Bignami 2017.

Methods	RCT, parallel design
Participants	Total number of randomized participants: 46 Inclusion criteria: undergoing cardiac surgery; ≥ 18 years of age; preoperative left ventricular end diastolic diameter > 60 mm and left ventricular ejection fraction < 50% Exclusion criteria: previous unusual response to esmolol; esmolol administration in previous 30 days; emergency surgery; inclusion in other RCTs Type of surgery: elective cardiac surgery (coronary, mitral valve, aortic valve) Baseline characteristics Intervention group (esmolol) Age, mean (SD): 62 (± 10.8) years Gender, M/F: 18/3 NYHA class III or IV: 10 History of coronary heart disease, n: 8 History of hypertension, n: 12 Ejection fraction, mean (SD), %: 37 (± 7.1) History of COPD, n: 4 Preoperative use of beta‐blockers, n: 13 Control group (placebo) Age, mean (SD): 63 (± 14.5) years Gender, M/F: 20/5 NYHA class III or IV: 7 History of coronary heart disease, n: 7 History of hypertension, n: 14 Ejection fraction, mean (SD), %: 38 (± 8.9) History of COPD, n: 2 Preoperative use of beta‐blockers, n: 15 Country: Italy Setting: single centre; teaching hospital
Interventions	Intervention group (esmolol) Randomized, n = 21; losses = 0; analysed, n = 21 (use of ITT analysis) Details: preoperative medication stopped on day of surgery, and continued after surgery if permitted by HR, BP, and cardiac index. 1st dose 1 mg/kg esmolol in a 10 mg/mL solution, given IV before aortic cross‐clamping, additional dose 2 mg/kg given via cardioplegic solution Control group (placebo) Randomized, n = 25; losses = 0; analysed, n = 25 (use of ITT analysis) Details: normal saline, given same as the intervention group
Outcomes	Outcomes measured/reported by study authors: myocardial damage; troponin levels, ventricular fibrillation, need for inotropic support, ICU and hospital length of stay, mortality (at 1 year) Outcomes relevant to the review: hospital length of stay (see notes below), mortality (at 1 year)
Notes	Funding/declarations of interest: study authors received no funding, and declare no conflicts Study dates: not reported Note: we did not include hospital length of stay in analysis because it was not reported as mean (SD) values; study authors reported median (IQR) length of hospital stay as 7 (6 to 12) days in the esmolol group, and 7 (6 to 10) days in the placebo group
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Computer‐generated random numbers
Allocation concealment (selection bias)	Low risk	Use of sealed, numbered, opaque envelopes for group assignment
Blinding of participants and personnel (performance bias) All outcomes	Low risk	All personnel were blinded to group assignment. Study drugs prepared so that they were identical in appearance
Blinding of outcome assessors (detection bias) All outcomes	Low risk	Outcome assessors blinded to group assignment
Incomplete outcome data (attrition bias) All outcomes	Low risk	No losses
Selective reporting (reporting bias)	Unclear risk	Study authors did not report prospective clinical trial registration or publication of a protocol. It was not feasible to effectively assess risk of reporting bias
Other bias	Low risk	Not detected