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Red cell transfusion management for patients undergoing cardiac surgery for congenital heart disease

  1. Kirstin L Wilkinson1,*,
  2. Susan J Brunskill2,
  3. Carolyn Doree2,
  4. Marialena Trivella3,
  5. Ravi Gill4,
  6. Michael F Murphy5

Editorial Group: Cochrane Heart Group

Published Online: 7 FEB 2014

Assessed as up-to-date: 11 DEC 2013

DOI: 10.1002/14651858.CD009752.pub2


How to Cite

Wilkinson KL, Brunskill SJ, Doree C, Trivella M, Gill R, Murphy MF. Red cell transfusion management for patients undergoing cardiac surgery for congenital heart disease. Cochrane Database of Systematic Reviews 2014, Issue 2. Art. No.: CD009752. DOI: 10.1002/14651858.CD009752.pub2.

Author Information

  1. 1

    Southampton University NHS Hospital, Paediatric and Adult Cardiothoracic Anaesthesia, Southampton, UK

  2. 2

    NHS Blood and Transplant, Systematic Review Initiative, Oxford, Oxon, UK

  3. 3

    University of Oxford, Centre for Statistics in Medicine, Oxford, UK

  4. 4

    Southampton University Hospital NHS Trust, Department of Anaesthetics, Southampton, Hampshire, UK

  5. 5

    John Radcliffe Hospital, NHS Blood and Transplant, Oxford, UK

*Kirstin L Wilkinson, Paediatric and Adult Cardiothoracic Anaesthesia, Southampton University NHS Hospital, Tremona Road, Southampton, SO16 6YD, UK. kirstinwilkinson@hotmail.com.

Publication History

  1. Publication Status: New
  2. Published Online: 7 FEB 2014

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Background

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. Contributions of authors
  13. Declarations of interest
  14. Sources of support
  15. Differences between protocol and review
  16. Notes
  17. Index terms
 

Description of the condition

Congenital heart disease describes the presence of a structural abnormality of the heart present form birth (Bédard 2008), and more specifically a gross structural abnormality of the heart or intrathoracic great vessels that is actually or potentially of functional importance (Mitchell 1971). Although there is worldwide variation, primarily due to the ability to detect trivial lesions (Hoffman 2002), the estimated incidence is four to nine cases per 1000 live born infants (Dolk 2011; Perloff 2001). It is the most common congenital condition diagnosed in neonates (Gatzoulis 2005) with congenital heart defects accounting for 30% of all live born infants with a major congenital anomaly (EURO-PERISTAT project 2008). Neonates are born with a wide range of defects, for example, atrial and ventricular septal defects, transposition of the great arteries and tetralogy of Fallot (Bédard 2008).

The defects may be broadly classified into cyanotic or acyanotic heart disease. Cyanotic heart disease is caused by an increased amount of reduced haemoglobin (non-oxygenated blood) from either mixing of oxygenated and non-oxygenated blood (right to left shunting or univentricular heart) or inadequate pulmonary blood flow (underdeveloped pulmonary vasculature or progressive pulmonary hypertension). Examples of cyanotic lesions are transposition of the great arteries, truncus arteriosus and hypoplastic left heart syndrome. Acyanotic heart disease describes infants with normal oxygen levels (e.g. congenital aortic stenosis, atrioseptal defect, ventricular septal defect (Gatzoulis 2005)). Patients with cyanotic heart disease have high haemoglobin and haematocrit levels and this has been shown to be a significant risk factor for perioperative bleeding and blood product use (Williams 1999).

Surgery for congenital heart disease aims to reduce mortality and morbidity. In the 1950s, without surgery, of 10 affected children born alive, two would die by the end of the first week, a further one or two by the end of the first month, with six in total having died by the end first year. Only three or four would survive to 10 years old (MacMahon 1953). Since this time, an improvement in diagnostic, interventional and surgical techniques has produced an overall dramatic decrease in mortality and morbidity rates (British Cardiac Society 2002). Between 1965 and 1975 in Canada, survival rates in the first month after surgery rose from 37% to 70% (Izukawa 1979). Between 1999 and 2006 in the US, overall mortality from congenital heart disease fell by 24.1% (Gilboa 2010). Surgical survival at one year in the UK was approximately 95% in 2006 to 2007 (CCAD 2008).

Patients present for surgery at a variable age according to the underlying defect but there are three main groups; neonates (within four weeks of birth), paediatrics (four weeks to 16 years) and adult congenital (over 16 years). The surgery may be either corrective (completely corrects the lesion into a normal circulation) or palliative (changes the anatomy/circulation into one that is more compatible with life). Whether the surgery is corrective or palliative depends on the underlying defect. Some patients will undergo a sequence of surgeries to correct their defects (e.g. patients with hypoplastic left heart syndrome) while other patients will need repeat operations. Almost half of adult congenital cardiac surgical operations are repeat operations (van der Bom 2011).

Mortality and morbidity are variable. For some defects (e.g. atrioseptal defects) surgery is relatively routine. For other defects, the patient is critically unwell and surgery has a very significant associated morbidity and mortality. Hypoplastic left heart syndrome is an example where children are often critically unwell at presentation and surgery has a significant mortality risk. These children will undergo a palliative three-stage repair throughout their early childhood. The first stage is the Norwood procedure where early mortality is estimated at 29% (McGuirk 2006). The second stage is the bidirectional Glenn procedure followed by the Fontan procedure (total cavopulmonary connection). One study in the US cited hypoplastic left heart syndrome as the greatest specific diagnosis contributor to overall congenital heart disease mortality at 10.9% of all deaths (Gilboa 2010).

More children are surviving after surgery for congenital heart disease with 80% to 85% expected to reach adulthood (Khairy 2010; Nieminen 2001; Wren 2001). Despite excellent outcomes for many individuals, challenges remain in all patient groups especially those at higher risk, such as neonates, premature infants and patients undergoing complex surgery (Cheng 2011; Padley 2011). About 10.4% of all UK infants who died in one UK-based study population had a cardiovascular malformation (Wren 2012). Adult re-operations are associated with significant morbidity and mortality with early mortality rates between 3.6% and 7.6%, and 15% to 24% of patients experiencing serious postoperative complications (Berdat 2004; Giamberti 2009). Research now focuses on further reducing mortality and maybe even more importantly, on decreasing perioperative morbidity (Gatzoulis 2005).

 

Description of the intervention

Patients undergoing cardiac surgery for congenital heart disease are potentially exposed to red cell transfusion at many points in the surgical pathway; to treat anaemia preoperatively, correct blood loss during surgery, haemodilution while on cardiopulmonary bypass (CPB), and ongoing blood loss or haemodilution in the intensive care unit (ICU) or the ward post surgery. 

CPB replaces the work of the heart and lungs allowing the heart to be stopped during surgery, providing a still and bloodless field for the surgeon (Allman 2002). The blood is oxygenated, carbon dioxide is removed and then the blood is returned to the patient. The circuit provides a continuous circulation between the venous cannula draining blood from the patient and the aortic cannula returning blood to the patient. The circuit tubing is primed with fluid to prevent air passing from the circuit into the patient. This fluid is known as the bypass prime and it may have a number of components (Allman 2002). If it does not contain any red cells, it is known as a clear or bloodless prime. As the bypass prime mixes with the patient's own circulation, there is a risk of excessive haemodilution so red cells are added to prevent this. Red cells can be added into the prime volume before bypass or into the bypass pump once the patient is on bypass. A neonate is likely to undergo 60% haemodilution on bypass (Eaton 2005), so is almost always likely to have donor red cells added to the CPB prime (Groom 2005). However, a number of centres have been investigating bloodless CPB prime to reduce exposure to red cell transfusion (Ging 2008; Golab 2009; Miyaji 2007; Olshove 2010).

Despite improvements in the risks associated with red cell transfusion, many still exist. These risks can result in increased morbidity and mortality, especially in the critically ill patient population (Hebert 1999; Vincent 2002). In previous years, the major concerns were with the transmission of infection, especially hepatitis C virus and human immunodeficiency virus (HIV) (Guzzetta 2011; Morley 2009). Through donor screening and donation testing, the infectious risks are now small in developed countries with the quoted risk of hepatitis C being one in 100 million, hepatitis B one in one million and HIV one in 6.25 million (SHOT 2011). However, some countries do not have the same rigorous testing systems and infection transmission remains a real risk. The 2007 World Health Organization (WHO) Blood Safety Survey showed that out of 162 countries, 41 were not able to screen for one or more transfusion-transmissible infections (HIV, hepatitis B and hepatitis C) (WHO Blood 2013).

As transfusion medicine practice has developed and improved, the focus of risks associated with red cell transfusion has shifted to non-infectious sequelae with the main current issues of adverse transfusion reactions, acute lung injury and the negative effects of immunomodulation (Raghavan 2005).

Adverse transfusion reactions are a real concern. Children under 18 years old receive 4.2% of all red cell transfusions while children under one year old receive 1.7% (Wallis 2006). However, children have a disproportionately higher number of adverse reactions when compared with adults: 37 in 100,000 for children under one year old, 18 in 100,000 transfusion for children under 18 years, while for adults it is 13 in 100,000 (Stainsby 2008).

Transfusion-related acute lung injury (TRALI): new acute lung injury occurring during or within six hours of a transfusion (Lavoie 2011) is estimated to have an incidence between 0.08% and 15% of patients receiving a transfusion (Benson 2010; Silliman 2003) with an adult mortality of 5% to 10% (Vlaar 2013). Although reported to be rare in children, it is probably under-reported as it can be difficult to diagnose (Harrison 2011).

The negative effects of immunomodulation and red cell storage are increased nosocomial infections and the development of autoimmune diseases or cancer (Raghavan 2005; Sanchez 2005). Critically ill patients have been shown to have a six-fold incidence of developing a nosocomial infection when transfused with red cells compared with those not transfused and this incidence is dose-related with each additional unit of blood increasing the risk by a factor of 1.5 (Taylor 2002).

The recognition of these risks associated with red cell transfusion has led to a more critical appraisal of the use of red cell transfusion. Although red blood cells are transfused more frequently than any other blood component, their overall usage in the UK has been declining with a decrease of around 20% in the 10 years from 1999/2000 (SHOT 2011).

Literature in critically unwell patient groups suggests that avoiding red cell transfusions may reduce morbidity, which explains the trend to reduce such exposure. Adult critical care patients subjected to a restrictive transfusion policy were shown to have a similar 30-day mortality during hospitalisation when compared with those with a liberal transfusion policy (18.7% versus 23.3%) (Hebert 1999), with red cell transfusions suggested as an independent predictor of death with an odds ratio of 1.7 (Marik 2008).

Relatively few studies have examined the effects of red cell transfusion on critically ill children (Istaphanous 2011). Lacroix reported the results of a prospective randomised controlled trial (RCTs) comparing a restrictive versus liberal transfusion strategy in critically ill children showing a decrease in transfusion requirements in the restrictive group without increasing adverse outcomes. The study did caution the use of a restrictive strategy in children with cyanotic heart disease (Lacroix 2007).

Neonatal studies have also examined restrictive versus liberal transfusion strategies. One of the largest studies, the Premature Infants in Need of Transfusion (PINT) study, suggested that a liberal transfusion strategy in extremely low birth weight neonates resulted in more infants receiving transfusions but conferred little evidence or benefit (Kirpalani 2006). When this study was combined with three others (Bell 2005; Chen 2009; Connelly 1998), a Cochrane review concluded that restrictive as compared with liberal transfusion thresholds resulted in modest reductions in transfusion and haemoglobin levels. Restrictive practice did not appear to have significant impact on death or major morbidities at hospital discharge or first hospital follow-up. However, there were uncertainties with these conclusions and further trials are needed (Whyte 2011).

 

How the intervention might work

The most important physiological consequence of anaemia is reduced oxygen-carrying capacity of the blood. The optimal concentration of haemoglobin for avoidance of severe morbidity is unknown but animal experiments suggest the critical haemoglobin level for oxygen delivery to be 3 to 4 g/dL (Van der Linden 1998). Although healthy adult volunteers tolerate a haemoglobin of 5 g/dL with no increase in lactate production or decrease in oxygen consumption, they do show an increase in heart rate and a decline in cognitive function suggesting borderline tissue oxygen delivery (Weiskopf 2002). The physiological response to anaemia is to increase cardiac output so anaemia effectively consumes some of the cardiac reserve (Morley 2009). Patients with congenital heart disease and a marginal cardiac reserve often have a precarious oxygen supply/demand balance so anaemia may adversely alter this balance. Red cell transfusion augments tissue oxygen delivery by increasing the oxygen-carrying capacity of the blood (Guzzetta 2011). Many centres transfuse at a higher starting haemoglobin for patients with congenital heart disease when they require surgery or intensive care (Morley 2009).

The red cells that are transfused can vary in age and nature. They may or may not contain leukocytes, they may be fresh or old and they may come as packed cells or in whole blood. Each of these factors may be important in determining outcome for the transfusion recipient.

The negative immunomodulatory effects of red cell transfusion may be due to the presence of donor lymphocytes in transfused components (Morley 2009), and leukoreduction may reduce these negative effects (van de Watering 1998; van Hilten 2004).

Red blood cell function may become impaired with increased storage time (Morley 2009). Prolonged storage time may increase mortality, pneumonia, infection, multiorgan failure and length of hospital stay but these observations are based on laboratory and observational clinical studies and further work is needed (Tinmouth 2006).

Theoretically, whole blood should improve haemostasis and decrease systemic inflammation in comparison with packed red cells. Manno 1991 compared the immediate postoperative transfusion needs of children undergoing open-heart surgery with CPB with either whole blood or reconstituted whole blood (packed red cells, fresh frozen plasma and platelets). Transfusion with reconstituted blood significantly increased mean 24-hour postoperative blood loss in those less than two years old (85% more blood loss) but for those aged over two years undergoing surgery for simple defects, there was no significant difference between treatment groups.When whole blood was added into the bypass circuit prime, there were no significant differences in terms of bleeding and inflammatory mediator levels. There was a trend to longer ICU stay, greater positive fluid balance and longer hospital stay (Mou 2004).

In summary, the issues concerning red cell transfusion for patients with congenital heart disease relate to:

  1. What haemoglobin trigger should blood be transfused - can patients tolerate a lower (restrictive) haemoglobin concentration before they need to be transfused?
  2. How much blood to give - what volume of red cell transfusion should be given to reach the intended haemoglobin target?
  3. Leukoreduced versus non-leukoreduced - is there a benefit to removing leukocytes from the transfused red blood cells?
  4. Whole blood versus packed cells - do patients benefit from whole blood more than packed red cells?
  5. The age of red cells transfused: new versus old - do patients have better outcomes if they are transfused 'newer' red blood cells?

 

Why it is important to do this review

The patient population with congenital heart disease is small but they are surviving longer. Epidemiological studies have confirmed this decreasing mortality and prolonged survival in young patients resulting in a growing and ageing population with congenital heart disease (Khairy 2010; Knowles 2012; Wren 2001).

Although mortality and morbidity have improved, cardiac surgery for congenital heart disease remains a risk especially in neonatal, premature and those undergoing complex surgery populations. Blood transfusion has been associated with adverse outcomes in other critically unwell patient populations and the specialty of congenital heart disease has begun to address the specific risks to this population (Guzzetta 2011). Studies have tried to elicit the risk factors for adverse outcomes in patients undergoing surgery for congenital heart disease (Székely 2006). One secondary analysis suggested that intraoperative and early postoperative blood transfusion was a powerful independent predictor of duration of mechanical ventilation in infants undergoing reparative cardiac surgery (Kipps 2011). Infants receiving the highest volume of transfusion had a hazard of remaining intubated that was twice as high as infants receiving the lowest volume of transfusion. The total amount of blood transfusion has been independently associated with infections but not mortality (Székely 2009). Red cell transfusions have also been associated with longer hospital stay with the strongest association in the high transfusion group (Salvin 2011). This association was limited to patients with a biventricular and not a univentricular circulation. For patients with hypoplastic left heart syndrome, a higher haemoglobin nadir on postoperative days two to five was associated with higher early mortality but neither haemoglobin concentrations nor transfusions were associated with two-year mortality or neurodevelopmental outcomes. More transfusions two to five days postoperatively were associated with morbidity measured by ventilation days (Blackwood 2010).

There are no systematic reviews examining red cell transfusion in this patent population (Dorée 2010). Unanswered clinical questions include at what haemoglobin concentration should blood be given, how much blood should be given, what age (new versus old) and what type of blood should be used (leukoreduced or non-leukoreduced, irradiated or non-irradiated, packed cells or whole blood). This review aims to address these knowledge gaps and direct future research and clinical practice.

Although the three patient groups of neonates, paediatrics and adults appear different, the same questions exist for all of them and it is likely that a neonate will survive to adulthood and possibly require further surgery at a later stage. We assessed the three groups separately but kept them in the same review. Clinicians often manage these patients from birth to adulthood so the review will cover all ages.

 

Objectives

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. Contributions of authors
  13. Declarations of interest
  14. Sources of support
  15. Differences between protocol and review
  16. Notes
  17. Index terms

To evaluate the effects of red cell transfusion on mortality and morbidity on patients with congenital heart disease at the time of cardiac surgery.

 

Methods

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. Contributions of authors
  13. Declarations of interest
  14. Sources of support
  15. Differences between protocol and review
  16. Notes
  17. Index terms
 

Criteria for considering studies for this review

 

Types of studies

 We included RCTs in this review.

 

Types of participants

We included all patients undergoing cardiac surgery for congenital heart disease with no restriction on age. The congenital heart disease could be cyanotic or acyanotic. We grouped patients by age: neonates (newborns up to four weeks old), paediatrics (children four weeks post birth to age 16 years) and adults (over 16 years) and analysed them separately.

We excluded patients with congenital heart disease undergoing non-cardiac surgery and considered all co-morbidities.

 

Types of interventions

The intervention was red cell transfusion at any point in the surgical pathway. This included red cell transfusion intraoperatively directly into the patient or into the CPB machine (either into the prime cardiopulmonary volume before bypass or subsequently into the cardiopulmonary pump volume during bypass) or postoperatively during their hospital stay.

We included the following comparisons:

  • Restrictive transfusion trigger versus liberal transfusion trigger - blood was transfused at two or more different patient haemoglobin concentrations with liberal transfusion trigger being higher than restrictive (different studies chose different haemoglobin concentrations but were around haemoglobin 7 to 8 g/dL for restrictive and 9 to 10 g/dL for liberal).
  • Volume A red cell transfusion versus volume B red cell transfusion (e.g. higher volume versus lower volume (different mL/kg)). The standard advised resuscitation volume for paediatric patients is 20 mL/kg so the doses were likely to be factors of 20 mL/kg.
  • Leukoreduced red cell transfusion versus non-leukoreduced red cell transfusion.
  • Whole blood versus packed red cell transfusion.
  • 'New' (not near to expiry date) versus 'old' (near to expiry date) red cell transfusion. In the UK, red blood cells up to five days old may be given for neonates and up to 35 days old for paediatric patients so each group contained comparison groups appropriate to the suggested national guidelines (BCSH 2004).
  • Standard CPB prime versus non-standard CPB prime (e.g. bloodless prime or different methods of processing the prime).

 

Types of outcome measures

 

Primary outcomes

  • All-cause mortality: short term (0 to 30 days post surgery).

 

Secondary outcomes

  • All-cause mortality: long term: 30 days to two years post surgery.
  • Severe adverse events: cardiac events, acute lung injury, stroke, thromboembolism, renal failure (needing renal replacement therapy), infection, haemorrhage (return to theatre for bleeding).
  • Haematocrit/haemoglobin (g/dL) concentrations post operative and at discharge.
  • Volume or number of red cell units transfused.
  • Volume or number of other blood products transfused (i.e. fresh frozen plasma, platelets, cryoprecipitate).
  • Postoperative chest drain output.
  • Duration of mechanical ventilation.
  • Duration of ICU stay.
  • Re-hospitalisation rates.
  • Biochemistry levels (added post-hoc).

 

Search methods for identification of studies

 

Electronic searches

The Systematic Review Initiative's information specialist (CD) formulated the search strategies in collaboration with the Cochrane Heart Group. We searched the following databases.

 

Bibliographic databases

  • Cochrane Central Register of Controlled Trials (CENTRAL, Issue 5, 2013).
  • MEDLINE (Ovid) (1950 to 11 June 2013).
  • EMBASE (Ovid) (1980 to 11 June 2013).
  • PubMed (e-publications only: searched 11 June 2013).
  • CINAHL (EBSCO) (1982 to 11 June 2013).
  • LILACS (searched 11 June 2013).
  • Transfusion Evidence Library (www.transfusionevidencelibrary.com) (searched 11 June 2013).
  • Conference Proceedings Citation Index - Science (Web of Science) (1990 to 11 June 2013).
  • IndMed (searched 11 June 2013).
  • KoreaMed (searched 11 June 2013).
  • PakMediNet (searched 11 June 2013).

 

Online databases of ongoing trials

We modified the search strategy that was used to search MEDLINE to search the other databases listed. Searches in MEDLINE were combined with the Cochrane RCT search filter as detailed in Chapter 6 of the Cochrane Handbook for Systematic Reviews of Interventions (Lefebvre 2011). We combined searches in EMBASE and CINAHL with adaptations of the relevant Scottish Intercollegiate Guidelines Network (SIGN) RCT filters (www.sign.ac.uk/methodology/filters.html). The search strategies for all databases are available in Appendix 1. We applied no restrictions by language of publication or publication status.

 

Searching other resources

We also:

  • handsearched reference lists;
  • checked references of all identified trials and relevant review articles for further literature. We limited these searches to the 'first generation' reference lists;
  • handsearched conference proceedings;
  • searched abstracts (published between 2006 and January 2011) of the most relevant conferences for further studies, including the European Society of Cardiology, World Congress of Cardiology, American Heart Association, Society of Cardiothoracic Surgeons, British Cardiovascular Society, European Association of Cardiothoracic Surgeons, American Association for Thoracic Surgery and Association for European Paediatric and Congenital Cardiology.

 

Data collection and analysis

 

Selection of studies

One review author (CD) screened all electronically derived citations and abstracts of papers identified by the review search strategy. We excluded studies that were clearly irrelevant (e.g. non-RCTs, non-cardiac surgery papers and duplicates) at this stage.

Two review authors (KW, SB) independently assessed the titles and abstracts of all potentially relevant trials for eligibility. We obtained the full text of any papers where eligibility could not be assessed on title and abstract alone and two review authors (KW, SB) independently assessed eligibility. At all stages, we resolved any disagreements by discussion or by consultation with a third review author (MM). We sought further information from the study authors where articles contained insufficient data to make a decision about eligibility. We designed a study eligibility form to help in the assessment of relevance using the criteria outlined above.

 

Data extraction and management

Two review authors (KW, SB) independently conducted data extraction according to the guidelines proposed by The Cochrane Collaboration. We resolved disagreements by consensus. The review authors were not blinded to names of authors, institutions, journals or the outcomes of the trials. We extracted data from the studies using a standardised data extraction form. The form was initially piloted on a sample of the eligible papers and any disagreements were resolved before the rest of the data extraction was completed.

We used both full-text versions and abstracts including additional information (e.g. slides) of eligible studies to retrieve the data. We extracted trials reported in more than one publication on one form only. Where these sources did not provide sufficient information, we requested additional details from the contact author.

 

Assessment of risk of bias in included studies

Two review authors (KW, SB) assessed all included studies for possible risk of bias, using the 'Risk of bias' tool, as described in Chapter 8 of the Cochrane Handbook of Systematic Reviews of Interventions (Higgins 2011). The assessment included information about the design, conduct and analysis of the trial. We evaluated the criteria using a three-point scale: low, high or unclear risk of bias.

 

Measures of treatment effect

For dichotomous outcomes, the numbers of outcomes in treatment and control groups were recorded and the risk ratio (RR) was reported with a 95% confidence interval (CI) that was used for reporting the treatment effect measures across individual studies.

For continuous outcomes, the mean and standard deviations (SD) were recorded. For continuous outcomes measured using the same scale, the effect measure was the mean difference (MD) with 95% CIs, and, if data had necessitated, the standardised mean difference (SMD) for outcomes measured using different scales. Three trials reported standard error of the means (SEM) (Komai 1998; Liu 2007; Swindell 2007): we calculated SDs from the SEM and used these for our calculations throughout this review.

Five trials reported outcome data using median values (with interquartile ranges) (Cholette 2011; Cholette 2012; de Vries 2004; Shimpo 2001; Ye 2013): these values have been commented on in the text and individual outcome data reported in  Table 1;  Table 2;  Table 3; and  Table 4. The trials report that some of their outcome data were reported as median and interquartile ranges due to a skew in particular distributions. Such skew is commonplace in measures of duration (e.g. duration of mechanical ventilation and length of hospital stay) and thus was expected by the authors of this review.

Two trials reported data that could have allowed a change from baseline analysis to be undertaken (Han 2004; Komai 1998). However, as no change from baseline SDs were reported by these trials, we have chosen to not calculate change from baseline scores. The findings from these studies has been reported using MDs with 95% CIs as per all other continuous outcomes in this review.

We had planned to calculate the number needed to treat for an additional beneficial outcome (NNTB) with 95% CI and the number needed to treat for an additional harmful outcome (NNTH) with 95% CI but were unable to do so as we had insufficient relevant data to undertake this calculation.

 

Unit of analysis issues

We did not encounter any unit of analysis issues, as we did not include any cluster-randomised trials in this review, and the unit of analysis and randomisation was always the patient. If any unit of analysis issues had arisen, we would have treated these in accordance with the advice given in Chapter 16 of the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011).

 

Dealing with missing data

We successfully contacted three study authors by email to obtain missing data. One was contacted for more information on randomisation sequence as it was unclear in the published report (Komai 1998). The second was contacted to request clarity on outcome data and information on whether study personnel were blinded to treatment allocation (Cholette 2012). The third was contacted to clarify some outcome data and in response we received the mean and SD values for the baseline characteristics and outcomes they reported in their manuscript (Ye 2013).

Where possible, we used intention-to-treat (ITT) data, but if not we included per-protocol (PP) data. One trial stated that they analysed data by both ITT and PP but the manuscript reported baseline data by ITT and outcome assessment data by PP (Cholette 2012). A second trial reported both ITT and PP data for their primary outcome: with the results being very similar by both analyses (Willems 2010). In accordance with our protocol, we have used the ITT data from this trial in our review.

 

Assessment of heterogeneity

We did perform any meta-analyses in this review, thus we did not make a formal assessment of heterogeneity. Should there have been sufficient data to support meta-analyses, the decision about whether or not to combine the results of individual studies would have depended on an assessment of heterogeneity. We would have assessed statistical heterogeneity of treatment effects between trials using a Chi2 test with a significance level at P value < 0.1. We would have used the I2 statistic to quantify the percentage of heterogeneity (I2 > 30% moderate heterogeneity, I2 > 75% considerable heterogeneity). We would have explored potential causes of heterogeneity using sensitivity and subgroup analyses. In any future updates of this review, assuming we find sufficient data, we will perform assessment of heterogeneity as outlined.

 

Assessment of reporting biases

As there were no meta-analyses with more than 10 trials, we did not perform an assessment of reporting biases. In future updates of this review, we will explore potential publication bias (small trial bias) by generating a funnel plot and do statistical testing using a linear regression test. A P value of less than 0.1 would be considered significant for this test (Lau 2006; Sterne 2011).

 

Data synthesis

We performed analyses according to the recommendations of The Cochrane Collaboration (Schunemann 2011), with aggregated data used for analysis. For statistical analysis, we used Review Manager 5 (RevMan 2012).

We used a fixed-effect model for meta-analysis and employed the Mantel-Haenszel method for dichotomous data outcomes (and the generic inverse variance method for survival data outcomes, should this data have been available). We found no unexplained statistical heterogeneity, but if we had, we would have undertaken a random-effects meta-analysis, and reported both fixed-effect and random-effects meta-analyses. As most outcome data did not allow for meta-analysis (due to clinical and outcome diversity), we have reported outcome data descriptively.

We created no 'Summary of findings' table for this review due to the lack of reported data across the included trials. If we had been able to produce a 'Summary of findings' table, we would have used the GRADE profiler as suggested in the Cochrane Handbook for Systematic Reviews of Interventions (Schunemann 2011a).

 

Subgroup analysis and investigation of heterogeneity

Sufficient data were not available to perform our intended subgroup analyses relating to whether a patient had acyanotic or cyanotic congenital heart disease and the timing of the transfusion: preoperatively, intraoperatively, postoperatively. In future updates of this review, we will explore these subgroup analyses should we find appropriate data.

 

Sensitivity analysis

We had intended to assess the robustness of our findings by the following sensitivity analyses:

  • including only those trials at low risk of bias on the dimensions of selection and performance bias (clinicians only);
  • including only those trials in which 25% of patients or less were lost to follow-up.

However, there were insufficient data to enable these assessments. In future updates of this review, we will explore these sensitivity analyses should we find appropriate data.

 

Results

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. Contributions of authors
  13. Declarations of interest
  14. Sources of support
  15. Differences between protocol and review
  16. Notes
  17. Index terms
 

Description of studies

 

Results of the search

The database search identified 1485 references. After initial screening of the database citations, we excluded 570 for being duplicates or not an RCT. We screened the remaining 915 records according to the criteria defined above and excluded 870 (see Figure 1).

 FigureFigure 1. Study flow diagram.

Handsearching of the abstracts from the annual conference proceedings identified 11,202 references. After initial screening, we excluded all but two as they were either not the correct intervention or not an RCT. We excluded the two remaining abstracts after obtaining further information: one was not an RCT and the other did not solely use red blood cells as the intervention.

We obtained the full text of 45 references. We deemed 23 references (providing data on 11 independent trials) eligible for inclusion, identified three references (providing data on two separate trials) as a 'trial awaiting assessment', found three references to be ongoing trials and excluded 17 references for not meeting the eligibility criteria of this review.

 

Included studies

We found 11 trials (from 22 references) to be eligible for inclusion in this review (see Characteristics of included studies table).

 

Design

The trials were published between 1990 and 2013 and all were published in English as full journal articles. All trials were parallel RCTs. One paper (Willems 2010) was a sub-study analysis of a larger RCT (Lacroix 2007). The larger trial was not eligible for inclusion in our review as it examined the general paediatric intensive care population and was not specific to children with congenital heart disease undergoing cardiac surgery (Lacroix 2007). The sub-study of Willems 2010 explored transfusion strategies for paediatric patients undergoing surgery for congenital heart disease in paediatric intensive care units (PICU).

 

Sample sizes

The trials included 862 patients. The number of patients ranged from 16 (Liu 2007) to 309 (Ye 2013). Three trials reported inadequate powering of their studies with reference to testing for statistical differences in clinical outcomes (Cholette 2011; Cholette 2012; Willems 2010).

 

Setting

The trials were conducted in eight countries with three trials in the US (Cholette 2012; Cholette 2011; Hosking 1990); two in China (Liu 2007; Ye 2013); and one in each of Japan (Komai 1998), Germany (Shimpo 2001), the Netherlands (de Vries 2004), Korea (Han 2004), and UK (Swindell 2007). One trial was multi-country, with patients included from Belgium, Canada and the US (Willems 2010).

 

Patients

The patients were neonates or children. There were no trials including adults with congenital heart disease. One trial looked at neonates only (Liu 2007), two trials included both neonates and children (Cholette 2012; Swindell 2007). The remaining eight trials examined children only (Cholette 2011; de Vries 2004; Han 2004; Hosking 1990; Komai 1998; Shimpo 2001; Willems 2010; Ye 2013). Three trials included only cyanotic patients (Cholette 2011; Liu 2007; Swindell 2007), four trials only acyanotic patients (Han 2004; Komai 1998; Shimpo 2001; Willems 2010), and four trials included both cyanotic and acyanotic patients (Cholette 2012; de Vries 2004; Hosking 1990; Ye 2013).

 

Interventions

The trials examined red cell transfusion as an intervention in several different ways (see  Table 5).

Two trials assessed a restrictive versus a liberal red blood cell transfusion policy (Cholette 2011; Willems 2010). In the restrictive arm, children (with single ventricle physiology post cavopulmonary connection (cyanotic group)) were transfused when their haemoglobin concentration was less than 9.0 g/dL (Cholette 2011), or when their haemoglobin concentration was less than 7.0 g/dL (Willems 2010). In the liberal arm, children (with new or progressive multiple organ dysfunction post cardiac surgery (acyanotic group) received a red blood cell transfusion when their haemoglobin concentration was greater than 13.0 g/dL (Cholette 2011), or when their haemoglobin concentration was less than 9.5 g/dL (Willems 2010).

Two trials assessed the impact of leukoreduction but at different time points in the operation and in different patient populations. One trial, in acyanotic neonates and paediatric patients, explored the benefits (postoperative oxygenation and circulating leukocyte counts) of a leukoreduction filter for the blood in the bypass circuit at the end of the operation (de Vries 2004). The other trial, in acyanotic paediatric patients, reported on the clinical effect (lung function) of applying leukoreduction filters to stored donor red blood cells added to the CPB circuit at the beginning of the operation (Komai 1998).

Seven trials assessed red blood cell usage during CPB, but each was for a different aspect of non-standard CPB prime. In addition, the age of the patients and inclusion of acyanotic or cyanotic patients differed between the trials. Three of these trials assessed the impact of washing packed red blood cells (Cholette 2012; Hosking 1990; Swindell 2007): in two trials the red blood cells had also been irradiated (Cholette 2012; Swindell 2007); one trial assessed CPB prime containing red blood cells versus crystalloid (bloodless) prime (Han 2004); one trial assessed cell salvage versus no cell salvage during CPB (Ye 2013); one trial compared the effects of unprocessed and processed packed red cells with the continuous autologous transfusion system (Liu 2007); and one trial compared red blood cells that had been ultrafiltrated versus red blood cells that had not been ultrafiltrated (Shimpo 2001).

 

Outcomes

No trial measured all outcomes of interest to this review. Two trials did not include any outcomes pre-defined as of interest to this review (Hosking 1990; Swindell 2007). However, they both included an outcome (biochemistry levels) that should be relevant to this review (and may be important in any future updates). We have added this outcome into this review, clearly marking it as an outcome that was identified and added after the review protocol was agreed.

 

Excluded studies

We excluded 17 studies from the review following full-text eligibility assessment (see Characteristics of excluded studies table). In summary, eight studies were not RCTs; seven had an incorrect intervention (five did not analyse red blood cell independently of other blood products) and two had an incorrect patient population (one contained neonates with cardiac neonates but they did not undergo cardiac surgery and one was in the general neonatal population).

 

Studies awaiting classification

We included two trials (from three references) in the 'studies awaiting classification' section of the review (see Characteristics of studies awaiting classification table).

 

Ongoing studies

We identified three ongoing studies (see Characteristics of ongoing studies table). We will monitor the progress of these trials and, on publication (assuming eligibility), will include them in future updates of this review. The ongoing RCTs cover two interventions: transfusion triggers (Cholette 2012a; Reeves 2008), and age of red blood cells to be transfused (Steiner 2010).

 

Risk of bias in included studies

See the 'Risk of bias' tables for details of our assessment for each study and Figure 2 and Figure 3 for a 'Risk of bias' graph and tabular summary.

 FigureFigure 2. Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
 FigureFigure 3. Risk of bias summary: review authors' judgements about each risk of bias item for each included study.

 

Allocation

Four trials reported details of the randomisation sequence (de Vries 2004; Han 2004; Komai 1998; Willems 2010). Three of these four trials were defined as being of low risk of bias, using computer generated lists (de Vries 2004; Han 2004) and assigning patients to intervention groups in blocks of two or four (Willems 2010). One trial was defined as being of high risk of bias as an alternation method was used (Komai 1998).

The generation of the randomisation sequence was defined as unclear risk of bias in the other seven trials (Cholette 2011; Cholette 2012; Hosking 1990; Liu 2007; Shimpo 2001; Swindell 2007; Ye 2013). Two trials used block randomisation to randomise into either transfusion strategy but no further description was provided as to how the random sequence was generated (Cholette 2011; Cholette 2012). Five trials did not report details of their generation of the randomisation sequence methods (Hosking 1990; Liu 2007; Shimpo 2001; Swindell 2007; Ye 2013), so we defined them as having an unclear risk of bias.

 

Concealment of treatment allocation

The method of randomisation (as described above) was deemed to be of low risk of bias to conceal treatment allocation in two trials (Shimpo 2001; Willems 2010), where only the perfusionist was informed of allocation in one trial (Shimpo 2001), and the physicians, nurses and research staff were unaware of the block-randomisation strategy in the other trial (Willems 2010). One trial had its method of randomisation deemed inadequate (high risk of bias) to conceal treatment allocation, as the author confirmed directly by email that unsealed envelopes were used (de Vries 2004). Eight trials did not provide information to enable assessment of adequate allocation concealment (Cholette 2012; Cholette 2011; Han 2004; Hosking 1990 Komai 1998; Liu 2007; Swindell 2007; Ye 2013); therefore, we defined them as having unclear risk of bias.

 

Blinding

Blinding of patients, clinicians or outcome assessors was reported in four trials (Cholette 2012; Cholette 2011; Shimpo 2001; Willems 2010). In one trial, only the perfusionist was informed of trial allocation and all other people involved in the trial were blind to treatment allocation (low risk of bias) (Shimpo 2001). We defined blinding as high risk of bias in the other three trials: no-one involved in the care of or outcome assessment of the patients was blinded to treatment allocation (Cholette 2012); the blinding of personnel and patients was inadequate as clinical staff and patients' families were aware of transfusion group assignment while the blinding of the outcome assessors was not reported so rated as unclear risk of bias in the one trial (Cholette 2011). In the third trial (Willems 2010), blinding of personnel and patients was also of high risk of bias, but the outcome assessors were stated as being "unaware of treatment assignment" and we have defined blinding as at a low risk of bias for outcome assessors.

The blinding of all trial personnel (patients, clinicians and outcome assessors) to treatment allocation was unclear in seven trials (de Vries 2004; Han 2004; Hosking 1990; Komai 1998; Liu 2007; Swindell 2007; Ye 2013).

 

Incomplete outcome data

Eight trials included all randomised patients in the analysis of outcome data and did not lose any patients during follow-up (de Vries 2004; Hosking 1990; Komai 1998; Liu 2007; Shimpo 2001; Swindell 2007; Willems 2010; Ye 2013). The remaining three trials did not include all randomised patients in the analysis of clinical, scientific or both clinical and scientific outcomes, but reported reasons for this non-inclusion (Cholette 2011; Cholette 2012; Han 2004).

In Cholette 2012, no patient was lost to follow-up, but six patients were excluded following randomisation for reported surgical reasons. Following randomisation, a further 34 patients (17 in each treatment arm) did not receive a transfusion and, therefore, were not included in the PP analysis. In Cholette 2011, two randomised patients (3% of patients in this trial) were excluded from the trials and, therefore, outcome analysis (one patient from each intervention arm). No other patient dropped out of the study or was lost to follow-up. In Han 2004, one patient (3% of patients in this trial) in the intervention group was excluded for clinical reasons and this patient's data were not included in any outcome analyses.

 

Selective reporting

In six RCTs, all outcomes defined in their methods section were reported on in their results section (low risk of bias) (Cholette 2012; Cholette 2011; de Vries 2004; Liu 2007; Swindell 2007; Willems 2010). Four RCTs did not define the outcomes they were interested in; therefore, it is impossible to identify whether there was reporting bias in these trials (Han 2004; Hosking 1990; Komai 1998; Shimpo 2001; Ye 2013), and we have rated them as having unclear risk of bias.

 

Other potential sources of bias

 

Protocol adherence

Three trials reported protocol adherence (Cholette 2011; Cholette 2012; Willems 2010). In one trial, there was 100% compliance with the trial protocol and the protocol was never suspended during the trial (Cholette 2011). There were three protocol violations in one trial; one in a neonate receiving washed red blood cells and two in neonates in the unwashed red blood cell group (Cholette 2012). In the other trial, 10 patients did not reach their pre-defined criteria for good protocol adherence (80%) and seven patients in the restrictive group and one in the liberal group were suspended temporarily from the transfusion protocol (Willems 2010).

 

Support and sponsorship

Eight trials did not report the source of funding (de Vries 2004; Han 2004; Hosking 1990; Komai 1998; Liu 2007; Shimpo 2001; Swindell 2007; Ye 2013). In the three trials that reported source of funding, two trials were supported in part by university grants (Cholette 2011; Cholette 2012) and the study authors did not disclose any potential conflicts of interest. The third trial was supported by government grants from the Canadian Institutes of Health Research (CIHR) and Fonds de la Recherche en Sante du Quebec (FRSQ). The authors conflicts of interest were reported and we assessed them as low risk of bias (Willems 2010).

 

Effects of interventions

The outcome data in this review are reported by outcome and then by intervention. Relevant eligible trials were only identified for three of the interventions of interest: restrictive transfusion trigger versus liberal transfusion trigger; leukoreduced red cell transfusion versus non-leukoreduced red cell transfusion; and standard CPB prime versus non-standard CPB prime.

The clinical diversity in the patient groups (cyanotic and acyanotic, and paediatric and neonate) has meant that there was no opportunity to pool data within these intervention groups. In addition, no data was pooled across the intervention standard versus non-standard CPB prime due to clinical diversity in the patient groups and also due to differences in the red blood cells (processed versus unprocessed, washed versus unwashed) used in the CPB machine.

 

Primary outcome

 

All-cause mortality: short term (30 days post surgery)

 
Restrictive transfusion trigger versus liberal transfusion trigger

Willems 2010 reported data for this outcome. There was no difference in the number of deaths between the restrictive and liberal threshold (RR 0.98, 95% CI 0.14 to 6.77, 125 patients). The time at which death occurred and the causes of death were not reported (Figure 4).

 
Leukoreduced red cell transfusion versus non-leukoreduced red cell transfusion

No trial reported data for this outcome.

 
Standard cardiopulmonary bypass prime versus non-standard cardiopulmonary bypass prime

Four trials report measuring this outcome (Cholette 2012; Liu 2007; Shimpo 2001; Ye 2013), although incidents of mortality were only reported in two trials (Cholette 2012; Ye 2013), as Liu 2007 and Shimpo 2001 reported no in-hospital deaths in their trials. We did not perform a meta-analysis due to clinical and intervention diversity.

There were no differences in the number of deaths between the intervention arms (RR, 95% CI 0.03 to 2.18; 128 patients, Cholette 2012; RR 0.21, 95% CI 0.02 to 2.31, 309 patients, Ye 2013) ( Figure 4). Where reported, details of the cause and time of death are provided in  Table 6.

 

Secondary outcomes

 

All-cause mortality: long term (at two years)

 
Restrictive transfusion trigger versus liberal transfusion trigger

Cholette 2011 reported data for this outcome. There was no difference in the number of deaths over a long (up to two years post surgery) period between the restrictive and liberal threshold group (RR 0.33, 95% CI 0.01 to 7.87, 60 patients) ( Analysis 1.2).

 
Leukoreduced red cell transfusion versus non-leukoreduced red cell transfusion

No trial reported data for this outcome.

 
Standard cardiopulmonary bypass prime versus non-standard cardiopulmonary bypass prime

Data for this outcome were obtained directly from the study author for one trial (Cholette 2012). There was no difference in the number of deaths over a long time period (at two years) between the washed intervention and the unwashed intervention groups (RR 0.33, 95% CI 0.07 to 1.59, 128 patients) ( Analysis 1.2). Details of the cause and time of death are provided in  Table 6.

 

Severe adverse events: cardiac events

 
Restrictive transfusion trigger versus liberal transfusion trigger

Willems 2010 reported data for this outcome. There was no difference in the number of patients who had cardiovascular dysfunction between the restrictive and liberal trigger arms (RR 0.98, 95% CI 0.71 to 1.36, 125 patients) ( Analysis 1.3). No further details were given as to when the dysfunction occurred, how it was treated or the outcome for these patients.

 
Leukoreduced red cell transfusion versus non-leukoreduced red cell transfusion

No trial reported data for this outcome.

 
Standard cardiopulmonary bypass prime versus non-standard cardiopulmonary bypass prime

Cholette 2012 reported data for this outcome, defining a cardiac event as arrhythmia that was haemodynamically significant, required intervention or both. There was no difference in the number of patients who had a cardiac event at any time during the hospital admission between the intervention arms (RR 0.88, 95% CI 0.47 to 1.64, 128 patients) ( Analysis 1.3).

 

Severe adverse events: acute lung injury

 
Restrictive transfusion trigger versus liberal transfusion trigger

Willems 2010 reported data for this outcome. There was no difference in the number of patients experiencing an acute lung injury between intervention arms (RR 0.96, 95% CI 0.73 to 1.26, 125 patients) ( Analysis 1.4). No further details were given as to when the acute lung injury occurred, how it was treated or the outcome for these patients.

 
Leukoreduced red cell transfusion versus non-leukoreduced red cell transfusion

No trial reported data for this outcome.

 
Standard cardiopulmonary bypass prime versus non-standard cardiopulmonary bypass prime

Ye 2013 reported data for this outcome. There was no difference in the number of patients experiencing an acute lung injury between the cell salvage and the no-cell salvage treated groups (RR 0.88, 95% CI 0.61 to 1.27, 309 patients) ( Analysis 1.4). No further details were given as to when the acute lung injury occurred, how it was treated or the outcome for these patients.

 

Severe adverse events: stroke

No trial reported data for this outcome.

 

Severe adverse events: thromboembolism

 
Restrictive transfusion trigger versus liberal transfusion trigger

No trial reported data for this outcome.

 
Leukoreduced red cell transfusion versus non-leukoreduced red cell transfusion

No trial reported data for this outcome.

 
Standard cardiopulmonary bypass prime versus non-standard cardiopulmonary bypass prime

Cholette 2012 reported data for this outcome. There was no difference in the number of patients who had a thromboembolism, at any time during the hospital admission, between the washed intervention and unwashed intervention groups (RR 0.88, 95% CI 0.34 to 2.27, 128 patients) ( Analysis 1.5).

 

Severe adverse events: renal failure (needing renal replacement therapy)

 
Restrictive transfusion trigger versus liberal transfusion trigger

Willems 2010 reported data for this outcome. There was no difference in the number of patients experiencing renal failure between the intervention arms (RR 0.33, 95% CI 0.01 to 7.90, 125 patients) ( Analysis 1.6). No details as to timing and severity of dysfunction were provided.

 
Leukoreduced red cell transfusion versus non-leukoreduced red cell transfusion

No trial reported data for this outcome.

 
Standard cardiopulmonary bypass prime versus non-standard cardiopulmonary bypass prime

Ye 2013 reported data for this outcome. There was a difference in the number of patients experiencing renal failure, with patients receiving cell salvaged red blood cells during CPB being less likely to have renal failure than patients not exposed to cell salvage (RR 0.26, 95% CI 0.09 to 0.79, 309 patients) ( Analysis 1.6).

 

Severe adverse events: infection

 
Restrictive transfusion trigger versus liberal transfusion trigger

Willems 2010 reported data for this outcome. There was no difference in the number of patients who had systemic inflammatory response syndrome between the intervention arms (RR 0.71, 95% CI 0.38 to 1.32, 125 patients) ( Analysis 1.7).

 
Leukoreduced red cell transfusion versus non-leukoreduced red cell transfusion

No trial reported data for this outcome.

 
Standard cardiopulmonary bypass prime versus non-standard cardiopulmonary bypass prime

Cholette 2012 reported data for this outcome. There was no difference in the number of patients who had an infection at some time during their hospital admission between the washed and unwashed red blood cell intervention arms (RR 1.00, 95% CI 0.50 to 1.99, 128 patients) ( Analysis 1.7). In all cases, a diagnosis of an infection was supported by culture data.

 

Severe adverse events: haemorrhage (return to theatre for bleeding)

 
Restrictive transfusion trigger versus liberal transfusion trigger

Cholette 2011 and Willems 2010 reported data for this outcome. We did not undertake a meta-analysis due to clinical diversity. Neither trial reported a difference in the number of patients experiencing a haemorrhage requiring a return to theatre for bleeding between their intervention arms (RR 0.33, 95% CI 0.01 to 8.03, 60 patients, Cholette 2011; RR 2.95, 95% CI 0.12 to 71.13, 125 patients, Willems 2010) ( Analysis 1.8).

 
Leukoreduced red cell transfusion versus non-leukoreduced red cell transfusion

No trial reported data for this outcome.

 
Standard cardiopulmonary bypass prime versus non-standard cardiopulmonary bypass prime

Cholette 2012 reported data for this outcome. There was no difference in the number of patients experiencing a haemorrhage requiring a return to theatre for bleeding between the washed and unwashed red blood cell intervention groups (RR 0.33, 95% CI 0.01 to 8.03, 128 patients) ( Analysis 1.8).

 

Haematocrit/haemoglobin (g/dL) levels postoperatively

 
Restrictive transfusion trigger versus liberal transfusion trigger

Cholette 2011 and Willems 2010 reported data for this outcome. We did not undertake a meta-analysis due to clinical and timing of outcome measurement diversity. There was a difference in haemoglobin concentrations after the first postoperative transfusion between the intervention arms favouring the restrictive threshold group in one trial (MD -1.20 g/dL, 95% CI -1.61 to -0.79, 125 patients, Willems 2010). The second trial found no difference in haemoglobin concentrations between the intervention arms when measured postoperatively (MD 0.10 g/dL, 95% CI -4.01 to 4.21, Cholette 2011) ( Analysis 1.9).

 
Leukoreduced red cell transfusion versus non-leukoreduced red cell transfusion

No trial reported data for this outcome.

 
Standard cardiopulmonary bypass prime versus non-standard cardiopulmonary bypass prime

Han 2004, Liu 2007, and Ye 2013 reported data for this outcome. We did not undertake a meta-analysis due to clinical diversity. In all three trials, there was a difference in haematocrit levels postoperatively between the intervention arms. In Han 2004, the difference favoured the CPB prime containing red blood cells (MD -3.90%, 95% CI -4.35 to -3.45, 36 patients); in Liu 2007, the difference favoured the processed red blood cell group (MD 23.30%, 95% CI 6.01 to 40.59, 16 patients). In Ye 2013, the difference favoured the cell salvage group (MD 1.19%, 95% CI 0.03 to 2.35, 309 patients) ( Analysis 1.9).

 

Haematocrit/haemoglobin (g/dL) levels at discharge

No trial reported data for this outcome.

 

Volume or number of red blood cell units transfused

 
Restrictive transfusion trigger versus liberal transfusion trigger

Cholette 2011 and Willems 2010 reported data for this outcome. We did not undertake a meta-analysis due to clinical diversity and how the outcome was measured. In one trial, there was a difference in the mean number of red blood cell units transfused within 48 hours of paediatric cardiac intensive care unit (PCICU) admission, favouring the restrictive threshold group (MD -1.67 units, 95% CI -2.15 to -1.19, 60 patients, Cholette 2011).

Willems 2010 reported no difference in the volume of red blood cell units transfused between intervention arms (MD -1.00 mL/kg, 95% CI -2.35 to 0.35, 125 patients) ( Analysis 1.10). Willems 2010 also reported the total number of transfusions (13 in the restrictive red blood cell trigger group and 82 in the liberal group).

 
Leukoreduced red cell transfusion versus non-leukoreduced red cell transfusion

Komai 1998 reported data for this outcome. There was no difference in the mean number of red blood cell units transfused across the study period between the intervention arms (MD 0.30 units, 95% CI -0.32 to 0.92, 46 patients) ( Analysis 1.10).

 
Standard cardiopulmonary bypass prime versus non-standard cardiopulmonary bypass prime

Cholette 2012 reported data for this outcome. There was no difference in the mean number of red blood cell units transfused over the entire hospitalisation period between the washed and unwashed red blood cell intervention groups (MD -0.30 units, 95% CI -1.62 to 1.02, 128 patients) ( Analysis 1.10).

 

Volume or number of other blood products transfused (i.e. fresh frozen plasma, platelets, cryoprecipitate)

 
Restrictive transfusion trigger versus liberal transfusion trigger

Cholette 2011 and Willems 2010 reported the number of patients receiving fresh frozen plasma and Willems 2010 reported the number of patients receiving platelets. We did not undertake a meta-analysis due to clinical diversity and the timing of the outcome measurement. There was no difference between intervention arms in the number of patients receiving fresh frozen plasma in the first 48 hours after admission (RR 3.00, 95% CI 0.13 to 70.83, 60 patients) (Cholette 2011); in the number of patients receiving fresh frozen plasma up to 28 days following randomisation (RR 1.97, 95% CI 0.37 to 10.36, 125 patients) (Willems 2010), or in the number of patients receiving platelets up to 28 days following randomisation (RR 1.23, 95% CI 0.35 to 4.37, 125 patients) (Willems 2010) ( Analysis 1.11;  Analysis 1.12).

 
Leukoreduced red cell transfusion versus non-leukoreduced red cell transfusion

No trial reported data for this outcome.

 
Standard cardiopulmonary bypass prime versus non-standard cardiopulmonary bypass prime

Cholette 2012 reported data for this outcome. There was no difference in the mean number of platelets, fresh frozen plasma and cryoprecipitate units transfused over the entire hospitalisation period between the washed and unwashed red blood cell intervention groups (platelets: MD -0.30 units, 95% CI -0.67 to 0.07; fresh frozen plasma: MD -0.17 units, 95% CI -0.47 to 0.13; cryoprecipitate: MD -0.11 units, 95% CI -0.27 to 0.05; 128 patients) ( Analysis 1.13;  Analysis 1.14;  Analysis 1.15).

 

Postoperative chest drain output

 
Restrictive transfusion trigger versus liberal transfusion trigger

Cholette 2011 (with 60 patients) reported data for this outcome. There was no difference in the mean volume of postoperative mediastinal tube drainage between the intervention arms at postoperative day 0 (MD -0.20 mL/kg/hour, 95% CI -0.88 to 0.48, 60 patients), postoperative day 1 (MD -0.20 mL/kg/hour, 95% CI -1.19 to 0.79, 60 patients) and postoperative day 2 (MD -0.20 mL/kg/hour, 95% CI -1.87 to 1.47, 60 patients) ( Analysis 1.16).

 
Leukoreduced red cell transfusion versus non-leukoreduced red cell transfusion

No trial reported data for this outcome.

 
Standard cardiopulmonary bypass prime versus non-standard cardiopulmonary bypass prime

Cholette 2012 and Ye 2013 reported data for this outcome. We did not undertake a meta-analysis due to clinical diversity and differences in how the outcome was measured. In both trials, there was no difference between the intervention arms in the mean duration of postoperative chest drain output (MD 0.14 days, 95% CI -1.66 to 1.94, 128 patients, Cholette 2012) or in the mean volume of postoperative chest drain output (MD -0.18 mL/kg, 95% CI -2.20 to 1.84, 309 patients, Ye 2013) ( Analysis 1.16).

 

Duration of mechanical ventilation

 
Restrictive transfusion trigger versus liberal transfusion trigger

Cholette 2011 and Willems 2010 reported data for this outcome. We did not undertake a meta-analysis due to clinical diversity and the method of statistical analysis. Cholette 2011 reported the length of mechanical ventilation as median (plus interquartile range). The restrictive threshold group requiring a greater duration of mechanical ventilation than the liberal threshold group. The skew of this data prevents a conversion to mean (and SD). Median values are reported in  Table 3. In the second trial (Willems 2010), there was no difference in the length of mechanical ventilation between the treatment arms after randomisation (MD -0.70 hours, 95% CI -2.01 to 0.61, 125 patients) and for total PICU stay (MD -0.10 hours, 95% CI -1.48 to 1.28, 125 patients) (see Figure 5).

 
Leukoreduced red cell transfusion versus non-leukoreduced red cell transfusion

de Vries 2004 and Komai 1998 reported data for this outcome. We did not undertake a meta-analysis due to clinical diversity and the method of statistical analysis. de Vries 2004 reported intubation time as median (plus interquartile range). The non-leukoreduced group required a greater duration of mechanical ventilation than the leukoreduced group. The skew of this data prevents a conversion to mean (and SD). Median values are reported in  Table 3. In the second trial (Komai 1998), there was no difference in intubation time between the two groups (MD -7.20 hours, 95% CI -20.62 to 6.22, 48 patients) ( Analysis 1.17).

 
Standard cardiopulmonary bypass prime versus non-standard cardiopulmonary bypass prime

Shimpo 2001, Cholette 2012, and Ye 2013 reported measuring this outcome. We did not undertake a meta-analysis due to lack of suitable data. Two trials reported intubation time as median (plus interquartile range) (Cholette 2012; Ye 2013). In Cholette 2012, the comparator group (unwashed red blood cells) required a greater duration of mechanical ventilation than the interventions group (washed red cell group), while in Ye 2013, the intervention group (cell salvage) required a greater duration of mechanical ventilation than the control group. The skew of this data prevents a conversion to mean (and SD). Median values are reported in  Table 3. No data were reported by the third trial (Shimpo 2001).

 

Duration of intensive care unit stay

 
Restrictive transfusion trigger versus liberal transfusion trigger

Cholette 2011 and Willems 2010 reported data for this outcome. We did not undertake a meta-analysis due to clinical diversity. There was no difference in the length of hospital stay between the restrictive and liberal threshold in both trials (MD 1.20 days, 95% CI -1.38 to 3.78, 60 patients, Cholette 2011; MD -0.40 days, 95% CI -2.42 to 1.62, 125 patients, Willems 2010) (Figure 6).

 
Leukoreduced red cell transfusion versus non-leukoreduced red cell transfusion

de Vries 2004 and Komai 1998 reported data for this outcome. We did not undertake a meta-analysis due to clinical diversity. de Vries 2004 reported similar lengths of median ICU stay for both groups. Median values are reported in  Table 4. In Komai 1998, there was no difference in the duration of ICU stay between the two groups (MD -1.10 days, 95% CI -2.21 to 0.01, 46 patients) (Figure 6).

 
Standard cardiopulmonary bypass prime versus non-standard cardiopulmonary bypass prime

Shimpo 2001 and Cholette 2012 reported data for this outcome. We did not undertake a meta-analysis due to clinical diversity in the intervention arms. In Shimpo 2001, there was a difference in the mean length of ICU stay favouring the ultrafiltration treated arm (MD -16.00 hours, 95% CI -21.89 to -10.11, 100 patients), but in Cholette 2012, there was no difference in the mean length of stay in paediatric cardiac intensive care between the washed and unwashed red blood cell intervention groups (MD -0.30 days, 95% CI -4.32 to 3.72, 128 patients) (Figure 6).

 

Re-hospitalisation rates

No trial reported data for this outcome.

 

Biochemistry levels (outcome identified and added post-hoc)

 
Restrictive transfusion trigger versus liberal transfusion trigger

Cholette 2011 measured lactate levels. There was no difference in mean lactate level between the intervention arms at baseline (RR -0.10, 95% CI -0.73 to 0.53, 60 patients) and the 'peak' level during the initial 48-hour postoperative period (RR -0.10, 95% CI -0.81 to 0.61, 60 patients) ( Analysis 1.19).

 
Leukoreduced red cell transfusion versus non-leukoreduced red cell transfusion

No trial reported data for this outcome.

 
Standard cardiopulmonary bypass prime versus non-standard cardiopulmonary bypass prime

Five trials measured this outcome (Cholette 2012; Hosking 1990; Liu 2007; Shimpo 2001; Swindell 2007). We did not undertake a meta-analysis due to clinical diversity in the nature of intervention.

 
Lactate levels

Cholette 2012, Liu 2007, and Swindell 2007 measured lactate levels at different time points ( Analysis 1.19). A difference was observed in mean lactate levels in two of these trials at different time points. In Liu 2007, there was a difference in lactate levels between the two groups favouring the processed packed red cells for the priming arm immediately after CPB with the clamp of arterial cannula (MD -1.60 mmol/L, 95% CI -2.65 to -0.55, 16 patients). In Swindell 2007, there was a difference in lactate levels on CPB prime prior to bypass (MD -2.00 mmol/L, 95% CI -0.94 to -3.06, 22 patients) and during re-warming at 28°C (MD -1.40 mmol/L, 95% CI -2.54 to -0.26, 22 patients). Comparisons for all three trials are available in  Analysis 1.19.

 
Sodium levels

Shimpo 2001 and Swindell 2007 measured sodium levels. Shimpo 2001 measured sodium levels before and after ultrafiltration in the patients who were treated with ultrafiltrated red blood cells only. Sodium levels remained within a clinically accepted normal range following receipt of ultrafiltrated red blood cells. Shimpo 2001 did not report the sodium levels for patients not receiving ultrafiltrated red blood cells, therefore, no further comparison of this outcome can be made.

In Swindell 2007, there was a difference in sodium levels on CPB prime prior to bypass (MD 4.00 mmol/L, 95% CI 0.94 to 7.06, 22 patients); during re-warming at 36°C (MD 3.10 mmol/L, 95% CI 0.44 to 5.76, 22 patients); and immediately after CPB with clamp of arterial cannula (MD 4.00 mmol/L, 95% CI 1.19 to 6.81, 22 patients). However, it should be notes that both sodium levels in the CPB circuit prime after line connection were not within normal clinical value ranges and would be of clinical concern. At the later time points (at 36°C during re-warming and immediately after CPB with clamp of arterial cannula) the sodium levels were within normal clinical levels. All comparisons for this trial are available in  Analysis 1.20.

 
Potassium levels

Shimpo 2001 and Swindell 2007 measured potassium levels. Shimpo 2001 measured potassium levels before and after ultrafiltration in the patients who were treated with ultrafiltrated red blood cells only. Potassium levels fell to within a clinically accepted normal range following receipt of ultrafiltrated red blood cells. Shimpo 2001 did not report the potassium levels for patients not receiving ultrafiltrated red blood cells, therefore, no further comparison of this outcome can be made. In Swindell 2007, there was a difference in potassium levels on CPB prime prior to bypass (MD -5.50 mmol/L, 95% CI -6.31 to -4.69, 22 patients); at 28°C during re-warming (MD -1.90 mmol/L, 95% CI -2.71 to -1.09); and immediately after CPB with clamp of arterial cannula (MD -1.00 mmol/L, 95% CI -1.44 to -0.56, 22 patients) ( Analysis 1.21).

 
Blood glucose levels

In Hosking 1990 measured blood glucose levels. There was a difference in blood glucose level favouring the washed red blood cells at four time points: in the bypass priming solution prior to initiation of CPB (MD -282.00 mg/dL, 95% CI -315.06 to -248.94, 20 patients); 10 minutes after the initiation of CPB (MD -132.00 mg/dL, 95% CI -147.64 to -116.36, 20 patients); prior to separation from bypass (MD -134.00 mg/dL, 95% CI -168.44 to -99.56, 20 patients); and after the administration of protamine (MD -117.00 mg/dL, 95% CI -151.31 to -82.69, 20 patients). Two patients, one in each group, had a blood glucose concentration less than 60 mg/dL (outside that accepted normal range) in the pre-bypass period. The patient in the washed red blood cell group received two doses of glucose to correct the low glucose before the start of CPB. The other patient did not require treatment to correct their low glucose level before starting CPB. All comparisons for this trial are available in  Analysis 1.22.

 

Discussion

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. Contributions of authors
  13. Declarations of interest
  14. Sources of support
  15. Differences between protocol and review
  16. Notes
  17. Index terms

The aim of this review was to evaluate the effects of red cell transfusion on mortality and morbidity on patients with congenital heart disease at the time of cardiac surgery. We identified 11 completed RCTs including 862 patients to evaluate red cell transfusion in three intervention areas: two trials explored transfusion triggers, two trials explored the benefit of leukoreduction and seven trials explored non-standard CPB. All trials were in neonatal or paediatric populations and there was a mix of cyanotic and acyanotic patients included across the trials.

 

Summary of main results

The 11 studies included in this review were heterogeneous in terms of study population, interventions, outcomes and data quality. Therefore, we were unable to pool any data and the analysis is descriptive.

 

Transfusion triggers

The two transfusion strategy trials showed no clear difference in mortality between the liberal and restrictive intervention arms (Cholette 2011; Willems 2010). Cholette 2011and Willems 2010 also showed no significant difference in the duration of mechanical ventilation or the duration of ICU stay between the intervention arms.

Willems 2010 showed no clear difference in the incidence of adverse cardiac events, acute lung injury and renal failure between intervention arms but showed an increase in the incidence of infection events in the liberal transfusion group. Both trials demonstrated no clear difference in postoperative haemorrhage rates between intervention arms (Cholette 2011; Willems 2010). As expected, both trials showed the liberal transfusion groups received more red cell transfusions. However, neither trial showed any significant difference in the transfusion of fresh frozen plasma or platelets between the two groups. Both trials showed the restrictive groups had a significantly lower haemoglobin concentration for the ICU period at the specific time points each trial measured.

The results suggest that restricting red blood cell transfusion is not detrimental to the survival of either acyanotic or cyanotic congenital cardiac patients. However, a restrictive transfusion trigger may prolong the ICU stay for the cyanotic population and a liberal transfusion trigger may increase the incidence of infection for the acyanotic population but both studies were inadequately powered to detect statistical differences in these clinical outcomes so conclusions are difficult.

 

Leukoreduction

Leukoreduction aims to reduce the deleterious effects of leukocytes from allogeneic red cell transfusions. For duration of mechanical ventilation and length of intensive care, Komai 1998 (acyanotic population) showed a statistically non-significant shorter duration of mechanical ventilation and a statistically significant shorter length of ICU stay for the leukoreduced group. In contrast, de Vries 2004 (mixed cyanotic and acyanotic population) showed no statistically significant difference in duration of mechanical ventilation or ICU stay between groups. Most of the other main outcomes of interest were not reported by the two studies in this intervention (de Vries 2004; Komai 1998).

There were only two studies in this intervention area and they gave contrasting results with respect to the impact of leukoreduction. In addition, the patient populations were different. Therefore, it is difficult to draw definite conclusions for this intervention.

 

Standard versus non-standard bypass

The aim of processing (washing) red blood cells that are added to the cardiopulmonary prime and returned to the patient is to reduce or eliminate any potential adverse effects of the altered biochemistry of stored allogeneic red blood cells.

Washing (pre-processing) red cells added to the CPB prime did not result in any clear difference in mortality for either of the two trials that reported mortality (Cholette 2012, early and late mortality; Liu 2007, early mortality). Ultrafiltration (Shimpo 2001) and cell salvage (Ye 2013) did not result in any clear difference in mortality. Han 2004 (bloodless bypass prime) did not report mortality.

Washing bypass prime red cells did not result in any clear difference in adverse events of infection, thrombosis, arrhythmias and postoperative bleeding in the one trial that reported all of these outcomes (Cholette 2012). Cell salvage did not result in any clear difference in respiratory morbidity but the incidence of an increase in serum creatinine more than two-fold 72 hours after the operation was significantly lower in the cell salvage group (Ye 2013). No patients in either group required dialysis postoperatively.

Unsurprisingly, a bloodless bypass prime showed lower haematocrit levels during bypass (statistical significance not reported; Han 2004). Processing prime red blood cells significantly increased haematocrit at 10 minutes during bypass and at the end of bypass (Liu 2007). Cell salvage significantly increased the haematocrit level on the first postoperative day but not at any other time points at baseline, during bypass or just after bypass (Ye 2013).

Washing bypass prime red cells did not result in any clear differences in duration of mechanical ventilation or ICU stay (Cholette 2012). Cell salvage did not result in any clear difference in duration of mechanical ventilation (Ye 2013). The study did not report length of ICU stay. Ultrafiltration resulted in a significantly reduced duration of mechanical ventilation and ICU stay (Shimpo 2001).

The different methods of washing (processing) bypass prime red cells resulted in significant reductions in potassium levels at various time points in two studies; Liu 2007 before CPB and Swindell 2007 prior to red cell addition to the bypass prime, throughout bypass and immediately post bypass. Ultrafiltration also reduced potassium levels with Shimpo 2001 reporting ultrafiltrated priming blood had a significantly lower potassium level when compared with pre-ultrafiltration.

Lactate levels were variably affected by the washing (processing) techniques. Liu 2007 showed processed packed red blood cells with continuous autologous transfusion system (CATS) had significantly higher lactate levels before CPB and lower lactate levels at 10 minutes during and at the end of CPB. However, Swindell 2007 showed significantly lower lactate levels in the washed packed red blood cells prior to addition to the bypass prime but no significant difference in lactate levels between the two groups during bypass apart from at 28°C re-warming when the unwashed group showed a significantly higher lactate level. Cholette 2012 reported no significant difference in either ICU admission lactate or peak ICU lactate levels between the two groups.

Overall, the studies were too heterogeneous in terms of patient populations and exact intervention types to make accurate conclusions about the impact of washing (processing) red cells. It does appear that washing and ultrafiltration reduces potassium levels. The data on lactate are less clear.

The important outcome for a bloodless bypass prime was intraoperative cerebral oxygen saturations, as reported by one trial (Han 2004). The crystalloid prime group showed significantly lower cerebral oxygen saturations when compared with blood containing prime three minutes after initiating bypass and 15 minutes after the start of re-warming. This may suggest excessive haemodilution in the bloodless bypass prime but the clinical significance of this is unknown as the trial did not specifically report neurological outcomes post surgery.

 

Overall completeness and applicability of evidence

The trials included in this review are insufficient to address the objectives of our systematic review. There are gaps in the evidence base in terms of patient population (we found no trials in adults), interventions (no trials examined the interventions of volumes of red cell transfusion, whole blood versus packed red cells or the age of red cells transfused), and the completeness of outcomes measured and reported by the included trials. Our primary outcome was reported by only five included trials. No trials reported data for two outcomes: stroke and re-hospitalisation rates. The number of trials providing data for individual outcomes ranged from one (thromboembolism) to seven (duration of mechanical ventilation and biochemistry levels). The outcome of biochemistry levels was added post hoc as it became clear during data extraction (and following consultation with clinical colleagues) that the outcome was of clinical significance to this review question, but had been overlooked when we prepared the protocol.

The trials that do exist are not in sufficient numbers or homogeneity to pool results for any of the outcomes of interest to this review. This may limit the applicability of the evidence within this review.

 

Quality of the evidence

Overall, it was difficult to assess the quality of the evidence accurately as much information was lacking; many elements of trial quality in each trial were marked as having an unclear risk of bias. Attrition was low across all included trials. We assessed five trials as having elements of high risk of bias on method of randomisation (Komai 1998), method of allocation concealment (de Vries 2004), blinding of study personnel (Cholette 2011; Cholette 2012; Willems 2010), and blinding of outcome assessors (Cholette 2012). Blinding would be difficult to achieve for some interventions within this review. Although, as none of the outcomes were patient reported, we did not deem blinding of participants to be an important risk of bias.

The sample size of the 11 included trials was generally small. Only four trials had greater than 50 patients in each treatment arm included in the analysis of outcome data (Cholette 2012; Shimpo 2001; Willems 2010; Ye 2013). This may well reflect the nature of the condition of interest to this review, but does limit the statistical power of these trials to detect differences in outcomes of interest in this clinical area.

As has already been noted, the substantial clinical diversity in the included trials and the variability in outcome data reported has prevented any pooling of outcome data, thus the consistency (or inconsistency of results across the included trials is difficult to ascertain. Addressing such variability should be a key component of future research in this area.

 

Potential biases in the review process

We identified no biases in the review process. The strengths of this review lie in the robust and comprehensive methodology employed to find and assess all relevant trials. We have followed standard Cochrane methods for data extraction and results analysis with reference to the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011), and have referred to a statistician where necessary. We have had a clinician and methodologist working on all stages, independently of each other to control any bias that ensues due to clinical or systematic review methodology knowledge. When we were limited by a lack of reporting data to allow inclusion and assessment of trials, we successfully contacted authors directly to obtain the necessary data.

 

Agreements and disagreements with other studies or reviews

To date, as far as we are aware, there have been no other systematic reviews specifically examining the effects of red cell transfusion on mortality and morbidity on the congenital heart disease population at the time of cardiac surgery (Dorée 2010). Guzzetta 2011 reviewed the risks and benefits of red cell transfusion and concluded that the efficacy of red cell transfusion has never been equivocally shown even in well-designed trials and further well-designed trials are needed in this heterogeneous population. Our review would appear to agree with this conclusion.

 

Authors' conclusions

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. Contributions of authors
  13. Declarations of interest
  14. Sources of support
  15. Differences between protocol and review
  16. Notes
  17. Index terms

 

Implications for practice

Transfusion practice in children with congenital heart disease is likely to be firmly based on individual centre practice, as there are no widely accepted guidelines for transfusion practice in this patient population. There is no high-quality evidence on which to provide guidelines for transfusion practice in this population. This is not surprising as congenital heart disease affects small numbers of people with a previously high mortality.

Congenital heart disease is now associated with a low mortality. Although cardiac surgery carries inherent risks in this population, the estimated effects on postoperative and longer-term mortality were imprecise in the trials assessing postoperative restrictive versus liberal transfusion triggers, and were consistent with benefit and harm. We were unable to determine whether transfusion plays a role in reducing morbidity. This review has found few studies to assess the impact of red cell transfusion on children undergoing cardiac surgery for congenital heart disease. These studies provide limited evidence, and the trials were underpowered for clinical outcomes.

 
Implications for research

This review highlights gaps and deficiencies in the current evidence base. Future trials need to be designed correctly: adequately powered, age specific (neonates, paediatrics and adult age groups) and specific for the type of congenital heart disease (cyanotic and acyanotic groups). The adult congenital heart disease population is one of the fastest growing populations in the UK but this review has not found any studies assessing the impact of red cell transfusion in this particular population group. These are all important considerations for future research.

 

Acknowledgements

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. Contributions of authors
  13. Declarations of interest
  14. Sources of support
  15. Differences between protocol and review
  16. Notes
  17. Index terms

Sally Hopewell is a methodological expert for this review and provided support with data analysis and contributed to the preparation of the protocol.

 

Data and analyses

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. Contributions of authors
  13. Declarations of interest
  14. Sources of support
  15. Differences between protocol and review
  16. Notes
  17. Index terms
Download statistical data

 
Comparison 1. Comparisons of red cell transfusion at the time of cardiac surgery in people with congenital heart disease

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 All-cause mortality: short term (30 days post surgery)3Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

    1.1 Transfusion trigger
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

    1.2 Standard/non-standard cardiopulmonary bypass
2Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

 2 All-cause mortality: long term - at 2 years2Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

    2.1 Transfusion trigger
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

    2.2 Standard/non-standard cardiopulmonary bypass
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

 3 Severe adverse events: cardiac events2Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

    3.1 Transfusion trigger
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

    3.2 Standard/non-standard cardiopulmonary bypass
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

 4 Severe adverse events: acute lung injury2Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

    4.1 Transfusion trigger
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

    4.2 Standard/non-standard cardiopulmonary bypass
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

 5 Severe adverse event: thromboembolism1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

    5.1 Standard/non-standard cardiopulmonary bypass prime
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

 6 Severe adverse events: renal failure (needing renal replacement therapy)2Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

    6.1 Transfusion trigger
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

    6.2 Standard/non-standard cardiopulmonary bypass
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

 7 Severe adverse events: infection2Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

    7.1 Transfusion trigger
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

    7.2 Standard/non-standard cardiopulmonary bypass
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

 8 Severe adverse events: haemorrhage (return to theatre for bleeding)2Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

    8.1 Transfusion trigger
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

    8.2 Standard/non-standard cardiopulmonary bypass
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

 9 Haematocrit (%)/haemoglobin (g/dL) levels postoperatively5Mean Difference (IV, Fixed, 95% CI)Totals not selected

    9.1 Transfusion trigger - haemoglobin (g/dL)
2Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    9.2 Standard/non-standard cardiopulmonary bypass prime - haematocrit (%)
3Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 10 Volume or number of red cell units transfused4Mean Difference (IV, Fixed, 95% CI)Totals not selected

    10.1 Transfusion trigger
2Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    10.2 Leukocyte depletion
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    10.3 Standard/non-standard cardiopulmonary bypass
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 11 Number of participants receiving fresh frozen plasma2Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

    11.1 Transfusion trigger
2Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

 12 Number of participants receiving a platelet transfusion1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

    12.1 Transfusion trigger
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

 13 Volume or number of other blood products transfused: platelets1Mean Difference (IV, Fixed, 95% CI)Totals not selected

    13.1 Standard/non-standard cardiopulmonary bypass prime
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 14 Volume or number of other blood products transfused: cryoprecipitate1Mean Difference (IV, Fixed, 95% CI)Totals not selected

    14.1 Standard/non-standard cardiopulmonary bypass prime
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 15 Volume or number of other blood products transfused: fresh frozen plasma1Mean Difference (IV, Fixed, 95% CI)Totals not selected

    15.1 Standard/non-standard cardiopulmonary bypass prime
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 16 Postoperative chest drain output3Mean Difference (IV, Fixed, 95% CI)Totals not selected

    16.1 Transfusion trigger
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    16.2 Standard/non-standard cardiopulmonary bypass
2Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 17 Duration of mechanical ventilation2Mean Difference (IV, Fixed, 95% CI)Totals not selected

    17.1 Transfusion trigger - after randomisation
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    17.2 Transfusion trigger - total paediatric intensive care unit stay
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    17.3 Leukocyte depletion
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 18 Duration of intensive care unit stay5Mean Difference (IV, Fixed, 95% CI)Totals not selected

    18.1 Transfusion trigger
2Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    18.2 Leukocyte depletion
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    18.3 Standard/non-standard cardiopulmonary bypass prime
2Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 19 Lactate Levels (mmol/L)4Mean Difference (IV, Fixed, 95% CI)Totals not selected

    19.1 At baseline
3Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    19.2 Cardiopulmonary bypass circuit prime after line connection and 5 minute re-circulation
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    19.3 10 minutes after the start of cardiopulmonary bypass
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    19.4 'Peak' as defined by the study
2Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    19.5 At 28°C during re-warming
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    19.6 Immediately after cardiopulmonary bypass and clamp of arterial cannula
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 20 Sodium (Na+) levels (mmol/L)1Mean Difference (IV, Fixed, 95% CI)Totals not selected

    20.1 At baseline
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    20.2 Cardiopulmonary bypass circuit prime after line connection and 5 minute re-circulation
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    20.3 At 36°C after re-warming
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    20.4 Immediately after cardiopulmonary bypass and clamp of arterial cannula
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 21 Potassium (K+) levels (mmol/L)1Mean Difference (IV, Fixed, 95% CI)Totals not selected

    21.1 Cardiopulmonary bypass circuit prime after line connection and 5 minute re-circulation
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    21.2 At 28°C during re-warming
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    21.3 Immediately after cardiopulmonary bypass and clamp of arterial cannula
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 22 Blood glucose (mg/dL)1Mean Difference (IV, Fixed, 95% CI)Totals not selected

    22.1 After induction
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    22.2 Prior to cardiopulmonary bypass
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    22.3 In the bypass priming solution prior to initiation of cardiopulmonary bypass
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    22.4 10 minutes after initiation of cardiopulmonary bypass
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    22.5 Prior to separation from cardiopulmonary bypass
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    22.6 After administration of protamine
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 

Appendices

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. Contributions of authors
  13. Declarations of interest
  14. Sources of support
  15. Differences between protocol and review
  16. Notes
  17. Index terms
 

Appendix 1. Search strategies

 

Cochrane Central Register of Controlled Trials (CENTRAL)

#1 MeSH descriptor: [Heart Defects, Congenital] explode all trees
#2 MeSH descriptor: [Heart Diseases] explode all trees and with qualifiers: [Congenital - CN]
#3 ((heart* or cardiac* or coronary or septal* or aortopulmonary or aorticopulmonary or atrial or ventricular or intraventricular) near/3 (congenital* or neonat* or defect* or abnormal* or anomal*))
#4 (digeorge next (syndrome* or anomal* or sequenc*))
#5 (transpos* near/3 (arteries or artery or vessel*))
#6 (alagille near/2 syndrome)
#7 arteriohepatic dysplasia* or gonadal dysgenesis or subdivided left atrium* or cardiovertebral syndrome* or pharyngeal pouch syndrome* or thymic aplasia syndrome* or conotruncal anomaly face syndrome
#8 hepatic hypoplasia or arteriohepatic dysplasia* or turner* syndrome or noonan syndrome or arteriohepatic dysplasia* or bicuspid aortic valve
#9 (taussig* near/2 anomal*)
#10 (pulmon* or aortic or subaortic or valve or mitral) next stenosis
#11 ((aortic or aorta*) near/3 coarctation*)
#12 (ventricular near/2 dysplasia*)
#13 (barth syndrome or cor triatriatum or cortriatriatum or triatrial heart*)
#14 (velo* near/3 syndrome*)
#15 (myocardial bridging* or crisscross heart* or criss-cross heart*)
#16 (dextrocardia* or kartagener* syndrome or kartagener* triad or siewert* syndrome or primary ciliary dyskinesia)
#17 "patent ductus arteriosus" or "scimitar syndrome" or "anomalous pulmonary venous connection" or "double inlet left ventricle" or "double outlet right ventricle" or "interrupted aortic arch"
#18 (ebstein* anomaly or ebstein* malformation* or ectopia cordis)
#19 (eisenmenger* next (complex or syndrome))
#20 (persistent truncus arteriosus or persistent ostium primum)
#21 endocardial cushion defect* or "atrioventricular canal"
#22 (foramen oval* or lutembacher* syndrome)
#23 (heart near/3 hypoplas*)
#24 ((noncompaction near/3 ventricular myocardium) or (non compaction near/3 ventricular myocardium))
#25 ((leopard or multiple lentigines) next syndrome*)
#26 levocardia or marfan* syndrome
#27 ((tetralogy or trilogy or syndrome) near/2 fallot*) or cantrell* or “shone's"
#28 (tricuspid atresia* or valve atresia* or pulmonary atresia or absent right atrioventricular connection)
#29 single ventricle physiology or GUCH or fontan procedure or cavopulmonary connection
#30 ((reparative or repair*) near/2 (cardiac surgery or heart surgery))
#31 (bonnevie near/2 (syndrome* or status)) or polynesian bronchiectas*
#32 ((congenital* or birth or born neonat* or newborn* or infant* or pediatric* or paediatric* or child* or prematur*) and (heart* or cardiac* or cardiomyopath* or coronary or myocard* or septal* or aortopulmonary or aorticopulmonary or atrial or ventricular or intraventricular or ventricle* or surg* or operat* or preoperat* or postoperat* or perioperat* or bypass* or intensive care or critical care or ICU or PICU)):ti
#33 ((congenital* or birth or born or neonat* or newborn* or infant* or pediatric* or paediatric* or child* or prematur*) near/5 (heart* or cardiac* or cardiomyopath* or coronary or myocard* or septal* or aortopulmonary or aorticopulmonary or atrial or ventricular or intraventricular or ventricle* or surg* or operat* or preoperat* or postoperat* or perioperat* or bypass* or intensive care or critical care or ICU or PICU)):ab
#34 #1 or #2 or #3 or #4 or #5 or #6 or #7 or #8 or #9 or #10 or #11 or #12 or #13 or #14 or #15 or #16 or #17 or #18 or #19 or #20 or #21 or #22 or #23 or #24 or #25 or #26 or #27 or #28 or #29 or #30 or #31 or #32 or #33
#35 MeSH descriptor: [Blood Transfusion] this term only
#36 MeSH descriptor: [Blood Component Transfusion] this term only
#37 MeSH descriptor: [Erythrocyte Transfusion] this term only
#38 MeSH descriptor: [Erythrocytes] this term only
#39 ((blood or erythrocyte* or red cell* or red blood cell* or RBC*) near/3 (transfus* or infus* or hypertransfus* or retransfus*))
#40 ((transfus* or retransfus*) near/1 (trigger* or level* or threshold* or rule* or restrict*))
#41 (transfusion* near/2 (management or practice* or polic* or strateg* or guideline* or indication* or protocol* or criteri* or autologous))
#42 ((blood near/2 management) or "blood sparing" or "cell salvage" or "blood support" or (blood near/2 requirement*) or autotransfus*)
#43 (red cell* management or red cell* sparing or red cell* support or (red cell* near/3 requirement*))
#44 (blood near/1 need*) or "whole blood"
#45 (leukodeplet* or leukoreduc* or leucodeplet* or leucoreduc* or leukofiltrat* or leucofiltrat*):ti
#46 ((leukocyte* or leucocyte*) near/2 (remov* or deplet* or reduc* or poor or filtrat*)):ti
#47 hemotransfus* or haemotransfus* or hemotherap* or haemotherap*
#48 (red cell* or red blood cell* or erythrocyte* or whole blood or RBC* or transfus*):ti
#49 (bypass near/5 (prime or priming))
#50 ((blood or erythrocyte* or red cell* or red blood cell* or RBC*) near/3 (exchang* or replac*))
#51 #35 or #36 or #37 or #38 or #39 or #40 or #41 or #42 or #43 or #44 or #45 or #46 or #47 or #48 or #49 or #50
#52#34 and #51

 

MEDLINE (Ovid)

1. exp Heart Defects, Congenital/
2. exp Heart Diseases/cn
3. ((heart* or cardiac* or coronary or septal* or aortopulmonary or aorticopulmonary or atrial or ventricular or intraventricular) adj3 (congenital* or defect* or abnormal* or anomal*)).tw.
4. (digeorge adj (syndrome* or anomal* or sequenc*)).tw.
5. (transpos* adj3 (arteries or artery or vessel*)).tw.
6. (alagille adj2 syndrome).tw.
7. (arteriohepatic dysplasia* or gonadal dysgenesis or subdivided left atrium* or cardiovertebral syndrome* or pharyngeal pouch syndrome* or thymic aplasia syndrome* or conotruncal anomaly face syndrome).tw.
8. (hepatic hypoplasia or arteriohepatic dysplasia* or turner* syndrome or noonan syndrome or arteriohepatic dysplasia* or bicuspid aortic valve).tw.
9. (taussig* adj2 anomal*).tw.
10. ((pulmon* or aortic or subaortic or valve or mitral) adj stenosis).tw.
11. ((aortic or aorta*) adj3 coarctation*).tw.
12. (ventricular adj2 dysplasia*).tw.
13. (barth syndrome or cor triatriatum or cortriatriatum or triatrial heart*).tw.
14. (velo* adj3 syndrome*).tw.
15. (myocardial bridging* or crisscross heart* or criss-cross heart*).tw.
16. (dextrocardia* or kartagener* syndrome or kartagener* triad or siewert* syndrome or primary ciliary dyskinesia).tw.
17. ("patent ductus arteriosus" or "scimitar syndrome" or "anomalous pulmonary venous connection" or "double inlet left ventricle" or "double outlet right ventricle" or "interrupted aortic arch").tw.
18. (ebstein* anomaly or ebstein* malformation* or ectopia cordis).tw.
19. (eisenmenger* adj (complex or syndrome)).tw.
20. (persistent truncus arteriosus or persistent ostium primum).tw.
21. (endocardial cushion defect* or atrioventricular canal).tw.
22. (foramen oval* or lutembacher* syndrome).tw.
23. (heart adj3 hypoplas*).tw.
24. ((noncompaction adj3 ventricular myocardium) or (non compaction adj3 ventricular myocardium)).tw.
25. ((leopard or multiple lentigines) adj syndrome*).tw.
26. (levocardia or marfan* syndrome).tw.
27. (((tetralogy or trilogy or syndrome) adj2 fallot*) or cantrell* or shon?s).tw.
28. (tricuspid atresia* or valve atresia* or pulmonary atresia or absent right atrioventricular connection).tw.
29. (single ventricle physiology or GUCH or fontan procedure or cavopulmonary connection).tw.
30. ((reparative or repair*) adj2 (cardiac surgery or heart surgery)).tw.
31. arterial switch.tw.
32. ((bonnevie adj2 (syndrome* or status)) or polynesian bronchiectas*).tw.
33. ((congenital* or birth or born or neonat* or newborn* or infant* or pediatric* or paediatric* or child* or prematur*) and (heart* or cardiac* or cardiomyopath* or coronary or myocard* or septal* or aortopulmonary or aorticopulmonary or atrial or ventricular or intraventricular or ventricle* or surg* or operat* or preoperat* or postoperat* or perioperat* or bypass* or intensive care or critical care or ICU or PICU)).ti.
34. ((congenital* or birth or born or neonat* or newborn* or infant* or pediatric* or paediatric* or child* or prematur*) adj5 (heart* or cardiac* or cardiomyopath* or coronary or myocard* or septal* or aortopulmonary or aorticopulmonary or atrial or ventricular or intraventricular or ventricle* or surg* or operat* or preoperat* or postoperat* or perioperat* or bypass* or intensive care or critical care or ICU or PICU)).ab.
35. or/1-34
36. BLOOD TRANSFUSION/
37. BLOOD COMPONENT TRANSFUSION/
38. ERYTHROCYTE TRANSFUSION/
39. ERYTHROCYTES/
40. ((blood or erythrocyte* or red cell* or red blood cell* or RBC*) adj3 (transfus* or infus* or hypertransfus* or retransfus*)).ti,ab.
41. ((transfus* or retransfus*) adj1 (trigger* or level* or threshold* or rule* or restrict*)).ti,ab.
42. ((blood or erythrocyte* or red cell* or red blood cell* or RBC*) adj3 (exchang* or replac*)).tw.
43. (transfusion* adj2 (management or practice* or polic* or strateg* or guideline* or indication* or protocol* or criteri* or autologous)).ti,ab.
44. ((blood adj2 management) or blood sparing or cell salvage or cell saver* or (blood adj2 salvag*) or blood support or (blood adj2 requirement*) or autotransfus*).ti,ab.
45. (red cell* management or red cell* sparing or red cell* support or (red cell* adj3 requirement*)).ti,ab.
46. ((blood adj1 need*) or whole blood or blood product* or blood component*).ti,ab.
47. (leukodeplet* or leukoreduc* or leucodeplet* or leucoreduc* or leukofiltrat* or leucofiltrat*).ti.
48. ((leukocyte* or leucocyte*) adj2 (remov* or deplet* or reduc* or poor or filtrat*)).ti.
49. (hemotransfus* or haemotransfus* or hemotherap* or haemotherap*).tw.
50. (red cell* or red blood cell* or erythrocyte* or whole blood or RBC* or transfus* or retransfus*).ti.
51. (bypass adj5 (prime or priming)).tw.
52. or/36-51
53. 35 and 52
54. randomized controlled trial.pt.
55. controlled clinical trial.pt.
56. randomi*.tw.
57. placebo.ab.
58. clinical trials as topic.sh.
59. randomly.ab.
60. groups.ab.
61. trial.ti.
62. or/54-61
63. exp animals/ not humans/
64. 62 not 63
65. 53 and 64

 

EMBASE (Ovid)

1. exp Congenital Heart Disease/
2. exp Congenital Blood Vessel Malformation/
3. exp Heart Disease/cn
4. ((heart* or cardiac* or coronary or septal* or aortopulmonary or aorticopulmonary or atrial or ventricular or intraventricular) adj3 (congenital* or defect* or abnormal* or anomal*)).tw.
5. (digeorge adj (syndrome* or anomal* or sequenc*)).tw.
6. (transpos* adj3 (arteries or artery or vessel*)).tw.
7. (alagille adj2 syndrome).tw.
8. (arteriohepatic dysplasia* or gonadal dysgenesis or subdivided left atrium* or cardiovertebral syndrome* or pharyngeal pouch syndrome* or thymic aplasia syndrome* or conotruncal anomaly face syndrome).tw.
9. (hepatic hypoplasia or arteriohepatic dysplasia* or turner* syndrome or noonan syndrome or arteriohepatic dysplasia* or bicuspid aortic valve).tw.
10. (taussig* adj2 anomal*).tw.
11. ((pulmon* or aortic or subaortic or valve or mitral) adj stenosis).tw.
12. ((aortic or aorta*) adj3 coarctation*).tw.
13. (ventricular adj2 dysplasia*).tw.
14. (barth syndrome or cor triatriatum or cortriatriatum or triatrial heart*).tw.
15. (velo* adj3 syndrome*).tw.
16. (myocardial bridging* or crisscross heart* or criss-cross heart*).tw.
17. (dextrocardia* or kartagener* syndrome or kartagener* triad or siewert* syndrome or primary ciliary dyskinesia).tw.
18. ("patent ductus arteriosus" or "scimitar syndrome" or "anomalous pulmonary venous connection" or "double inlet left ventricle" or "double outlet right ventricle" or "interrupted aortic arch").tw.
19. (ebstein* anomaly or ebstein* malformation* or ectopia cordis).tw.
20. (eisenmenger* adj (complex or syndrome)).tw.
21. (persistent truncus arteriosus or persistent ostium primum).tw.
22. (endocardial cushion defect* or atrioventricular canal).tw.
23. (foramen oval* or lutembacher* syndrome).tw.
24. (heart adj3 hypoplas*).tw.
25. ((noncompaction adj3 ventricular myocardium) or (non compaction adj3 ventricular myocardium)).tw.
26. ((leopard or multiple lentigines) adj syndrome*).tw.
27. (levocardia or marfan* syndrome).tw.
28. (((tetralogy or trilogy or syndrome) adj2 fallot*) or cantrell* or shon?s).tw.
29. (tricuspid atresia* or valve atresia* or pulmonary atresia or absent right atrioventricular connection).tw.
30. (single ventricle physiology or GUCH or fontan procedure or cavopulmonary connection).tw.
31. ((reparative or repair*) adj2 (cardiac surgery or heart surgery)).tw.
32. arterial switch.tw.
33. ((bonnevie adj2 (syndrome* or status)) or polynesian bronchiectas*).tw.
34. ((congenital* or birth or born or neonat* or newborn* or infant* or pediatric* or paediatric* or child* or prematur*) and (heart* or cardiac* or cardiomyopath* or coronary or myocard* or septal* or aortopulmonary or aorticopulmonary or atrial or ventricular or intraventricular or ventricle* or surg* or operat* or preoperat* or postoperat* or perioperat* or bypass* or intensive care or critical care or ICU or PICU)).ti.
35. ((congenital* or birth or born or neonat* or newborn* or infant* or pediatric* or paediatric* or child* or prematur*) adj5 (heart* or cardiac* or cardiomyopath* or coronary or myocard* or septal* or aortopulmonary or aorticopulmonary or atrial or ventricular or intraventricular or ventricle* or surg* or operat* or preoperat* or postoperat* or perioperat* or bypass* or intensive care or critical care or ICU or PICU)).ab.
36. or/1-35
37. BLOOD TRANSFUSION/
38. BLOOD COMPONENT THERAPY/
39. ERYTHROCYTE TRANSFUSION/
40. ERYTHROCYTE/
41. ((blood or erythrocyte* or red cell* or red blood cell* or RBC*) adj3 (transfus* or infus* or hypertransfus* or retransfus*)).ti,ab.
42. ((transfus* or retransfus*) adj1 (trigger* or level* or threshold* or rule* or restrict*)).ti,ab.
43. (transfusion* adj2 (management or practice* or polic* or strateg* or guideline* or indication* or protocol* or criteri* or autologous)).ti,ab.
44. ((blood adj2 management) or blood sparing or cell salvage or cell saver* or (blood adj2 salvag*) or blood support or (blood adj2 requirement*) or autotransfus*).ti,ab.
45. (red cell* management or red cell* sparing or red cell* support or (red cell* adj3 requirement*)).ti,ab.
46. ((blood adj1 need*) or whole blood or blood product* or blood component*).ti,ab.
47. ((blood or erythrocyte* or red cell* or red blood cell* or RBC*) adj3 (exchang* or replac*)).tw.
48. (leukodeplet* or leukoreduc* or leucodeplet* or leucoreduc* or leukofiltrat* or leucofiltrat*).ti.
49. ((leukocyte* or leucocyte*) adj2 (remov* or deplet* or reduc* or poor or filtrat*)).ti.
50. (hemotransfus* or haemotransfus* or hemotherap* or haemotherap*).tw.
51. (red cell* or red blood cell* or erythrocyte* or whole blood or RBC* or transfus* or retransfus*).ti.
52. (bypass adj5 (prime or priming)).tw.
53. or/37-52
54. 36 and 53
54. Randomized Controlled Trial/
55. Randomization/
56. Single Blind Procedure/
57. Double Blind Procedure/
58. Crossover Procedure/
59. Placebo/
60. exp Clinical Trial/
61. Prospective Study/
62. (randomi* or double-blind* or single-blind* or RCT*).tw.
63. (random* adj2 (allocat* or assign* or divid* or receiv*)).tw.
64. (crossover* or cross over* or cross-over* or placebo*).tw.
65. ((treble or triple) adj blind*).tw.
66. or/54-65
67. Case Study/
68. case report*.tw.
69. (note or letter or editorial).pt.
70. or/67-69
71. 66 not 70
72. 54 and 71
73. limit 72 to embase

 

PubMed (epublications only)

#1 ((blood[ti] OR erythrocyte*[ti] OR red cell*[ti] OR red blood cell*[ti] OR RBC*[ti]) AND (transfus*[ti] OR infus*[ti] OR hypertransfus*[ti] OR retransfus*[ti])) OR ((transfus*[ti] OR retransfus*[ti]) AND (trigger*[ti] OR level*[ti] OR threshold*[ti] OR rule*[ti] OR restrict*[ti])) OR (transfusion*[ti] AND (management[ti] OR practice*[ti] OR polic*[ti] OR strateg*[ti] OR guideline*[ti] OR indication*[ti] OR protocol*[ti] OR criteri*[ti]))
#2 (“blood management” OR “blood sparing” OR “cell salvage” OR “blood salvage” OR “blood support” OR “blood requirement*[ti]” OR “blood product*” OR “blood component*”) OR (red cell*[ti] AND (management[ti] OR sparing[ti] OR support[ti] OR requirement*[ti])) OR (“need for blood”[ti] OR whole blood[ti] OR “use of blood”[ti])
#3 (leukodeplet*[ti] OR leukoreduc*[ti] OR leucodeplet*[ti] OR leucoreduc*[ti] OR leukofiltrat*[ti] OR leucofiltrat*[ti]) OR ((leukocyte*[ti] OR leucocyte*[ti]) AND (remov*[ti] OR deplet*[ti] OR reduc*[ti] OR poor[ti] OR filtrat*[ti])) OR (hemotransfus*[ti] OR haemotransfus*[ti] OR red cell*[ti] OR red blood cell*[ti] OR erythrocyte*[ti] OR RBC*[ti] OR transfus*[ti]) OR (bypass[ti] AND (prime*[ti] OR priming[ti]))
#4 #1 OR #2 OR #3
#5 ((congenital*[ti] OR birth[ti] OR born[ti] OR neonat*[ti] OR newborn*[ti] OR infant*[ti] OR pediatric*[ti] OR paediatric*[ti] OR child*[ti] OR prematur*[ti] OR defect*[ti] OR abnormal*[ti] OR anomal*[ti]) AND (heart*[ti] OR cardiac*[ti] OR cardiomyopath*[ti] OR coronary[ti] OR myocard*[ti] OR septal*[ti] OR aortopulmonary[ti] OR aorticopulmonary[ti] OR atrial[ti] OR ventricular[ti] OR intraventricular[ti] OR ventricle*[ti] OR surg*[ti] OR operat*[ti] OR preoperat*[ti] OR postoperat*[ti] OR perioperat*[ti] OR bypass*[ti] OR intensive care[ti] OR critical care[ti] OR ICU[ti] OR PICU[ti]))
#6 #4 AND #5
#7 (random* OR blind* OR trial OR allocat* OR assign* OR "control group" OR groups OR intervention*)
#8 #6 AND #7
#9 publisher[sb] NOT pubstatusnihms
#10 #8 AND #9

 

CINAHL (EBSCO)

S1 (MH "Heart Defects, Congenital+")
S2 TI ((heart* or cardiac* or coronary or septal* or aortopulmonary or aorticopulmonary or atrial or ventricular or intraventricular) N3 (congenital* or neonat* or defect* or abnormal* or anomal*)) OR AB ((heart* or cardiac* or coronary or septal* or aortopulmonary or aorticopulmonary or atrial or ventricular or intraventricular) N3 (congenital* or neonat* or defect* or abnormal* or anomal*))
S3 TI (transpos* N3 (arteries or artery or vessel*)) OR AB (transpos* N3 (arteries or artery or vessel*))
S4 TI (alagille N2 syndrome) OR AB (alagille N2 syndrome)
S5 TI ((hepatic hypoplasia) OR (arteriohepatic dysplasia*) OR (turner* syndrome) OR (noonan syndrome) OR (arteriohepatic dysplasia*) OR (bicuspid aortic valve)) OR AB ((hepatic hypoplasia) OR (arteriohepatic dysplasia*) OR (turner* syndrome) OR (noonan syndrome) OR (arteriohepatic dysplasia*) OR (bicuspid aortic valve))
S6 TI ((pulmon* or aortic or subaortic or valve or mitral) N1 stenosis) OR AB ((pulmon* or aortic or subaortic or valve or mitral) N1 stenosis)
S7 TI ((aortic or aorta*) N3 coarctation) OR AB ((aortic or aorta*) N3 coarctation)
S8 TI (ventricular N2 dysplasia*) OR AB (ventricular N2 dysplasia*)
S9 TI ((barth syndrome) or (cor triatriatum) or cortriatriatum or (triatrial heart*)) OR AB ((barth syndrome) or (cor triatriatum) or cortriatriatum or (triatrial heart*))
S10 TI (coronary vessel* N2 anomal*) OR AB (coronary vessel* N2 anomal*)
S11 TX (myocardial bridging) or TX (arterial switch*) or TX (crisscross heart*) or TX (criss-cross heart*)
S12 TI (dextrocardia*) or TX (kartagener* syndrome) or TX (kartagener* triad) or TX (siewert* syndrome) or TX (primary ciliary dyskinesia)
S13 TI ("patent ductus arteriosus" or "scimitar syndrome" or "anomalous pulmonary venous connection" or "double inlet left ventricle" or "double outlet right ventricle" or "interrupted aortic arch") OR AB ("patent ductus arteriosus" or "scimitar syndrome" or "anomalous pulmonary venous connection" or "double inlet left ventricle" or "double outlet right ventricle" or "interrupted aortic arch")
S14 TI ("ebstein* anomaly" or "ebstein* malformation*" or "ectopia cordis") OR AB ("ebstein* anomaly" or "ebstein* malformation*" or "ectopia cordis")
S15 TI (eisenmenger* N1 (complex or syndrome)) OR AB (eisenmenger* N1 (complex or syndrome))
S16 TI ("persistent truncus arteriosus" or "persistent ostium primum" or "endocardial cushion defect*" or "atrioventricular canal" or "foramen oval*" or "lutembacher* syndrome") OR AB ("persistent truncus arteriosus" or "persistent ostium primum" or "endocardial cushion defect*" or "atrioventricular canal" or "foramen oval*" or "lutembacher* syndrome")
S17 TI (heart N3 hypoplas*) OR AB (heart N3 hypoplas*)
S18 TI ((noncompaction N3 "ventricular myocardium") or TI ("non compaction" N3 "ventricular myocardium"))
S19 AB ((noncompaction N3 "ventricular myocardium") or AB ("non compaction" N3 "ventricular myocardium"))
S20 TI ((leopard or multiple lentigines) N1 syndrome*) OR AB ((leopard or multiple lentigines) N1 syndrome*)
S21 TI (levocardia or marfan* syndrome) OR AB (levocardia or marfan* syndrome)
S22 TI (((tetralogy or trilogy or syndrome) N2 fallot*) or cantrell* or shone?s) OR AB (((tetralogy or trilogy or syndrome) N2 fallot*) or cantrell* or shone?s)
S23 TI ((double outlet N3 ventricle) or taussig bing anomaly) OR AB ((double outlet N3 ventricle) or taussig bing anomaly)
S24 TI (tricuspid atresia* or valve atresia* or pulmonary atresia* or absent right atrioventricular connection) OR AB (tricuspid atresia* or valve atresia* or pulmonary atresia* or absent right atrioventricular connection)
S25 TI (single ventricle physiology or GUCH or fontan procedure or cavopulmonary connection) OR AB (single ventricle physiology or GUCH or fontan procedure or cavopulmonary connection)
S26 TI ((reparative or repair*) N2 TX (cardiac surgery or heart surgery)) OR AB ((reparative or repair*) N2 TX (cardiac surgery or heart surgery))
S27 TI ((bonnevie N2 TX (syndrome* or status)) or polynesian bronchiectas*) OR AB ((bonnevie N2 TX (syndrome* or status)) or polynesian bronchiectas*)
S28 TI ((congenital* or birth or born or neonat* or newborn* or infant* or pediatric* or paediatric* or child* or prematur*) N5 (heart* or cardiac* or cardiomyopath* or coronary or myocard* or septal* or aortopulmonary or aorticopulmonary or atrial or ventricular or intraventricular or ventricle* or surg* or operat* or preoperat* or postoperat* or perioperat* or bypass* or intensive care or critical care or ICU or PICU))
S29 AB ((congenital* or birth or born or neonat* or newborn* or infant* or pediatric* or paediatric* or child* or prematur*) N5 (heart* or cardiac* or cardiomyopath* or coronary or myocard* or septal* or aortopulmonary or aorticopulmonary or atrial or ventricular or intraventricular or ventricle* or surg* or operat* or preoperat* or postoperat* or perioperat* or bypass* or intensive care or critical care or ICU or PICU))
S30 S1 OR S2 OR S3 OR S4 OR S5 OR S6 OR S7 OR S8 OR S9 OR S10 OR S11 OR S12 OR S13 OR S14 OR S15 OR S16 OR S17 OR S18 OR S19 OR S20 OR S21 OR S22 OR S23 OR S24 OR S25 OR S26 OR S27 OR S28 OR S29
S31 (MH BLOOD TRANSFUSION)
S32 (MH BLOOD COMPONENT TRANSFUSION)
S33 (MH ERYTHROCYTE TRANSFUSION)
S34 (MH ERYTHROCYTES)
S35 TI ((blood or erythrocyte* or red cell* or red blood cell* or RBC*) N3 (transfus* or infus* or hypertransfus* or retransfus*)) OR AB ((blood or erythrocyte* or red cell* or red blood cell* or RBC*) N3 (transfus* or infus* or hypertransfus* or retransfus*))
S36 TI ((transfus* or retransfus*) N2 (trigger* or level* or threshold* or rule* or restrict*)) OR AB ((transfus* or retransfus*) N2 (trigger* or level* or threshold* or rule* or restrict*))
S37 TI (transfusion* N2 (management or practice* or polic* or strateg* or guideline* or indication* or protocol* or criteri* or autologous)) OR (transfusion* N2 (management or practice* or polic* or strateg* or guideline* or indication* or protocol* or criteri* or autologous))
S38 TI ((blood N2 management) or blood sparing or cell salvage or (blood N2 salvag*) or blood support or (blood N2 requirement*) or autotransfus*) OR AB ((blood N2 management) or blood sparing or cell salvage or (blood N2 salvag*) or blood support or (blood N2 requirement*) or autotransfus*)
S39 TI (red cell* management or red cell* sparing or red cell* support or (red cell* N3 requirement*)) OR AB (red cell* management or red cell* sparing or red cell* support or (red cell* N3 requirement*))
S40 TI ((blood N1 need*) or whole blood or blood product* or blood component*) OR AB ((blood N1 need*) or whole blood or blood product* or blood component*)
S41 TI (leukodeplet* or leukoreduc* or leucodeplet* or leucoreduc* or leukofiltrat* or leucofiltrat*)
S42 TI ((leukocyte* or leucocyte*) N2 (remov* or deplet* or reduc* or poor or filtrat
S43 TI (hemotransfus* or haemotransfus*) OR AB (hemotransfus* or haemotransfus*)
S44 TI (red cell* or red blood cell* or erythrocyte* or whole blood or RBC* or transfus*)
S45 TI (bypass N5 (prime or priming)) OR AB (bypass N5 (prime or priming))
S46 S31 OR S32 OR S33 OR S34 OR S35 OR S36 OR S37 OR S38 OR S39 OR S40 OR S41 OR S42 OR S43 OR S44 OR S45
S47 S30 AND S46
S48 (MH "Clinical Trials+")
S49 PT Clinical trial
S50 TI ((controlled trial*) or (clinical trial*)) OR AB ((controlled trial*) or (clinical trial*))
S51 TI ((singl* blind*) OR (doubl* blind*) OR (trebl* blind*) OR (tripl* blind*) OR (singl* mask*) OR (doubl* mask*) OR (tripl* mask*)) OR AB ((singl* blind*) OR (doubl* blind*) OR (trebl* blind*) OR (tripl* blind*) OR (singl* mask*) OR (doubl* mask*) OR (tripl* mask*))
S52 TI randomi* OR AB randomi*
S53 (MH "Random Assignment")
S54 TI ((phase three) or (phase III) or (phase three)) or AB ((phase three) or (phase III) or (phase three))
S55 TI (random* N2 (assign* or allocat*)) ) OR ( AB (random* N2 (assign* or allocat*))
S56 TI placebo* OR AB placebo*
S57 (MH "Placebos")
S58 (MH "Quantitative Studies")
S59 S48 OR S49 OR S50 RO S51 OR S52 OR S53 OR S54 OR S55 OR S56 OR S57 OR S58
S60 S47 AND S59

 

LILACS

(mh:("Blood Transfusion") OR mh:("Erythrocyte Transfusion") OR ti:(blood) OR ti:(erythrocyte*) OR ti:("red cell*") OR ti:(rbc*) OR ti:(transfus*) OR ti:(retransfus*) OR ti:("cell salvage")) AND (congenital* OR birth OR born OR neonat* OR newborn* OR infant* OR pediatric* OR paediatric* OR child* OR prematur* OR defect* OR abnormal* OR anomal* OR heart* OR cardiac* OR cardiomyopath* OR coronary OR myocard* OR septal* OR aortopulmonary OR aorticopulmonary OR atrial OR ventricular OR intraventricular OR ventricle* OR surg* OR operat* OR preoperat* OR postoperat* OR perioperat* OR bypass* OR “intensive care” OR “critical care” OR icu OR picu) AND db:("LILACS") AND type_of_study:("clinical_trials" OR "systematic_reviews")

 

Transfusion Evidence Library

(blood OR erythrocyte* OR red cell* OR RBC* OR transfus* OR retransfus* OR cell salvage) AND (congenital* OR birth OR born OR neonat* OR newborn* OR infant* OR pediatric* OR paediatric* OR child* OR prematur* OR defect* OR abnormal* OR anomal*) AND (heart* OR cardiac* OR cardiomyopath* OR coronary OR myocard* OR septal* OR aortopulmonary OR aorticopulmonary OR atrial OR ventricular OR intraventricular OR ventricle* OR surg* OR operat* OR preoperat* OR postoperat* OR perioperat* OR bypass* OR "intensive care" OR "critical care" OR ICU OR PICU)

 

Conference Proceedings Citation Index - Science (Web of Science)

(blood OR erythrocyte* OR red cell* OR RBC* OR transfus* OR retransfus* OR cell salvage) AND (congenital* OR birth OR born OR neonat* OR newborn* OR infant* OR pediatric* OR paediatric* OR child* OR prematur* OR defect* OR abnormal* OR anomal*) AND (heart* OR cardiac* OR cardiomyopath* OR coronary OR myocard* OR septal* OR aortopulmonary OR aorticopulmonary OR atrial OR ventricular OR intraventricular OR ventricle* OR surg* OR operat* OR preoperat* OR postoperat* OR perioperat* OR bypass* OR "intensive care" OR "critical care" OR ICU OR PICU)
AND (random* OR blind* OR trial OR allocat* OR assign* OR "control group" OR groups OR intervention*)

 

INDMED

(blood OR erythrocyte$ OR "red cell$" OR RBC$ OR transfus$ OR retransfus$ OR "cell salvage" OR autotransfus$)
AND
((congenital$ OR birth OR neonat$ OR newborn$ OR infant$ OR pediatric$ OR paediatric$ OR child$ OR prematur$ OR defect$ OR abnormal$ OR anomal$) AND (heart$ OR cardiac$ OR cardiomyopath$ OR coronary OR myocard$ OR septal$ OR aort$ OR atrial OR ventric$))
AND
(random$ OR blind$ OR trial OR allocat$ OR assign$ OR control$ OR groups)

 

KOREAMED & PAKMEDINET (n.b. these databases require free-text searching using various combinations of the following search terms)

(blood OR erythrocyte* OR "red cell*" OR RBC* OR transfus* OR retransfus* OR "cell salvage" OR autotransfus*) AND (heart* OR cardiac* OR cardiomyopath* OR coronary OR myocard* OR septal* OR aort* OR atrial OR ventric*) AND (random* OR blind* OR trial OR allocat* OR assign* OR control* OR groups)

 

ClinicalTrials.gov

Search Terms: infant OR infants OR neonate OR neonates OR neonatal OR newborn OR newborns OR congenital
Condition: heart OR cardiac OR cardiomyopathy OR coronary OR myocardial OR septal OR aortic OR atrial OR ventricular OR intraventricular OR aortopulmonary OR aorticopulmonary OR congenital
Intervention: blood OR erythrocyte OR "red cell" OR RBC OR transfusion OR retransfusion OR "cell salvage" OR autotransfusion OR bypass
Study Type: Interventional

 

ISRCTN

(infant OR infants OR birth OR neonate OR neonates OR neonatal OR newborn OR newborns OR premature OR prematurity OR congenital) AND (transfusion OR transfused OR red cell OR red cells OR RBC OR RBCs) AND (randomized OR randomised OR randomly)

 

WHO ICTRP

Condition: heart OR cardiac OR cardiomyopathy OR coronary OR myocardial OR septal OR aortic OR atrial OR ventricular OR intraventricular OR aortopulmonary OR aorticopulmonary OR congenital
Intervention: blood OR erythrocyte OR red cell OR RBC OR transfusion OR retransfusion OR autotransfusion OR bypass

 

What's new

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. Contributions of authors
  13. Declarations of interest
  14. Sources of support
  15. Differences between protocol and review
  16. Notes
  17. Index terms

Last assessed as up-to-date: 11 December 2013.


DateEventDescription

15 February 2013AmendedWe have added in a new (post hoc) outcome (biochemistry levels). Whilst there is only one of our included trials that measures this outcome, we are aware that this could be an important outcome both in this version of the review and in future updates. We overlooked the outcome at the protocol stage, hence its addition now.



 

Contributions of authors

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. Contributions of authors
  13. Declarations of interest
  14. Sources of support
  15. Differences between protocol and review
  16. Notes
  17. Index terms

Kirstin Wilkinson was the content expert for this review (congenital heart disease) and undertook the screening and selection of trials; data extraction; and assessment of risk of bias, analysis of results, and preparation of the protocol and final report.

Susan Brunskill was the methodological expert for this review and initially project managed the review, provided support and training to KW, undertook data extraction and assessment of risk bias, and provided support with data analysis and the initial preparation of the protocol and final report.

Carolyn Dorée was the information specialist who developed and implemented the search strategies, undertook the first sift of identified references, and contributed to the preparation of the protocol and final report.  

Marialena Trivella was a methodological and statistical expert and provided support with data analysis and contributed to the preparation of the final report.

Ravi Gill was a content expert for this review (congenital heart disease) and contributed to the final report.

Mike Murphy was a content expert for this review (red cells and transfusion) and contributed to the preparation of the protocol and final report.

 

Declarations of interest

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. Contributions of authors
  13. Declarations of interest
  14. Sources of support
  15. Differences between protocol and review
  16. Notes
  17. Index terms

None.

 

Sources of support

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. Contributions of authors
  13. Declarations of interest
  14. Sources of support
  15. Differences between protocol and review
  16. Notes
  17. Index terms
 

Internal sources

  • NHS Blood and Transplant, Research and Development, UK.

 

External sources

  • No sources of support supplied

 

Differences between protocol and review

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. Contributions of authors
  13. Declarations of interest
  14. Sources of support
  15. Differences between protocol and review
  16. Notes
  17. Index terms

February 2013: We have added in a new (post hoc) outcome, biochemistry levels. While there is only one of our included trials that measures this outcome, we are aware that this could be an important outcome both in this version of the review and in future updates. We overlooked the outcome at the protocol stage, hence its addition now. We have also updated the references in the background to included recently published, hence more up-to-date data.

 

Notes

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. Contributions of authors
  13. Declarations of interest
  14. Sources of support
  15. Differences between protocol and review
  16. Notes
  17. Index terms

None.

* Indicates the major publication for the study

References

References to studies included in this review

  1. Top of page
  2. AbstractRésumé scientifique
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Differences between protocol and review
  17. Notes
  18. Characteristics of studies
  19. References to studies included in this review
  20. References to studies excluded from this review
  21. References to studies awaiting assessment
  22. References to ongoing studies
  23. Additional references
Cholette 2011 {published data only}
  • Cholette J. A prospective, randomised, controlled clinical trial comparing two transfusion strategies in pediatric patients undergoing cavopulmonary connection. clinicaltrials.gov/show/NCT00350220 (accessed 3 February 2014).
  • Cholette JM, Rubenstein JS, Alfieris GM, Powers KS, Eaton M, Lerner NB. Children with single ventricle physiology do not benefit from higher hemoglobin levels post cavopulmonary connection: results of a prospective, randomized, controlled trial of a restrictive versus liberal red-cell transfusion strategy. Pediatric Critical Care Medicine 2011;12(1):39-45.
Cholette 2012 {published and unpublished data}
  • Cholette JM. Washed versus standard blood cell transfusions in pediatric open heart surgery. clinicaltrials.gov/show/NCT00693498 (accessed 3 February 2014).
  • Cholette JM, Henrichs K, Alfieris GM, Phipps R, Blum-Berg N. Washing blood transfused in pediatric open heart surgery reduces post-operative inflammation and immunomodulation: results of a prospective, randomized controlled trials. Pediatric Clinical Care Medicine 2011;12(4 Suppl 1):s83.
  • Cholette JM, Henrichs KF, Alferis GM, Phipps RP, Spinelli SL, Gensini FJ, et al. Washed red cells reduce the inflammatory response to transfusion in pediatric cardiac surgery: results of a randomized clinical trial. Transfusion 2011;21:18A.
  • Cholette JM, Henrichs KF, Alfieris GM, Powers KS, Phipps R, Spinelli, et al. Washing red blood cells and platelets transfused in cardiac surgery reduces postoperative inflammation and number of transfusions: results of a prospective, randomized, controlled clinical trials. Pediatric Critical Care Medicine 2012;13(3):290-9.
de Vries 2004 {published and unpublished data}
Han 2004 {published data only}
Hosking 1990 {published data only}
  • Hosking MP, Beynen FM, Raimundo HS, Oliver WC, Williamson KR. A comparison of washed red blood cells versus packed red blood cells (AS-1) for cardiopulmonary bypass prime and their effects on blood glucose concentration in children. Anesthesiology 1990;72:987-90.
Komai 1998 {published and unpublished data}
Liu 2007 {published data only}
  • Liu J, Ji B, Feng Z, Zhao J, Li C, Li B, et al. The effect of preprocessing stored red blood cells on neonates undergoing corrective cardiac surgery. American Society for Artificial Internal Organs 2007;53(6):680-3.
Shimpo 2001 {published data only}
  • Shimpo H, Shimamoto A, Sawamura Y, Fujinaga K, Kanemitsu S, Onoda K, et al. Ultrafiltration of the priming blood before cardiopulmonary bypass attenuates inflammatory response and improves postoperative clinical course in pediatric patients. Shock 2001;16(Suppl 1):51-4.
Swindell 2007 {published data only}
  • Swindell CG, Barker TA, McGuirk SP, Jones TJ, Barron DJ, Brawn WJ, et al. Washing of irradiated red blood cells prevents hyperkalemia during cardiopulmonary bypass in neonates and infants undergoing surgery for complex congenital heart disease. European Journal of Cardio-thoracic Surgery 2007;31:659-64.
Willems 2010 {published data only}
  • Adams ES. A critical appraisal of "transfusion strategies for patients in pediatric intensive care units" by Lacroix J, Hebert PC, Hutchison, et al (New England Journal of Medicine 2007; 356:1609-1619). Pediatric Critical Care Medicine 209;10(3):393-6.
  • Gauvin F, Spinella PC, Lacroix J, Choker G, Ducruet T, Karam O, et al. Association between length of storage of transfused red blood cells and multiple organ dysfunction syndrome in pediatric intensive care patients. Transfusion 2010;50(9):1902-13.
  • Lacroix J. Transfusion requirements in paediatric intensive care unit: a multicentre randomised controlled non-inferiority clinical trial. CIHR-RCT 130770 2001.
  • Lacroix J. Transfusion requirements in pediatric intensive care units study: a multicenter randomised controlled non-inferiority clinical trial. ISCRTN register, record number 130770 2007.
  • Lacroix J,  Hebert PC,  Collet J,  Ducruet T,  Gauvin F,  Hume HA, et al. Transfusion requirements in pediatric intensive care units - a multicenter randomized controlled clinical trial. Transfusion 2006;49 (9s)(2A):Abstract No. P4 - 030A.
  • Rouette J, Trottier H, Ducruet T, Beaunoyer M, Lacroix J, Tucci M. Transfusion threshold in post-surgical pediatric intensive care patients. Transfusion 2008;48(Suppl):48A Abstract S128-040D.
  • Rouette J, Trottier H, Ducruet T, Beaunoyer M, Lacroix J, Tucci M, et al. Red blood cell transfusion threshold in postsurgical pediatric intensive care patients: a randomized clinical trial. Annals of Surgery 2010;251(3):421-7.
  • Willems A, Harrington K, Lacroix J, Biarent D, Joffe AR, Wensley D, et al. Comparison of two red-cell transfusion strategies after pediatric cardiac surgery: a subgroup analysis. Critical Care Medicine 2010;38(2):649-56.
Ye 2013 {published data only}
  • Ye L, Lin R, Fan Y, Yang L, Hu JL, Shu Q. Effects of circuit residual volume salvage reinfusion on the postoperative clinical outcome for pediatric patients undergoing cardiac surgery. Pediatric Cardiology 2013;34:1088-93.

References to studies excluded from this review

  1. Top of page
  2. AbstractRésumé scientifique
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Differences between protocol and review
  17. Notes
  18. Characteristics of studies
  19. References to studies included in this review
  20. References to studies excluded from this review
  21. References to studies awaiting assessment
  22. References to ongoing studies
  23. Additional references
Blackwood 2010 {published data only}
  • Blackwood J, Joffe AR, Robertson CMT, Dinu, IA, Alton G, Penner K, et al. Association of hemoglobin and transfusion with outcome after operations for hypoplastic left heart. Annals of Thoracic Surgery 2010;89(5):1378-84.
Chicella 2003 {published data only}
  • Chicella MF, Jansen P, Falkos S, Krueger KP. Randomized, double-blind, placebo-controlled trial of recombinant human erythropoietin administration to reduce red blood cell transfusions in anaemic pediatric intensive care patients. Pharmacotherapy 2003;23(3):110.
Cholette 2013 {published data only}
  • Cholette JM, Powers KS, Alfieris GM, Angona R, Henrichs KF, Masel D, et al. Transfusion of cell saver salvaged blood in neonates and infants undergoing open heart surgery significantly reduces RBC and coagulant product transfusions and donor exposures: results of a prospective, randomized, clinical trial. Pediatric Critical Care Medicine 2013;14(2):137-47.
Dietrich 2005 {published data only}
  • Dietrich W, Thuermel K, Heyde S, Busley R, Berger K. Autologous blood donation in cardiac surgery: reduction of allogeneic blood transfusion and cost-effectiveness. Journal of Cardiothoracic and Vascular Anesthesia 2005;19(5):589-96.
Embil 1968 {published data only}
  • Embil JA, Folkins DF, Haldane EV, van Rooyen CE. Cytomegalovirus infection following extracorporeal circulation in children. A prospective study. Lancet 1968;2(7579):1151-5.
Fergusson 2009 {published data only}
  • Fergusson D, Hutton B, Hogan DL, LeBel L, Blajchman MA, Ford JC, et al. The age of red blood cells in premature infants (ARIPI) randomized controlled trial: study design. Transfusion Medicine Reviews 2009;23(1):55-61.
Germann 1998 {published data only}
  • Germann R, Filar TB, Schmid ER. Strategies to reduce blood loss and transfusion requirements in pediatric cardiac surgery. Anaesthesiologica Scandinavica 1998;42(112):81-4.
Gruenwald 2008 {published data only}
  • Gruenwald CE, McCrindle BE, Crawford- Lean L, Holtby H, Parshuram C, Massicotte P, et al. Reconstituted fresh whole blood improves clinical outcomes compared with stored component blood therapy for neonates undergoing cardiopulmonary bypass for cardiac surgery: a randomized controlled trial. Journal of Thoracic and Cardiovascular Surgery 2008;136(6):1442-9.
Gupta 2007 {published data only}
  • Gupta S, Wyllie J. Hemodynamic effects of packed red blood cell transfusion volume in premature infants - results of a randomised controlled trial. Paediatric Academic Societies Meeting. 2007; Vol. Board number 405, Course number 5899:Abstract number 250.
Hertfelder 1992 {published and unpublished data}
  • Hertfelder H-J, Papov-Cenic S, Urban A, Dusterwald M, Brecher AM. Activation of hemostasis by transfusions of whole blood or blood components in open heart surgery of children. Annals of Hematology 1992;64 (Suppl):A32.
Kaltmann 2010 {published data only}
  • Kaltman JR, Andropoulos DB, Checchia PA, Gaynor JW, Hoffman TM, Laussen PC, et al. Report of the Pediatric Heart Network and National Heart, Lung, and Blood Institute Working Group on the perioperative management of congenital heart disease. Circulation 2010;121(25):2766-73.
Kipps 2011 {published data only}
  • Kipps AK, Wypij D, Thiagarajan RR, Bacha EA, Newburger JW. Blood transfusion is associated with prolonged duration of mechanical ventilation in infants undergoing reparative cardiac surgery. Pediatric Critical Care Medicine 2011;12(1):52-6.
Manno 1991 {published data only}
  • Manno C,  Hedberg K,  Kim H,  Bunin G,  Nicolson S,  Jobes D, et al. Comparison of the hemostatic effects of fresh whole blood, stored whole blood, and components after open heart surgery in children. Blood 1991;77(5):930-6.
McEwan 2007 {published data only}
Moritz 2000 {published data only}
  • Moritz A,  Tschaut R,  Latz S, Leon-Wyss J,  Schmitz C,  Hillyer P, et al. The use of fresh blood, whole blood and blood components in pediatric open heart surgery. Kardiotechnik 2009;9(1):16-20.
Mou 2004 {published data only}
  • Mou S,  Giroir B,  Molitor-Kirsch E, Leonard S,  Nikaidoh H,  Nizzi F, et al. Fresh whole blood versus reconstituted blood for pump priming in heart surgery in infants. New England Journal of Medicine 2004;351(16):1635-44.
Newburger 2008 {published data only}
  • Newburger JW, Jonas RA, Soul J, Kussman BD, Bellinger DC, Laussen PC, et al. Randomized trial of haematocrit 25% versus 35% during hypothermic cardiopulmonary bypass in infant heart surgery. Journal of Thoracic and Cardiovascular Surgery 2008;135(2):347-54.

References to studies awaiting assessment

  1. Top of page
  2. AbstractRésumé scientifique
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Differences between protocol and review
  17. Notes
  18. Characteristics of studies
  19. References to studies included in this review
  20. References to studies excluded from this review
  21. References to studies awaiting assessment
  22. References to ongoing studies
  23. Additional references
Cholette 2010a {published data only}
  • Cholette JM. Use of cell salvage post-operatively in infants to decrease use of allogeneic blood product transfusions. clinicaltrials.gov/show/NCT01211366 (accessed 3 February 2014).
  • Cholette JM, Powers KS, Alfieris GM, Angona R, Henrichs KF, Masel D, et al. Transfusion of salvaged blood in pediatric heart surgery reduces allogeneic transfusion: a prospective randomized trial. Transfusion. 2012; Vol. 52:121A.
Hajjar 2010 {published data only}
  • Hajjar LA. Liberal or restrictive strategy of red blood cell transfusion in cardiac surgery: a randomized controlled clinical trial [Estudo prospectivo e randomizado das estragias liberal e restritiva de transfusúo de hemicias em cirurgia cardaca]. LILACS database 2010; Vol. 169.

References to ongoing studies

  1. Top of page
  2. AbstractRésumé scientifique
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Differences between protocol and review
  17. Notes
  18. Characteristics of studies
  19. References to studies included in this review
  20. References to studies excluded from this review
  21. References to studies awaiting assessment
  22. References to ongoing studies
  23. Additional references
Cholette 2012a {published and unpublished data}
  • Cholette J. Restrictive versus liberal transfusion protocol in infants undergoing cardiac surgery. clinicaltrials.gov/show/NCT01484886 (accessed 3 February 2014).
Reeves 2008 {published data only}
  • Reeves B. A multi-centre randomised controlled trial of transfusion indication threshold reduction on transfusion rates, morbidity and healthcare resource use following cardiac surgery. ISCRTN register 2008; Vol. 70923932.
Steiner 2010 {published data only}
  • Steiner ME, Assmann SF, Levy JH, Marshall J, Pulkrabek S, Sloan SR, et al. Addressing the question of the effect of RBC storage on clinical outcomes: the Red Cell Storage Duration Study (RECESS). Transfusion & Apheresis Science 2010; Vol. 43, issue 1:107-16.

Additional references

  1. Top of page
  2. AbstractRésumé scientifique
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Differences between protocol and review
  17. Notes
  18. Characteristics of studies
  19. References to studies included in this review
  20. References to studies excluded from this review
  21. References to studies awaiting assessment
  22. References to ongoing studies
  23. Additional references
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Benson 2010
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Sanchez 2005
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Silliman 2003
  • Silliman CC, Boshkov LK, Mehdizodehleashi Z, Elzi DJ, Dickey WO, Podlosky L, et al. Transfusion-related acute lung injury: epidemiology and a prospective analysis of etiologic factors. Blood 2003;101:454-62.
Stainsby 2008
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Székely 2006
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Székely 2009
  • Székely A, Cserep Z, Sapi E, Breuer T, Nagy CA, Vargha P, et al. Risks and predictors of blood transfusion in pediatric patients undergoing open heart operations. Annals of Thoracic Surgery 2009;87:187-97.
Taylor 2002
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