Azau 2014.

Study characteristics
Methods	Study design: randomised, open‐label controlled clinical trial Study duration: 30 months between January 2008 and June 2010 'Run‐in' period: none Number of study centres and location: 1 in France
Participants	Total number of study participants: 300 Number of randomised participants: 300 Number lost to follow‐up: 0 Number withdrawn: 8 Number analysed: 292 Mean age: 76 years Gender: 200 men Inclusion criteria: elective cardiac surgery, including CABG, valvular surgery or reconstructive surgery of the ascending aorta performed under normothermic CPB in people with known risk factors for AKI. These risk factors were serum creatinine clearance 30–60 mL/minute/1.73 m² or 2 factors among the following: aged > 60 years, diabetes mellitus, and diffuse atherosclerosis. Exclusion criteria: infusion of a radiocontrast agent 1 week before surgery or treatment with a nephrotoxic agent 3 weeks before surgery; chemotherapy within last 3 months; liver cirrhosis; heart failure (left ventricular ejection fraction < 30%); renal artery stenosis; pulmonary hypertension (systolic pulmonary pressure > 60 mmHg); endocarditis; surgery requiring hypothermic CPB. Patients who eventually had a major perioperative complication (shock, emergent reoperation) identified as AKI cause disclosed a major perioperative complication (shock, emergent reoperation)
Interventions	Experimental: maintaining MAP during CPB at 75–85 mmHg by infusing noradrenaline Comparison: maintaining MAP during CPB at 50–60 mmHg. Vasopressors were administered when MAP < 50 mmHg. Concomitant treatment: following anaesthesia induction, a systematic 12 mL/kg saline infusion load was administered in all participants. CPB was performed with a roller pump. Before and after CPB, and in both groups, the MAP endpoint was 70–90 mmHg, with venous oxygen saturation > 70% until the end of surgery. CPB flow was set at 2.4 L/minute/m2 and further adjusted to maintain SvO2 > 70%.
Outcomes	Primary endpoint: 30% rise in serum creatinine was the primary endpoint and surrogate for AKI. Renal function assessed at day 28 and 6 months after surgery. There were additional surrogate endpoints for AKI: RIFLE "risk" category (50% rise in serum creatinine or glomerular filtration rate decrease > 25%, urine output < 0.5 mL/kg/hour × 6 hours); RIFLE 'injury' category (100% rise in serum creatinine or glomerular filtration rate decrease > 50%, urine output < 0.5 mL/kg/hour × 12 hours); > 50% postoperative rise of serum creatinine; and need for haemodialysis. Neurological complications of surgery (stroke, seizure, transient mental confusion/agitation) were also recorded. Death date was identified either by medical records received from doctors who cared for the patients after discharge from hospital or, in the absence of such records, the authors asked the national registry of deaths.
Notes	Supported by a grant from the "Programme Hospitalier pour la Recherche Clinique" (PHRC Inter‐Régional, 2007) from the French Health Ministry.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Information not provided.
Allocation concealment (selection bias)	Unclear risk	Although this study used opaque sealed envelopes, their random sequence generation was unclear.
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	In the methods section, the authors reported that participants were blinded but study personnel were not.
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	The definitions and assessors for several outcomes, i.e. cognitive deterioration, acute ischaemic stroke, haemorrhagic stroke, delirium, and perioperative myocardial infarction, were unclear.
Incomplete outcome data (attrition bias) All outcomes	Low risk	Lost to follow‐up 2.7% (8/300).
Selective reporting (reporting bias)	Unclear risk	Study protocol not available.
Other bias	Low risk	Review authors believed the study free of other sources of bias.