Brueckmann 2015.

Methods	Study design: randomized, controlled study Sample size calculation: powered to detect a significant difference in the incidence of TOFR < 0.9 between groups
Participants	Number of randomized participants: 154 Inclusion criteria: > 18 years of age, ASA I to III, scheduled to undergo an elective abdominal surgical procedure under general anaesthesia, and expected to undergo neuromuscular relaxation with rocuronium for endotracheal intubation Exclusion criteria: suspected difficult intubation; neuromuscular disorder(s); known or suspected severe renal insufficiency (defined as estimated creatinine clearance < 30 mL/min) or significant hepatic dysfunction; history or family history of malignant hyperthermia; allergies to sugammadex, opioids, NMBs, or other medication(s) used during general anaesthesia; toremifene application 24 hours before or within 24 hours after study drug administration; planned ICU admission after surgery or overnight (> 12 hours); stay in the PACU; cardiac pacemaker; pregnancy and breastfeeding; use of any other investigational drugs within 30 days of randomization; or participation in another clinical trial within 30 days
Interventions	Anaesthesia: induced and maintained according to clinical need of the participant, and per usual centre practice, with IV induction agents, IV opioids, inhaled anaesthetics, and other agent(s), most commonly a combination of fentanyl, propofol, and sevoflurane NMBA: single intubating dose: rocuronium ˜ 0.6 mg/kg; maintenance dose: rocuronium ˜ 0.15 mg/kg Comparison: sugammadex 2 mg/kg or 4 mg/kg (n = 76) vs neostigmine + glycopyrrolate (n = 78) (dosing per usual clinical practice; maximum dose 5 mg) Administration time of sugammadex or neostigmine: moderate neuromuscular blockade: TOF 1 to 3 or deep neuromuscular blockade: PTC ≥ 1
Outcomes	Primary endpoint: presence of residual neuromuscular blockade at PACU admission, defined as TOFR < 0.9 on arrival to PACU Key secondary endpoint: time from start of study medication administration to time patient was ready for discharge from the operating room, defined as time point deemed by the providing anaesthesiologist as medically appropriate for the patient to leave the operating room Exploratory endpoints: Those related to surgical efficiency parameters were also measured Safety assessments: physical examination at screening and at postanaesthetic visit, vital signs at screening, continuous ECG, oxygen saturation throughout anaesthesia and postoperatively, vital signs at PACU, signs of partial neuromuscular blockade, adverse events and serious adverse events
Notes	Publication type: peer‐reviewed article Country: USA, Massachusetts General Hospital Conversions: PACU time ‐ range to SD following guidelines from Hozo 2005 Handling of adverse events: More detailed information regarding adverse events possibly, probably, or definitely related to study drug was provided by study authors through email correspondence Authors’ conclusions: After abdominal surgery, sugammadex reversal eliminated residual neuromuscular blockade in the PACU and shortened time from start of study medication administration to time patient was ready for discharge from the operating room Contact: corresponding trial author M. EIkermann contacted by email: meikermann@partners.org; has replied * Indicates unpublished data
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Computer‐based randomization*
Allocation concealment (selection bias)	Unclear risk	Sample of 200 sealed envelopes were prepared by the sponsor: 100 for the sugammadex group and 100 for the neostigmine/glycopyrrolate group; however, no information on whether envelopes were sequentially numbered and opaque
Blinding of participants (performance bias)	Low risk	Participants were blinded*
Blinding of personnel (performance bias)	High risk	Anaesthesiologist was unblinded to study drug, as he/she needed to be able to adjust anaesthesia and neuromuscular blockade according to treatment group, and to assess effects of sugammadex on patient flow through the operating room
Blinding of primary outcome assessment (detection bias)	Low risk	TOF‐watch assessors were blinded to treatment group, did not observe preparation of trial medications and were not involved in randomization or preparation of study drug, or were not allowed in the operating room during surgery
Blinding of safety assessment (detection bias)	Low risk	Safety assessors were blinded to treatment group, did not observe preparation of trial medications and were not involved in randomization or preparation of study drug, or were not allowed in the operating room during surgery
Incomplete outcome data (attrition bias) All outcomes	Low risk	All participants are accounted for, and missing outcome data are balanced in numbers across intervention groups, with similar reasons for missing data across groups: 154 participants were randomized (2 were excluded owing to adverse events, 1 withdrew consent), 151 participants received study drug (1 participant was excluded owing to unplanned admission to intensive care unit), resulting in 150 participants who had available primary endpoint (sugammadex group n = 74, neostigmine group n = 76)
Selective reporting (reporting bias)	Low risk	Study protocol is available on clinicaltrials.gov (NCT01479764), and all of the study’s prespecified outcomes of interest to the review have been reported in the prespecified way
Funding bias	High risk	Declaration of interest: M.K.L. and T.W. are employees of Merck Sharp & Dohme Corp., Whitehouse Station, NJ, USA. P.G. is an employee of MSD Oss, The Netherlands. All may own stock and/or hold stock options in the Company. J.de B. was formerly an employee of Merck Sharp & Dohme Corp., Whitehouse Station, NJ, USA. M. E., B.B., M.M., J.L., J.K., A.S.S., F.McG., N.S., and R.P. work for institutions that received research funding for conduct of the study from Merck Sharp & Dohme Corp., Whitehouse Station, NJ, USA
Other bias	Low risk	Appears free of other sources of bias. Study sample size calculation designed to address this review's secondary outcome. No statistically significant differences regarding baseline characteristics between participant groups