Anemia in the critical care setting is a common condition frequently resulting in
the use of red cell transfusions. Of particular concern are those anemic, critically
ill patients with ischemic heart disease. This critically ill population may be predisposed
to the adverse consequences of anemia, by the very nature of their underlying cardiac
disease. However, they may also be more predisposed to the adverse consequences of
RBC transfusion. Research to date has provided opposing views in terms of the optimal
transfusion strategies for use in this ¿at risk¿ population. While observational studies
have indicated that a liberal strategy is more beneficial, a recent RCT found that
a strategy maintaining hemoglobin concentrations between 70 and 90 g/L may result
in similar, if not better, outcomes. Further studies are needed, however, to clarify
whether the results of this trial can be generalized to patients with cardiovascular
disease.
References
- 1
Linman J W.
Physiologic and pathophysiologic effects of anemia.
N.Engl.J.Med..
1968;
279
812-818
- 2 Brazier J, Cooper N, Maloney M r, Buckberg G. Acute normovolemic anemia: effect
on the adequacy and distribution of coronary blood flow. Surgical Forum 1973: 203-204
- 3
Fowler N O, Holmes J C.
Blood viscosity and cardiac output in acute experimental anemia.
J.Appl.PhysioL.
1975;
39
453-456
- 4
Escobar E, Jones N L, Rapaport E, Murray J F.
Ventricular performance in acute normovolemic anemia and effects of beta blockade.
Am. J.Physiol..
1966;
211
877-884
- 5
Fowler N O, Shabetai R, Anderson D, Braunstein J R.
Sorne circulatory effects of experimental hypovolemic anemia.
Am. Heart. J..
1960;
60
551-561
- 6
Cole D J, Drummond J C, Shapiro H M, Hertzog R E, Brauer F S.
The adequacy of subendocardial oxygen dellvery. The interaction of deterrninants of
flow, arterial oxygen content and myocardial oxygen need.
Circulation.
1974;
49
968-977
- 7
Levine E, Rosen A, Sehgal L, Gould S, Sehgal H, Moss G.
Physiologic effects of aeute anemia: implications for a reduced transfusion trigger.
Transfusion.
1990;
30
11-14
- 8
Richardson T Q, Guyton A C.
Effects of polycythemia and anemia on cardiac output and other circulatory factors.
Am. J.Physiol..
1959;
197
1167-1170
- 9
Marini J J.
Transfusion Triggers and Occam's rusty razor.
Crit Care Med.
1998;
26
1775-1776
- 10
Corwin H L, Parsonnet K C, Gettinger A.
RBC transfusion in the ICU. Is there a reason?.
Chest.
1995;
108
767-771
- 11
Geha A S.
Coronary and cardiovascular dynamics and oxygen availability during acute normovolemic
anemia.
Surgery.
1976;
80
47-53
- 12
Geha A S, Baue A E.
Graded coronary stenosis and coronary flow during acute normovolemic anemia.
World J. Surg..
1978;
2
645-652
- 13
Bordin J O, Heddle N M, Blajchman M A.
Biologic effects of leukocytes present in transfused cellular blood products.
Blood.
1994;
84
1703-1721
- 14
Houbiers J GA, Brand A, van de Watering L MG, Hermans J, Verwey P JM, Bijnen A B,
Pahlplatz P, Schattenkerk M E, Wobbes T, de Vries J E, Klementschitsch P, van de Maas A HM,
van de Velde C JH.
Randomised controlled trial comparing transfusion of leucocyte-depleted or buffy-coat-depleted
blood in surgery for colorectal cancer.
Lancet.
1996;
344
573-578
- 15
Crosby E T.
Perioperative haemotherapy. II. Risks and complications of blood transfusion.
Can. J.Anesth..
1992;
39
822-837
- 16
van de Watering L MG, Houbiers J GA, Hermans J, Harvey M S, Bouter H, Boer F, Huysmans H A,
Brand A.
Leukocyte depletion reduces postoperative mortality in patients undergoing cardiac
surgery.
Br. J.HaematoL.
1996;
93
312
- 17
Jensen L S, Andersen A J, Christiansen P M, Hokland P, Juhl C O, Madsen G, Mortensen J,
Moller-Nielsen C, Hanberg-Sorensen F, Hokland M.
Postoperative infection and natural killer cell function following blood transfusion
in patients undergoing elective colorectal surgery.
Br. J.Surg..
1992;
79
513-516
- 18
Jensen L S, Kissmeyer-Nielsen P, Wolff B, Qvist N.
Randomised comparison of leucocyte-depicted versus buffy-coat-poor blood transfusion
and complications after colorectal surgery.
Lancet.
1996;
348
841-845
- 19
Heiss M M, Memple W, Jauch K -W, Delanoff C, Mayer G, Mempel M, Eissner H -J, Schildberg F -W.
Beneficial effects of autologous blood transfusion on infectious complications after
colorectal cancer surgery.
Lancet.
1993;
342
1328-1333
- 20
Messmer K FW.
Acceptable hematocrit levels in surgical patients.
World J.Surg..
1987;
11
41-46
- 21
Hersch M, Bersten A D, Rutledge F S, Troster M, Groom A, Sibbald W J.
Quantitative evidence of microcirculatory compromise in skeletal muscle of normotensive
hyperdynamic septic sheep [abstract].
Crit.Care Med..
1989;
17
S60
- 22
Hurd T C, Dasmahapatra K S, Rush B F, Machiedo G W.
Red blood cell deformability in human and experimental sepsis.
Arch.Surg..
1988;
123
217-220
- 23
Langenfeld J E, Livingston D H, Machiedo G W.
Red cell deformability is an early indicator of infection.
Surgery.
1991;
110
398-404
- 24
Baker C H, Wilmoth F R, Sutton E T.
Reduced RBC versus plasma microvascular flow due to endotoxin.
Circ.Shock.
1986;
20
127-139
- 25
Cane R D.
Hemoglobin: how much is enough?.
Crit.Care Med..
1990;
18
1046-1047
- 26
Carson J L, Duff A, Poses R M, Berlin J A, Spence R K, Trout R, Noveck H, Strom B L.
Effect of anaemia and cardiovascular disease on surgical mortality and morbidity.
Lancet.
1996;
348
1055-1060
- 27
Sugerman H J, Davidson D T, Vibul S, Delivoria-Papadopoulos M, Miller L D, Oski F A.
The basis of defective oxygen delivery from stored blood.
Surg.Gynecol.Obstet..
1970;
137
733-741
- 28
Myburgh J A, Webb R K, Worthley L IG.
The P50 is reduced in critically ill patients.
Intensive Care Med..
1991;
17
355-358
- 29
Parris W CW, Kambam J R, Blanks S, Dean R.
The effect of intentional hemodilution on 1250.
J.Cardiovasc.Surg..
1988;
19
560-562
- 30
Iapichino G, Radrizzani D, Solca M, Franzosi M G, Pallavicini F B, Spina G, Scherini A.
Restoration of blood 2,3-diphosphoglycerate levels in multi-transfused patients: effect
of organic and inorganic phosphate.
Int.Surg..
1984;
69
113-116
- 31
Rodman T, Close H P, Purcell M K.
The oxyhemoglobin dissociation curve in anemia.
Ann.Intem.Med..
1960;
52
295-309
- 32
Kennedy A C, Valtis D J.
The oxygen dissociation curve in anemia of various types.
J.Clin.Invest..
1954;
33
1372-1381
- 33
Kahn R C, Zaroulis C, Goetz W, Howland W S.
Hemodynamic oxygen transport and 2,3-diphosphoglycerate changes after transfusion
of patients in acute respiratory failure.
Intensive Care Med..
1986;
12
22-25
- 34
Oski F A, Marshall B E, Cohen P J, Sugerman H J, Miller L D.
Exercise with anemia. The rolle of the left-shifted or right-shifted oxygen-hemoglobin
equilibrium curve.
Ann.Intem.Med..
1971;
74
44-46
- 35
Oski F A, Gottlieb A J, Delavoria-Papadopoulos M, Miller W W.
Red-cell 2,3-diphosphoglycerate levels in subjects with chronic hypoxemia.
N.Engl. J.Med..
1969;
280
1165-1166
- 36
Brecher M E, Zylstra-Halling V W, Pineda A A.
Rejuvenation of erythrocytes preserved with AS-1 and AS-3.
Am. J.Clin.Pathol..
1991;
96
767-769
- 37
Studzinski T, Czarnecki A, Gluszak A.
Effect of acute posthaemorrhagic anaemia on the level of 2,3-diphosphoglycerate (2,3-DPG)
in the erythrocytes of Sheep.
Acta Phys.Poi..
1980;
31
365-373
- 38
Chanutin A, Curnish R R.
Effect of organic and inorganic phosphates on the oxygen equilibrium of human erythrocytes.
Arch.Biochem.Biophys..
1967;
121
96-102
- 39
Benesch R, Benesch R E.
The effect of organic phosphates from the human erythrocytes on the allosteric properties
of hemoglobin.
Biochem.Biophys.Res.Commun..
1967;
26
162-167
- 40
Benesch R, Benesch R E, Yu C I.
Reciprocal binding of oxygen and diphosphoglycerate by human hemoglobin.
Proc. Nat. Acad. Sci. USA.
1968;
59
526-532
- 41 Wyman J.
Hemoglobin function. In: Hemoglobin: molecular, genetic and clinical aspects Edited by Bunn HF, Forget
BG. Philadelphia; W.B. Saunders & Co. 1986: 37-60
- 42
Bohr C, Hasselbalch K A, Krogh A.
Ueber einen in biologischer Beziehung wichtigen Einfluss, den die Kohlensäurespannung
des Blutes auf dessen Sauerstoff Bindung uebt. Scand.Arch.
Physiol.
1904;
16
402-412
- 43 Snyder J V.
Oxygen transport: the model and reality. In: Oxygen Transport in the Critically Ill. Edited by Snyder JV, Pinsky MR. Chicago,
Illinois; Year Book Medical Publishers, Inc. 1987: 3-15
- 44
Schumacker P T, Samsel R W.
Oxygen delivery and uptake by peripheral tissues: physiology and pathophysiology.
Crit.Care Clin..
1989;
5
255-269
- 45
Tuman K J.
Tissue oxygen dellvery. The physiology of anemia.
Anesth.Clin. N.Am..
1990;
8
451-469
- 46
The Multicenter Diltiazem Postinfarction Trial Research Group. The effect of diltiazem on mortality and reinfarction after myocardial infarction. N.Engl.
J.Med 1988 319: 385-392
- 47
Finch C A, Lenfant C.
Oxygen transport in man.
N.Engl. J.Med..
1972;
286
407-415
- 48 Alexander R H, Ali J, Aprahamian C, Bell R M, Bianco E, Brown R, Collicott P E,
Doto F X, George J H, Hughes I K, Judd R L, Jurkovich G J, Krantz B E, Lapiana F G,
Maull K I, McGehee J A, McManus W F, McSwain N E, Meyer C L, Nichols J B, Olson F,
Peitzman A B, Proctor H, Ramenofsky M L, Reynolds S A, Salander J M, Simmonds R C,
Tepaslll J J, Trafton P G, Watts C, West J. Advanced Trauma Life Support. Program
for Physicians, edn 5th. Chicago, Illinois; American College of Surgeons 1993
- 49
Brannon E S, Merrill A J, Warren V J, Stead E A.
The cardiac output in patients with chronic anemia as measured by the technique
of right atrial catheterization.
J.Clin.Invest..
1945;
24
332-336
- 50
Welch H G, Meehan K R, Goodnough L T.
Prudent strategies for elective red blood cell transfusion.
Ann. Intern. Med..
1992;
116
393-402
- 51
Duke M, Abelmann W H.
The hemodynamic response to chronic anemia.
Circulation.
1969;
39
503-515
- 52
Chapler C K, Cain S M.
The physiologic reserve in oxygen carrying capacity: studies in experimental hemodilution.
Can. J.Physiol. Pharmacol..
1985;
64
7-12
- 53
Bowens C Jr, Spahn D R, Frasco P E, Smith L R, McRae R L, Leone B J.
Hemodilution induces stable changes in global cardiovascular and regional myocardial
function.
Anesth. Analg..
1993;
76
1027-1032
- 54
Crystal G J, Salem M R.
Myocardial oxygen consumption and segmental shortening during selective coronary hemodilution
in dogs.
Anesth. Analg..
1988;
67
500-508
- 55
Laks H, Pilon R N, Klovekorn W P, Anderson W P, MacCallum J R, O'Connor N T.
Acute hemodilution: its effect on hemodynamics and oxygen transport in anesthetized
man.
Ann.Surg..
1974;
180
103-109
- 56
Rosberg B, Wulff K.
Hemodynamics following normovolemic hemodilution in elderly patients.
Acta Anaesthesiol. Scand..
1981;
25
402-406
- 57
Shah D M, Prichard M N, Newell J C, Karmody A M, Scovill W A, Powers S R Jr.
Increased cardiac output and oxygen transport after intraoperative isovolemic hemodilution.
A study in patients with peripheral vascular disease.
Arch.Surg..
1980;
115
597-600
- 58
Rose D, Coutsoftides T.
Intraoperative normovolemic hemodilution.
J.Surg.Res..
1981;
31
375-381
- 59
Boldt J, Kling D, Weidler B, Zickmann B, Herold C, Dapper F, Hempelman G.
Acute preoperative hemodilution in cardiac surgery: volume replacement with a hypertonic
saline-hydroxyethyl starch solution.
J.Cardiothorac.Vasc.Anesth..
1991;
5
23-28
- 60
Mouren S, Baron J -F, Hag B, Arthaud M, Viars P.
Normovolemie hemodilution and lumbar epidural anesthesia.
Anesth.Analg..
1989;
69
174-179
- 61
Herregods L, Foubert L, Moerman A, Francois K, Rolly G.
Comparative study of limited intentional normovolaemic haemodilution in patients with
left main coronary artery stenosis.
Anaesthesia.
1995;
50
950-953
- 62
Welch M, Knight D G, Carr M H, Smyth J V, Walker M G.
The preservation of renal function by isovolemic hemodilution during aortic operations.
J.
Vasc.Surg.
1993;
18
858-866
- 63
Duke M, Herbert V D, Abelmann W H.
Hemodynamic effects of blood transfusion in chronic anemia.
N.Engl.J.Med..
1964;
271
975-980
- 64
Cropp G JA.
Cardiovascular function in children with severe anemia.
Circulation.
1969;
39
775-784
- 65
Roy S B, Bhatia M L, Mathur V S, Virmani S.
Hernodynamic effects of chronic severe anemia.
Circulation.
1963;
28
346-356
- 66
Weiskopf R B, Viele M K, Feiner J, Kelley S, Lieberman J, Noorani M, Leung J M, Fisher D M,
Murray W R, Toy P, Moore M A.
Human cardiovascular and metabolic response to acute, severe isovolemic anemia.
JAMA.
1998;
279
217-221
- 67
Whitaker W.
Some effects of severe chronic anaemia on the circulatory system.
Quart. J.Med..
1956;
25
175-183
- 68
Woodson R D, Auerbach S.
Effect of increased oxygen affinity and anemia on cardiac output and its distribution.
J. Appl. Physiol..
1982;
53
1299-1306
- 69
Messmer K.
Hemodilution - possibilities and safety aspects.
Acta Anaesthesiol. Scand..
1988;
32
49-53
- 70
Messmer K, Lewis D H, Sunder-Plassmann L, Klovekorn W P, Mendler N, Holper K.
Acute normovolemic hemodilution.
Eur. Surg.Res..
1972;
4
55-70
- 71
Spahn D R, Leone B J, Reves J G, Pasch T.
Cardiovascular and coronary physiology of acute isovolemic hemodilution: a review
of nonoxygen-carrying and oxygen-carrying solutions.
Anesth. Analg..
1994;
78
1000-1021
- 72
Crosby E T.
Perioperative haemotherapy: I. Indications for blood component transfusion.
Can. J.Anesth..
1992;
39
695-707
- 73
Hatcher J D, Chiu L K, Jennings D B.
Anemia as a stimulus to aortic and carotid chemoreceptors in the cat.
J. Appl. Physiol..
1978;
44
696-702
- 74
Murray J F, Escobar E, Rapaport E.
Effects of blood viscosity on hemodynamic responses in acute normovolemic anemia.
Am. J.Physiol..
1969;
216
638-642
- 75
Baer R W, Vlahakes G J, Uhlig P N, Hoffman J IE.
Maximum myocardial oxygen transport during anemia and polycythemia in dogs.
Am. J.Physiol..
1987;
252
H 1086-H 1095
- 76
Kowalyshyn T J, Prager D, Young J.
Preoperative hemoglobin requirements.
Anesth. Analg..
1972;
51
75-79
- 77
Glick G, Plauth W H Jr, Braunwald E.
Role of autonomic nervous system in the circulatory response to acutely induced anemia
in unanesthetized dogs.
J.Clin.Invest..
1964;
43
2112-2124
- 78
American Society of Anesthesiologists Task Force on Blood Component Therapy. Practice guidelines for blood component therapy. Anesthesiology 1996 84: 732-747
- 79
Murray J F, Rapaport E.
Coronary blood flow and myocardial metabolism in acute experimental anaemia.
Cardiovasc.Res..
1972;
6
360-367
- 80
Hatcher J D, Jennings D B, Parker J O, Garvock W B.
The role of a humoral mechanism in the cardiovascular adjustments over a prolonged
period following the production of acute exchange anaemia.
Can. J. Biochem. Physiol..
1963;
41
1887-1899
- 81
Race D, Dedichen H, Schenk W G Jr.
Regional blood flow during dextran-induced normovolemic hemodilution in the dog.
J.Thorac.Cardiovasc.Surg..
1967;
53
578-586
- 82
Martin E, Ott E.
Extreme hemodilution in the Harrington procedure.
Biblthca.Haemat..
1981;
47
322-337
- 83
Fontana J L, Welborn L, Mongan P D, Sturm P, Martin G, Bunger R.
Oxygen consumption and cardiovascular function in children during profound intraoperative
normovolemic hemodilution.
Anesth. Analg..
1995;
80
219-225
- 84
Neill W A, Phelps N C, Oxendine J M, Mahler D J, Sim D N.
Effect of heart rate on coronary blood flow distribution in dogs.
Am. J. Cardiol..
1973;
32
306-312
- 85
Neill W A, Oxendine J, Phelps N, Anderson R P.
Subendocardial ischemia provoked by tachycardia in conscious dogs with coronary stenosis.
Am. J. Cardiol..
1975;
35
30-36
- 86
Kiel J W, Shepherd A P.
Optimal hematocrit for canine gastric oxygenation.
Am. J.PhysioL.
1989;
256
H472-H477
- 87
Kiel J W, Riedel G L, Shepherd A P.
Effects of hemodilution on gastric and intestinal oxygenation.
Am. J. Physiol..
1989;
256
Hl71-H178
- 88
Hebert P C, Hu L Q, Biro G P.
Review of physiologic mechanisms in response to anemia.
Can.Med.Assoc. J..
1997;
156
S27-S40
- 89
Hebert P C, Wells G, Tweeddale M, Martin C, Marshall J, Pham B, Blajchman M, Schweitzer I,
Pagliarello G.
Does transfusion practice affect mortallty in critically ill patients? [abstract].
Am. J.Respir.Crit.Care Med..
1997;
155
A20
- 90
Rao T LK, Montoya A.
Cardiovascular, electrocardiographic and respiratory changes following acute anemia
with volume replacement in patients with coronary artery disease.
Anesthesiology.
1985;
12
49-54
- 91
Nelson A H, Fleisher L A, Rosenbaum S H.
Relationship between postoperative anemia and cardiac morbidity in high-risk vascular
patients in the intensive care unit.
Crit.Care Med..
1993;
21
860-866
- 92
Spence R K.
Anemia in the patient undergoing surgery and the transfusion decision (Narrative review
including 64 references).
Clinical Orthopaedics and Related Research.
1998;
357
19-29
- 93
Hebert P C.
Anemia and red cell transfusion in critical care (Narrative review focused on care
of the critically ill. Includes 93 references).
Minerva.Anestesiol..
1999;
65
293-304
- 94
Corwin H L, Gettinger A, Rodriguez R M, Pearl R G, Gubler K D, Enny C, Colton T, Coryell W.
Efficacy of recombinant human erythropoietin in the critically ill patient: a randomized
clouble blind placebo controlled trial (This study demonstrated that erythropoietin
decreased transfusion requirements in ICU patients. However, this superb RCT should
be reproduced with smaller doses of medication).
Crit.Care Med..
1999;
27
2346-2350
- 95
Hebert P C, Wells G, Blajchman M A, Marshall J, Martin C, Pagliarello G, Tweeddale M,
Schweitzer I, Yetisir E.
The Transfusion Requirements in Critical Care Investigators (This study demonstrated
that hemoglobin concentrations as low as 70 g/L are safe and possibly superior to
100 g/L). A multicenter, randomized, controlled clinical trial of transfusion requirements
in critical care.
N.Engl. J.Med..
1999;
340
409-417
- 96
Tadikonda L K, Mathru M, Salem M R, EI-Etr A A.
Hemodynamic and ECG changes due to normovolemic anemia in patients with coronary artery
disease [abstract].
Crit.Care Med..
1979;
7
128
- 97 Hebert P C, Blajchman M A, Yetisir E, Wells G, Martin C, Hall R, Russell J A, Schweitzer I.
For the Transfusion Requirements in Critical Care Investigators and the Canadian Critical
Care Trials Group: Is a low transfusion threshold safe in critically ill patients
with cardiovascular disase. Crit.Care Med 2000:
- 98
Bracey A W, Radovancevic R, Riggs S A, Houston S, Cozart H, Vaughn W K, Radovancevic B,
McAllister H A Jr, Cooley D A.
Lowering the hemoglobin threshold for transfusion in CABG procedures: effect on patient
outcome (This study found that a lower Hb threshold of 8 g per dL does not adversely
affect outcomes in patients undergoing coronary artery bypass graft surgery).
Transfusion.
1999;
39
((10))
1070-1077
- 99
Bayer W L, Coenen W M, Jenkins D C, Zucker M L.
The use of blood and blood components in 1,769 patients undergoing open-heart surgery.
Ann.
Thorac.Surg..
1980;
29
117-122
- 100
Marik P E, Sibbald W J.
Effect of stored-blood transfusion on oxygen delivery in patients with sepsis.
JAMA.
1993;
269
3024-3029
- 101
Longster G H, Buckley T, Sikorski J, Tovey L AD.
Scanning electron microscope studies of red cell morphology. Changes occurring in
red cell shape during storage and post transfusion.
Vox Sang.
1972;
22
161-170
- 102
LaCelle P L.
Alteration of deformability of the erythrocyte membrane in stored blood.
Transfusion.
1969;
9
238-245
- 103
Sielenkamper A U, Chin-Yee I H, Martin C M, Sibbald W J.
Diaspirin crosslinked hemoglobin improves systemic 02 uptake in 02 supply-dependent
septic rats.
Am. J.Respir.Crit.Care Med..
1997;
156
1066-1072
- 104
Martin C M, lwao Y, Potter R, Chin-Yee I H, Sibbald W J.
Decreased mucosal capillary perfusion following transfusion of stored blood in control
and septic rats.
Am. J.Respir.Crit.Care Med..
1996;
153
A464
Paul C. Hébert, MD, FRCP(C), MHSc, (Epid.)
Associate Professor, Medicine and Epidemiology
Director, Clinical Epidemiology Program,
Ottawa Hospital Research Institute
Ottawa Hospital General Campus
501 Smyth Road, Box 201
Ottawa, Ontario K1 H 8L6
eMail: phebert@ottawahospital.on.ca