Donati 2014.

Methods	Design: Parallel group RCT Country: Italy Multicentre study: No Setting: Hospital Follow‐up: Not clearly reported, outcomes were measured up to 1 hour after blood transfusion Unit of allocation: Patients Unit of analysis: Patients
Participants	Inclusion criteria: Adult patients admitted to ICU of the AOU Ospedali Riuniti of Ancona with sepsis, severe sepsis or septic shock as diagnosed according to standard criteria and requiring blood transfusion for haemoglobin (Hb) levels of less than 8 g/dL or as indicated by the attending physician in accordance with the local hospital guidelines. Exclusion criteria: Aged < 18 years, previous blood transfusions during ICU stay, previous history of coagulation disorders, cardiogenic or hemorrhagic shock, pregnancy and factors impeding the sublingual microcirculation evaluation (oral surgery and maxillofacial trauma) Patients enrolled: 20 Patients randomised: 20 Leukodepleted RBC transfusion: 10 Non‐leukodepleted RBC transfusion: 10 Patients transfused: 20 Patients considered for the analysis: 20 Main characteristics of patients: Age: Non‐leukodepleted group = 70 (65 to 72) years; leukodepleted group = 74 (64 to 79) years Percentage of men: Non‐leukodepleted group = 50%; leukodepleted group = 70%
Interventions	Experimental: Leukodepleted RBC transfusion: leukoreduction was performed by a blood bank physician using the filter Sepacell RZ‐200 (Fenwal, Inc., Lake Zurich, IL, USA) within a maximum of 5 days after donor blood withdrawal (post‐storage leukoreduction). Control: Non‐leukodepleted RBC transfusion. Cointervention: Related to sepsis treatment (fluid therapy, vasopressors and inotropic agents, antibiotics, etc.)
Outcomes	Primary: Microcirculatory Flow Index (MFI) before and after blood transfusion. Secondary: Peripheral tissue oxygen saturation (StO2). Tissue Hb index (THI). Vascular lumen perfused boundary region (PBR). Glycocalyx damage markers.
Notes	Trial Registration: NCT01584999 Funding: Not reported Role of sponsor: Not reported A priori sample size estimation: Yes Conducted: February 2011 and 2012 Declared conflicts of interest: One trial author "CI is the inventor of Sidestream Dark Field imaging technology" technique used to measure the outcomes, this author "holds shares in MicroVision Medical and was a consultant for this company more than four years ago but has had no further contact with the company since then. He declares that he has no other competing interests in this field other than his commitment to promoting the importance of the microcirculation during patient care and no other relationships or activities that could appear to have influenced the submitted work. HV holds the position of chief scientific officer in GlycoCheck BV. The other authors declare that they have no competing interests".
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Not reported.
Allocation concealment (selection bias)	Low risk	"Blood product randomization was performed through sealed envelopes by a physician at the blood bank" (Page 2).
Blinding of participants and personnel (performance bias) All outcomes	Low risk	"a physician at the blood bank blindly provided the blood bags to the ICU; neither the attending physician nor the investigators nor the patients were aware of the type of RBCs transfused" (Page 2).
Blinding of outcome assessment (detection bias) All outcomes	Low risk	"a physician at the blood bank blindly provided the blood bags to the ICU; neither the attending physician nor the investigators nor the patients were aware of the type of RBCs transfused" (Page 2).
Incomplete outcome data (attrition bias) All outcomes	Low risk	Comment: All patients transfused were analysed. Patients lost to follow‐up: None.
Selective reporting (reporting bias)	Low risk	Comment: The study protocol is not available but it is clear that the published reports include all expected outcomes, including those that were pre‐specified.
Other bias	Low risk	—