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Crit Care Clin 20 (2004) 225 235

Clinical consequences of anemia and red cell


transfusion in the critically ill
Paul C. Hebert, MD, MHSc, FRCP(C)a,*,
Bernard J. McDonald, MD, PhD, FRCP(C)a,b,
Alan Tinmouth, MD, FRCP(C), MSca
a

University of Ottawa Centre for Transfusion Research and the Clinical Epidemiology Program of the
Ottawa Health Research Institute, Department of Medicine, The Ottawa Hospital (General Campus),
501 Smyth Road, Box 201, Ottawa, Ontario K1H 8L6, Canada
b
University of Ottawa Heart Institute, 40 Ruskin Street, Ottawa, Ontario K1Y 4W7, Canada

Transfusion of packed red cells, a complex biologic product prepared from


donated blood, is unique in many respects when compared with other health
interventions. Decisions concerning the use of allogeneic red blood cell (RBC)
transfusion in the treatment of anemia and hemorrhage require a clear understanding of both the risks and benefits of both the condition and its treatment. Although
we have developed a much clearer appreciation for the infectious and immunomodulatory risks of RBC transfusion over the past 2 decades, the risks of anemia in
many clinical settings and the benefits of RBC transfusion are still inadequately
characterized. We presume that the most significant risk associated with anemia is
the harm resulting from the decrease in oxygen carrying capacity and plasma volume. The development of adverse health consequences from anemia will, in part,
depend on the capacity of the individual patient to compensate for these changes.
The benefits of transfusions are related to the capacity of RBCs to correct these
risks and possibly provide additional benefits such as increasing oxygen delivery
to supranormal ranges. Such a framework highlights the concept that the tradeoffs
of risks and benefits may not be equivalent. With the exception of patients who
refuse blood for religious reasons, it is impossible to clearly distinguish between
these competing risk and benefits outside a randomized clinical trial.

Natural history of uncorrected anemia


Numerous laboratory experiments indicate that extreme hemodilution is well
tolerated in healthy animals. Animals subjected to acute hemodilution tolerate
* Corresponding author.
E-mail address: phebert@ohri.ca (P.C. Hebert).
0749-0704/04/$ see front matter D 2004 Elsevier Inc. All rights reserved.
doi:10.1016/j.ccc.2003.12.006

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decreasing hemoglobin concentration down to 50 to 30 g/L, with ischemic


electrocardiographic changes and depressed ventricular function occurring respectively at these levels of hemoglobin concentration [1]. However, acute
hemodilution is less well tolerated in experimental animal models of coronary
stenosis, with ischemic electrocardiographic changes and depressed cardiac
function occurring at hemoglobin concentrations between 70 to 100 g/L. Human
data regarding the limits of anemia tolerance is inadequate and often conflicting.
Leung et al [2] found electrocardiographic changes that may have been indicative
of myocardial ischemia in three of 55 conscious resting volunteers subjected to
acute isovolemic hemodilution to hemoglobin concentration of 50 g/L.
While providing insight to the human physiologic response to acute anemia,
the above experimental data are of limited applicability to the perioperative
setting where many of the factors that influence oxygen consumption including
muscle activity, body temperature, heart rate, sympathetic activity and metabolic
state are altered. Instead, we need to determine the risk of withholding RBC
transfusions in the perioperative setting. From a systematic review completed for
the Canadian Guidelines on Red cells, Hebert et al [3] identified numerous
reports of severe anemia being well tolerated in surgical patients [4 16]. Additional reports or case series [14,17 19] describe successful outcomes in patients
with chronic anemia as a result of renal failure. Finally, descriptive studies in
patients refusing red cell transfusion [5 7,13] and from regions experiencing
limited blood supplies [8,20] have demonstrated that patients can survive surgical
interventions with hemoglobin levels as low as 45 g/L.
In examining some of these studies in more detail, there appears to be an
association between preoperative hemoglobin concentrations, intraoperative
estimated blood loss and postoperative mortality [6,7]. Indeed, there were no
reported deaths in more than 100 major elective surgical patients when preoperative hemoglobin was > 80 g/L and the estimated blood loss was less than
500 mL. In a single-center series of 542 Jehovahs Witness patients undergoing a
cardiac surgical procedure, the overall mortality was 10.7%; only 2.2% of the
deaths observed were considered to be a direct consequence of anemia. More
recently, Viele and Weiskopf [16] identified 134 Jehovahs Witness patients with
a hemoglobin concentration < 80 g/L or hematocrit < 24% who were treated for
various medical and surgical conditions without the use of blood or blood
components. There were 50 reported deaths, 23 of which were attributed
primarily or exclusively to anemia defined as deaths with hemoglobin concentration < 50 g/L. For those patients dying from their anemia, 60% were more than
50 years old. However, in 27 survivors with hemoglobin concentration < 50 g/L,
65% were less than 50 years of age. Although publication bias must be kept in
mind in examining these data, young healthy patients may survive without
transfusion at hemoglobin concentration in the range of 50 g/L. From these data,
it is clear that extreme anemia is tolerated in the perioperative setting but also
appears to increase the risk of death. However, these observations should not be
interpreted as support for a restrictive or conservative transfusion strategy
especially because most of the literature related to tolerance of anemia has not

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227

explored patient characteristics that predispose patients to adverse outcomes from


moderate to severe anemia.

Anemia in high-risk groups


A number of risk factors for adverse outcomes associated with anemia have
been identified in clinical practice guidelines [21 23] and reviews [24 26].
Anemia is believed to be less well tolerated in older patients, in the severely ill
and in patients with clinical conditions such as coronary, cerebrovascular, or
respiratory disease. However, the clinical evidence confirming that these factors are independently associated with an increased risk of adverse outcome is
lacking. One small case control study following high-risk vascular surgery suggests an increase in postoperative cardiac events with increasing severity of
anemia [10]. In perioperative [27] and critically ill patients [28], two large cohort
studies have documented that increasing degrees of anemia were associated with
a disproportionate increase in mortality rate in the subgroup of patients with
cardiac disease. In 1958 Jehovahs Witness patients [27], the adjusted odds
of death increased from 2.3 (95% CI of 1.4 to 4.0) to 12.3 (95% CI of 2.5 to 62.1)
as preoperative hemoglobin concentrations declined from the range of 100 to
109 g/L to 60 to 69 g/L in patients with cardiac disease (Fig. 1). There was not a
significant increase in mortality in noncardiac patients with comparable levels of
anemia. In a separate study of critically ill patients [28], patients with cardiac
disease and hemoglobin concentrations less than 95 g/L also had a trend toward
an increased mortality (55% versus 42%, P = 0.09) as compared with anemic
patients with other diagnoses. Although both cohort studies were retrospective in
nature and may not have controlled for a number of important confounders, the
evidence may suggests that anemia increases the risk of death in patients with

Fig. 1. Preoperative hemoglobin by cardiovascular disease status. Adjusted odds ratio for mortality by
cardiovascular disease and preoperative hemoglobin. (Adapted from Carson JL, Duff A, Poses RM,
Berlin JA, Spence RK, Trout R, et al. Severity of anemia and operative mortality and morbidity. Lancet
1996;348:1055 60; with permission.)

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significant cardiac disease. Severity of illness also appears to be a risk factor in


the critically ill [6,28]. Two retrospective studies document that the degree of
blood loss contributes to perioperative mortality [6,28]. However, no studies
examine the independent contribution of age, cerebrovascular disease, and
respiratory disease to an increased mortality risk in anemic patients. This
relationship may well be complex given that age and cerebrovascular disease
are risk factors associated with coronary artery disease. Smoking-related respiratory diseases may have similar associations to cardiac disease. Therefore, the
association between anemia and increased rates of adverse outcomes in these
patients can best be described as speculative.

Benefits of transfusion
Four large observational studies that were specifically designed to compare
clinical outcomes at varying hemoglobin concentration in transfused and nontransfused patients have been conducted in various clinical settings. In the first of
these, Hebert et al [28] used a combined retrospective and prospective cohort
design to examine 4470 critically ill patients admitted to six Canadian tertiary
level intensive care units (ICUs) during 1993. In patients with cardiac diagnoses
(ischemic heart disease, arrhythmia, cardiac arrest, and cardiac and vascular
surgical procedures), there was a trend toward increased mortality when hemoglobin concentrations were < 95 g/L. Furthermore, analysis of a subgroup of
202 patients with anemia, an Acute Physiology and Chronic Health Evaluation
II (APACHE II) score > 20, and a cardiac diagnosis revealed that transfusion of
1 to 3 units or 4 to 6 units of RBCs was associated with a significantly lower
mortality rate when compared with those patients who did not receive transfusion
[55% (no transfusions) versus 35% (1 to 3 units) or 32% (4 to 6 units),
respectively, P = 0.01]. Although the design of the analysis attempted to control
for the confounding influence of disease severity, it is quite possible that the
complex interrelationship between disease severity, the number of transfusions,
and the degree of anemia may have resulted in a spurious association between a
cardiovascular diagnosis and the reported mortality risk with anemia.
Wu et al [29] retrospectively studied Medicare records of 78,974 patients older
than age 65 who were hospitalized with a primary diagnosis of acute myocardial
infarction. The authors then categorized patients according to their admitting
hematocrit. Although anemia defined in the study as a hematocrit < 39% was
present in nearly half the patients, only 3680 patients received a RBC transfusion.
Lower admission hematocrit values were associated with increased 30-day
mortality with a mortality rate approaching 50% among patients with a hematocrit of 27% or lower who did not receive a RBC transfusion. Unfortunately, this
study did not have any data on nadir hemoglobins and their relationship to
mortality. Interestingly, RBC transfusion was associated with a reduction in
30-day mortality for patients who received at least 1 RBC transfusion if their
admitting hematocrit was less than 33%, whereas RBC transfusion was associ-

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229

ated with increased 30-day mortality for patients whose admitting hematocrit
values were 36.1% or higher. In the analysis, these associations were present even
when adjustments were made for clinical patient factors including APACHE II
scores, location of myocardial infarction and presence of congestive heart failure and treatment factors including use of reperfusion therapies, aspirin, and
b-adrenergic blockade.
In the only study exclusively focusing on the perioperative period, Carson
et al [30] attempted to determine the effect of perioperative transfusion on 30- and
90-day postoperative mortality with a retrospective cohort study involving
8787 patients with hip fractures undergoing repair between 1983 and 1993 in
20 different United States hospitals. This was a large, high-risk, elderly (median
age 80.3 years) population with extensive co-existing disease and with an overall
30-day mortality rate of 4.6%. A total of 3699 patients (42%) received a
perioperative transfusion within 7 days of the surgical repair. After controlling
for trigger hemoglobin concentrations level, cardiovascular disease, and other risk
factors for death, the results suggested that patients who had hemoglobin
concentrations as low as 80 g/L and did not receive transfusion were no more
likely to die than those with similar hemoglobin concentrations levels who received a transfusion. (With hemoglobin concentrations < 80 g/L, nearly all patients received a transfusion which did not allow investigators to draw conclusions
about the effect of transfusion at these lower hemoglobin concentrations levels.)
However, as the authors point out, despite the large sample size, inadequate power
may still explain the inability to detect a reduction in mortality related to
transfusion, and they estimated that the study would need to be 10 times larger
to detect a 10% difference in 30-day mortality with 80% power.
More recently, Vincent et al [31] completed a prospective observational crosssectional study involving 3534 patients admitted to 146 western European ICUs
during a 2-week period in November 1999. Of these patients, 37% received an
RBC transfusion during their ICU admission with the overall transfusion rate
increasing to 41.6% over a 28-day period. For those patients who were transfused, the mean pretransfusion hemoglobin concentration was 84 13 g/L. In an
effort to control for confounding created by illness severity and the need for
transfusion, these investigators used a strategy of matching transfused and
nontransfused patients based on their propensity to receive a transfusion, thereby
defining two well-balanced groups (516 patients in each group) to determine the
influence of RBC transfusions on mortality. Using this approach, the associated
risk of death was increased instead of decreased, by 33% for patients who
received a transfusion compared with similar patients who did not receive blood.
However, as pointed out in the accompanying editorial [32], the results may have
differed if the propensity scores were derived separately for categories of prehemoglobin concentrations (eg, < 80, 80 to 100, and > 100 g/L) instead of
hemoglobin concentrations at ICU admission. For example, if one were to
consider groups of patients with a pretransfusion hemoglobin concentration
< 60 g/L, it is unlikely that the observed 33% increase in mortality would hold
true or blood transfusion would never be recommended.

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Fig. 2. Effect of restrictive transfusion triggers on the need for allogenic RBCs. Forrest plot
describing the effect of restrictive transfusion triggers on the use of allegeneic blood transfusion in
seven published randomized trials. (Adapted from Carson JL, Hill S, Carless P, Hebert PC, Henry D.
Transfusion triggers: a systematic review of the literature. Trans Med Rev 2002;16(3):187 99.)

Unfortunately as evidenced by a recent systematic review, there is a paucity of


clinical trials comparing restrictive to liberal transfusion studies to examine
efficacy of RBC transfusion. Carson et al [33] (Fig. 2) were able to identify only
10 randomized clinical trials of adequate methodologic quality in which different
RBC transfusion triggers were evaluated. Included were a total of 1780 surgery,
trauma, and intensive care unit patients enrolled in trials conducted over the past
40 years. The transfusion triggers evaluated in these trials varied between 70 and
100 g/L. Data on mortality or hospital length of stay was only available in six of
these trials. Conservative transfusion triggers were not associated with an
increase in mortality; on average, mortality was one fifth lower (RR 0.80; 95%
CI 0.63, 1.02) with conservative compared with liberal transfusion triggers.
Likewise, cardiac morbidity and length of hospital stay did not appear to be
adversely affected by the lower use of red cell transfusions. There was inFig. 3. ICU survival over 30 days in study patients in the restrictive and liberal allogeneic RBC
transfusion strategy groups. (A) illustrates Kaplan-Meier survival curves for all patients in both study
groups. There is a trend toward lower mortality in patients in the restrictive group (dotted line) as
compared with the liberal group (solid line) (P = 0.10). In the subgroup with an APACHE II score < 20
(B), fewer patients died in the restrictive group than in the liberal group (P = 0.02). There were
also significant differences in survival between groups in the subgroup with ages less than 55 years
(P = 0.02) as depicted in (C). (Adapted from Hebert PC, Wells G, Blajchman MA, Marshall J, Martin C,
Pagliarello G, et al. A multicentre, randomized, controlled clinical trial of transfusion requirements in
critical care. N Engl J Med 1999;340(6):409 17; with permission.)

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sufficient data on potentially relevant clinical outcomes such as stroke, thromboembolism, multi-organ failure, delirium, infection or delayed wound healing to
perform any pooled analysis. Carson and colleagues [33] stated there were
insufficient data to address the full range of risks and benefits associated with
different transfusion thresholds, particularly in patients with coexisting disease.
They also noted that their meta-analysis was dominated by a single trial: the
Transfusion Requirements in Critical Care (TRICC) Trial [34], which enrolled
838 patients and was the only individual trial identified that was adequately
powered to evaluate the impact of different transfusion strategies on mortality
and morbidity.
The TRICC Study [30] documented an overall nonsignificant trend toward
decreased 30-day mortality (18.7% versus 23.3%, P = 0.11) and significant
decreases in mortality among patients who were less acutely ill (8.7% versus
16.1%, P = 0.03) in the group treated using a hemoglobin transfusion trigger
of 70 g/L compared with a more liberally transfused group that received 54%
more red cell transfusions. The investigators also noted that the 30-day mortality
rates were significantly lower with the restrictive transfusion strategy among
patients who were less acutely ill (APACHE II scores < 20) and among patients
who were less than 55 years of age (Fig. 3).
A number of additional questions arose from the TRICC Trial. The investigators were particularly interested in the risks and benefits of anemia and
transfusion in patients with cardiovascular disease and in patients attempting to
wean from mechanical ventilation. In the first of these subgroup analyses [35],
357 patients (43%) were identified with cardiovascular disease. Of these, 160 had
been in the restrictive RBC transfusion group and 197 in the liberal transfusion
strategy group. The two groups were fairly equally balanced with regards to
baseline characteristics and concurrent therapies with a few exceptions: there was
less frequent diuretic use in the restrictive group (43% versus 58%, P < 0.01) and
the use of epidural anesthetics was greater in the restrictive group (8% versus 2%,
P < 0.01). Overall, in this subgroup analysis, there was no significant difference
in the mortality rate between the two treatment groups. However, there was a
nonsignificant (P = 0.3) decrease in overall survival rate in the restrictive group
for patients with confirmed ischemic heart disease, severe peripheral vascular
disease, or severe comorbid cardiac disease.
The subgroup analysis of patients receiving mechanical ventilation was
limited to 713 (85% of the 838 patients in the TRICC Trial who required
invasive mechanical ventilatory support [36]. Of these, 357 had been in the
restrictive RBC transfusion group and 356 in the liberal group. The mean duration of mechanical ventilation was 8.3 8.1 days in the restrictive group and
8.8 8.7 days in the liberal group (P = 0.48). Ventilator-free days were
17.5 10.9 and 16.1 11.4 in the restrictive and liberal RBC transfusion
groups, respectively (P = 0.09). Eighty two percent of the patients in the
restrictive transfusion group were considered successfully weaned and extubated
for at least 24 hours, compared with 78% for the liberal group (P = 0.19).
Amongst the 219 patients who required mechanical ventilation for more than

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Fig. 4. Time remaining on mechanical ventilation in the 283 patients requiring mechanical ventilation
for > 1 week. The time to successful weaning from mechanical ventilation is illustrated using KaplanMeier survival curves in patients who required mechanical ventilation for > 1 week. Weaning success
is defined as remaining off mechanical ventilation, once extubated, during the 30 days of observation.
Hatched line refers to the restrictive group, whereas the solid line refers to the liberal group. Survival
curves were not statistically different when compared using a log rank test (P = 0.08). (Adapted from
Hebert PC, Blajchman MA, Cook DJ, Yetisir E, Wells G, Marshall J, et al. Do blood transfusions
improve outcomes related to mechanical ventilation? Chest 2001;119:1850 7; with permission.)

7 days, there were no differences in the time to successful weaning (Fig. 4). The
independent effects of RBC transfusions and hemoglobin concentration were
also examined. Each additional transfusion was associated with an increased duration of mechanical ventilation (RR = 1.10; 95% CI 1.14 to 1.06, P < 0.01)
adjusting for the effect of age, APACHE II score and co-morbid illnesses.
Hemoglobin concentrations did not influence the duration of mechanical ventilation (RR = 0.99; 95% CI 1.01 to .98, P = 0.45). Complications including
pulmonary edema and adult respiratory distress syndrome (ARDS) were increased in patients in the liberal strategy.
Even though a large randomized clinical trial (RCT) has been completed, a
number of questions remain to be answered. One of the most important questions is why the liberal RBC transfusion strategy failed to improve 30-day mortality and rates of organ failure in critically ill patients? The greater number of
allogeneic RBC units in the liberal group may have significantly depressed
host immune responses [36,37] or resulted in altered microcirculatory flow as a
consequence of prolonged storage times.

Summary
Despite the frequent use of red cell transfusions, only one large randomized
trial has examined red cell administration perioperative and in the critical care

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setting. However, the TRICC Trial does not provide sufficient evidence to
determine optimal transfusion practice in postoperative care, in critically ill
children, or in patients with a myocardial infarction or acute coronary syndromes.
In addition, most transfusion practice guidelines published before the completion
of the TRICC Trial [33 35] are now dated and need to have expert opinion
informed by solid evidence in diverse clinical settings. In the next several years,
several randomized trials will provide additional evidence in support of bedside
decision-making. For example, two transfusion studies will be evaluating
transfusion triggers, including one in premature infants and the other in critically
ill children. At this juncture, high-quality clinical evidence is not yet available for
many decisions related to red cell transfusions. We anticipate that risks and
benefits of red cells and alternatives will be elucidated in the coming years.

References
[1] Wilkerson DK, Rosen AL, Sehgal LR, Gould SA, Sehgal HL, Moss GS. Limits of cardiac
compensation in anemic baboons. Surgery 1988;103:665 70.
[2] Leung JM, Weiskopf RB, Feiner J, Hopf HW, Kelley S, Viele M, et al. Electrocardiographic STsegment changes during acute, severe isovolemic hemodilution in humans. Anesthesiology
2000;93(4):1004 10.
[3] Expert Working Group. Guidelines for red blood cell and plasma transfusion for adults and
children. Report of the expert working group. Can Med Assoc J 1997;156(Suppl 11):S1 24.
[4] Bayer WL, Coenen WM, Jenkins DC, Zucker ML. The use of blood and blood components in
1,769 patients undergoing open-heart surgery. Ann Thorac Surg 1980;29:117 22.
[5] Gollub S, Bailey CP. Management of major surgical blood loss without transfusion. JAMA
1966;198:149 52.
[6] Carson JL, Spence RK, Poses RM, Bonavita G. Severity of anaemia and operative mortality and
morbidity. Lancet 1988;1:727 9.
[7] Spence RK, Carson JA, Poses R, McCoy S, Pello M, Alexander J, et al. Elective surgery without
transfusion: influence of preoperative hemoglobin level and blood loss on mortality. Am J Surg
1990;159:320 4.
[8] Fullerton WT, Turner AG. Exchange transfusion in treatment of severe anaemia in pregnancy.
Lancet 1962;282:75 8.
[9] Kawaguchi A, Bergsland J, Subramanian S. Total bloodless open heart surgery in the pediatric
age group. Circulation 1984;70:1 30.
[10] Nelson AH, Fleisher LA, Rosenbaum SH. Relationship between postoperative anemia and
cardiac morbidity in high-risk vascular patients in the intensive care unit. Crit Care Med
1993;21(6):860 6.
[11] Lunn JN, Elwood PC. Anaemia and surgery. BMJ 1970;3:71 3.
[12] Gopalrao T. Should anemia stop surgery? Int Surg 1971;55:250 5.
[13] Ott DA, Cooley DA. Cardiovascular surgery in Jehovahs Witnesses. Report of 542 operations
without blood transfusion. JAMA 1977;238:1256 8.
[14] Graves CL, Allen RM. Anesthesia in the presence of severe anemia. Rocky Mountain Medical J
1974;67:35 40.
[15] Simmons Jr CW, Messmer BJ, Hallman GL, Cooley DA. Vascular surgery in Jehovahs Witnesses. JAMA 1970;213:1032 4.
[16] Viele MK, Weiskopf RB. What can we learn about the need for transfusion from patients
who refuse blood? The experience with Jehovahs Witnesses. Transfusion 1994;34:396 401.
[17] Slawson KB. Anaesthesia for the patient in renal failure. Br J Anaesth 1972;44:277 82.

P.C. Hebert et al / Crit Care Clin 20 (2004) 225235

235

[18] Aldrete JA, Daniel W, OHigghins JW, Homatas J, Starzl TE. Analysis of anesthetic-related
morbidity in human recipients of renal holografts. Anesth Analg 1971;50:321 9.
[19] Samuel JR, Powell D. Renal transplantation. Anesthetic experience of 100 cases. Anaesthesia
1970;25:165 76.
[20] Alexiu O, Mircea N, Balaban M, Furtunescu B. Gastro-intestinal haemorrhage from peptic ulcer.
An evaluation of bloodless transfusion and early surgery. Anaesthesia 1975;30:609 15.
[21] Audet A-M, Goodnough LT. Practice strategies for elective red blood cell transfusion. Ann Intern
Med 1992;116:403 6.
[22] American Society of Anesthesiologists Task Force on Blood Component Therapy. Practice
guidelines for blood component therapy. Anesthesiology 1996;84:732 47.
[23] Consensus Conference. (National Institutes of Health). Perioperative red blood cell transfusion.
JAMA 1988;260:2700 3.
[24] Welch HG, Meehan KR, Goodnough LT. Prudent strategies for elective red blood cell transfusion. Ann Intern Med 1992;116:393 402.
[25] Cane RD. Hemoglobin: how much is enough? Crit Care Med 1990;18:1046 7.
[26] Crosby ET. Perioperative haemotherapy: I. Indications for blood component transfusion. Can J
Anesth 1992;39:695 707.
[27] Carson JL, Duff A, Poses RM, Berlin JA, Spence RK, Trout R, et al. Effects of anaemia and
cardiovascular disease on surgical mortality and morbidity. Lancet 1996;348:1055 60.
[28] Hebert PC, Wells G, Tweeddale M, Martin C, Marshall J, Pham B, et al. Does transfusion
practice affect mortality in critically ill patients? Am J Respir Crit Care Med 1997;155:1618 23.
[29] Wu WC, Rathore SS, Wang Y, Radford MJ, Krumholz HM. Blood transfusion in elderly
patients with acute myocardial infarction. N Engl J Med 2001;345(17):1230 6.
[30] Carson JL, Duff A, Berlin JA, Lawrence VA, Poses RM, Huber EC, et al. Perioperative blood
transfusion and postoperative mortality. JAMA 1998;279:199 205.
[31] Vincent JL, Baron J-F, Reinhart K, Gattinoni L, Thijs L, Webb A, et al. Anemia and blood
transfusion in critically ill patients. JAMA 2002;288(12):1499 507.
[32] Hebert PC, Fergusson DA. Red blood cell transfusions in critically ill patients. JAMA
2002;288(12):1525 6.
[33] Carson JL, Hill S, Carless P, Hebert PC, Henry D. Transfusion triggers: a systematic review of
the literature. Trans Med Rev 2002;16(3):187 99.
[34] Hebert PC, Wells G, Blajchman MA, Marshall J, Martin C, Pagliarello G, et al. A multicenter,
randomized, controlled clinical trial of transfusion requirements in critical care. N Engl J Med
1999;340(6):409 17.
[35] Hebert PC, Yetisir E, Martin C, Blajchman M, Wells G, Marshall J, et al. Is a low transfusion
threshold safe in critically ill patients with cardiovascular disease? Crit Care Med 2001;29(2):
227 34.
[36] Hebert PC, Blajchman MA, Cook DJ, Yetisir E, Wells G, Marshall J, et al. Do blood transfusions
improve outcomes related to mechanical ventilation? Chest 2001;119:1850 7.
[37] Bordin JO, Heddle NM, Blajchman MA. Biologic effects of leukocytes present in transfused
cellular blood products. Blood 1994;84:1703 21.

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