LETTER TO THE EDITOR

The Risks of Blood Transfusion in Patients with SubarachnoidHemorrhage

Paul E. Marik

Published online: 23 November 2011

� Springer Science+Business Media, LLC 2011

To the Editor:

I read with much interest the recently published recom-

mendations of the Neurocritical Care Society’s Consensus

Conference on the ‘‘Critical Care management of patients

following aneurysmal subarachnoid hemorrhage (SAH)’’

[1]. These guidelines state ‘‘there was wide agreement…that data supporting restrictive transfusion in medical

patients do not apply to SAH’’ and that ‘‘patients should

receive packed RBC transfusion to maintain hemoglobin

concentration above 8–10 g/dl (moderate quality evidence,

strong recommendation).’’ I believe that the literature does

not support these recommendations.

The pathophysiologic consequences following allogenic

red blood cell (RBC) transfusion are complex and poorly

understood [2]. It is however well recognized that RBC

transfusions result in immunosuppression (perhaps life-

long) with an increased risk of infection (and tumor recur-

rence), are proinflammatory increasing the risk of acute lung

injury and multi-organ failure as well as being prothrom-

botic [2–6]. The effects of RBC transfusion on tissue

oxygenation are complex, with clinical and experimental

data demonstrating that an increase in the calculated oxygen

delivery does not necessarily translate into increased oxy-

gen uptake, even in patients with an oxygen debt [7, 8]. Dhar

et al. [9] evaluated the effect of RBC transfusion on oxygen

kinetics in eight anemic patients following a SAH. While

transfusion resulted in a 15% rise in hemoglobin and an 18%

increase in calculated oxygen delivery, the global cerebral

metabolic rate of oxygen (in ml/100 g/min) remained

unchanged. In addition, it is important to recognize that the

mean age of transfused blood in the United States in

24 days, being considerably older in major metropolitan

medical centers [10]. ‘‘Aged’’ RBC’s have been shown to

paradoxically decrease tissue oxygenation and are inde-

pendent predictors of hospital complications and death in

medical and surgical patients [7, 11–16]. Despite the fact

that 13 million units of blood are transfused annually in the

US and over 60 million worldwide [17], there is scanty

evidence that non-bleeding, hemodynamically stable

patients actually benefit from blood transfusion. Indeed,

current data suggest that in these patients blood transfusion

increases the risk of infection, ARDS, and death [18].

Anemia is a common finding in patients who have suf-

fered a SAH, with over 50% of patients having a nadir

hematocrit less than 30% [19–22]. Multiple factors likely

contribute to the development of an anemia following

SAH, including blood loss during surgery, venesection,

gastrointestinal and other sources of blood loss, decreased

production of erythropoietin, and impaired erythropoiesis

[22]. The nadir hemoglobin is generally related to the

admission Hunt and Hess grade [21, 22]. Anemia after

SAH has been reported to be associated with worse out-

comes [21, 23]. The association between anemia and worse

outcomes does not necessarily imply that correction of the

anemia with blood transfusions will improve outcome. This

is important, as data suggest that between 35 and 60%

of patients suffering a SAH receive a blood transfusion

during their hospitalization [21–26]. Apart from the risks

noted in ICU patients, there may be additional risks of

blood transfusion in patients with SAH. Nitric oxide (NO)

plays a critical role in regulating vasomotor tone and NO

metabolism may influence the risk and severity of vaso-

spasm after SAH [27]. Erythrocytes carry NO for release in

vessels, whereas transfused erythrocytes lack stored NO

and may exacerbate vasospasm [28, 29].

P. E. Marik (&)

Department of Medicine, Eastern Virginia Medical School,

825 Fairfax Ave, Suite 410, Norfolk, VA 23507, USA

e-mail: marikpe@evms.edu

123

Neurocrit Care (2012) 16:343–345

DOI 10.1007/s12028-011-9654-0

Four cohort studies have been published that have

evaluated the outcomes of blood transfusion in patients

with SAH [21, 24, 26, 30]. These studies enrolled a total of

1,718 patients; all were conducted in the USA and pub-

lished between 2004 and 2010. These studies demonstrate

that blood transfusion was an independent predictor of

death or disability (OR 1.8; 95% CI 1.3–2.2, P = 0.000),

clinical vasospasm or infarction (OR 1.6; 95% CI 1.3–2.1,

P = 0.000), and infectious complications (OR 2.9; 95% CI

2.1–3.8, P = 0.000). Using data from the American Col-

lege of Surgeons National Surgical Quality Improvement

Database, Musallamet al. [31] evaluated the role anemia

and blood transfusions on the morbidity and mortality of

227,425 patients undergoing non-cardiac surgery. In this

study, anemia was an independent predictor of postopera-

tive morbidity (OR 1.35; 95% CI 1.30–1.40) and mortality

(OR 1.42, 95% CI 1.31–1.54). However, perioperative

blood transfusion was associated with a significant increase

in morbidity (OR 1.83; 95% CI 1.74–1.92) and death (OR

2.03; 95% CI 1.86–2.21). The findings from this very large

study are strikingly similar to the results of our meta-

analysis in patients with SAH. It however needs to be

acknowledged that the majority of data on the risks and

benefits of blood transfusion in hospitalized patients has

been derived from cohort studies rather than randomized

controlled trials (RCT’s) [18, 31]. However, in general

there is a good correlation between the treatment effect

of cohort and subsequently performed RCT’s [32, 33].

Furthermore, the risks of blood transfusion are remarkably

consistent across multiple studies [18], as well as the two

randomized controlled studies that have been performed

[34, 35]. In summary, until randomized controlled trials

assessing the risks and benefits of blood transfusion in

patients with SAH are performed, a restrictive blood

transfusion strategy would appear to be prudent.

Conflict of interest None.

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