Inhaled oxygen has been administered to all patients suspected of having an acute myocardial infarction. Oxygen therapy may raise blood pressure and lower cardiac index, heart rate, cardiac oxygen consumption. In patients with both acute coronary syndromes and stable coronary disease, oxygen administration may constrict the coronary vessels.
Inhaled oxygen has been administered to all patients suspected of having an acute myocardial infarction. Oxygen therapy may raise blood pressure and lower cardiac index, heart rate, cardiac oxygen consumption. In patients with both acute coronary syndromes and stable coronary disease, oxygen administration may constrict the coronary vessels.
Inhaled oxygen has been administered to all patients suspected of having an acute myocardial infarction. Oxygen therapy may raise blood pressure and lower cardiac index, heart rate, cardiac oxygen consumption. In patients with both acute coronary syndromes and stable coronary disease, oxygen administration may constrict the coronary vessels.
Oxygen Therapy for Acute Myocardial InfarctionThen
and Now. A Century of Uncertainty Richard Kones, MD, FAHA, FESC Cardiometabolic Research Institute, Houston, Tex. ABSTRACT For about 100 years, inhaled oxygen has been administered to all patients suspected of having an acute myocardial infarction. The basis for this practice was the belief that oxygen supplementation raised often-decient arterial oxygen content to improve myocardial oxygenation, thereby reducing infarct size. This assumption is conditional and not evidence-based. While such physiological changes may pertain in some patients who are hypoxemic, considerable data suggest that oxygen therapy may be detrimental in others. Acute oxygen therapy may raise blood pressure and lower cardiac index, heart rate, cardiac oxygen consumption, and blood ow in the cerebral and renal beds. Oxygen also may lower capillary density and redistribute blood in the microcirculation. Several reports now conrm that these changes occur in humans. In patients with both acute coronary syndromes and stable coronary disease, oxygen administration may constrict the coronary vessels, lower myocardial oxygen delivery, and may actually worsen ischemia. There are no large, contemporary, randomized studies that examine clinical outcomes after this interven- tion. Hence, this long-accepted but potentially harmful tradition urgently needs reevaluation. Clinical guidelines appear to be changing, favoring use of oxygen only in hypoxemic patients, and then cautiously titrating to individual oxygen tensions. 2011 Elsevier Inc. All rights reserved. The American Journal of Medicine (2011) 124, 1000-1005 KEYWORDS: Acute coronary syndrome guidelines; Acute myocardial infarction; Coronary artery disease; Hyper- oxia; Hyperoxic vasoconstriction; Hypoxemia; Myocardial oxygenation; Oxygen inhalation; Oxygen toxicity In September 1955, President Eisenhower, who had been a 4-pack/day smoker and followed an atherogenic diet, sus- tained an anterior myocardial infarction. He was placed in an oxygen tent, given anticoagulants despite a friction rub, and kept at strict bed rest for 4 weeks. Observers blamed chronic low intensity exercisegolfas an etiological fac- tor in producing the episode. Dr Paul Dudley White was not only criticized for mobilizing him early, allowing him to begin walking at 6 weeks, but also for suggesting that chronic exercise was cardioprotective. 1 The Presidents per- sonal experience may have led him to establish, by Execu- tive Order, the Presidents Council on Youth Fitness some months later. The management of acute coronary syndromes has changed markedly from the 1950s, when medicine was organized as a cottage industry and about to transition from a descriptive discipline. During the 61 years since, medicine has undergone a metamorphosis to an increasingly quantitative science based upon the scientic method, physico- chemical principles, and evidence-based medicine. One of the holdovers from that era, when patients with acute myocardial infarction (AMI) were treated with bed rest for 4-6 weeks and were relatively unmonitored, is the use of oxygen supplementation. Because heart muscle death during AMI is associated with oxygen and substrate deprivation caused by acutely diminished coronary blood ow, and hypoxemia, frequently observed in such patients, reduces the ability of the blood to carry oxygen, the belief evolved that oxygen inhalation raised oxygen deliv- ery to ischemic myocardium, leading to reduced infarct size. Based upon this assumption, it appeared reasonable to admin- ister oxygen by nasal cannula, mask, or tent, and this practice has continued rather routinely for all patients suspected of having an AMI for about 100 years. In 2011, however, with Funding: None. Conict of Interest: None. Authorship: The author is solely responsible for the entire content of this review. Requests for reprints should be addressed to Richard Kones, MD, FAHA, FESC, Cardiometabolic Research Institute, 8181 Fannin St, U314, Houston, TX 77054. E-mail address: drrkones@comcast.net 0002-9343/$ -see front matter 2011 Elsevier Inc. All rights reserved. doi:10.1016/j.amjmed.2011.04.034 Published in the Nov 2011 issue. Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/22017777. Full access available through MDconsult.com, OVID, or Science Direct. more sophisticated and rigorous criteria, advanced technology, and relying more upon demonstrable clinical outcomes than translating directly from the laboratory to the bedside, the use of inhaled oxygen in patients with uncomplicated acute coronary syndromes is being questioned. Closer examinat- ion reveals that the long-standing assumption upon which oxygen therapy is based is conditional, and is not evidence-based. There is no better example of being misled by observational reports than the past, overzealous use of prophylactic in- travenous lidocaine in such patients, only to discover that actual out- comes were convincingly detrimen- tal. 2 Similarly, because evidence of harm was not striking during tradi- tional oxygen use in AMI during these many years, a laissez-faire attitude prevailed. In hypoxemic pa- tients with complicated AMI, oxy- gen therapy was, and remains, clearly evidence-based. 3 EARLY LABORATORY AND CLINICAL TRIALS After Steele successfully used inhaled oxygen to relieve angina in 1900, 4 the practice endured, based upon the pop- ular notion that administered oxygen increased oxygen de- livery to the myocardium and reduced infarct size. 5,6 Fifty years later Russek et al 7 found that 100% oxygen given by mask not only failed to relieve or modify angina, but ac- centuated and prolonged some electrocardiographic changes of ischemia. They postulated that hyperoxic blood pre- vented reactive hyperemia in ischemic myocardium and might be contraindicated during normoxemia but not during hypoxia. Two decades later, when techniques capable of decreasing infarct size were being explored, Maroko et al 8 showed that 40% oxygen administration reduced the extent of myocardial ischemic injury assessed by ST-segment and biochemical marker elevations in a canine model. Madias and Hood 9 also reported reductions in ST-segment eleva- tions on precordial mapping in patients inhaling 16% oxy- gen through masks, which was again attributed to a decrease in the volume of ischemic myocardium. Both of these stud- ies, however, had signicant methodological limitations. A trial by Horvat et al 10 in 11 patients with coronary heart disease (CHD) found that oxygen supplementation raised the threshold to pacing-induced angina, that is, at a greater rate-pressure product associated with a higher left ventric- ular oxygen consumption. Rawles and Kenmure 11 conducted a double-blind study of the effects of oxygen in 200 consecutive patients with suspected myocardial infarction who were randomized to receive either oxygen 6 L/min by mask or compressed air during their rst 24 hours in the hospital. After 43 patients were excluded who proved not to have a myocardial infarc- tion, both groups were comparable except for higher serum aspartate aminotransferase and PaO 2 levels in the oxygen group. The incidence of arrhythmias and mortality was no better in the oxygen group than in the nontreated subjects. Although not statistically signi- cant, 9 of 80 (11.25%) patients in the oxygen group died, compared with 3 of 77 (3.8%) in the com- pressed air group. Wilson and Channer 12 sur- veyed coronary care units in Eng- land regarding use of pulse oxim- etry to guide oxygen therapy after AMI. They randomized 50 pa- tients who presented within 24 hours of AMI to either inhaled ox- ygen or room air. Among patients breathing room air, 70% had an oxygen saturation (SpO 2 ) 90%, and 35% of them had an SpO 2 35%, compared with 27% and 4%, respectively, among patients who received oxygen. There were no differences between groups in the incidence of arrhythmias or ST-segment changes. Oxygen therapy was easily guided by pulse oximetry, although un- common at that time. HEMODYNAMIC EFFECTS OF OXYGEN AND MYOCARDIAL OXYGEN AVAILABILITY Oxygen is a vasoactive substance, and the hemodynamic effects upon healthy subjects and patients with AMI are fairly well known. Acute oxygen administration may raise blood pressure 13 and lower cardiac index, heart rate, and cardiac oxygen consumption. 14,15 Coronary blood ow falls in response to hyperoxia-induced vasoconstriction regard- less of initial saturation. 16 Oxygen-induced vasoconstriction may similarly lower cerebral 17 and renal blood ow. 18 Thomas et al 19 found that 40% oxygen given to patients within a few days of onset of AMI increased arterial blood pressure with a fall in cardiac output, later conrmed by Kenmure et al. 20 Foster et al 21 were able to document a continuous increase in systemic vascular resistance and ar- terial pressure as arterial oxygen tension increased, but not a fall in cardiac output. Preclinical studies show that hyperoxia may lower myo- cardial oxygen consumption for reasons unrelated to cardiac output or heart rate. Because high oxygen tensions lower capillary density, thereby reducing oxygen transport into muscle, hyperoxia may decrease myocardial oxygen con- sumption. 22,23 In addition, high-ow oxygen administration may disturb blood distribution in the microcirculation, lead- ing to functional oxygen shunting and lowered total-body CLINICAL SIGNIFICANCE The practice of administering inhaled oxygen to patients suspected of having an acute myocardial infarction is wide- spread, has been followed for about a century, and is advised in major text- books of emergency care, general med- icine, and cardiology. A review of the evolution of supplemen- tal oxygen therapy reveals that it is not evidence-based, and in fact, guidelines appear to be changing. Based upon available data, a revision of this practice is suggested. 1001 Kones Oxygen Therapy for Acute Myocardial Infarction oxygen consumption, 24 perhaps teleologically to protect tis- sues from toxic effects of high oxygen tensions. Indeed, Sukumalchantra et al 25 reported that in AMI patients whose arterial oxygen saturation was over 90%, oxygen administration did not produce a net increase in oxygen transport in the myocardium because the effects of lowered cardiac output, associated with decreases in coro- nary blood ow and higher coronary vascular resistance, 26 overcame the increase in oxygen content. However, when arterial oxygen saturation was 90%, the resulting increase in both cardiac output and oxygen content after oxygen supplementation increased net oxygen transport. By mea- suring lactate/pyruvate ratios in coronary venous blood, Neill 27 demonstrated that in patients with CHD, anaerobic metabolism, reecting ischemia, occurred when arterial ox- ygen saturation was between 70% and 85%, but in healthy subjects, hypoxia did not cause such changes until oxygen saturation was about 50%. Hyperoxia did not raise myocar- dial oxygen availability or reverse ischemia in patients with heart disease. Bourassa and associates 28 noted further that in patients with advanced triple vessel disease, abnormal lac- tate values were associated with 100% oxygen therapy. Thus, while high-ow oxygen may increase oxygen content, a simultaneous fall in coronary blood ow may not only fail to improve overall myocardial oxygenation, but actually worsen the effects of ischemia. Oxidant stress is also asso- ciated with endothelial dysfunction and a cascade of subse- quent deleterious molecular events. More recently, McNulty et al 26 measured the effects of breathing 100% oxygen by face mask for 15 minutes on coronary blood ow (via coronary Doppler ow wire) in 18 patients with stable CHD. Breathing 100% oxygen promptly decreased coronary blood ow by 29% and raised coronary vascular resistance by 41% without changing the diameter of large-conduit coronary arteries, suggesting in- volvement of the microcirculation. Momen et al 29 used duplex ultrasound to measure coronary blood velocity, an index of coronary blood ow, in 7 healthy volunteers breathing room air and 100% oxygen for 5 minutes. Com- pared with room air, coronary blood velocity fell 15% while coronary vascular resistance rose by 20%. Because similar changes also were observed in patients who received cardiac transplants several months before, hyperoxia appar- ently produced vasoconstriction of the coronary arteries through a direct effect, rather than through autonomic nerves. SYSTEMATIC REVIEWS Several systematic reviews of the effects of oxygen in patients with CHD are available. In 2004, a review of 9 trials failed to demonstrate effectiveness because of insuf- cient evidence. 30 In 2008, Wijesinghe et al 31 identied 51 studies, but only 2 met inclusion criteria of substantive clinical outcomes. It was concluded that evidence was lim- ited, but primarily using the trial results of Rawles and Kenmure, 11 support for oxygen therapy in all patients with uncomplicated AMI was lacking, and oxygen may in fact have resulted in a larger infarct size, as reected by the increase in aspartate aminotransferase levels observed. A Cochrane study 32 reviewed bibliographic databases for randomized controlled trials of patients with suspected or proven AMI in which oxygen was administered within 24 hours after onset, and outcomesparticularly pain and deathwere compared with patients breathing room air. Of 2228 articles screened, only 3 trials qualied: Rawles and Kenmure, 11 Wilson and Channer, 12 both older studies con- ducted in the UK, and a Russian study, Ukholkina et al. 33,34 Caution was urged because of the differences in current management of AMI and, during the study periods, high risk of bias for the main outcomes, and the curiously low death rate among control participants, which averaged just 1.7%. A total of 387 patients were included, with a total of 14 deaths, about 3 times as many in patients randomized to oxygen treatment than room air, not statistically signicant, and no benet regarding pain relief, as assessed by analgesic use. The pooled relative risk of death was 2.88 (95% con- dence interval [CI], 0.88-9.39) in an intention-to-treat analysis, and 3.03 (95% CI, 0.93-9.83) in patients with proven AMI. The pooled relative risk for analgesic use was 0.97 (95% CI, 0.78-1.20). Noting the paucity and poor quality of the evidence, the authors concluded certainly no benet accrued from oxygen therapy in uncomplicated AMI patients, but their analysis could not demonstrate any harm. A denitive randomized controlled trial was deemed of urgent importance. A commentary accompanying the Cochrane study 35 la- mented the continuation of oxygen therapy in uncompli- cated AMI patients, including use of oxygen in ambulances before evaluation. The expense and difculty of organizing and performing a large randomized trial, especially without funding and impetus of the pharmaceutical industry, were cited. Another obstacle noted was the entrenchment of a practice which was believed to be reasonable, simple, inex- pensive, convenient, and apparently innocuous, together with the psychological benet to the paramedic, patient, and physician by doing something. An editorial in the British Medical Journal surprised many readers by arguing in favor of routine use of supple- mental oxygen, given the positive physiological reasons and no trial evidence of harm. 36 To be sure, the methodol- ogy was poor in all 3 trials analyzed by Cochrane; 2 studies were performed unblinded and the third was accessible only in abstract form in English. 33 The editorialist opined that these limitations, combined with absence of demonstrable harm, suggested the practice should continue. A urry of letters contesting this view followed. 37 Of interest is the report by Kilgannon et al, 38 who ana- lyzed data collected for the Project IMPACT database in- volving 6326 adults with nontraumatic cardiac arrest admit- ted to 120 US intensive care units after resuscitation. Hyperoxia was present in 18% of the patients, hypoxia present in 63%, and normoxia in 19%. The presence of hyperoxia conferred an odds ratio for death of 1.8 (95% CI, 1002 The American Journal of Medicine, Vol 124, No 11, November 2011 1.5-2.2), indicating that arterial hyperoxia was indepen- dently associated with increased in-hospital mortality com- pared with either normoxia or hypoxia. Extension of this work suggested a dose-dependent, linear relationship be- tween supranormal oxygen tension and risk of in-hospital death in postresuscitation patients. 51 WHAT THE GUIDELINES SAY Of guidelines that no longer recommend oxygen for all AMI patients, one of the rst was the British Thoracic Society Guideline for Emergency Oxygen use, in which oxygen was recommended only for hypoxemic patients. 39 The National Institute for Health and Clinical Excellence (NICE) Guideline on the management of chest pain of suspected cardiac origin, the UK Ambulance Service oxygen guideline, and a number of other societies sub- sequently adopted similar advice. 40-42 The NICE guide- line species the level of hypoxia that needs attention with lower levels for patients with chronic obstructive pulmonary disease (COPD). 43 Specically, recommenda- tions are: Do not routinely administer oxygen, but monitor oxygen saturation using pulse oximetry as soon as possible, ide- ally before hospital admission. Only offer supplemental oxygen to people with oxygen saturation (SaO 2 ) of 94% who are not at risk of hypercapnic respiratory failure, aiming for SaO 2 of 94%98%. In patients with COPD who are at risk of hypercapnic respiratory failure, try to achieve a target SpO 2 of 88% 92% until blood gas analysis is available. 40 The American College of Cardiology/American Heart Association (ACC/AHA) guideline on ST-elevation myo- cardial infarction (STEMI) 43 assigned a class IIa, level of evidence (LOE) C recommendation to the use of oxygen, considering it reasonable to give supplemental oxygen to all patients with uncomplicated STEMI during the rst 6 hours. The ACC/AHA guidelines for unstable angina (UA)/non- STEMI (NSTEMI) 44 gave a class I, LOE B recommenda- tion for administration of oxygen to all patients with UA/ NSTEMI with SaO 2 90%, respiratory distress, or other risk-risk features for hypoxemia, also recommending con- tinuous monitoring with pulse oximetry. They also assigned a class IIa, LOE C recommendation for supplemental oxy- gen to all patients with UA/NSTEMI during the rst 6 hours after presentation. The current European Society of Cardiology (ESC) guideline on STEMI advises that in patients presenting with chest pain, oxygen 2-4 L/min by mask or nasal prongs should be administered to those who are breathless or who have any features of heart failure or shock. 45 Members of the ESC AMI-STEMI task force are aware of the issue and a review is planned for the new ESC Clinical Practice Guidelines due in 2012. In addition to the variation in guidelines, there is some further evidence that oxygen is inconsistently and casually prescribed. 46-48 Garg and Lagan 46 audited 20 patients on cardiology wards with respect to oxygen indication, mode of delivery, documentation, and prescriptions written over a 2-month period. Numerous defects and issues were identi- ed; prescriptions for oxygen were described as very poor, resulting in signicant potential for patient harm. A call for greater quality and appropriateness in prescribing oxygen was made. Most crucial was the need to improve assessment for oxygen therapy and adequate titration to individual patient requirement. 49 CONCLUSION Oxygen is a vasoactive drug and should be prescribed only when indicated. The burden of proof properly falls on the intervention, and there is no large, contemporary, randomized study available. Evidence supporting use of oxygen in patients suspected of having an AMI who are normoxemic is of poor quality and now old, predating modern trial methods, reperfusion, and other advances in management. Recent data suggest that physiological ev- idence of harm is strong, clinical evidence of harm is weak, and there is no evidence for benet. A large ran- domized clinical trial is urgently needed. Currently, the Air Versus Oxygen in myocardial Infarction Study (AVOID) is in progress, a randomized trial with a pri- mary end-point of infarct size as assessed with cardiac troponin I and creatine kinase. 50 In the interim, and consistent with the doctrine of primum non nocere, it is suggested that in patients with acute myocardial infarction who are hypoxemic, oxygen is indicated to maintain arterial oxygen saturation from 94% to 96%. Sufcient evidence now exists that hyper- oxia has the potential to induce unfavorable hemody- namic and metabolic changes and should be avoided. In patients with comorbidities, adjustments may be pro- vided by proven therapies for those conditions. In pa- tients at risk of hypercapnic respiratory failure, for in- stance, a target oxygen saturation of 88% to 92% might be appropriate until arterial blood gas results are avail- able, with possible revision upward if PaCO 2 is not elevated and there is no prior history of blunting hypox- emia-driven respiratory drive with oxygen. References 1. Messerli FH, Messerli AW, Lscher TF. Eisenhowers billion-dollar heart attack50 years later. N Engl J Med. 2005;353(12):1205-1207. 2. Hine LK, Laird N, Hewitt P, Chalmers TC. Meta-analytic evidence against prophylactic use of lidocaine in acute myocardial infarction. Arch Intern Med. 1989;149(12):2694-2698. 3. Kones R. Oxygen therapy for acute myocardial infarction: basis for a practical approach. South Med J. 1974;67(11):1322-1328. 4. Steele C. Severe angina pectoris relieved by oxygen inhalations. BMJ. 1900;2:1568. 5. Boothby WM, Mayo CW, Lovelace WR Jr. One hundred percent oxygen: indications for its use and methods of its administration. JAMA. 1939;113:477-482. 6. Boland EW. Oxygen in high concentrations for relief of pain in coronary thrombosis and severe angina pectoris. JAMA. 1940;114: 1512-1514. 1003 Kones Oxygen Therapy for Acute Myocardial Infarction 7. Russek HI, Regan FD, Naegele CF. One hundred percent oxygen in the treatment of acute myocardial infarction and severe angina pecto- ris. JAMA. 950;144(5):373-375. 8. Maroko PR, Radvany P, Braunwald E, Hale SL. Reduction of infarct size by oxygen inhalation following acute coronary occlusion. Circu- lation. 1975;52(3):360-368. 9. Madias JE, Hood WB Jr. Reduction of precordial ST-segment eleva- tion in patients with anterior myocardial infarction by oxygen breath- ing. Circulation. 1976;53(3 Suppl):I198-I200. 10. Horvat M, Yoshida S, Prakash R, Marcus HS, Swan HJC, Ganz W. Effect of oxygen breathing on pacing-induced angina pectoris and other manifestations of coronary insufciency. Circulation.1972; 45(4):837-845. 11. Rawles JM, Kenmure ACF. Controlled trial of oxygen in uncompli- cated myocardial infarction. Br Med J. 1976;1(6018):1121-1123. 12. Wilson AT, Channer KS. Hypoxaemia and supplemental oxygen ther- apy in the rst 24 hours after myocardial infarction: the role of pulse oximetry. J R Coll Physicians Lond. 1997;31(6):657-661. 13. Waring WS, Thomson AJ, Adwani SH, et al. Cardiovascular effects of acute oxygen administration in healthy adults. J Cardiovasc Pharma- col. 2003;42(2):245-250. 14. Ganz W, Donoso R, Marcus H, Swan HJ. Coronary hemodynamics and myocardial oxygen metabolism during oxygen breathing in pa- tients with and without coronary artery disease. Circulation. 1972; 45(4):763-768. 15. Thomson AJ, Drummond GB, Waring WS, Webb DJ, Maxwell SR. Effects of short-term isocapnic hyperoxia and hypoxia on cardiovas- cular function. J Appl Physiol. 2006;101(3):809-816. 16. Farquhar H, Weatherall M, Wijesinghe M, et al. Systematic review of studies of the effect of hyperoxia on coronary blood ow. Am Heart J. 2009;158(3):371-377. 17. Kety SS, Schmidt CF. The effects of altered arterial tensions of carbon dioxide and oxygen on cerebral blood ow and cerebral oxygen con- sumption in normal young men. J Clin Invest. 1948;27(4):484-492. 18. Aber GM, Harris AM, Bishop JM. The effect of acute changes in inspired oxygen concentration on cardiac, respiratory and renal func- tion in patients with chronic obstructive airways disease. Clin Sci. 1964;26:133-143. 19. Thomas M, Malmcrona R, Shillingford J. Haemodynamic effects of oxygen in patients with acute myocardial infarction. Br Heart J. 1965;27:401-407. 20. Kenmure ACF, Murdoch WR, Beattie AD, Marshall JCB, Cameron AJV. Circulatory and metabolic effects of oxygen in myocardial in- farction. Br Med J. 1968;4(5627):360-364. 21. Foster GL, Casten GG, Reeves TJ. The effects of oxygen breathing in patients with acute myocardial infarction. Cardiovasc Res. 1969;3(2): 179-189. 22. Lindbom L, Tuma RF, Arfors KE. Inuence of oxygen on perfused capillary density and capillary red cell velocity in rabbit skeletal muscle. Microvasc Res. 1980;19(2):197-208. 23. Lindbom L, Arfors KE. Mechanisms and site of control for variation in the number of perfused capillaries in skeletal muscle. Int J Micro- circ Clin Exp. 1985;4(1):19-30. 24. Reinhart K, Bloos F, Konig F, Bredle D, Hannemann L. Reversible decrease of oxygen consumption by hyperoxia. Chest. 1991;99(3): 690-694. 25. Sukumalchantra Y, Levy S, Danzig R, Rubins S, Alpern H, Swan HJC. Correcting arterial hypoxemia by oxygen therapy in patients with acute myocardial infarction. Am J Cardiol. 1969;24(6):838-852. 26. McNulty PH, King N, Scott S, et al. Effects of supplemental oxygen administration on coronary blood ow in patients undergoing cardiac catheterization. Am J Physiol Heart Care Physiol. 2005;288(3): H1057-H1062. 27. Neill WA. Effects of arterial hypoxemia and hyperoxia on oxygen availability for myocardial metabolism: patients with and without coronary heart disease. Am J Cardiol. 1969;24(2):166-171. 28. Bourassa MG, Campeau L, Bois MA, Rico O. The effects of inhalation of 100 per cent oxygen on myocardial lactate metabolism in coronary heart disease. Am J Cardiol. 1969;24(2):172-177. 29. Momen A, Mascarenhas V, Gahremanpour A, et al. Coronary blood ow responses to physiological stress in humans. Am J Physiol Heart Circ Physiol. 2009;296(3):H854-H861. 30. Nicholson C. A systematic review of the effectiveness of oxygen in reducing acute myocardial ischaemia. J Clin Nurs. 2004;13(8):996- 1007. 31. Wijesinghe M, Perrin K, Ranchord A, Simmonds M, Weatherall M, Beasley R. Routine use of oxygen in the treatment of myocardial infarction: systematic review. Heart. 2009;95(3):198-202. 32. Cabello JB, Burls A, Emparanza JI, Bayliss S, Quinn T. Oxygen therapy for acute myocardial infarction. Cochrane Database Syst Rev. 2010;(6):CD007160. 33. Ukholkina GB, Kostianov II, Kuchkina NV, Grendo EP, Gofman I. Effect of oxygen therapy used in combination with reperfusion in patients with acute myocardial infarction. Kardiologiia 2005;45(5):59. 34. Ukholkina GB, Kostyanov I Yu, Kuchkina NV, Grendo EP, Gofman Ya B. Oxygen therapy in combination with endovascular reperfusion during the rst hours of acute myocardial infarction: clinical and laboratory ndings. Int J Intervent Cardioangiol. Q J Russ Sci Soc Intervent Cardioangiol. 2005;9:45-51. 35. Weston C. Oxygen therapy in acute myocardial infarction too much of a good thing? [editorial]. The Cochrane Library 2010 (16 June). Available at: http://www.thecochranelibrary.com/details/editorial/742329/Oxygen- therapy-in-acute-myocardial-infarction--too-much-of-a-good-thing-- by-Dr-C.html. Accessed July 27, 2011. 36. Atar D. Should oxygen be given in myocardial infarction? BMJ. 2010;340:c3287. 37. Rapid responses. Available at: http://www.bmj.com/content/340/bmj. c3287.short/reply#bmj_el_237986 and http://www.bmj.com/content/ 340/bmj.c3227.extract. Accessed July 27, 2011. 38. Kilgannon JH, Jones AE, Shapiro NI; et al. Association between arterial hyperoxia following resuscitation from cardiac arrest and in- hospital mortality. JAMA. 2010;303(21):2165-2171. 39. ODriscoll BR, Howard LS, Davison AG; British Thoracic Society. BTS guideline for emergency oxygen use in adult patients. Thorax. 2008;63(Suppl 6):vi1-68. 40. National Clinical Guideline Centre for Acute and Chronic Conditions. Chest pain of recent onset: assessment and diagnosis of recent onset chest pain or discomfort of suspected cardiac origin. NICE Clinical Guideline 95. March 2010. Available at http://guidance.nice.org.uk/CG95 http:// www.nice.org.uk/nicemedia/pdf/CG95NICEGuidance.pdf. Accessed July 27, 2011. 41. Joint Royal Colleges Ambulance Liaison Committee Oxygen Update. April 2009. Available at http://jrcalc.org.uk/newjrcalcguidance/oxygen_ guideline_combined220409.pdf. Accessed July 27, 2011. 42. ST-Elevation Myocardial Infarction Guidelines Group; New Zealand Branch of the Cardiac Society of Australia and New Zealand. ST- elevation myocardial infarction: New Zealand management guidelines. N Z Med J. 2005;118(1223):1-21. 43. Antman EM, Anbe DT, Armstrong PW; et al. ACC/AHA guidelines for the management of patients with ST-elevation myocardial in- farction. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 1999 Guidelines for the Management of Patients With Acute Myocardial Infarction). Circulation. 2004; 110(5):588-636. 44. Anderson JL, Adams CD, Antman EM, et al; American College of Cardiology; American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines for the Management of Patients With Unstable Angina/Non-ST-Elevation Myocardial Infarction); American College of Emergency Physicians; Society for Cardiovascular Angiography and Interventions; Society of Thoracic Surgeons; American Association of Cardiovascular and Pul- monary Rehabilitation; Society for Academic Emergency Medicine. ACC/AHA 2007 guidelines for the management of patients with unstable 1004 The American Journal of Medicine, Vol 124, No 11, November 2011 angina/non-ST-elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines for the Management of Patients With Unstable Angina/Non-ST-Elevation Myocardial Infarction) developed in collaboration with the American College of Emergency Physicians, the Society for Cardiovascular Angiography and Interventions, and the Society of Thoracic Surgeons endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation and the Society for Academic Emergency Medicine. J Am Coll Cardiol. 2007;50(7):e1-e157 45. Van de Werf F, Bax J, Betriu A, et al. Management of acute myocar- dial infarction in patients presenting with persistent ST-segment ele- vation: the Task Force on the Management of ST-Segment Elevation Acute Myocardial Infarction of the European Society of Cardiology. Eur Heart J. 2008;29(23):2909-2945. 46. Garg P, Lagan J. Oxygen therapy in cardiology: local prescribing expe- rience at a large regional cardiac centre. Internet J Cardiol. 2010;9:2. Available at http://www.ispub.com/journal/the_internet_journal_of_ cardiology/volume_9_number_2_16/article_printable/oxygen-therapy- in-cardiology-local-prescribing-experience-at-a-large-regional-cardiac- centre-1.html. Accessed July 27, 2011. 47. Dodd ME, Kellet F, Davis A, et al. Audit of oxygen prescribing before and after the introduction of a prescription chart. BMJ. 2000; 321(7265):864-865. 48. Kbar FA, Campbell IA. Oxygen therapy in hospitalized patients: the impact of local guidelines. J Eval Clin Pract. 2006; 12(1);31-36. 49. Wijesinghe M, Shirtcliffe P, Perrin K, et al. An audit of the effect of oxygen prescription charts on clinical practice. Postgrad Med J. 2010; 86(1012):89-93. 50. Air Versus Oxygen in myocardial Infarction Study (AVOID). Avail- able at: http://clinicaltrials.gov/ct2/show/NCT01272713. Accessed July 27, 2011. 51. Kilgannon JH, Jones AE, Parrillo JE, et al. Relationship between supranormal oxygen tension and outcome after resuscitation from cardiac arrest. Circulation. 2011;123(23):2717-2722. 1005 Kones Oxygen Therapy for Acute Myocardial Infarction