Kaufhold 2016.

Methods	Study design: Single‐centre, randomized, parallel‐group, double‐blinded study (SUNDRO20) Sample size calculation: powered to detect doses necessary to accelerate time between study drug administration at a TOFR ≥ 0.2 to a TOFR ≥ 0.9 in 50% of participants within 2 minutes
Participants	Number of randomized participants: 99 Inclusion criteria: age > 18 years; ASA physical status I to III; undergoing elective surgery under general anaesthesia with rocuronium for tracheal intubation; written informed consent Exclusion criteria: expected to have a difficult airway or with known neuromuscular disease, significant hepatic or renal dysfunction, family history of malignant hyperthermia, known allergy to one of the drugs used in this protocol; or intake of any medication that might interact with muscle relaxants; pregnant women or women who were breastfeeding; individuals who have participated in another clinical study in the past 30 days
Interventions	Anaesthesia: induced with propofol 2 to 3 mg/kg IV and fentanyl 0.1 to 0.2 μg/kg IV and maintained with propofol and remifentanil according to clinical need and preference for the anaesthetist NMBA: single intubating dose: rocuronium 0.6 mg/kg; maintenance dose: rocuronium 0.1 to 0.2 mg/kg Comparison: sugammadex 0.25 mg/kg (n = 9), 0.5 mg/kg (n = 9), 0.75 mg/kg (n = 9), 1.0 mg/kg (n = 9), and 1.25 mg/kg (n = 9), neostigmine 10 μg/kg (n = 9), 25 μg/kg (n = 9), 40 μg/kg (n = 9), 55 μg/kg (n = 9), and 70 μg/kg (n = 9) in a mixture with 1 μg glycopyrrolate per 5 μg neostigmine, or saline (n = 9) Administration time of sugammadex or neostigmine or placebo: TOFR ≥ 0.2
Outcomes	Primary endpoints: doses necessary to achieve this effect in 50% of patients within 2 minutes or in 95% of patients within 5 minutes Secondary endpoints: doses for less advanced acceleration (i.e. in 50% of participants within 5 minutes or in 95% of participants within 10 minutes) Safety assessment: heart rate, blood pressure, and clinical muscle test function (eye opening, head‐lift test, arm‐lift test, swallowing a bolus of 20 mL of water, test for general muscle weakness)
Notes	Publication type: peer‐reviewed article Country: Germany Conversions: none Handling of adverse events: No discrepancy exists between AEs presented in the original article and those reported in this review Authors’ conclusions: A residual neuromuscular block for a TOFR = 0.2 cannot be reversed reliably with neostigmine within 10 minutes. In the conditions studied, substantially lower doses of sugammadex than the approved dose of 2.0 mg/kg may be sufficient to reverse residual rocuronium‐induced neuromuscular block at recovery of TOFR ≥ 0.2 Contact: first trial author S. Schaller contacted by email: s.schaller@tum.de on 07.06.2016; no reply received
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	"Computer‐generated randomization list"; every participants received a consecutive number
Allocation concealment (selection bias)	Unclear risk	Unable to assess owing to insufficient information
Blinding of participants (performance bias)	Unclear risk	Unable to assess owing to insufficient information
Blinding of personnel (performance bias)	Low risk	In the operating room, unblinded study staff attending anaesthetist, who was the only person with access to the randomization list, prepared the study drug corresponding to the randomization number in an unlabelled syringe. Upon request of the blinded anaesthetist, responsible for the participant (without access to the randomization list and study medication); unlabelled study drug was injected
Blinding of primary outcome assessment (detection bias)	Unclear risk	Unable to assess owing to insufficient information
Blinding of safety assessment (detection bias)	Low risk	Safety assessor was blinded
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: A total of 99 participants were initially enrolled after 109 had been screened. One participant, who had received neostigmine 70 μg/kg, withdrew his written informed consent after surgery. Therefore, 98 participants were included in statistical analysis. No protocol violations occurred
Selective reporting (reporting bias)	Low risk	Study protocol is available on clinicaltrials.gov (NCT01006720), 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: N.K. has received a travel grant from MSD Sharpe & Dohme. S.J.S. holds stocks for the following companies in the healthcare sector in small amounts: Bayer AG, Siemens AG, GE, Merck & Co. Inc., Rhoen‐Klinikum AG, and Fresenius SE; however, these holdings did not influence any decisions regarding the study. C.G.S. has received honoraria and a travel grant from MSD Sharpe & Dohme. H.F. has received honoraria and travel grants from the following companies: MSD Sharp & Dohme, Essex, Baxter, Care Fusion, and GE Healthcare. M.B. has received honoraria and travel grants from MSD Sharp & Dohme and GlaxoSmithKline. E.B. and K.U. have declared no conflicts Funding: Klinik für Anaesthesiologie, Klinikum rechts der Isar der Technischen Universität München, Munich, Germany
Other bias	High risk	Study sample size calculation not designed to address this review's primary or secondary outcome. Groups did not differ regarding age, weight, height, sex, and ASA physical status