388 Indian J. Anaesth.

2003; 47 (5) : 388-395

INDIAN JOURNAL OF ANAESTHESIA, OCTOBER 2003 388

BLOOD TRANSFUSION IN CRITICAL CARE

Col T. P. Madhusudanan1 Lt Col Rajinder Singh2
Introduction Relocation of tissues from a healthy person to a patient as a therapeutic modality began with the development of blood transfusion. This life saving measure has increasingly been the subject of study, with increasing body of scientific knowledge and techniques of scientific exploration. Patients in critical care units, by their nature of illness, form a large group of potential recipients of blood prescriptions. However the ever increasing literature on the subject demands the intensivists to ponder over the current literature before prescribing this complex biochemical compound that may not necessarily always contribute to the intended outcome. Much before William Harvey gave the theory of blood circulation in 1628, the idea of blood transfusion from young and healthy individuals to the old for restoration of good health had appeared in the mind of man. Richards Lowers performed the first documented experimental blood transfusion in dogs in the middle of 17th century. It was established by James Blundell and Dr. Leacock in 18th century that only humans could serve as the source for human blood transfusion. The discovery of ABO blood groups by Karl Landsteiner in 1901 and citrate anticoagulant by A Hustin and L Agota in 1914 laid the foundation for modern blood transfusion on a firm footing. K Landsteiner and A Wiener discovered the Rh blood group system in 1940. Since then, the blood transfusion techniques have been transformed greatly; from whole blood collected in glass bottles, stored at variable temperatures and transfused without any screening for any infections to aseptic collection in pouches with high class anticoagulants, preservation at optimal temperatures, screening for any infections and then made available as whole blood or in various components for use. In 1981, after the discovery of AIDS virus, blood transfusion services gained special attention and a separate specialty name Transfusion Medicine. However, the increase in the safety in blood transfusion practice was, to an extent, responsible for use of blood transfusion where its use could be restricted
1. D.A., M.D., Senior Advisor and Head 2. M.D., Classified Specialist Dept of Anaesthesiology and Critical Care,Command Hospital (WC), Chandimandir - 134107. Correspond to : E-mail : madusri@sify.com

if not completely eliminated, especially in critically ill patients. The aim of this review article is to analyse various aspects of blood transfusion in critically ill patients. The problem Anaemia, with associated reduction in oxygen carriage, is a common problem in patients admitted to intensive care units (ICUs). However, there are divergent views on risks of anaemia and benefits of blood transfusion in this setting. One concern is that anaemia may not be well tolerated by critically ill patients as it has been shown in recent studies that anaemia increases the risk of mortality after surgery in patients with cardiac disease and in critically ill patients,1,2 besides causing a generalized decrease in oxygen carrying capacity. Blood transfusions are used with a view to augment the oxygen delivery to tissues and to avoid the ill effects of oxygen debt. Many as a routine, transfuse blood/red cells (RBCs) to patients with haemoglobin below 10 gdL-1. Among the causes of anaemia in the critically ill, the most important are sepsis,3 haemolyis, decreased production of endogenous erythropoitin and immune associated functional iron deficiency,4 a blunted reticulocyte response and overt or covert blood loss (including frequent blood sampling). Smoller and Kruskall5 found that an average of 65 mL of blood was phlebotomized from ICU patients per day. The specific impact of anaemia on ICU patient morbidity and mortality is poorly defined, as is the optimal haemoglobin level for this class of patients. Critically ill patients, however, are at an increased risk of immunosuppression6,7 and microcirculatory complications related to blood transfusion8,9 besides other well documented problems. This has led to a move towards a more conservative transfusions in the USA in 1980, with number peaking at nearly 12.2 million units in1986 and then declining to 11.4 million units in 1997.10-13 The most frequent reasons for administering RBCs to patients were acute bleeding (35%) and augmentation of oxygen delivery (25%). However transfusion may not augment oxygen delivery in such situations.14 One study showed that transfusion of stored blood for upto six hours after infusion did not affect oxygen delivery in patients with sepsis.15 Hence the dilemma remains whether to transfuse blood in a patient or not. On one hand, a severely anaemic patient suffers from a low oxygen carrying capacity, leading to an increasing cardiac output, which in turn increases

MADHUSUDANAN, SINGH : BLOOD TRANSFUSION IN CRITICAL CARE

389

the cardiac workload and thus increasing the risk of myocardial ischaemia, especially in elderly patients or those with a compromised cardiac status. The deleterious effects of chronic low oxygen supply to various organs are well documented. On the other hand, there are genuine concerns about the ill effects of blood/blood component transfusion, namely the risk of infection, immunosuppression and thus increased risk of tumours flaring up, V:Q mismatch due to micro aggregates and the reports that in patients with sepsis, blood transfusion does not always increase oxygen carriage. Evidence from a variety of sources indicates that allogeneic blood transfusion may increase the recurrence rate of resected malignancies16 and the incidence of postoperative bacterial infections,17-21 or activate infections with cytomegalovirus22 or human immunodeficiency virus.23 This clinical syndrome, the mechanisms of which remain to be defined, has been referred to in the transfusion medicine literature as allogeneic blood transfusionassociated immunomodulation (TRIM). Blood and blood products Blood is transfused either as whole blood or in the form of one of its components. a. Whole Blood : Whole blood is obtained from human donors by venesection and is collected into a sterile, disposable plastic pack, which contains an anticoagulant -preservative solution. This solution usually contains citrate, phosphate, dextrose and adenine. There are variations in the volume collected and in the type of anticoagulant used in different countries. Blood Components : Red Cell Concentrate (Packed Red Cells): It is the simplest cell component and is prepared by allowing the blood to separate under gravity overnight in a refrigerator at a temperature of +2 degree C to +6 degree C or by centrifuging the blood pack in a special refrigerated centrifuge. The plasma is removed by transferring it into a second empty plastic bag. The red cell concentrate also contains white cells from the donated blood. Red Cell Suspension : it is prepared by adding an additive diluent solution formulated for the best preservation of red cells. Frozen red cell techniques are improving to provide longer shelf life and to avoid inventory shortages in blood banks. Leucocytes : White cells have no proven clinical uses. The removal of these cells from other blood products can reduce the incidence of febrile reactions

and the risk of transmitting cytomegalovirus (CMV) and other intracellular infectious agents by transfusion. iv. Buffy Coat depleted red cells : The removal of the leucocytes from whole blood requires controlled centrifugation so that the red cells settle to the bottom of the pack. The leucocytes and most of the platelets remain in a layer called the buffy coat that forms the interface between red cells and plasma. Leucocyte depleted red cells : Special leucocyte filters are used to remove virtually all leucocytes at the time of transfusion. The filters are expensive and it is controversial as to whether clinical outcomes other than prevention of CMV transmission are improved by them. Plasma : Plasma is separated from the whole blood by centrifugation or by allowing RBCs to settle under gravity in a blood bank refrigerator. It can also be collected from the donors by plasmapheresis.

v.

vi.

vii. Platelet Concentrates : Platelets are generally separated from pooled plasma. A fresh blood administration set primed with saline should be used to infuse them. viii. Plasma Fractionation : Albumin, coagulation factors and immunoglobulins are obtained from plasma by fractionation. Transfusion trigger The question of when to transfuse, is of particular importance in light of the risks associated with blood transfusion. Conventionally, a patient with a haematocrit value less than 30% is a candidate for blood transfusion. While low Hb levels may be detrimental to the ICU patient, studies have not clearly shown the benefit of blood transfusion in these patients. Although transfusion increases oxygen delivery, tissue utilization of oxygen does not increase in patients with sepsis.24 One reason is that old, stored blood does not function as well as the patients own blood, particularly in the first 12 to 24 hours post transfusion, due to decreased levels of 2,3diphosphoglycerate (DPG) and the presence of deformed cells. In fact, Marik and Sibbald observed that transfusion with blood stored for more than 15 days was associated with the development of splanchnic ischemia in patients with sepsis.24 Furthermore, in a study comparing liberal transfusion strategies (maintaining Hb levels between 10 gdL-1 and 12 gdL-1) to restrictive transfusion strategies (maintaining Hb levels between 7 gdL-1 and 9 gdL-1), there were actually trends toward better outcomes in the restrictive group.25

b. i.

ii.

iii.

390

INDIAN JOURNAL OF ANAESTHESIA, OCTOBER 2003

Blood transfusion related concerns Blood being a biological product, there is an inherent possibility of adverse reactions to its transfusion to patients and they have to be guarded against. These reactions can be broadly classified in following groups: a. Haemolytic Reactions : Despite advances in understanding of red cell antigens and their reactivity, fatal acute haemolytic reactions to transfusion still occur in the range of 1 in 2,50,000 to 1 in 1 million transfusions.26,27 Most of these deaths occur due to ABO incompatibility as a result of administrative errors related to mismatching of patient and the blood unit.28 In recent times, due to increased vigilance regarding identification of patients, the fatalities have shown a downward trend.27 In addition, 1 in 1000 patients has clinical manifestations of a delayed reaction to transfusion29 and 1 in 260,000 patients has a haemolytic reaction related to minor antigens carried by RBCs30 that were not detected by routine antibody assay before transfusion. These reactions are more in patients with sickle cell disease.31 Contamination of Red Cells : Though uncommon, Yersinia enterocolitica has been implicated in contamination of RBCs32 Bacterial contamination of red cell units is directly related to the duration of storage, with Yersinia red cell sepsis having been reported after as short a period of storage as 7-14 days before transfusion. In the USA, between January 1987 to February 1996, 20 recipients of Yersiniainfected red cells were reported to the Centers for Disease Control and Prevention (CDC), of which 12 died.33 A report from New Zealand indicated that the rate of contamination by Y. enterocolitica was 1 per 65,000 red cell units transfused, with a fatality rate of 1 per 104,000.34 Contamination of blood with bacteria leads to haemolysis, which in some cases may be recognized by darker colour of blood in the pouch as compared to that of blood in attached segmented tubing.35 Contamination of Platelets : The risk of contamination of platelets is higher with transfusion of pooled platelets from multiple donors as compared to platelet units obtained from single donor by apheresis.36 In descending order, the organisms most commonly implicated in deaths are Staphylococcus aureus, Klebsiella pneumoniae, Serratia marcescens, and Staph. epidermidis.36 The clinical presentation of patients with platelet related sepsis can range from mild fever to acute sepsis. In any patient who develops fever within six hours of platelet infusion, the

possibility of contamination of the component should be examined and empirical antibiotics considered. The storage techniques of platelet concentrates favour bacterial proliferation and risk of infection. d. Transmission of Viruses : The first descriptions of transfusion associated HIV infection occurred in late 1982 and early 1983,37,38 and blood banks began to ask potential donors about specific types of high-risk behaviour39,40 and these measures resulted in impressive decrease in transfusion-associated HIV infections. After the implementation of HIV antibody testing in March 1985, only about 5 cases of transfusion-associated HIV infections per year were reported in the USA.41 Testing of blood for HBV before transfusion and widespread use of vaccination against HBV has drastically cut down the transmission of this virus through blood transfusion. The risk of transmission of non-A, non-B hepatitis was greatly reduced with the discovery of HCV and the implementation of a test for HCV antibody.42-44 The importance of post-transfusion HCV infection is that 85% of cases become chronic, 20% cases develop cirrhosis and 1-5% leads to hepatocellular carcinoma45,46 Infection will develop in 20-60% recipients of blood infected with HTLV-I or HTLVII. However, blood that has been stored for more than 14 days and non-cellular blood products dont appear to be infectious.47 Transfusion-Related Immunodilution : The immunosuppressive effect of allogenic blood transfusion has been found to be clinically important in patients undergoing renal transplantation and in women who have multiple miscarriages.48,49 Of much greater concern to the critically ill patient is the profound effect of allogenic blood transfusion on the immune system.50-52 Both cellular and humoral immunity is adversely affected. Following PRBC transfusion, decreased production of interleukin-2 and increased production of prostaglandin-E2 have been documented. A decrease in CD4 helper cells, interleukin-2 receptor-positive helper cells, and natural killer cells is seen, while an increase in B cells and CD 8 suppressor cells occurs. Some immune functions return to normal within hours following PRBC transfusion, but evidence suggests that long-term or permanent alteration in immune function may occur.53 Transfusion-Related Acute Lung Injury (TRALI): This term denotes an acute respiratory distress syndrome that occurs within four hours after transfusion and is characterized by dyspnoea and hypoxia due to noncardiogenic pulmonary oedema.

b.

e.

c.

f.

MADHUSUDANAN, SINGH : BLOOD TRANSFUSION IN CRITICAL CARE

391

Its estimated frequency is 1 in 5000 transfusions.54 This condition is attributed to a number of factors. In some cases, blood-donor antibodies with HLA or neutrophil antigenic specificity react with recipient neutrophils, leading to increased permeability of pulmonary microcirculation, while in others, reactive lipid products from donor blood cell membranes that arise during storage of blood products have been implicated.55 High degree of suspicion and prompt treatment are necessary to reduce unfavourable outcomes. Salvaging plasma remaining in bags for antibody testing and patient serum for HLA and neutrophil antigen typing are needed for confirming the diagnosis. In addition to conventional measures, plasmapheresis and extra corporeal membrane oxygenation have been used effectively to treat cases. Implicated donors are mostly multiparous women immunized by leucocyte antigens during prgnancy. g. Finally, it was anticipated that the use of autologous blood might minimize the risk of perioperative transfusion, but studies have unexpectedly shown similar postoperative infectious complications and cancer recurrence and/or survival rates in patients receiving autologous blood donated before operation and those receiving allogeneic blood.56

which is biologically and immunologically indistinguishable from endogenous EPO, can be used to stimulate red blood cell production in anemic patients. This treatment has been shown to raise Haemoglobin levels and reduce the need for transfusion in a variety of settings, including anemic cancer patients receiving chemotherapy and anemic HIV patients receiving AZT regimens. Transfusion independence, defined as surviving and not receiving a transfusion between study days 8 and 42, also trended upward with epoetin alfa (55% vs 45% for placebo). Thus, the use of Epoetin alfa has been shown to significantly decrease the number of blood transfusions in the ICU while significantly increasing HCT concentrations. Although transfusion triggers and optimal Hb levels remain a matter of controversy, it is clear that risks still remain with blood transfusion. Epoetin alfa therapy has been shown to be an important alternative, diminishing the number of transfusions and therefore reducing transfusion-associated risk. Blood salvage Perioperative red cell salvage (PCS) is a technique that has been widely used in the USA and Europe for over twenty years. It is usually employed as one of a number of measures aimed at conserving or avoiding the use of allogeneic blood. The available technology for PCS has been considerably refined over the last twenty years both in terms of safety and ease of use. By far the most extensively documented method for performing PCS is the technique known as centrifugal cell separation. This technique employs a machine to process the blood spilt into the wound during operation, concentrating the red cells and washing them with saline. The end product, the patients own red cells suspended in saline, is then reinfused to the patient. There are a number of large series published that demonstrate the safety and efficacy of this technique.61,62 Another method of salvaging blood is by using a Blood filtration and cleaning device to allow quick salvaging, washing and reinfusion of low to medium volume of blood during surgery. The method uses lower pressures (80-100 mmHg) as compared to centrifuging and thus causes lesser haemolysis of red cells during processing. Several methods of whole blood reinfusion are also in use, in particular single unit reinfusion devices in orthopaedic surgery. Whole blood reinfusion systems have been generally used with lower volume losses, and are less extensively documented in the medical literature. The safety of whole blood reinfusion has been questioned by several authors.63-65 Taking their reports together, it would appear that whole blood reinfusion has the potential to increase postoperative bleeding, and that this untoward

Blood alternatives From the above description, it is clear that transfusion of blood or blood products is not without hazards. Therefore, a lot of effort is being made to develop alternatives to blood for use in patients who conventionally need blood transfusion. Efforts have included the development of cell-free haemoglobin solutions that approximate the oxygen carrying capacity of cellular haemoglobin and development of perfluorocarbon emulsions. The haemoglobin solutions are polymerized or cross-linked or both to maximize the time in which they are in circulation and to minimize their nephrotoxicity. The potential advantages of such products include a prolonged shelf life, ability to be stored at room temperature, universal biocompatibility. These products can be subjected to viral inactivation procedures.57 However they have their disadvantages. They may interfere with laboratory tests,58 have a relatively short circulation time of 24-48 hours and perfluorocarbons require a forced inspiratory concentration of 100% oxygen to be effective. Role of erythropoisis stimulants Studies in critically ill patients with anemia (both adults and children) also showed inappropriately low levels of circulating erythropoietin (EPO).59-60 Treatment with recombinant human erythropoietin (r-HuEPO, epoetin alfa),

392

INDIAN JOURNAL OF ANAESTHESIA, OCTOBER 2003

effect is not present if cell-washing techniques are employed. Faught and colleagues have recently reviewed adverse effects occurring with cell salvage techniques.66 They concluded that cell salvage with modern devices is generally safe, and that the frequency of serious complications is rare. PCS has advantages over other methods of autologous transfusion in that it can be used in emergency cases (cf. autologous predeposit) and it does not involve additional, potentially hazardous physiological manoeuvres in unstable patients (cf. acute normovolaemic haemodilution). It provides a ready supply of blood that is available in proportion to the losses that are occurring and, in the event of massive haemorrhage; its use may occasionally be lifesaving if the rate of blood loss outstrips the availability of the allogeneic supply. In such circumstances it can represent a relatively inexpensive way of saving life years.67 When properly practised it should be associated with no risk of clerical error. These techniques are used when it is anticipated that blood will be shed from a clean wound from which it can be retrieved at a rate permitting aspiration without undue haemolysis, anticipated blood loss is 20% or more of the patients estimated blood volume, blood loss cannot be accurately predicted or when there is no alternative source of blood. Salvage and reinfusion of blood from a wound containing malignant cells has been considered a contraindication as has been contamination of the wound with bowel contents, infection at the site of blood retrieval, blood containing beta dine or similar wound irritants, antibiotics not licensed for parenteral use. Aspiration of topical haemostatic agents such as collagen, cellulose, gelatin and thrombin is not recommended as they may initiate coagulation. As of now, blood salvage techniques are in use on a very limited scale in India though many institutions are showing interest in this method to avoid allogeneic blood transfusion. The role of PCS in patients admitted to ICUs is very limited. Blood safety With over 75 million units of blood estimated to be donated every year, the concern for blood safety is increasing. Avoiding mistransfusions and minimizing transfusion transmitted infections are to be high priority. Nucleic acid testing of minipools from blood donations to reduce HIV and HCV transfusions during window periods can reduce the risks, though three apparent HIV and one hepatitis C transmissions have taken place from blood negative from testing.68 Automated liquid media culture systems are used to reduce platelet contamination related infections. It is already mandatory in Belgium and the

Netherlands. Pathogen inactivation techniques (eg psoralen with ultraviolet radiation) is promising. Serious hazards of transfusion (SHOT) voluntary reporting scheme in UK and such systems will help in investigating adverse effects and understanding the events with a view to prevent recurrences. Warming of blood Warming of blood to be transfused will be required if large volume rapid transfusions are needed (>50 mlkg-1hr-1 in adults and >15 mlkg-1hr-1 in children), for exchange transfusions in infants and in patients with cold agglutinins69 Infusion rates greater than 100 ml/minute of cold blood has been suggested to be a contributing factor in cardiac arrest. Blood warmers are available as thermostatically controlled water baths (Portex), tubing heated by convective patient warming systems (Bair Hugger) and dry heat warming systems with or without co-axial warming sleeves. Heat in excess of 420C will result in denaturation of proteins and must not be used. Keeping the patient warm may be more important than warming blood in transfusions at lower flow rates. Microaggregate filters Common indications for use of micro aggregate filters are massive transfusions and transfusions during cardiopulmonary bypass and for polytrauma patients. They add to the cost of transfusions but controlled trials have not established any clinical benefit. However reduction or prevention of febrile reactions in patients who receive long term red cell replacement with stored red cells is possible by use of such filters.69 Future directions Blood and components are likely to be rendered safer by newer testing methods and pathogen deactivation technologies. Cell free haemoglobin solutions, perflurocarbon emulsions are in various stages of clinical development.68 Newer biotechnology products such as solvent detergent plasma, transgenic blood component derivatives and such are likely to reduce the use of blood transfusions in ICUs. Unit costs of blood is likely to rise with the advanced safety precautions, where as promotion of alternatives by commercial sector directly to consumers is likely to bring in new ethical challenges. Conclusion Critically ill patients admitted to ICUs may be suffering from a variety of diseases but they have one thing in common: that their systems are under tremendous strain and their capacity to tolerate physiological upheavals is very limited. For a very long time, blood transfusion,

MADHUSUDANAN, SINGH : BLOOD TRANSFUSION IN CRITICAL CARE

393

especially fresh blood transfusion has been used on the premise of augmenting oxygen carrying capacity, and improving general resistance of the patient. The problems of blood transfusion, notably transmission of infections and evidence of immunodilution have put a damper on the proponents of liberal transfusion policy. Therefore, we have to seriously debate whether we are doing harm to patients by pursuing a liberal transfusion policy. All over the developed countries, the transfusion trigger is shifting from 10 gdL-1 to ~7 gdL-1 except in patients with associated coronary artery disease. In addition, a lot of attention is being focused on the use of erythropoitin and blood salvaging techniques to reduce allogeneic blood transfusion. In India, where anaemia is a common condition amongst general population and voluntary blood donation is still not very common, the proven safety and benefits of a restrictive transfusion policy may prove to be a relief to doctors manning the ICUs. However, as in other spheres of medical practice, it may be prudent to tread slowly and cautiously. References
1. Carson JL, Duff A, Poses RM et al. Effect of anaemia and cardiovascular disease on surgical mortality and morbidity. Lancet 1996; 348: 1055-60. 2. Herbert PC, Wells G, Tweeddale M et al. Does transfusion practice affect mortality in critically ill patients? Am J Respir Crit Care Med 1997; 155: 1618-23 3. Rogers P, Zhang H, Leeman M et al. Erythropoitin response is blunted in critically ill patients. Intensive Care Med. 1997; 23: 159-62. 4. Viljoen M, Coetzee IH, Pretorius JP, Anamia insurgical intensive care patients. Haematologica.1994; 79: 19-24. 5. Smoller BR, Kruskall MS : Phlebotomy for diagnostic laboratory tests in adults: Pattern of use and effect on transfusion requirements. N Engl J Med 1986; 314: 1233-5. 6. Bordin JO, Heddle NM, Blajchman MA. Biological effects of leukocytespresent in transfused cellular products. Blood 1994; 84: 1703-21. 7. van de Watering LMG, Hermans J, Houbiers JGA, et al. Beneficial effects of leukocyte depletion of transfused blood onpostoperative complications in patients undergoing cardiac surgery: a randomised clinical trial. Circulation 1998; 97: 562-68. 8. Langenfeld JE, Livinston DH, Machiedo GW . Red cell deformability is an early indicator of infection. Surgery 1991; 110: 398-404. 9. Baker CH, Wilmoth JR, Sutton ET. Reduced RBC versus plasma microvascular flow due to endotoxin. Circ Shock 1986;20: 127-39. 10. Surgenor DM, Wallace EL, Hao SHS, Chapman RH. Collection and transfusion of blood in the United States, 19821988. N Engl J Med 1990; 322: 1646-51.

11. Wallace EL, Surgenor DM, Hao HS, An J, Chapman RH, Churchill WH. Collection and transfusion of blood and blood components in the United States, 1989. Transfusion 1993; 33: 139-44. 12. Wallace EL, Churchill WH, Surgenor DM et al. Collection and transfusion of blood and blood components in the United States, 1992. Transfusion 1995; 35: 802-12. 13. Wallace EL, Churchill WH, Surgenor DM, Cho GS, McGurk S. collection and transfusion of blood and blood components in the United States, 1994. Transfusion 1998; 38: 625-36. 14. Heyland DK, Cook DJ, King D, Kernerman P, Brun-Buisson C. Maximizing oxygen delivery in critically ill patients: a methodologic appraisal of the evidence. Crit Care Med 1996; 24: 517-24. 15. Mark PE, Sibbald WJ. Effect of stored blood transfusion on oxygen delivery in patients with sepsis. JAMA 1993; 269: 3024-9. 16. Heiss MN, Mempel W, Delanoff C, et al. Blood transfusionmodulated tumor recurrence: first results of a randomized study of autologous versus allogeneic blood transfusion in colorectal cancer surgery. J Clin Oncol 1994; 12: 1859-67. 17. Jensen LS, Andersen AJ, Christiansen PM, et al. Postoperative infection and natural killer cell function following blood transfusion in patients undergoing elective colorectal surgery. Br J Surg 1992; 79: 513-6. 18. Heiss MM, Mempel W, Jausch K-W, et al. Beneficial effect of autologous blood transfusion on infectious complications after colorectal cancer surgery. Lancet 1993; 342: 1328-33. 19. Jensen LS, Kissmeyer-Nielsen P, Wolff B, et al. Randomized comparison of leucocyte-depleted versus buffy-coat-poor blood transfusion and complications after colorectal surgery. Lancet 1996; 348: 841-5. 20. van de Watering LMG, Hermans J, Houbiers JGA, et al. Beneficial effect of leukocyte depletion of transfused blood on post-operative complications in patients undergoing cardiac surgery: a randomized clinical trial. Circulation 1998; 97: 562-8. 21. Tartter PI, Mohandas K, Azar P, et al. Randomized trial comparing packed red cell blood transfusion with and without leukocyte depletion for gastrointestinal surgery. Am J Surg 1998; 176: 462-6 22. Tegtmeier GE. Post transfusion cytomegalovirus infection. Arch Pathol Lab Med 1989; 113: 236-45. 23. Vamvakas EC, Kaplan HS. Early transfusion and length of survival in acquired immune deficiency syndrome: experience with a population receiving medical care at a public hospital. Transfusion 1993; 33: 111-8 24. Marik PE, Sibbald WJ. Effect of stored-blood transfusion on oxygen delivery in patients with sepsis. JAMA 1993; 269: 3024-9. 25. Hebert PC, Wells G, Blajchman MA, et al, and the Transfusion Requirements in Critical Care Investigators for the Canadian Critical Care Trials Group. A multicenter, randomized, controlled clinical trial of transfusion requirements in critical

394 care [published erratum appears in N Engl J Med. 1999;340:1056]. N Engl J Med 1999;340:409-17 26. Sazma K. Reports of 355 transfusion-associated deaths: 1976 through 1985. Transfusion 1990; 30: 583-90. 27. Linden JV, Tourault MA, Scribner CL. Decrease in frequency of transfusion fatalities. Transfusion 1997; 37: 243-4. 28. Linden JV, Paul B, Dressler KP. A report of 104 transfusion errors in New York State. Transfusion 1992; 32: 601-6. 29. Ness PM, Shirley RS, Thoman SK, Buck SA. The differentiation of delayed serologic and delayed hemolytic transfusion reactions: incidence, long-term serologic findings, and clinical significance. Transfusion 1990; 30: 688-93. 30. Shulman IA. The risk of an overt hemolytic transfusion reaction following the use of an immediate spin crossmatch. Arch Pathol Lab Med 1990; 114: 412-4. 31. Garratty G. Severe reactions associated with transfusion of patients with sickle cell disease. Transfusion 1997; 37: 357-61. 32. Red blood cell transfusions contaminated with Yersinia enterocolitica - United States, 1991-1996, and initiation of a national study to detect bacteria-associated transfusion reactions. MMWR Morb Mortal Wkly Rep 1997; 46: 553-5. 33. Cookson ST, Arduino MJ, Aguero SM, Jarvis WR, Yersinia Study Group. Yersinia enterocolitica-contaminated red blood cells - an emerging threat to blood safety. In: Program and abstracts of the 36th Interscience Conference on Antimicrobial Agents and Chemotherapy, New Orleans, September 1518, 1996. Washington, D.C.: American Society for Microbiology, 1996; 237. 34. Theakston EP, Morris AJ, Streat SJ, Baker BW, Woodfield DG. Transfusion transmitted Yersinia enterocolitica infection in New Zealand. Aust N Z J Med 1997; 27: 62-7. 35. Kim DM, Brecher ME, Bland LA, Estes TJ, Carmen RA, Nelson EJ. Visual identification of bacterially contaminated red cells. Transfusion 1992; 32: 221-5. 36. Klein HG, Dodd RY, Ness PM, Fratantoni JA, Nemo GJ. Current status of microbial contamination of blood components: summary of a conference. Transfusion 1997; 37: 95-101. 37. Ammann AJ, Cowan MJ, Wara DW, et al . Acquired immunodeficiency in an infant: possible transmission by means of blood products. Lancet 1983; 1: 956-8. 38. Joint statement on acquired immune deficiency syndrome (AIDS) related to transfusion. Transfusion 1983; 23: 87-8. 39. Gimble JG, Friedman LI. Effects of oral donor questioning about high-risk behaviors for human immunodeficiency virus infection. Transfusion 1992; 32: 446-9. 40. Silvergleid AJ, Leparc GF, Schmidt PJ. Impact of explicit questions about high-risk activities on donor attitudes and donor deferral patterns: results in two community blood centers. Transfusion 1989; 29: 362-4. 41. Provisional Public Health Service inter-agency recommendations for screening donated blood and plasma for antibody to the

INDIAN JOURNAL OF ANAESTHESIA, OCTOBER 2003 virus causing acquired immunodeficiency syndrome. MMWR Morb Mortal Wkly Rep 1985; 34:1-5. 42. Alter HJ, Purcell RH, Shih JW, et al. Detection of antibody to hepatitis C virus in prospectively followed transfusion recipients with acute and chronic non-A, non-B hepatitis. N Engl J Med 1989; 321: 1494-1500. 43. Alter HJ. New kit on the block: evaluation of second-generation assays for detection of antibody to the hepatitis C virus. Hepatology 1992; 15: 350-3. 44. Vrielink H, Zaaijer HL, Reesink HW, Lelie PN, van der Poel CL. Comparison of two anti-hepatitis C virus enzyme-linked immunosorbent assays. Transfusion 1995; 35: 601-4. 45. Conry-Cantilena C, VanRaden M, Gibble J, et al. Routes of infection, viremia, and liver disease in blood donors found to have hepatitis C virus infection. N Engl J Med 1996; 334: 1691-96. 46. Tong MJ, El-Farra NS, Reikes AR, Co RL. Clinical outcomes after transfusion-associated hepatitis C. N Engl J Med 1995; 332: 1463-66 47. Manns A, Wilks RJ, Murphy EL, et al. A prospective study of transmission by transfusion of HTLV-I and risk factors associated with seroconversion. Int J Cancer 1992; 51: 886-91. 48. Opelz G, Vanrenterghem Y, Kirste G, et al. Prospective evaluation of pretransplant blood transfusions in cadaver kidney recipients. Transplantation 1997; 63: 964-67 49. Gatenby PA, Cameron K, Simes RJ, et al. Treatment of recurrent spontaneous abortion by immunization with paternal lymphocytes: results of a controlled trial. Am J Reprod Immunol 1993; 29: 88-94. 50. berg N, Heal JM: Effects of transfusion on immune function. Arch Pathol Lab Med 1994; 118: 371-9. 51. Landers DF, Hill GE, Wong KC, et al: Blood transfusioninduced immunomodulation. Anesth Analg 1996; 82: 187-204. 52. Mickler TA, Longnecker DE: The immunosuppressive aspects of blood transfusion. J Intensive Care Med 1992; 7: 176-188. 53. Triulzi DJ, Heal JM, Blumberg N : Transfusion-induced immunomodulation and its clinical consequences. In: Transfusion Therapy in the 1990s. Nance SJ (Ed). Arlington, VA: American Association of Blood Banks, 1990, pp 1-32. 54. Popovsky MA, Moore SB . Diagnostic and pathogenetic considerations in transfusion-related acute lung injury. Transfusion 1985; 25: 573-7. 55. Silliman CC, Paterson AJ, Dickey WO, et al. The association of biologically active lipids with the development of transfusion-related acute lung injury: a retrospective study. Transfusion 1997; 37: 719-26. 56. Nielsen HJ Detrimental effects of perioperative blood transfusion. Br J Surg 1995; 82(5): 582-7. 57. Scott MG, Kucik DF, GoodnoughLT, Monk TG : Blood sustitutes: evolution and future applications. Clin Chem 1997; 43: 1724-31. 58. Ma Z, Monk TG, Goodnough LT et al. Effect of hemoglobin and Pertlubron based oxygen carriers on common clinical laboratory tests. Clin Chem1997; 43: 1732-7.

MADHUSUDANAN, SINGH : BLOOD TRANSFUSION IN CRITICAL CARE 59. Krafte-Jacobs B, Levetown ML, Bray GL, Ruttimann UE, Pollack MM. Erythropoietin response to critical illness. Crit Care Med. 1994; 22: 821-6. 60. Rogiers P, Zhang H, Leeman M, et al. Erythropoietin response is blunted in critically ill patients. Intensive Care Med. 1997; 23: 159-62. 61. Tawes R L Jnr. Duvall T B. Is the salvaged-cell syndrome myth or reality? American Journal of Surgery. 1996; 172(2): 172-4. 62. Giordano G F, Giordano G M, Wallace B A, et al. An analysis of 9,918 consecutive perioperative autotransfusions. Surg Gynaecol Obstet 1993; 176: 103-10. 63. Milne A A. Drummond G B. Paterson D A. Murphy W G. Ruckley C V. Disseminated intravascular coagulation after aortic aneurysm repair, intraoperative salvage autotransfusion, and aprotinin [letter]. Lancet 1994; 44(8920): 470-1. 64. Vertrees R A. Conti V R. Lick S D. Zwischenberger J B. Et al . Adverse effects of postoperative infusion of shed

395

mediastinal blood. Annals of Thoracic Surgery 1996; 62(3): 717-23. 65. Southern EP. Huo M H. Mehta J R. Keggi K J. Unwashed wound drainage blood. What are we giving our patients? Clinical Orthopaedics and Related Research 1995 ; 320: 235-46. 66. Faught C, Wells P, Fergusson D and Laupacis A. Adverse Effects of Methods for Minimising Perioperative Allogeneic Transfusion: A Critical Review of the Literature. Transfusion Medicine Reviews 1998; 12(3): 206-25. 67. Desmond M J, Thomas M J G, Gillon J, Fox M A . Perioperative Red Cell Salvage. Royal College of Physicians of Edinburgh Consensus Conference on Autologous Transfusion, Oct 1995 Transfusion 1996; 36: 644-51. 68. Goodnough LT, Shander A, Brecher. Transfusion medicine,: looking to the future. Lancet 2003; 361(9352): 161-69 69. World Health Organisation. The Clinical Use of Blood in Medicine Obstetrics Paediatrics Surgery and Anaesthesia, Trauma and Burns. WHO Geneva., 2001; Pp 120-21.

BD ADV