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Hemoglobin threshold and clinical predictors for perioperative blood

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Review

Hemoglobin threshold and clinical predictors for perioperative blood

transfusion in elective surgery: Systemic review
Wubie Birlie Chekol*, Muleta Teshome, Yonas Addisu Nigatu, Debas Yaregal Melesse
Department of Anesthesia, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia

a r t i c l e i n f o a b s t r a c t

Article history: Background: Lack of consensus on hemoglobin threshold and transfusion strategies have led to a wide
Received 27 October 2019 variation in transfusion practices and inappropriate use of blood. This may result in over ordering of
Received in revised form blood with minimal utilization or unnecessary allogenic blood transfusion. This may lead to financial
16 December 2019
crisis due to costs for blood handling, laboratory tests and blood administration. So, saving of blood and
Accepted 18 December 2019
resources are required by rationalizing blood transfusion indications based on evidence-based hemo-
globin threshold and clinical predictive factors in resource limiting setup.
Keywords:
Methods: Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocol was used to
Hemoglobin
Threshold
conduct this study. PubMed, Google Scholar and Cochrane Library search engines were used to find
Blood transfusion evidences that help to draw recommendations and conclusions.
Anemia Discussion: Half of clinical specialties used red blood cell transfusion with 7 g/dl threshold and the other
Perioperative blood loss half used 8 g/dl to 9 g/dl. Restrictive strategy of blood transfusion is as effective as liberal transfusion
Anesthesia strategy in critically ill patients except in patients with cardiovascular diseases.
Conclusions: Transfusion is required at hemoglobin levels <7 g/dl. Recent guidelines and literatures have
consistently expressed the transfusion threshold between 7 and 10 g/dl with clinical indicators further
defining the need for allogenic transfusion in between.
© 2019 Elsevier Ltd. All rights reserved.

Contents

1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
2. Methodology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
3. Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
3.1. Haemoglobin transfusion thresholds and target . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
3.2. Liberal versus restrictive transfusion strategy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
3.3. Risks of allogenic blood transfusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
3.4. Predictors of allogenic blood transfusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
3.5. Area of controversies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
3.6. Summary of evidences . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
4. Conclusions and recommondations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
Declarations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
Ethical approval . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
Funding . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
Conflict of interest . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
Declaration of competing interest . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
Acronyms and Abbreviations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00

* Corresponding author.
E-mail addresses: birliewubie@[Link] (W. Birlie Chekol),
Teshomemuleta94@[Link] (M. Teshome), yonasaddisu71@[Link]
(Y.A. Nigatu), dabyyaregal82@[Link] (D.Y. Melesse).

[Link]
2210-8440/© 2019 Elsevier Ltd. All rights reserved.

Please cite this article as: W. Birlie Chekol et al., Hemoglobin threshold and clinical predictors for perioperative blood transfusion in elective
surgery: Systemic review, Trends in Anaesthesia and Critical Care, [Link]
2 W. Birlie Chekol et al. / Trends in Anaesthesia and Critical Care xxx (xxxx) xxx

Supplementary data . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00

1. Introduction inappropriate use of blood. Therefore great saving of blood and

resources are required by rationalizing blood transfusion indication
Blood transfusion is a crucial component of patient care in based on evidence based hemoglobin threshold and clinical pre-
surgical disciplines such as life-saving management [1]. This is dictive factors in resource limiting setup [1].
usually done as a life-saving maneuver to replace blood cells or Health care professionals commonly use hemoglobin concen-
blood products lost through severe bleeding, during surgery when tration to decide when to transfuse. But there is variation in indi-
blood loss occurs or to increase the blood count in an anemic pa- cation and initiation of transfusion between institution and among
tients [2]. individual within the similar surgical procedure and clinical con-
During the perioperative period, some patients may require ditions due to many factors including different personal opinion of
transfusion of blood products. The most common cause and indi- worst case assumption, hemoglobin value, estimation of blood loss,
cation for administration of blood components is acute surgical surgical techniques and lack of transfusion protocol [14].
blood loss and when the concentration of hemoglobin is low or the Most guidelines stress that blood transfusion should not be only
oxygen carrying capacity is reduced [3]. hemoglobin value alone, it should be considered the clinical sign/
Blood transfusion is triggered for acute anemia secondary to; symptoms of anemia and the predictors of transfusion. So, the aim
surgical hemorrhage (Hb
8 g/dl), traumatic hemorrhage (hem- of this review is to support clinical decisions about perioperative
orrhagic shock, inadequate oxygen delivery), non-trauma and non- blood transfusion by discussing the current evidences and in-
surgical hemorrhage(<7 g/dl), critical illness(<7 g/dl), early sepsis dications for blood. Finally, this review will have some contribu-
with inadequate oxygen tissue delivery(<9 g/dl), septic shock and tions in clinical decisions on perioperative hemoglobin threshold in
late sepsis(Hg < 7 g/dl) and acute coronary syndrome with ische- patients scheduled for elective surgery at University of Gondar
mia(Hb 8e9 g/dl) [4]. Comprehensive Specialized Hospital.
Current evidence shows that restrictive transfusion of blood is
safe in stable post-operative and normovolemic critically ill pa- 2. Methodology
tients with the trigger for transfusion being Hb of 7e8 g/dl or
symptoms of anemia. Several factors contribute to anemia in crit- The Preferred Reporting Items for Systematic Reviews and
ically ill patients. The most important factors are chronic disease, Meta-Analysis (PRISMA) protocol was used to conduct this study
blood loss, increased red blood cell destruction, hemodilution and (Fig. 1). For the development of this systemic review selection of
reduced red cell production with variable etiology. Determination appropriate search methods were conducted with PubMed, Google
of the cause of the anemia can impact perioperative surgical and Scholar and the Cochrane database library. Systemic reviews, meta-
medical management and outcome [4e6]. analysis, guidelines, randomized controlled trials, systemic reviews
Blood transfusion related immunomodulation results in of cohort studies and cohort studies were included in the review
immunosuppresion, transfusion reaction, postsurgical cancer with the following terms “Blood Transfusion”, “Hemoglobin”, “Red
recurrence and an increased in predisposition to infectious diseases Blood Cell”, “Transfusion”, “Trigger”, “Threshold”, “Strategy”, Lib-
[7]. Carson et al. studied 110 patients with acute coronary syn- eral” AND “Restrictive” combined each other with Boolean opera-
drome with a mean age of 71 years and found fewer major cardiac tors (AND,OR). Appraisal and evaluation of the study quality with
events and deaths if red blood cell transfusion increased hemo- different institutional appraisal checklists were done to categorize
globin >10 g/dl compared to a restrictive strategy(10.9% VS 25.5%) evidences in to levels. Final conclusions and recommendations
[8]. Non-infectious serious hazards of transfusion have emerged as were done by balancing the benefits and downsides of the alter-
the most common complications of transfusion that includes mis- native strategies for hemoglobin threshold for perioperative blood
transfusion, transfusion related acute lung injury, transfusion transfusion in elective surgical patients. The level of evidences and
associated circulatory overload, post transfusion purpura and recommendations were given based on good clinical practices of
metabolic derangements [7e10]. world health organization 2011(Table 1).
The preoperative request of blood units, especially in elective Studies done in emergency management of acute blood loss and
surgery, is often based on the worst-case assumptions, demanding researches on perioperative blood transfusion in pediatric surgeries
large quantities of blood or overestimating the anticipated blood were not selected to include in the current review.
loss, of which little is ultimately used. In South Africa, for example,
7e10% of blood is wasted annually because of over ordering of
3. Discussion
blood, India, Kuwait and Nigeria also showed utilization of blood
28%, 13.6% and 69.7% respectively [11]. Inappropriate use of blood
3.1. Haemoglobin transfusion thresholds and target
may lead to financial crisis related with costs for blood bank
handling, laboratory tests and blood administration [12].
Traditionally, the rule of 10/30 was followed for blood trans-
Common variations in rates of transfusion may be due to many
fusion to which Hb level of 10 g/dl or a hematocrit of 30% was
factors, including differences in opinions on the threshold level of
recommended in surgical patients. Over the years, the trigger for
hemoglobin below which patient needs blood transfusion, differ-
transfusion has become more conservative or restrictive based on
ences in surgical and anesthetic techniques, cancellation of cases,
both laboratory value and objective clinical conditions of the pa-
differences in case mix, preoperative anemia and lack of availability
tient’s age, co-morbidities, severity of illness and the rate and
of transfusion protocols [13].
amount of hemorrhage [15]1a.
Lack of consensus on hemoglobin threshold and transfusion
Preoperative anemia increases the likelihood of allogenic
strategies have led to wide variation in transfusion practices and
transfusion and should be investigated and where possible

Please cite this article as: W. Birlie Chekol et al., Hemoglobin threshold and clinical predictors for perioperative blood transfusion in elective
surgery: Systemic review, Trends in Anaesthesia and Critical Care, [Link]
 W. Birlie Chekol et al. / Trends in Anaesthesia and Critical Care xxx (xxxx) xxx 3

Fig. 1. PRISMA 2009 flow diagram.

Table 1
Level of evidences and recommendations.

Level Type of evidences Recommendations

1a Meta-analyses, systematic reviews of randomized controlled trials, evidence-based guidelines Strongly recommended/directly applicable
1b Randomized clinical trials/Randomized controlled trials Highly recommended/directly applicable
2a Systematic reviews of case control or cohort studies. Extrapolated evidence from other studies
3a Non-analytic studies, e.g. Case reports, case series Extrapolated evidence from other studies

corrected prior to major elective surgery. However, there is limited dl and also suggested that patients with cardiovascular problems
evidence available on appropriate preoperative hemoglobin con- should have this limit raised to 8 g/dl. A large retrospective study of
centrations. All patients undergoing major elective surgery should surgical patients confirmed that there was no difference in mor-
have proper history taking, physical examination and full blood tality using a lower threshold of either 8 or 10 g/dl. Transfuse one
count performed prior to surgery to avoid short term cancellation RBC unit at a time in hemodynamically stable, non-bleeding pa-
and to allow those patients presenting with anemia to be investi- tients, with assessment of symptoms and post-transfusion Hb level
gated and treated appropriately [3,6]1b. prior to giving the next unit. Laboratory assessment of Hb may be
In postoperative surgical patients, transfusion should be performed as early as 15 min following blood transfusion [19] 1b.
considered at hemoglobin concentration of 8 g/dl and with clinical Transfusion is required at hemoglobin levels <7 g/dl. More ev-
symptoms (chest pain, orthostatic hypotension or tachycardia un- idence exists on which to base an upper limit for the transfusion
responsive to fluid resuscitation). In hemodynamically stable pa- range. A large randomized controlled trial done on patients of
tients without pre-existing cardiovascular disease transfusion transfusion thresholds either on conservative (7e9 g/dl) or liberal
should be considered at a hemoglobin concentration of less than (10e11 g/dl) threshold and no difference in 30 or 60-day mortality
7 g/dl and with clinical symptoms [2,16] 1a. was found. In addition, there was no significance difference in se-
When there is ongoing surgical blood loss, hemoglobin mea- vere ventricular dysfunction, with the overall mortality in this
surements should be interpreted in the context of a multifaceted population [20] 1b.
clinical assessment, which should include clinical evaluation of
blood volume status. There is no indication that thresholds should 3.2. Liberal versus restrictive transfusion strategy
differ during this period but, the use of intraoperative transfusion
must reflect the ongoing rate of surgical blood loss, continued he- A meta-analysis of 3 studies done by Salpeter et al. showed that
modynamic instability and anticipated postoperative bleeding the restricting blood transfusions to patients whose hemoglobin is
[17,18] 1a. less than 7 g/dl leads to a significant reduction in total mortality,
Recent guidelines and consensus statements have consistently pulmonary edema, re-bleeding, and bacterial infection and
expressed the transfusion threshold as a range of hemoglobin compared with a more liberal transfusion strategy [21] 1a.
usually between 7 and 10 g/dl, with clinical indicators further A meta-analysis of 7 studies done by Franchini et al. identified
defining the need for allogenic transfusion in between. No evidence that the transfusion of blood in normal hemoglobin concentrations
was found to suggest that cardiovascular function is improved does not improve organ failure and mortality in the critically ill
blood transfusion at hemoglobin values > 10 g/dl [1,8] (1a, 1b). patients. The studies recommended that restrictive transfusion
A review of consensus statements supported lower limit of 7 g/ strategy will reduce exposure to allogenic transfusions which

Please cite this article as: W. Birlie Chekol et al., Hemoglobin threshold and clinical predictors for perioperative blood transfusion in elective
surgery: Systemic review, Trends in Anaesthesia and Critical Care, [Link]
4 W. Birlie Chekol et al. / Trends in Anaesthesia and Critical Care xxx (xxxx) xxx

results in more efficient use of red blood cells, save blood overall patients to a transfusion hematocrit trigger of 24% versus 28% to
and decreases health care cost [2] 1a. compare morbidity, mortality and resource use. Nonetheless,
A systemic review of 31 studies done by Holist et al. revealed postoperative complications and lengths of stay were similar in the
that there was a reduction in both the proportion of transfused two groups suggesting balanced risk. Finally the author recom-
patients and a reduction in the number of red blood cell units mended that lower transfusion threshold because, it supports
transfused in restrictive transfusion strategies when compared blood conservation efforts without increasing adverse events [23]
with liberal transfusion strategies but, mortality, morbidity and 1b.
myocardial infarction seems to be unaltered. Generally the authors According to the National Blood Authority guideline, red blood
strongly recommended that restrictive transfusion strategies are cell transfusion should not be dictated by hemoglobin concentra-
safe in most clinical settings [15] 1a. tion alone but, should also be based on assessment of the patient’s
A Meta-analysis of randomized trials done by Fominisky et al. clinical status. Where indicated, transfusion of a single unit of RBC
stated about the perioperative mortality in adult patients either followed by clinical reassessment to determine the need for further
receiving a restrictive or liberal transfusion strategies [22]1a. transfusion is appropriate. This guideline strongly recommendeds
A Meta-analysis of 6 randomized controlled trials done by to transfuse RBC when Hb concentration <7 g/dl [28]1a.
Ripolles et al. showed that in acute coronary syndrome, a restrictive For patients with acute coronary syndrome with Hb concen-
hemoglobin transfusion threshold of 7 g/dl for hospitalized adult tration <8 g/dl, the red blood cell transfusion may be associated
patients who are hemodynamically stable, including critically ill with reduced mortality and is likely to be appropriate. However, the
patients; but, a hemoglobin transfusion threshold of 8 g/dl for pa- effect of RBC transfusion on mortality is uncertain with hemoglobin
tients undergoing orthopedic or cardiac surgery and for those with concentration of 8e10 g/dl and may be associated with an
underlying cardiovascular disease [19] 1a. increased risk of recurrence of myocardial ischemia [23,27] 1a.
A systematic review done by Carson et al. claimed that about The European Society of Anesthesiologists recommended that
half of clinical specialties used 7 g/dl threshold and the other half the target hemoglobin concentration should be 7e9 g/dl during
used 8 g/dl to 9 g/dl threshold. The studies concluded that active bleeding. Continuous hemoglobin monitoring can be used as
restrictive transfusion strategies reduced the risk of receiving red a trend monitor and a restrictive transfusion strategy which is
blood cell transfusion by 43% across a broad range of clinical spe- beneficial in reducing exposure to allogenic blood products [29]1a.
cialties [1]1a. The American Society of Anesthesiologists recommended the
A meta-analysis of 11 randomized controlled trials done by restrictive red blood cell transfusion strategy to reduce transfusion
Docherty et al. recommended not to use a restrictive transfusion administration. The determination of whether hemoglobin con-
threshold of less than 8 g/dl in patients with ongoing acute coro- centrations between 6 and 10 g/dl justify or require red blood cell
nary syndrome or chronic cardiovascular diseases. These data transfusion should be based on potential or actual ongoing
support the use of a more liberal transfusion threshold (>8 g/dl) for bleeding, intravascular volume status, signs of organ ischemia and
patients with both acute and chronic cardiovascular disease until adequacy of cardiopulmonary reserve [30]1a.
adequately powered high quality randomized trials have been The recent National Institute for Health and Care Excellence
undertaken in patients with cardiovascular diseases [23] 1a. (NICE) blood transfusion guideline recommended using restrictive
A systematic review done by Hovaguimain et al. described transfusion thresholds for patients who need red blood cell trans-
cautiously to use restrictive transfusion strategies in high-risk pa- fusions and are not having a major hemorrhage. Consideration of
tients undergoing major surgery [24] 1a. single unit transfusion is also recommended. These strategies are
Among total of 921 patients with severe acute upper gastroin- applicable to the stable anemic postoperative patient but not for
testinal bleeding, the outcome of the patients were significantly the intraoperative active major hemorrhage. The NICE guideline
improved with a restrictive transfusion strategy in which the he- recommended to use restrictive red blood cell transfusion thresh-
moglobin threshold was 7 g/dl as compared with a liberal trans- olds for patients who need red blood cell transfusions and who do
fusion strategy in which the hemoglobin threshold was 9 g/dl [25] not have major hemorrhage or acute coronary syndrome and those
1b. who require regular blood transfusions for chronic anemia [31]1a.
In patients aged 50 years undergoing cardiac surgery to repair The American Association of Blood Banks (AABB) recommended
heart failure and history of cardiovascular disease with post- Hb 7e8 g/dl as the target in stable patients without coronary artery
operative hemoglobin concentrations lower than 10 g/dl; liberal disease. The AABB recommended that hospitalized patients with
blood transfusion did not affect 3-year mortality compared with a pre-existing cardiovascular disease should be transfused for
restrictive transfusion strategy in heart failure patients with car- Hb
8 g/dl or for anemic symptoms [32] 1a.
diovascular diseases [26] 1b.
A restrictive transfusion threshold after cardiac surgery was not 3.3. Risks of allogenic blood transfusion
superior to a liberal threshold with respect to morbidity in patients
older than 16 years undergoing non-emergency cardiac surgery. The risk of transmission of infectious diseases has reduced
During the entire admission, 63.7% of the patients in the restrictive significantly in recent years through improved manufacturing and
threshold group and 94.9% of those in the liberal threshold group laboratory processes. Nevertheless, there is still a small potential
received transfusions. Post-operative cardiovascular complications, for transfusion of an unrecognized infectious agent. Despite im-
infections and duration of stay in hospital were the same in both provements in systems management, there remains a risk of
study arms [27] 1b. transfusion related harm due to administrative error. Such an error
Transfusion requirements in surgical oncology patients is has the potential to result in acute hemolytic reaction from ABO
studied by De Almaida et al. and the results showed that liberal incompatibility, which may be fatal [19]1b.
transfusion strategy with a hemoglobin trigger of 9 g/dl is associ-
ated with fewer major postoperative complications in patients 3.4. Predictors of allogenic blood transfusion
having major cancer surgery compared with a restrictive strategy
[20]1b. Cohort studies of predictors of allogenic blood transfusion after
A randomized clinical trial done by Korch et al. identified that shoulder arthroplasty by Ponce et al. shows that allogenic blood
the red blood cell transfusion triggers in cardiac surgery allocated transfusion during shoulder arthroplasty had a significantly higher

Please cite this article as: W. Birlie Chekol et al., Hemoglobin threshold and clinical predictors for perioperative blood transfusion in elective
surgery: Systemic review, Trends in Anaesthesia and Critical Care, [Link]
 W. Birlie Chekol et al. / Trends in Anaesthesia and Critical Care xxx (xxxx) xxx 5

Table 2
List of recent transfusion articles on guidelines.

Guidelines

SN Society, year of publication Red blood cell Clinical setting References

transfusion
threshold

1 National Blood Authority, 2013 Hb level <8 g/dl In the absence of acute myocardial or cerebrovascular ischemia, postoperative [40]
transfusion may be inappropriate for patients with Hb level >8 g/dl.
Hb level <8 g/dl Patients with acute coronary syndrome
2 European Society of Anesthesiology, 2017 Maintain Hb 7e9 g/ Active bleeding [41]
dl
3 American Society of Anesthesiologists, 2015 Hb level <6 g/dl Perioperative blood management [39]
4 The National Institute for Health and Care Hb level
8 g/dl (Target: Hb 8e10 g/dl after transfusion) for patients with acute coronary [38]
Excellence blood transfusion guideline, 2015 syndrome.
Individual thresholds and Hb concentration targets for each patient who needs
regular blood transfusions for chronic anemia.
5 American Association of Blood Banks, 2016 Hb level <7 g/dl Hospitalized adult patients who are hemodynamically stable, including critically ill [32]
patients
Hb level <8 g/dl Patients undergoing orthopedic surgery or cardiac surgery and patients with
preexisting cardiovascular disease

Table 3
Meta-analysis and Systematic review.

Meta-analysis and Systematic Review

SN Author, year Number of Target population Results (Restrictive Transfusion Threshold Vs Liberal Transfusion Threshold) Ref.
RCT/Patients

1 Salpeter, 2014 3/2,3641 Critically ill patients Significant reduction in cardiac events. [21]
2 Curley, 2014 6/1,262 Patients undergoing cardiovascular surgery No significant differences in terms of adverse event rates (mortality, myocardial [42]
infarction, stroke, acute renal failure, infections, duration of stay).
3 Brunskill, 6/2,272 Patients undergoing hip fracture surgery No differences in mortality functional recovery, and post-operative morbidity. [43]
2015
4 Holst, 2015 31/9,813 Surgical and medical patients No significant differences in terms of overall morbidity and mortality risks. [15]
5 Fominisky, 27/11,021 Perioperative and critically ill adult patients Liberal transfusion strategy compared with restrictive strategy improved [22]
2015 survival in peri-operative patients.
6 Ripolles, 2016 6/2,156 Critically ill patients/patients with acute coronary No significant differences in terms of mortality. [19]
syndrome
7 Carson, 2016 31/12,587 Hospitalized adult patients No significant differences in terms of mortality. [1]
8 Hovaguimian, 31/14252 Patients with cardiovascular disease undergoing Restrictive strategies seemed to increase the risk of events reflecting inadequate [24]
2016 cardiac or vascular procedures or orthopedic oxygen supply.
9 Docherty, 11/3033 patients with cardiovascular disease The risk of acute coronary syndrome in patients managed with restrictive [36]
2016 compared with liberal transfusion was increased.

Table 4
Randomized controlled trial.

RCT

SN Author/Year Study Population/Patient Number Transfusion Results Ref.

threshold

1 Villanueva C Patients with history of Patients with severe acute upper Restrictive Restrictive transfusion strategy was associated [44]
et al. upper GIT bleeding gastrointestinal bleeding/921 (Hb < 7 g/dl) with improved outcomes in patients with acute
(target: Hb 8.0 upper gastrointestinal bleeding.
and 10 g/dl).
Vs Liberal
(Hb < 9 g/dl)
(Target: Hb 9.0
e11.0 g/dl).
2 Carson,2015 Functional outcomes in Patients aged 50 years undergoing surgery to Restrictive Liberal blood transfusion did not affect 3-year [26]
cardiovascular patients repair a heart failure and history of cardio (Hb < 8 g/dL) Vs mortality compared with a restrictive transfusion
undergoing surgical hip vascular disease or risk factor for Liberal strategy in heart failure patients with
fracture repair cardiovascular disease (Hb < 10 g/dl) cardiovascular disease.
3 Murphy,2015 Transfusion indication Patients older than 16 years undergoing non- Restrictive A restrictive transfusion threshold after cardiac [37]
threshold reduction emergency cardiac surgery (Hb < 7.5 g/dl) surgery was not superior to a liberal threshold with
VS respect to morbidity.
Liberal (Hb < 9 g/
dl)
4 De Transfusion requirements Patients undergoing major cancer surgery Restrictive Liberal transfusion threshold transfusion therapy is [20]
almeida,2015 in surgical oncology admitted to intensive care unit (Hb < 7 g/dl) VS more effective than restrictive transfusion
patients Liberal (Hb < 9 g/ threshold
dl)

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predictive value with patient medical co morbidities [33] 2a. 4. Conclusions and recommondations
The factors determining risk of allogenic transfusion are low
preoperative hemoglobin or hematocrit, either before intervention Most guidelines and literature stress that blood transfusion
or on day of surgery, low weight, female sex, age over 70 years, should not be only hemoglobin value alone, it should be considered
estimated surgical blood loss, coagulopathy, type of surgery, pri- clinical symptom of anemia and predictor of transfusion. The use of
mary or revision surgery [17,33e35] 2a,1b,2a,1b. only single value of hemoglobin level as a trigger for transfusion
should be avoided. Evaluation of the patient’s clinical situation
3.5. Area of controversies should be a factor in the decision for blood transfusion including
individual patient’s intravascular volume status, evidence of shock,
The recent clinical trials in adults have provided level I evidence
to support restrictive red blood cell transfusion practices. However,
some advocates have attempted to identify “correct” Hb threshold
for RBC transfusion whereas others assert that management of
anemia including transfusion decisions must be taken into account
based on clinical patient variables rather than simply one diag-
nostic laboratory test. The heterogeneity of guidelines for blood
transfusion by a number of medical societies reflects this contro-
versy [14]1a.
Data from three randomized controlled trials of critically ill
patients showed that a hemoglobin threshold <7 g/dl significantly
reduces negative outcomes as well as in-hospital and total mor-
tality when compared to a hemoglobin threshold <8 g/dl. The
systematic reviews clearly suggest that a restrictive RBC transfusion
strategy is equivalent or superior to a more liberal strategy in
morbidity and mortality [21] 1a.
In contradiction, Fominisky and colleagues, after analysis of RCT
with 11,021 patients, concluded that liberal transfusion therapy is
superior to restrictive transfusion therapy in terms of overall sur-
vival in preoperative adult patients. Restrictive red cell transfusion
policies are recommended as safe for most hospital patients with
anemia. Uncertainty exists for patients with cardiovascular disease,
whose hearts may be more susceptible to limited coronary oxygen
supply [36]1a.
Guidelines such as the American Society of Anesthesiologists,
the American Association of Blood Banks and National Institute for
Health and Care Excellence are recommended to use restrictive
transfusion strategy [37e39]1a. However, several randomized
studies in different clinical contexts have recorded an increase in
morbidity-mortality among patients assigned to restrictive trans-
fusion criteria [20,22].

3.6. Summary of evidences

The red blood cell transfusion threshold for patients with acute
coronary syndrome is determined as (Hb < 8 g/dl).On the other
hand, the red blood cell transfusion threshold of patients under-
going orthopedic surgery, cardiac surgery and patients with pre-
existing cardiovascular disease is determined as (Hb < 8 g/dl);
while in hospitalized adult patients who are hemodynamically
stable, including critically ill patient is (<7 g/dl) (Table 2).
The liberal transfusion strategy compared with restrictive
strategy improves the survival rate in peri-operative critically adult
patients. However, Meta-analysis and systemic reviews stated the
non-significant differences in restrictive VS liberal transfusion
strategy in terms of postoperative morbidity and mortality; in pa-
tients undergoing cardiovascular surgery, hip fracture surgery, pa-
tients with acute coronary syndrome and hospitalized adult
patients (Table 3).
The liberal transfusion threshold is more effective than restric-
tive transfusion threshold in patients undergoing major cancer
surgery admitted to the intensive care unit. However; restrictive
transfusion threshold after cardiac surgery is not superior to the
liberal transfusion threshold with respect to morbidity in patients
older than 16 years undergoing non-emergency cardiac surgery Fig. 2. Flow diagram on hemoglobin threshold and clinical predictors for perioperative
(Table 4). blood transfusion in elective surgery..

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 W. Birlie Chekol et al. / Trends in Anaesthesia and Critical Care xxx (xxxx) xxx 7

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