Geldner 2012.

Methods	Study design: randomized, active‐controlled, parallel‐group, multi‐centre, safety assessor‐blinded trial Sample size calculation: powered to detect a difference with respect to length of stay in theatre and post‐anaesthesia recovery unit between the 2 treatments of half a standard deviation
Participants	Number of randomized participants: 140 Inclusion criteria: age ≥ 18 years; ASA physical status I to III; scheduled laparoscopic cholecystectomy or appendectomy under general anaesthesia; and written, informed consent Exclusion criteria: suspected difficult tracheal intubation; disorder affecting neuromuscular blockade; known or suspected significant renal dysfunction; known or suspected severe hepatic dysfunction; history of malignant hyperthermia; allergy to opioids, neuromuscular blocking drugs, or other medications used during general anaesthesia; contraindication to neostigmine and ⁄or atropine; pregnancy (excluded both by medical history and by a human chorionic gonadotropin test within 24 hours of surgery in women of childbearing age) and breastfeeding; already participated in another sugammadex study or participated in another clinical study not preapproved by the sponsor within 30 days
Interventions	Anaesthesia: induced and maintained using intravenous propofol and opioids (most frequently fentanyl) as required; choice and dose of which were decided by the responsible anaesthetist NMBA: single intubating dose: rocuronium 0.6 mg/kg; maintenance dose: rocuronium 0.1 to 0.2 mg/kg Comparison: sugammadex 4 mg/kg (n = 70) vs neostigmine 50 µg/kg + atropine 10 µg/kg (n = 70) Administration time of sugammadex or neostigmine: PTC 1 to 2 for sugammadex and reappearance of T2 for neostigmine + atropine
Outcomes	Primary efficacy parameter: time from start of sugammadex or neostigmine administration to TOFR > 0.9 Secondary outcome parameters: safety and length of stay in the operating room and the PACU following administration of study drug Safety assessments: adverse events, vital signs, physical examination findings
Notes	Publication type: peer‐reviewed article Country: European study ‐ 3 centres in Russia, 4 in Germany, 2 in Finland, and 1 in UK Conversions: none Handling of adverse events: No discrepancy exists between AEs presented in the original article and those reported in this review Authors’ conclusions: In participants undergoing laparoscopic surgery under propofol anaesthesia, neuromuscular blockade reversal with sugammadex administered at a PTC of 1 to 2 (deep neuromuscular blockade) after rocuronium was well tolerated and resulted in faster recovery of the TOFR to 0.9 compared with neostigmine administered at reappearance of T2 (moderate neuromuscular blockade) (P < 0.0001). Sugammadex therefore may allow rapid reversal of deep neuromuscular blockade at completion of surgery without a delay in recovery Contact: first trial author G. Geldner contacted by email: goetz.geldner@kliniken‐lb.de; has replied
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Online randomization list created by Orcapharma (Heesch, The Netherlands) using the software package SAS̀ (SAS Institute, Cary, NC, USA) in compliance with international protocols
Allocation concealment (selection bias)	Low risk	Central allocation (secondary to web randomization)
Blinding of participants (performance bias)	Low risk	Participants were blinded
Blinding of personnel (performance bias)	Unclear risk	Unable to assess owing to insufficient information
Blinding of primary outcome assessment (detection bias)	Unclear risk	No specific information on identity or blinding of the TOF‐watch assessor
Blinding of safety assessment (detection bias)	Low risk	Safety assessor was blinded to treatment assignment, was not involved in the randomization process, was not present during anaesthesia, and was not involved in preparation of the trial medication
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: 140 participants were assigned to sugammadex (70) or neostigmine (70); 4 participants in the sugammadex group and three in the neostigmine group did not receive study drug. Two participants in the neostigmine group were not included in the efficacy analysis because of failure of the neuromuscular monitoring device. Data were imputed by a conservative approach towards sugammadex for 3 participants in the sugammadex group and 5 in the neostigmine group, because time to recovery of the TOFR to 0.9 was not available. Out of these, for 2 in the sugammadex group and 2 in the neostigmine group, the TOFR did not reach 0.9; for the remaining 2 participants, times were considered unreliable owing to an unstable trace (neostigmine group) or unsuccessful calibration (sugammadex group)
Selective reporting (reporting bias)	Low risk	Study protocol is available on clinicaltrials.gov (NCT00724932), and all of the study’s prespecified outcomes of interest to the review have been reported in the prespecified way
Funding bias	High risk	Study sponsor, MSD, was involved in both study design and analysis of the data. The overall design and conduct of the study, as well as final analysis of study data and opinions, conclusions, and interpretation of the data, are the responsibility of the study authors. Medical writing assistance was provided by Neil Venn, PhD, of Prime Medica Ltd (Knutsford, UK); this assistance was funded by Merck Sharp and Dohme Corp., a subsidiary of Merck & Co., Inc., Whitehouse Station, NJ. The study sponsor was allowed to review the manuscript before submission, but final decisions on content remained the responsibility of trial authors, and all trial authors approved the final text of the manuscript before submission Götz Geldner has acted as a scientific advisor to MSD (formerly Organon) and GlaxoSmithKline and has delivered lectures for and received research funding from both companies. Henk Rietbergen is an employee of MSD. The other study authors declare no competing interests
Other bias	High risk