " </a>",
    " ], but others [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/263/abstract/27,28,31,34\">",
    " 27,28,31,34",
    " </a>",
    " ], including two larger, longer-term trials [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/263/abstract/29,30\">",
    " 29,30",
    " </a>",
    " ], have reported no effect of DHEA [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/263/abstract/27-31,34\">",
    " 27-31,34",
    " </a>",
    " ].",
    " </li>",
    " <li>",
    " One small trial reported an improvement in insulin sensitivity with DHEA
    therapy [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/263/abstract/33\">",
    " 33",
    " </a>",
    " ], but a larger, longer-term study did not [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/263/abstract/29\">",
    " 29",
    " </a>",
    " ].",
    " </li>",
    " </ul>",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H12\">",
    " <span class=\"h3\">",
    " Bone",
    " </span>",
    " &nbsp;&mdash;&nbsp;Although data are somewhat limited, DHEA replacement
    improved bone mineral density in elderly subjects with low serum DHEA
    concentrations in some [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/263/abstract/25,34\">",
    " 25,34",
    " </a>",
    " ], but not all [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/263/abstract/26\">",
    " 26",
    " </a>",
    " ], studies. In the largest trial, 140 older men and women were randomly
    assigned to DHEA 50",
    " <span class=\"nowrap\">",
    " mg/day",
    " </span>",
    " or placebo for 12 months. DHEA increased bone density significantly more than
    placebo at the hip, and in women, the lumbar spine [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/263/abstract/34\">",
    " 34",
    " </a>",
    " ]. Similar results were noted in a two-year trial [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/263/abstract/29\">",
    " 29",
    " </a>",
    " ]. However, the improvements in bone density reported are very small when
    compared with those seen with approved drugs for osteoporosis. In the absence of
    fracture data, the clinical significance of these findings is unclear.",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H13\">",
    " <span class=\"h3\">",
    " Dementia",
    " </span>",
    " &nbsp;&mdash;&nbsp;In elderly individuals with established dementia, DHEA
    therapy does not appear to improve cognitive performance [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/263/abstract/35\">",
    " 35",
    " </a>",
    " ]. A systematic review of the literature concluded that DHEA replacement does
    not appear to improve memory or other aspects of cognitive function in older adults
    [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/263/abstract/36\">",
    " 36",
    " </a>",
    " ].",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H14\">",
    " <span class=\"h2\">",
    " Vaginal atrophy",
    " </span>",
    " &nbsp;&mdash;&nbsp;Intravaginal DHEA administration may be a novel therapy for
    postmenopausal women with atrophic vaginitis and sexual dysfunction. In a trial of
    postmenopausal women with symptomatic vaginal atrophy, 12 weeks of intravaginal
    DHEA administration corrected signs and symptoms of atrophy and, when compared with
    placebo, appeared to improve some measures of sexual function [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/263/abstract/37,38\">",
    " 37,38",
    " </a>",
    " ]. No significant increases in serum DHEA or estrogen concentrations were
    seen. Further study is necessary to know if this will be a safe and effective
    therapy. This agent is not commercially available. Other treatments for vaginal
    atrophy are reviewed separately. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?6/50/6954?
    source=see_link\">",
    " \"Treatment of vaginal atrophy\"",
    " </a>",
    " .)",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H15\">",
    " <span class=\"h1\">",
    " ADVERSE EFFECTS",
    " </span>",
    " &nbsp;&mdash;&nbsp;Women taking DHEA may achieve serum DHEA concentrations in
    the supraphysiologic range [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/263/abstract/23,26,33\">",
    " 23,26,33",
    " </a>",
    " ], and increases in serum testosterone concentrations [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/263/abstract/29\">",
    " 29",
    " </a>",
    " ], raising concerns about long-term metabolic. Most studies report androgenic
    side effects including oily skin, hirsutism, and acne.",
    " </p>",
    " <p>",
    " Other adverse effects include:",
    " </p>",
    " <p>",
    " <ul class=\"bullet-block\">",
    " <li>",
    " Lower serum HDL cholesterol concentrations in most [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/263/abstract/23,24,27\">",
    " 23,24,27",
    " </a>",
    " ], but not all [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/263/abstract/28\">",
    " 28",
    " </a>",
    " ] trials.",
    " </li>",
    " <li>",
    " DHEA replacement has been associated with cases of mania and palpitations
    [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/263/abstract/39,40\">",
    " 39,40",
    " </a>",
    " ].",
    " </li>",
    " </ul>",
    " </p>",
    " <p>",
    " Although serious adverse effects have not been reported, the long-term safety
    of DHEA therapy has not been established. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?41/47/42745?
    source=see_link&amp;anchor=H13#H13\">",
    " \"Treatment of adrenal insufficiency in adults\", section on 'Androgen
    replacement (DHEA)'",
    " </a>",
    " .)",
    " </p>",
    " <p>",
    " In summary, most data suggest that DHEA replacement in older men and women
    does not have a significant effect on psychological well-being, body composition,
    muscle strength, or insulin sensitivity. While there may be improvements in bone
    density, the changes are very small and of uncertain clinical importance.",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H16\">",
    " <span class=\"h1\">",
    " SUMMARY AND RECOMMENDATIONS",
    " </span>",
    " &nbsp;&mdash;&nbsp;DHEA has been proposed to have many actions, including
    vasodilatory, anti-aging, anti-inflammatory, anti-atherosclerotic, and anti-
    depressant actions. However, the clinical benefits and safety of DHEA for a number
    of clinical conditions is not well established. While DHEA is available by
    prescription only in most countries, in the United States, DHEA is widely available
    in stores that sell health foods and nutritional supplements. However, quality
    control (purity and potency) of these over-the-counter products has been shown to
    be quite poor [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/263/abstract/4,5\">",
    " 4,5",
    " </a>",
    " ].",
    " </p>",
    " <p>",
    " <ul class=\"bullet-block\">",
    " <li>",
    " We suggest DHEA therapy only in women with adrenal insufficiency with
    impaired mood or sense of well-being despite optimal glucocorticoid and, if needed,
    mineralocorticoid replacement. However, this approach is limited by the lack of
    reliable source of this compound in some countries (",
    " <a class=\"grade\" href=\"._grade_5?title=Grade 2B\">",
    " Grade 2B",
    " </a>",
    " ). Its role in men with adrenal insufficiency is not well-established.
    (See",
    " <a class=\"local\" href=\"#H3\">",
    " 'Use in adrenal insufficiency'",
    " </a>",
    " above and",
    " <a class=\"medical medical_review\" href=\"UTD.htm?41/47/42745?
    source=see_link&amp;anchor=H13#H13\">",
    " \"Treatment of adrenal insufficiency in adults\", section on 'Androgen
    replacement (DHEA)'",
    " </a>",
    " .)",
    " </li>",
    " <li>",
    " We suggest not using DHEA for other indications, including athletic
    performance enhancement, treatment of SLE, Sj&ouml;gren&rsquo;s syndrome
    depression, or as androgen replacement in otherwise healthy postmenopausal women
    and elderly individuals (",
    " <a class=\"grade\" href=\"._grade_5?title=Grade 2B\">",
    " Grade 2B",
    " </a>",
    " ). (See",
    " <a class=\"local\" href=\"#H4\">",
    " 'Other proposed uses'",
    " </a>",
    " above.)",
    " </li>",
    " <li>",
    " In preliminary studies, locally administered intra-vaginal DHEA at low doses
    may be effective for vaginal dryness. (See",
    " <a class=\"local\" href=\"#H14\">",
    " 'Vaginal atrophy'",
    " </a>",
    " above.)",
    " </li>",
    " </ul>",
    " </p>",
    " </div>",
    " <div id=\"topicAgreement\">",
    " Use of UpToDate is subject to the",
    " <a class=\"licenseLink\" href=\"./license\" id=\"sla_in_page\"
    target=\"_blank\">",
    " Subscription and License Agreement",
    " </a>",
    " .",
    " </div>",
    " <div class=\"headingAnchor\" id=\"references\">",
    " <h1>",
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    " </h1>",
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    " Morales AJ, Haubrich RH, Hwang JY, et al. The effect of six months treatment
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    " Huppert FA, Van Niekerk JK. Dehydroepiandrosterone (DHEA) supplementation
    for cognitive function . Cochrane Database Syst Rev 2001; :CD000304.",
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    " Labrie F, Archer D, Bouchard C, et al. Serum steroid levels during 12-week
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    " Labrie F, Archer D, Bouchard C, et al. Intravaginal dehydroepiandrosterone
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    " </li>",
    " <li>",
    " The Medical Letter May 9, 2005; 47:37.",
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    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/16/263/abstract/40\">",
    " Sahelian R, Borken S. Dehydroepiandrosterone and cardiac arrhythmia. Ann
    Intern Med 1998; 129:588.",
    " </a>",
    " </li>",
    " </ol>",
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    var title_f0_16_264="Technical aspects of nocturnal hemodialysis";
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    " <div id=\"topicContent\">",
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    " Technical aspects of nocturnal hemodialysis",
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    " Author",
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    0/16/264/contributors\">",
    " Andreas Pierratos, MD, FRCPC",
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    " Steve J Schwab, MD",
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    " <p class=\"headingAnchor\" id=\"H1\">",
    " <span class=\"h1\">",
    " INTRODUCTION AND OVERVIEW",
    " </span>",
    " &nbsp;&mdash;&nbsp;The mortality rate of patients undergoing maintenance
    hemodialysis is unacceptably high [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/264/abstract/1\">",
    " 1",
    " </a>",
    " ]. An extremely high morbidity, relatively low quality of life (due in part to
    a high level of dependence and unemployment), and high cost of care have also been
    observed.",
    " </p>",
    " <p>",
    " Instituting more intensive dialysis regimens appears to improve morbidity and
    possible mortality in this patient population. Compared to conventional three times
    per week regimens, for example, dialysis associated with longer duration",
    " <span class=\"nowrap\">",
    " and/or",
    " </span>",
    " higher frequency correlates with enhanced outcomes [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/264/abstract/2-7\">",
    " 2-7",
    " </a>",
    " ]. However, the HEMO study found that increasing the dialysis dose within the
    general restrictions of a thrice weekly regimen failed to decrease patient
    mortality [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/264/abstract/8-10\">",
    " 8-10",
    " </a>",
    " ]. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?36/13/37082?
    source=see_link\">",
    " \"Patient survival and maintenance dialysis\"",
    " </a>",
    " and",
    " <a class=\"medical medical_review\" href=\"UTD.htm?6/14/6378?
    source=see_link\">",
    " \"Kt/V and the adequacy of hemodialysis\"",
    " </a>",
    " .)",
    " </p>",
    " <p>",
    " Given these findings, nocturnal hemodialysis (eg, long nightly home
    hemodialysis) was introduced as a (possibly) more desirable alternative to
    conventional dialysis, since it provides superior dialysis based upon dose,
    duration, and frequency. This can be accomplished because it is performed during
    nightly sleep, an otherwise unproductive time [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/264/abstract/11\">",
    " 11",
    " </a>",
    " ].",
    " </p>",
    " <p>",
    " Although Sheldon is credited for overnight dialysis at home [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/264/abstract/12\">",
    " 12",
    " </a>",
    " ], Uldall started the first quotidian (daily) nocturnal hemodialysis program
    in 1994 in Toronto [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/264/abstract/11,13\">",
    " 11,13",
    " </a>",
    " ]. Since then, its use has been extended to more centers in Canada, the United
    States, Australia, and several European countries [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/264/abstract/14-17\">",
    " 14-17",
    " </a>",
    " ].",
    " </p>",
    " <p>",
    " A description of nocturnal hemodialysis, particularly the exact regimen
    associated with the procedure, will be presented here. Outcomes associated with
    nocturnal hemodialysis and an overview of short daily hemodialysis are presented
    separately. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?3/24/3465?
    source=see_link\">",
    " \"Outcomes associated with nocturnal hemodialysis\"",
    " </a>",
    " and",
    " <a class=\"medical medical_review\" href=\"UTD.htm?17/45/18137?
    source=see_link\">",
    " \"Short daily hemodialysis\"",
    " </a>",
    " .)",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H2\">",
    " <span class=\"h1\">",
    " DIALYSIS REGIMEN AND PRESCRIPTION",
    " </span>",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H541554921\">",
    " <span class=\"h2\">",
    " Regimen schedule",
    " </span>",
    " &nbsp;&mdash;&nbsp;Nocturnal hemodialysis is performed either at home or in a
    dialysis facility. When it is done at home, the frequency of dialysis varies from
    three to seven nights per week. Facility-based nocturnal hemodialysis is performed
    three nights per week [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/264/abstract/18\">",
    " 18",
    " </a>",
    " ].",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H3\">",
    " <span class=\"h2\">",
    " Required personnel",
    " </span>",
    " &nbsp;&mdash;&nbsp;Facility-based dialysis is usually performed by the
    facility staff. Home dialysis is performed by the patient or a helper (unpaid or
    paid). A partner is",
    " <strong>",
    " NOT",
    " </strong>",
    " absolutely required for nocturnal dialysis at home since this procedure is
    associated with significant hemodynamic stability.",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H4\">",
    " <span class=\"h2\">",
    " Time",
    " </span>",
    " &nbsp;&mdash;&nbsp;Nocturnal hemodialysis is performed during sleep for a
    variable amount of time (usually 6 to more than 10 hours) depending upon the length
    of sleep desired. For facility-based dialysis, the duration of the dialysis session
    is generally also dictated by facility logistics.",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H5\">",
    " <span class=\"h2\">",
    " Dialysate composition",
    " </span>",
    " &nbsp;&mdash;&nbsp;The typical composition of the dialysate is as follows:",
    " </p>",
    " <p>",
    " <ul class=\"bullet-block\">",
    " <li>",
    " Sodium &mdash; 140",
    " <span class=\"nowrap\">",
    " mEq/L",
    " </span>",
    " </li>",
    " <li>",
    " Potassium &mdash; 2",
    " <span class=\"nowrap\">",
    " mEq/L",
    " </span>",
    " </li>",
    " <li>",
    " Bicarbonate &mdash; 30",
    " <span class=\"nowrap\">",
    " mEq/L",
    " </span>",
    " for nightly regimen and 35 mEq for every other night or thrice weekly
    regimens",
    " </li>",
    " <li>",
    " Calcium &mdash; 2.5 to 4",
    " <span class=\"nowrap\">",
    " mEq/L",
    " </span>",
    " (1.25 to 2",
    " <span class=\"nowrap\">",
    " mmol/L),",
    " </span>",
    " with average of 3.2",
    " <span class=\"nowrap\">",
    " mEq/L",
    " </span>",
    " (1.6",
    " <span class=\"nowrap\">",
    " mmol/L).",
    " </span>",
    " The dialysate calcium concentration is adjusted to keep parathyroid hormone
    levels in the desirable range while maintaining normal predialysis calcium
    concentrations. This may require the postdialysis serum calcium to be often in the
    hypercalcemic range. The dialysate calcium concentration can be adjusted by varying
    the amount of",
    " <a class=\"drug drug_general\" href=\"UTD.htm?15/27/15799?
    source=see_link\">",
    " calcium chloride",
    " </a>",
    " powder added to the dialysate by the patient (eg, 7 mL of calcium chloride
    powder added to 4 L of acid dialysate concentrate increases calcium concentration
    by approximately 0.5",
    " <span class=\"nowrap\">",
    " mEq/L",
    " </span>",
    " [0.25",
    " <span class=\"nowrap\">",
    " mmol/L]).",
    " </span>",
    " <br/>",
    " <br/>",
    " A higher dialysate calcium is prescribed in patients with high
    ultrafiltration volumes (see below). Such patients are more likely to be in
    negative calcium balance since the ultrafiltrate contains ionized calcium; thus,
    the larger the volume removed, the more calcium is lost [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/264/abstract/19\">",
    " 19",
    " </a>",
    " ]. Pregnancy or hungry bone syndrome also requires higher levels of
    dialysate calcium [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/264/abstract/20\">",
    " 20",
    " </a>",
    " ]. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?3/13/3287?
    source=see_link\">",
    " \"Hungry bone syndrome following parathyroidectomy\"",
    " </a>",
    " .)",
    " </li>",
    " <li>",
    " Phosphate &mdash; 0 to 4.5",
    " <span class=\"nowrap\">",
    " mg/dL",
    " </span>",
    " (0 to 1.5",
    " <span class=\"nowrap\">",
    " mmol/L),",
    " </span>",
    " typically 1.2",
    " <span class=\"nowrap\">",
    " mg/dL",
    " </span>",
    " (0.4",
    " <span class=\"nowrap\">",
    " mmol/L).",
    " </span>",
    " <a class=\"drug drug_general\" href=\"UTD.htm?5/22/5480?source=see_link\">",
    " Sodium phosphate",
    " </a>",
    " (in the form of Fleet enema) is added, if needed, into the acid or
    bicarbonate concentrate. The dialysate phosphate concentration is adjusted to
    maintain pre- and postdialysis phosphate concentrations within the normal range.
    The typical dose of Fleet enema is 30 to 60 mL per dialysate concentrate jug, but
    amounts as high as 200 mL can be used as a source of phosphate for those with
    higher requirements such as pregnant patients or those with hungry bone syndrome
    [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/264/abstract/20,21\">",
    " 20,21",
    " </a>",
    " ]. Calcium and phosphate do not precipitate in the presence of the acidic pH
    of the acid concentrate [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/264/abstract/22\">",
    " 22",
    " </a>",
    " ]. Patients on intermittent nocturnal hemodialysis are less likely to need
    phosphate additive.",
    " </li>",
    " </ul>",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H6\">",
    " <span class=\"h2\">",
    " Blood and dialysate flow rates",
    " </span>",
    " &nbsp;&mdash;&nbsp;Since blood flow as low as or below 200",
    " <span class=\"nowrap\">",
    " mL/min",
    " </span>",
    " is adequate for most patients undergoing nocturnal hemodialysis, a poorly
    functioning dialysis catheter and a single-needle system (when using a fistula or
    graft) can provide adequate flow. A single needle system provides extra safety, as
    accidental disconnection can trigger an air detector alarm. A typical blood flow is
    200 to 300",
    " <span class=\"nowrap\">",
    " mL/min.",
    " </span>",
    " Lower flows can be used in children [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/264/abstract/23\">",
    " 23",
    " </a>",
    " ], although higher flows can be used as well [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/264/abstract/24\">",
    " 24",
    " </a>",
    " ].",
    " </p>",
    " <p>",
    " The dialysate flow rate is also variable. This can range from 100 to 800",
    " <span class=\"nowrap\">",
    " mL/min.",
    " </span>",
    " </p>",
    " <p>",
    " A typical regimen is a blood flow rate of 200 to 300",
    " <span class=\"nowrap\">",
    " mL/min",
    " </span>",
    " and a dialysate flow rate of 300",
    " <span class=\"nowrap\">",
    " mL/min.",
    " </span>",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H7\">",
    " <span class=\"h2\">",
    " Ultrafiltration",
    " </span>",
    " &nbsp;&mdash;&nbsp;The typical volume of ultrafiltrate removed per day is
    approximately one to two liters, but larger volumes are well tolerated. Patients
    weigh themselves daily to maintain dry weight, which is defined as normotension
    without the need for antihypertensive medications or edema.",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H8\">",
    " <span class=\"h2\">",
    " Dialyzer membrane and hemodialysis machine",
    " </span>",
    " &nbsp;&mdash;&nbsp;Any dialyzer membrane can be used, including smaller
    surface area dialyzers. Although there are no published data, most centers use high
    flux dialyzers. In addition, nocturnal hemodialysis can be performed with any
    hemodialysis machine. Existing machines have been modified and new machines have
    been designed for use at home [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/264/abstract/25-31\">",
    " 25-31",
    " </a>",
    " ]. In the case of the NxStage machine, the usual dialysate volume is 20 to 25
    L [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/264/abstract/29\">",
    " 29",
    " </a>",
    " ]. Using this volume for nocturnal hemodialysis may not increase the removal
    of small molecules but phosphate and large molecule removal increases. In addition,
    higher dialysate volume enhances small molecule clearance. Attractive attributes of
    a home dialysis machine include ease of operation, low noise, easily accessible
    screen that dims at night, back-up battery to protect from power failure, easy
    disinfection process, and easy single needle system use.",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H9\">",
    " <span class=\"h2\">",
    " Dialyzer reuse",
    " </span>",
    " &nbsp;&mdash;&nbsp;Delayed dialyzer reprocessing has been used [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/264/abstract/32,33\">",
    " 32,33",
    " </a>",
    " ]. With this technique, dialyzer membranes are rinsed with heparinized saline
    after dialysis and subsequently stored in a small refrigerator at home. Once a
    week, these membranes are transported to the center and exchanged with a set of the
    patient's own reprocessed dialyzers. Most of the centers use new dialyzers.",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H10\">",
    " <span class=\"h2\">",
    " Anticoagulation",
    " </span>",
    " &nbsp;&mdash;&nbsp;To maintain systemic anticoagulation, the standard",
    " <a class=\"drug drug_general\" href=\"UTD.htm?39/34/40489?source=see_link\">",
    " heparin",
    " </a>",
    " regimen is the administration of approximately 1000 units of heparin per
    hour.",
    " <a class=\"drug drug_general\" href=\"UTD.htm?40/18/41254?source=see_link\">",
    " Danaparoid",
    " </a>",
    " and",
    " <a class=\"drug drug_general\" href=\"UTD.htm?19/57/20375?source=see_link\">",
    " Argatroban",
    " </a>",
    " have also been used successfully in the case of heparin allergy [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/264/abstract/34\">",
    " 34",
    " </a>",
    " ].",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H11\">",
    " <span class=\"h2\">",
    " Access",
    " </span>",
    " &nbsp;&mdash;&nbsp;Both central venous catheters and peripheral vascular
    accesses have been successfully used for nocturnal hemodialysis. When peripheral
    accesses are used however, more frequent access cannulation may result in decreased
    access survival. This was suggested by the Frequent Hemodialysis Network (FHN)
    Daily and Nocturnal trials, in which the primary vascular outcome was time to first
    access event (including repair, loss of access or access-related hospitalization),
    and the secondary vascular outcome was the time to all repairs and time to all
    losses [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/264/abstract/35\">",
    " 35",
    " </a>",
    " ].",
    " </p>",
    " <p>",
    " In the FHN Nocturnal trial 87 participants were randomly assigned to receive
    in-center six days per week hemodialysis or conventional three days per week
    hemodialysis [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/264/abstract/35\">",
    " 35",
    " </a>",
    " ]. Compared with conventional dialysis, there was a non-significant trend
    toward a higher rate of first access events associated with nocturnal dialysis (32
    versus 58 events per 100 patient years, respectively, hazard ratio [HR] 1.81, 95%
    CI 0.94&ndash;3.48). When patients with a tunneled catheter were excluded from the
    analysis, nocturnal dialysis was associated with a significantly increased risk of
    a first access event (HR 3.23, 95% CI 1.07&ndash;10.34). In the FHN Daily trial, (n
    = 245 participants), there was a higher incidence of a first access event in the
    daily group compared with the conventional group. The FHN Daily trial is discussed
    elsewhere. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?17/45/18137?
    source=see_link&amp;anchor=H26#H26\">",
    " \"Short daily hemodialysis\", section on 'Vascular access'",
    " </a>",
    " .)",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H12\">",
    " <span class=\"h3\">",
    " Catheters",
    " </span>",
    " &nbsp;&mdash;&nbsp;Any type of central venous catheter can be used for
    nocturnal hemodialysis. The capability of the catheter to provide blood flow of
    more than 200",
    " <span class=\"nowrap\">",
    " mL/min",
    " </span>",
    " is not important for most patients. A safe connection for the central catheter
    includes the use of pre-perforated catheter caps, which are not removed during
    dialysis. The InterLink (Becton-Dickinson, Utah, USA), the TEGO (ICU Medical, CA,
    USA), and the Swan-Lock (Codan, Lensahn, Germany) systems have been used [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/264/abstract/11,36,37\">",
    " 11,36,37",
    " </a>",
    " ]. Careful taping of the catheter-tubing connection is of paramount
    importance. Accidental disconnection of the venous limb can cause exsanguination
    without triggering machine alarms.",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H541554937\">",
    " <span class=\"h3\">",
    " Complications",
    " </span>",
    " </p>",
    " <p>",
    " <ul class=\"bullet-block\">",
    " <li>",
    " Thrombosis &mdash; The local instillation of 2 mg of",
    " <a class=\"drug drug_general\" href=\"UTD.htm?11/41/11929?
    source=see_link\">",
    " alteplase",
    " </a>",
    " (tissue-type plasminogen activator or tPA) has been very successful in
    restoring adequate blood flow in thrombosed catheters. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?16/3/16442?
    source=see_link&amp;anchor=H79683300#H79683300\">",
    " \"Overview of central catheters for acute and chronic hemodialysis
    access\", section on 'Catheter malfunction'",
    " </a>",
    " .) The instillation of lyophilized tPA has been practiced successfully by
    patients at home.",
    " <br/>",
    " <br/>",
    " The approach to the prevention of catheter thrombosis is variable in
    different centers. The prophylactic use of tPA has been advocated to prevent
    catheter thrombosis [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/264/abstract/38\">",
    " 38",
    " </a>",
    " ]. Most patients in our center use a small dose of",
    " <a class=\"drug drug_general\" href=\"UTD.htm?27/41/28314?
    source=see_link\">",
    " warfarin",
    " </a>",
    " to prevent catheter thrombosis. The initial dose is usually 2",
    " <span class=\"nowrap\">",
    " mg/day.",
    " </span>",
    " For patients with recurrent thrombosis, the warfarin dose is increased by 1
    mg until patency is maintained, providing the INR remains below the levels that the
    physician considers safe (usually INR below 2). [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/264/abstract/11,39\">",
    " 11,39",
    " </a>",
    " ]. A prospective randomized controlled study did not find the use of low
    dose warfarin useful in preventing catheter dysfunction however [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/264/abstract/40\">",
    " 40",
    " </a>",
    " ]. The risk of bleeding, vascular calcification related to the use of
    warfarin, and the negative trial cited should be considered for individual
    patients.",
    " </li>",
    " <li>",
    " Infection &mdash; The incidence of catheter-induced bacteremias with
    nocturnal hemodialysis is relatively low (approximately 0.35 to",
    " <span class=\"nowrap\">",
    " 1.5/1000",
    " </span>",
    " days) [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/264/abstract/36\">",
    " 36",
    " </a>",
    " ]. At our center, patients with fever and chills during the initiation of
    dialysis but without severe symptoms, such as hypotension, usually draw blood
    cultures at home and begin empiric treatment with intravenous antibiotics (usually
    1 gm of",
    " <a class=\"drug drug_general\" href=\"UTD.htm?41/41/42649?
    source=see_link\">",
    " Vancomycin",
    " </a>",
    " and 1.5",
    " <span class=\"nowrap\">",
    " mg/kg",
    " </span>",
    " of",
    " <a class=\"drug drug_general\" href=\"UTD.htm?33/35/34352?
    source=see_link\">",
    " Tobramycin",
    " </a>",
    " if they have previously tolerated such agents). The treatment is
    subsequently modified based upon culture results and continues for two weeks. If
    appropriate based upon culture results, continuation of treatment with",
    " <a class=\"drug drug_general\" href=\"UTD.htm?4/2/4136?source=see_link\">",
    " Cefazolin",
    " </a>",
    " rather than Vancomycin is encouraged. If the infection recurs (in our
    experience usually one month later), the catheter is replaced over a guidewire
    after restarting or continuing antibiotic coverage. A different site should be
    chosen if an exit site is present.",
    " <br/>",
    " <br/>",
    " Many bacteremias resolve successfully with antibiotics. We immediately
    remove the catheter with severe sepsis especially if associated with hemodynamic
    instability or suspicion of metastatic infection. The infection rate and survival
    of the catheters on nocturnal hemodialysis may be better than conventional
    hemodialysis, but data from randomized controlled studies are absent [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/264/abstract/36,41\">",
    " 36,41",
    " </a>",
    " ].",
    " <br/>",
    " <br/>",
    " This approach differs somewhat from that presented elsewhere within
    UpToDate, relating to the management of conventionally dialyzed patients with
    possibly infected hemodialysis catheters. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?29/8/29834?
    source=see_link\">",
    " \"Tunneled, cuffed hemodialysis catheter-related bacteremia\"",
    " </a>",
    " .)",
    " </li>",
    " </ul>",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H13\">",
    " <span class=\"h3\">",
    " Arteriovenous fistulas",
    " </span>",
    " &nbsp;&mdash;&nbsp;An arteriovenous (AV) fistula is the access of choice. The
    standard steel needles, blunt needles, and plastic cannulas have been used
    successfully. The buttonhole technique, which involves the insertion of the",
    " <span class=\"nowrap\">",
    " needle/cannula",
    " </span>",
    " through exactly the same hole and at the same angle and depth of penetration
    [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/264/abstract/42-45\">",
    " 42-45",
    " </a>",
    " ] is used by most patients. After 8 to 10 cannulations (or 12 to 14 in
    diabetic patients) using the buttonhole method, an epithelialized track develops
    that allows the use of blunt needles [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/264/abstract/44\">",
    " 44",
    " </a>",
    " ]. Sharp needles should be used for the first week, followed by
    &ldquo;blunt&rdquo; needles thereafter. Before cannulation, the fistula and
    surrounding skin are cleansed with",
    " <a class=\"drug drug_general\" href=\"UTD.htm?12/36/12870?source=see_link\">",
    " chlorhexidine gluconate",
    " </a>",
    " (0.5 percent in 70 percent alcohol) or povidone-iodine solution. Scabs are
    covered with an alcohol pad for five minutes and then removed using a sterile
    needle.",
    " <a class=\"drug drug_general\" href=\"UTD.htm?32/30/33252?source=see_link\">",
    " Mupirocin",
    " </a>",
    " calcium 2 percent cream (Bactroban, Glaxo-Smith-Klein) is applied to each
    buttonhole with a sterile cotton swab after hemostasis is achieved and allowed to
    air dry. A single application is provided for each HD procedure. Mupirocin
    prophylaxis appears to significantly lower the risk of staphylococcus aureus
    bacteremia with buttonhole cannulation [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/264/abstract/45\">",
    " 45",
    " </a>",
    " ].",
    " </p>",
    " <p>",
    " Buttonhole cannulation without the use of local",
    " <a class=\"drug drug_general\" href=\"UTD.htm?32/30/33252?source=see_link\">",
    " mupirocin",
    " </a>",
    " can be associated with staphylococcus aureus bacteremia often leading to life
    threatening metastatic infections. The risk of infection was examined in a
    randomized trial of 140 conventional hemodialysis patients assigned to either the
    buttonhole technique or to conventional &ldquo;rope ladder&rdquo; needling [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/264/abstract/46\">",
    " 46",
    " </a>",
    " ]. At eight weeks, the rate of localized infection was higher among patients
    assigned to the buttonhole technique compared with conventional needling (50 versus
    22.4 per 1000, respectively). There was one episode of staphylococcus aureus
    bacteremia at eight weeks and two more episodes after the study ended, but within
    twelve months, in the group utilizing the buttonhole technique versus none in the
    conventional needling group. At twelve months, the number of needling site
    abscesses requiring intravenous antibiotics was higher in the buttonhole group
    versus the conventional needling group (9 versus 0, respectively). The degree to
    which these data from conventional hemodialysis patients may be extrapolated to
    nocturnal daily hemodialysis or self-cannulating patients is not clear [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/264/abstract/47\">",
    " 47",
    " </a>",
    " ].",
    " </p>",
    " <p>",
    " As a result of the increased risk of infection, avoidance of buttonhole
    cannulation has been advocated by some experts. We have not seen any case of
    staphylococcus aureus bacteremia in our center since the",
    " <a class=\"drug drug_general\" href=\"UTD.htm?32/30/33252?source=see_link\">",
    " mupirocin",
    " </a>",
    " use started a number of years ago. Most centers do not practice the buttonhole
    technique for facility based dialysis.",
    " </p>",
    " <p>",
    " The buttonhole technique may be associated with fewer thrombotic complications
    among patients undergoing nocturnal or daily dialysis. In the FHN trial, compared
    with the rope-ladder technique, the buttonhole technique was associated with longer
    intervals between access-related events (HR 0.44, 95% CI 0.20-0.97) [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/264/abstract/35\">",
    " 35",
    " </a>",
    " ]. This benefit was driven mostly by a reduction in thrombotic episodes.
    Irrespective of technique (ie, buttonhole versus rope ladder), more frequent
    cannulation may lead to more frequent access-related complications. (See",
    " <a class=\"local\" href=\"#H11\">",
    " 'Access'",
    " </a>",
    " above.)",
    " </p>",
    " <p>",
    " To ensure the safety of the procedure, adequate taping of the needle and
    anchoring of the blood tubing are essential; enuresis pads wrapped around the
    connection are also considered essential [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/264/abstract/48\">",
    " 48",
    " </a>",
    " ]. Blood leaks trigger an audible alarm. Dedicated disposable leak sensors are
    available (RedSense Medical AB) as well as non-disposable wireless leak sensors
    that stop the blood pump when triggered (Fresenius Medical Care, Waltham, MA). No
    case of accidental disconnection has been reported.",
    " </p>",
    " <p>",
    " The single needle system provides adequate blood flow (average 200",
    " <span class=\"nowrap\">",
    " mL/min)",
    " </span>",
    " while providing extra safety in case of accidental disconnection by triggering
    an air detection alarm. Thus, it may be the access system of choice for nocturnal
    hemodialysis.",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H14\">",
    " <span class=\"h3\">",
    " Arteriovenous grafts",
    " </span>",
    " &nbsp;&mdash;&nbsp;Arteriovenous (AV) grafts have been successful. The
    buttonhole technique is not practiced with these accesses. A different hole is used
    with every dialysis following the conventional technique. Steel needles or plastic
    cannulas can be used. Preference should be given to the single needle technique to
    minimize the number of punctures.",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H15\">",
    " <span class=\"h2\">",
    " Remote monitoring",
    " </span>",
    " &nbsp;&mdash;&nbsp;Some centers practice live remote monitoring of patients at
    home via either regular telephone lines or the Internet [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/264/abstract/48-50\">",
    " 48-50",
    " </a>",
    " ]. All the information available on the dialysis machine, including conditions
    that trigger alarms, is available to an observer at the center. The patient who is
    not awakened by the alarm is called.",
    " </p>",
    " <p>",
    " Live monitoring provides the following benefits:",
    " </p>",
    " <p>",
    " <ul class=\"bulletCompact-block\">",
    " <li>",
    " Helps prevent blood from clotting in an idle extracorporeal system",
    " </li>",
    " <li>",
    " Provides reassurance to the patient",
    " </li>",
    " <li>",
    " Ensures compliance",
    " </li>",
    " <li>",
    " Aides the collection of data",
    " </li>",
    " </ul>",
    " </p>",
    " <p>",
    " Despite these benefits, such monitoring has not yet detected life-threatening
    conditions. Thus, its use should be considered optional [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/264/abstract/24\">",
    " 24",
    " </a>",
    " ]. Most centers do not practice remote monitoring of patients on nocturnal
    hemodialysis although some centers use remote monitoring for selected patients or
    for short periods of time (three months).",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H16\">",
    " <span class=\"h2\">",
    " Additional safety measures",
    " </span>",
    " &nbsp;&mdash;&nbsp;Two inexpensive moisture sensors are placed strategically
    on the floor to detect dialysate and blood leaks.",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H17\">",
    " <span class=\"h1\">",
    " PATIENT SELECTION AND TRAINING",
    " </span>",
    " &nbsp;&mdash;&nbsp;All patients capable of performing home hemodialysis or
    those with home helpers are eligible for nocturnal hemodialysis. Exclusion criteria
    include acute illnesses, uncontrolled seizure activity, and contraindication to
    systemic anticoagulation [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/264/abstract/24\">",
    " 24",
    " </a>",
    " ]. The presence of older age, an unstable cardiovascular system, hypotension,
    diabetes mellitus,",
    " <span class=\"nowrap\">",
    " and/or",
    " </span>",
    " ascites are all indications, and not contraindications, for nocturnal
    hemodialysis. An aid to facilitate the home dialysis choice for patients has been
    published [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/264/abstract/51\">",
    " 51",
    " </a>",
    " ].",
    " </p>",
    " <p>",
    " Patient groups that can be preferentially targeted for nocturnal hemodialysis
    include the following:",
    " </p>",
    " <p>",
    " <ul class=\"bullet-block\">",
    " <li>",
    " Incident patients followed in a chronic kidney disease (CKD) clinic. To
    prevent the state of dependence frequently encountered in in-center dialysis units,
    training should be instituted early or patients should be dialyzed temporarily in
    self-care settings.",
    " </li>",
    " <li>",
    " Patients ineligible for kidney transplantation. Nocturnal hemodialysis can
    be viewed as the dialysis modality closest to kidney transplantation [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/264/abstract/52\">",
    " 52",
    " </a>",
    " ].",
    " </li>",
    " <li>",
    " Patients with significant morbidity, including cardiac disease, diabetes
    mellitus, severe hypertension, dialysis-related symptoms, or large intradialytic
    weight gains.",
    " </li>",
    " <li>",
    " Patients who require conversion from peritoneal dialysis to hemodialysis and
    who want to maintain independence.",
    " </li>",
    " <li>",
    " Large-size patients or patients not adequately dialyzed because of poor
    access flow.",
    " </li>",
    " </ul>",
    " </p>",
    " <p>",
    " The length of training depends upon the patient's previous experience. The
    typical duration for a previously untrained patient is six weeks [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/264/abstract/53\">",
    " 53",
    " </a>",
    " ]. During the first five weeks, patients are dialyzed on conventional or short
    daily hemodialysis. Although not mandatory, patients generally sleep in the
    training facility while on nocturnal hemodialysis during the last one to three
    nights. Training includes drawing blood samples for laboratory tests and blood
    cultures, as well as self-administering intravenous medications including
    antibiotics and iron preparations. Supplies at home include test tubes, a
    centrifuge, blood culture bottles, antibiotics, and in selected cases lyophilized
    rTPA.",
    " </p>",
    " <p>",
    " The adoption of nocturnal hemodialysis may be hampered by patient-perceived
    barriers, including lack of confidence in their ability to perform necessary duties
    (eg, self-cannulation), fear of a possible catastrophic event, and the reluctance
    to burden family members [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/264/abstract/54\">",
    " 54",
    " </a>",
    " ]. Financial barriers can be significant. Costs include increased home utility
    fees for the patients and low dialysis reimbursement rates especially when more
    than thrice weekly dialysis is planned.",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H18\">",
    " <span class=\"h1\">",
    " SUMMARY AND RECOMMENDATIONS",
    " </span>",
    " </p>",
    " <p>",
    " <ul class=\"bullet-block\">",
    " <li>",
    " Nocturnal hemodialysis can be practiced in the facility (thrice weekly) or
    at home (three to seven nights per week). Home nocturnal hemodialysis is performed
    either by the patient or partner (a partner not being absolutely required) during
    sleep for a variable amount of time, based upon the length of sleep desired
    (usually 6 to 10 hours in total). (See",
    " <a class=\"local\" href=\"#H3\">",
    " 'Required personnel'",
    " </a>",
    " above and",
    " <a class=\"local\" href=\"#H4\">",
    " 'Time'",
    " </a>",
    " above.)",
    " </li>",
    " <li>",
    " Compared with conventional hemodialysis and depending on the frequency the
    dialysate contains lower levels of bicarbonate, higher levels of calcium, and often
    contains phosphate. Typical flow rates are a blood flow rate of 200 to 300",
    " <span class=\"nowrap\">",
    " mL/min",
    " </span>",
    " and a dialysate flow rate of 300",
    " <span class=\"nowrap\">",
    " mL/min.",
    " </span>",
    " The typical volume of ultrafiltrate removed per day is approximately 1 to 2
    liters but higher volumes are well tolerated. (See",
    " <a class=\"local\" href=\"#H5\">",
    " 'Dialysate composition'",
    " </a>",
    " above and",
    " <a class=\"local\" href=\"#H7\">",
    " 'Ultrafiltration'",
    " </a>",
    " above and",
    " <a class=\"local\" href=\"#H6\">",
    " 'Blood and dialysate flow rates'",
    " </a>",
    " above.)",
    " </li>",
    " <li>",
    " To maintain systemic anticoagulation, the standard",
    " <a class=\"drug drug_general\" href=\"UTD.htm?39/34/40489?
    source=see_link\">",
    " heparin",
    " </a>",
    " regimen is the administration of approximately 1000 units of heparin per
    hour. Central venous catheters, arteriovenous fistulas, and arteriovenous grafts
    have been successfully used for nocturnal hemodialysis. Safety devices are
    important to prevent accidental access disconnection and bleeding during sleep. An
    arteriovenous (AV) fistula is the preferred vascular access using a single needle
    system. The use of the &lsquo;buttonhole&rsquo; technique offers advantages, but is
    associated with high rate of systemic infections by staphylococcus aureus. Local
    application of",
    " <a class=\"drug drug_general\" href=\"UTD.htm?32/30/33252?
    source=see_link\">",
    " mupirocin",
    " </a>",
    " cream at the puncture site appears to decrease or eliminate this risk.
    (See",
    " <a class=\"local\" href=\"#H10\">",
    " 'Anticoagulation'",
    " </a>",
    " above and",
    " <a class=\"local\" href=\"#H11\">",
    " 'Access'",
    " </a>",
    " above.)",
    " </li>",
    " <li>",
    " Some centers practice live remote monitoring of patients at home either via
    regular telephone lines or the Internet, while others do not practice remote
    monitoring. Its use should be considered optional. (See",
    " <a class=\"local\" href=\"#H15\">",
    " 'Remote monitoring'",
    " </a>",
    " above.)",
    " </li>",
    " <li>",
    " All patients capable of performing home hemodialysis are eligible for
    nocturnal hemodialysis. Exceptions include acute illnesses, uncontrolled seizures,
    and contraindication to systemic anticoagulation. Significant comorbidities can be
    indications rather than contraindications for nocturnal hemodialysis. (See",
    " <a class=\"local\" href=\"#H17\">",
    " 'Patient selection and training'",
    " </a>",
    " above.)",
    " </li>",
    " </ul>",
    " </p>",
    " </div>",
    " <div id=\"topicAgreement\">",
    " Use of UpToDate is subject to the",
    " <a class=\"licenseLink\" href=\"./license\" id=\"sla_in_page\"
    target=\"_blank\">",
    " Subscription and License Agreement",
    " </a>",
    " .",
    " </div>",
    " <div class=\"headingAnchor\" id=\"references\">",
    " <h1>",
    " REFERENCES",
    " </h1>",
    " <ol id=\"reference\">",
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    " Al-Hejaili F, Kortas C, Leitch R, et al. Nocturnal but not short hours
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    " Barua M, Hladunewich M, Keunen J, et al. Successful pregnancies on nocturnal
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    " Ing TS, Yu AW, Agrawal B, et al. Increasing plasma phosphorus values by
    enriching with phosphorus the \"acid concentrate\" of a bicarbonate-buffered
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    " Geary DF, Piva E, Tyrrell J, et al. Home nocturnal hemodialysis in children.
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    " Kelly TD. Baxter Aurora dialysis system. Semin Dial 2004; 17:154.",
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    " Schlaeper C, Diaz-Buxo JA. The Fresenius Medical Care home hemodialysis
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    " Clark WR, Turk JE Jr. The NxStage System One. Semin Dial 2004; 17:167.",
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    " Ash SR. The Allient dialysis system. Semin Dial 2004; 17:164.",
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    " Trewin E. Bellco Formula Domus Home Care System. Semin Dial 2004; 17:156.",
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    " Pierratos, A, Francoeur, R, Ouwendyk, M. Delayed dialyzer reprocessing for
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    " Twardowski ZJ. Dialyzer reuse-Part I: Historical perspective. Semin Dial
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    " Faratro R, D'Gama C, Chan C. The use of alternative anti-coagulation
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    " Suri RS, Larive B, Sherer S, et al. Risk of vascular access complications
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    " Pipkin M, Craft V, Spencer M, Lockridge RS Jr. Six years of experience with
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    " Eloot S, De Vos JY, Hombrouckx R, Verdonck P. How much is catheter flow
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    " Hemmelgarn BR, Moist LM, Lok CE, et al. Prevention of dialysis catheter
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    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/16/264/abstract/39\">",
    " Twardowski, ZJ. Stepwise Anticoagulation with Warfarin for Prevention of
    Intravenous Catheter Thrombosis. Hemodialysis Int 2000; 4:37.",
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    " Wilkieson TJ, Ingram AJ, Crowther MA, et al. Low-intensity adjusted-dose
    warfarin for the prevention of hemodialysis catheter failure: a randomized,
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    " Perl J, Lok CE, Chan CT. Central venous catheter outcomes in nocturnal
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    " Twardowski, Z, Kubara, H. Different sites versus constant sites of needle
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    " Hashmi A, Cheema MQ, Moss AH. Hemodialysis patients' experience with and
    attitudes toward the buttonhole technique for arteriovenous fistula cannulation.
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    " </a>",
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    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/16/264/abstract/45\">",
    " Nesrallah GE, Cuerden M, Wong JH, Pierratos A. Staphylococcus aureus
    bacteremia and buttonhole cannulation: long-term safety and efficacy of mupirocin
    prophylaxis. Clin J Am Soc Nephrol 2010; 5:1047.",
    " </a>",
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    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/16/264/abstract/46\">",
    " MacRae JM, Ahmed SB, Atkar R, Hemmelgarn BR. A randomized trial comparing
    buttonhole with rope ladder needling in conventional hemodialysis patients. Clin J
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    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/16/264/abstract/47\">",
    " Zimmerman D, Lok CE. Accessing the access. Clin J Am Soc Nephrol 2012;
    7:1548.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/16/264/abstract/48\">",
    " Pierratos A. Nocturnal home haemodialysis: an update on a 5-year experience.
    Nephrol Dial Transplant 1999; 14:2835.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/16/264/abstract/49\">",
    " Hoy, CD. Remote Monitoring of Daily Nocturnal Hemodialysis. Hemodialysis Int
    2001; 4:8.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/16/264/abstract/50\">",
    " Heidenheim AP, Leitch R, Kortas C, et al. Patient monitoring in the London
    Daily/Nocturnal Hemodialysis Study. Am J Kidney Dis 2003; 42:61.",
    " </a>",
    " </li>",
    " <li>",
    " MATCH-D group. Method to assess treatment choices for home dialysis (MATCH-
    D). 2011. file://www.homedialysis.org/files/pros/MatchD2009.pdf.",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/16/264/abstract/52\">",
    " Pauly RP, Gill JS, Rose CL, et al. Survival among nocturnal home
    haemodialysis patients compared to kidney transplant recipients. Nephrol Dial
    Transplant 2009; 24:2915.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/16/264/abstract/53\">",
    " Leitch R, Ouwendyk M, Ferguson E, et al. Nursing issues related to patient
    selection, vascular access, and education in quotidian hemodialysis. Am J Kidney
    Dis 2003; 42:56.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/16/264/abstract/54\">",
    " Cafazzo JA, Leonard K, Easty AC, et al. Patient-perceived barriers to the
    adoption of nocturnal home hemodialysis. Clin J Am Soc Nephrol 2009; 4:784.",
    " </a>",
    " </li>",
    " </ol>",
    " </div>",
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    " <div id=\"innerOutline\">",
    " <h1>",
    " TOPIC OUTLINE",
    " </h1>",
    " <div id=\"outline\">",
    " <ul>",
    " <li>",
    " <a class=\"sr_button\" href=\"#H18\" id=\"summRecButton\">",
    " <span>",
    " SUMMARY &amp; RECOMMENDATIONS",
    " </span>",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#H1\">",
    " INTRODUCTION AND OVERVIEW",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#H2\">",
    " DIALYSIS REGIMEN AND PRESCRIPTION",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H541554921\">",
    " Regimen schedule",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H3\">",
    " Required personnel",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H4\">",
    " Time",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H5\">",
    " Dialysate composition",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H6\">",
    " Blood and dialysate flow rates",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H7\">",
    " Ultrafiltration",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H8\">",
    " Dialyzer membrane and hemodialysis machine",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H9\">",
    " Dialyzer reuse",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H10\">",
    " Anticoagulation",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H11\">",
    " Access",
    " </a>",
    " </li>",
    " <li class=\"dashItem\">",
    " <a class=\"outlineLink\" href=\"#H12\">",
    " - Catheters",
    " </a>",
    " </li>",
    " <li class=\"dashItem\">",
    " <a class=\"outlineLink\" href=\"#H541554937\">",
    " - Complications",
    " </a>",
    " </li>",
    " <li class=\"dashItem\">",
    " <a class=\"outlineLink\" href=\"#H13\">",
    " - Arteriovenous fistulas",
    " </a>",
    " </li>",
    " <li class=\"dashItem\">",
    " <a class=\"outlineLink\" href=\"#H14\">",
    " - Arteriovenous grafts",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H15\">",
    " Remote monitoring",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H16\">",
    " Additional safety measures",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#H17\">",
    " PATIENT SELECTION AND TRAINING",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#H18\">",
    " SUMMARY AND RECOMMENDATIONS",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a href=\"#references\">",
    " REFERENCES",
    " </a>",
    " </li>",
    " </ul>",
    " </div>",
    " <h1>",
    " RELATED TOPICS",
    " </h1>",
    " <div id=\"relatedTopics\">",
    " <ul>",
    " <li class=\"plainItem\">",
    " <a class=\"medical medical_review\" href=\"UTD.htm?3/13/3287?
    source=related_link\">",
    " Hungry bone syndrome following parathyroidectomy",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"medical medical_review\" href=\"UTD.htm?6/14/6378?
    source=related_link\">",
    " Kt/V and the adequacy of hemodialysis",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"medical medical_review\" href=\"UTD.htm?3/24/3465?
    source=related_link\">",
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    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"medical medical_review\" href=\"UTD.htm?16/3/16442?
    source=related_link\">",
    " Overview of central catheters for acute and chronic hemodialysis access",
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    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"medical medical_review\" href=\"UTD.htm?36/13/37082?
    source=related_link\">",
    " Patient survival and maintenance dialysis",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"medical medical_review\" href=\"UTD.htm?17/45/18137?
    source=related_link\">",
    " Short daily hemodialysis",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"medical medical_review\" href=\"UTD.htm?29/8/29834?
    source=related_link\">",
    " Tunneled, cuffed hemodialysis catheter-related bacteremia",
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    " </li>",
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    " </div>",
    " </div>"].join("\n");
    var title_f0_16_265="Treatment and prognosis of Guillain-Barré syndrome in adults";
    var content_f0_16_265=[" <noscript>",
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    " <!-- TC:TOPIC_PAGE -->",
    " <div id=\"topicContent\">",
    " <div id=\"topicTitle\">",
    " Treatment and prognosis of Guillain-Barr&eacute; syndrome in adults",
    " </div>",
    " <div id=\"topicContributors\">",
    " <div>",
    " <a id=\"authors\">",
    " </a>",
    " <a class=\"contributor contributor_credentials contributorType\"
    href=\"UTD.htm?0/16/265/contributors\">",
    " Author",
    " </a>",
    " <br/>",
    " <a class=\"contributor contributor_credentials\" href=\"UTD.htm?
    0/16/265/contributors\">",
    " Francine J Vriesendorp, MD",
    " </a>",
    " <br/>",
    " </div>",
    " <div>",
    " <a class=\"contributor contributor_credentials contributorType\"
    href=\"UTD.htm?0/16/265/contributors\">",
    " Section Editor",
    " </a>",
    " <br/>",
    " <a class=\"contributor contributor_credentials\" href=\"UTD.htm?
    0/16/265/contributors\">",
    " Jeremy M Shefner, MD, PhD",
    " </a>",
    " <br/>",
    " </div>",
    " <div>",
    " <a class=\"contributor contributor_credentials contributorType\"
    href=\"UTD.htm?0/16/265/contributors\">",
    " Deputy Editor",
    " </a>",
    " <br/>",
    " <a class=\"contributor contributor_credentials\" href=\"UTD.htm?
    0/16/265/contributors\">",
    " John F Dashe, MD, PhD",
    " </a>",
    " <br/>",
    " </div>",
    " </div>",
    " <div id=\"disclosures\">",
    " <a href=\"UTD.htm?0/16/265/contributor-disclosure\" target=\"_blank\">",
    " Disclosures",
    " </a>",
    " </div>",
    " <div id=\"reviewProcess\">",
    " <span>",
    " All topics are updated as new evidence becomes available and our",
    " </span>",
    " <a href=\"/home/editorial-policy\" target=\"_blank\">",
    " peer review process",
    " </a>",
    " <span>",
    " is complete.",
    " </span>",
    " </div>",
    " <div id=\"literatureReviewDate\">",
    " <span class=\"emphasis\">",
    " Literature review current through:",
    " </span>",
    " Oct 2013.",
    " <span class=\"pipeSpace\">",
    " |",
    " </span>",
    " <span class=\"emphasis\">",
    " This topic last updated:",
    " </span>",
    " Mar 20, 2013.",
    " </div>",
    " <div id=\"topicText\">",
    " <p class=\"headingAnchor\" id=\"H1\">",
    " <span class=\"h1\">",
    " INTRODUCTION",
    " </span>",
    " &nbsp;&mdash;&nbsp;The acute immune-mediated polyneuropathies are classified
    under the eponym Guillain-Barr&eacute; syndrome (GBS), after the authors of early
    descriptions of the disease. GBS is an acute monophasic paralyzing illness usually
    provoked by a preceding infection.",
    " </p>",
    " <p>",
    " The treatment and prognosis of GBS in adults will be discussed here. Other
    aspects of GBS are discussed separately. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?5/22/5481?
    source=see_link\">",
    " \"Clinical features and diagnosis of Guillain-Barr&eacute; syndrome in
    adults\"",
    " </a>",
    " and",
    " <a class=\"medical medical_review\" href=\"UTD.htm?27/3/27705?
    source=see_link\">",
    " \"Overview of Guillain-Barr&eacute; syndrome in children\"",
    " </a>",
    " and",
    " <a class=\"medical medical_review\" href=\"UTD.htm?40/51/41781?
    source=see_link\">",
    " \"Treatment of Guillain-Barr&eacute; syndrome in children\"",
    " </a>",
    " .)",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H2\">",
    " <span class=\"h1\">",
    " SUPPORTIVE CARE",
    " </span>",
    " &nbsp;&mdash;&nbsp;Supportive care is extremely important in Guillain-
    Barr&eacute; syndrome (GBS) since up to 30 percent of patients develop
    neuromuscular respiratory failure requiring mechanical ventilation [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/265/abstract/1\">",
    " 1",
    " </a>",
    " ]. In addition, autonomic dysfunction may be severe enough to require
    intensive care unit (ICU) monitoring [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/265/abstract/2\">",
    " 2",
    " </a>",
    " ]. Thus, many patients with GBS are initially admitted to the ICU for close
    monitoring of respiratory, cardiac, and hemodynamic function. Less severely
    affected patients can be managed in intermediate care units, and mildly affected
    patients can be managed on the general ward with telemetry, along with monitoring
    of blood pressure and vital capacity every four hours.",
    " </p>",
    " <p>",
    " Prophylaxis for deep vein thrombosis, bladder and bowel care, physical and
    occupational therapy, and psychological support are essential. Subcutaneous
    fractionated or unfractionated",
    " <a class=\"drug drug_general\" href=\"UTD.htm?39/34/40489?source=see_link\">",
    " heparin",
    " </a>",
    " and support stockings are recommended until patients are able to walk
    independently [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/265/abstract/1\">",
    " 1",
    " </a>",
    " ]. Adequate pain control is necessary. (See",
    " <a class=\"local\" href=\"#H9\">",
    " 'Pain control'",
    " </a>",
    " below.)",
    " </p>",
    " <p>",
    " Issues related to the respiratory management of patients with neuromuscular
    weakness are also discussed separately. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?34/20/35142?
    source=see_link\">",
    " \"Respiratory muscle weakness due to neuromuscular disease: Clinical
    manifestations and evaluation\"",
    " </a>",
    " .)",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H3\">",
    " <span class=\"h2\">",
    " Respiratory failure",
    " </span>",
    " &nbsp;&mdash;&nbsp;Vigilance is essential when caring for a patient with GBS,
    since deterioration due to progression of muscle weakness can occur rapidly.",
    " </p>",
    " <p>",
    " Respiratory failure in GBS is common, and 15 to 30 percent of patients need
    ventilatory support. Thus, close respiratory monitoring with frequent measurement
    of vital capacity and negative inspiratory force (NIF) should be instituted
    initially in all patients [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/265/abstract/1\">",
    " 1",
    " </a>",
    " ]. Bulbar dysfunction with swallowing problems and inability to clear
    secretions may add to the need for ventilatory support.",
    " </p>",
    " <p>",
    " <a class=\"drug drug_general\" href=\"UTD.htm?32/46/33510?source=see_link\">",
    " Succinylcholine",
    " </a>",
    " should be avoided when invasive airway management becomes necessary. The
    techniques and medications for rapid sequence intubation in adults are discussed
    separately. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?1/55/1912?
    source=see_link\">",
    " \"Rapid sequence intubation in adults\"",
    " </a>",
    " .)",
    " </p>",
    " <p>",
    " The following parameters warn of impending respiratory arrest and are an
    indication for intubation [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/265/abstract/3\">",
    " 3",
    " </a>",
    " ]:",
    " </p>",
    " <p>",
    " <ul class=\"bulletCompact-block\">",
    " <li>",
    " Forced vital capacity &lt;20",
    " <span class=\"nowrap\">",
    " mL/kg",
    " </span>",
    " </li>",
    " <li>",
    " Maximum inspiratory pressure &lt;30 cmH2O",
    " </li>",
    " <li>",
    " Maximum expiratory pressure &lt;40 cmH2O",
    " </li>",
    " </ul>",
    " </p>",
    " <p>",
    " Specific clinical findings and measurements on admission predict a high risk
    for respiratory failure. In a French prospective study of 722 patients with GBS not
    ventilated at admission, mechanical ventilation was needed in 313 (43 percent) [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/265/abstract/4\">",
    " 4",
    " </a>",
    " ]. The following factors were identified as predictors of respiratory
    failure:",
    " </p>",
    " <p>",
    " <ul class=\"bulletCompact-block\">",
    " <li>",
    " Time of onset to admission less than seven days",
    " </li>",
    " <li>",
    " Inability to cough",
    " </li>",
    " <li>",
    " Inability to stand",
    " </li>",
    " <li>",
    " Inability to lift the elbows",
    " </li>",
    " <li>",
    " Inability to lift the head",
    " </li>",
    " <li>",
    " Liver enzyme increases",
    " </li>",
    " </ul>",
    " </p>",
    " <p>",
    " In patients with at least four of these six predictors, mechanical ventilation
    was required in &gt;85 percent.",
    " </p>",
    " <p>",
    " In the 196 patients whose vital capacity was measured on admission, time from
    onset to admission of less than seven days, inability to lift the head, and vital
    capacity &lt;60 percent of normal predicted mechanical ventilation [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/265/abstract/4\">",
    " 4",
    " </a>",
    " ]. In patients with all three of these predictors, mechanical ventilation was
    required in 85 percent.",
    " </p>",
    " <p>",
    " Weaning from mechanical ventilation should be guided by improvement in
    strength and serial pulmonary function tests (PFTs) [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/265/abstract/1\">",
    " 1",
    " </a>",
    " ]. Tracheostomy should be performed after two weeks if PFTs do not show any
    significant improvement from baseline, but can be deferred for another week if PFTs
    do show improvement [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/265/abstract/1\">",
    " 1",
    " </a>",
    " ].",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H4\">",
    " <span class=\"h2\">",
    " Autonomic dysfunction",
    " </span>",
    " &nbsp;&mdash;&nbsp;Autonomic dysfunction is a well-recognized feature of GBS
    and is a significant source of mortality [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/265/abstract/5\">",
    " 5",
    " </a>",
    " ]. Dysautonomia occurs in 70 percent of patients and manifests as symptoms
    that include tachycardia (the most common), urinary retention, hypertension
    alternating with hypotension, orthostatic hypotension, bradycardia, other
    arrhythmias, ileus, and loss of sweating.",
    " </p>",
    " <p>",
    " Severe autonomic disturbances occur in about 20 percent of patients, mostly
    (but not always) in patients who develop severe weakness and respiratory failure.",
    " </p>",
    " <p>",
    " Consequently, close monitoring of blood pressure, fluid status, and cardiac
    rhythm is essential to the management of patients with GBS.",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H5\">",
    " <span class=\"h2\">",
    " Cardiovascular management",
    " </span>",
    " &nbsp;&mdash;&nbsp;In agreement with a 2005 expert review and consensus
    opinion of supportive care for patients with GBS, we recommend pulse and blood
    pressure monitoring for patients with GBS who are becoming severely affected [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/265/abstract/1\">",
    " 1",
    " </a>",
    " ]. Monitoring should be instituted at time of admission.",
    " </p>",
    " <p>",
    " Monitoring should be continued until ventilatory support is no longer
    necessary or until recovery is underway in patients not needing mechanical
    ventilation.",
    " </p>",
    " <p>",
    " Practical tips for the management of patients with GBS include the following
    [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/265/abstract/6\">",
    " 6",
    " </a>",
    " ]:",
    " </p>",
    " <p>",
    " <ul class=\"bullet-block\">",
    " <li>",
    " Quadriplegic patients should not be left unattended in the sitting position
    without assessment of orthostatic hypotension",
    " </li>",
    " <li>",
    " Intravascular volume should be maintained, particularly during positive-
    pressure ventilation",
    " </li>",
    " <li>",
    " Drugs with hypotensive side effects should be avoided if possible",
    " </li>",
    " <li>",
    " Arrhythmias frequently occur during suctioning",
    " </li>",
    " <li>",
    " Plasma exchange can cause hypotension and electrolyte disturbances",
    " </li>",
    " </ul>",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H6\">",
    " <span class=\"h3\">",
    " Blood pressure",
    " </span>",
    " &nbsp;&mdash;&nbsp;Both paroxysmal hypertension and orthostatic hypotension
    are frequent, occurring in 24 and 19 percent of patients with GBS, respectively,
    while sustained hypertension occurs in 3 percent, as described in a series of 169
    patients [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/265/abstract/6\">",
    " 6",
    " </a>",
    " ].",
    " </p>",
    " <p>",
    " Intraarterial monitoring should be instituted in the presence of significant
    blood pressure fluctuations. Hypotension can usually be treated with fluids, but
    low-dose",
    " <a class=\"drug drug_general\" href=\"UTD.htm?38/36/39488?source=see_link\">",
    " phenylephrine",
    " </a>",
    " can be used if fluids are not effective. In the presence of dysautonomia, only
    low doses of carefully titrated short-acting vasoactive agents should be used for
    treatment of hypotension and hypertension because of the potential to overshoot the
    target blood pressure in the setting of possible denervation hypersensitivity.",
    " </p>",
    " <p>",
    " Episodes of severe hypertension (MAP&gt;125) can be treated with",
    " <a class=\"drug drug_general\" href=\"UTD.htm?34/45/35544?source=see_link\">",
    " labetalol",
    " </a>",
    " ,",
    " <a class=\"drug drug_general\" href=\"UTD.htm?39/37/40536?source=see_link\">",
    " esmolol",
    " </a>",
    " , or",
    " <a class=\"drug drug_general\" href=\"UTD.htm?20/51/21302?source=see_link\">",
    " nitroprusside",
    " </a>",
    " [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/265/abstract/6,7\">",
    " 6,7",
    " </a>",
    " ]. In cases of autonomic cardiovascular dysfunction, other conditions must be
    excluded, such as pulmonary thromboembolism, hypoxemia, sepsis, gastrointestinal
    (GI) bleeding, and fluid and electrolyte disturbances [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/265/abstract/2\">",
    " 2",
    " </a>",
    " ].",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H7\">",
    " <span class=\"h3\">",
    " Arrhythmias",
    " </span>",
    " &nbsp;&mdash;&nbsp;Sustained sinus tachycardia occurs in 37 percent of
    patients and requires no treatment [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/265/abstract/6\">",
    " 6",
    " </a>",
    " ].",
    " </p>",
    " <p>",
    " Severe cardiac arrhythmias, including bradycardia and asystole, occur in about
    4 percent of patients with GBS. Other arrhythmias and electrocardiogram (EKG)
    changes have also been described: atrial fibrillation, atrial flutter, paroxysmal
    tachycardia, ventricular tachycardia, elevated or depressed ST segments, flat or
    inverted T waves, Q-T interval prolongation, axis deviation, and various conduction
    blocks [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/265/abstract/2\">",
    " 2",
    " </a>",
    " ]. Other causes of cardiovascular disease need to be excluded.",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H8\">",
    " <span class=\"h2\">",
    " Bowel and bladder care",
    " </span>",
    " &nbsp;&mdash;&nbsp;Additional autonomic problems include adynamic ileus and
    urinary retention. Daily abdominal auscultation to monitor for bowel silence and
    the development of adynamic ileus is recommended, as is monitoring of opioid
    administration.",
    " </p>",
    " <p>",
    " For treating ileus,",
    " <a class=\"drug drug_general\" href=\"UTD.htm?35/29/36304?source=see_link\">",
    " erythromycin",
    " </a>",
    " or",
    " <a class=\"drug drug_general\" href=\"UTD.htm?10/41/10901?source=see_link\">",
    " neostigmine",
    " </a>",
    " may be effective [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/265/abstract/1\">",
    " 1",
    " </a>",
    " ].",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H9\">",
    " <span class=\"h2\">",
    " Pain control",
    " </span>",
    " &nbsp;&mdash;&nbsp;Neuropathic pain occurs in about 40 to 50 percent of
    patients during the course of GBS and often requires treatment.",
    " </p>",
    " <p>",
    " <a class=\"drug drug_general\" href=\"UTD.htm?19/19/19768?source=see_link\">",
    " Gabapentin",
    " </a>",
    " or",
    " <a class=\"drug drug_general\" href=\"UTD.htm?25/10/25770?source=see_link\">",
    " carbamazepine",
    " </a>",
    " may be used for intensive care unit pain control during the acute phase of GBS
    [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/265/abstract/1,8,9\">",
    " 1,8,9",
    " </a>",
    " ]. Simple analgesics or nonsteroidal antiinflammatory drugs (NSAIDS) may be
    tried, but they often do not provide adequate pain relief. Appropriate narcotic
    analgesics may be used but require careful monitoring for adverse effects in the
    setting of autonomic denervation. Epidural",
    " <a class=\"drug drug_general\" href=\"UTD.htm?19/31/19962?source=see_link\">",
    " morphine",
    " </a>",
    " also can be useful [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/265/abstract/7\">",
    " 7",
    " </a>",
    " ].",
    " </p>",
    " <p>",
    " For the long-term management of neuropathic pain, tricyclic antidepressants,",
    " <a class=\"drug drug_general\" href=\"UTD.htm?41/50/42792?source=see_link\">",
    " tramadol",
    " </a>",
    " ,",
    " <a class=\"drug drug_general\" href=\"UTD.htm?19/19/19768?source=see_link\">",
    " gabapentin",
    " </a>",
    " ,",
    " <a class=\"drug drug_general\" href=\"UTD.htm?25/10/25770?source=see_link\">",
    " carbamazepine",
    " </a>",
    " , or",
    " <a class=\"drug drug_general\" href=\"UTD.htm?16/31/16887?source=see_link\">",
    " pregabalin",
    " </a>",
    " may be useful.",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H10\">",
    " <span class=\"h2\">",
    " Rehabilitation",
    " </span>",
    " &nbsp;&mdash;&nbsp;Acute-phase rehabilitation should include an individualized
    program of gentle strengthening, involving isometric, isotonic, isokinetic, and
    manual resistive and progressive resistive exercises [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/265/abstract/1\">",
    " 1",
    " </a>",
    " ]. Rehabilitation should emphasize proper limb positioning, posture, and
    orthotics as well as nutrition. A device to help with communication may be
    necessary.",
    " </p>",
    " <p>",
    " After the acute phase, disabled patients should be treated by a
    multidisciplinary rehabilitation team [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/265/abstract/10\">",
    " 10",
    " </a>",
    " ]. An exercise program may be beneficial for persistent fatigue [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/265/abstract/1\">",
    " 1",
    " </a>",
    " ].",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H11\">",
    " <span class=\"h1\">",
    " DISEASE MODIFYING TREATMENT",
    " </span>",
    " &nbsp;&mdash;&nbsp;The main modalities of therapy for Guillain-Barr&eacute;
    syndrome (GBS) include plasma exchange (also called plasmapheresis) and
    administration of intravenous immune globulin (IVIG).",
    " </p>",
    " <p>",
    " Plasmapheresis is thought to remove circulating antibodies, complement, and
    soluble biological response modifiers.",
    " </p>",
    " <p>",
    " The precise mechanism of action for intravenous immune globulin (IVIG) in GBS
    is unknown but may include providing anti-idiotypic antibodies, modulating
    expression and function of Fc receptors, interfering with activation of complement
    and production of cytokines, and interfering with activation and effector functions
    of T and B cells [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/265/abstract/11-13\">",
    " 11-13",
    " </a>",
    " ].",
    " </p>",
    " <p>",
    " The roles of the immune response, molecular mimicry, and antiganglioside
    antibodies in the pathogenesis of GBS are discussed separately. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?39/6/40038?
    source=see_link\">",
    " \"Pathogenesis of Guillain-Barr&eacute; syndrome in adults\"",
    " </a>",
    " .)",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H12\">",
    " <span class=\"h2\">",
    " Plasma exchange",
    " </span>",
    " &nbsp;&mdash;&nbsp;Large, randomized multicenter trials have established the
    effectiveness of plasma exchange in patients with severe GBS [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/265/abstract/14-17\">",
    " 14-17",
    " </a>",
    " ]. Earlier improvement in muscle strength, reduced need for mechanical
    ventilation, and better recovery have been demonstrated.",
    " </p>",
    " <p>",
    " In an updated (2012) meta-analysis of six randomized controlled trials and 649
    patients with GBS, treatment with plasma exchange was superior to supportive care
    [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/265/abstract/18\">",
    " 18",
    " </a>",
    " ]:",
    " </p>",
    " <p>",
    " <ul class=\"bullet-block\">",
    " <li>",
    " The median time to recover walking with aid was shorter in the plasma
    exchange group than the control group in two trials that reported this primary
    outcome measure.",
    " </li>",
    " <li>",
    " The time to onset of motor recovery in mildly affected patients was
    significantly shorter in the plasma exchange group in the one trial that reported
    this primary outcome measure.",
    " </li>",
    " <li>",
    " Among secondary outcome measures, plasma exchange was associated with a
    significantly increased proportion of patients who improved by one or more
    disability grades at four weeks in five trials. Additionally, plasma exchange
    treatment compared with control was associated with significant improvement as
    assessed by the time to recover walking without aid, the percentage of patients
    requiring mechanical ventilation, the duration of ventilation, full muscle strength
    recovery after one year, and severe sequelae after one year.",
    " </li>",
    " <li>",
    " Plasma exchange was most effective when started within seven days of symptom
    onset. However, in the North American study that allowed enrollment up to 30 days
    after symptom onset, there was still an improvement in outcome in the plasma
    exchange group compared with controls.",
    " </li>",
    " <li>",
    " Four exchanges were superior to two in patients with moderately severe GBS.
    However, in subjects with severe disease requiring mechanical ventilation, six
    exchanges were",
    " <strong>",
    " not",
    " </strong>",
    " superior compared with four.",
    " </li>",
    " <li>",
    " The methodologic quality of the trials was generally good. However, none
    were patient blinded, as sham apheresis was considered unethical. Furthermore, none
    of the trials were observer blinded, and only two trials [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/265/abstract/14,15\">",
    " 14,15",
    " </a>",
    " ] used centralized review of cases in an attempt to minimize unblinded
    outcome assessment.",
    " </li>",
    " </ul>",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H13\">",
    " <span class=\"h2\">",
    " Intravenous immune globulin",
    " </span>",
    " &nbsp;&mdash;&nbsp;Intravenous immune globulin (IVIG) is as effective as
    plasma exchange for the treatment of GBS. This conclusion was reached by a 2012
    systematic review and meta-analysis [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/265/abstract/19\">",
    " 19",
    " </a>",
    " ] and by a 2012 American Academy of Neurology guideline on IVIG in the
    treatment of neuromuscular disorders [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/265/abstract/20\">",
    " 20",
    " </a>",
    " ].",
    " </p>",
    " <p>",
    " As an example of these reports, a 2012 meta-analysis found no significant
    difference in the primary outcome measure, the change in a seven-grade disability
    scale at four weeks, with IVIG compared with plasma exchange (weighted mean
    difference -0.02, 95% CI -0.25 to 0.20) [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/265/abstract/19\">",
    " 19",
    " </a>",
    " ]. In addition, there were no statistically significant differences in other
    outcome measures.",
    " </p>",
    " <p>",
    " There are no randomized controlled trials comparing IVIG with placebo for the
    treatment of GBS; rather, the trials have compared IVIG with plasma exchange [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/265/abstract/21-24\">",
    " 21-24",
    " </a>",
    " ]. The 2012 meta-analysis found that patients assigned to IVIG were
    significantly less likely to discontinue treatment than patients assigned to plasma
    exchange (relative risk 0.14, 95% CI 0.05-0.36) [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/265/abstract/19\">",
    " 19",
    " </a>",
    " ].",
    " </p>",
    " <p>",
    " Patients with more severe clinical disease may benefit from longer duration of
    IVIG treatment. This observation is suggested but not established by a small study
    that compared outcomes in 39 patients with contraindications to plasma exchange
    randomly assigned to either three or six days of IVIG 0.4",
    " <span class=\"nowrap\">",
    " g/kg",
    " </span>",
    " [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/265/abstract/24\">",
    " 24",
    " </a>",
    " ]. The primary outcome measure (time until patients were able to stand with
    assistance) was nonsignificantly shorter in the group treated with IVIG for six
    days compared with those treated for three days. However, six days of treatment
    significantly improved the rate of recovery for the subgroup of patients who
    required mechanical ventilation. A trial studying the efficacy of a repeat course
    of IVIG in severely affected patients has been planned.",
    " </p>",
    " <p>",
    " A retrospective analysis of randomized trial data found that the increase in
    serum levels of IgG after IVIG treatment compared with baseline varied considerably
    among patients with GBS, and that a small increase in serum IgG levels two weeks
    after treatment was associated with a worse clinical outcome [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/265/abstract/25\">",
    " 25",
    " </a>",
    " ]. These data suggest that a higher dose or a repeat course of IVIG may be
    useful in patients with a small increase in serum IgG, but this hypothesis requires
    confirmation [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/265/abstract/26\">",
    " 26",
    " </a>",
    " ].",
    " </p>",
    " <p>",
    " Combining IVIG with plasma exchange does not appear to be beneficial for
    patients with GBS [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/265/abstract/20\">",
    " 20",
    " </a>",
    " ]. Supporting evidence comes from a trial of 379 nonambulatory patients with
    severe GBS who were within two weeks of symptom onset and were randomly assigned to
    treatment with five or six plasma exchanges, or five days of IVIG, or plasma
    exchange followed by IVIG [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/265/abstract/23\">",
    " 23",
    " </a>",
    " ]. There were no significant differences in measures of recovery among
    patients treated with plasma exchange, IVIG, or the combination of plasma exchange
    and IVIG.",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H14\">",
    " <span class=\"h2\">",
    " Other therapies",
    " </span>",
    " &nbsp;&mdash;&nbsp;Once the mainstay of therapy for GBS, glucocorticoids have
    not been shown to be beneficial and no longer have a role [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/265/abstract/27,28\">",
    " 27,28",
    " </a>",
    " ]. In a systematic review and meta-analysis of six trials with 587
    participants, glucocorticoid-treated patients with GBS showed no significant
    difference in disability grade, the primary outcome measure, compared with patients
    who were not treated with glucocorticoids [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/265/abstract/29\">",
    " 29",
    " </a>",
    " ]. Furthermore, in four small trials, patients treated with oral
    glucocorticoids had significantly less improvement than patients who were not
    treated with oral glucocorticoids.",
    " </p>",
    " <p>",
    " One randomized controlled trial found that combined treatment with
    intravenous",
    " <a class=\"drug drug_general\" href=\"UTD.htm?30/25/31129?source=see_link\">",
    " methylprednisolone",
    " </a>",
    " and IVIG showed no significant benefit compared with IVIG alone for patients
    with GBS [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/265/abstract/30\">",
    " 30",
    " </a>",
    " ].",
    " </p>",
    " <p>",
    " Aside from plasma exchange and intravenous immune globulin (IVIG), no other
    pharmacologic agents have been found to be effective for GBS [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/265/abstract/31\">",
    " 31",
    " </a>",
    " ]. Interferon-beta has been reported to be beneficial in individual cases [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/265/abstract/32,33\">",
    " 32,33",
    " </a>",
    " ], but in a small randomized controlled trial, interferon-beta therapy was not
    associated with significant clinical improvement, and possible medication-related
    side effects were common [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/265/abstract/34\">",
    " 34",
    " </a>",
    " ].",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H17\">",
    " <span class=\"h2\">",
    " Choice of therapy",
    " </span>",
    " &nbsp;&mdash;&nbsp;Disease-modifying therapy with plasma exchange or IVIG is
    recommended for nonambulatory patients with GBS who present within four weeks of
    neuropathic symptom onset. Therapy with plasma exchange or IVIG is suggested for
    ambulatory patients with GBS who present within the same time frame, except for
    those who are mildly affected and already recovering. Patients recover sooner and
    better when treated early.",
    " </p>",
    " <p>",
    " The choice between plasma exchange and IVIG is dependent on local availability
    and on patient-related risk factors, contraindications, and preference. Because of
    its ease of administration and wide availability, IVIG is frequently the preferred
    treatment.",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H18\">",
    " <span class=\"h3\">",
    " Guideline recommendations",
    " </span>",
    " &nbsp;&mdash;&nbsp;Guidelines from the American Academy of Neurology (AAN)
    have made the following observations [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/265/abstract/20,35\">",
    " 20,35",
    " </a>",
    " ]:",
    " </p>",
    " <p>",
    " <ul class=\"bulletCompact-block\">",
    " <li>",
    " Treatment with plasma exchange or IVIG hastens recovery from GBS",
    " </li>",
    " <li>",
    " The beneficial effects of plasma exchange and IVIG are equivalent",
    " </li>",
    " <li>",
    " Combining the two treatments is not beneficial",
    " </li>",
    " <li>",
    " Glucocorticoid treatment alone is not beneficial",
    " </li>",
    " </ul>",
    " </p>",
    " <p>",
    " The AAN recommends plasma exchange or IVIG for GBS treatment as follows [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/265/abstract/35\">",
    " 35",
    " </a>",
    " ]:",
    " </p>",
    " <p>",
    " <ul class=\"bullet-block\">",
    " <li>",
    " Plasma exchange is recommended for nonambulatory adult patients with GBS who
    start treatment within four weeks of the onset of neuropathic symptoms. Plasma
    exchange is also recommended for ambulatory patients who start treatment within two
    weeks of the onset of neuropathic symptoms",
    " </li>",
    " <li>",
    " IVIG is recommended for nonambulatory adult patients with GBS who start
    treatment within two or possibly four weeks of the onset of neuropathic symptoms",
    " </li>",
    " </ul>",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H19\">",
    " <span class=\"h3\">",
    " Doses and side effects",
    " </span>",
    " &nbsp;&mdash;&nbsp;Intravenous immune globulin is given for five days at 0.4",
    " <span class=\"nowrap\">",
    " gram/kg",
    " </span>",
    " per day. Side effects include aseptic meningitis, rash, acute renal failure
    (mostly related to sucrose containing products), and (rarely) hyperviscosity
    leading to stroke. IgA deficiency can lead to anaphylaxis [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/265/abstract/13\">",
    " 13",
    " </a>",
    " ]. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?28/11/28857?
    source=see_link\">",
    " \"General principles in the use of immune globulin\"",
    " </a>",
    " .)",
    " </p>",
    " <p>",
    " Plasma exchange is usually given for four to six treatments over eight to 10
    days. The main complications are hypotension, sepsis, and problems with intravenous
    access. The implementation of therapeutic plasma exchange, including techniques and
    regimens, is discussed in detail separately. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?37/33/38420?
    source=see_link\">",
    " \"Prescription and technique of therapeutic plasma exchange\"",
    " </a>",
    " .)",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H78344571\">",
    " <span class=\"h2\">",
    " Retreatment for poor response or relapse",
    " </span>",
    " &nbsp;&mdash;&nbsp;Some patients with GBS may continue to deteriorate after
    initial treatment with plasma exchange or intravenous immune globulin (IVIG). This
    may reflect the natural history of the disease or an error in diagnosis [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/265/abstract/26,36\">",
    " 26,36",
    " </a>",
    " ]. Thus, it is useful to confirm that the diagnosis of GBS is correct prior to
    retreatment. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?5/22/5481?
    source=see_link&amp;anchor=H15#H15\">",
    " \"Clinical features and diagnosis of Guillain-Barr&eacute; syndrome in
    adults\", section on 'Differential diagnosis'",
    " </a>",
    " .)",
    " </p>",
    " <p>",
    " There are no data from randomized trials to guide retreatment for patients
    with poor response or relapse after initial treatment for GBS. We suggest observing
    the patient for one week after finishing treatment. For those who show no
    improvement or further deterioration and are severely affected, we suggest
    retreating with the same modality (plasma exchange or IVIG), under close
    observation for side effects. We suggest not switching from IVIG to plasma exchange
    because it will remove the potentially beneficial circulating IVIG.",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H20\">",
    " <span class=\"h1\">",
    " CLINICAL COURSE",
    " </span>",
    " &nbsp;&mdash;&nbsp;The natural history of Guillain-Barr&eacute; syndrome (GBS)
    is illustrated by a retrospective series of 162 patients who were evaluated in the
    era before the advent of disease-modifying treatment [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/265/abstract/37\">",
    " 37",
    " </a>",
    " ]. Most (74 percent) showed continued progression for up to two weeks,
    followed by a plateau phase of two to four weeks, and then recovery of function. At
    four weeks after onset, recovery was underway in 67 percent of patients.",
    " </p>",
    " <p>",
    " The time period to onset of recovery is shortened by about 40 to 50 percent by
    treatment with plasma exchange or IVIG. Data from the North American plasma
    exchange trial that studied 245 patients treated within 30 days after onset of
    motor deficit illustrates the degree of improvement with disease-modifying therapy
    [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/265/abstract/14\">",
    " 14",
    " </a>",
    " ].",
    " </p>",
    " <p>",
    " <ul class=\"bullet-block\">",
    " <li>",
    " The median time to improve one grade in the plasma exchange and control
    groups was 19 and 40 days",
    " </li>",
    " <li>",
    " The median time to walking unaided in the plasma exchange and control groups
    was 53 and 85 days",
    " </li>",
    " <li>",
    " Improvement by at least one grade at one month in the plasma exchange and
    control groups occurred in 59 and 39 percent of patients",
    " </li>",
    " </ul>",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H21\">",
    " <span class=\"h2\">",
    " Prognostic factors",
    " </span>",
    " &nbsp;&mdash;&nbsp;Factors associated with a poor prognosis for recovery from
    GBS include [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/265/abstract/38-41\">",
    " 38-41",
    " </a>",
    " ]:",
    " </p>",
    " <p>",
    " <ul class=\"bulletCompact-block\">",
    " <li>",
    " Older age",
    " </li>",
    " <li>",
    " Rapid onset (less than seven days) prior to presentation",
    " </li>",
    " <li>",
    " Severe muscle weakness on admission",
    " </li>",
    " <li>",
    " Need for ventilatory support",
    " </li>",
    " <li>",
    " An average distal motor response amplitude reduction to &lt;20 percent of
    normal",
    " </li>",
    " <li>",
    " Preceding diarrheal illness",
    " </li>",
    " </ul>",
    " </p>",
    " <p>",
    " In a study that analyzed 388 patients with GBS from two randomized controlled
    trials and a pilot study, independent predictors of poor six-month outcome (defined
    as the inability to walk 10 m without assistance) were age, preceding diarrhea, and
    the degree of disability at two weeks after study entry [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/265/abstract/42\">",
    " 42",
    " </a>",
    " ].",
    " </p>",
    " <p>",
    " Although initial studies suggested a possible correlation between anti-GM1
    antibodies and poor recovery, a prospective trial of 96 patients with GBS from
    Great Britain found no such correlation [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/265/abstract/43\">",
    " 43",
    " </a>",
    " ].",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H22\">",
    " <span class=\"h3\">",
    " Electrophysiology",
    " </span>",
    " &nbsp;&mdash;&nbsp;Electrophysiology studies can have prognostic value,
    especially when repeated over the first five weeks. Axonal degeneration and poor
    prognosis (ie, slower recovery",
    " <span class=\"nowrap\">",
    " and/or",
    " </span>",
    " severe residual disability) are suggested by markedly reduced distal motor
    response amplitude (&lt;20 percent of normal) and profuse fibrillation potentials
    on needle examination, starting at two to four weeks after disease onset. In
    contrast, demyelination and a good prognosis are associated with a pattern
    characterized by preservation of the distal motor response amplitude above 20
    percent of normal, conduction block, and temporal dispersion [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/265/abstract/44\">",
    " 44",
    " </a>",
    " ].",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H23\">",
    " <span class=\"h2\">",
    " Long-term outcome",
    " </span>",
    " &nbsp;&mdash;&nbsp;The proportion of patients with GBS who walk independently
    at six months and one year after diagnosis is approximately 80 and 84 percent,
    respectively [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/265/abstract/41\">",
    " 41",
    " </a>",
    " ]. At one year, full recovery of motor strength occurs in about 60 percent of
    patients, while severe motor problems persist in about 14 percent. Approximately 5
    to 10 percent of patients with GBS have a prolonged course with several months of
    ventilator dependency and very delayed and incomplete recovery [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/265/abstract/45\">",
    " 45",
    " </a>",
    " ].",
    " </p>",
    " <p>",
    " Within one year of diagnosis, approximately 5 percent of patients with GBS die
    despite intensive care [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/265/abstract/41,46\">",
    " 41,46",
    " </a>",
    " ]. Of patients who become ventilator dependent, about 20 percent will die.
    Causes of death include acute respiratory distress syndrome, sepsis, pulmonary
    emboli, and unexplained cardiac arrest [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/265/abstract/47\">",
    " 47",
    " </a>",
    " ].",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H24\">",
    " <span class=\"h2\">",
    " Relapses",
    " </span>",
    " &nbsp;&mdash;&nbsp;Relapses with increased weakness occur in up to 10 percent
    of patients with GBS [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/265/abstract/48,49\">",
    " 48,49",
    " </a>",
    " ]. Relapses are usually treated with a partial or complete repeat course of
    the initial plasma exchange or IVIG treatment. (See",
    " <a class=\"local\" href=\"#H78344571\">",
    " 'Retreatment for poor response or relapse'",
    " </a>",
    " above.)",
    " </p>",
    " <p>",
    " About 2 percent of GBS patients will develop the chronic relapsing weakness of
    chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/265/abstract/50\">",
    " 50",
    " </a>",
    " ]. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?39/33/40472?
    source=see_link\">",
    " \"Chronic inflammatory demyelinating polyneuropathy: Etiology, clinical
    features, and diagnosis\"",
    " </a>",
    " .)",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H25\">",
    " <span class=\"h2\">",
    " Immunizations",
    " </span>",
    " &nbsp;&mdash;&nbsp;While Guillain-Barr&eacute; syndrome (GBS) has followed
    vaccinations, the true risk of vaccine-associated GBS is uncertain. This issue is
    discussed separately. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?39/6/40038?
    source=see_link&amp;anchor=H9#H9\">",
    " \"Pathogenesis of Guillain-Barr&eacute; syndrome in adults\", section on
    'Vaccination'",
    " </a>",
    " .)",
    " </p>",
    " <p>",
    " In general, vaccination in patients with GBS should be considered on an
    individual basis. The following recommendations are in agreement with a 2005 expert
    review of supportive care for patients with GBS, and are based on observational
    studies and expert opinion [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/265/abstract/1\">",
    " 1",
    " </a>",
    " ]:",
    " </p>",
    " <p>",
    " <ul class=\"bullet-block\">",
    " <li>",
    " Immunizations are not recommended during the acute phase of GBS and are not
    suggested for a period of one year or more after the onset of GBS",
    " </li>",
    " <li>",
    " After one year, immunizations need not be withheld, but the need for the
    immunization should be reviewed on an individual basis",
    " </li>",
    " <li>",
    " Future avoidance is suggested for any particular immunization that is
    followed within six weeks by the onset of GBS",
    " </li>",
    " </ul>",
    " </p>",
    " <p>",
    " For the majority of patients who have risk factors for severe influenza
    complications and who have a history of GBS not provoked by influenza vaccination,
    the established benefits of influenza vaccination justifies yearly vaccination. The
    utility of influenza vaccination in adults is discussed separately. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?36/8/37002?
    source=see_link\">",
    " \"Seasonal influenza vaccination in adults\"",
    " </a>",
    " .)",
    " </p>",
    " <p class=\"headingAnchor\" id=\"PATIENT_INFORMATION\">",
    " <span class=\"h1\">",
    " INFORMATION FOR PATIENTS",
    " </span>",
    " &nbsp;&mdash;&nbsp;UpToDate offers two types of patient education materials,
    &ldquo;The Basics&rdquo; and &ldquo;Beyond the Basics.&rdquo; The Basics patient
    education pieces are written in plain language, at the 5",
    " <sup>",
    " th",
    " </sup>",
    " to 6",
    " <sup>",
    " th",
    " </sup>",
    " grade reading level, and they answer the four or five key questions a patient
    might have about a given condition. These articles are best for patients who want a
    general overview and who prefer short, easy-to-read materials. Beyond the Basics
    patient education pieces are longer, more sophisticated, and more detailed. These
    articles are written at the 10",
    " <sup>",
    " th",
    " </sup>",
    " to 12",
    " <sup>",
    " th",
    " </sup>",
    " grade reading level and are best for patients who want in-depth information
    and are comfortable with some medical jargon.",
    " </p>",
    " <p>",
    " Here are the patient education articles that are relevant to this topic. We
    encourage you to print or e-mail these topics to your patients. (You can also
    locate patient education articles on a variety of subjects by searching on
    &ldquo;patient info&rdquo; and the keyword(s) of interest.)",
    " </p>",
    " <p>",
    " <ul class=\"bullet-block\">",
    " <li>",
    " Basics topics (see",
    " <a class=\"medical medical_basics\" href=\"UTD.htm?36/37/37457?
    source=see_link\">",
    " \"Patient information: Guillain-Barr&eacute; syndrome (The Basics)\"",
    " </a>",
    " )",
    " </li>",
    " </ul>",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H26\">",
    " <span class=\"h1\">",
    " SUMMARY AND RECOMMENDATIONS",
    " </span>",
    " </p>",
    " <p>",
    " <ul class=\"bullet-block\">",
    " <li>",
    " Supportive care is extremely important in Guillain-Barr&eacute; syndrome
    (GBS) since about 30 percent of patients develop neuromuscular respiratory failure
    requiring mechanical ventilation. In addition, severe autonomic dysfunction occurs
    in about 20 percent and warrants intensive care unit (ICU) monitoring. (See",
    " <a class=\"local\" href=\"#H2\">",
    " 'Supportive care'",
    " </a>",
    " above.)",
    " </li>",
    " <li>",
    " Close respiratory monitoring with frequent measurement of vital capacity and
    negative inspiratory force should be instituted in all patients with GBS on
    admission and continued while weakness is progressing. Patients with a forced vital
    capacity &lt;20",
    " <span class=\"nowrap\">",
    " mL/kg,",
    " </span>",
    " maximum inspiratory pressure &lt;30 cmH2O, or maximum expiratory pressure
    &lt;40 cmH2O are at high risk of impending respiratory failure and should undergo
    urgent intubation and mechanical ventilation. (See",
    " <a class=\"local\" href=\"#H3\">",
    " 'Respiratory failure'",
    " </a>",
    " above.)",
    " </li>",
    " <li>",
    " For patients with GBS and progressive weakness, we recommend cardiac and
    blood pressure monitoring. (See",
    " <a class=\"local\" href=\"#H5\">",
    " 'Cardiovascular management'",
    " </a>",
    " above.)",
    " </li>",
    " <li>",
    " For patients with GBS and progressive weakness, we recommend daily abdominal
    auscultation to monitor for bowel silence and the development of adynamic ileus.
    (See",
    " <a class=\"local\" href=\"#H8\">",
    " 'Bowel and bladder care'",
    " </a>",
    " above.)",
    " </li>",
    " <li>",
    " Neuropathic pain occurs in about 40 to 50 percent of patients during the
    course of GBS and often requires treatment. (See",
    " <a class=\"local\" href=\"#H9\">",
    " 'Pain control'",
    " </a>",
    " above.)",
    " </li>",
    " <li>",
    " In the absence of disease-modifying treatment, most patients with GBS show
    continued progression for up to two weeks, followed by a plateau phase of about two
    weeks, and then recovery of function over several weeks to months. (See",
    " <a class=\"local\" href=\"#H11\">",
    " 'Disease modifying treatment'",
    " </a>",
    " above.)",
    " </li>",
    " <li>",
    " The main modalities of disease modifying therapy for GBS are plasma exchange
    and intravenous immune globulin (IVIG). The treatments are equivalent and improve
    outcome. Treatment shortens the time to walking independently by 40 to 50 percent.
    (See",
    " <a class=\"local\" href=\"#H11\">",
    " 'Disease modifying treatment'",
    " </a>",
    " above.)",
    " </li>",
    " <li>",
    " For nonambulatory adult patients with GBS who are within four weeks of
    neuropathic symptom onset, we recommend treatment with plasma exchange or IVIG (",
    " <a class=\"grade\" href=\"._grade_1?title=Grade 1A\">",
    " Grade 1A",
    " </a>",
    " ). For ambulatory adult patients with GBS who are not yet recovering within
    four weeks of neuropathic symptom onset, we suggest treatment with plasma exchange
    or IVIG (",
    " <a class=\"grade\" href=\"._grade_5?title=Grade 2B\">",
    " Grade 2B",
    " </a>",
    " ). The choice between plasma exchange and IVIG is dependent on local
    availability and on patient preference, risk factors, and contraindications. When
    both therapies are equally available and there are no contraindications for either,
    we suggest treatment with IVIG (",
    " <a class=\"grade\" href=\"._grade_5?title=Grade 2B\">",
    " Grade 2B",
    " </a>",
    " ). (See",
    " <a class=\"local\" href=\"#H12\">",
    " 'Plasma exchange'",
    " </a>",
    " above and",
    " <a class=\"local\" href=\"#H13\">",
    " 'Intravenous immune globulin'",
    " </a>",
    " above and",
    " <a class=\"local\" href=\"#H17\">",
    " 'Choice of therapy'",
    " </a>",
    " above.)",
    " </li>",
    " <li>",
    " For adult patients with GBS, we recommend",
    " <strong>",
    " not",
    " </strong>",
    " treating with glucocorticoids (",
    " <a class=\"grade\" href=\"._grade_1?title=Grade 1A\">",
    " Grade 1A",
    " </a>",
    " ). (See",
    " <a class=\"local\" href=\"#H14\">",
    " 'Other therapies'",
    " </a>",
    " above.)",
    " </li>",
    " <li>",
    " Even with treatment, approximately 5 to 10 percent of patients have a
    prolonged course with very delayed and incomplete recovery, and 5 percent die
    despite intensive care. In addition, relapses occur in up to 10 percent of
    patients. (See",
    " <a class=\"local\" href=\"#H20\">",
    " 'Clinical course'",
    " </a>",
    " above.)",
    " </li>",
    " </ul>",
    " </p>",
    " </div>",
    " <div id=\"topicAgreement\">",
    " Use of UpToDate is subject to the",
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    target=\"_blank\">",
    " Subscription and License Agreement",
    " </a>",
    " .",
    " </div>",
    " <div class=\"headingAnchor\" id=\"references\">",
    " <h1>",
    " REFERENCES",
    " </h1>",
    " <ol id=\"reference\">",
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    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/16/265/abstract/2\">",
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    " </li>",
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    " </li>",
    " <li>",
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    " <li>",
    " Ropper, AH. Critical care of Guillain-Barre syndrome. In: Neurological and
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    " </li>",
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    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/16/265/abstract/8\">",
    " Moulin DE, Hagen N, Feasby TE, et al. Pain in Guillain-Barr&eacute;
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    " </a>",
    " </li>",
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    " Pandey CK, Bose N, Garg G, et al. Gabapentin for the treatment of pain in
    guillain-barr&eacute; syndrome: a double-blinded, placebo-controlled, crossover
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    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/16/265/abstract/10\">",
    " Meythaler JM. Rehabilitation of Guillain-Barr&eacute; syndrome. Arch Phys
    Med Rehabil 1997; 78:872.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/16/265/abstract/11\">",
    " Buchwald B, Ahangari R, Weishaupt A, Toyka KV. Intravenous immunoglobulins
    neutralize blocking antibodies in Guillain-Barr&eacute; syndrome. Ann Neurol 2002;
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    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/16/265/abstract/12\">",
    " Jacobs BC, O'Hanlon GM, Bullens RW, et al. Immunoglobulins inhibit
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    " </li>",
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    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/16/265/abstract/13\">",
    " Dalakas MC. The use of intravenous immunoglobulin in the treatment of
    autoimmune neuromuscular diseases: evidence-based indications and safety profile.
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    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/16/265/abstract/14\">",
    " Plasmapheresis and acute Guillain-Barr&eacute; syndrome. The Guillain-
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    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/16/265/abstract/15\">",
    " Osterman PO, Fagius J, Lundemo G, et al. Beneficial effects of plasma
    exchange in acute inflammatory polyradiculoneuropathy. Lancet 1984; 2:1296.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/16/265/abstract/16\">",
    " Efficiency of plasma exchange in Guillain-Barr&eacute; syndrome: role of
    replacement fluids. French Cooperative Group on Plasma Exchange in Guillain-
    Barr&eacute; syndrome. Ann Neurol 1987; 22:753.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/16/265/abstract/17\">",
    " Appropriate number of plasma exchanges in Guillain-Barr&eacute; syndrome.
    The French Cooperative Group on Plasma Exchange in Guillain-Barr&eacute; Syndrome.
    Ann Neurol 1997; 41:298.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/16/265/abstract/18\">",
    " Rapha&euml;l JC, Chevret S, Hughes RA, Annane D. Plasma exchange for
    Guillain-Barr&eacute; syndrome. Cochrane Database Syst Rev 2012; 7:CD001798.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/16/265/abstract/19\">",
    " Hughes RA, Swan AV, van Doorn PA. Intravenous immunoglobulin for Guillain-
    Barr&eacute; syndrome. Cochrane Database Syst Rev 2012; 7:CD002063.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/16/265/abstract/20\">",
    " Patwa HS, Chaudhry V, Katzberg H, et al. Evidence-based guideline:
    intravenous immunoglobulin in the treatment of neuromuscular disorders: report of
    the Therapeutics and Technology Assessment Subcommittee of the American Academy of
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    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/16/265/abstract/21\">",
    " van der Mech&eacute; FG, Schmitz PI. A randomized trial comparing
    intravenous immune globulin and plasma exchange in Guillain-Barr&eacute; syndrome.
    Dutch Guillain-Barr&eacute; Study Group. N Engl J Med 1992; 326:1123.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/16/265/abstract/22\">",
    " Bril V, Ilse WK, Pearce R, et al. Pilot trial of immunoglobulin versus
    plasma exchange in patients with Guillain-Barr&eacute; syndrome. Neurology 1996;
    46:100.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/16/265/abstract/23\">",
    " Randomised trial of plasma exchange, intravenous immunoglobulin, and
    combined treatments in Guillain-Barr&eacute; syndrome. Plasma
    Exchange/Sandoglobulin Guillain-Barr&eacute; Syndrome Trial Group. Lancet 1997;
    349:225.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/16/265/abstract/24\">",
    " Raphael JC, Chevret S, Harboun M, et al. Intravenous immune globulins in
    patients with Guillain-Barr&eacute; syndrome and contraindications to plasma
    exchange: 3 days versus 6 days. J Neurol Neurosurg Psychiatry 2001; 71:235.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/16/265/abstract/25\">",
    " Kuitwaard K, de Gelder J, Tio-Gillen AP, et al. Pharmacokinetics of
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    Neurol 2009; 66:597.",
    " </a>",
    " </li>",
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    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/16/265/abstract/26\">",
    " Cornblath DR, Hughes RA. Treatment for Guillain-Barr&eacute; syndrome. Ann
    Neurol 2009; 66:569.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/16/265/abstract/27\">",
    " Hughes RA. Ineffectiveness of high-dose intravenous methylprednisolone in
    Guillain-Barr&eacute; syndrome. Lancet 1991; 338:1142.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/16/265/abstract/28\">",
    " Double-blind trial of intravenous methylprednisolone in Guillain-
    Barr&eacute; syndrome. Guillain-Barr&eacute; Syndrome Steroid Trial Group. Lancet
    1993; 341:586.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/16/265/abstract/29\">",
    " Hughes RA, van Doorn PA. Corticosteroids for Guillain-Barr&eacute; syndrome.
    Cochrane Database Syst Rev 2012; 8:CD001446.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/16/265/abstract/30\">",
    " van Koningsveld R, Schmitz PI, Mech&eacute; FG, et al. Effect of
    methylprednisolone when added to standard treatment with intravenous immunoglobulin
    for Guillain-Barr&eacute; syndrome: randomised trial. Lancet 2004; 363:192.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/16/265/abstract/31\">",
    " Hughes RA, Pritchard J, Hadden RD. Pharmacological treatment other than
    corticosteroids, intravenous immunoglobulin and plasma exchange for Guillain-
    Barr&eacute; syndrome. Cochrane Database Syst Rev 2013; 2:CD008630.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/16/265/abstract/32\">",
    " Cr&eacute;ange A, Lerat H, Meyrignac C, et al. Treatment of Guillain-
    Barr&eacute; syndrome with interferon-beta. Lancet 1998; 352:368.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/16/265/abstract/33\">",
    " Schaller B, Radziwill AJ, Steck AJ. Successful treatment of Guillain-
    Barr&eacute; syndrome with combined administration of interferon-beta-1a and
    intravenous immunoglobulin. Eur Neurol 2001; 46:167.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/16/265/abstract/34\">",
    " Pritchard J, Gray IA, Idrissova ZR, et al. A randomized controlled trial of
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    61:1282.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/16/265/abstract/35\">",
    " Hughes RA, Wijdicks EF, Barohn R, et al. Practice parameter: immunotherapy
    for Guillain-Barr&eacute; syndrome: report of the Quality Standards Subcommittee of
    the American Academy of Neurology. Neurology 2003; 61:736.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/16/265/abstract/36\">",
    " Winer JB. When the Guillain-Barre patient fails to respond to treatment.
    Pract Neurol 2009; 9:227.",
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    " </li>",
    " <li>",
    " Ropper, AH, Wijdicks, EFM, Truax, BT. Guillain-Barr&eacute; syndrome, FA
    Davis, Philadelphia 1991.",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/16/265/abstract/38\">",
    " McKhann GM, Griffin JW, Cornblath DR, et al. Plasmapheresis and Guillain-
    Barr&eacute; syndrome: analysis of prognostic factors and the effect of
    plasmapheresis. Ann Neurol 1988; 23:347.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/16/265/abstract/39\">",
    " Rees JH, Soudain SE, Gregson NA, Hughes RA. Campylobacter jejuni infection
    and Guillain-Barr&eacute; syndrome. N Engl J Med 1995; 333:1374.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/16/265/abstract/40\">",
    " Walgaard C, Lingsma HF, Ruts L, et al. Early recognition of poor prognosis
    in Guillain-Barre syndrome. Neurology 2011; 76:968.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/16/265/abstract/41\">",
    " Rajabally YA, Uncini A. Outcome and its predictors in Guillain-Barre
    syndrome. J Neurol Neurosurg Psychiatry 2012; 83:711.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/16/265/abstract/42\">",
    " van Koningsveld R, Steyerberg EW, Hughes RA, et al. A clinical prognostic
    scoring system for Guillain-Barr&eacute; syndrome. Lancet Neurol 2007; 6:589.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/16/265/abstract/43\">",
    " Rees JH, Gregson NA, Hughes RA. Anti-ganglioside GM1 antibodies in Guillain-
    Barr&eacute; syndrome and their relationship to Campylobacter jejuni infection. Ann
    Neurol 1995; 38:809.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/16/265/abstract/44\">",
    " Albers JW. AAEE case report #4: Guillain-Barr&eacute; syndrome. Muscle Nerve
    1989; 12:705.",
    " </a>",
    " </li>",
    " <li>",
    " Kissel, JT, Cornblath, DR, Mendell, JR. Guillain-Barre syndrome. In:
    Diagnosis and management of peripheral nerve disorders, Oxford University Press,
    New York 2001.",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/16/265/abstract/46\">",
    " Chi&ograve; A, Cocito D, Leone M, et al. Guillain-Barr&eacute; syndrome: a
    prospective, population-based incidence and outcome survey. Neurology 2003;
    60:1146.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/16/265/abstract/47\">",
    " Lawn ND, Wijdicks EF. Fatal Guillain-Barr&eacute; syndrome. Neurology 1999;
    52:635.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/16/265/abstract/48\">",
    " WIEDERHOLT WC, MULDER DW, LAMBERT EH. THE LANDRY-GUILLAIN-BARR'E-STROHL
    SYNDROME OR POLYRADICULONEUROPATHY: HISTORICAL REVIEW, REPORT ON 97 PATIENTS, AND
    PRESENT CONCEPTS. Mayo Clin Proc 1964; 39:427.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/16/265/abstract/49\">",
    " Asbury AK. New concepts of Guillain-Barr&eacute; syndrome. J Child Neurol
    2000; 15:183.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/16/265/abstract/50\">",
    " Odaka M, Yuki N, Hirata K. Patients with chronic inflammatory demyelinating
    polyneuropathy initially diagnosed as Guillain-Barr&eacute; syndrome. J Neurol
    2003; 250:913.",
    " </a>",
    " </li>",
    " </ol>",
    " </div>",
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    " SUMMARY &amp; RECOMMENDATIONS",
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    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#H1\">",
    " INTRODUCTION",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#H2\">",
    " SUPPORTIVE CARE",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H3\">",
    " Respiratory failure",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H4\">",
    " Autonomic dysfunction",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H5\">",
    " Cardiovascular management",
    " </a>",
    " </li>",
    " <li class=\"dashItem\">",
    " <a class=\"outlineLink\" href=\"#H6\">",
    " - Blood pressure",
    " </a>",
    " </li>",
    " <li class=\"dashItem\">",
    " <a class=\"outlineLink\" href=\"#H7\">",
    " - Arrhythmias",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H8\">",
    " Bowel and bladder care",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H9\">",
    " Pain control",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H10\">",
    " Rehabilitation",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#H11\">",
    " DISEASE MODIFYING TREATMENT",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H12\">",
    " Plasma exchange",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H13\">",
    " Intravenous immune globulin",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H14\">",
    " Other therapies",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H17\">",
    " Choice of therapy",
    " </a>",
    " </li>",
    " <li class=\"dashItem\">",
    " <a class=\"outlineLink\" href=\"#H18\">",
    " - Guideline recommendations",
    " </a>",
    " </li>",
    " <li class=\"dashItem\">",
    " <a class=\"outlineLink\" href=\"#H19\">",
    " - Doses and side effects",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H78344571\">",
    " Retreatment for poor response or relapse",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#H20\">",
    " CLINICAL COURSE",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H21\">",
    " Prognostic factors",
    " </a>",
    " </li>",
    " <li class=\"dashItem\">",
    " <a class=\"outlineLink\" href=\"#H22\">",
    " - Electrophysiology",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H23\">",
    " Long-term outcome",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H24\">",
    " Relapses",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H25\">",
    " Immunizations",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#PATIENT_INFORMATION\">",
    " INFORMATION FOR PATIENTS",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#H26\">",
    " SUMMARY AND RECOMMENDATIONS",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a href=\"#references\">",
    " REFERENCES",
    " </a>",
    " </li>",
    " </ul>",
    " </div>",
    " <h1>",
    " RELATED TOPICS",
    " </h1>",
    " <div id=\"relatedTopics\">",
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    var title_f0_16_266="Blunt cerebrovascular injury: Mechanisms, screening, and
    diagnostic evaluation";
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    " <div id=\"topicContent\">",
    " <div id=\"topicTitle\">",
    " Blunt cerebrovascular injury: Mechanisms, screening, and diagnostic
    evaluation",
    " </div>",
    " <div id=\"topicContributors\">",
    " <div>",
    " <a id=\"authors\">",
    " </a>",
    " <a class=\"contributor contributor_credentials contributorType\"
    href=\"UTD.htm?0/16/266/contributors\">",
    " Authors",
    " </a>",
    " <br/>",
    " <a class=\"contributor contributor_credentials\" href=\"UTD.htm?
    0/16/266/contributors\">",
    " Walter L. Biffl, MD",
    " </a>",
    " <br/>",
    " <a class=\"contributor contributor_credentials\" href=\"UTD.htm?
    0/16/266/contributors\">",
    " Clay Cothren Burlew, MD",
    " </a>",
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    0/16/266/contributors\">",
    " Ernest E Moore, MD",
    " </a>",
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    href=\"UTD.htm?0/16/266/contributors\">",
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    " Heidi L Frankel, MD, FACS",
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    0/16/266/contributors\">",
    " John F Eidt, MD",
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    " Joseph L Mills, Sr, MD",
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    " Kathryn A Collins, MD, PhD, FACS",
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    " Literature review current through:",
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    " Nov 15, 2012.",
    " </div>",
    " <div id=\"topicText\">",
    " <p class=\"headingAnchor\" id=\"H19563948\">",
    " <span class=\"h1\">",
    " INTRODUCTION",
    " </span>",
    " &nbsp;&mdash;&nbsp;Blunt carotid and vertebral artery injury, collectively
    termed blunt cerebrovascular injury, are rare but potentially devastating events.
    Blunt carotid injury is associated with mortality rates that range from 23 to 28
    percent with 48 to 58 percent of survivors suffering permanent severe neurologic
    deficits [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/266/abstract/1\">",
    " 1",
    " </a>",
    " ].",
    " </p>",
    " <p>",
    " The overall incidence is low in patients sustaining blunt trauma [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/266/abstract/2-5\">",
    " 2-5",
    " </a>",
    " ]. Clinical studies in the early 1990s suggested that these injuries were
    being under-diagnosed [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/266/abstract/4,6\">",
    " 4,6",
    " </a>",
    " ]. Increased recognition through screening (arteriography, computed
    tomographic angiography) based upon specific clinical criteria has increased the
    reported incidence to about one percent in patients with blunt trauma [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/266/abstract/1,7-9\">",
    " 1,7-9",
    " </a>",
    " ]. When such injury occurs, it is often bilateral.",
    " </p>",
    " <p>",
    " Injury mechanisms, screening, and diagnosis of blunt cerebrovascular injury
    will be reviewed here. The treatment of blunt cerebrovascular injury is discussed
    separately. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?8/47/8953?
    source=see_link\">",
    " \"Blunt cerebrovascular injury: Treatment and outcomes\"",
    " </a>",
    " .)",
    " </p>",
    " <p>",
    " The diagnosis and management of penetrating cerebrovascular injury and
    spontaneous cerebrovascular dissection are reviewed elsewhere. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?1/62/2026?
    source=see_link\">",
    " \"Penetrating neck injuries\"",
    " </a>",
    " and",
    " <a class=\"medical medical_review\" href=\"UTD.htm?10/30/10730?
    source=see_link\">",
    " \"Spontaneous cerebral and cervical artery dissection: Clinical features and
    diagnosis\"",
    " </a>",
    " .)",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H19563955\">",
    " <span class=\"h1\">",
    " CEREBROVASCULAR ANATOMY",
    " </span>",
    " &nbsp;&mdash;&nbsp;The vascular supply to the brain is divided into the
    anterior and posterior circulations originating from the carotid and vertebral
    arteries, respectively. The circle of Willis connects the anterior and posterior
    circulations, but is completely intact and symmetric in only about 20 percent of
    individuals [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/266/abstract/10\">",
    " 10",
    " </a>",
    " ]. The anatomic variability of the collateral circulation helps explain the
    clinical presentations of patients with cerebrovascular injuries, and underscores
    the need for complete imaging of cerebral circulation when injury is suspected.
    (See",
    " <a class=\"local\" href=\"#H3987108\">",
    " 'Imaging evaluation'",
    " </a>",
    " below.)",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H3979546\">",
    " <span class=\"h2\">",
    " Anterior circulation",
    " </span>",
    " &nbsp;&mdash;&nbsp;The anterior circulation supplies the majority of the
    cerebral hemispheres except the occipital and medial temporal lobes. Injury to the
    vessels of the anterior circulation can lead to ischemic or hemorrhagic hemispheric
    stroke. (See",
    " <a class=\"local\" href=\"#H3979590\">",
    " 'Clinical presentation'",
    " </a>",
    " below and",
    " <a class=\"medical medical_review\" href=\"UTD.htm?8/63/9208?
    source=see_link\">",
    " \"Etiology and classification of stroke\"",
    " </a>",
    " .)",
    " </p>",
    " <p>",
    " The left common carotid artery (CCA) originates from the aortic arch, whereas
    the right CCA originates from the brachiocephalic trunk (innominate artery) (",
    " <a class=\"graphic graphic_figure graphicRef51410 \" href=\"UTD.htm?
    2/4/2122\">",
    " figure 1",
    " </a>",
    " ). The CCA divides into the internal carotid artery (ICA) and external carotid
    artery (ECA) at the level of the superior border of the thyroid cartilage
    corresponding to the disc space between the third and fourth cervical vertebral
    bodies",
    " <span class=\"nowrap\">",
    " (C3/C4).",
    " </span>",
    " </p>",
    " <p>",
    " The external carotid artery (ECA) has multiple branches which supply the face
    and scalp (",
    " <a class=\"graphic graphic_figure graphicRef50495 \" href=\"UTD.htm?
    31/61/32728\">",
    " figure 2",
    " </a>",
    " ) and provide collateral circulation to the brain. Traumatic injuries to the
    ECA are usually tolerated neurologically with the occasional exception of patients
    with pre-existing cerebrovascular disease. When the ICAs or vertebral arteries (VA)
    have significant stenoses or occlusion, the ECA branches may provide critical
    collateral pathways for cerebral blood flow (",
    " <a class=\"graphic graphic_figure graphicRef82579 \" href=\"UTD.htm?
    31/46/32487\">",
    " figure 3",
    " </a>",
    " ).",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H2918748\">",
    " <span class=\"h3\">",
    " Internal carotid artery segments",
    " </span>",
    " &nbsp;&mdash;&nbsp;The ICA (",
    " <a class=\"graphic graphic_figure graphicRef63286 \" href=\"UTD.htm?
    4/48/4874\">",
    " figure 4",
    " </a>",
    " ) is divided into four segments based upon anatomic landmarks.",
    " </p>",
    " <p>",
    " <ul class=\"bullet-block\">",
    " <li>",
    " Cervical &ndash; The cervical portion usually has no named branches as it
    ascends anterior to the spine. Blunt trauma to the neck in this region can lead to
    compression of the ICA against the transverse processes of the first through third
    (C1-C3) vertebral bodies.",
    " </li>",
    " <li>",
    " Petrous &ndash; The petrous segment traverses the carotid canal in the
    petrous portion of the temporal bone. Basilar skull fractures can cause laceration
    of the ICA at this site.",
    " </li>",
    " <li>",
    " Cavernous &ndash; The cavernous portion, also called the carotid siphon
    because of its S-shape, is the first portion of the ICA within the cranial vault.
    This segment is suspended between the layers of the dura mater that form the
    cavernous sinus. Fracture of the sphenoid bone may injure the cavernous portion.",
    " </li>",
    " <li>",
    " Cerebral",
    " <strong>",
    " </strong>",
    " &ndash; The ICA perforates the dura mater at the anterior clinoid process to
    become the cerebral (or supraclinoid) segment which divides into the anterior and
    middle cerebral arteries [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/266/abstract/11\">",
    " 11",
    " </a>",
    " ].",
    " </li>",
    " </ul>",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H3979568\">",
    " <span class=\"h2\">",
    " Posterior circulation",
    " </span>",
    " &nbsp;&mdash;&nbsp;The posterior circulation supplies the midbrain,
    cerebellum, occipital lobe and medial temporal lobes. Injuries to the vessels that
    supply these regions can lead to a variety of syndromes depending upon the specific
    nature of the injury (See",
    " <a class=\"local\" href=\"#H3979590\">",
    " 'Clinical presentation'",
    " </a>",
    " below and",
    " <a class=\"medical medical_review\" href=\"UTD.htm?8/63/9208?
    source=see_link\">",
    " \"Etiology and classification of stroke\"",
    " </a>",
    " and",
    " <a class=\"medical medical_review\" href=\"UTD.htm?38/22/39273?
    source=see_link\">",
    " \"Posterior circulation cerebrovascular syndromes\"",
    " </a>",
    " .)",
    " </p>",
    " <p>",
    " The VAs most commonly originate from the subclavian arteries, although some
    variation can occur. The VAs originate directly from the aortic arch in 3 to 5
    percent of individuals [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/266/abstract/12\">",
    " 12",
    " </a>",
    " ]. The VAs are commonly asymmetric in diameter and it is not uncommon for one
    VA to be atretic, a finding that is slightly more common on the left than the right
    [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/266/abstract/11\">",
    " 11",
    " </a>",
    " ].",
    " </p>",
    " <p>",
    " The VA traverses the neck anterior to the scalene muscle, enters the vertebral
    foramina of the sixth cervical vertebra and exits the transverse foramina of the
    second cervical vertebra.",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H2918703\">",
    " <span class=\"h3\">",
    " Vertebral segments",
    " </span>",
    " &nbsp;&mdash;&nbsp;The VA is divided into four anatomic segments (V1-V4) (",
    " <a class=\"graphic graphic_figure graphicRef56466 \" href=\"UTD.htm?
    36/0/36867\">",
    " figure 5",
    " </a>",
    " ).",
    " </p>",
    " <p>",
    " <ul class=\"bullet-block\">",
    " <li>",
    " V1 &ndash; Origin of the vessel to the foramina of the sixth cervical (C6)
    transverse process.",
    " </li>",
    " <li>",
    " V2 &ndash; Intraforaminal segment from the sixth to the second cervical
    vertebral body (C6 to C2).",
    " </li>",
    " <li>",
    " V3 &ndash; From the second cervical (C2) foramina to the base of the skull",
    " </li>",
    " <li>",
    " V4 &ndash; Intracerebral segment of the vertebral artery. The vertebral
    arteries merge to form the basilar artery and are intradural.",
    " </li>",
    " </ul>",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H182474602\">",
    " <span class=\"h2\">",
    " Site of injury",
    " </span>",
    " &nbsp;&mdash;&nbsp;Bilateral cerebrovascular injuries are common, occurring in
    18 to 25 percent of patients [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/266/abstract/4,6,13\">",
    " 4,6,13",
    " </a>",
    " ]. Carotid injuries appear to occur more frequently than vertebral injuries.
    In a retrospective review of 171 patients found to have blunt cerebrovascular
    injury, 114 patients had 157 carotid artery injuries and 79 patients had 97
    vertebral artery injuries [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/266/abstract/6\">",
    " 6",
    " </a>",
    " ]. However, some studies have shown equal number or a preponderance of
    vertebral injuries [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/266/abstract/14,15\">",
    " 14,15",
    " </a>",
    " ].",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H219286045\">",
    " <span class=\"h1\">",
    " MECHANISMS OF INJURY",
    " </span>",
    " &nbsp;&mdash;&nbsp;A variety of trauma mechanisms including motor vehicle
    crashes, falls, assaults, and suicide attempts can result in blunt cerebrovascular
    injury. Motor vehicle crashes account for more than half of blunt cerebrovascular
    injuries [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/266/abstract/4,6,13\">",
    " 4,6,13",
    " </a>",
    " ]. The absence of trauma from an individual&rsquo;s history does not exclude
    trauma as an etiology, because patients often consider the inciting event to be
    insignificant or too embarrassing to tell their physician.",
    " </p>",
    " <p>",
    " Blunt injury to the carotid or vertebral arteries is usually the result of a
    significant force that twists or stretches the vessel, or impinges the vessel
    against the underlying bone, often for only a brief period of time. The carotid or
    vertebral artery may also be lacerated by bone that has fractured.",
    " </p>",
    " <p>",
    " In 1974 four fundamental mechanisms of blunt carotid injuries were described
    [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/266/abstract/16\">",
    " 16",
    " </a>",
    " ]:",
    " </p>",
    " <p>",
    " <ul class=\"bullet-block\">",
    " <li>",
    " Type I carotid injuries involve the direct application of force to the neck
    (eg, seatbelt, strangulation, near-hanging) and account for up to about 10 percent
    of blunt carotid injuries.",
    " </li>",
    " <li>",
    " Type II carotid injuries are due to hyperextension and contralateral
    rotation of the head and neck (",
    " <a class=\"graphic graphic_figure graphicRef56047 \" href=\"UTD.htm?
    26/17/26899\">",
    " figure 6",
    " </a>",
    " ). This is probably the most common mechanism of injury. The lateral
    articular processes and pedicles of the upper three cervical vertebrae (C1-C3)
    project more anteriorly than those of the lower four cervical (C4-C7) vertebrae.
    Thus, in the upper region, the cervical internal carotid artery (ICA) can be
    stretched across the lateral processes with cervical hyperextension. Rotation at
    the atlanto-axial joint aggravates stretch injury because it can cause anterior
    movement of the contralateral C1 transverse process [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/266/abstract/17\">",
    " 17",
    " </a>",
    " ].",
    " </li>",
    " <li>",
    " Type III carotid injuries involve intraoral trauma that affect the internal
    carotid artery at the angle of the jaw (",
    " <a class=\"graphic graphic_figure graphicRef56047 \" href=\"UTD.htm?
    26/17/26899\">",
    " figure 6",
    " </a>",
    " ). This type of injury is seen in patients who fall with a hard object in
    the mouth such as in children who have fallen with a toothbrush in their mouth [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/266/abstract/18\">",
    " 18",
    " </a>",
    " ].",
    " </li>",
    " <li>",
    " Type IV injuries are due to laceration of the carotid artery resulting from
    basilar skull fracture, most commonly in the region of the carotid canal [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/266/abstract/19\">",
    " 19",
    " </a>",
    " ]. &nbsp;",
    " </li>",
    " </ul>",
    " </p>",
    " <p>",
    " Regardless of the underlying mechanism of injury, the pathologic insult in
    most cases is an intimal tear. The exposed subendothelial collagen promotes
    platelet aggregation and thrombus formation, which may occlude the vessel
    altogether or embolize to the cerebral circulation.",
    " </p>",
    " <p>",
    " The intimal tear may remain static or there may be a subintimal dissection
    that progresses cranially, which can cause luminal narrowing or acute vessel
    occlusion as the false lumen collapses against the true lumen. Less commonly,
    partial or complete transection of the artery occurs, resulting in pseudoaneurysm
    formation or free rupture. A pseudoaneurysm may increase in size to compress and
    occlude the vessel lumen, or rupture; if it contains thrombus, it may be a source
    of platelet thromboembolism. Rupture may result in intracranial or extracranial
    hemorrhage, or formation of an arteriovenous fistula.",
    " </p>",
    " <p>",
    " Other cerebrovascular injury mechanisms have been reported. As an example,
    numerous case reports document blunt injuries (mostly dissection) following
    mechanisms that would not typically raise a suspicion for injury, so-called
    &ldquo;trivial trauma.&rdquo; These mechanisms include chiropractic manipulation,
    hyperflexion or hyperextension during hair washing, &ldquo;head banging&rdquo; to
    music, &ldquo;bottoms-up&rdquo; drinking, rapid head turning, virtually any
    athletic endeavor, and everyday activities such as coughing, shaving, vomiting, and
    nose-blowing [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/266/abstract/11\">",
    " 11",
    " </a>",
    " ].",
    " </p>",
    " <p>",
    " &ldquo;Spontaneous&rdquo; carotid and vertebral artery dissections occur in
    the absence of apparent etiologic factors and account for about 2 to 3 percent of
    primary strokes [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/266/abstract/20\">",
    " 20",
    " </a>",
    " ]. Risk factors include hypertension, Marfan syndrome, fibromuscular
    dysplasia, syphilis, arteriopathies, and Erdheim&rsquo;s cystic medial necrosis.
    Some speculate that the presence of these medical risk factors (whether or not
    their presence is known) predisposes these patients to cerebrovascular injury
    following lesser degrees of trauma. Spontaneous carotid and vertebral artery
    dissections are discussed separately. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?10/30/10730?
    source=see_link\">",
    " \"Spontaneous cerebral and cervical artery dissection: Clinical features and
    diagnosis\"",
    " </a>",
    " .)",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H3981270\">",
    " <span class=\"h1\">",
    " TRAUMA EVALUATION",
    " </span>",
    " &nbsp;&mdash;&nbsp;The initial resuscitation, diagnostic evaluation, and
    management of the patient with blunt or penetrating injury is based upon protocols
    from the Advanced Trauma Life Support (ATLS&reg;) program, established by the
    American College of Surgeons Committee on Trauma. The initial resuscitation and
    evaluation of the patient with blunt trauma is discussed elsewhere. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?19/5/19545?
    source=see_link\">",
    " \"Initial evaluation and management of blunt abdominal trauma in adults\"",
    " </a>",
    " and",
    " <a class=\"medical medical_review\" href=\"UTD.htm?33/39/34426?
    source=see_link\">",
    " \"Initial evaluation and management of blunt thoracic trauma in adults\"",
    " </a>",
    " and",
    " <a class=\"medical medical_review\" href=\"UTD.htm?7/49/7962?
    source=see_link&amp;anchor=H25#H25\">",
    " \"Facial trauma in adults\", section on 'Midface'",
    " </a>",
    " .)",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H219286132\">",
    " <span class=\"h2\">",
    " Associated injuries",
    " </span>",
    " &nbsp;&mdash;&nbsp;Blunt cerebrovascular injury is associated with mechanisms
    that can cause severe head, facial, spine, chest, and abdominal injuries [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/266/abstract/2,7-9\">",
    " 2,7-9",
    " </a>",
    " ]. In a review of 171 patients with blunt cerebrovascular injury, the average
    injury severity score was 28 &plusmn; 1, which is consistent with other reports.
    Associated injuries included the brain (57 percent), spine (44 percent), chest (43
    percent), and face (34 percent) [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/266/abstract/6\">",
    " 6",
    " </a>",
    " ].",
    " </p>",
    " <p>",
    " Cervical spine fracture has the strongest association with blunt
    cerebrovascular injury [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/266/abstract/21,22\">",
    " 21,22",
    " </a>",
    " ]. A systematic review and metaanalysis identified only cervical spine injury
    and thoracic injury as significantly increasing the risk for blunt cerebrovascular
    injury (odds ratio [OR] 5.45, 95% CI 2.24-13.27, OR 1.98, 95% CI 1.35-2.92,
    respectively) [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/266/abstract/22\">",
    " 22",
    " </a>",
    " ]. In a retrospective review that stratified cervical spine fractures as high-
    risk (C1-C3) or low-risk (isolated, low [C4-C7]) for blunt cerebrovascular injury,
    the incidence of blunt cerebrovascular injury was 8 and 2 percent, respectively,
    suggesting the need to screen all cervical spine injuries [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/266/abstract/23\">",
    " 23",
    " </a>",
    " ]. (See",
    " <a class=\"local\" href=\"#H19564013\">",
    " 'Screening'",
    " </a>",
    " below.)",
    " </p>",
    " <p>",
    " Delayed recognition of blunt cerebrovascular injury may result from the need
    for clinicians to manage life-threatening thoracic or abdominal injuries [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/266/abstract/9\">",
    " 9",
    " </a>",
    " ]. In some cases, a meaningful neurologic examination is not possible due to
    head injuries or the need to sedate or intubate the patient.",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H3979590\">",
    " <span class=\"h1\">",
    " CLINICAL PRESENTATION",
    " </span>",
    " &nbsp;&mdash;&nbsp;The clinical presentation of blunt cerebrovascular injury
    can vary greatly depending upon the vessel affected, site of injury, injury grade
    and any pre-existing cerebrovascular disease. (See",
    " <a class=\"local\" href=\"#H19563955\">",
    " 'Cerebrovascular anatomy'",
    " </a>",
    " above and",
    " <a class=\"medical medical_review\" href=\"UTD.htm?8/47/8953?
    source=see_link&amp;anchor=H280052#H280052\">",
    " \"Blunt cerebrovascular injury: Treatment and outcomes\", section on 'Injury
    grading'",
    " </a>",
    " .)",
    " </p>",
    " <p>",
    " Approximately 80 percent of patients with blunt cerebrovascular injury have no
    obvious neurologic manifestations at presentation [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/266/abstract/6\">",
    " 6",
    " </a>",
    " ]. A latent period between the time of injury and the appearance of clinical
    manifestations is typically seen. Unless the vessel immediately occludes, time is
    required for thrombus formation that might limit flow or lead to distal
    embolization. In various studies, 25 to 50 percent of patients first developed
    signs or symptoms of blunt carotid injury more than 12 hours after the traumatic
    event [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/266/abstract/4,9,24-28\">",
    " 4,9,24-28",
    " </a>",
    " ].",
    " </p>",
    " <p>",
    " The following observations have been made in studies in which screening for
    cerebrovascular injury was performed in patients with blunt trauma:",
    " </p>",
    " <p>",
    " <ul class=\"bullet-block\">",
    " <li>",
    " In 17 patients diagnosed with blunt cerebrovascular injury identified from
    3480 blunt trauma admissions, 10 deaths were attributable to the injury [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/266/abstract/9\">",
    " 9",
    " </a>",
    " ]. The median time until diagnosis was 12.5 hours for the entire group and
    19.5 hours for non-survivors. Four of five patients whose diagnosis was delayed for
    more than 48 hours did not survive.",
    " </li>",
    " <li>",
    " In an analysis of 45 blunt cerebrovascular injury-related strokes occurring
    in patients who could not receive antithrombotic therapy, 11 out of 45 occurred
    within two hours of injury; the average time to stroke in the remaining 34 of 45
    patients was 75 hours [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/266/abstract/27\">",
    " 27",
    " </a>",
    " ].",
    " </li>",
    " <li>",
    " In another retrospective review of 76 patients with blunt cerebrovascular
    injury, 42 percent of symptomatic patients manifested symptoms more than 18 hours
    following injury, with two patients becoming symptomatic at seven days [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/266/abstract/28\">",
    " 28",
    " </a>",
    " ].",
    " </li>",
    " <li>",
    " The average time to stroke can range from two hours to one week, but most
    occurs between 12 and 75 hours [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/266/abstract/4,9,24-30\">",
    " 4,9,24-30",
    " </a>",
    " ].",
    " </li>",
    " </ul>",
    " </p>",
    " <p>",
    " When neurologic manifestations of cerebral ischemia occur, the symptoms and
    findings on neurologic examination depend upon the specific artery involved, the
    presence (or absence) of adequate collateral circulation (",
    " <a class=\"graphic graphic_figure graphicRef82579 \" href=\"UTD.htm?
    31/46/32487\">",
    " figure 3",
    " </a>",
    " ), and the presence (or absence) of underlying cerebrovascular disease.
    Approximately 10 to 15 percent of symptomatic patients have lateralizing symptoms,
    and at least 50 percent develop a completed stroke. No single neurologic finding
    allows a precise diagnosis, but the constellation of findings may identify the
    involved artery [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/266/abstract/2\">",
    " 2",
    " </a>",
    " ]. The manifestations of cerebral ischemia are reviewed elsewhere. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?27/47/28410?
    source=see_link\">",
    " \"Overview of the evaluation of stroke\"",
    " </a>",
    " and",
    " <a class=\"medical medical_review\" href=\"UTD.htm?39/46/40678?
    source=see_link\">",
    " \"Etiology and clinical manifestations of transient ischemic attack\"",
    " </a>",
    " and",
    " <a class=\"medical medical_review\" href=\"UTD.htm?8/63/9208?
    source=see_link\">",
    " \"Etiology and classification of stroke\"",
    " </a>",
    " and",
    " <a class=\"medical medical_review\" href=\"UTD.htm?38/22/39273?
    source=see_link\">",
    " \"Posterior circulation cerebrovascular syndromes\"",
    " </a>",
    " .)",
    " </p>",
    " <p>",
    " Certain clinical signs are so suggestive of blunt cerebrovascular injury that
    they should prompt emergent diagnostic evaluation, usually with CT (see",
    " <a class=\"local\" href=\"#H3987108\">",
    " 'Imaging evaluation'",
    " </a>",
    " below). These include acute arterial hemorrhage from the neck, mouth, nose, or
    ear; expanding cervical hematoma; cervical bruit in a patient younger than 50 years
    of age; and focal or lateralizing neurologic deficits (eg, hemiparesis, transient
    ischemic attack, Horner's syndrome, oculosympathetic paresis, vertebrobasilar
    insufficiency) (",
    " <a class=\"graphic graphic_algorithm graphicRef78174 \" href=\"UTD.htm?
    1/42/1698\">",
    " algorithm 1",
    " </a>",
    " ). Patients with acute hemorrhage are treated to limit the amount of blood
    loss and prevent shock. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?13/20/13639?
    source=see_link\">",
    " \"Treatment of severe hypovolemia or hypovolemic shock in adults\"",
    " </a>",
    " and",
    " <a class=\"medical medical_review\" href=\"UTD.htm?8/47/8953?
    source=see_link&amp;anchor=H280052#H280052\">",
    " \"Blunt cerebrovascular injury: Treatment and outcomes\", section on 'Injury
    grading'",
    " </a>",
    " .)",
    " </p>",
    " <p>",
    " Symptoms such as, neck, ear, face, or periorbital pain occur in up to 60
    percent of patients with carotid or vertebral artery dissection in the neck [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/266/abstract/31\">",
    " 31",
    " </a>",
    " ]. However, pain may be difficult to elicit in the multiply-injured patient,
    or may be attributed to other injuries. Thus, any patient with neck pain or
    headache following blunt trauma should be suspected of having cerebrovascular
    injury.",
    " </p>",
    " <p>",
    " Neurologic signs associated with local arterial injury, which occur in
    approximately 5 percent of symptomatic patients, suggest that blunt cerebrovascular
    injury has occurred even though patients have no manifestations of cerebral
    ischemia. As an example, blunt carotid injury can disrupt the periarterial
    sympathetic plexus, leading to Horner&rsquo;s syndrome (ptosis, myosis, anhidrosis)
    or oculosympathetic paresis, which is a partial Horner&rsquo;s syndrome that
    includes ptosis and miosis. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?31/32/32262?
    source=see_link\">",
    " \"Horner's syndrome\"",
    " </a>",
    " .)",
    " </p>",
    " <p>",
    " Although pupillary asymmetry can have a number of etiologies in the trauma
    patient, blunt cerebrovascular injury should be suspected ipsilateral to the side
    of the smaller pupil if the larger of the pupils is reactive and the smaller pupil
    is not [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/266/abstract/32\">",
    " 32",
    " </a>",
    " ].",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H19564013\">",
    " <span class=\"h1\">",
    " SCREENING",
    " </span>",
    " &nbsp;&mdash;&nbsp;Screening for blunt cerebrovascular injury has been
    controversial. As described in the preceding section, a majority of patients with
    blunt cerebrovascular injury do not have neurologic symptoms at presentation but
    may develop signs or symptoms hours or days later. (See",
    " <a class=\"local\" href=\"#H3979590\">",
    " 'Clinical presentation'",
    " </a>",
    " above.)",
    " </p>",
    " <p>",
    " Most clinicians feel that this delay provides a window of opportunity during
    which patients at risk for adverse outcomes can be identified and stroke-prevention
    therapy initiated [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/266/abstract/1,7,33,34\">",
    " 1,7,33,34",
    " </a>",
    " ]. Screening has clearly increased the number of blunt cerebrovascular
    injuries being diagnosed [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/266/abstract/6,14,33,35-37\">",
    " 6,14,33,35-37",
    " </a>",
    " ]. Although failure to identify and treat blunt cerebrovascular injury when
    symptoms occur results in significant morbidity and mortality, it is unclear
    whether aggressive screening leads to improved outcomes [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/266/abstract/38,39\">",
    " 38,39",
    " </a>",
    " ]. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?8/47/8953?
    source=see_link&amp;anchor=H259262#H259262\">",
    " \"Blunt cerebrovascular injury: Treatment and outcomes\", section on 'Stroke
    and mortality'",
    " </a>",
    " .)",
    " </p>",
    " <p>",
    " Some investigators have suggested that blunt cerebrovascular injury cannot be
    reliably predicted based upon the injury mechanism and clinical presentation [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/266/abstract/40\">",
    " 40",
    " </a>",
    " ]. However, others have critically evaluated specific injury mechanisms,
    patterns of injury, and clinical symptoms and signs of blunt cerebrovascular injury
    to define criteria by which to perform diagnostic testing. (See",
    " <a class=\"local\" href=\"#H4011653\">",
    " 'Indications for imaging'",
    " </a>",
    " below.)",
    " </p>",
    " <p>",
    " In the earliest study of screening, 171 patients with indications to exclude
    thoracic aortic injury using arteriography also underwent carotid arteriography.
    Although these patients had no symptoms or signs to suggest blunt cerebrovascular
    injury, 3.5 percent of the studies were positive [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/266/abstract/41\">",
    " 41",
    " </a>",
    " ]. Subsequently, using defined clinical criteria, blunt cerebrovascular injury
    was identified in 27 percent of the asymptomatic patients screened [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/266/abstract/42\">",
    " 42",
    " </a>",
    " ]. After instituting a policy of screening, the incidence of blunt carotid
    injury increased from 0.1 to 1.6 percent [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/266/abstract/1,6\">",
    " 1,6",
    " </a>",
    " ]. These findings have been replicated at several other trauma centers [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/266/abstract/14,33,35-38\">",
    " 14,33,35-38",
    " </a>",
    " ].",
    " </p>",
    " <p>",
    " A multivariate analysis identified independent risk factors for blunt carotid
    injury (",
    " <a class=\"graphic graphic_algorithm graphicRef78174 \" href=\"UTD.htm?
    1/42/1698\">",
    " algorithm 1",
    " </a>",
    " ) that included Glasgow coma scale (GCS) &lt;6 (",
    " <a class=\"graphic graphic_table graphicRef81854 \" href=\"UTD.htm?
    28/62/29676\">",
    " table 1",
    " </a>",
    " ), petrous bone fracture, diffuse axonal brain injury, and LeFort II or LeFort
    III fracture (",
    " <a class=\"graphic graphic_figure graphicRef55687 \" href=\"UTD.htm?
    2/57/2966\">",
    " figure 7",
    " </a>",
    " ) [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/266/abstract/42\">",
    " 42",
    " </a>",
    " ]. The presence of any one of these factors identified 41 percent of the
    patients with blunt carotid injury and increased to 93 percent in the presence of
    all four factors. On the other hand, 20 percent of patients who had blunt
    cerebrovascular injury did not have any of these risk factors. The only independent
    predictor of blunt vertebral artery injury was cervical spine fracture.",
    " </p>",
    " <p>",
    " Another retrospective review used the above criteria to screen patients for
    blunt cerebrovascular injury and included additional criteria to capture specific
    cervical spine fracture patterns (",
    " <a class=\"graphic graphic_algorithm graphicRef78174 \" href=\"UTD.htm?
    1/42/1698\">",
    " algorithm 1",
    " </a>",
    " ) [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/266/abstract/34\">",
    " 34",
    " </a>",
    " ]. Of those who met the screening criteria, 244 patients had a blunt
    cerebrovascular injury for an incidence of 1.5 percent. Carotid and vertebral
    injuries were seen nearly equally (141 carotid, 124 vertebral). More than one
    injury was seen in 37 percent of the patients.",
    " </p>",
    " <p>",
    " Optimal screening criteria continue to be debated [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/266/abstract/33,43-45\">",
    " 33,43-45",
    " </a>",
    " ]. More restrictive criteria might yield a higher proportion of positive
    results, decreased complications related to arteriography, and lower cost, but an
    increase in the likelihood of missing an injury in an unscreened patient. The use
    of noninvasive studies for screening, particularly computed tomography, may allow
    the criteria used for screening to be broadened [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/266/abstract/46\">",
    " 46",
    " </a>",
    " ]. (See",
    " <a class=\"local\" href=\"#H3987108\">",
    " 'Imaging evaluation'",
    " </a>",
    " below.)",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H282468\">",
    " <span class=\"h2\">",
    " Cost-effectiveness",
    " </span>",
    " &nbsp;&mdash;&nbsp;In a retrospective review that used defined criteria to
    perform screening arteriography in 727 of 15,767 patients with blunt trauma (4.6
    percent), blunt cerebrovascular injury was identified in 244 (34 percent) [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/266/abstract/34\">",
    " 34",
    " </a>",
    " ]. Antithrombotic therapy was initiated in 187 asymptomatic patients with",
    " <a class=\"drug drug_general\" href=\"UTD.htm?39/34/40489?source=see_link\">",
    " heparin",
    " </a>",
    " (117), low molecular-weight heparin (11), or antiplatelet agents (59). The
    following findings were noted:",
    " </p>",
    " <p>",
    " <ul class=\"bullet-block\">",
    " <li>",
    " One of the treated patients suffered a stroke (0.5 percent). In contrast,
    symptomatic patients who were not able to be anticoagulated had an ischemic
    neurologic event rate of 21 percent.",
    " </li>",
    " <li>",
    " Using estimated stroke rates for each grade of injury, the authors estimated
    that 32 neurologic events were averted by the early identification and treatment of
    asymptomatic patients with blunt cerebrovascular injury. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?8/47/8953?
    source=see_link&amp;anchor=H280052#H280052\">",
    " \"Blunt cerebrovascular injury: Treatment and outcomes\", section on
    'Injury grading'",
    " </a>",
    " .)",
    " </li>",
    " <li>",
    " The expense for arteriography was $6800 per patient for a total cost of
    $4,943,600 in the 727 patients. For each of the 32 estimated neurologic events, an
    incremental increase in the cost of treatment and rehabilitation over the
    patient&rsquo;s lifetime that exceeds $154,000 would justify the screening process.
    The use of less expensive screening modalities, such as computed tomography, might
    further increase cost savings, but screening a greater proportion of patients would
    offset this savings. (See",
    " <a class=\"local\" href=\"#H19564013\">",
    " 'Screening'",
    " </a>",
    " above.)",
    " </li>",
    " </ul>",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H4011653\">",
    " <span class=\"h1\">",
    " INDICATIONS FOR IMAGING",
    " </span>",
    " &nbsp;&mdash;&nbsp;Neurovascular imaging is indicated for patients with any
    clinical symptom or sign suggestive of blunt cerebrovascular injury, patients with
    unexplained neurologic symptoms and in asymptomatic patients with any of the risk
    factors listed below (",
    " <a class=\"graphic graphic_algorithm graphicRef78174 \" href=\"UTD.htm?
    1/42/1698\">",
    " algorithm 1",
    " </a>",
    " ). &nbsp;",
    " </p>",
    " <p>",
    " The following clinical signs are suggestive of blunt cerebrovascular injury in
    the trauma patient and should prompt emergent evaluation and interventions directed
    at hemorrhage control or stroke management. (See",
    " <a class=\"local\" href=\"#H3979590\">",
    " 'Clinical presentation'",
    " </a>",
    " above.)",
    " </p>",
    " <p>",
    " <ul class=\"bullet-block\">",
    " <li>",
    " Arterial hemorrhage from the neck, mouth, nose, or ear",
    " </li>",
    " <li>",
    " Cervical hematoma",
    " </li>",
    " <li>",
    " Cervical bruit in a patient younger than 50 years of age",
    " </li>",
    " <li>",
    " Focal or lateralizing neurologic deficit (eg, hemiparesis, transient
    ischemic attack, Horner's syndrome, oculosympathetic paresis, vertebrobasilar
    insufficiency)",
    " </li>",
    " </ul>",
    " </p>",
    " <p>",
    " The following risk factors for blunt cerebrovascular injury have been endorsed
    by both the Eastern and Western Trauma Associations of the United States to
    screen",
    " <strong>",
    " asymptomatic",
    " </strong>",
    " patients (",
    " <a class=\"graphic graphic_algorithm graphicRef78174 \" href=\"UTD.htm?
    1/42/1698\">",
    " algorithm 1",
    " </a>",
    " ) [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/266/abstract/47,48\">",
    " 47,48",
    " </a>",
    " ]:",
    " </p>",
    " <p>",
    " <ul class=\"bullet-block\">",
    " <li>",
    " Injury mechanism compatible with severe cervical",
    " <span class=\"nowrap\">",
    " hyperextension/rotation",
    " </span>",
    " or hyperflexion",
    " </li>",
    " <li>",
    " LeFort II or LeFort III midface fractures",
    " </li>",
    " <li>",
    " Basilar skull fracture involving the carotid canal",
    " </li>",
    " <li>",
    " Closed head injury consistent with diffuse axonal injury with Glasgow Coma
    Score &lt;6",
    " </li>",
    " <li>",
    " Cervical vertebral body or transverse foramen fracture, subluxation, or
    ligamentous injury at any level, or any fracture at the level of C1-C3",
    " </li>",
    " <li>",
    " Near-hanging resulting in cerebral anoxia",
    " </li>",
    " <li>",
    " Clothesline-type injury or seat belt abrasion associated with significant
    cervical pain, swelling or altered mental status",
    " </li>",
    " </ul>",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H3987108\">",
    " <span class=\"h1\">",
    " IMAGING EVALUATION",
    " </span>",
    " &nbsp;&mdash;&nbsp;Patients with symptoms, signs or risk-factors for injury
    are presumed to have blunt cerebrovascular injury until proven otherwise. (See",
    " <a class=\"local\" href=\"#H4011653\">",
    " 'Indications for imaging'",
    " </a>",
    " above.)",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H282240\">",
    " <span class=\"h2\">",
    " Imaging modalities",
    " </span>",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H19564062\">",
    " <span class=\"h3\">",
    " CT angiography",
    " </span>",
    " &nbsp;&mdash;&nbsp;Although most studies have used arteriography to screen for
    blunt cerebrovascular injury, computed tomographic (CT) angiography is becoming the
    screening test of choice under both urgent and emergent circumstances (",
    " <a class=\"graphic graphic_algorithm graphicRef78174 \" href=\"UTD.htm?
    1/42/1698\">",
    " algorithm 1",
    " </a>",
    " ). This is primarily because patients who are candidates for screening often
    have indications for scanning other regions of the body such as the head, face,
    cervical spine, chest and abdomen. Another benefit of CT is a reduction in the
    volume of contrast needed to perform these studies which can be up to half that
    needed for arch aortography and four-vessel cerebral arteriography. (See",
    " <a class=\"local\" href=\"#H3981270\">",
    " 'Trauma evaluation'",
    " </a>",
    " above and",
    " <a class=\"local\" href=\"#H4011653\">",
    " 'Indications for imaging'",
    " </a>",
    " above.)",
    " </p>",
    " <p>",
    " The sensitivity and specificity of CT angiography for blunt cerebrovascular
    injury has increased with improvements in CT technology [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/266/abstract/49\">",
    " 49",
    " </a>",
    " ]. Studies comparing one, two or four-slice CT scanners with digital
    subtraction arteriography have found unacceptably low sensitivities for blunt
    cerebrovascular injury [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/266/abstract/35,50\">",
    " 35,50",
    " </a>",
    " ]. The sensitivity of four and eight-slice scanners for blunt carotid injury
    ranges from 83 to 92 percent and specificity is from 88 to 92 percent, while the
    sensitivity for blunt vertebral injury ranges from 50 percent to 60 percent with
    specificity from 90 to 97 percent [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/266/abstract/49\">",
    " 49",
    " </a>",
    " ].",
    " </p>",
    " <p>",
    " Sixteen slice or greater slice CT angiography is more reliable in the
    diagnosis of blunt cerebrovascular injuries [",
    " <a class=\"abstract\" href=\"UTD.htm?
    0/16/266/abstract/14,15,36,37,46,51,52\">",
    " 14,15,36,37,46,51,52",
    " </a>",
    " ]. Using a 16-slice scanner, the detected incidence of blunt cerebrovascular
    injury is consistent with that seen using digital subtraction arteriography [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/266/abstract/36,37\">",
    " 36,37",
    " </a>",
    " ]. Whole-body multidetector-row CT has now been adopted in some centers. It
    offers more rapid imaging, with a single dose of intravenous contrast. A
    preliminary report suggests an accuracy equivalent to 16-slice CTA but further
    evaluation is needed [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/266/abstract/53\">",
    " 53",
    " </a>",
    " ].",
    " </p>",
    " <p>",
    " The true sensitivity of CT angiography can be obtained only by direct
    comparison to digital subtraction arteriography as the standard. Four studies have
    performed these comparisons using 16 or 64-slice CT scanners with mixed results [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/266/abstract/14,15,51,52\">",
    " 14,15,51,52",
    " </a>",
    " ].",
    " </p>",
    " <p>",
    " <ul class=\"bullet-block\">",
    " <li>",
    " One study screened 146 patients for blunt cerebrovascular injury with both
    arteriography and CT angiography [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/266/abstract/14\">",
    " 14",
    " </a>",
    " ]. Injuries were identified in 46 patients (20 carotid, 26 vertebral). The
    sensitivity, specificity, positive predictive value, negative predictive value, and
    accuracy of CT angiography were 98, 100, 100, 99, and 99 percent, respectively. The
    single false positive results occurred in a patient with a grade I vertebral artery
    injury.",
    " </li>",
    " <li>",
    " Another study screened 372 blunt trauma patients with 16-slice CT
    angiography identifying 271 normal studies [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/266/abstract/51\">",
    " 51",
    " </a>",
    " ]. Arteriography was performed on a subset (82 patients) with normal CT
    angiography and identified 7 missed blunt cerebrovascular injuries. However, on re-
    review of the CT images, the injuries were evident in six of the seven patients;
    the seventh patient&rsquo;s abnormality was most likely not traumatic in origin.
    The inaccuracy of CT angiography appeared to be related, in part, to the
    radiologists&rsquo; experience, as all of the missed blunt cerebrovascular injury
    occurred in the first half of the study period.",
    " </li>",
    " <li>",
    " In a retrospective review of 7000 blunt trauma patients, 119 were screened
    using CT angiography using a 16-slice scanner and 92 of these patients underwent
    arteriography (3 refused consent, 24 were at high risk of contrast nephropathy) [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/266/abstract/52\">",
    " 52",
    " </a>",
    " ]. The sensitivity and specificity of CT angiography among the patients who
    underwent both studies was 74 and 84 percent, respectively. As with the study
    described above, the false negative studies were interpreted during the first half
    the study period indicating a learning curve on the part of the radiologists; the
    negative predictive value in the second half of the study was 100 percent.",
    " </li>",
    " <li>",
    " A study that screened 232 patients reported sensitivities of 29 percent for
    the 16-slice scanner and of 54 percent for 64-slice scanner [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/266/abstract/15\">",
    " 15",
    " </a>",
    " ]. The combined specificity was 97 percent. The major drawback with this
    study was a lack of quality control with no effort made to reconcile false positive
    results on CT imaging with the digital subtraction images; only the initial
    &ldquo;real-time&rdquo; interpretation was considered. Although it is important to
    acknowledge how things work in &ldquo;real time,&rdquo; a program of quality
    improvement is needed to overcome the learning curve associated with the
    interpretation of these injuries on CT angiography.",
    " </li>",
    " </ul>",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H2918853\">",
    " <span class=\"h3\">",
    " Digital subtraction arteriography",
    " </span>",
    " &nbsp;&mdash;&nbsp;Although four-vessel biplanar cerebral digital subtraction
    arteriography is the gold standard for the diagnosis of blunt cerebrovascular
    injury, CT angiography has largely supplanted its use. (See",
    " <a class=\"local\" href=\"#H19564062\">",
    " 'CT angiography'",
    " </a>",
    " above.)",
    " </p>",
    " <p>",
    " Arteriography is invasive and associated with access site complications (eg,
    hematoma, pseudoaneurysm), contrast nephropathy, contrast allergy, and stroke, and
    increased cost [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/266/abstract/6,54\">",
    " 6,54",
    " </a>",
    " ]. In addition, arteriography is expensive and may not be uniformly available.
    As such, CT angiography is being used as the primary screening modality while
    arteriography is reserved for further evaluation if the results of CT angiography
    are equivocal, or are negative but the clinical suspicion remains high (",
    " <a class=\"graphic graphic_algorithm graphicRef78174 \" href=\"UTD.htm?
    1/42/1698\">",
    " algorithm 1",
    " </a>",
    " ).",
    " </p>",
    " <p>",
    " When arteriography is needed to obtain a definitive diagnosis, each of the
    four vessels (bilateral carotid, bilateral vertebral) should be imaged from their
    origins in the chest and cerebral arteriography included to identify the presence
    of occluded terminal vessels and evaluate collateral circulation to the brain.",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H19564069\">",
    " <span class=\"h3\">",
    " MR angiography",
    " </span>",
    " &nbsp;&mdash;&nbsp;A number of studies describe the use of magnetic resonance
    (MR) angiography to identify blunt cerebrovascular injury [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/266/abstract/55-60\">",
    " 55-60",
    " </a>",
    " ]. The advantages of MR include the avoidance of iodinated contrast agents,
    lack of bony artifact, and earlier detection of cerebral infarction. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?16/56/17290?
    source=see_link&amp;anchor=H17#H17\">",
    " \"Neuroimaging of acute ischemic stroke\", section on 'CT versus MRI
    techniques in hyperacute stroke'",
    " </a>",
    " .)",
    " </p>",
    " <p>",
    " However, screening studies have found poor specificity at 67 percent with
    sensitivities ranging from 50 to 75 percent compared with conventional
    arteriography [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/266/abstract/35,50,61\">",
    " 35,50,61",
    " </a>",
    " ]. Given issues such as the time required for the study and incompatibility
    with implanted devices, MR angiography is not used as an independent modality for
    screening blunt cerebrovascular injury.",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H19564076\">",
    " <span class=\"h3\">",
    " Duplex ultrasonography",
    " </span>",
    " &nbsp;&mdash;&nbsp;Duplex ultrasonography was the first noninvasive study
    considered for the evaluation of blunt cerebrovascular injury [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/266/abstract/2,3,62\">",
    " 2,3,62",
    " </a>",
    " ], and although it is the test of choice for evaluating other pathologies (eg,
    atherosclerosis) of the extracranial carotid arteries, the data do not support
    ultrasound as an appropriate screening modality for blunt cerebrovascular injury
    [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/266/abstract/48\">",
    " 48",
    " </a>",
    " ].",
    " </p>",
    " <p>",
    " Duplex sonography is not a highly sensitive test to screen for blunt
    cerebrovascular injury primarily because imaging is limited to the cervical
    portions of the vessels; the majority of these injuries, particularly",
    " <span class=\"nowrap\">",
    " hyperextension/flexion",
    " </span>",
    " injuries, occur at the base of the skull [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/266/abstract/4,63-65\">",
    " 4,63-65",
    " </a>",
    " ]. Although duplex ultrasound can provide indirect evidence of distal injuries
    (eg, obstructive waveforms proximal to a flow limiting lesion), indirect findings
    are not reliable when the degree of stenosis is less significant (ie, &lt;60
    percent). Thus, grade I, grade III, and many grade II injuries could potentially be
    missed. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?8/47/8953?
    source=see_link&amp;anchor=H280052#H280052\">",
    " \"Blunt cerebrovascular injury: Treatment and outcomes\", section on 'Injury
    grading'",
    " </a>",
    " .)",
    " </p>",
    " <p>",
    " In addition, patients with skin abrasion and soft tissue swelling may not
    tolerate the examination due to pain. In addition, removal of the cervical collar
    is required to perform the examination. Given that these patients are at risk for
    cervical spine fracture, collar removal is often contraindicated.",
    " </p>",
    " <p>",
    " Duplex ultrasonography may have a limited role in evaluating select cases that
    involve direct blows to the anterior neck, follow-up of proximal lesions, and
    possibly in children, in whom other imaging techniques might require conscious
    sedation. When ultrasound is used, the ultrasonographer must be skilled and the
    interpreting clinician must recognize the limitations of the study in the trauma
    population.",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H282373\">",
    " <span class=\"h2\">",
    " Choice of imaging",
    " </span>",
    " &nbsp;&mdash;&nbsp;Conventional arteriography has historically been used to
    diagnose blunt cerebrovascular injury; however, the use of noninvasive imaging
    predominates for the reasons defined in the sections above. Computed tomographic
    (CT) angiography (&ge;16 slice) is the most reliable noninvasive screening modality
    for blunt cerebrovascular injury. A relatively high false positive rate is reported
    in some series, and thus, follow-up arteriography may be warranted to definitively
    exclude an injury, or provide a diagnosis when a high clinical suspicion remains
    but the CT study is normal. (See",
    " <a class=\"local\" href=\"#H19564062\">",
    " 'CT angiography'",
    " </a>",
    " above.)",
    " </p>",
    " <p>",
    " As discussed above, the sensitivity for CT angiography for blunt
    cerebrovascular injury depends upon the number of scanner slices. Thus, the
    evaluation of blunt cerebrovascular injury at a given institution will depend upon
    the available resources; arteriography should be used if an appropriately sensitive
    CT scanner is not available. If arteriography and high quality CT scanning are not
    available, the patient should be transferred to a trauma center for further
    evaluation. (See",
    " <a class=\"local\" href=\"#H2918853\">",
    " 'Digital subtraction arteriography'",
    " </a>",
    " above.)",
    " </p>",
    " <p>",
    " Duplex ultrasonography may play a role in the long-term follow-up of cervical
    carotid injuries; however, duplex ultrasound and magnetic resonance imaging are not
    sufficiently sensitive to be used for screening. (See",
    " <a class=\"local\" href=\"#H19564076\">",
    " 'Duplex ultrasonography'",
    " </a>",
    " above and",
    " <a class=\"local\" href=\"#H19564069\">",
    " 'MR angiography'",
    " </a>",
    " above.)",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H19564083\">",
    " <span class=\"h2\">",
    " Injury grading",
    " </span>",
    " &nbsp;&mdash;&nbsp;Grading the injury based upon its appearance on imaging was
    created to standardize clinical communication and guide therapy [",
    " <a class=\"abstract\" href=\"UTD.htm?0/16/266/abstract/28\">",
    " 28",
    " </a>",
    " ]. The treatment of blunt cerebrovascular also depends, in part, on the grade
    of injury. Injury grading is discussed in detail elsewhere. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?8/47/8953?
    source=see_link&amp;anchor=H280052#H280052\">",
    " \"Blunt cerebrovascular injury: Treatment and outcomes\", section on 'Injury
    grading'",
    " </a>",
    " .)",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H219284334\">",
    " <span class=\"h2\">",
    " Follow-up imaging",
    " </span>",
    " &nbsp;&mdash;&nbsp;A significant number of injuries evolve in a manner that
    could alter therapy and follow-up imaging is warranted in patients with blunt
    cerebrovascular injury (",
    " <a class=\"graphic graphic_algorithm graphicRef78174 \" href=\"UTD.htm?
    1/42/1698\">",
    " algorithm 1",
    " </a>",
    " ). The choice and timing of follow-up imaging is discussed elsewhere. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?8/47/8953?
    source=see_link&amp;anchor=H259255#H259255\">",
    " \"Blunt cerebrovascular injury: Treatment and outcomes\", section on 'Follow-
    up for healing or progression'",
    " </a>",
    " .)",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H3979752\">",
    " <span class=\"h1\">",
    " SUMMARY AND RECOMMENDATIONS",
    " </span>",
    " </p>",
    " <p>",
    " <ul class=\"bullet-block\">",
    " <li>",
    " Blunt carotid and vertebral artery injury are collectively termed blunt
    cerebrovascular injury and are rare but potentially disastrous injuries. The
    overall incidence of these injuries is about one percent of all blunt trauma
    admissions. (See",
    " <a class=\"local\" href=\"#H19563948\">",
    " 'Introduction'",
    " </a>",
    " above.)",
    " </li>",
    " <li>",
    " The circulation to the brain originates from the carotid and vertebral
    arteries comprising the anterior and posterior circulations, respectively. The
    circle of Willis, which provides communication between the anterior and posterior
    circulation, is completely intact and symmetric in only about 20 percent of
    individuals. Because of the inconsistency, the neurologic presentation of patients
    with blunt cerebrovascular injury is highly variable. (See",
    " <a class=\"local\" href=\"#H19563955\">",
    " 'Cerebrovascular anatomy'",
    " </a>",
    " above.)",
    " </li>",
    " <li>",
    " Patients sustaining blunt trauma who have the following clinical symptoms or
    signs should undergo",
    " <span class=\"nowrap\">",
    " urgent/emergent",
    " </span>",
    " imaging to evaluate for cerebrovascular injury:",
    " </li>",
    " </ul>",
    " </p>",
    " <p>",
    " <ul class=\"hyphen-block\">",
    " <li>",
    " Arterial hemorrhage from the neck, mouth, nose, or ear",
    " </li>",
    " <li>",
    " Expanding cervical hematoma",
    " </li>",
    " <li>",
    " Cervical bruit in patients &lt;50 years old",
    " </li>",
    " <li>",
    " Focal or lateralizing neurologic deficits",
    " </li>",
    " </ul>",
    " </p>",
    " <p>",
    " <ul class=\"bullet-block\">",
    " <li>",
    " We screen for blunt cerebrovascular injury in asymptomatic patients who have
    the risk factors for blunt cerebrovascular injury listed below. We prefer to use
    computed tomography (&ge;16 slice) for screening. If an appropriately sensitive CT
    scanner is not available, arteriography should be performed. For institutions
    without this imaging capability, transfer to a trauma facility is indicated. (See",
    " <a class=\"local\" href=\"#H4011653\">",
    " 'Indications for imaging'",
    " </a>",
    " above and",
    " <a class=\"local\" href=\"#H282373\">",
    " 'Choice of imaging'",
    " </a>",
    " above.)",
    " </li>",
    " </ul>",
    " </p>",
    " <p>",
    " <ul class=\"hyphen-block\">",
    " <li>",
    " Injury mechanism compatible with severe cervical",
    " <span class=\"nowrap\">",
    " hyperextension/rotation",
    " </span>",
    " or hyperflexion",
    " </li>",
    " <li>",
    " LeFort II or LeFort III midface fractures",
    " </li>",
    " <li>",
    " Basilar skull fracture that involves the carotid canal",
    " </li>",
    " <li>",
    " Closed head injury consistent with diffuse axonal injury with Glasgow Coma
    Score &lt;6",
    " </li>",
    " <li>",
    " Cervical vertebral fracture, subluxation, or ligamentous injury at any
    level",
    " </li>",
    " <li>",
    " Near-hanging resulting in cerebral anoxia",
    " </li>",
    " <li>",
    " Clothesline-type injury or seat-belt abrasion associated with significant
    cervical pain, swelling or altered mental status",
    " </li>",
    " </ul>",
    " </p>",
    " </div>",
    " <div id=\"topicAgreement\">",
    " Use of UpToDate is subject to the",
    " <a class=\"licenseLink\" href=\"./license\" id=\"sla_in_page\"
    target=\"_blank\">",
    " Subscription and License Agreement",
    " </a>",
    " .",
    " </div>",
    " <div class=\"headingAnchor\" id=\"references\">",
    " <h1>",
    " REFERENCES",
    " </h1>",
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    " </ol>",
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    " <a href=\"#\" title=\"Collapse Topic Outline\">",
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    " </a>",
    " </div>",
    " <div id=\"innerOutline\">",
    " <h1>",
    " TOPIC OUTLINE",
    " </h1>",
    " <div id=\"outline\">",
    " <ul>",
    " <li>",
    " <a class=\"sr_button\" href=\"#H3979752\" id=\"summRecButton\">",
    " <span>",
    " SUMMARY &amp; RECOMMENDATIONS",
    " </span>",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#H19563948\">",
    " INTRODUCTION",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#H19563955\">",
    " CEREBROVASCULAR ANATOMY",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H3979546\">",
    " Anterior circulation",
    " </a>",
    " </li>",
    " <li class=\"dashItem\">",
    " <a class=\"outlineLink\" href=\"#H2918748\">",
    " - Internal carotid artery segments",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H3979568\">",
    " Posterior circulation",
    " </a>",
    " </li>",
    " <li class=\"dashItem\">",
    " <a class=\"outlineLink\" href=\"#H2918703\">",
    " - Vertebral segments",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H182474602\">",
    " Site of injury",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#H219286045\">",
    " MECHANISMS OF INJURY",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#H3981270\">",
    " TRAUMA EVALUATION",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H219286132\">",
    " Associated injuries",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#H3979590\">",
    " CLINICAL PRESENTATION",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#H19564013\">",
    " SCREENING",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H282468\">",
    " Cost-effectiveness",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#H4011653\">",
    " INDICATIONS FOR IMAGING",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#H3987108\">",
    " IMAGING EVALUATION",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H282240\">",
    " Imaging modalities",
    " </a>",
    " </li>",
    " <li class=\"dashItem\">",
    " <a class=\"outlineLink\" href=\"#H19564062\">",
    " - CT angiography",
    " </a>",
    " </li>",
    " <li class=\"dashItem\">",
    " <a class=\"outlineLink\" href=\"#H2918853\">",
    " - Digital subtraction arteriography",
    " </a>",
    " </li>",
    " <li class=\"dashItem\">",
    " <a class=\"outlineLink\" href=\"#H19564069\">",
    " - MR angiography",
    " </a>",
    " </li>",
    " <li class=\"dashItem\">",
    " <a class=\"outlineLink\" href=\"#H19564076\">",
    " - Duplex ultrasonography",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H282373\">",
    " Choice of imaging",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H19564083\">",
    " Injury grading",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H219284334\">",
    " Follow-up imaging",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#H3979752\">",
    " SUMMARY AND RECOMMENDATIONS",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a href=\"#references\">",
    " REFERENCES",
    " </a>",
    " </li>",
    " </ul>",
    " </div>",
    " <h1>",
    " <div class=\"openRelatedGraphics\" id=\"SURG/15154\" rel=\"outline_link\">",
    " GRAPHICS",
    " <a class=\"graphics_icon\" href=\"#\" title=\"View All Related Graphics\">",
    " View All",
    " </a>",
    " </div>",
    " </h1>",
    " <div id=\"relatedGraphics\">",
    " <ul>",
    " <li class=\"plainItem\">",
    " <div class=\"openRelatedGraphics\" id=\"SURG/15154|ALG\">",
    " <a href=\"#\" title=\"ALGORITHMS\">",
    " ALGORITHMS",
    " </a>",
    " </div>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"graphic graphic_algorithm\" href=\"UTD.htm?1/42/1698\"
    title=\"algorithm 1\">",
    " Blunt cerebrovascular injury algorithm",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <div class=\"openRelatedGraphics\" id=\"SURG/15154|FIG\">",
    " <a href=\"#\" title=\"FIGURES\">",
    " FIGURES",
    " </a>",
    " </div>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"graphic graphic_figure\" href=\"UTD.htm?2/4/2122\" title=\"figure
    1\">",
    " Cerebral arterial circulation",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"graphic graphic_figure\" href=\"UTD.htm?31/61/32728\"
    title=\"figure 2\">",
    " External carotid artery anatomy",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"graphic graphic_figure\" href=\"UTD.htm?31/46/32487\"
    title=\"figure 3\">",
    " Collateral circulation between external and internal carotid",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"graphic graphic_figure\" href=\"UTD.htm?4/48/4874\" title=\"figure
    4\">",
    " Lateral view of the internal carotid artery",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"graphic graphic_figure\" href=\"UTD.htm?36/0/36867\"
    title=\"figure 5\">",
    " Segments of the vertebral artery",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"graphic graphic_figure\" href=\"UTD.htm?26/17/26899\"
    title=\"figure 6\">",
    " Mechanism of blunt cerebrovascular injury",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"graphic graphic_figure\" href=\"UTD.htm?2/57/2966\" title=\"figure
    7\">",
    " LeFort fractures of the midface",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <div class=\"openRelatedGraphics\" id=\"SURG/15154|TAB\">",
    " <a href=\"#\" title=\"TABLES\">",
    " TABLES",
    " </a>",
    " </div>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"graphic graphic_table\" href=\"UTD.htm?28/62/29676\" title=\"table
    1\">",
    " Glasgow coma scale",
    " </a>",
    " </li>",
    " </ul>",
    " </div>",
    " <h1>",
    " RELATED TOPICS",
    " </h1>",
    " <div id=\"relatedTopics\">",
    " <ul>",
    " <li class=\"plainItem\">",
    " <a class=\"medical medical_review\" href=\"UTD.htm?8/47/8953?
    source=related_link\">",
    " Blunt cerebrovascular injury: Treatment and outcomes",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"medical medical_review\" href=\"UTD.htm?8/63/9208?
    source=related_link\">",
    " Etiology and classification of stroke",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"medical medical_review\" href=\"UTD.htm?39/46/40678?
    source=related_link\">",
    " Etiology and clinical manifestations of transient ischemic attack",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"medical medical_review\" href=\"UTD.htm?7/49/7962?
    source=related_link\">",
    " Facial trauma in adults",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"medical medical_review\" href=\"UTD.htm?31/32/32262?
    source=related_link\">",
    " Horner's syndrome",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"medical medical_review\" href=\"UTD.htm?19/5/19545?
    source=related_link\">",
    " Initial evaluation and management of blunt abdominal trauma in adults",
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    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"medical medical_review\" href=\"UTD.htm?33/39/34426?
    source=related_link\">",
    " Initial evaluation and management of blunt thoracic trauma in adults",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"medical medical_review\" href=\"UTD.htm?16/56/17290?
    source=related_link\">",
    " Neuroimaging of acute ischemic stroke",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"medical medical_review\" href=\"UTD.htm?27/47/28410?
    source=related_link\">",
    " Overview of the evaluation of stroke",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"medical medical_review\" href=\"UTD.htm?1/62/2026?
    source=related_link\">",
    " Penetrating neck injuries",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"medical medical_review\" href=\"UTD.htm?38/22/39273?
    source=related_link\">",
    " Posterior circulation cerebrovascular syndromes",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"medical medical_review\" href=\"UTD.htm?10/30/10730?
    source=related_link\">",
    " Spontaneous cerebral and cervical artery dissection: Clinical features and
    diagnosis",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"medical medical_review\" href=\"UTD.htm?13/20/13639?
    source=related_link\">",
    " Treatment of severe hypovolemia or hypovolemic shock in adults",
    " </a>",
    " </li>",
    " </ul>",
    " </div>",
    " </div>"].join("\n");
    var title_f0_16_267="Thallium 201 protocols";
    var content_f0_16_267=[" <div id=\"graphicsToolbar\">",
    " <div id=\"graphicsCopy\">",
    " &copy;2013 UpToDate",
    " <sup>",
    " &reg;",
    " </sup>",
    " </div>",
    " <div id=\"graphicsLinks\">",
    " <a href=\"?imageKey=CARD
    %2F74921&amp;source=image_view&amp;view=print&amp;elapsedTimeMs=7\" onclick=\"\">",
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    title=\"Print this page\"/>",
    " </a>",
    " <a class=\"icontxt textLink\" href=\"?imageKey=CARD
    %2F74921&amp;source=image_view&amp;view=print&amp;elapsedTimeMs=7\" onclick=\"\"
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    " </a>",
    " <a class=\"etacLink\" href=\"#\">",
    " <img alt=\"Email graphic(s)\" src=\"./../images/icn_email.myextg\"
    title=\"Email graphic(s)\"/>",
    " </a>",
    " <a class=\"icontxt textLink etacLink\" href=\"#\" title=\"Email graphic(s)\">",
    " Email",
    " </a>",
    " </div>",
    " </div>",
    " <div class=\"graphic\">",
    " <div class=\"figure\">",
    " <div class=\"ttl\">",
    " Thallium-201 protocols for viability detection",
    " </div>",
    " <div class=\"cntnt\">",
    " <table cellspacing=\"0\">",
    " <tbody>",
    " <tr>",
    " <td>",
    " 1. Stress - 4 hour redistribution",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " 2. Stress - 4 hour redistribution, late-delayed imaging",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " 3. Stress - 4 hour redistribution, rest reinjection and immediate
    imaging",
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    " </tr>",
    " <tr>",
    " <td>",
    " 4. Rest - 4 hour redistribution",
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    " </tr>",
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    " <div class=\"footnotes\">",
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    var title_f0_16_268="Cancers associated with hypercalcemia";
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    " &copy;2013 UpToDate",
    " <sup>",
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    " Email",
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    " </div>",
    " </div>",
    " <div class=\"graphic\">",
    " <div class=\"figure\">",
    " <div class=\"ttl\">",
    " Malignancies associated with hypercalcemia",
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    " <tr>",
    " <td class=\"subtitle1_single\">",
    " Osteolytic metastases:",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " Breast cancer",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " Multiple myeloma",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " Lymphoma",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " Leukemia",
    " </td>",
    " </tr>",
    " <tr>",
    " <td class=\"subtitle1_single\">",
    " Humoral hypercalcemia (PTHrP):",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " Squamous cell carcinomas",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " Renal carcinomas",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " Bladder carcinoma",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " Breast cancer",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " Ovarian carcinoma",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " Non-Hodgkin lymphoma",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " CML",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " Leukemia",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " Lymphoma",
    " </td>",
    " </tr>",
    " <tr>",
    " <td class=\"subtitle1_single\">",
    " 1,25-dihydroxyvitamin D:",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " Lymphoma (Non-Hodgkin, Hodgkin, lymphomatosis/granulomatosis)",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " Ovarian dysgerminomas",
    " </td>",
    " </tr>",
    " <tr>",
    " <td class=\"subtitle1_single\">",
    " Ectopic PTH sectretion:",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " Ovarian carcinoma",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " Lung carcinomas",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " Neuroectodermal tumor",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " Thyroid papillary carcinoma",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " Rhabdomyosarcoma",
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    " </tr>",
    " <tr>",
    " <td>",
    " Pancreatic cancer",
    " </td>",
    " </tr>",
    " </tbody>",
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    " </div>",
    " <div class=\"lgnd\">",
    " <div class=\"footnotes\">",
    " </div>",
    " <div class=\"reference\">",
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    var title_f0_16_269="Prevalence of UTI in febrile infants and children";
    var content_f0_16_269=[" <div id=\"graphicsToolbar\">",
    " <div id=\"graphicsCopy\">",
    " &copy;2013 UpToDate",
    " <sup>",
    " &reg;",
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    title=\"Print this page\"/>",
    " </a>",
    " <a class=\"icontxt textLink\" href=\"?imageKey=PEDS
    %2F76804&amp;source=image_view&amp;view=print&amp;elapsedTimeMs=2\" onclick=\"\"
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    " Email",
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    " </div>",
    " </div>",
    " <div class=\"graphic\">",
    " <div class=\"figure\">",
    " <div class=\"ttl\">",
    " Prevalence of urinary tract infection in febrile* infants and children by
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    " </div>",
    " <div class=\"cntnt\">",
    " <table cellspacing=\"0\">",
    " <tbody>",
    " <tr>",
    " <td class=\"subtitle1\">",
    " Demographic group",
    " </td>",
    " <td class=\"subtitle1\">",
    " Prevalence or pretest probability (95% CI)",
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    " <tr>",
    " <td class=\"subtitle2_left\">",
    " 0 to 24 months",
    " </td>",
    " <td class=\"subtitle2_left\">",
    " 7.0 percent (5.5-8.4)",
    " </td>",
    " </tr>",
    " <tr>",
    " <td class=\"indent1\">",
    " Girls",
    " </td>",
    " <td>",
    " 7.3 percent (5.0-9.6)",
    " </td>",
    " </tr>",
    " <tr>",
    " <td class=\"indent1\">",
    " White girls with temperature &ge;39&deg;C",
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    " 16 percent",
    " <sup>",
    " &bull;",
    " </sup>",
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    " <tr>",
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    " Boys",
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    " 8.0 percent (5.1-11)",
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    " </tr>",
    " <tr>",
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    " <td>",
    " 4.7 percent (2.1-7.3)",
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    " 0 to 3 months",
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    " Girls",
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    " <td>",
    " 7.5 percent (5.1-10)",
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    " Uncircumcised boys",
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    " <td>",
    " 20.1 percent (16.8-23.4)",
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    " <td class=\"subtitle2_left\">",
    " 3 to 6 months",
    " </td>",
    " <td class=\"subtitle2_left\">",
    " 6.6 percent (1.7-11.5)",
    " </td>",
    " </tr>",
    " <tr>",
    " <td class=\"indent1\">",
    " Girls",
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    " <td>",
    " 5.7 percent (2.3-9.4)",
    " </td>",
    " </tr>",
    " <tr>",
    " <td class=\"indent1\">",
    " Boys",
    " </td>",
    " <td>",
    " 3.3 percent (1.3-5.3)",
    " </td>",
    " </tr>",
    " <tr class=\"divider_top\">",
    " <td class=\"subtitle2_left\">",
    " 6 to 12 months",
    " </td>",
    " <td class=\"subtitle2_left\">",
    " 5.4 percent (3.4-7.4)",
    " </td>",
    " </tr>",
    " <tr>",
    " <td class=\"indent1\">",
    " Girls",
    " </td>",
    " <td>",
    " 8.3 percent (3.9-12.7)",
    " </td>",
    " </tr>",
    " <tr>",
    " <td class=\"indent1\">",
    " Boys",
    " </td>",
    " <td>",
    " 1.7 percent (0.5-2.9)",
    " </td>",
    " </tr>",
    " <tr class=\"divider_top\">",
    " <td class=\"subtitle2_left\">",
    " 12 to 24 months",
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    " <td class=\"subtitle2_left\">",
    " 4.5 percent",
    " <sup>",
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    " </td>",
    " </tr>",
    " <tr>",
    " <td class=\"indent1\">",
    " Girls",
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    " <td>",
    " 2.1 percent (1.2-3.6)",
    " </td>",
    " </tr>",
    " <tr>",
    " <td class=\"indent1\">",
    " Circumcised boys &gt;1 year",
    " </td>",
    " <td>",
    " &lt;1 percent",
    " <sup>",
    " &bull;",
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    " </td>",
    " </tr>",
    " <tr class=\"divider_top\">",
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    " &lt;19 years with urinary symptoms and/or fever",
    " <sup>",
    " &Delta;",
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    " </td>",
    " <td class=\"subtitle2_left\">",
    " 7.8 percent (6.6-8.9)",
    " </td>",
    " </tr>",
    " </tbody>",
    " </table>",
    " </div>",
    " <div class=\"lgnd\">",
    " <div class=\"footnotes\">",
    " * Temperature &ge;38&deg;C.",
    " <br>",
    " <span class=\"bullet\">",
    " &bull;",
    " </span>",
    " 95% confidence interval not available.",
    " <br>",
    " &Delta; Most of these children were older than two years.",
    " </br>",
    " </br>",
    " </div>",
    " <div class=\"reference\">",
    " Data from: Shaikh N, Morone NE, Bost JE, Farrell MH. Prevalence of Urinary
    Tract Infection in Childhood: A Meta-Analysis. Pediatr Infect Dis J 2008; 27:302.",
    " </div>",
    " </div>",
    " </div>",
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    " </div>",
    " <div class=\"lgnd\">",
    " Exercise test in a woman who presented for evaluation of dyspnea on running
    and a dry cough of 18 months duration. She did not smoke or have a history of lung
    disease. The chest x-ray and lung function tests were normal. Her resting room air
    arterial blood gases (elevation 5000 feet) revealed PO2: 78; PCO2: 34; pH: 7.43;
    Sat: 94 percent; AaO2: 3.8. The patient performed an exercise test on a cycle
    ergometer. The work rate was increased 10 watts per minute to her symptom limited
    maximum. Blood was sampled every minute from an indwelling catheter. Her resting
    and exercise ECG was normal. The patient achieved 94 watts (65 percent of predicted
    workload). The PO2 decreased, AaO2 increased, and minute ventilation (Ve) increased
    systematically with increasing work rate (shown as the percent of predicted maximal
    VO2). The study was stopped because of mild shortness of breath and leg fatigue.
    Lung biopsy revealed UIP.",
    " <div class=\"footnotes\">",
    " </div>",
    " <div class=\"reference\">",
    " </div>",
    " </div>",
    " </div>",
    " </div>",
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    " </div>",
    " <div class=\"lgnd\">",
    " The Bonney tissue forceps have horizontal serration and sharp teeth.",
    " <div class=\"footnotes\">",
    " </div>",
    " <div class=\"reference\">",
    " </div>",
    " </div>",
    " </div>",
    " </div>",
    "</div>"].join("\n");
    var script_f0_16_271=[""].join("\n");
    var outline_f0_16_271=null;

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