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. 2014 Feb 7;2014(2):CD009752. doi: 10.1002/14651858.CD009752.pub2

Cholette 2012.

Methods Type of study: parallel RCT
Type of publication: full
Setting: URMC, Rochester, NY, USA
Number of centres: 1
Dates of trial (start and end): October 2008 to September 2010
Follow‐up: not clearly stated, but duration of hospital stay was up to 78 days
Number of patients randomised: 81 in each group
Number of patients analysed (primary outcome): 64 in each group
Only those randomised patients who received a transfusion on study entrance were included in the analysis of outcomes. No patients were lost to follow‐up
Participants Inclusions: Children up to 18 years presenting to the URMC for cardiac surgical repair/palliation with CPB
The surgical procedures undergone by the study patients included stage 1 palliation; arterial switch operation; bidirectional Glenn; tetralogy of Fallot repair; atrial, ventricular or atrioventricular septal defect repair; aortic arch reconstruction and Fontan
Age: washed group: median 6 months (IQR 3 days to 17 years); unwashed group: median 7 months (IQR range 2 days to 17 years)
Gender (M/F): washed group: 63/18; unwashed group: 64/17
Exclusions: patent ductus arteriosus repair, if parent/guardian did not speak English, if consent could not be obtained or patient participating in another clinical trial
Statistically significant baseline imbalances between the 2 groups: no
Interventions 2 groups: washed and unwashed
Intervention arm: all red cell and platelets transfusions were washed after storage for the duration of the hospital stay. The protocol could be temporarily suspended at the discretion of the attending physician if the time taken to wash blood products (2 hours for platelets; 30 minutes for red blood cells) interfered with patient care
Comparator arm: all red cell and platelet transfusions were prepared according to standard protocol at the URMC for the duration of the hospital admission
The study transfusion strategy was initiated for the operating room and maintained until hospital discharge. All blood products were leukoreduced before storage, irradiated and ABO blood group identical, without restrictions on storage age
Outcomes Primary:
  • 12 hour post CPB IL‐6:IL‐10 ratio


Other outcomes:
  • mortality up to 30 days

  • severe adverse events: cardiac, thromboembolism, infection, haemorrhage

  • red blood cell units and other blood products transfused to discharge

  • duration of mechanical ventilation

  • duration of ICU stay


In addition, the following outcomes were reported by the trial (but not included in this review): inotropic/vasopressor hours, central venous line duration, mediastinal tube days, antibiotics, PCICU admission lactate, peak lactate, volume, highest white blood count postoperatively on days 0‐2, PCICU complication and ECMO duration
Notes Funding: Strong Children's Research development award from URMC ‐ Department of Pediatrics, National Institute of Environmental Health Sciences/National Institute of Health (ESO1247) and the National Heart Lung and Blood Institute/National Institute of Health (HL100051, HL095467)
ClinicalTrials.gov record number: NCT00693498
Protocol violations: 1 in the washed group (a neonate who received 1 unwashed platelet transfusion) and 2 in the unwashed group (both patients required ECMO and all products for ECMO were washed to prevent hyperkalaemia)
Sample size calculation: Cholette 2012 calculated that a sample of 64 patients per group would provide 80% power to detect a relatively small group difference of 2 units (one half of SD) of the mean IL‐6:IL‐10 ratio. 64 patients were included in each group making the study adequately powered for differences in IL‐6:IL‐10 ratios. However, these study numbers were not large enough to power the study to test for clinical outcomes
Risk of bias
Bias Authors' judgement Support for judgement
Random sequence generation (selection bias) Unclear risk Quote (p. 291): "... block randomisation was used to randomise to the unwashed or washed transfusion strategy". Insufficient information about sequence generation process to permit judgement of 'Yes' or 'No'
Allocation concealment (selection bias) Unclear risk No information was provided to enable an assessment of adequate allocation concealment
Blinding of participants and personnel (performance bias) 
 All outcomes High risk Email communication with the main author identified that no one involved in patient care could be blinded to treatment allocation due to packaging differences of the blood products that were not allowed to be concealed under FDA, New York state and hospital regulations. The blood bank sent blood appropriate to the allocation (washed or unwashed). When blood was not hanging the treatment allocation was not obvious and the clinician would not be aware of trial assignment
Blinding of outcome assessment (detection bias) 
 All outcomes High risk Email communication with the main author identified that outcome assessment was determined from inpatient notes from the PCICU attending physician and cardiothoracic surgery nurse practitioner: both of whom were not blinded to treatment allocation
Incomplete outcome data (attrition bias) 
 All outcomes Low risk The trial authors report that there were no missing outcome data: no patients were lost to follow‐up and data were analysed by both ITT and per‐protocol principles. 34 randomised patients (17 from each treatment group) did not receive a transfusion and were thus excluded from the per‐protocol analysis
6 patients were excluded following randomisation: 3 because shunts were performed off by‐pass, 2 because surgical palliation was not offered and 1 patient in whom surgery was not performed. These patients did not receive a transfusion and were excluded from all outcome analyses
Selective reporting (reporting bias) Low risk The trial protocol is available and all outcomes pre‐specified (IL‐6:IL‐10 ratio and wide‐range C‐reactive protein levels) in the protocol have been reported in this trial as pre‐specified
Other bias Low risk None reported