British Journal of Anaesthesia, 120 (5): 988e998 (2018)

doi: 10.1016/j.bja.2017.11.108
Advance Access Publication Date: 2 February 2018
Review Article

NEUROSCIENCE AND NEUROANAESTHESIA

Anaemia and red blood cell transfusion in

intracranial neurosurgery: a comprehensive review
A. Kisilevsky1, A. W. Gelb2, M. Bustillo3 and A. M. Flexman1,*
1
Department of Anesthesiology, Pharmacology and Therapeutics, University of British Columbia,
Vancouver General Hospital, Vancouver, BC, Canada, 2Department of Anesthesia and Perioperative Care,
University of California, San Francisco, CA, USA and 3Department of Anesthesiology, Weill Cornell Medical
College, New York Presbyterian Hospital, New York, NY, USA

*Corresponding author. E-mail: alana.flexman@vch.ca

Abstract
Both anaemia and blood transfusion are associated with poor outcomes in the neurosurgical population. Based on the
available literature, the optimal haemoglobin concentration for neurologically injured patients appears to be in the range
of 9.0e10.0 g dl
1, although the individual risks and benefits should be weighed. Several perioperative blood conservation
strategies have been used successfully in neurosurgery, including correction of anaemia and coagulopathy, use of
antifibrinolytics, and intraoperative cell salvage. Avoidance of non-steroidal anti-inflammatory drugs and starch-
containing solutions is recommended given the potential for platelet dysfunction.

Keywords: anaemia; coagulation; neurosurgery; transfusion

The development of modern neurosurgery was facilitated by
the evolution of general anaesthesia, intravenous fluid man-
agement, aseptic technique, and advances in neurosurgical
haemostasis in the 19th and 20th centuries.1 In 1904, pioneering
American neurosurgeon Harvey Cushing described the use of
a pneumatic tourniquet to reduce intraoperative bleeding
from the scalp.2 He went on to describe the utility of high
frequency electrocautery in the excision of previously inac-
cessible intracranial tumours3 and the use of operative cell
salvage and return of autologous blood.4 In 1946, Gardner
provided an account of induced hypotension to reduce blood
loss and improve neurosurgical operating conditions.5 Cush-
ing’s landmark publication in 1911 provided a summary of
neurosurgical haemostasis techniques and highlighted his
appreciation for the importance of a bloodless field to achieve
surgical precision, avoid haemorrhagic shock, and prevent
complications of anaemia.6 Taken for granted today, these
tenets were radical in the early 20th century and not univer-
sally accepted. In particular, Cushing’s recognition of the as-
sociation between anaemia and poor neurosurgical outcome
was ahead of its time. Although an accumulating body of ev-
idence now supports his observation, many questions
regarding haemostasis and anaemia in the neurosurgical
population remain. This paper aims to review the epidemi-
ology and clinical outcomes associated with anaemia and
blood transfusion, and identify perioperative blood conserva-
tion strategies to minimise blood loss in patients undergoing
intracranial neurosurgical procedures.

Editorial decision: November 30, 2017; Accepted: November 30, 2017

© 2017 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.
For Permissions, please email: permissions@elsevier.com

988

What is the significance of anaemia in the
neurosurgical population?
Although it constitutes only 2% of total body weight, the hu-
man brain has high metabolic requirements and receives
20e25% of cardiac output (CO). Total cerebral oxygen delivery
is a function of cerebral blood flow (CBF) multiplied by the
oxygen content of the blood (CaO2). CBF is ordinarily autor-
egulated over a wide range of cerebral perfusion pressures
(CPP) at approximately 50 ml 100 g
1 min
1 where CPP is
determined by the mean arterial pressure (MAP) minus the
cerebral venous pressure (or intracranial pressure, whichever
is higher). Outside the normal physiological limits of CPP
(~60e160 mm Hg), CBF is linearly dependent upon MAP. During
periods of acute anaemia (reduced CaO2), oxygen delivery is
maintained via compensatory cardiovascular and cerebro-
vascular changes including an increase in CO, preferential
distribution of CO to the cerebral circulation, increased cere-
bral oxygen extraction, and, importantly, an increase in CBF
secondary to active cerebral vasodilatation.7 In the setting of
normovolaemic anaemia, reduced blood viscosity is a major
determinant of increased CO through enhanced preload and
reduced afterload.8 Reduced viscosity may also improve the
flow characteristics (i.e. rheology) of blood particularly
through areas of cerebral vascular stenoses. However, these
compensatory mechanisms have limitations. As cerebral ox-
ygen utilisation becomes supply dependent, anaemia may
contribute to reduced cerebral oxygen delivery and a second-
ary hypoxic insult to the injured brain. In healthy volunteers,
anaemia-induced cognitive dysfunction is evident at haemo-
globin (Hb) concentrations between 5.0 and 6.0 g dl
1.9
Following acute brain injury, impaired autoregulatory mech-
anisms may allow anaemia-induced cerebral dysfunction and
injury at higher Hb thresholds. In a recent retrospective cohort
study of patients with severe traumatic brain injury (TBI), the
amount of time spent with an Hb concentration 9.0 g dl
1
was associated with improved neurological outcome at 6
months.10 Similarly, in a previous cohort of patients with se-
vere TBI, the association of anaemia (Hb<9.0 g dl
1) with low
brain tissue oxygen tension (<20 mm Hg) was a risk factor for
poor neurological outcome.11 In patients with subarachnoid
haemorrhage (SAH), a reduction in red cell volume precedes
neurological deterioration.12 An Hb threshold >11 g dl
1 is
associated with a reduced incidence of symptomatic cerebral
vasospasm13 and more favourable neurological outcome.14 At
higher Hb concentrations, however, the benefit of increased
oxygen carrying capacity may be offset by increases in blood
viscosity and reduced CBF.15
The incidence of anaemia in neurosurgical procedures
varies depending on the population and surgery. Data from the
National Surgical Quality Improvement Program reveal that
the incidence of moderate to severe anaemia (i.e. haematocrit
<30%) in elective cranial surgery is 2.7%.16,17 In critically-ill
neurosurgical patient populations, however, the incidence
increases; at least 50% of patients with TBI18 and 47% of pa-
tients after SAH are anaemic.19 In the critically-ill population,
anaemia may be multifactorial resulting from systemic
inflammatory-mediated suppression of haematopoiesis,
frequent phlebotomy, haemorrhage, and haemodynamic
resuscitation-induced haemodilution. In the context of SAH,
anaemia may result from deliberate hypervolaemia and hae-
modilution for the prevention and treatment of vasospasm. A
growing body of evidence in neurosurgical patients supports
anaemia as an independent predictor of cerebral vasospasm,
Transfusion in intracranial neurosurgery - 989
medical complications, poor neurological outcome, and
increased mortality.14,17,20,21
What is the significance of transfusion in the
neurosurgical population?
In the setting of anaemia, transfusion of blood products can
rapidly increase Hb concentrations and oxygen delivery.
Overall, cohort studies including all types of neurosurgical
procedures have reported a rate of allogeneic transfusion of
1.7e5.4%.22,23 However, the reported incidence of transfusion
for specific patient populations undergoing intracranial
neurosurgery ranges from 10 to 95% with a much higher
incidence among paediatric patients undergoing craniosy-
nostosis surgery and cranial vault reconstruction (Table 1). In
the paediatric population undergoing brain tumour resection,
age <4 years, duration of surgery >270 min, and a preoperative
Hb concentration <12.2 g dl
1 were independent predictors of
allogeneic blood transfusion.24 In the context of isolated TBI,
the presence of acute traumatic coagulopathy increased the
risk of transfusion by 41% and increased hospital length of
stay and mortality.25 In aneurysmal SAH, administration of
packed red blood cells is strongly related to intraoperative
aneurysm rupture26 and may be as high as 25%.27 The rate of
transfusion also varies depending on the procedure, from 10%
in complex skull base neurosurgical procedures28 to 36% in
patients with TBI29 and as high as 45% in paediatric cranio-
synostosis surgery.30 In the latter instance, risk factors for
large volume blood loss and transfusion include syndromic
craniosynostosis, pansynostosis, age <18 months, and longer
duration of procedure.31 A recent multicentre observational
study of children undergoing complex cranial vault recon-
struction in North America demonstrated that 95% of infants
aged <24 months and 79% of children aged >24 months un-
derwent perioperative allogeneic blood transfusion.32 Future
strategies to reduce transfusion should focus on the identifi-
cation and mitigation of modifiable risk factors in these
populations.
Paradoxically, while the definitive management of
anaemia-induced organ dysfunction remains the transfusion
of allogeneic red blood cells, transfusion itself confers an
increased risk of morbidity and mortality.33e36 Changes in
immunomodulation, infectious and allergic complications,
and transfusion associated lung injury and circulatory over-
load are all potential pathological consequences of trans-
fusion. These complications result in an increased risk of
respiratory failure, prolonged intubation, acute respiratory
distress syndrome, wound infection, sepsis, cardiac events,
increased hospital length of stay and death. In the setting of
TBI, a clinical trial comparing Hb transfusion thresholds of 7.0
g dl
1 vs 10.0 g dl
1 revealed an increased risk of thrombo-
embolic events in the latter with no significant improvement
in neurological outcome.37 Further analysis of this data
demonstrated a more than two-fold increase in the risk of
progressive haemorrhagic injury with a Hb transfusion
threshold >10.0 g dl
1 when compared with a more restrictive
threshold (i.e. 7.0 g dl
1).38 In patients undergoing open
neurosurgical intervention for intracranial aneurysm, periop-
erative blood transfusion was shown to be an independent risk
factor for major morbid complications.39
Unfortunately, the optimal trigger for Hb transfusion in
neurosurgical populations remains elusive and the relative
risks and benefits of anaemia and transfusion must be
 990 - Kisilevsky et al.

Table 1 Risk factors for allogeneic red blood cell transfusion in intracranial neurosurgical patient populations. Hb, haemoglobin;
WFNS, World Federation of Neurological Surgeons

Population Transfusion Risk (%) Risk Factors for Transfusion References

Traumatic brain injury 36 Acute traumatic coagulopathy Epstein et al25

Boutin et al29
Aneurysmal subarachnoid haemorrhage 25 Intraoperative aneurysmal rupture Luostarinen et al26
lower preoperative Hb Le Roux et al27
higher WFNS classification
Complex skull-based 10 Lower preoperative Hb Mebel et al28
larger tumour diameter
surgical procedure
year of surgery
Paediatric brain tumour 25 Age <4 years Vassal et al24
surgical duration >270 min
preoperative Hb <12.2 g dl
1
Paediatric cranio-synostosis 45 Syndromic craniosynostosis Dadure et al30
pansynostosis White et al31
age <18 months
surgical duration > 5 h
Paediatric major cranial vault reconstruction
Age 24 months 95
Age >24 months 79 Surgical techniquea Stricker et al32

a
This study was not designed to identify risk factors for transfusion; based on their data the authors suggest that surgical technique may be the
greatest potential variant in the need for blood transfusion in this population.

weighed (Fig. 1). Current recommendations vary amongst setting of both normal and elevated ICP as compared with
clinician specialty, procedure, and severity of the underlying trauma surgeons and intensivists. Although strict Hb trans-
brain injury.40 When surveyed, neurosurgeons recommended fusion triggers for neurologically injured patients remain un-
a higher Hb threshold for transfusion following TBI in the clear, the mitigation of cerebral ischaemia is likely to require a

Fig 1. Theoretical risks and benefits of perioperative anaemia and transfusion in neurosurgical patients.

higher threshold than in the general critically-ill patient pop-
ulation where a restrictive transfusion strategy is often advo-
cated.41 Based on the available evidence, the minimum
acceptable Hb concentration for neurologically injured pa-
tients would appear to be in the range of 9.0e10.0 g dl
1, rec-
ognising that higher thresholds may be associated with
adverse outcomes such as thrombosis or haemorrhagic pro-
gression. Although both anaemia and allogeneic blood trans-
fusion are associated with worse clinical outcomes in
neurologically injured patients, these variables are either
reflective of increased severity of injury or a result of trans-
fusion in and of itself and active blood conservation should be
considered whenever possible.
What strategies are effective to minimise
anaemia and transfusion in neurosurgical
patients?
Perioperative blood conservation strategies in intracranial
neurosurgery are summarised in Figure 2 with the evidence
supporting each strategy summarised in Table 2. Appropriate
blood conservation should include the identification and
correction of underlying coagulopathy including withholding
of anticoagulation as appropriate. As discussed above, the
presence of acute traumatic coagulopathy in TBI is associated
with poorer outcomes and should be identified and definitively
managed in this patient population.25 The importance of
correction of coagulopathy is illustrated by the population of
patients with atrial fibrillation taking oral anticoagulation who
present with intracranial haemorrhage (ICH). A recent retro-
spective cohort study evaluating haematoma enlargement in
relation to international normalised ratio (INR) and blood
pressure in the setting of ICH concluded that reversal of INR to
<1.3 within 4 h of admission and systolic blood pressure to
<160 mm Hg at 4 h lowered the rate of haematoma enlarge-
ment.42 These data also suggested that INR reversal was
Fig 2. Potential strategies for perioperative blood conservation in neurosurgical patients. ANH, acute normovolaemic haemodilution;
NSAID, non-steroidal anti-inflammatory drugs.
Transfusion in intracranial neurosurgery - 991
greater with prothrombin complexes as compared with fresh
frozen plasma, although the authors note that the sample size
was too small to draw firm conclusions. Novel oral anticoag-
ulants (e.g. dabigatran, rivaroxaban) are rapidly replacing
warfarin in the setting of stroke prevention in atrial fibrillation
but, with the exception of dabigatran, these agents currently
have no specific reversal agents and are challenging to manage
in the urgent perioperative setting.43 The Neurocritical Care
Society in conjunction with the Society of Critical Care Medi-
cine has developed evidence-based guidelines for the reversal
of antithrombotic agents, including the newer oral anticoag-
ulants in the setting of ICH (Fig. 3).44
Avoidance of pharmacological disruption of coagulation
intraoperatively is also prudent. Non-steroidal anti-inflam-
matory drugs (NSAIDs), such as flurbiprofen, have potent an-
tiplatelet effects and are associated with an increased risk of
intracranial haematoma following intracranial procedures.45
NSAIDs should be avoided during intracranial procedures.
Similarly, synthetic starch solutions inhibit platelet function46
and recent evidence demonstrated that their use results in
alteration in rotational thromboelastography parameters in
elective brain tumour resection.47 Nevertheless, a retrospec-
tive cohort study failed to demonstrate an association be-
tween post-craniotomy haematoma and the use of
hydroxyethyl starch solutions,45 and further research is
needed to clarify their safety in this population. In contrast,
certain neurosurgical populations may benefit from anti-
coagulation, such as those patients with symptomatic carotid
stenosis. A prospective audit in patients with symptomatic
internal carotid stenoses (50e99%) found a reduction in
recurrent neurological events without increasing the risk of
major perioperative bleeding in those who received dual an-
tiplatelet therapy with acetylsalicylic acid (ASA) and clopi-
dogrel before carotid endarterectomy.48 Low-dose ASA (<325
mg) is associated with better short-term outcomes than high-
dose ASA (>650 mg) in these patients.49 The maintenance or
Table 2 Summary of evidence supporting perioperative blood conservation techniques in intracranial neurosurgery.

992
Intervention Level of Reference Methodology Population Outcomes Results Number of

-
Evidencea Participants

Kisilevsky et al.
Reversal of 3 Epstein et al.25 Systematic review and þ/e ATC in isolated TBI Allogeneic blood ATC increased the risk of transfusion 7037
coagulopathy meta-analysis of transfusion; (41%) and mortality [OR 3.0 (CI 95: 2.3
cohort studies Mortality e3.8) to 9.6 (CI 95: 4.1e25)].
3 Kuramatsu et al.42 Retrospective, ICH in patients with atrial Haematoma 50% reduction in risk with INR<1.3 (vs 853
multicentre cohort fibrillation on oral enlargement INR1.3) at 4 h.
anticoagulation
Antifibrinolytic 2 Goobie et al.63 Randomised, blinded, þ/e TXA in paediatric Blood loss; TXA reduced mean blood loss (65 vs 119 43
therapy single-centre craniosynostosis Allogeneic ml kg
1) and total blood transfused (33
blood vs 56 ml kg
1).
transfusion
2 Dadure et al.30 Randomised, blinded, þ/e TXA and pre- Allogeneic TXA reduced the percentage of children 40
single-centre treatment with EPO in blood requiring blood transfusion (45% vs
paediatric transfusion 11%).
craniosynostosis
3 Mebel et al.28 Retrospective cohort þ/e TXA in complex skull- Allogeneic TXA reduced the risk of transfusion (7% 519
base surgery blood vs 13%).
transfusion
1 Baharoglu et al.64 Systematic review and þ/e TXA in aneurysmal Re-bleeding Reduced risk of re-bleeding with TXA 1904
meta-analysis of subarachnoid Cerebral RR 0.65 (CI 95: 0.44e0.97).
RCTs haemorrhage ischaemia Increased risk of cerebral ischaemia
with TXA RR 1.4 (CI 95: 1.04e1.91).
Administration of 2 Robertson et al.37 Randomised, blinded, þ/e EPO in traumatic brain Neurological No improvement in outcome with EPO. 200
erythropoiesis multicentre injury outcome at 6
stimulating months
agentsb 2 Nichol et al.52 Randomised, blinded, þ/e EPO in traumatic brain Neurological No improvement in outcome with EPO 606
multicentre injury outcome at 6 RR 0.99 (CI 95: 0.83e1.18).
months
Avoidance of 4 Jian et al.45 Retrospective, single- þ/e NSAIDS in elective Postoperative Increased risk with intraoperative 42359
coagulopathy centre craniotomy haematoma flurbiprufen
caseecontrol formation OR 2.14 (CI 95: 1.23e3.15).
3 Li et al.47 Prospective, non- þ/e HES in elective ROTEM Increased risk of abnormal ROTEM with 39
blinded, craniotomy for tumour 130/0.42 HES infusion.
observational cohort resection
Acute 2 Naqash et al.57 Prospective, þ/e ANH in intracranial Allogeneic blood Reduced risk of exposure with ANH (25% 40
normovolaemic randomised, single- meningioma resection transfusion vs 100%).
haemodilution centre
(ANH) 3 Oppitz and Prospective, non- þ/e ANH in ruptured Allogeneic blood No difference in intraoperative exposure 147
Stefani58 randomised, single- cerebral aneurysm transfusion with ANH.
centre clipping
Continuous SpHb 3 Awada et al.70 Prospective, non- Elective intracranial Allogeneic blood No difference in percentage of patients 106
monitoring blinded, single- surgery transfusion transfused between groups.
centre cohort In those undergoing transfusion,
continuous SpHb resulted in fewer
pRBCs transfused (2.3 vs 3.9 units) and
a shorter wait time to transfusion [9.2
(SD 1.7) vs 50.2 (7.9) min).

Continued
 Transfusion in intracranial neurosurgery - 993

withholding of anticoagulation should be made on an indi-

ATC, acute traumatic coagulopathy; TBI, traumatic brain injury; ICH, intracranial haemorrhage; NSAIDs, non-steroidal anti-inflammatory drugs; pRBCs; packed red blood cells; HES, hydroxyethyl starch;

Based on the Oxford Centre for Evidence-based Medicine 2011 Levels of Evidence for evaluation of potential treatment benefits, OCEBM Levels of Evidence Working Group. “The Oxford Levels of Evidence 2”.
Participants vidual basis following careful consideration of the riskebenefit
Number of

profile.
During the preoperative evaluation, anaemia should be
identified, and reversible causes treated whenever possible.

472
57

Iron deficiency is relatively easy to identify in those with a low

serum ferritin (<100 mg litre
1) or transferrin saturation
(<20%).50 Treatment should include a standardised approach
Greater number of RBCs transfused

probable reduction in exposure to

autologous blood interpreted as a
No difference in exposure between

using oral iron therapy. In more urgent circumstances (i.e.

25% of patients received 500 ml

surgery scheduled within 4 weeks), I.V. iron should be

considered. If absolute iron deficiency is ruled out, screening
for chronic kidney disease and nutritional deficiencies should
be carried out. The use of erythropoiesis-stimulating agents
(ESAs), such as erythropoietin (EPO), is recommended for
allogeneic blood.

anaemic patients in whom nutritional deficiencies have been

corrected or excluded. ESAs are of particular interest in neu-
with PAD.

rocritical care because of potential cerebral protection during

groups.

periods of ischaemia (e.g. ischaemic stroke, vasospasm) via

Results

effects on the innate stress response51 although recent rand-

omised trials in TBI have failed to demonstrate a neurological
benefit.37,52 Prior to initiation of an ESA, the increased risk of
allogeneic blood
Allogeneic blood

deep vein thrombosis (DVT) and pulmonary embolism (PE),

Conservation of

particularly in high risk individuals such as those with un-

transfusion

derlying malignancy,53 must be weighed against the potential

Outcomes

The administration of EPO was for evaluation of potential direct neuroprotective effects and NOT for correction of anaemia.

neurological benefit of the treatment of anaemia. The two

randomised trials comparing EPO with placebo in TBI have
provided conflicting evidence; Robertson and colleagues37
ROTEM, rotational thromboelastometry; RCTs, randomised controlled trials; EPO, erythropoietin; TXA, tranexamic acid.

revealed an increased risk of DVT and cardiovascular com-

neurosurgery (including

plications in the EPO group whereas Nichol and colleagues52

did not find any difference in thrombotic complications.37,52
Elective intracranial

In elective surgery, preoperative autologous donation (PAD)

EPO þ/e PAD in

may reduce the need for allogeneic blood transfusion in

certain patient populations including those undergoing car-
Population

diac surgery with cardiopulmonary bypass.54 In intracranial

surgery
spine)

neurosurgery, however, the evidence for PAD is limited. A

retrospective matched cohort study of neurosurgical patients
receiving EPO in the presence and absence of PAD found
Oxford Centre for Evidence-Based Medicine. http://www.cebm.net/index.aspx?o¼5653.

increased perioperative anaemia and no difference in expo-

sure to allogeneic blood transfusion in the presence of PAD.55
Retrospective case

Prospective, non-
blinded, single-

Overall, PAD cannot currently be recommended as a blood

conservation technique for neurosurgical patients. Acute
Methodology

normovolaemic haemodilution (ANH), another blood conser-

econtrol

vation technique involving autologous blood withdrawal

centre

currently advocated by the ASA practice guidelines on peri-

operative blood management,56 also has limited evidence in
neurosurgery. A small prospective, randomised controlled
study on patients undergoing elective intracranial meningi-
Cataldi et al.67
McGirr et al.55

oma resection found a significant reduction in the amount of

allogeneic blood transfused to patients following ANH as
Reference

compared with control.57 A more recent prospective, non-

randomised trial on the use of ANH during intracranial
neurosurgery for ruptured cerebral aneurysm, however, found
no significant difference between ANH and control in the
Evidencea
Level of

number of patients requiring allogeneic blood transfusion.58

ANH may be considered as a possible blood conservation
technique in elective neurosurgical cases of otherwise healthy
4

individuals where large volume blood loss is anticipated.

Table 2 Continued

donation (PAD)

Baseline Hb concentrations which permit haemodilution to a

Intervention

target haematocrit that will maintain adequate tissue

autologous
Preoperative

Cell salvage

oxygenation are required; assuming normovolaemia and

adequate cardiac performance, the ‘safe’ lower limit is a
haematocrit of approximately 20e25% and a preoperative Hb
of >12 g dl
1 has been proposed.59 Synthetic starch solutions
a

are often cited as the preferred nonered cell containing

 994 - Kisilevsky et al.

Fig 3. Recommendations for antithrombotic reversal in the setting of intracranial haemorrhage (adapted from Frontera et al 201544). aPCC,
activated prothrombin complex concentrate; DDAVP, desmopressin; FFP, fresh frozen plasma; INR, international normalised ratio; i.v.,
intravenous; LMWH, low molecular weight heparin; max, maximum; NSAIDs, non-steroidal anti-inflammatory drugs; PCC, prothrombin
complex concentrate; rVIIa, recombinant factor VIIa; TXA, tranexamic acid.

replacement fluid secondary to increased intravascular half-
life but, given the antiplatelet effect of starches, crystalloids
may be more favourable in the setting of neurosurgery. Con-
traindications to ANH include coronary artery disease, hypo-
volaemic or hypervolaemic states (i.e. liver cirrhosis),
increased oxygen requirements (i.e. sepsis, fever), underlying
coagulopathy, and any major cardiac, respiratory, or renal
disease.
The use of antifibrinolytic agents such as tranexamic acid
(TXA) reduces allogeneic blood transfusion requirements in
multiple surgical patient populations such as joint arthro-
plasty, cardiac, spine, and trauma.60 Data from the CRASH-2
Intracranial Bleeding Study, a nested randomised controlled
trial in trauma patients with reduced Glasgow Coma Scale and
ICH, suggested a reduction in ICH size and lower mortality in
patients randomised to TXA compared with control, although
these results did not achieve statistical significance.61 The
CRASH-3 trail was thus designed to investigate the effect of
TXA on mortality and disability in isolated TBI with results
expected in the near future.62 Data on antifibrinolytics in
neurosurgical populations other than TBI are limited. In pae-
diatric patients undergoing craniosynostosis surgery, TXA
significantly reduced blood loss and blood transfusion re-
quirements when compared with control.63 Similarly, in chil-
dren undergoing craniosynostosis surgery and pretreated with
EPO, intraoperative TXA (compared with placebo) resulted in a
reduction in transfusion.30 In a retrospective cohort study of
patients undergoing complex skull base neurosurgery, those
who received TXA were less likely to require a blood trans-
fusion than those who did not.28 In the setting of SAH, anti-
fibrinolytics might be expected to reduce the risk of
aneurysmal re-bleeding and subsequent poor neurological
outcome. A recent Cochrane review of randomised controlled
trials examining antifibrinolytic therapy in SAH did demon-
strate a reduction in re-bleeding but found an increase in ce-
rebral ischaemia.64 This review has been criticised for
including older studies in which TXA administration was
prolonged (i.e. >10 days) and further research is anticipated.
Although TXA is well-tolerated, several adverse effects
must be considered such as thromboembolic complications
and seizures. The use of high dose TXA in cardiac surgery is
associated with an increased incidence of seizures, particu-
larly in those with an underlying predisposition (e.g. structural
brain abnormality) as might occur in the neurosurgical popu-
lation.65,66 In skull base tumour resection, however, rates of
seizures and thrombosis in patients receiving TXA were
similar to those who did not receive TXA, although the overall
rates were low.28 Overall, although antifibrinolytics may be of
benefit in certain neurosurgical populations such as TBI, cra-
niosynostosis and skull base surgery, current evidence does
not support the routine use of antifibrinolytic therapy in
aneurysmal SAH.
Intraoperative cell salvage is commonly used in surgical
procedures such as cardiac, major vascular, and spine; how-
ever, the literature on the use of cell salvage for intracranial
surgery is extremely sparse. An older prospective cohort study
on patients undergoing elective intracranial surgery and cell
salvage found mild coagulation abnormalities without signif-
icant clinical bleeding and concluded that cell salvage was safe
and cost-effective.67 Notably, this study excluded patients
with malignant tumours and sepsis and no long-term follow-
up data were reported. Possible barriers to the use of cell
salvage in neurosurgery include concern over tumour
dissemination in the setting of malignancy, perceived lack of
Transfusion in intracranial neurosurgery - 995
need, and the unpredictable nature of major haemorrhage in
this patient population.68 However, a recent systematic review
on cell salvage in spine surgery secondary to metastatic dis-
ease concluded that concern over tumour dissemination is
unfounded and a leucocyte-reducing filter is recommended.69
In the absence of sufficient data, it seems reasonable to
conclude that cell salvage should be available in intracranial
surgery cases when large volume blood loss is anticipated
such as cerebral aneurysm rupture or vascular meningioma
resection.
The relatively recent availability of non-invasive, contin-
uous Hb (SpHb) monitoring provides another potential peri-
operative blood conservation tool. A prospective cohort study
comparing intraoperative SpHb monitoring with traditional
intermittent blood sampling to achieve an Hb concentration
10.0 g dl
1 in elective neurosurgical patients found that SpHb
monitoring influenced blood utilisation.70 Although the per-
centage of patients transfused in the control and SpHb groups
was similar, in those patients receiving a transfusion the use
of SpHb monitoring resulted in fewer total units of blood
transfused and a shorter time to transfusion (if required). The
authors speculated that use of real-time SpHb monitoring
allowed for earlier identification of attainment of the Hb
threshold and thus avoidance of multiunit transfusions. More
research is required to validate continuous Hb monitoring
protocols given the concerns about the reliability of these
monitors.71
Conclusion
It is clear that anaemia is common in critically ill, brain-
injured patients and that both anaemia and blood trans-
fusion are associated with complications and poor outcomes
in this population. The incidence and risk factors for trans-
fusion are influenced by patient factors including the under-
lying neurological pathology yet optimal Hb concentrations in
these patients are not presently well defined. A higher Hb
threshold (i.e. >9.0 g dl
1) than that reserved for the general
critically-ill patient is likely necessary to avoid the risk of
secondary cerebral injury, however high thresholds (i.e. >10.0
g dl
1) may be associated with thrombosis or haemorrhagic
progression. Blood conservation strategies in individual pa-
tients should take into account the underlying pathology and
comorbid disease. Perioperatively, consideration should be
given to the correction of underlying coagulopathy and
anaemia, primarily through the use of iron replacement and
EPO. Preoperative autologous donation is not recommended
based on current evidence. Intraoperatively, acute normovo-
laemic haemodilution, continuous Hb monitoring, cell salvage
and antifibrinolytic therapy should be considered, and NSAIDs
and starch-containing resuscitation solutions should be avoi-
ded given the potential for platelet dysfunction.
Author contributions
Literature search and first draft of the manuscript: A.K. and
A.F.
Final version of the manuscript, figures and tables: All authors.
Declaration of interests
A.G. and A.F. have received honoraria for lectures from
Masimo, Inc and Hospira, Inc, respectively. A.G. has provided
paid consultation for Masimo, Inc.
 996 - Kisilevsky et al.
Funding
No funding.
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