Raby 1999.

Methods	RCT, parallel design
Participants	Total number of randomized participants: 26 Inclusion criteria: undergoing aortic aneurysm repair, infrainguinal arterial bypass, carotid endarterectomy, having myocardial ischaemia 1‐12 days before surgery Exclusion criteria: receiving digitalis therapy, baseline left bundle branch block or left ventricular hypertrophy, baseline ST‐T changes that would preclude accurate interpretation of Holter monitor for ischaemia Type of surgery: aortic aneurysm repair, infrainguinal arterial bypass, carotid endarterectomy Baseline characteristics Intervention group (esmolol) Age, mean: 69 years Gender, M/F: 8/7 History of MI, n: 6 Preoperative use of beta‐blockers, n: 5 Control group (placebo) Age, mean: 67 years Gender, M/F: 4/7 History of MI, n: 4 Preoperative use of beta‐blockers, n: 4 Country: USA Setting: single centre; hospital
Interventions	Intervention group (esmolol) Randomized, n = 15; losses = 0; analysed, n = 15 (use of ITT analysis not reported) Details: esmolol 100 µg/kg/min via continuous infusion, beginning immediately after surgery and before arrival in the PACU. Infusion was adjusted every h for 48 h to a maximum dose of 300 µg/kg/min depending on HR Control group (placebo) Randomized, n = 11; losses = 0; analysed, n = 11 Details: isotonic saline solution, given same as the intervention group
Outcomes	Outcomes measured/reported by study authors: perioperative myocardial ischaemia, MI, unstable angina Outcomes relevant to the review: MI
Notes	Funding/declarations of interest: supported in part by a grant from Ohmeda Inc. Study dates: not reported (study duration 2 years) Note: some participants did not have GA ‐ 4 in the esmolol group (26.7%), and 1 in the placebo group (9.1%)
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Coin flipping
Allocation concealment (selection bias)	Low risk	See above
Blinding of participants and personnel (performance bias) All outcomes	High risk	Despite the double‐blind study design, a "significantly higher use of alternative beta‐blockers in the placebo group compared with the esmolol group" was noted. The study authors suggested that "managing clinicians recognized patients receiving the active drug or placebo despite blinding"
Blinding of outcome assessors (detection bias) All outcomes	Low risk	Holter monitoring was interpreted "by a technician blinded to patient characteristics and randomization"
Incomplete outcome data (attrition bias) All outcomes	Low risk	Quote: "No patient in our study had beta‐blocker therapy suspended because of unacceptable side effects"
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	High risk	Quote: "The use of alternative beta‐blocker therapy, calcium channel blocker therapy, nitrates, and various formas of analgesia were permitted per the judgment of the independent managing physicians in both groups, without a specific protocol". Comment: we noted that more participants in the placebo group had alternative postoperative beta‐blockers.