Optimizing Red Blood Cell Transfusion Practice

S. D. Surgenor, M. J. Hampers, and H. L. Corwin

Introduction

What constitutes optimal red blood cell (RBC) transfusion practice remains contro-
versial. Tremendous variation in the indications for, and timing of RBC, transfusions
exists. The presence of significant variation in RBC transfusion rates implies that the
best practice has yet to be identified, and that indications for transfusion are not
consistent among providers. This chapter will review the risks and benefits of RBC
transfusion, as well as strategies to optimize transfusion practice.

Variation in Transfusion Practice

Variation has been documented in the coronary artery bypass graft surgery (CABG)
population, which consumes 10-20% of national RBC transfusions [1].Among elec-
tive primary CABG operations at 23 academic centers, institutional RBC transfusion
rates varied widely from 16 to 90% of patients [2]. Goodnough et al. [3] also ob-
served variation in transfusion practice among 18 institutions performing CABG
surgery. Mean RBC transfusion rates ranged from 0.4 to 6.3 units per patient in this
study. The observed variation was not explained by patient or surgical variables, but
rather by differences in transfusion practice. Goodnough et al. [4] determined that
15% of the RBC transfusions in this study were inappropriate.
The Collaborative Hospital Transfusion Study (CHTS) also observed institution
transfusion rates that ranged from 33% to 90% among males given internal mam-
mary artery and venous conduits [5]. Furthermore, CHTS documented significant
variation in the timing of these transfusions. In the hospital with the highest utiliza-
tion rate, a high proportion of cases were transfused on the operative day. In con-
trast, at the hospital with the lowest utilization rate, less than 20% of transfusions
were given on the operative day. CHTS also observed that the variation in trans-
fusion practice did not differ significantly among surgeons within one hospital,
with one exception. This suggests that the majority of surgeons are practicing
similar transfusion policies within hospitals. The variability in RBC transfusion
practice among the five hospitals was ascribed to the unique process of care in each
hospital.
Populations other than the CABG surgery population have been studied as well.
Among non-intensive care unit (lCU) medical patients, 35% of RBC transfusions
were judged either non-justified or equivocal [6] . The number of inappropriate

J.-L. Vincent (ed.), Yearbook of Intensive Care and Emergency Medicine 2001
© Springer-Verlag Berlin Heidelberg 2001
310 S. D. Surgenor et al.

transfusions in another study ranged from 4% to as high as 57% [7]. Corwin et al. [8]
found that among ICU patients, almost half of all transfusions, and almost two
thirds of those for non-acute blood loss, were performed for either no identifiable
indication or for low hematocrit alone [8].

Practice Guidelines

This variation in the indications for, and timing of RBC, transfusions has been not-
ed despite the availability of practice guidelines. One widely quoted 'transfusion
trigger' from 1982 is a hemoglobin less than 10 g/dl [9]. The advantages of a single
transfusion trigger include ease, low cost of measurement, and simplicity. However,
this trigger failed to provide a consistent indication for RBC transfusion for several
reasons which illustrate the limitations of a single trigger. First, this trigger is not
based on solid evidence, such as a randomized trial [10]. Second, while a trigger of
10 g/dl may be appropriate in some situations, an abrupt and consistent change in
physiology is certainly not observed in all patients when the hemoglobin falls below
this value. For example, reports from the Jehovah's Witness population, who refuse
transfusion for religious reasons, have shown survival without sequel after active
hemorrhage to values of hemoglobin as low as 4 g/dl [11,12]. As a result, strict ad-
herence to this trigger would lead to unnecessary RBC transfusions.
Three guideline statements have been published. First, the National Institutes of
Health (NIH) Consensus Conference in 1988 stated that "otherwise healthy patients
with hemoglobin values of 10 g/dl or greater rarely require peri-operative transfu-
sion, whereas those with acute anemia with resulting hemoglobin values ofless than
7 g/dl frequently will require transfusion:' Other clinical data was recognized as
contributory to the decision to transfuse, with emphasis on assessment of volume
status [10]. Second, the 1992 American College of Physicians (ACP) consensus con-
ference lacked explicit guidelines [l3]. This conference concluded that "good clinical
judgment" could not be replaced by any single measure. The conference provided
guidelines for transfusion decisions among anesthetized patients. These stated that
transfusion was not indicated in anesthetized, hemodynamically stable patients in-
dependent of hemoglobin level, in the absence of cardiovascular or cerebrovascular
risks. Most recently, the Blood Management Practice Guidelines Conference estab-
lished explicit practice guidelines for RBC transfusion in 1995 [14]. This thorough
effort established 11 policies to achieve maximization of oxygen delivery, cost -effec-
tive minimization of transfusion risks, and education of physicians and patients. A
majority of the proposed interventions for these policies were regarded as options,
consistent with the uncertainty surrounding transfusion practice.
Medical practice guidelines have been promoted as a method to improve the cost
effectiveness of medical care [15]. However, the persistent variation in transfusion
practice despite the publication of these three guidelines demonstrates the limited
efficacy of guidelines for optimizing transfusion practice. Specifically, the lack of
studies documenting either the risk of anemia or the benefit from transfusion has
limited the development of effective practice policies [16]. A final limitation is that
44 % of physicians were unaware of transfusion guidelines [17]. Forty five percent of
those who were aware of the existence of guidelines stated that they had little or no
 Optimizing Red Blood Cell Transfusion Practice 311

influence on their decision. In sum, 70% of physicians were unaffected by the trans-
fusion guidelines.

Risks of RBC Transfusion

In general, the risks of RBC transfusion are well characterized. Some adverse effect
to the recipient may occur in as many as 20% of blood transfusions [18].Acute mor-
tality after transfusion is rare and is usually caused by erroneous administration of
blood incompatible with the patient or bacterial contamination of blood, however,
its frequency exceeds the rate of human immunodeficiency virus (HIV) transmis-
sion. While most of these adverse events are minor in nature they still may result in
patient morbidity.
Some of the known viruses which can be transmitted by blood products include
cytomegalovirus, hepatitis C, hepatitis B, HIV, and human T-celllymphotropic virus
(HTLV). Recent estimates put the risk of transfusion associated HIV at 1: 200 000 to
1 : 2 000 000 and hepatitis C infection at 1 : 30000 to 1 : 150000 [19]. Risks of infection
are fixed per unit of exposure, and thus this component of transfusion knowledge is
perhaps the most straightforward. Informed consent often focuses on risks of trans-
fusion, because a common concern of patients is HIV infection. Fifty percent of pa-
tients were reported to have voiced concern about risks of transfusion in one study
[17]. However, more than half of physicians incorrectly identified transfusion risks
during the informed consent process in this study. In particular, the risk of HIV in-
fection was commonly overestimated.
For the critically ill patient, the risk of a blood transfusion transmitted infection
is not the major concern. What is of more consequence for the critically ill patient is
the accumulating evidence that blood transfusion has profound negative effects on
the immune system. Clearly, in an environment like the ICU, where much of the mor-
bidity and mortality is directly related to infection, if blood transfusion does in fact
increase the risk of infection it is of major concern.
In the late 1970s, it was found that renal transplant outcome was improved among
patients receiving pre-transplant blood transfusions. Several studies have suggested
that exposure to RBC transfusion increased the risks of recurrence of cancer and the
development of post-operative infection [20]. Colorectal cancer surgery patients
who received allogenic blood transfusions have been reported to experience in-
creased morbidity, hospital stays, and cost [21]. Fransen et al. [22] demonstrated that
intra-operative allogeneic blood transfusions were associated with increased con-
centrations of inflammatory mediators as well as increased post-operative morbid-
ity. Moore et al. [23] reported the results of a prospective cohort study of trauma pa-
tients. These authors found that there was a dose response relationship between
early blood transfusion and later development of multiple organ failure (MOF). This
was independent of other measures of shock. The mechanism for this effect is un-
clear, however the immuno-suppressive effect of blood transfusion could be playing
a role.
Leukoreduction of transfused RBCs, on the other hand, has been associated with
a significant reduction of infection rates following colorectal surgery [24]. Universal
leukocyte reduction of transfused RBCs has been suggested as a means of reducing
312 S. D. Surgenor et al.

the toxicity of RBC transfusion [25,26]. However, others have questioned whether
the available data at this point supports the considerable expense associated with the
universal adoption of this change in transfusion practice [27]. Regardless, this
approach has recently been adopted in Europe and Canada, and will likely soon be
accepted in the US [28].
Potential cardiopulmonary effects of RBC transfusion include congestive heart
failure, and transfusion related acute lung injury (TRALI). TRALI is characterized
by pulmonary edema, hypoxemia, tachycardia, fever, and hypotension, and occurs
within one to six hours after transfusion of plasma containing blood products
[29].
Transfused RBCs, especially during the time period immediately following trans-
fusion, are not 'normal'. Storage of RBCs temporarily decreases 2,3 diphospho-gly-
cerate (DPG) levels, interfering with the ability of RBCs to unload oxygen, and tem-
porarily impairs RBC deformability. In a study of septic patients on mechanical ven-
tilation, no acute improvement in oxygen uptake was observed after the transfusion
of three units of RBCs (hemoglobin 9.0 g/dl to 11.9 g/dl). The duration of storage
may be an important determinant of the efficacy of RBCs. One study found that pa-
tients receiving units stored for greater than 15 days developed more evidence of
splanchnic ischemia compared with those receiving blood stored for less than 15
days [30]. A subsequent study, employing a rat sepsis model, found that transfusion
of 'fresh' RBCs acutely increased systemic oxygen uptake, whereas transfusion of
RBCs stored for 28 days failed to improve tissue oxygenation [31].

Risks of Anemia

The risks of anemia are much less clear than the risks of transfusion exposure. There
is evidence that low levels of hemoglobin can be well tolerated in healthy subjects.
Hematocrits of 10 to 20% have been achieved in both dogs and baboons using nor-
movolemic hemodilution without untoward effects to the animals [32,33]. Weiskopf
et al. [34] performed normovolemic hemodilution to hemoglobin levels of 5 g/dl in
healthy human patients prior to surgery as well as to volunteers not undergoing sur-
gery. They found no evidence for reduced oxygen delivery associated with this acute
anemia. Rawstron [35] compared surgical patients with pre-operative hemoglobin
levels > 10 g/dl to patients with pre-operative hemoglobin levels < 10 g/dl, and
found no difference in post -operative complications.
The available evidence is less certain for anemic patients with cardiac disease.
Among humans with preserved left ventricular function undergoing CABG, hemo-
dilution to a target hematocrit of 15% was well tolerated [36, 37]. There was no
evidence of myocardial ischemia noted and tissue autoregulation of oxygen uptake
and utilization was not impaired. However, animal studies document that cardiac
failure and anaerobic metabolism occurs at higher hemoglobin levels in animal with
critical left anterior descending artery stenosis [38]. Hardy et al. [39] studied the
association between the nadir hemoglobin in the 24 hours after surgery and major
morbidity among 2664 cardiac surgical patients. They found that the lower mini-
mum hemoglobin concentration was associated with increased hemodynamic
instability and renal failure. In a study of high risk patients undergoing arterial by-
 Optimizing Red Blood Cell Transfusion Practice 313

pass procedures, Nelson et al. [40] found that a post-operative hematocrit of < 28%
was significantly associated with increased myocardial ischemia and morbid cardiac
events.
Studies from prospective, observational cardiac surgical databases have reported
the association of hemodilutional anemia and increased mortality during CABG
surgery. Fang et al. [41] observed that a lowest hematocrit during cardiopulmonary
bypass (CPB) of < 14% for low risk patients, and < 17% for high risk patients, was
an independent risk factor for mortality among 2 738 consecutive isolated CABG pa-
tients. The Northern New England Cardiovascular Study Group recently reported
that lowest hematocrit during CPB was significantly associated with increased in-
hospital mortality, need for intra-aortic balloon pump counter-pulsation, and return
to CPB after initial separation among 6980 consecutive isolated CABG patients [42].
This study identified that smaller patients and those with lower pre-operative
hematocrits are at higher risk of low hematocrit during CPB. The association of
lowest hematocrit during CPB and increased risk of acute renal failure requiring
dialysis was observed by Smith et al. [43] among 1404 consecutive first time CABG
patients.
A wealth of data regarding the impact of anemia on surgical outcome comes from
studies ofJehovah's Witness patients. Carson et al. [44] observed 125 Jehovah's Wit-
ness patients undergoing surgery; no patient with a hemoglobin> 8 g/dL and blood
loss < 500 ml died in this series. More recently, Carson et al. [45] studied the risk of
death and morbidity among 1958 non-cardiac surgery Jehovah's Witness patients.
They found that both a low pre-operative hematocrit and a substantial blood loss in-
creased the risk of serious morbidity or death. The effect was significantly more pro-
nounced among patients with cardiovascular disease. They concluded that even
mild anemia is associated with some increased risk of peri-operative death and that
patients with cardiovascular disease have a substantially higher risk.
In a study of elective surgery in 107 Jehovah's Witness patients, Spence et al. [46]
noted that mortality was related more to blood loss than pre-operative hemoglobin.
These authors observed that surgery was safely performed in patients with hemo-
globin levels as low as 6 g/dl, providing blood loss was less than 500 ml. Kitchens has
summarized recent published experience in Jehovah's Witness patients undergoing
major surgery [47]. A 1.4% mortality rate attributable to anemia was observed
among 1404 patients. Ninety percent of these deaths were in patients undergoing
cardiovascular operations. Other complications, such as renal failure, infection,
myocardial infarction, etc., were not increased.
In summary, it appears that anemia is well tolerated by patients who do not have
cardiovascular disease. The risk associated with hemoglobin levels significantly be-
low the '10/30' threshold is low among healthy humans. However, it is not clear that
this is applicable to patients who are critically ill or those with cardiac and/or vascu-
lar disease. Therefore, while hemoglobin levels in the 7-10 g/dl range are well toler-
ated in the 'stable', 'non -stressed' patient, this range might not be optimal for the crit-
ically ill patient.
314 S. D. Surgenor et al.

Benefits of RBC Transfusion

The expected and logical benefit of a transfusion is improvement of oxygen delivery,

and prevention of irreversible cellular injury. The implicit assumption is that the
RBC transfusion alleviates inadequate oxygen delivery. However, it has been difficult
to demonstrate a benefit attributable to blood transfusion. In fact, one study of pa-
tients with gastrointestinal bleeding documented that patients who received only
colloid solutions had lower mortality and morbidity than patients who were trans-
fused with RBCs [48]. Other studies document a lack of oxygen delivery improve-
ment after RBC transfusion. Dietrich et al. [49] observed no improvement in oxygen
utilization or "shock state" among patients with shock who had hemoglobin levels
increased from 8.3 gldl to 10.5 g/dl. Similarly, in another study of septic patients,
blood transfusion (hemoglobin 9.6 gldl to 11.6 g/dl) did not effect oxygen uptake,
despite a significant increase in calculated oxygen delivery [50]. In contrast, others
have found that some critically ill patients will increase oxygen uptake in response
to blood transfusion, but no predictor could be found to identify the patients who
responded to transfusion [51,52].
The best evidence available regarding the efficacy of blood transfusion among
critically ill patients is the randomized controlled trial by Hebert et al. [53]. These
authors compared a liberal transfusion strategy (hemoglobin 10 to 12 g/dl) to a re-
strictive transfusion strategy (hemoglobin 7.0 to 9.0 g/dl). Patients in the liberal
transfusion arm received significantly more RBC transfusions. Overall in-hospital
mortality was significantly lower in the restrictive strategy group, although 30 day
mortality rate was not significantly different. However, in those patients who were
less ill (APACHE < 20) or younger ( < 55 years of age), the 30 day mortality rates
were significantly lower for the patients in the restrictive transfusion group. There-
fore, a restrictive strategy was at least equivalent and possibly superior to a more
liberal transfusion strategy. This was true even for those patients with cardiac dis-
ease.

Transfusion Strategies

Overall, there is little evidence that 'routine' transfusion of stored allogeneic RBCs is
beneficial to critically ill patients. Based on the available evidence regarding the
risks and benefits of transfusion, and the risks of anemia, we recommend the follow-
ing approach to transfusion of critically ill patients. For critically ill patients who are
not actively bleeding and without cardiovascular disease, anemia to at least a hemo-
globin of 7.0 gldl is well tolerated by most. For critically ill patients with cardiovas-
cular disease, there is some evidence to support an association between the magni-
tude of anemia and increased myocardial ischemia, renal insufficiency, and mortal-
ity [39-43]. It has been suggested that in high-risk vascular surgery patients with
impaired ventricular function, the lack of a compensatory increase in cardiac output
leaves blood transfusion as the only means to increase oxygen delivery post-opera-
tively [54]. These authors recommend hemoglobin levels of 10-12 gldl to optimize
oxygen delivery. However, the study by Hebert and colleagues [53], suggests that
most critically ill patients with cardiac disease tolerate hemoglobin levels as low as
 Optimizing Red Blood Cell Transfusion Practice 315

7 mg/dl. The exception to this may be the patient with active ischemic cardiac dis-
ease in whom a higher transfusion trigger would be appropriate.
Strategies to minimize loss of blood and increase the production of blood may al-
so be important to the management of all critically ill. A major factor contributing to
the need for blood transfusions in the critically ill patient is phlebotomy [8,55-57].
An important variable impacting the extent of phlebotomy is having easy access to
the circulation via an indwelling arterial catheter [58,59]. The importance of blood
conservation in the critical care setting has been stressed by Chernow and col-
leagues [60,61]. Methods for reducing phlebotomy blood loss include use of small
volume (pediatric) tubes, elimination of arterial line blood discard, elimination of
unnecessary laboratory tests, and altering test ordering behavior [62-65].
Critically ill patients may also benefit from improved RBC production. These pa-
tients are unable to mount an erythropoietic response of sufficient magnitude to
compensate for the anemia that develops in the ICU [66-68]. Critically ill patients
look similar hematologically to patients with anemia of chronic disease [69]. It has
been recently demonstrated that erythropoietin (EPO) therapy results in a signifi-
cant reduction in the number of blood transfusions in critically ill patients in the
ICU [70]. In a prospective, randomized, double blind, placebo controlled, multicen-
ter trial, the administration of recombinant human EPO (rHuEPO) to critically ill
patients resulted in an almost 50% reduction in the number of blood transfusions.
The final hematocrit of the rHuEPO patients was also significantly greater than the
final hematocrit of placebo patients (35.1 ± 5.6 versus 31.6 ± 4.1 [p < 0.01]).

Conclusion

Anemia is a common clinical problem seen in the critically ill and results in a large
transfusion requirement for these patients. If blood transfusion were 'risk free' the
current intense evaluation of transfusion practice would not be taking place. The de-
cision to transfuse involves balancing the risks of anemia and the risks of transfu-
sion. The optimal hematocrit for the ICU patient remains to be determined. It seems
clear that hemoglobin levels falling significantly below the '10/30' threshold can be
tolerated. For most critically ill patients a restrictive transfusion strategy, tolerating
hemoglobin levels as low as 7 mg/dl, is acceptable. For patients with active ischemic
cardiac disease higher hemoglobin levels are probably desirable. Limiting laboratory
testing and minimizing phlebotomy are also important components of blood man-
agement in the ICU. An intriguing possibility is the use of EPO in the long term criti-
cally ill population to raise hemoglobin levels and avoid blood transfusion.
316 S. D. Surgenor et al.

References

1. Lawrence L (1986) Detailed Diagnoses and Procedures for Patients Discharged from Short Stay
Hospitals, United States, 1984. Vital and Health Statistics, Series 13, No 86. National Center for
Health Statistics, Hyattsville
2. Stover EP, Seigel LC, Parks R, et al (1994) Variability in transfusion practice for coronary artery
bypass surgery despite national consensus guidelines. Anesthesiology 81: 1224A (Abst)
3. Goodnough LT, Johnston MFM, Toy PTCY (1991) The variability of transfusion practice in cor-
onary artery bypass surgery. JAMA 265: 86-90
4. Goodnough LT, Soegiarso RW, Birkmeyer JD, Welch HG (1993) Economic impact of inappropri-
ate blood transfusions in coronary artery bypass graft surgery. Am J Med 94: 509-514
5. Surgenor DM, Churchill EL, Wallace WH, et al (1996) Determinants of red cell, platelet, plasma
and cryoprecipitate transfusions during coronary artery bypass graft surgery: the Collaborative
Hospital Transfusion Study. Transfusion 36: 521-532
6. Saxena S, Weiner JM, Rabinowitz A, Fridey J, Shulman lA, Carmel R (1993) Transfusion practice
in medical patients. Arch Intern Med 153: 2575-2580
7. Welch HG, Meehan KR, Goodnough LT (1992) Prudent strategies for elective red blood cell
transfusion. Ann Intern Med 116: 393-402
8. Corwin HC, Parsonnet KC, Gettinger A (1995) RBC transfusion in the ICU: Is there a reason?
Chest 108:767-771
9. Allen JB, Allen FB (1982) The minimum acceptable level of hemoglobin. Int Anesthesiol Clin
20: 1-22
10. Anonymous (1988) National Institutes of Health Consensus Conference. Perioperative red
blood cell transfusion. JAMA 260:2700-2703
11. van Woerkens EC, Trouwborst A, Lanschot JJ (1992) Profound hemodilution: What is the criti-
cal level of hemodilution at which oxygen delivery-dependent oxygen consumption starts in an
anesthetized human? Anesth Analg 75: 818-821
12. Spence RK, Carson JA, Poses R, et al (1990) Elective surgery without transfusion: Influence of
preoperative hemoglobin level and blood loss on mortality. Am J Surg 159: 320-324
13. American College of Physicians (1992). Practice strategies for elective red blood cell trans-
fusion. Ann Intern Med 116: 403-406
14. Spence RK (1995) Surgical red blood cell transfusion practice policies. Am J Surg 170 (suppl
6A):3S-13S
15. Audet AM, Greenfield S, Field M (1990) Medical practice guidelines: current activities and fu-
ture directions. Ann Intern Med 113: 709-714
16. Faust RJ (1993) Perioperative indications for red blood cell transfusion - Has the pendulum
swung too far? Mayo Clin Proc 68 :512-514
17. Salem-Schatz Sr, Avorn 1, Soumerai SB (1990) Influence of clinical knowledge, organizational
context, and practice style on transfusion decision making. JAMA 264: 476-483
18. Walker RH (1987) Transfusion risks. Am J Clin Pathol88: 374-378
19. Goodnough LT, Brecher ME, Kanter MH, AuBuchon JP (1999) Transfusion medicine: Blood
transfusion. N Engl J Med 340:438-447
20. Vamvakas EC (1996) Transfusion associated cancer recurrence and postoperative infection:
Meta-analysis of randomized, controlled, clinical trials. Transfusion 36: 175-186
21. Vamvakas EC, Craven JH (1998) Allogenic blood transfusion, hospital charges, and length of
hospitalization: A study of 487 consecutive patients undergoing colorectal cancer resection.
Arch Pathol Lab Med 122: 145-151
22. Fransen E, Maessen J, Dentener M, Senden N, Buurman W (1999) Impact of blood transfusions
on inflammatory mediator release in patients undergoing cardiac surgery. Chest 116:
1233-1239
23. Moore FA, Moore EE, Sauaia A (1997) Blood transfusion: An independent risk factor for post-
injury multiple organ failure. Arch Surg 132: 620-625
24. Jensen LS, Kissmeyer-Nielsen P, Wolff B, Qvist N (1996) Randomised comparison of leukocyte
depleted versus buffy coat poor blood transfusion and complications after colorectal surgery.
Lancet 348:841-845
25. American Association of Blood Banks (1998) BPAC recommends universalleukoreduction.
AABB News Briefs 20: 16
 Optimizing Red Blood Cell Transfusion Practice 317

26. Blumberg N, Heal JM (1998) Blood transfusion: The silent epidemic. Arch Pathol Lab Med
122: 117-118
27. Goodnough LT, Brecher ME, Kanter MH, AuBuchon JP (1999) Transfusion medicine: Blood con-
servation. N Engl J Med 340 : 525-533
28. Sharma AD, Sreeram G, Erb T, Grocott HP, Skaughter TF (2000) Leukocyte-reduced blood trans-
fusions: Perioperative indications, adverse effects, and cost analysis. Anesth Analg 90: 1315-1323
29. Popovsky MA, Chaplin HC, Moore SB (1992) Transfusion-related acute lung injury: A neglected,
serious complication of hemotherapy. Transfusion 32: 589-592
30. Marik PE, Sibbald WJ (1993) Effect of stored-blood transfusion on oxygen delivery in patients
with sepsis. JAMA 269: 3024-3029
31. Fitzgerald RD, Martin CM, Dietz GE, Doig GS, Potter RF, Sibbald WJ (1997) Transfusing red
blood cells stored in citrate phosphate dextrose adenine-l for 28 days fails to improve tissue
oxygenation in rats. Crit Care Med 25: 726-732
32. Levine E, Rosen A, Sehgal L, Gould S, Sehgal H, Moss G (1990) Physiologic effects of acute
anemia: Implications for a reduced transfusion trigger. Transfusion 30: 11-14
33. Geha AS (1976) Coronary and cardiovascular dynamics and oxygen availability during acute
normovolemic anemia. Surgery 80: 47-53
34. Weiskopf RB, Viele MK, Feiner J, et al (1998) Human cardiovascular and metabolic response to
acute, severe isovolemic anemia. JAMA 279: 217-221
35. Rawstron RE (1970) Anemia and surgery. A retrospective clinical study. Aust NZ J Surg
39:425-432
36. Mathru M, Kleinman B, Blakeman B, Dries D, Zecca A, Rao T (1991) Cardiovascular adjustments
and gas exchange during extreme hemodilution in humans. Crit Care Med 19: 700-704
37. Mathru M, Kleinman B, Blakeman B, Sullivan H, Kumar P, Dries DJ (1992) Myocardial me-
tabolism and adaptation during extreme hemodilution in humans after coronary revasculariza-
tion. Crit Care Med 20: 1420-1425
38. Geha AS, Baue AE (1978) Graded coronary stenosis and coronary flow during acute normovo-
lemic anemia. World J Surg 2: 645-652
39. Hardy JF, Martineau R, Couturier A, et al (1998) Influence of haemoglobin concentration after
extracorporeal circulation on mortality and morbidity in patients undergoing cardiac surgery.
Br J Anaesth 1 : 38-45
40. Nelson AH, Fleisher LA, Rosenbaum SH (1993) Relationship between postoperative anemia and
cardiac morbidity in high-risk vascular patients in the intensive care unit. Crit Care Med
21:860-866
41. Fang WC, Helm RE, Krieger KH, et al (1997) Impact of minimum hematocrit during cardiopul-
monary bypass on mortality in patients undergoing coronary artery surgery. Circulation
96: 194-199
42. DaFoe GR, Ross CS, Olmstead EM, et al (2001) Lowest hematocrit on bypass and adverse out-
comes associated with coronary artery bypass grafting. Ann Thorac Surg (In press)
43. Smith MS, Conlon PI, White ED, et al (1998) Low hematocrit but not perfusion pressure dur-
ing CPB is predictive for renal failure following CABG surgery. Anesth Analg 86: SAC102
(Abst)
44. Carson JL, Spence RK, Poses RM (1988) Severity of anaemia and operative mortality and mor-
bidity. Lancet i:727-729
45. Carson JL, Duff A, Poses RM, et al (1996) Effect of anaemia and cardiovascular disease on surgi-
cal mortality and morbidity. Lancet 348: 1055-1060
46. Spence RK, Carson JA, Poses R, et al (1990) Elective surgery without transfusion: Influence of
preoperative hemoglobin level and blood loss on mortality. Am J Surg 159: 320-324
47. Kitchens CS (1993) Are transfusions overrated? Surgical outcome of Jehovah's Witnesses. Am J
Med 94: 117-119
48. Alexiu 0, Mircea N, Balaban M, Furtunescu B (1975) Gastrointestinal hemorrhage from peptic
ulcer. An evaluation of bloodless transfusion and early surgery. Anaesthesia 30: 609-615
49. Dietrich KA, Conrad SA, Hebert CA, Levy GL, Romero MD (1990) Cardiovascular and metabol-
ic response to red blood transfusion in critically ill volume resuscitated patients. Crit Care Med
18:940-944
50. Lorente JA, Landin L, De Pablo R, Renes E, Rodriguez-Diaz R, Liste D (1993) Effects of blood
transfusion on oxygen transport variables in sepsis. Crit Care Med 21: 1312-1318
318 s. D. Surgenor et al.: Optimizing Red Blood Cell Transfusion Practice

51. Robbins JM, Keating K, Orlando R, Yeston NS (1993) Effects of blood transfusion on oxygen de-
livery and consumption in critically ill surgical patients. Contemp Surg 43 : 281-285
52. Steffes CP, Bender JS, Levison MA (1991) Blood transfusion and oxygen consumption in surgi-
cal sepsis. Crit Care Med 19: 512-517
53. Hebert P, Wells G, Blajchman MA, et al (1999) A multicenter, randomized, controlled clinical trial
of transfusion requirements in critical care. N Engl J Med 340: 409-417
54. Baxter BT, Minion DJ, McCance CL, Eskildsen JM, Heffele JJ, Lynch TG (1993) Rational approach
to postoperative transfusion in high- risk patients. Am J Surg 166 : 720-725
55. Smoller BR, Kruskall MS (1986) Phlebotomy for diagnostic laboratory tests in adults: Pattern of
use and effect on transfusion requirements. N Engl J Med 314: 1233-1235
56. Eyster E, Bernene J (1973) Nosocomial anemia. JAMA 223: 73-74
57. Tarpey J, Lawler PG (1990) Iatrogenic anaemia? A survey of venesection in patients in the inten-
sive therapy unit. Anaesthesia 45: 396-398
58. Muakkassa FF, Rutledge R, Fakhry SM, Meyer AA, Sheldon GF (1990) ABGs and arterial lines:
The relationship to unnecessarily drawn arterial blood gas samples. JTrauma 30: 1087-1095
59. Low LL, Harrington GR, Stoltzfus DP (1995) The effect of arterial lines on blood-drawing prac-
tices and costs in intensive care units. Chest 108: 216-219
60. Chernow B, Salem M, Stacey J (1991) Blood conservation - A critical care imperative. Crit Care
Med 19:313-314
61. Chernow B (1993) Blood conservation in critical care - The evidence accumulates. Crit Care
Med 21 :481-482
62. Foulke GE, Harlow OJ (1989) Effective measures for reducing blood loss from diagnostic labor-
atory tests in intensive care unit patients. Crit Care Med 17: 1143-1145
63. Smoller BR, Kruskall MS, Horowitz GL (1989) Reducing adult phlebotomy blood loss with the
use of pediatric sized blood collection tubes. Am J Clin Pathol 91 : 701-703
64. Civetta JM, Hudson-Civetta JA (1985) Maintaining quality of care while reducing charges in the
ICU. Ann Surg 202: 524-530
65. Valenstein P, Leiken A, Lehmann C (1988) Test-ordering by multiple physicians increases un-
necessary laboratory examinations. Arch Pathol Lab Med 112: 238-241
66. Corwin HL, Rodriguez RM, Pearl RG, Corwin MJ, Enny C, Gettinger A (1997) Erythropoietin
response in critically ill patients. Crit Care Med 25: A82 (Abst)
67. Rodriguez RM, Corwin HL, Pearl RG, Corwin MJ, Enny C, Gettinger A (1997) Iron, B12, and
folate deficiency in rcu patients. Crit Care Med 25: A80 (Abst)
68. Gabriel A, Kozek S, Chiari A, et al (1998) High dose recombinant human erythropoietin stimu-
lates reticulocyte production in patients with multiple organ dysfunction syndrome. J Trauma
44:361-367
69. Corwin H, Krantz S (2000) Anemia in the critically ill: "Acute" anemia of chronic disease. Crit
Care Med 28: 3098-3099
70. Corwin HL, Rodriguez RM, Pearl RG, Corwin MJ, Enny C, Gettinger A (1999) Efficacy of recom-
binant erythropoietin in critically ill patients: A randomized, double blind, placebo controlled
trial. Crit Care Med 27: 2346-2350