Feneck 2001.

Study characteristics
Methods	Study design: multicentre, 2‐arm parallel group RCT (UK) Recruitment period: ‐ Follow‐up: 4 h after termination of drug infusion
Participants	n = 318 (randomised), n = 120 (enrolled) Inclusion criteria: LCOS after elective cardiac surgery within 2 h after separation from cardiopulmonary bypass and at least 15 min after protamine administration Exclusion criteria: age < 18 years; fertility (women); hepatic disease or renal impairment (serum creatinine > 250 µg/L); history of allergy to anaesthetic drugs; receipt of other investigational drugs; receipt of long‐acting vasodilators within 12 h of surgery; receipt of short‐acting vasodilators within 5 min or short‐acting inotropic infusions within 1 h of baseline haemodynamic measurements; uncontrolled supraventricular arrhythmia; clinically significant ventricular ectopic activity LCOS definition: CI < 2.0 L/min/m2, PCWP ≥ 10 mmHg Characteristics: (milrinone/dobutamine, mean ± SEM) Age (years): 63.9 ± 1.2/64.4 ± 1.1 Sex (male, %): 55/63 Diabetes (%): ‐ Hypertension (%): ‐ Smoker (%): ‐ Prior AMI/vascular intervention (%): ‐ MAP (mmHg): 67.4 ± 2.0/60.2 ± 1.8 HR (bpm): 83 ± 2/84 ± 3 SBP (mmHg): 94.5 ± 2.5/83.3 ± 2.5 DBP (mmHg): 54.4 ± 1.8/47.8 ± 1.6 CI (L/min/m2): 1.68 ± 0.03/1.7 ± 0.03 PCWP (mmHg): 13.7 ± 0.5/12.7 ± 0.4 LVEF (%): ‐ SVR (dyne.s/cm5): 1596 ± 55/1383 ± 61 Timetable: treatment for at least 4 h (as long as clinically indicated); observation at 0/15 min, 1/2/4 h, treatment termination and 2 h after treatment termination
Interventions	Milrinone (n = 60): loading dose of 50 µg/kg over 10 min followed by an infusion of 0.5 µg/kg/min; after 1 h an upward dose adjustment could be made if clinically indicated by giving a second loading dose (50 µg/kg over 10 min) and an infusion of 0.75 µg/kg/min; the study drug was continued as long as clinically indicated Dobutamine (n = 60): continuous infusion started at 10 µg/kg/min; at 15 min intervals an upward dose adjustment to 15 µg/kg/min, then 20 µg/kg/min could be made if clinically indicated; the study drug was continued as long as clinically indicated Concomitant medication: anaesthetic agents (intravenous opioid analgesia and sedation) Concomitant intervention: ventilation to normocarbia and normoxia Intervention before baseline: elective cardiac surgery
Outcomes	Primary: clinical efficacy (number of participants achieving an increase in CI of at least 30% from the baseline value at 1 h) Secondary: number of participants achieving a decrease on PCWP of at least 25% from the baseline value at 1 h Safety: assessment of reported incidence of adverse events; participants withdrawals from the study; changes in biochemistry and haematology before surgery/before study drug infusion/at 4 h after treatment termination
Notes	Funding: supported by grants from Sanofi Winthrop Limited, Guildford, UK with statistical advice from J.M. White Associate, Jamesville, NY Contact: R.O. Feneck (Department of Anesthesia, St. Thomas Hospital, London) Trial registration: ‐ Other: ‐
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Central allocation; no further information provided
Allocation concealment (selection bias)	High risk	Open‐label trial
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open‐label trial
Blinding of outcome assessment (detection bias) All outcomes	High risk	Open‐label trial
Incomplete outcome data (attrition bias) All outcomes	High risk	Exclusion of 20 (milrinone group) and 29 (dobutamine group) participants due to adverse events requiring treatment outside of the protocol; no data reported for these participants
Selective reporting (reporting bias)	Low risk	Pre‐planned endpoints were reported.
Other bias	High risk	Cross‐over: no Baseline differences: yes (MAP, SBP, DBP, SVR significantly higher in participants receiving milrinone) Influence of interim results on the conduct of the study: no Deviation from study protocol: no Inappropriate administration of an intervention: yes (49 participants (20 in milrinone group, 29 in dobutamine group) had adverse events requiring treatment outside of the protocol) Contra‐active or similar supporting pre‐randomisation intervention: yes (intravenous opioid analgesia and sedation)
Adverse effects	High risk	Definitions of AEs given: no Monitoring of AEs: report of all adverse events occurring in > 5 participants Participants excluded from AE analysis: no Numerical data by intervention: yes