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Meta-Analysis
. 2017 Aug 14;8(8):CD012763.
doi: 10.1002/14651858.CD012763.

Efficacy and safety of sugammadex versus neostigmine in reversing neuromuscular blockade in adults

Ana-Marija Hristovska  1 , Patricia Duch, Mikkel Allingstrup, Arash Afshari
Affiliations
Meta-Analysis

Efficacy and safety of sugammadex versus neostigmine in reversing neuromuscular blockade in adults

Ana-Marija Hristovska et al. Cochrane Database Syst Rev. .

Abstract

Background: Acetylcholinesterase inhibitors, such as neostigmine, have traditionally been used for reversal of non-depolarizing neuromuscular blocking agents. However, these drugs have significant limitations, such as indirect mechanisms of reversal, limited and unpredictable efficacy, and undesirable autonomic responses. Sugammadex is a selective relaxant-binding agent specifically developed for rapid reversal of non-depolarizing neuromuscular blockade induced by rocuronium. Its potential clinical benefits include fast and predictable reversal of any degree of block, increased patient safety, reduced incidence of residual block on recovery, and more efficient use of healthcare resources.

Objectives: The main objective of this review was to compare the efficacy and safety of sugammadex versus neostigmine in reversing neuromuscular blockade caused by non-depolarizing neuromuscular agents in adults.

Search methods: We searched the following databases on 2 May 2016: Cochrane Central Register of Controlled Trials (CENTRAL); MEDLINE (WebSPIRS Ovid SP), Embase (WebSPIRS Ovid SP), and the clinical trials registries www.controlled-trials.com, clinicaltrials.gov, and www.centerwatch.com. We re-ran the search on 10 May 2017.

Selection criteria: We included randomized controlled trials (RCTs) irrespective of publication status, date of publication, blinding status, outcomes published, or language. We included adults, classified as American Society of Anesthesiologists (ASA) I to IV, who received non-depolarizing neuromuscular blocking agents for an elective in-patient or day-case surgical procedure. We included all trials comparing sugammadex versus neostigmine that reported recovery times or adverse events. We included any dose of sugammadex and neostigmine and any time point of study drug administration.

Data collection and analysis: Two review authors independently screened titles and abstracts to identify trials for eligibility, examined articles for eligibility, abstracted data, assessed the articles, and excluded obviously irrelevant reports. We resolved disagreements by discussion between review authors and further disagreements through consultation with the last review author. We assessed risk of bias in 10 methodological domains using the Cochrane risk of bias tool and examined risk of random error through trial sequential analysis. We used the principles of the GRADE approach to prepare an overall assessment of the quality of evidence. For our primary outcomes (recovery times to train-of-four ratio (TOFR) > 0.9), we presented data as mean differences (MDs) with 95 % confidence intervals (CIs), and for our secondary outcomes (risk of adverse events and risk of serious adverse events), we calculated risk ratios (RRs) with CIs.

Main results: We included 41 studies (4206 participants) in this updated review, 38 of which were new studies. Twelve trials were eligible for meta-analysis of primary outcomes (n = 949), 28 trials were eligible for meta-analysis of secondary outcomes (n = 2298), and 10 trials (n = 1647) were ineligible for meta-analysis.We compared sugammadex 2 mg/kg and neostigmine 0.05 mg/kg for reversal of rocuronium-induced moderate neuromuscular blockade (NMB). Sugammadex 2 mg/kg was 10.22 minutes (6.6 times) faster then neostigmine 0.05 mg/kg (1.96 vs 12.87 minutes) in reversing NMB from the second twitch (T2) to TOFR > 0.9 (MD 10.22 minutes, 95% CI 8.48 to 11.96; I2 = 84%; 10 studies, n = 835; GRADE: moderate quality).We compared sugammadex 4 mg/kg and neostigmine 0.07 mg/kg for reversal of rocuronium-induced deep NMB. Sugammadex 4 mg/kg was 45.78 minutes (16.8 times) faster then neostigmine 0.07 mg/kg (2.9 vs 48.8 minutes) in reversing NMB from post-tetanic count (PTC) 1 to 5 to TOFR > 0.9 (MD 45.78 minutes, 95% CI 39.41 to 52.15; I2 = 0%; two studies, n = 114; GRADE: low quality).For our secondary outcomes, we compared sugammadex, any dose, and neostigmine, any dose, looking at risk of adverse and serious adverse events. We found significantly fewer composite adverse events in the sugammadex group compared with the neostigmine group (RR 0.60, 95% CI 0.49 to 0.74; I2 = 40%; 28 studies, n = 2298; GRADE: moderate quality). Risk of adverse events was 28% in the neostigmine group and 16% in the sugammadex group, resulting in a number needed to treat for an additional beneficial outcome (NNTB) of 8. When looking at specific adverse events, we noted significantly less risk of bradycardia (RR 0.16, 95% CI 0.07 to 0.34; I2= 0%; 11 studies, n = 1218; NNTB 14; GRADE: moderate quality), postoperative nausea and vomiting (PONV) (RR 0.52, 95% CI 0.28 to 0.97; I2 = 0%; six studies, n = 389; NNTB 16; GRADE: low quality) and overall signs of postoperative residual paralysis (RR 0.40, 95% CI 0.28 to 0.57; I2 = 0%; 15 studies, n = 1474; NNTB 13; GRADE: moderate quality) in the sugammadex group when compared with the neostigmine group. Finally, we found no significant differences between sugammadex and neostigmine regarding risk of serious adverse events (RR 0.54, 95% CI 0.13 to 2.25; I2= 0%; 10 studies, n = 959; GRADE: low quality).Application of trial sequential analysis (TSA) indicates superiority of sugammadex for outcomes such as recovery time from T2 to TOFR > 0.9, adverse events, and overall signs of postoperative residual paralysis.

Authors' conclusions: Review results suggest that in comparison with neostigmine, sugammadex can more rapidly reverse rocuronium-induced neuromuscular block regardless of the depth of the block. Sugammadex 2 mg/kg is 10.22 minutes (˜ 6.6 times) faster in reversing moderate neuromuscular blockade (T2) than neostigmine 0.05 mg/kg (GRADE: moderate quality), and sugammadex 4 mg/kg is 45.78 minutes (˜ 16.8 times) faster in reversing deep neuromuscular blockade (PTC 1 to 5) than neostigmine 0.07 mg/kg (GRADE: low quality). With an NNTB of 8 to avoid an adverse event, sugammadex appears to have a better safety profile than neostigmine. Patients receiving sugammadex had 40% fewer adverse events compared with those given neostigmine. Specifically, risks of bradycardia (RR 0.16, NNTB 14; GRADE: moderate quality), PONV (RR 0.52, NNTB 16; GRADE: low quality), and overall signs of postoperative residual paralysis (RR 0.40, NNTB 13; GRADE: moderate quality) were reduced. Both sugammadex and neostigmine were associated with serious adverse events in less than 1% of patients, and data showed no differences in risk of serious adverse events between groups (RR 0.54; GRADE: low quality).

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Conflict of interest statement

Ana‐Marija Hristovska declares no conflict of interest.

Patricia Duch declares no conflict of interest.

Mikkel Allingstrup declares no conflict of interest.

Arash Afshari declares no conflict of interest.

Figures

1
1
TSA of all trials comparing sugammadex 2.0 mg/kg vs neostigmine 0.05 mg/kg; recovery time from T2 to TOFR > 0.9 minutes. With a required information size of 106, firm evidence in place favours sugammadex in a random‐effects model, with an alfa‐boundary adjusted MD of ‐10.22 (95% CI ‐12.11 to ‐8.33; diversity (D2) = 87%, I2 = 84%, random‐effects model). The cumulative Z‐curve crosses the monitoring boundary constructed for the required information size with 80% power and alpha of 0.05. However, none of the included trials had low risk of bias, and because TSA is ideally designed for trials with low risk of bias and cannot be adjusted for risk of bias, the precision of our findings has to be downgraded. Furthermore, the degree of diversity and heterogeneity is high, which once again raises questions about the reliability of the calculated required information size.
2
2
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
3
3
TSA of dichotomous data on drug‐related risk of adverse events; sugammadex (any dose) vs neostigmine (any dose). This analyses includes continuity adjustment for zero event trials (0.001 in each arm) resulting in an alfa‐boundary adjusted RR of 0.62 (95% CI 0.51 to 0.74; diversity (D2) = 34%, I2 = 14%, random‐effects model), with a control event proportion of 27.97%. With the required information size of 502, analyses indicated firm evidence favouring sugammadex with 2298 participants included corresponding to a relative risk reduction (RRR) of 38% with 80% power and alpha of 0.05. Despite the fact that the cumulative Z‐curve does not cross the monitoring boundary directly, it is hard to imagine future trials radically changing the overall picture of this analysis. However, none of the included trials were at low risk of bias, and this does downgrade the reliability of our finding.
4
4
TSA of dichotomous data on risk of signs of residual neuromuscular blockade; sugammadex (any dose) vs neostigmine (any dose). With continuity adjustment for zero event trials (0.001 in each arm), TSA resulted in an alfa‐boundary adjusted RR of 0.4 (95% CI 0.27 to 0.59; diversity (D2) = 0%, I2 = 0%, random‐effects model, with 80% power and alpha of 0.05), with a control event proportion of 13.08%. Cumulative Z‐curve crosses the monitoring boundary constructed for a required information size of 424 participants, indicating firm evidence in favour of sugammadex. However, none of the included trials had low risk of bias, and this equally diminishes the reliability and precision of our estimates.
5
5
Study flow diagram.
6
6
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
1.1
1.1. Analysis
Comparison 1 Sugammadex 2.0 mg/kg vs neostigmine 0.05 mg/kg, Outcome 1 Recovery time from T2 to TOFR > 0.9.
1.2
1.2. Analysis
Comparison 1 Sugammadex 2.0 mg/kg vs neostigmine 0.05 mg/kg, Outcome 2 Subgroup analysis: TIVA vs volatile anaesthetics.
1.3
1.3. Analysis
Comparison 1 Sugammadex 2.0 mg/kg vs neostigmine 0.05 mg/kg, Outcome 3 Sensitivity analysis: meeting abstracts excluded.
2.1
2.1. Analysis
Comparison 2 Sugammadex 4.0 mg/kg vs neostigmine 0.07 mg/kg, Outcome 1 Recovery time from PTC 1 to 5 to TOFR > 0.9.
3.1
3.1. Analysis
Comparison 3 Sugammadex (any dose) vs neostigmine (any dose), Outcome 1 Risk of composite adverse events.
3.2
3.2. Analysis
Comparison 3 Sugammadex (any dose) vs neostigmine (any dose), Outcome 2 Composite adverse events: subgroup analysis for dosage.
3.3
3.3. Analysis
Comparison 3 Sugammadex (any dose) vs neostigmine (any dose), Outcome 3 Composite adverse events: subgroup analysis ‐ TIVA vs volatile anaesthetics.
3.4
3.4. Analysis
Comparison 3 Sugammadex (any dose) vs neostigmine (any dose), Outcome 4 Composite adverse events: sensitivity analysis ‐ excluding meeting abstracts.
3.5
3.5. Analysis
Comparison 3 Sugammadex (any dose) vs neostigmine (any dose), Outcome 5 Participants with ≥ adverse event.
3.6
3.6. Analysis
Comparison 3 Sugammadex (any dose) vs neostigmine (any dose), Outcome 6 Bradycardia: subgroup analysis ‐ atropine vs glycopyrrolate.
3.7
3.7. Analysis
Comparison 3 Sugammadex (any dose) vs neostigmine (any dose), Outcome 7 PONV: subgroup analysis ‐ TIVA vs volatile anaesthetics.
3.8
3.8. Analysis
Comparison 3 Sugammadex (any dose) vs neostigmine (any dose), Outcome 8 Desaturation.
3.9
3.9. Analysis
Comparison 3 Sugammadex (any dose) vs neostigmine (any dose), Outcome 9 Procedural complications.
3.10
3.10. Analysis
Comparison 3 Sugammadex (any dose) vs neostigmine (any dose), Outcome 10 Transitory oxygen supplementation.
3.11
3.11. Analysis
Comparison 3 Sugammadex (any dose) vs neostigmine (any dose), Outcome 11 Not able to perform 5 second head‐lift after extubation.
3.12
3.12. Analysis
Comparison 3 Sugammadex (any dose) vs neostigmine (any dose), Outcome 12 General muscle weakness after extubation.
3.13
3.13. Analysis
Comparison 3 Sugammadex (any dose) vs neostigmine (any dose), Outcome 13 Nausea.
3.14
3.14. Analysis
Comparison 3 Sugammadex (any dose) vs neostigmine (any dose), Outcome 14 Vomiting.
3.15
3.15. Analysis
Comparison 3 Sugammadex (any dose) vs neostigmine (any dose), Outcome 15 Postprocedural nausea.
3.16
3.16. Analysis
Comparison 3 Sugammadex (any dose) vs neostigmine (any dose), Outcome 16 Headache.
3.17
3.17. Analysis
Comparison 3 Sugammadex (any dose) vs neostigmine (any dose), Outcome 17 Hypertension.
3.18
3.18. Analysis
Comparison 3 Sugammadex (any dose) vs neostigmine (any dose), Outcome 18 Hypotension.
3.19
3.19. Analysis
Comparison 3 Sugammadex (any dose) vs neostigmine (any dose), Outcome 19 Cough.
3.20
3.20. Analysis
Comparison 3 Sugammadex (any dose) vs neostigmine (any dose), Outcome 20 Dry mouth.
3.21
3.21. Analysis
Comparison 3 Sugammadex (any dose) vs neostigmine (any dose), Outcome 21 Dizziness.
3.22
3.22. Analysis
Comparison 3 Sugammadex (any dose) vs neostigmine (any dose), Outcome 22 Tachycardia.
3.23
3.23. Analysis
Comparison 3 Sugammadex (any dose) vs neostigmine (any dose), Outcome 23 Pruritus.
3.24
3.24. Analysis
Comparison 3 Sugammadex (any dose) vs neostigmine (any dose), Outcome 24 Pyrexia.
3.25
3.25. Analysis
Comparison 3 Sugammadex (any dose) vs neostigmine (any dose), Outcome 25 Shivering.
3.26
3.26. Analysis
Comparison 3 Sugammadex (any dose) vs neostigmine (any dose), Outcome 26 Chills.
3.27
3.27. Analysis
Comparison 3 Sugammadex (any dose) vs neostigmine (any dose), Outcome 27 Rash.
3.28
3.28. Analysis
Comparison 3 Sugammadex (any dose) vs neostigmine (any dose), Outcome 28 Supraventricular extrasystoles.
3.29
3.29. Analysis
Comparison 3 Sugammadex (any dose) vs neostigmine (any dose), Outcome 29 Laryngospasm.
3.30
3.30. Analysis
Comparison 3 Sugammadex (any dose) vs neostigmine (any dose), Outcome 30 Increased upper airway secretion.
3.31
3.31. Analysis
Comparison 3 Sugammadex (any dose) vs neostigmine (any dose), Outcome 31 Procedural hypertension.
3.32
3.32. Analysis
Comparison 3 Sugammadex (any dose) vs neostigmine (any dose), Outcome 32 Procedural hypotension.
3.33
3.33. Analysis
Comparison 3 Sugammadex (any dose) vs neostigmine (any dose), Outcome 33 Abdominal pain.
3.34
3.34. Analysis
Comparison 3 Sugammadex (any dose) vs neostigmine (any dose), Outcome 34 Clinical signs of residual NMB.
3.35
3.35. Analysis
Comparison 3 Sugammadex (any dose) vs neostigmine (any dose), Outcome 35 Clinical signs of inadequate reversal of NMB.
3.36
3.36. Analysis
Comparison 3 Sugammadex (any dose) vs neostigmine (any dose), Outcome 36 Clinical signs of recurrence of residual NMB.
3.37
3.37. Analysis
Comparison 3 Sugammadex (any dose) vs neostigmine (any dose), Outcome 37 General muscle weakness at PACU discharge.
3.38
3.38. Analysis
Comparison 3 Sugammadex (any dose) vs neostigmine (any dose), Outcome 38 Not able to perform 5 second head‐lift at PACU discharge.
3.39
3.39. Analysis
Comparison 3 Sugammadex (any dose) vs neostigmine (any dose), Outcome 39 Overall signs of postoperative residual paralysis.
3.40
3.40. Analysis
Comparison 3 Sugammadex (any dose) vs neostigmine (any dose), Outcome 40 Risk of composite serious adverse events.
3.41
3.41. Analysis
Comparison 3 Sugammadex (any dose) vs neostigmine (any dose), Outcome 41 Participants with ≥ 1 serious adverse event.
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References

References to studies included in this review

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    1. Riga M, Batistaki C, Matsota P, Lyrakos G, Zafeiropoulou F, Kostopanagiotou G. Effect of sugammadex versus neostigmine/atropine combination on cognitive function of adult patients after elective surgery: preliminary results. European Journal of Anaesthesiology. 2014; Vol. 31:157‐8.
Sabo 2011 {published data only (unpublished sought but not used)}
    1. Sabo D, Jones RK, Berry J, Sloan T, Chen JY, Groudine S. Residual neuromuscular blockade at extubation: a randomized comparison of sugammadex and neostigmine reversal of rocuronium‐induced blockade in patients undergoing abdominal surgery. Anesthesia and Clinical Research Journals 2011;2(6):Open assess journal, no pages.
Schaller 2010 {published data only (unpublished sought but not used)}
    1. Schaller SJ, Fink H, Ulm K, Blobner M. Sugammadex and neostigmine dose‐finding study for reversal of shallow residual neuromuscular block. Anesthesiology 2010;113(5):1054‐60. [DOI: 10.1097/ALN.0b013e3181f4182a; PUBMED: 20885293] - DOI - PubMed
Sherman 2014 {published data only (unpublished sought but not used)}
    1. Sherman A, Abelansky Y, Evron S, Ezri T. The effect of sugammadex vs. neostigmine on the postoperative respiratory complications following laparoscopic sleeve gastrectomy. European Journal of Anaesthesiology. 2014; Vol. 31:152.
Sustic 2012 {published data only}
    1. Sustic A, Dijana D. Early postoperative gastric emptying in patients undergoing laparoscopic cholecystectomy: sugammadex vs. neostigmine/atropine neuromuscular blockade reversal agents. European Anaesthesiology Congress, EUROANAESTHESIA. Lippincott Williams and Wilkins, 2012; Vol. 29:140.
Tas 2015 {published data only (unpublished sought but not used)}
    1. Taş N, Korkmaz H, Yağan Ö, Korkmaz M. Effect of sugammadex on postoperative bleeding and coagulation parameters after septoplasty: a randomized prospective study. Medical Science Monitor 2015;14:2382‐6. [PUBMED: 26271275] - PMC - PubMed
Woo 2013 {published and unpublished data}
    1. Woo T, Kim KS, Shim YH, Kim MK, Yoon SM, Lim YJ, et al. Sugammadex versus neostigmine reversal of moderate rocuronium‐induced neuromuscular blockade in Korean patients. Korean Journal of Anesthesiololgy 2013;65(6):501‐7. [PUBMED: 24427455] - PMC - PubMed
Wu 2014 {published data only (unpublished sought but not used)}
    1. Wu X, Oerding H, Liu J, Vanacker B, Yao S, Dahl V, et al. Rocuronium blockade reversal with sugammadex vs. neostigmine: randomized study in Chinese and Caucasian subjects. BMC Anesthesiology 2014;14(53):eCollection. [DOI: 10.1186/1471-2253-14-53; PUBMED: 25187755] - DOI - PMC - PubMed
Yagan 2015 {published and unpublished data}
    1. Yagan O, Karakahya RH, Tas N, Canakci E, Hanci V, Yurtlu BS. Intraocular pressure changes associated with tracheal extubation: comparison of sugammadex with conventional reversal of neuromuscular blockade. Journal of the Pakistan Medical Assosication 2015;65(11):1219‐25. [PUBMED: 26564297] - PubMed

References to studies excluded from this review

Aho 2012 {published data only}
    1. Aho Aj, Kamata K, Yli‐Hankala A, Lyytikäinen L‐P, Kulkas A, Jäntti V. Elevated BIS and entropy values after sugammadex or neostigmine: an electroencephalographicor electromyographic phenomenon?. Acta Anaesthesiologica Scandinavica 2012;56(4):465‐73. [PUBMED: 22289106] - PubMed
Baysal 2013 {published data only}
    1. Baysal A, Dogukan M, Toman H, Sagiroglu G, Kocak T. The use of sugammadex for reversal of residual blockade after administration of neostigmine and atropine. European Anaesthesiology Congress, EUROANAESTHESIA. Lippincott Williams and Wilkins, 2013; Vol. 30:142.
Dahaba 2012 {published data only}
    1. Dahaba AA, Bornemann H, Hopfgartner E, Ohran M, Kocher K, Liebmann M, et al. Effect of sugammadex or neostigmine neuromuscular block reversal on bispectral index monitoring of propofol/remifentanil anaesthesia. British Journal of Anaesthesia 2012;108(4):602‐6. [PUBMED: 22315331] - PubMed
Gaona 2012 {published data only}
    1. Gaona D, Carceles MD, Veiga G, Tedesco M, Motta P. Efficacy and safety of the reversal with sugammadex in deep neuromuscular blockade induced by rocuronium in pediatrics. 15th WFSA World Congress of Anaesthesiologists Predio Ferial de Buenos Aires Argentina. Oxford University Press, 2012; Vol. 108:308‐9.
Ghoneim 2015 {published data only}
    1. Ghoneim AA, Beltagy MA. Comparative study between sugammadex and neostigmine in neurosurgical anesthesia in pediatric patients. Saudi Journal of Anaesthesia 2015;9(3):247‐52. [PUBMED: 26240540] - PMC - PubMed
Harazim 2014 {published data only}
    1. Harazim H, Stourac P, Seidlova D, Adamus M, Krikava I, Pavlik T. Use of rocuronium and active reversal of neuromuscular blockade with sugammadex in anaesthesia for caesarean section led to reduction of myalgia incidence in early postoperative period: prospective randomised interventional multicentric trial. European Journal of Anaesthesiology. 2014; Vol. 31:194‐5.
Kakinuma 2013 {published data only (unpublished sought but not used)}
    1. Kakinuma A, Nagatani H, Yasuda A, Yoshimura T, Sawai J, Nakata Y. Combined use of sugammadex and neostigmine for the reversal of rocuronium‐induced profound neuromuscular blockade. Anesthesia and Clinical Research Journal 2013;4(7):337. [DOI: 10.4172/2155-6148.1000337] - DOI
Kara 2014 {published data only}
    1. Kara T, Ozbagriacik O, Turk HS, Isil CT, Gokuc O, Unsal O, et al. Sugammadex versus neostigmine in pediatric patients: a prospective randomized study. Revista Brasileira de Anestesiologia 2014;64(6):400‐5. [PUBMED: 25437696] - PubMed
Kzlay 2013 {published data only (unpublished sought but not used)}
    1. Kzlay D, Dal D, Saraçoğlu T, Eti Z, Göğüş Y. The effects of sugammadex and neostigmine‐atropine administration on hemodynamic parameters in cardiac patients undergoing non‐cardiac surgery. European Journal of Anaesthesiology. 2013; Vol. 30:75.
Nagashima 2016 {published and unpublished data}
    1. Nagashima S, Takasusuki T, Yamaguchi S, Hamaguchi S. Effects of neostigmine and sugammadex on QT interval and QT dispersion. Dokkyo Journal of Medical Sciences 2016;43:15‐22.
Nagy 2014 {published data only}
    1. Nagy HIA, Elkadi HW. Can sugammadex improve the reversal profile of atracurium under sevoflurane anesthesia?. Egyptian Journal of Anaesthesia 2014;30(1):95‐9. [DOI: 10.1016/j.egja.2013.09.007] - DOI
NCT03111121 {unpublished data only}
    1. NCT03111121. Use of Sugammadex for Reversal of Paralysis in Microlaryngoscopy. https://clinicaltrials.gov/show/NCT03111121, March 23, 2017.
Nemes 2016 {published and unpublished data}
    1. Nemes R, Fülesdi B, Pongrácz A, Asztalos L, Szabó‐Maák Z, Lengyel S, et al. Impact of reversal strategies on the incidence of postoperative residual paralysis after rocuronium relaxation without neuromuscular monitoring: a partially randomised placebo controlled trial. European Journal of Anaesthesiology 2016;1:1. [PUBMED: 28030444] - PubMed
Ozgun 2014 {published data only}
    1. Ozgün C, Cakan T, Baltacı B, Başar H. Comparison of reversal and adverse effects of sugammadex and combination of anticholinergic‐anticholinesterase agents in pediatric patients. Journal of Research in Medical Sciences 2014;19(8):762‐8. [PUBMED: 25422663] - PMC - PubMed
Pecek 2013 {published data only}
    1. Pecek B, Hollan J, Priman T, Tokic Crnic N, Stankovic V, Polh D. New way of dosing sugammadex for termination of vecuronium induced neuromuscular block. Zdravniski Vestnik 2015;84:439–46.
Sacan 2007 {published data only}
    1. Sacan O, White PF, Tufanogullari B, Klein K. Sugammadex reversal of rocuronium‐induced neuromuscular blockade: a comparison with neostigmine‐glycopyrrolate and edrophonium‐atropine. Anesthesia and Analgesia 2007;104(3):569‐74. [PUBMED: 17312210 ] - PubMed
Schepens 2015 {published data only}
    1. Schepens T, Cammu G, Saldien V, Neve N, Jorens PG, Foubert L, et al. Electromyographic activity of the diaphragm during neostigmine or sugammadex‐enhanced recovery after neuromuscular blockade with rocuronium: a randomised controlled study in healthy volunteers. European Journal of Anaesthesiology 2015;32(1):49‐57. [PUBMED: 25111539] - PubMed
Stourac 2016 {published and unpublished data}
    1. Stourac P, Adamus M, Seidlova D, Pavlik T, Janku P, Krikava I, et al. Low‐dose or high‐dose rocuronium reversed with neostigmine or sugammadex for cesarean delivery anesthesia: a randomized controlled noninferiority trial of time to tracheal intubation and extubation. Anesthesia and Analgesia 2016;122(5):1536‐45. [DOI: 10.1213/ANE.0000000000001197; PUBMED: 26974018] - DOI - PubMed
Veiga Ruiz 2011 {published data only}
    1. Veiga Ruiz G, Carceles Baron MD, Dominguez Serrano N, Lopez Fuentes L, Orozco Montes J, Alvarez‐Gomez JA. Sugammadex reversal efficacy and security vs neostigmine in the rocuronium‐induced neuromuscular blockade in paediatric patients. European Journal of Anaesthesiology. Abstracts and Programme: EUROANAESTHESIA 2011: The European Anaesthesiology Congress: Paediatric Anaesthesia and Intensive Care, 2011; Vol. 28:153.

References to studies awaiting assessment

Kim 2016 {published data only}
    1. Kim K, Oh Y, Kim T, Oh S, Sin Y. Relationship between first‐twitch depression and train‐of‐four ratio during sugammadex reversal of rocuronium‐induced neuromuscular blockade. Korean Journal of Anesthesiology 2016;1:1. [PUBMED: 27274368] - PMC - PubMed
NCT02243943 {unpublished data only}
    1. NCT02243943. Effect of Neuromuscular Reversal With Sugammadex on Postoperative Recovery Profile (Neuropa). https://clinicaltrials.gov/show/NCT02243943, September 12, 2014.
Sen 2016 {unpublished data only}
    1. Sen A, Erdivanli B, Tomak Y, Pergel A. Reversal of neuromuscular blockade with sugammadex or neostigmine/atropine: effect on postoperative gastrointestinal motility. Journal of Clinical Anesthesia 2016;1:1. [PUBMED: 27290978] - PubMed

References to ongoing studies

NCT01539044 {unpublished data only}
    1. NCT01539044. Optimal Relaxation Technique for Laparotomies With Rocuronium Infusion Followed by Sugammadex Reversal (ProjectO5Rs). https://clinicaltrials.gov/show/NCT01539044, February 15, 2012.
NCT01748643 {unpublished data only}
    1. NCT01748643. CURES: The Effect of Deep Curarisation and Reversal With Sugammadex on Surgical Conditions and Perioperative Morbidity (CURES). https://clinicaltrials.gov/show/NCT01748643, December 6, 2012.
NCT02160223 {unpublished data only}
    1. NCT02160223. Sugammadex Compared With Neostigmin/Atropin for Neuromuscular Block Reversal in Patients With Obstructive Sleep Apnea. https://clinicaltrials.gov/show/NCT02160223, June 8, 2014.
NCT02256280 {unpublished data only}
    1. NCT02256280. A Randomized Double Blind Controlled Trial Comparing Sugammadex and Neostigmine After Thoracic Anesthesia (DATA). https://clinicaltrials.gov/show/NCT02256280, September 24, 2014.
NCT02330172 {unpublished data only}
    1. NCT02330172. Sugammadex Provide Better Surgical Condition Compared With Neostigmine in Laryngeal Microsurgery. https://clinicaltrials.gov/show/NCT02330172, December 9, 2014.
NCT02361060 {unpublished data only}
    1. NCT02361060. Effects of Neuromuscular Block Reversal With Sugammadex vs Neostigmine on Postoperative Respiratory Outcomes After Major Abdominal Surgery. https://clinicaltrials.gov/show/NCT02361060, December 23, 2014.
NCT02414880 {unpublished data only}
    1. NCT02414880. Sugammadex Versus Neostigmine in Patients With Liver Cirrhosis Undergoing Liver Resection. https://clinicaltrials.gov/show/NCT02414880, April 5, 2015.
NCT02454504 {unpublished data only}
    1. NCT02454504. Quality of Awakening and Impact on Cognitive Function After Administration of Sugammadex in Robotic Radical Cystectomy. https://clinicaltrials.gov/show/NCT02454504, May 6, 2015.
NCT02648503 {unpublished data only}
    1. NCT02648503. Deep Neuromuscular Block and Sugammadex Versus Standard of Care on Quality of Recovery in Patients Undergoing Elective Laparoscopic Cholecystectomy. https://clinicaltrials.gov/show/NCT02648503, December 7, 2015.
NCT02666014 {unpublished data only}
    1. NCT02666014. Sugammadex Versus Neostigmine for Postoperative Nausea and Vomiting After Laparoscopic Gynaecological Surgery. https://clinicaltrials.gov/show/NCT02666014, February 2, 2015.
NCT02697929 {unpublished data only}
    1. NCT02697929. Sugammadex/Neostigmine and Liver Transplantation. https://clinicaltrials.gov/show/NCT02697929, February 13, 2016.
NCT02698969 {unpublished data only}
    1. NCT02698969. Recovery of Muscle Function After Deep Neuromuscular Block by Means of Diaphragm Ultrasonography. https://clinicaltrials.gov/show/NCT02698969, February 15, 2016.
NCT02845375 {unpublished data only}
    1. NCT02845375. Effect of Neuromuscular Blockade and Reversal on Breathing (BREATH). https://clinicaltrials.gov/show/NCT02845375, July 14, 2016.
NCT02860507 {unpublished data only}
    1. NCT02860507. Study to Determine if Administration of Sugammadex Impacts Hospital Efficiency. https://clinicaltrials.gov/show/NCT02860507, August 2, 2016.
NCT02861131 {unpublished data only}
    1. NCT02861131. The Effect of Sugammadex Versus Neostigmine on Postoperative Pulmonary Complications. https://clinicaltrials.gov/show/NCT02861131, July 14, 2016.
NCT02909439 {unpublished data only}
    1. NCT02909439. Quality of Recovery After Reversal With Neostigmine or Sugammadex. https://clinicaltrials.gov/show/NCT02909439, August 31, 2016.
NCT02939430 {unpublished data only}
    1. NCT02939430. Sugammadex Reversal of Neuromuscular Blockade and Postoperative Bleeding (Suga_bleeding). https://clinicaltrials.gov/show/NCT02939430, October 17, 2016.
NCT03108989 {unpublished data only}
    1. NCT03108989. Comparison the Postoperative Quality of Recovery Between Neostigmine and Sugammadex in Elderly Patients Undergoing Trans Pars Plana Vitrectomy With General Anesthesia ‐ Randomized Controlled Trial. https://clinicaltrials.gov/show/NCT03108989, April 6, 2017.
NCT03116997 {unpublished data only}
    1. NCT03116997. Study of Recovery of Strength After Surgery Comparing Two Different Medications for Reversal of Muscle Relaxant. https://clinicaltrials.gov/show/NCT03116997, April 12, 2017.
NCT03144453 {unpublished data only}
    1. NCT03144453. Recovery From Anesthesia After Robotic Assisted Radical Cystectomy. https://clinicaltrials.gov/show/NCT03144453, May 3, 2017.

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