Title Page
A prospective study on anemia and blood transfusion in critically ill patients
Ali A. Faydhia, Sami Bahlasb, Maimoona M. Ahmedb
aDepartment of ICU, King Abdul Aziz University Hospital, Jeddah, Saudi Arabia, bDepartment of Medicine,
King Abdul Aziz University Hospital, Jeddah, Saudi Arabia.
Address all correspondence to:
Assistant professor Sami Bahlas
Department of Internal Medicine
King Abdul Aziz University Hospital
Jeddah, Saudi Arabia
P.O. Box 80215 Jeddah 21589
Telephone: 0966505625857
Fax #: 0996(2)6408315
E-mail: drsamibahlas@yahoo.com
Short title: The incidence of anemia and blood transfusion
Key words: blood transfusion, anemia, hemoglobin, normocytic normochromic.
1
ABSTRACT:
Objective: To quantify the incidence of anemia and red blood cell (RBC) transfusion practice in
critically ill patients and to examine the relationship of anemia and RBC transfusion in clinical
outcomes.
Design: The cohort study included 100 critically ill patients from King Abd El Aziz University
Hospital, Saudi Arabia in 2010. Complete blood count was done detecting types and causes of
anemia, and accordingly patients were divided into two groups - those who received blood
transfusion versus those who did not. Anemic patients were identified, when having Hemoglobin
(Hb) less than 14g/dl in males and Hb less than 12g/dl in females. The study contained 23% Saudi
patients and 77% non-Saudi patients. There were 53% enrolled males and 47% females with an
average age of 59.74 + 2.03 years. The data was analyzed based on the overall and the blood
transfusion basis (50/50)
Results: The study enrolled 100 patients, 50% of whom had blood transfusion. 82% of the patients in
the ICU had anemia, mainly Normocytic Normochromic. There is an association between blood
transfusion and mortality in critically ill patients, as 66% of patients, who had transfusion, died.
Conclusion: Although critically ill patients with anemia have an increased risk of death, especially in
the case of blood transfusion (66% of patients who received a transfusion died), however each of
them must be assessed individually.
2
Introduction:
Anemia is a common problem among critically ill patients that the majority of them need blood
transfusion during their stay in the intensive care unit (ICU). However, the decision to transfuse is
not always clearly defined and in the recent years, this issue has seen considerable debate and
controversy.[1]
Two decades ago, a hematocrit between 0.20 and 0.25 was considered an urgent indication for
transfusion, but at the turn of this century, maintaining a hematocrit at this level is considered to be
"best- practice medicine".[2]
Although the definition and grading of anemia varies among different organizations, most of them
agree that a hemoglobin level below 6.5 g/dl indicates severe or life-threatening anemia. [3]
Anemia of critical illness, a commonly encountered clinical situation, is hematologically similar to
that of chronic anemia, except that its onset is generally sudden. The etiology is usually multifactorial,
occurring as a consequence of direct inhibitory effects of inflammatory cytokines, erythropoietin
deficiency, blunted erythropoietic response, blood loss, nutritional deficiencies, and renal
insufficiency. Although anemia is not well tolerated by critically ill patients, aggressive treatment of
anemia can be just as detrimental as no treatment. [3] It can also be due to reduced erythropoiesis, or
increased red cell destruction.[1]
The possible relationship between blood transfusion and poor outcome has led many to review their
transfusion practices. There are two main reasons to give a blood transfusion in a critically ill patient:
1. To increase tissue oxygenation: The hemoglobin level is, with the cardiac output and the PaO2, an
essential determinant of oxygen transport. Nevertheless, increasing hemoglobin levels via transfusion
will not necessarily increase tissue oxygenation. Indeed, increasing the number of red blood cells can
increase blood viscosity, which in turn can decrease cardiac output, and hence, limit oxygen delivery.
In addition, a reduction in the hematocrit can have beneficial effects on the microcirculation, with
oxygen extraction capacities being greater when the hematocrit is reduced whether under
physiological conditions[4] or during sepsis.[5] It should also be stressed that blood transfusion rarely
increases oxygen uptake, except under extreme conditions, where oxygen uptake is directly dependent
3
on oxygen delivery, essentially in circulatory shock associated with hyperlactatemia[6,7,8] or in severe
anemia with hemoglobin levels generally less than 6 g/dl. Hebert and Chin-Yee[9] identified 14 studies,
in which the impact of blood transfusion on oxygen kinetics was assessed, and noted that only five
reported an increase in VO2 following transfusion.
2. To avoid myocardial ischemia: During anemia, the increased cardiac output (due to decreased
viscosity and adrenergic stimulation) augments myocardial oxygen demands, and patients with acute
myocardial instability tolerate anemia poorly.[10]
Anemia, because of its associated morbidity and mortality, is of a clinical importance in critically ill
patients. Among patients who have normal hemoglobin levels on admission to an intensive care unit
(ICU), nearly all become anemic during the course of their ICU stay.[11,12]
The whole transfusion issue has become a hot area of debate in the last five years; triggered by the
study by Hebert et al[13] noting that a more restrictive transfusion protocol (transfusions given when
the hemoglobin concentration drops below 7.0 g/dl and hemoglobin concentrations maintain at 7.09.0 g/dl) was at least as effective and possibly more than a more conservative approach (transfusions
given when the hemoglobin concentration fall below 10.0 g/dl and hemoglobin concentrations
maintain at 10.0-12.0 g/dl). [1]
Study Objectives:
To assess the prevalence of anemia and study the association of blood transfusion and mortality
in critically ill patients.
Methodology:
It is a cohort study; it recruited 100 critically ill patients divided into 2 group, 50 of whom received
blood transfusion versus the remaining 50, who did not.
Enrolled patients were evaluated to detect the association of anemia in critically ill patients and the
incidence of mortality with blood transfusion.
The data was analyzed based on overall and blood transfusion.
4
Statistical Methodology
Frequency statistics (number, percent) were mainly calculated for all the measurements.
Comparability was assessed using chi-square test for categorical variables, like sex, etc. and t-test for
continuous variables, like Hb levels.
5
Patients’ Demographics:
The study cohort of 100 patients, 50% of whom had blood transfusion, while the other 50% did not.
The study contained 23% Saudi patients, 13% of whom had blood transfusion, while the remaining
10 % did not; and 77% non-Saudi patients, 37% of whom had a transfusion and the remaining 40%
did not. There were 53% enrolled males and 47% females with average age of 59.74 + 2.03 years.
Table (1) shows the sample characteristics:
Sex:
Age:
Overall
Blood
Transfusion
No Blood
Transfusion
Males
53% (53)
26% (26)
27% (27)
Females
47% (47)
24% (24)
23% (23)
59.74 +
2.03
14 – 97
years
56.72 + 2.89
years
62.76 + 2.82
years
14 – 90 years
21 – 97 years
23% (23)
13% (13)
10% (10)
77% (77)
37% (37)
40% (40)
Mean
SE
Range
Nationality:
Saudi
Non
Saudi
+
P-Value
0.842
0.138
0.476
6
Results:
Out of the 100 patients, 82% (82 patients) were anemic with Hb average of 10.06 + 0.28, 48 of
whom had blood transfusion. There was a very high significance between the patients who had blood
transfusion and those who did not. (P value=0.000)
Table (2) shows the level of Hemoglobin:
Anemic:
Hb range:
Overall
Blood
Transfusion
No Blood
Transfusion
Yes
82% (82)
96% (48)
68% (34)
No
18% (18)
4% (2)
32% (16)
Mean +
SE
Range
10.06 +
0.28
4.9 – 16.1
8.82 + 0.31
11.3 + 0.39
4.9 – 14
5.4 – 16.1
P-Value
0.000
0.000
7
The predominant peripheral smear picture was of Normocytic normochromic type (68%). The others
were microcytic hypochromic with 25% showing a leukemoid reaction. There was no significance
between patients who received blood transfusion and those who did not.
Figure 1: The predominant peripheral smear picture was Normocytic Normochromic
100%
80%
68% 68%
60%
40%
30%
20%
20%
4% 8%
6% 4%
Blood Transfusion
Dimorphic
Normocytic
Normoochromic
Microcytic Hypochromic
Leukomoid
0%
No Blood Transfusion
8
Sepsis was the most common clinical setting associated with anemia in 72% of the patients followed
by Chronic Renal Failure in 56% of the patients. The others being gastrointestinal bleeding,
hemolysis and internal hemorrhage. The blood transfusion group, also, had the same most common
clinical setting associated with anemia as sepsis, which was 76% of the cases followed by Chronis
renal failure in 62%. There was no significance between patients who received blood transfusion and
those who did not.
Figure 2: Causes of anemia identified in the study
100%
80%
76%
68%
62%
60%
50%
40%
32%
36%
20%
4% 4%
8%
2%
Blood Transfusion
Hemolysis
Internal Hemorrhage
Gastro-intestinal Bleeding
Chronic Renal Failure
Sepsis
0%
No Blood Transfusion
9
The mortality rate of the 100 patients studied was 50% (50 patients), 66% (33 patients) of whom
were given blood transfusion, while the other 34% (17 patients) had no blood transfusion showing a
very high significant rate (P-value 0.001).
The mortality rate, in those who were transfused at Hb< 7 g/l, was 80% compared to 40% of the
mortality rate, in those who were transfused at Hb>10 g/l (P-value 0.015).
The duration of stay in the ICU for patients who got blood transfusion was 10.94 + 1.5 compared to
4.1 + 0.79 in patients who had no blood transfusion having a very high significant rate (P-value
0.000).
The range of blood units received by patients was 3.32 + 0.3.
Table (3) shows the mortality and morbidity rates:
Mortality:
Duration of
ICU Stay:
Overall
Blood
Transfusion
No Blood
Transfusion
Yes
50% (50)
66% (33)
34% (17)
No
50% (50)
34% (17)
66% (33)
7.52 + 0.91
10.94 + 1.5
4.1 + 0.79
1 – 54 days
1 – 54 days
1 – 32 days
Mean +
SE
Range
P-Value
0.001
0.000
10
Discussion:
A study shows that nearly half the patients admitted to an ICU have Hb levels less than 10 g/l, while
another study showed that two-thirds of patients admitted to an ICU have Hb levels less than 10 g/l
[2] and this was close to another study that showed that 29% of the patients had a hemoglobin
concentration of less than 10 g/dl. [1]
The mortality rate of patients who received a transfusion versus who did not was 66% versus 34%
showing a similar very high significant rate (P-value 0.001), similar as another study that included
3534 patients from 146 Western European ICUs.[2]
Sepsis was the most common clinical setting associated with anemia for 72% of the patients
followed by Chronic Renal Failure in 56% of the patients. Another study, also, showed that sepsis
was the most common association with anemia followed by chronic renal failure. [2]
The complications of blood transfusion include volume overload, febrile reactions and fatal
hemolytic reactions, which may all contribute to increased mortality rate.[15,16,17,18,19,]
In our study, anemic patients had a shorter duration of stay in the ICU (7.3 days) compared to
normal patients (8.5 days), this result was contradicting to another study that showed that anemic
patients had a longer ICU stay (P-value < 0.001).[1]
The relationship of anemia and red blood cell transfusion with clinical outcomes, in anemia and
blood transfusion in the critically ill study, was examined before.[2] They found that as the number
of red blood cell units transfused increased, the longer ICU & hospital stay increased, in addition to
increased mortality rate. [3]
Conclusion:
In the recent years, we have seen conflicting reports for the association of blood transfusion with
different outcomes,[1] leading to no universally accepted treatment guidelines for managing anemia,
in addition to different practices performed among clinicians, hospitals, regions, and countries. [20]
Thus, each patient must be individually assessed and the decision to transfuse the patient should be
based on many parameters including clinical condition, age, pre-existing and current disease
11
processes, oxygenation parameters with indexes of tissue hypoxia available, as well as the traditional
hemoglobin values. [1]
12
References:
1. Vincent JL, Yalavatti G. Transfusion practice in the ICU: When to transfuse?. Indian J Crit Care
Med 2003 ;7:237-41.
2. Naveen Manchal, S Jayaram, A prospective cohort study on anemia and blood transfusion in
critically ill patients. Indian Journal of Critical Care Medicine, 2007 | Volume : 11 | Issue :
4 | Page : 182-185.
3. Kwame Asare, PharmD, Anemia of Critical Illness. Pharmacotherapy Publications. Posted:
12/05/2008; Pharmacotherapy. 2008;28(10):1267-1282.
4. Van der Linden P, Gilbert E, Engelman E, Schmartz D, Vincent JL. Effects of anesthetic agents
on systemic critical O2 delivery. J Appl Physiol 1991;71:83-93.
5. Creteur J, Sun Q, Abid O, De Backer D, Van der LP, Vincent JL. Normovolemic hemodilution
improves oxygen extraction capabilities in endotoxic shock. J Appl Physiol 2001;91:1701-7.
6. Fenwick JC, Dodek PM, Ronco JJ, Phang PT, Wiggs B, Russell JA. Increased concentrations of
plasma lactate predict pathological dependence of oxygen consumption on oxygen delivery in
patients with adult respiratory distress syndrome. J Crit Care 1990;5:81-7.
7. Bakker J, Vincent JL. The oxygen supply dependency phenomenon is associated with increased
blood lactate levels. J Crit Care 1991;6:152-9.
8. Gilbert EM, Haupt MT, Mandanas RY, Huaringa AJ, Carlson RW. The effect of fluid loading,
blood transfusion and catecholamine infusion on oxygen delivery and consumption in patients with
sepsis. Am Rev Respir Dis 1986;134:873-8.
9. Hébert PC, Chin-Yee I. Should old red cells be transfused in critically ill patients? In: Vincent JL,
editor. 2000 Yearbook of Intensive Care and Emergency Medicine. Heidelberg: Springer
2000:494-506.
10. Wu WC, Rathore SS, Wang Y, Radford MJ, Krumholz HM. Blood transfusion in elderly
patients with acute myocardial infarction. N Engl J Med 2001;345:1230-6.
11. Corwin HL, Parsonnet K, Gettinger A. RBC transfusion in the ICU: Is there a reason? Chest
1995;108:767-71.
12. Corwin HL, Gettinger A, Pearl RG, et al. The CRIT study: anemia and blood transfusion in the
critically ill—current clinical practice in the United States. Crit Care Med 2004;32:39-52.
13. 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;340:409-17.
14. Carson JL, Duff A, Poses RM, Berlin JA, Spence RK, Trout R, et al. effect of anemia and
cardiovascular disease on surgical mortality and morbidity. Lancet 1996;348:1055-60.
15. Edna TH, Bjerkeset T. Association between blood transfusion and infection in injured patients. J
Trauma 1992;33:659-61.
16. Stephan F, Montblanc Jd, Cheffi A, Bonnet F. Thrombocytopenia in critically ill surgical
patients: A case-control study evaluating attributable mortality and transfusion requirements. Crit
Care 1999;3:151-8.
17. Goodnough LT, Brecher ME, Kanter MH, AuBuchon JP. Transfusion medicine: First of two
parts-blood transfusion. N Engl J Med 1999;340:438-47.
18. Thurer RL. Blood transfusion in cardiac surgery. Can J Anesth 2001;48:S6-12.
19. Vamvakas ES, Moore SB, Cabanela M. Blood Transfusion and septic complications after hip
replacement surgery. Transfusion 1995;35:150-6.
13
20. Shander A. Anemia in the critically ill. Department of Anesthesiology, Critical Care Medicine,
Pain Management and Hyperbaric Medicine, Englewood Hospital and Medical Center, NJ 07631,
USA.
14
‫العالقة بين مرض فقر الدم و نقل الدم مع المرضى ذوى الحاالت الحرجة‬
‫(ا)على الفايدى‪)2( ,‬سامى بحلس‪)2( ,‬ميمونه أحمد‬
‫(‪)1‬قسم العناية المركزة‪ ،‬مستشفى جامعة الملك عبدالعزيز بجدة‪ ،‬المملكة العربية السعودية‬
‫(‪)2‬قسم الطب الباطنى ‪،‬مستشفى جامعة الملك عبد العزيز بجدة‪ ،‬المملكة العربية السعودية‬
‫الهدف‪ :‬لتحديد معدل انتشارو العالقة بين فقر الدم الناجم عن ممارسة ونقل خاليا الدم الحمراء في المرضى ذوي‬
‫الحاالت الحرجة‪.‬‬
‫تصميم الدراسة ‪ :‬تشتمل الدراسة على ‪100‬مريض من ذوى الحاالت الحرجة فى مستشفى جامعة الملك عبد العزيز‬
‫المملكة العربية السعودية عام ‪. 0202‬تم الكشف عن صورة الدم الكامل لتحديد أنواع وأسباب فقر الدم‪ ،‬وبالتالي تم‬
‫تقسيم المرضى إلى مجموعتين‪ :‬أولئك الذين تلقوا نقل الدم مقابل أولئك الذين لم يفعلوا ذلك ‪.‬وقد تم تحديد مرض فقر الدم‬
‫حيث الهيموغلوبين أقل من ‪14g/dl‬في الذكور وأقل من ‪12g/dl‬في اإلناث ‪.‬وتضمنت الدراسة ‪ ٪23‬من المرضى‬
‫السعوديين و ‪ ٪ 77‬من المرضى من غير السعوديين ‪.‬كان هناك ‪ ٪53‬من الذكور و ‪ ٪47‬من اإلناثث‪ ,‬متوسط‬
‫أعمارهم ‪59.74 + 2.03‬سنة ‪.‬وتم تحليل البيانات استنادا على أساس نقل الدم )‪(50/50‬‬
‫النتائج ‪ :‬التحق بالدراسة ‪100‬مريض‪ ٪50 ،‬منهم قد نقل لهم دم ‪.‬وكان ‪ ٪82‬من المرضى في وحدة العناية المركزة‬
‫لديهم مرض فقر الدم‪ .‬هناك ارتباط بين نقل الدم ومعدل وفيات المرضى ذوى الحاالت الحرجة حيث ‪ ٪66‬من‬
‫المرضى الذين كانوا قد نقل لهم دم لقوا حتفهم‪.‬‬
‫الخالصة ‪ :‬المرضى ذوي الحاالت الحرجة اللذين يعانون من مرض فقر الدم تزيد لديهم مخاطر الوفاة‪ ،‬وخاصة في‬
‫حالة نقل الدم حيث زادت نسبة الوفاة لتصل الى ‪ , ٪66‬ولذلك يمكن تقييم كل حالة على حدة‪.‬‬
‫‪15‬‬