Preoperative Blood Transfusions For Sickle Cell Disease (Review)

Preoperative blood transfusions for sickle cell disease (Review)
Hirst C, Williamson L
This is a reprint of a Cochrane review, prepared and maintained by The Cochrane Collaboration and published in The Cochrane Library 2010, Issue 2 http://www.thecochranelibrary.com
Preoperative blood transfusions for sickle cell disease (Review) Copyright 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
TABLE OF CONTENTS HEADER . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ABSTRACT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . PLAIN LANGUAGE SUMMARY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . BACKGROUND . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . OBJECTIVES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . METHODS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . RESULTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . DISCUSSION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . AUTHORS CONCLUSIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . REFERENCES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . CHARACTERISTICS OF STUDIES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . DATA AND ANALYSES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 1.1. Comparison 1 Aggressive versus conservative blood transfusion, Outcome 1 Perioperative mortality. . Analysis 1.2. Comparison 1 Aggressive versus conservative blood transfusion, Outcome 2 Serious complications related to sickle cell disease. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 1.3. Comparison 1 Aggressive versus conservative blood transfusion, Outcome 3 Postoperative Infection. . Analysis 1.4. Comparison 1 Aggressive versus conservative blood transfusion, Outcome 4 Life-threatening surgical complications. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 1.5. Comparison 1 Aggressive versus conservative blood transfusion, Outcome 5 Transfusion related complications. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 1.6. Comparison 1 Aggressive versus conservative blood transfusion, Outcome 6 Blood counts. . . . . . Analysis 1.7. Comparison 1 Aggressive versus conservative blood transfusion, Outcome 7 Volume of blood transfusion/venesected. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 2.2. Comparison 2 Preoperative blood transfusion versus no transfusion, Outcome 2 Serious complications related to sickle cell disease. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 2.3. Comparison 2 Preoperative blood transfusion versus no transfusion, Outcome 3 Postoperative Infection. Analysis 2.5. Comparison 2 Preoperative blood transfusion versus no transfusion, Outcome 5 Transfusion related complications. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . WHATS NEW . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . HISTORY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . CONTRIBUTIONS OF AUTHORS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . DECLARATIONS OF INTEREST . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . SOURCES OF SUPPORT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . INDEX TERMS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 1 2 2 3 3 5 9 10 11 12 15 16 17 17 18 18 19 19 20 20 21 21 21 22 22 22 23
[Intervention Review]
Preoperative blood transfusions for sickle cell disease

Ceri Hirst1 , Lorna Williamson2
1 AstraZeneca,
Alderley Park, UK. 2 National Blood Service, East Anglia Centre, Cambridge, UK (90HW2Q1), Alderley Park, Cheshire, SK10 4TG, UK.
Contact address: Ceri Hirst, AstraZeneca, Parklands Ceri.Hirst@astrazeneca.com. criddington@hotmail.com.
Editorial group: Cochrane Cystic Fibrosis and Genetic Disorders Group. Publication status and date: New search for studies and content updated (no change to conclusions), published in Issue 2, 2010. Review content assessed as up-to-date: 14 December 2009. Citation: Hirst C, Williamson L. Preoperative blood transfusions for sickle cell disease. Cochrane Database of Systematic Reviews 2001, Issue 3. Art. No.: CD003149. DOI: 10.1002/14651858.CD003149. Copyright 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
ABSTRACT Background Sickle cell disease is one of the most common inherited diseases in the world, and can cause haemolytic anaemia, vaso-occlusive crises and dysfunction in virtually any organ system in the body. Surgical procedures are often required. Blood transfusion regimens can be used preoperatively in an attempt to increase transport of oxygen around the body and dilute the sickled red blood cells, thus reducing the risk of vaso-occlusion. Objectives To assess the relative risks and benets of preoperative blood transfusion regimens in people with sickle cell disease undergoing surgery of any type in any setting. Search strategy We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register which comprises references identied from comprehensive electronic database searches, handsearches of relevant journals and abstract books of conference proceedings. Date of the most recent search: 15 December 2009. Selection criteria All randomised or quasi-randomised controlled studies comparing preoperative blood transfusion regimens to different regimens or no transfusion in people with sickle cell disease undergoing surgery. Data collection and analysis Both authors independently assessed study quality and extracted data. Main results The searches identied three studies, of which two, involving a total of 920 participants, were eligible for inclusion in the review. The rst study compared an aggressive transfusion regimen (decreasing sickle haemoglobin to less than 30%) to a conservative transfusion regimen (increasing haemoglobin to 10 g/dl) in 604 elective operations in people with sickle cell disease. The conservative regimen was found to be as effective as the aggressive regimen in preventing perioperative complications, and was associated with fewer transfusionrelated adverse events. The second study compared a preoperative transfusion group to a group receiving standard care, and did not show an advantage to preoperative transfusion.
Preoperative blood transfusions for sickle cell disease (Review) Copyright 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. 1
Authors conclusions While in general, conservative therapy appears to be as effective as aggressive therapy in preparation for surgery in people with sickle cell disease, further research is needed to examine the optimal regimen for different surgical types, and to address whether preoperative transfusion is needed in all surgical situations.
PLAIN LANGUAGE SUMMARY Blood transfusions for people with sickle cell disease before they undergo surgery Once they have given up their oxygen, red blood cells in people with sickle cell disease become shaped like crescents. These cells can block blood vessels, which causes problems throughout the body. People with sickle cell disease often need surgery, but this can increase the number of sickle-shaped cells in the blood. Blood transfusions before an operation can help dilute the sickled red blood cells and increase the level of oxygen in the blood. This reduces the risk of blood vessels becoming blocked causing further damage. Blood transfusions can be full or partial. They can be linked to adverse events such as the development of antibodies to foreign red blood cells, iron overload, infection rates after surgery and length of stay in hospital. Two studies with 920 people are included in the review. One study compared full transfusion to partial transfusion. This showed no difference between the two treatments in preventing complications immediately after surgery, but partial transfusion was linked to fewer adverse events. The second study compared transfusion to standard care and did not show an advantage in transfusion. Both studies reported a range of complications related to transfusion. However, many details of study design were not recorded in the published papers and statistical analysis indicated a lack of certainty in the ndings. There is not enough evidence to recommend blood transfusions before surgery for people with sickle cell disease as standard practice. A large study should look at the best use of this treatment and consider different risk groups.
BACKGROUND
monly haemoglobin SC disease (SC) and sickle beta thalassaemia (S Thal). In sickle cell disease, the oxygenated red blood cells appear normal, but, once they have transported and given up their oxygen, the haemoglobin molecules associate as crystals and distort the red blood cells, giving the appearance of sickle-shaped cells. Blood transfusions are undertaken in many people to maintain the oxygen-carrying potential of blood and, in some situations, to dilute the circulating sickle cells, thus reducing the risk of vaso-occlusive episodes and anaemia (Serjeant 1992). Surgical interventions are relatively common in people with sickle cell disease, treating problems associated with persistent or acute organ dysfunction. For example haemolytic anaemia causes increased bilirubin levels and a high incidence of gallstones and therefore cholecystectomy is frequently needed (Haberkern 1997). Hypersplenism and splenic sequestration and infarction may be treated with splenectomy. Orthopaedic complications resulting from avascular necrosis, bone infection and musculoskeletal malformations may require joint replacement, drainage or surgical correction (Vichinsky 1999). Ear, nose and throat (ENT) opera2
Description of the condition

Sickle cell disease is a genetic haemoglobin disorder, which can cause severe pain crises and dysfunction of virtually every organ system in the body, ultimately causing premature death. Populations originating from sub-Saharan Africa, the Middle East and parts of the Mediterranean are predominantly affected, but population movement has made this a worldwide problem. Approximately 10,000 people in the UK and one in sixty people in West Africa now suffer from the disease (Davies 1997; Hickman 1999). Despite vastly improved care services for people with sickle cell disease, the average life expectancy for men and women with homozygous disease (SS) is still only 42 years and 48 years, respectively (Platt 1994). There are many different types of sickle cell disease, but the dening disease, homozygous sickle cell disease (SS), is caused by the inheritance from both parents of an abnormal gene for a haemoglobin chain. Variations with similar symptoms arise when one sickle gene is inherited along with another abnormal beta chain haemoglobin gene (Serjeant 1992), most com-
tions account for approximately one-fth of surgical procedures in this population (Waldron 1999). Surgical trauma, however, can increase sickling and anaemia, and this may be exacerbated by respiratory depression associated with anaesthesia. Surgery in people with sickle cell disease is associated with postoperative complications with frequencies ranging from 7% to 32% (Serjeant 1992).
4. is associated with severe adverse events (as reported in the included studies). If transfusion had been shown to be benecial, with minimal adverse events, we would have compared the effectiveness of different transfusion regimens (e.g. top-up versus exchange, timing of the treatment) within and between studies.
Description of the intervention

Blood transfusions are frequently used in preparation for surgery. Several regimens are used in current clinical practice. These include top-up transfusion (conservative), in which normal red cells are given to dilute the sickle cells; and partial or full exchange transfusion (aggressive), in which the individuals own blood is removed and replaced. This can be done either immediately or up to 14 days prior to surgery, although in preparation for elective surgery it is usually undertaken at least 24 hours before the operation to maximise the oxygen transport capacity of the transfused blood. Various practises are used, but with no consensus over the best method or the necessity of transfusion in specic surgical cases (Bischoff 1988; Buchanan 1995; Fullerton 1981).
METHODS
Criteria for considering studies for this review
Types of studies All those randomised or quasi-randomised studies in which preoperative blood transfusion regimens are compared to either no transfusion or a different transfusion regimen, in people with sickle cell disease undergoing either elective or emergency surgery. Studies for people undergoing elective and emergency surgery would have been analysed separately. Studies in which quasi-randomised methods, such as alternation, are used would have been included if there were sufcient evidence that the treatment and control groups were similar at baseline. If there had been sufcient numbers of studies using quasi-randomisation methods, then this group would have been analysed separately. Studies should include sufcient information regarding the clinical setting, as factors relating to the availability of trained staff, adequate surgical and anaesthetic equipment, safe blood and a sanitary environment may have a profound effect on outcome.
Why it is important to do this review

As well as the direct and indirect nancial cost of blood transfusions, they can adversely affect the individual, causing hyperviscous blood (precipitating vaso-occlusion), alloimmunisation (development of antibodies to foreign red blood cells), haemolytic transfusion reactions and infection from blood products. Red cell transfusions can also contribute to iron overload and may affect the postoperative infection rate and inpatient stay (Vichinsky 1990). These adverse costs and events are particularly relevant in the developing world where resources and equipment are limited and the infection risks of transfused blood can be higher than in developed countries (Ohene-Frempong 1999). We aimed to examine the available evidence for the relative risks and benets of preoperative blood transfusion regimens.
Types of participants People with homozygous sickle cell disease (SS), sickle beta thalassaemia (S 0 and S +) and sickle haemoglobin C disease (SC) (proven by electrophoresis and sickle solubility test, with family studies or DNA tests as appropriate) of all ages and both sexes undergoing surgery of any type in any setting.
OBJECTIVES
To determine whether there is evidence that preoperative blood transfusion in people with sickle cell disease undergoing surgery: 1. reduces mortality; 2. reduces complications directly related to the surgical procedure, such as local infection and bleeding; 3. reduces serious perioperative complications related to sickle cell disease, including pain, acute sickle chest syndrome and the postoperative frequency and severity of infections; Types of interventions Preoperative blood transfusion regimens compared to no transfusion or alternative preoperative transfusion regimens (e.g. top-up compared with partial or full exchange). Types of outcome measures
Primary outcomes
3
1. Perioperative mortality 2. Serious complications related to sickle cell disease e.g. acute chest syndrome, cerebrovascular accident, painful crisis 3. Postoperative infection (site, organism and severity)
Data collection and analysis
Selection of studies Two authors (CH and LW) independently selected the studies. If disagreement arose on the suitability of a study for inclusion in the review, we reached a consensus by discussion.
Secondary outcomes
1. Life-threatening surgical complications, including a fall in haemoglobin greater than 2 g/dl 2. Recognised and reported transfusion-related complications, including alloimmunisation, infection from blood products, procedural complications and transfusion reactions 3. Recovery period (intensive care unit and inpatient stay) 4. Quality of life (mobility, ability to work or attend school, self-reliance) 5. Measures of organ damage (postoperative difference from baseline) for example creatinine (kidney function), liver function tests, lung function tests 6. Haemoglobin level and haemoglobin S percentage (pretransfusion, post-transfusion and post-operative) 7. Volume of red cells infused and, where known, volume of blood venesected, with haematocrit
Data extraction and management Two authors (CH and LW) independently extracted data using standard data acquisition forms. If the data had been available, outcome data, with the exception of transfusion related complications, would have been grouped into those measured during surgery and at 3 hours, 24 hours, 1 week and 1 month after surgery.
Assessment of risk of bias in included studies In order to assess the risk of bias in the included studies, we assessed their methodological quality based on a method described by Schulz (Schulz 1995). We categorised the following dimensions of methodological quality as adequate, unclear or inadequate and related these to a low, unclear or high risk of bias: allocation concealment; and generation of the randomisation sequence. We categorised RCTs according to whether double blinding had been reported or not and estimated that the risk of bias would increase when fewer people were blinded to the intervention. If disagreement arose on the assessment of quality of an included trial, we reached a consensus by discussion.
Search methods for identication of studies
Electronic searches Relevant studies were identied from the Groups Haemoglobinopathies Trials Register using the terms: sickle cell AND blood transfusion AND preoperative. The Haemoglobinopathies Trials Register is compiled from electronic searches of the Cochrane Central Register of Controlled Trials (Clinical Trials) (updated each new issue of The Cochrane Library) and quarterly searches of MEDLINE. Unpublished work is identied by searching the abstract books of ve major conferences: the European Haematology Association conference; the American Society of Hematology conference; the British Society for Haematology Annual Scientic Meeting; the Caribbean Health Research Council Meetings; and the National Sickle Cell Disease Program Annual Meeting. For full details of all searching activities for the register, please see the relevant section of the Cystic Fibrosis and Genetic Disorders Group Module. Date of the most recent search of the Groups Haemoglobinopathies Trials Register: 15 December 2009.
Measures of treatment effect We recorded dichotomous outcomes (e.g. life or death), as present or absent, whilst we recorded continuous data such as blood counts and organ function tests (creatinine, etc) as either mean change from baseline for each group or mean post-treatment values and standard deviation for each group. We aimed to calculate a pooled estimate of the treatment effect for each outcome across studies, (for binary outcomes the odds of an outcome among treatment allocated participants to the corresponding odds among controls).
Dealing with missing data We would have sought full reports from authors if studies had been published in abstract form, presented at meetings or reported to the co-authors. Where information was missing or unclear, we would have contacted the primary investigator. In order to allow an intention-to-treat analysis, irrespective of later exclusion (regardless of cause) or loss to follow up, data were collected by allocated treatment groups.
4
Searching other resources The bibliographic references of all retrieved literature were reviewed for additional reports of studies.
Assessment of heterogeneity Heterogeneity between studies would have been tested for using a standard chi-squared test and the I2 statistic (Higgins 2003). The I2 statistic describes the percentage of the variability in effect estimates that is due to heterogeneity rather than chance and its values lie between 0% and 100%. A simplied categorization of heterogeneity that we plan to use is of low (I2 value of 25%), moderate (I2 value of 50%), and high (I2 value of 75%) (Higgins 2003). Data synthesis We based overall estimates on the xed-effect model. If further trials are included in the future, and if there is signicant heterogeneity identied, we plan to use the random-effects model. Subgroup analysis and investigation of heterogeneity If heterogeneity between studies had been found, we would have undertaken examination of subgroups to help to explain the reasons for this. Subgroup analysis of type of surgery, severity of disease and participant age were performed where possible. Sensitivity analysis If heterogeneity between studies had been found, sensitivity analysis based on the methodological quality of the studies would have been performed, including and excluding quasi-randomised studies.
Results of the search Three studies were identied through literature searches (AlJaouni 2006; Vichinsky 1995; Wali 2003).
Included studies Two studies, including 920 participants, met the predened inclusion criteria (Al-Jaouni 2006; Vichinsky 1995). In the Vichinsky study, 551 participants who underwent a total of 604 elective operations were included (Vichinsky 1995). The surgical procedure was randomised into two groups for preoperative transfusion: aggressive, designed to decrease the haemoglobin S level to less than 30% (Group 1); and conservative, which was designed to increase the haemoglobin level to 10 g/dl (Group 2). Blood was from SS negative donors, and participants with a history of allergic reactions to transfusion received leuco-depleted blood. In Group 1, 57% of participants received exchange transfusions and 30% had repeated transfusions. In contrast, 77% of participants in Group 2 received a single transfusion. Participant characteristics were similar in both groups (Table 1) ( Vichinsky 1995). Fifty-four per cent in Group 1 were males, compared to 48% in Group 2. Age distribution was also balanced for the age groups 0 years to 9 years, 10 years to 19 years and over 20 years. All participants were followed up for 30 days. Data regarding risk factors for complications, participant history and surgical risk category, dened according to a previously established system (Cohen 1988), were also recorded. More participants in Group 1 had a history of cardiac disease, smoking or central nervous system disease, although only the latter was statistically signicant (P = 0.049). Surgical procedures were dened as low risk (e.g. inguinal hernia repair), medium risk (e.g. intra-abdominal procedures), or high-risk (e.g. intracranial procedures). The distribution was similar between groups, although only one participant, who had received the aggressive transfusion regimen, underwent a high-risk procedure during the study.
RESULTS
Description of studies
See: Characteristics of included studies; Characteristics of excluded studies. Table 1. Patient characteristics - Vichinsky 1995 Characteristic Male Age 0-9 Age 10-19 Age >20 Group 1 % of patient 54 40 35 25
Group 2 % of patient 48 40 36 24
5
Table 1. Patient characteristics - Vichinsky 1995
(Continued)
Anaesthetic risk score 2 3 4 Screening ndings Oxygen saturation <90% Abnormal chest lm Abnormal LFTs Creatinine Medical History Pulmonary disease Asthma Smoking Cardiac disease Renal disease CNS disease Hospitalisations in previous year 0 1-4 >4 Previous transfusions 0 1-10 >10 Alloimmunization 23 53 24 19 25 54 21 13
6
47 51 2
48 51 1
2 14 8 5
4 13 11 4
35 8 8 8 3 11
30 8 5 5 4 7
28 60 12
22 64 13
Table 1. Patient characteristics - Vichinsky 1995
(Continued)
Reaction
5 Neither study reported on double blinding and we therefore judged both to have an unclear risk of bias (Al-Jaouni 2006; Vichinsky 1995). We consider that double blinding would not have been possible for either clinicians or participants in these studies due to the nature of the treatment under investigation; however, it would be possible for outcome assessors to be blinded to treatment group, but neither study reported on this.
Complications were recorded and classied as minor (brief temperature elevations and mild wound infections), serious (complications requiring prolonged hospitalisations), or life threatening. Specically dened complications included alloimmunisation, painful crisis, acute chest syndrome, neurological events, renal complications and fever or infection. Data regarding transfusion-related complications were also collected. Results were presented as a percentage of each group of operations. Further publications based on subsets of data from this study, and also including non-randomised data, are discussed in more detail below (Vichinsky 1995). In the Al-Jaouni study, 369 participants were enrolled in two Saudi Arabian hospitals between January 1996 and June 2001 (Al-Jaouni 2006). Participants were randomised to receive either preoperative transfusion (simple or partial exchange transfusion) or no preoperative transfusion. In both groups, transfusions were allowed during surgery to compensate for blood loss. Baseline characteristics of patients were similar between groups, in terms of participant age, sickle cell disease type, gender and surgery type. Median participant age was 16 years (range: 1 year to 35 years). Surgical procedures included adenoidectomy, tonsillectomy, total hip arthroplasty, cholecystectomy, splenectomy, and obstetric and gynaecological surgeries. Participants were hydrated and oxygenated perioperatively. Data were collected on complications in the intraoperative and postoperative periods (timing not specied). Excluded studies One study was ineligible because it did not use a randomised study design (Wali 2003).
Incomplete outcome data Neither study stated whether an intention-to-treat analysis was used (Al-Jaouni 2006; Vichinsky 1995). In the Vichinsky study, of the original data collected on 692 surgical procedures, which had been randomly allocated, 88 were subsequently excluded due to cancellation of the surgery, diagnostic error or refusal of the individual to participate in the study ( Vichinsky 1995). This represents 12.7% of the study population. Forty-two were from Group 1 and 46 from Group 2. While it is stated that the participant characteristics of this group were similar in both groups, and that the age range was representative of the whole sample, the fairly limited information of participant characteristics provided in the paper, and the high exclusion rate, detracts somewhat from the study. We judged both studies to have an unclear risk of bias (Al-Jaouni 2006: Vichinsky 1995).
Effects of interventions
Risk of bias in included studies
Aggressive versus conservative blood transfusions One study evaluated this comparison (Vichinsky 1995).
Allocation Both studies were described as randomised but neither gave any details of the method, hence we judged them to have an unclear risk of bias. Likewise, neither study reported on concealment of allocation and were also judged to have an unclear risk of bias for this criteria (Al-Jaouni 2006; Vichinsky 1995).
Primary outcomes
1. Perioperative mortality Two participants died in the Vichinsky study, odds ratio (OR) 4.95 (95% condence interval (CI) 0.24 to 103.49). Both men had received aggressive transfusion therapy prior to splenectomy and hip replacement operations. Both had a history of pulmonary
Blinding
disease and developed respiratory failure after surgical complications which progressed to multi-organ failure and death (Vichinsky 1995).
and uid overload resulting in respiratory distress (three participants, all in the aggressive group).
3. Recovery period 2. Serious complications related to sickle cell disease The following complications were reported (Vichinsky 1995): a. acute chest syndrome: 11% aggressive, 10% conservative, OR 1.10 (95% CI 0.65 to 1.86); b. painful crisis: 5% aggressive, 7% conservative, OR 0.69 (95% CI 0.35 to 1.37); c. neurological event: 1% aggressive, 1% conservative, OR 0.99 (95% CI 0.20 to 4.96); d. renal complication: 1% aggressive, less than 1% conservative, OR 3.00 (95% CI 0.31 to 29.00); e. miscellaneous: 6% aggressive, 5% conservative, OR 1.20 (95% CI 0.60 to 2.44). Therefore, it can be seen that serious complications were no more prevalent in the conservative transfusion group than the aggressive transfusion group. Only the sickle pain rate appears to be raised, but this is not statistically signicant (P = 0.09) (Vichinsky 1995). The average inpatient stay in both groups was eight days ( Vichinsky 1995).
4. Quality of life This was not recorded as an outcome measure in the Vichinsky study (Vichinsky 1995).
5. Measures of organ damage This was not recorded as an outcome measure in the Vichinsky study (Vichinsky 1995). However, renal complications were seen in 1% of participants who received aggressive transfusion therapy and less than 1% of those who received conservative therapy, and neurological events occurred in 1% of participants in both groups.
3. Postoperative infection Vichinsky reported that both aggressive and conservative regimen groups had a perioperative infection rate of 7% (Vichinsky 1995). However, post-operatively 7% of participants in the aggressive regimen group had infections, 2% higher, although not signicantly different in statistical terms, OR 1.49 (95% CI 0.76 to 2.94), than that of the conservative group (5%).
6. Haemoglobin level and haemoglobin S percentage (pretransfusion, post-transfusion and post-operative) The average haemoglobin levels were similar in both groups before and after transfusion: 8 g and 7.9 g at the time of enrolment, 11 g and 10.6 g prior to surgery (Vichinsky 1995). The average preoperative sickle haemoglobin (HbS) was 31% in group 1 and 59% in Group 2. White blood cell counts were not recorded in the study (Vichinsky 1995).
Secondary outcomes
7. Volume of blood transfused, and where known venesected 1. Life-threatening surgical complications Vichinsky reported that miscellaneous intra-operative complications occurred in 19% of participants receiving aggressive transfusion therapy, and 20% of those in the conservative therapy group, OR 0.85 (95% CI 0.57 to 1.28) (Vichinsky 1995). On average the participants in Group 1 received 5 units of blood, compared to 2.5 units in Group 2. The volume of blood venesected was not recorded as an outcome measure in this study (Vichinsky 1995).
Preoperative blood transfusion versus no transfusion
2. Transfusion-related complications
In the Vichinsky study, alloimmunisation occurred in 10% of participants in the aggressive transfusion group, but only 5% in the conservative group, OR 2.34 (95% CI 1.22 to 4.49) (Vichinsky 1995). Haemolysis, delayed or immediate, was seen in 6% of participants in the aggressive group and 1% in the conservative group, OR 4.97 (95% CI 1.67 to 14.78). Only four participants suffered allergic or anaphylactic reactions, three in the conservative group (1%) and one in the aggressive group (less than 1%). Other transfusion-related complications included fever (four in each group)
One study evaluated this comparison (Al-Jaouni 2006).
Primary outcomes
1. Perioperative mortality Deaths were not specically reported in the Al-Jaouni study; however the report states that there were no major intra- or post-operative complications in either group (Al-Jaouni 2006).
8
2. Serious complications related to sickle cell disease In the Al-Jaouni study, there were more painful crises, OR 1.62 (95% CI 0.38 to 6.88); neurological complications (unspecied), OR 8.85 (95% CI 0.47 to 165.63); and respiratory complications, OR 1.36 (95% CI 0.42 to 4.37) in the transfusion group than in the no transfusion group, although differences were not statistically signicant (Al-Jaouni 2006).
fewer transfusion reactions. However, since concealment of allocation, randomisation sequence generation, double blinding and intention-to-treat analysis were not recorded in the published papers, this could depreciate the reliability of the ndings. In addition, the wide condence intervals for many of the outcomes measured could indicate a lack of certainty in these ndings, and the implications for research should be viewed in light of these relative limitations. Subsets of these data have been included in several studies, which also include non-randomised data, to ascertain the generalisability for specic operations or participants groups. In addition, other, non-randomised studies address the role of preoperative blood transfusions in sickle cell disease. An increasing body of observational data suggests that preoperative blood transfusion may reduce morbidity and mortality associated with surgery in people with sickle cell disease (Bhattacharyya 1993; Fullerton 1981; Halvorson 1997; Ware 1988). This is backed by ndings from the Cooperative Study of Sickle Cell Disease, the largest study undertaken with sickle cell participants, which included 1079 surgical procedures on 717 participants and spanned 10 years of clinical practice in North America. However, many clinicians refute these ndings and practise successfully with minimal use of transfusions (Bischoff 1988; Grifn 1993). In the latter study Grifn found an overall complication rate of 26%, which rose to 52% for major procedures such as cholecystectomy, but was only 5% for minor operations such as herniorrhaphy and tympanostomy. This data, though non-randomised, would support use of transfusions in major, but not minor, surgical procedures. In the rst included study, 22.5% of participants underwent tonsillectomy, adenoidectomy or myringotomy (Vichinsky 1995). A subgroup analysis, including these 118 randomised and a further 47 non-randomised participants, was undertaken (Waldron 1999), and it was again concluded that a conservative regimen was as effective as a more aggressive one in reducing adverse events. Although the non-transfused group was small, the authors speculated that while preoperative blood transfusions may be benecial in higher risk surgical procedures, the shorter duration of surgery, decreased risk of blood loss and lack of airway involvement evident in myringotomy may make transfusions unnecessary in these participants. Similarly, a non-randomised comparison of sickle participants undergoing myringotomy showed a higher overall complication rate in transfused participants (43%) than those without transfusion (13%) (Orringer 1995). However, with the more invasive procedure of hip core decompression, non-transfused participants had a signicantly greater risk of postoperative complications. Cholecystecomy is the most common surgical procedure required by people with sickle cell disease. In a subset of 230 participants from the Preoperative Transfusion in Sickle Cell Disease Study, plus a non-randomised branch which included 37 non-transfused and 97 transfused participants, it was suggested that preoperative
9
3. Postoperative infection There was no difference in incidence of perioperative infection between groups, OR 0.96 (95% CI 0.19 to 4.83) (Al-Jaouni 2006).
Secondary outcomes
1. Life-threatening surgical complications This outcome was not reported in the included study (Al-Jaouni 2006).
2. Transfusion-related complications
In the Al-Jaouni study, there were ve cases of circulatory overload or heart failure in the transfusion group, but none in the no transfusion group, OR 10.88 (95% CI 0.60 to 198.20) (Al-Jaouni 2006). The wide condence intervals around this non-signicant result indicate a lack of statistical power (due to low number of cases). None of the other secondary outcomes were reported in the AlJaouni study (Al-Jaouni 2006).
DISCUSSION
It is widely agreed that people with sickle cell disease should be warm, well-hydrated and well-oxygenated for surgery in order to avoid conditions that could lead to relative or regional hypoxia, increased sickling and compromised oxygen delivery to tissues ( Serjeant 1992). However, use of various blood transfusion regimens, while theoretically efcacious, has not been conclusively shown to be benecial, and has signicant associated costs, both economic and physical. This systematic review has highlighted a lack of prospective randomised controlled studies of preoperative blood transfusion for people with sickle cell disease. The rst study included in this review, by the Preoperative Transfusion in Sickle Cell Disease Study Group (Vichinsky 1995), has shown that, in general, conservative transfusion (Hb 10 g/dl) does not carry an increased risk of perioperative complications over aggressive transfusion (HbS less than 30%), and is associated with
transfusion reduced sickle-related adverse events in participants undergoing cholecystectomy (Haberkern 1997). Although the untransfused group had a higher incidence of perioperative pain and acute chest problems, there was no increased morbidity overall, and no adverse events and costs associated with transfusion. Because of the small number of participants in the non-transfused group, the differences in participant characteristics and the partially non-randomised study design, the results of this subset may not be generalisable. However, smaller, non-randomised, studies have also advocated the use of transfusions prior to cholecystectomy (Bhattacharyya 1993; Ware 1988). Orthopaedic surgery appears to carry a very high risk of complications (Vichinsky 1999), and this subset of the study group plus non-randomised data showed 67% of participants suffered a serious adverse event. Most common were excessive intra-operative blood loss, sickle-related events and infection. There are no randomised data available addressing the effectiveness of transfusion in these cases. There is also a lack of data regarding surgery in people with haemoglobin sickle cell disease (HbSC). In a non-randomised study by the same group, Neumayr recommended selective transfusions prior to surgery, although with minor procedures such as myringotomy he speculated that this may be unnecessary ( Neumayr 1998). The second study, which included 369 participants in Saudi Arabia, demonstrated no advantage, in terms of reduced sickle-related complications, perioperative infection and transfusion-related complications, for preoperative transfusion compared to no preoperative transfusion, but these ndings are limited by lack of information on methodological quality and patient characteristics (Al-Jaouni 2006). No major complications were reported in either the transfusion or no-transfusion groups, but there were signicantly more complications overall in participants receiving transfusion, and surgery was delayed in 24% of participants in the transfusion group, compared to 0.6% in the no transfusion group, due largely to the protocol need to full the criteria of HbS concentration of greater than 40% (Al-Jaouni 2006).
frequently in countries such as Jamaica than in North America, and interestingly, observational studies from this setting do not report signicantly increased morbidity or mortality in operations without transfusion (Homi 1979; Thame 1999). Whether this is due to the setting or clinical differences is unclear, but such studies imply overuse of preoperative transfusion in sickle cell disease. With recent research demonstrating potential for several pharmacological therapies (Brugnara 2000; Charache 1995) and bone marrow or stem cell transplants becoming increasingly feasible ( Davies 1996), the quality of life for people with sickle cell disease is set to improve. Indeed, the demand for blood transfusions is likely to decline with the introduction of alternative treatments, less invasive surgical techniques, such as laparoscopic surgery, and improved anaesthetic agents. However, more sound evidence in the form of well-run, multi-centre, randomised controlled studies is required to optimise the clinical management regimen for these people.
AUTHORS CONCLUSIONS Implications for practice

While the rst included study did not show evidence that aggressive transfusion presents an advantage over conservative transfusion for preoperative management of people with sickle cell disease, recommendations concerning the optimal use of the therapy for subgroups of surgical and patient type cannot be made and need further elucidation in randomised studies (Vichinsky 1995). In addition, the second included study did not show an advantage to preoperative transfusion over standard care, but these ndings are limited by lack of methodological data (Al-Jaouni 2006). There is, therefore, insufcient reliable evidence to show that routine preoperative transfusions compared to no transfusion is benecial for surgical procedures.
Implications for research

Information from a well-designed prospective randomised controlled study of preoperative blood transfusion in people with sickle cell disease is urgently required in order to make recommendations for the optimal use of this therapy. The study should include transfused and non-transfused participants. Subgroup analysis for different surgical risk groups and participant risk factors should also be done to provide guidance on the optimal preoperative management regimen for each individual with sickle cell disease undergoing surgery. Without conclusive data of this type, people with sickle cell disease may be undergoing unnecessary treatment, suffering avoidable adverse events and incurring considerable economic costs through inefcient use of the therapies available.
Preoperative transfusion has become almost routine for people with sickle cell disease in North America. However, developing countries often do not have the resources to support such an extensive programme. The potential risks associated with transfusion therapy are increased in such settings due to a lack of trained staff, modern equipment, sanitary conditions and clean, infection free blood products (Ohene-Frempong 1999). Therefore, the riskbenet ratio will be different in developing countries to those in the included study, and the results discussed in this review may not be generalisable to this setting. Transfusions are undertaken less
10
REFERENCES
References to studies included in this review

Al-Jaouni 2006 {unpublished data only} Al-Jaouni S, Al-Muhayawi S, Qari M, Nawas MA, Abdel-Razeq H. The safety of avoiding transfusion preoperatively in patients with sickle cell hemoglobinopathies [abstract]. Blood 2002;100(11 Pt 2 of 2):21b. Al-Jaouni S, Al-Muhayawi SM, Qari MH, Nawas MA, AlMazrooa A. Randomized clinical trial to evaluate the safety of avoiding pre-operative transfusion in sickle cell anemia. Bahrain Medical Bulletin 2006;28(4):1647. Vichinsky 1995 {published data only} Haberkern CM, Neumayr L, Earles AN, Robertson S, Black D, Orringer EP, et al.Cholecystectomy in sickle cell anaemia (SCA) patients: report of 364 patients from the Preoperative Transfusion Study [abstract]. Blood 1995;86(10, Suppl 1):142a. Haberkern CM, Neumayr L, Earles AN, Robertson S, Black D, Orringer EP, et al.Cholecystectomy in sickle cell anemia patients: report of 364 patients from the Preoperative Transfusion Study [abstract]. Proceedings of the 21st Annual Meeting of the National Sickle Cell Disease Program. 1996:45. Haberkern CM, Neumayr LD, Orringer EP, Earles AN, Robertson SM, Black D, et al.Cholecystectomy in sickle cell anemia patients: perioperative outcome of 364 cases from the National Preoperative Transfusion Study. Preoperative Transfusion in Sickle Cell Disease Study Group.. Blood 1997;89(5):153342. Neumayr L, Koshy M, Haberkern C, Earles AN, Bellevue R, Hassell K, et al.Surgery in patients with hemoglobin SC disease. Preoperative Transfusion in Sickle Cell Disease Study Group. American Journal of Hematology 1998;57(2):1018. Orringer EP, Olivieri NF, Neumayr L, Haberkern C, Vichinsky EP. Is preoperative transfusion always necessary in sickle cell anemia (SCA)? [abstract]. Blood 1995;86 Suppl:300a. Preoperative Transfusion Study Group. Preliminary report on preoperative transfusion study in sickle cell disease [abstract]. Proceedings of the 14th Annual Meeting of the National Sickle Cell Disease Program. 1989:63. Vichinsky EP. High rates of complications in sickle cell anemia (SCA) patients undergoing orthopedic surgery [abstract]. Proceedings of the 22nd Annual Meeting of the National Sickle Cell Disease Program. 1997:125. Vichinsky EP, Haberkern CM, Neumayr L, Earles AN, Black D, Koshy M, et al.A comparison of conservative and aggressive transfusion regimes in the perioperative management of sickle cell disease. New England Journal of Medicine 1995;333(4):20613. Vichinsky EP, Neumayr LD, Haberkern C, Earles AN, Eckman J, Koshy M, et al.The perioperative complication rate of orthopedic surgery in sickle cell disease: report of the National Sickle Cell Surgery Study Group. American Journal of Hematology 1999;62(3): 12938. Waldron P, Pegelow C, Neumayr L, Haberkern C, Earles A, Wesman R, et al.ENT surgery in sickle cell disease: perioperative morbidity [abstract]. Proceedings of the 22nd Annual Meeting of the National Sickle Cell Disease Program. 1997:124. Waldron P, Pegelow C, Neumayr L, Haberkern C, Earles A,
Wesman R, et al.Tonsillectomy, adenoidectomy and myringotomy in sickle cell disease: perioperative morbidity. Journal of Pediatric Hematology/Oncology 1999;21(2):12935.
References to studies excluded from this review

Wali 2003 {published data only} Wali YA, al Okbi H, al Abri R. A comparison of two transfusion regimens in the perioperative management of children with sickle cell disease undergoing adenotonsillectomy. Pediatric Hematology and Oncology 2003;20(1):713.
Additional references
Bhattacharyya 1993 Bhattacharyya N, Wayne AS, Kevy SV, Shamberger RC. Perioperative management for cholecystectomy in sickle cell disease. Journal of Pediatric Surgery 1993;28(1):725. Bischoff 1988 Bischoff RJ, Williamson A, Dalali MJ, Rice JC, Kerstein MD. Assessment of the use of transfusion therapy perioperatively in patients with sickle cell hemoglobinopathies. Annals of Surgery 1988;207(4):4348. Brugnara 2000 Brugnara C. Red cell dehydration in pathophysiology and treatment of sickle cell disease. Web-site: Joint centre for sickle cell and thalassaemic disorders, Harvard Medical School 2000. Buchanan 1995 Buchanan GR, Rogers ZR. Conservative versus aggressive transfusion regimens in sickle cell disease [letter]. New England Journal of Medicine 1995;333(24):16412. Charache 1995 Charache S, Terrin ML, Moore RD, Dover GJ, Barton FB, Eckert SV, et al.Effect of hydroxyurea on the frequency of painful crises in sickle cell anemia. New England Journal of Medicine 1995;332(20): 131722. Cohen 1988 Cohen MM, Duncan PG, Tate RB. Does anaesthesia contribute to operative mortality?. Journal of the American Medical Association 1988;260(19):285963. Davies 1996 Davies SC, Roberts IA. Bone marrow transplant for sickle cell disease - an update. Archives of Disease in Childhood 1996;75(1): 36. Davies 1997 Davies SC, Oni L. Management of patients with sickle cell disease. British Medical Journal 1997;315(7109):65660. Fullerton 1981 Fullerton MW, Philippart AI, Sarnaik S, Lusher JM. Preoperative exchange transfusion in sickle cell anaemia. Journal of Pediatric Surgery 1981;16(3):297300. Grifn 1993 Grifn TC, Buchanan GR. Elective surgery in children with sickle cell disease without preoperative blood transfusion. Journal of Pediatric Surgery 1993;28(5):6815.
11
Haberkern 1997 Haberkern CM, Neumayr LD, Orringer EP, Earles AN, Robertson SM, Black D, et al.Cholecystectomy in sickle cell anaemia patients: perioperative outcome of 364 cases from the National Preoperative Transfusion Study. Blood 1997;89(5):153342. Halvorson 1997 Halvorson DJ, McKie V, McKie K, Ashmore PE, Porubsky ES. Sickle cell disease and tonsillectomy: preoperative management and postoperative complications. Archives in Otolaryngol Head and Neck Surgery 1997;123(7):68992. Hickman 1999 Hickman M, Modell B, Greengross P, Chapman C, Layton M, Falconer S, et al.Mapping the prevalence of sickle cell and beta thalassaemia in England: estimating and validating ethnic-specic rates. British Journal of Haematology 1999;104(4):8607. Higgins 2003 Higgins JPT, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ 2003;327(7414):55760. Homi 1979 Homi J, Reynolds J, Skinner A, Hanna W, Serjeant G. General anaesthesia in sickle cell disease. British Medical Journal 1979;1 (6178):15991601. Neumayr 1998 Neumayr L, Koshy M, Haberkern C, Earles AN, Bellevue R, Hassell, K, et al.Surgery in patients with hemoglobin SC disease. American Journal of Hematology 1998;57:1018. Ohene-Frempong 1999 Ohene-Frempong K. Sickle cell disease in the United States of America and Africa [abstract]. Hematology 1999:64. Orringer 1995 Orringer EP, Olivieri NF, Neumayr L, Haberkern C, Vichinsky EP. Is preoperative transfusion always necessary in sickle cell anemia (SCA)? [abstract]. Blood 1995;86 Suppl:300a. Platt 1994 Platt OS, Brambilla DJ, Rosse WF, Milner PF, Castro O, Steinberg MH, et al.Mortality in sickle cell disease: life expectancy and risk
factors for early death. New England Journal of Medicine 1994;330 (23):163944. Schulz 1995 Schulz KF, Chalmers I, Hayes RJ, Altman DG. Empirical evidence of bias. Dimensions of methodological quality associated with estimates of treatment effects in controlled trials. Journal of the American Medical Association 1995;273(5):40812. Serjeant 1992 Serjeant GR. Surgery and anaesthesia. Sickle Cell Disease. Oxford Medical Publications, 1992:4558. Thame 1999 Thame JR, Hambleton IR, Serjeant GR. Transfusion experience in the Jamaican cohort study of sickle cell disease [abstract]. West Indian Medical Journal 1999;48(Suppl 2):21. Vichinsky 1990 Vichinsky EP, Earles A, Johnson RA, Hoag MS, Williams A, Lubin B. Alloimmunization in sickle cell anaemia and transfusion of racially unmatched blood. New England Journal of Medicine 1990; 322(23):161721. Vichinsky 1999 Vichinsky EP, Neumayr LD, Haberkern C, Earles AN, Eckman J, Koshy M, et al.The perioperative complication rate of orthopedic surgery in sickle cell disease: report of the National Sickle Cell Surgery Study Group. American Journal of Hematology 1999;62(3): 12938. Waldron 1999 Waldron P, Pegelow C, Neumayr L, Haberkern C, Earles A, Wesman R, et al.Tonsillectomy, adenoidectomy and myringotomy in sickle cell disease: perioperative morbidity. Journal of Pediatric Hematology/Oncology 1999;21(2):12935. Ware 1988 Ware R, Filston H, Schultz WH, Kinney TR. Elective cholecystectomy in children with sickle hemoglobinopathies. Successful outcome using a preoperative transfusion regimen. Annals of Surgery 1988;208(1):1722. Indicates the major publication for the study
12
CHARACTERISTICS OF STUDIES
Characteristics of included studies [ordered by study ID]

Al-Jaouni 2006 Methods Participants Interventions Outcomes Randomised controlled trial, method of randomisation not specied. 369 participants with sickle cell anaemia. Preoperative simple or partial exchange transfusion versus no preoperative transfusion. Painful crises, neurological complications, respiratory complications, circulatory overload, infections, delay of surgery.
Notes Risk of bias Item Adequate sequence generation? Allocation concealment? Blinding? All outcomes Authors judgement Unclear Unclear Unclear Description Not reported. Not reported. Double blinding not possible for participants and clinicians, not clear of outcome assessors were blinded. It was not stated whether an intention-totreat analysis was used.
Incomplete outcome data addressed? All outcomes
Unclear
Vichinsky 1995 Methods Participants Interventions Randomised controlled trial, method of randomisation not specied. 551 participants with homozygous sickle cell disease conrmed by electrophoresis. Aggressive (HbS < 30%) versus conservative (Hb > 10 g/dl) preoperative blood transfusion. Death, miscellaneous intra-operative event, acute chest syndrome, fever or infection, miscellaneous post-operative event, painful crisis, neurological event, renal complication.
Outcomes
Notes Risk of bias
13
Vichinsky 1995
(Continued)
Item Adequate sequence generation?
Authors judgement Unclear
Description Randomisation sequence generation was not recorded. Concealment of allocation was not recorded. Double blinding not possible for participants and clinicians, not clear of outcome assessors were blinded. It was not stated whether an intention-totreat analysis was used. Of the original data collected on 692 randomly allocated surgical procedures, 88 (12.7% of study population) were subsequently excluded due to cancellation of the surgery, diagnostic error or refusal of the individual to participate in the study. 42 were from Group 1 and 46 from Group 2. While it is stated that the participant characteristics of this group were similar in both groups, and that the age range was representative of the whole sample, the fairly limited information of participant characteristics provided in the paper, and the high exclusion rate, detracts somewhat from the study.
Allocation concealment?
Unclear
Blinding? All outcomes
Unclear
Incomplete outcome data addressed? All outcomes
Unclear
Hb: haemoglobin HbS: sickle cell haemoglobin
Characteristics of excluded studies [ordered by study ID]
Wali 2003
Participants were not randomised to treatment groups.
14
DATA AND ANALYSES
Comparison 1. Aggressive versus conservative blood transfusion
Outcome or subgroup title 1 Perioperative mortality 2 Serious complications related to sickle cell disease 2.1 Acute chest syndrome 2.2 Painful crisis 2.3 Neurological event 2.4 Renal complication 2.5 Miscellaneous 3 Postoperative Infection 3.1 Perioperative 3.2 Postoperative 4 Life-threatening surgical complications 5 Transfusion related complications 5.1 Alloimmunisation 5.2 Haemolysis 5.3 Allergic or anaphylactic reaction 5.4 Miscellaneous 6 Blood counts 6.1 Pre-transfusion haemoglobin 6.2 Preoperative haemoglobin 6.3 Preoperative haemoglobin S percentage 6.4 White blood cells 7 Volume of blood transfusion/ venesected
No. of studies 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 0 1
No. of participants
Statistical method Odds Ratio (M-H, Fixed, 95% CI) Odds Ratio (M-H, Fixed, 95% CI) Odds Ratio (M-H, Fixed, 95% CI) Odds Ratio (M-H, Fixed, 95% CI) Odds Ratio (M-H, Fixed, 95% CI) Odds Ratio (M-H, Fixed, 95% CI) Odds Ratio (M-H, Fixed, 95% CI) Odds Ratio (M-H, Fixed, 95% CI) Odds Ratio (M-H, Fixed, 95% CI) Odds Ratio (M-H, Fixed, 95% CI) Odds Ratio (M-H, Fixed, 95% CI) Odds Ratio (M-H, Fixed, 95% CI) Odds Ratio (M-H, Fixed, 95% CI) Odds Ratio (M-H, Fixed, 95% CI) Odds Ratio (M-H, Fixed, 95% CI) Odds Ratio (M-H, Fixed, 95% CI) Mean Difference (IV, Fixed, 95% CI) Mean Difference (IV, Fixed, 95% CI) Mean Difference (IV, Fixed, 95% CI) Mean Difference (IV, Fixed, 95% CI) Mean Difference (IV, Fixed, 95% CI) Mean Difference (IV, Fixed, 95% CI)
Effect size Totals not selected Totals not selected Not estimable Not estimable Not estimable Not estimable Not estimable Totals not selected Not estimable Not estimable Totals not selected Totals not selected Not estimable Not estimable Not estimable Not estimable Totals not selected Not estimable Not estimable Not estimable Not estimable Not estimable
604
15
Comparison 2. Preoperative blood transfusion versus no transfusion
Outcome or subgroup title 1 Perioperative mortality 2 Serious complications related to sickle cell disease 2.1 Painful crises 2.2 Neurological complications 2.3 Respiratory complications 3 Postoperative Infection 4 Life-threatening surgical complications 5 Transfusion related complications 5.1 Circulatory overload 6 Blood counts 7 Volume of blood transfused/ venesected
No. of studies 0 1 1 1 1 1 0 1 1 0 0
No. of participants 0
Statistical method Odds Ratio (M-H, Fixed, 95% CI) Odds Ratio (M-H, Fixed, 95% CI) Odds Ratio (M-H, Fixed, 95% CI) Odds Ratio (M-H, Fixed, 95% CI) Odds Ratio (M-H, Fixed, 95% CI) Odds Ratio (M-H, Fixed, 95% CI) Odds Ratio (M-H, Fixed, 95% CI) Odds Ratio (M-H, Fixed, 95% CI) Odds Ratio (M-H, Fixed, 95% CI) Mean Difference (IV, Fixed, 95% CI) Mean Difference (IV, Fixed, 95% CI)
Effect size Not estimable Totals not selected Not estimable Not estimable Not estimable Totals not selected Not estimable Totals not selected Not estimable Not estimable Not estimable
0 0
Analysis 1.1. Comparison 1 Aggressive versus conservative blood transfusion, Outcome 1 Perioperative mortality.
Review: Preoperative blood transfusions for sickle cell disease
Comparison: 1 Aggressive versus conservative blood transfusion Outcome: 1 Perioperative mortality
Study or subgroup
Aggressive n/N
Conservative n/N 0/273
Odds Ratio M-H,Fixed,95% CI
Odds Ratio M-H,Fixed,95% CI 4.95 [ 0.24, 103.49 ]
Vichinsky 1995
2/278
0.01
0.1
10
100
Favours aggressive
Favours conservative
16
Analysis 1.2. Comparison 1 Aggressive versus conservative blood transfusion, Outcome 2 Serious complications related to sickle cell disease.
Comparison: 1 Aggressive versus conservative blood transfusion Outcome: 2 Serious complications related to sickle cell disease
Study or subgroup
Aggressive n/N
Conservative n/N
1 Acute chest syndrome Vichinsky 1995 2 Painful crisis Vichinsky 1995 3 Neurological event Vichinsky 1995 4 Renal complication Vichinsky 1995 5 Miscellaneous Vichinsky 1995 18/303 15/301 1.20 [ 0.60, 2.44 ] 3/303 1/301 3.00 [ 0.31, 29.00 ] 3/303 3/301 0.99 [ 0.20, 4.96 ] 15/303 21/301 0.69 [ 0.35, 1.37 ] 33/303 30/301 1.10 [ 0.65, 1.86 ]
0.1 0.2
0.5
10
Favours aggressive
Analysis 1.3. Comparison 1 Aggressive versus conservative blood transfusion, Outcome 3 Postoperative Infection.
Comparison: 1 Aggressive versus conservative blood transfusion Outcome: 3 Postoperative Infection
Study or subgroup
Aggressive n/N
Conservative n/N
1 Perioperative Vichinsky 1995 2 Postoperative Vichinsky 1995 22/303 15/301 1.49 [ 0.76, 2.94 ] 22/303 21/301 1.04 [ 0.56, 1.94 ]
0.2
0.5
Favours aggressive
17
Analysis 1.4. Comparison 1 Aggressive versus conservative blood transfusion, Outcome 4 Life-threatening surgical complications.
Comparison: 1 Aggressive versus conservative blood transfusion Outcome: 4 Life-threatening surgical complications
Study or subgroup
Aggressive n/N
Conservative n/N 60/301
Vichinsky 1995
53/303
0.1 0.2
0.5
10
Favours aggressive
Analysis 1.5. Comparison 1 Aggressive versus conservative blood transfusion, Outcome 5 Transfusion related complications.
Comparison: 1 Aggressive versus conservative blood transfusion Outcome: 5 Transfusion related complications
Study or subgroup
Aggressive n/N
Conservative n/N
1 Alloimmunisation Vichinsky 1995 2 Haemolysis Vichinsky 1995 3 Allergic or anaphylactic reaction Vichinsky 1995 4 Miscellaneous Vichinsky 1995 10/303 4/301 2.53 [ 0.79, 8.17 ] 1/303 3/301 0.33 [ 0.03, 3.18 ] 19/303 4/301 4.97 [ 1.67, 14.78 ] 31/303 14/301 2.34 [ 1.22, 4.49 ]
0.1 0.2
0.5
10
Favours aggressive
18
Analysis 1.6. Comparison 1 Aggressive versus conservative blood transfusion, Outcome 6 Blood counts.
Comparison: 1 Aggressive versus conservative blood transfusion Outcome: 6 Blood counts
Study or subgroup
Aggressive N Mean(SD)
Conservative N Mean(SD)
Mean Difference IV,Fixed,95% CI
1 Pre-transfusion haemoglobin Vichinsky 1995 2 Preoperative haemoglobin Vichinsky 1995 303 11 (0) 301 10.6 (0) 0.0 [ 0.0, 0.0 ] 303 8 (0) 301 7.9 (0) 0.0 [ 0.0, 0.0 ]
3 Preoperative haemoglobin S percentage Vichinsky 1995 4 White blood cells 303 31 (0) 301 59 (0) 0.0 [ 0.0, 0.0 ]
-10
-5
10
Favours aggressive
Analysis 1.7. Comparison 1 Aggressive versus conservative blood transfusion, Outcome 7 Volume of blood transfusion/venesected.
Comparison: 1 Aggressive versus conservative blood transfusion Outcome: 7 Volume of blood transfusion/venesected
Study or subgroup
Aggressive N Mean(SD) 5 (0)
Conservative N 301 Mean(SD) 2.5 (0)
Mean Difference IV,Fixed,95% CI 0.0 [ 0.0, 0.0 ]
Vichinsky 1995
303
Total (95% CI)

Heterogeneity: not applicable
303
301
0.0 [ 0.0, 0.0 ]
Test for overall effect: Z = 0.0 (P < 0.00001)
-10
-5
10
Favours aggressive
19
Analysis 2.2. Comparison 2 Preoperative blood transfusion versus no transfusion, Outcome 2 Serious complications related to sickle cell disease.
Comparison: 2 Preoperative blood transfusion versus no transfusion Outcome: 2 Serious complications related to sickle cell disease
Study or subgroup
Transfusion n/N
No transfusion n/N
1 Painful crises Al-Jaouni 2006 2 Neurological complications Al-Jaouni 2006 3 Respiratory complications Al-Jaouni 2006 7/188 5/181 1.36 [ 0.42, 4.37 ] 4/188 0/181 8.85 [ 0.47, 165.63 ] 5/188 3/181 1.62 [ 0.38, 6.88 ]
0.01
0.1
10
100
Favours transfusion
Favrs no transfusion
Analysis 2.3. Comparison 2 Preoperative blood transfusion versus no transfusion, Outcome 3 Postoperative Infection.
Comparison: 2 Preoperative blood transfusion versus no transfusion Outcome: 3 Postoperative Infection
Study or subgroup
Transfusion n/N
No transfusion n/N 3/181
Al-Jaouni 2006
3/188
0.1 0.2
0.5
10
Favours transfusion
Favrs no transfusion
20
Analysis 2.5. Comparison 2 Preoperative blood transfusion versus no transfusion, Outcome 5 Transfusion related complications.
Comparison: 2 Preoperative blood transfusion versus no transfusion Outcome: 5 Transfusion related complications
Study or subgroup
Transfusion n/N
No transfusion n/N
1 Circulatory overload Al-Jaouni 2006 5/188 0/181 10.88 [ 0.60, 198.20 ]
0.001 0.01 0.1 Favours transfusion
10 100 1000 Favrs no transfusion
WHATS NEW
Last assessed as up-to-date: 14 December 2009.
15 December 2009
New search has been performed
A search of the Groups Trials Register identied the full published paper to an already included abstract (Al-Jaouni 2006).
HISTORY
Protocol rst published: Issue 3, 2001 Review rst published: Issue 3, 2001
1 October 2008 1 August 2007 1 August 2007
Amended Amended New search has been performed
Converted to new review format. The Synopsis has been replaced by a Plain language summary. The search of the Haemoglobinopathies Trials Register identied no new trials eligible for inclusion in this review. The search of the Haemoglobinopathies Trials Register identied no new trials eligible for inclusion in this review. The search of the Haemoglobinopathies Trials Register identied no new trials eligible for inclusion in the review. The lead author has changed her family name from Riddington to Hirst.
1 August 2006
1 April 2005
21
(Continued)
1 March 2004
The searches found two new trials. One trial was eligible for inclusion (AlJaouni 2002), but the other was ineligible, as it did not use a randomised design (Wali 2003). The new data from the Al-Jaouni trial demonstrated no advantage in using preoperative blood transfusion in 369 people with sickle cell disease undergoing surgery in Saudi Arabia. There was no signicant reduction in sickle related events in the preoperative transfusion group, and an increase in transfusion related complications. The searches found no new trials eligible for inclusion. No further data to add, no substantive update.
3 March 2003 1 February 2002
New search has been performed New search has been performed
CONTRIBUTIONS OF AUTHORS
The review was conceived by the Cochrane Cystic Fibrosis and Genetic Disorders Group and designed by Dr Hirst (ne Riddington). Dr Hirst and the Cochrane Cystic Fibrosis and Genetic Disorders Group conducted searches for relevant studies. Dr Hirst and Dr Williamson screened, appraised and abstracted data for the review. Dr Hirst sought additional information from authors where necessary. Dr Hirst performed data entry and interpretation with advice from the Cochrane Cystic Fibrosis and Genetic Disorders Group. Dr Hirst, with support from Dr Williamson, undertook subsequent updates of the review.
DECLARATIONS OF INTEREST
Since completion of the review, Ceri Hirst has received funding from several pharmaceutical companies for contract research unrelated to the review topic.
SOURCES OF SUPPORT Internal sources

No sources of support supplied
22
External sources
Research and Development - Research & Development Programme, UK.
INDEX TERMS Medical Subject Headings (MeSH)

Anemia, Sickle Cell [surgery; therapy]; Blood Transfusion [ methods]; Preoperative Care
MeSH check words

Humans
23

Preoperative Blood Transfusions For Sickle Cell Disease (Review)

Загружено:

Сведения о документе

Оригинальное название

Авторское право

Доступные форматы

Поделиться этим документом

Поделиться или встроить документ

Параметры публикации

Этот документ был вам полезен?

Это неприемлемый материал?

Авторское право:

Доступные форматы

Preoperative Blood Transfusions For Sickle Cell Disease (Review)

Загружено:

Авторское право:

Доступные форматы

Preoperative blood transfusions for sickle cell disease (Review)

Preoperative blood transfusions for sickle cell disease

Contact address: Ceri Hirst, AstraZeneca, Parklands Ceri.Hirst@astrazeneca.com. criddington@hotmail.com.

Description of the condition

Description of the intervention

Criteria for considering studies for this review

Why it is important to do this review

Data collection and analysis

Search methods for identication of studies

Table 1. Patient characteristics - Vichinsky 1995

Table 1. Patient characteristics - Vichinsky 1995

Risk of bias in included studies

Preoperative blood transfusion versus no transfusion

One study evaluated this comparison (Al-Jaouni 2006).

AUTHORS CONCLUSIONS Implications for practice

Implications for research

References to studies included in this review

References to studies excluded from this review

Characteristics of included studies [ordered by study ID]

Incomplete outcome data addressed? All outcomes

Notes Risk of bias

Item Adequate sequence generation?

Authors judgement Unclear

Blinding? All outcomes

Incomplete outcome data addressed? All outcomes

Hb: haemoglobin HbS: sickle cell haemoglobin

Characteristics of excluded studies [ordered by study ID]

Participants were not randomised to treatment groups.

DATA AND ANALYSES

Comparison 1. Aggressive versus conservative blood transfusion

Comparison 2. Preoperative blood transfusion versus no transfusion

Comparison: 1 Aggressive versus conservative blood transfusion Outcome: 1 Perioperative mortality

Conservative n/N 0/273

Odds Ratio M-H,Fixed,95% CI

Odds Ratio M-H,Fixed,95% CI 4.95 [ 0.24, 103.49 ]

Odds Ratio M-H,Fixed,95% CI

Odds Ratio M-H,Fixed,95% CI

Comparison: 1 Aggressive versus conservative blood transfusion Outcome: 3 Postoperative Infection

Odds Ratio M-H,Fixed,95% CI

Odds Ratio M-H,Fixed,95% CI

Conservative n/N 60/301

Odds Ratio M-H,Fixed,95% CI

Odds Ratio M-H,Fixed,95% CI 0.85 [ 0.57, 1.28 ]

Odds Ratio M-H,Fixed,95% CI

Odds Ratio M-H,Fixed,95% CI

Comparison: 1 Aggressive versus conservative blood transfusion Outcome: 6 Blood counts

Mean Difference IV,Fixed,95% CI

Mean Difference IV,Fixed,95% CI

Aggressive N Mean(SD) 5 (0)

Conservative N 301 Mean(SD) 2.5 (0)

Mean Difference IV,Fixed,95% CI

Mean Difference IV,Fixed,95% CI 0.0 [ 0.0, 0.0 ]

Total (95% CI)

0.0 [ 0.0, 0.0 ]

Test for overall effect: Z = 0.0 (P < 0.00001)

Odds Ratio M-H,Fixed,95% CI

Odds Ratio M-H,Fixed,95% CI

Comparison: 2 Preoperative blood transfusion versus no transfusion Outcome: 3 Postoperative Infection

No transfusion n/N 3/181

Odds Ratio M-H,Fixed,95% CI

Odds Ratio M-H,Fixed,95% CI 0.96 [ 0.19, 4.83 ]

Odds Ratio M-H,Fixed,95% CI

Odds Ratio M-H,Fixed,95% CI