Pellicer 2013.

Study characteristics
Methods	Study design: randomised controlled trial, parallel arm Setting: La Paz University Hospital, Madrid, Spain Study start/end dates or study duration: November 2009 to November 2010 Funding sources: Spanish Fondo de Investigación Sanitaria (Spanish Healthcare Research Fund), and the SAMID network, as well as the Orion Pharma Spanish Division, for the pharmacokinetic studies Declarations of interest: "The authors declared no conflict of interest."
Participants	Sample size: 20 Patient age: 6 to 34 days Patient sex: 11 male, 9 female Diagnosis/severity: d‐transposition of the great arteries with or without ventricular septal defect, tetralogy of fallot, total anomalous pulmonary venous return, coarctation or hypoplasia of the aorta with atrial septal defect with or without ventricular septal defect Inclusion criteria: neonates undergoing cardiovascular surgery with CPB who were in stable preoperative haemodynamic condition
Interventions	Intervention 1: milrinone infusion starting at 0.5 μg/kg/min for the duration of surgery, starting when the central lines were placed (dose 1), increase to 0.75 μg/kg/min at the time of admission to the ICU (dose 2) for 2 hours, increase to 1 μg/kg/min 2 hours after ICU admission. Infusion of milrinone for 48 hours, followed by unblinding and open‐label infusion if needed. Intervention 2: levosimendan infusion at 0.1 μg/kg/min for the duration of surgery, starting when the central lines were placed (dose 1), increase to 0.15 μg/kg/min at the time of admission to the ICU (dose 2) for 2 hours, increase to 0.2 μg/kg/min 2 h after ICU admission. Infusion of levosimendan for 48 hours. Co‐interventions: volume, other cardiovascular drugs (dopamine, epinephrine, dobutamine, urapidil, sodium nitroprusside, nitroglycerin, nitric oxide), 3 doses of methylprednisolone 8 h apart starting the night before surgery.
Outcomes	Primary outcome(s): continuous, time‐locked, physiological, and near‐infrared spectroscopy (NIRS) (cerebral and peripheral) recordings during the first 24 h, and at 48 and 96 h postsurgery Secondary outcome(s) Mortality within 30 days Heart rate Blood pressure Inotrope score Serial biochemistry (e.g. lactate) and pharmacokinetic studies Adverse events Echocardiography for LVFS < 28%: at baseline, at 24 hours, and at 48 hours (and also later, after un‐blinding)
Notes	Intention‐to‐treat analysis: yes Trialists contacted: yes Unpublished information received: blinding of outcome assessors, timing of unblinding, time to death, incidence of adverse events
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Computer‐generated randomisation list. "The randomisation was stratified by type of congenital heart defect and risk adjustment using the congenital heart surgery method "Jenkins KJ et al. J Thorac Cardiovasc Surg 2002;123:110‐8"", with 3 strata (20% of patients in low‐risk, 60% in moderate‐low risk, 20% in moderate‐high risk)
Allocation concealment (selection bias)	Low risk	“A study nurse who was not involved in the clinical care of the infants prepared the study medication and was the custodian of the allocation code.”
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Same infusion rates for both drugs, opaque black syringes and catheters. Drugs were prepared by a study nurse who was not involved in the care of the patients.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Low risk for the first 48 hours while blinded according to the study protocol (including the 48 hours measurements). Then high risk while continued as open study, follow‐up until 6 days post surgery.
Incomplete outcome data (attrition bias) All outcomes	Low risk	Study authors were contacted and asked for additional data.
Selective reporting (reporting bias)	Low risk	Study authors were contacted and asked for additional data.
Other bias	Low risk	The manufacturer of one intervention (levosimendan, Orion Pharma Spanish Division, Espoo, Finland) supported the pharmacokinetic part of the study financially. Not deemed an important source of bias, because this financial support was restricted to pharmacokinetics instead of the RCT itself.