Sugammadex, a selective reversal medication for preventing postoperative residual neuromuscular blockade

 

Abstract

Background

Sugammadex is the first selective relaxant binding agent that has been studied for reversal of neuromuscular blockade induced by rocuronium and other steroidal non-depolarizing neuromuscular blocking agents (NMBAs).

Objectives

To assess the efficacy and safety of sugammadex in reversing neuromuscular blockade induced by steroidal non-depolarizing NMBAs and in preventing postoperative residual neuromuscular blockade.

Search methods

We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2008, Issue 3), MEDLINE (1950 to August 2008), and EMBASE (1980 to August 2008). In addition, we handsearched reference lists of relevant articles and meeting abstracts. Furthermore, we contacted the medication's manufacturer for more information.

Selection criteria

All randomized controlled trials (RCTs) on adult patients (≥ 18 years old) in which sugammadex was compared with placebo or other medications, or in which different doses of sugammadex were compared with each other. We excluded non-randomized trials and studies on healthy volunteers.

Data collection and analysis

We independently performed determination of trial inclusion, quality assessment, and data extraction. We applied standard meta-analytic techniques.

Main results

We included18 RCTs (n = 1321 patients). Seven trials were published as full-text papers, and 11 trials only as meeting abstracts. All the included trials had adequate methods of randomization and allocation concealment. The results suggest that, compared with placebo or neostigmine, sugammadex can more rapidly reverse rocuronium-induced neuromuscular blockade regardless of the depth of the block. We identified 2, 4, and 16 mg/kg of sugammadex for reversal of rocuronium-induced neuromuscular blockade at T₂ reappearance , 1 to 2 post-tetanic counts, and 3 to 5 minutes after rocuronium, respectively. The number of trials are very limited regarding vecuronium and pancuronium. Serious adverse events occurred in < 1% of all patients who received the medication. There was no significant difference between sugammadex and placebo in terms of the prevalence of drug-related adverse events (RR 1.20, 95% CI 0.61 to 2.37; P = 0.59, I² = 0%, 5 RCTs). Also, no significant difference was found between sugammadex and neostigmine for adverse events (RR 0.98, 95% CI 0.48 to1.98; P = 0.95, I² = 43%, 3 RCTs).

Authors' conclusions

Sugammadex was shown to be effective in reversing rocuronium-induced neuromuscular blockade. This review has found no evidence of a difference in the instance of unwanted effects between sugammadex, placebo or neostigmine. These results need to be confirmed by future trials on larger patient populations and with more focus on patient-related outcomes.

 

Plain language summary

Sugammadex, a new medication for selective reversal of muscle weakness after surgery

Muscle relaxation is required to facilitate some surgical procedures. If it is not completely reversed after surgery, the muscle relaxation effects might lead to remaining muscle weakness, breathing problems, lung infection and delayed recovery. Neostigmine and other medications from the same drug family are currently used to restore muscle function after surgery. These medications, however, are not effective in all situations and may cause complications as well. Complications include changes in the heart and lung function, and nausea and vomiting after surgery. Sugammadex is a new medication that is used after surgery in order to reverse the effects of muscle relaxation medications. In this review article we have included 18 trials on the efficacy and safety of sugammadex. The trials included a total of 1321 patients. Sugammadex was shown to be more effective than placebo (no medication) or neostigmine in reversing muscle relaxation caused by neuromuscular blockade during surgery and is relatively safe. Serious complications occurred in less than 1% of the patients who received sugammadex. The results of this review article (specially the safety results) need to be confirmed by future trials on larger patient populations.

 

摘要

背景

Sugammadex是一種用來避免術後肌肉鬆弛劑作用殘餘的選擇性回復藥物

Sugammadex是第一個被研究用來回復rocuronium及其他固醇類非去極化神經肌肉阻斷劑所導致之神經肌肉阻斷的選擇性鬆弛劑結合劑。

目標

評估Sugammadex回復固醇類非去極化神經肌肉劑阻斷造成之神經肌肉阻斷及預防術後殘餘神經肌肉阻斷的效果及安全性。

搜尋策略

我們搜尋了Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2008, Issue 3)、MEDLINE (1950 to August 2008)、和EMBASE (1980 to August 2008)。我們也人工查詢了相關文章的參考資料和摘要。此外，我們聯絡了該藥物的製造商並取得更多資訊。

選擇標準

所有針對成年病人(大於18歲)比較sugammadex和安慰劑或其他藥物、或不同劑量的sugammadex的隨機臨床試驗被互相比較。我們排除了非隨機試驗及針對健康受試者做的研究。

資料收集與分析

我們獨立地決定臨床試驗是否納入、品質評估、及資料分析。我們運用標準的整合性分析法。

主要結論

我們採用了18個隨機對照試驗、包括1321位病人。其中7個試驗是全文期刊，另外11個則是會議摘要。所有納入研究的試驗都經過充分的隨機分配及遮盲。結果指出：和安慰劑或neostigmine相較，不論神經肌肉阻斷的深度、sugammadex都能更快地逆轉rocuronium導致的肌肉鬆弛。我們分析不同時機給予不同劑量的sugammadex(每公斤體重2、4、或16毫克)：連續四次刺激之第二次刺激再度出現(T2 reappearance)、1至2次強直後，以及給予rocuronium 3至5分鐘後。針對vecuronium和pancuronium的臨床試驗非常有限。使用該藥物的嚴重不良事件發生率小於百分之一。Sugammadex和安慰劑在藥物不良反應的發生率上無顯著差異(RR 1.20，95％ CI為 0.61至2.37，P值0.59，I2 = 0％，5篇隨機對照試驗)。Sugammadex和neostigmine在藥物不良反應的發生率上亦無顯著差異(RR 0.98，95％ CI為 0.48 to1.98; P值0.95，I2 = 43％，3個隨機對照試驗)。

作者結論

Sugammadex能有效逆轉rocuronium導致之肌肉神經阻斷。這篇回顧性文章發現沒有實例證據顯示sugammadex、安慰劑、或neostigmine間有不良反應發生率的差異。這些結果仍有待未來更大型及更針對病人相關預後之臨床試驗的證實。

翻譯人

本摘要由臺灣大學附設醫院王曼玲翻譯。

此翻譯計畫由臺灣國家衛生研究院(National Health Research Institutes, Taiwan)統籌。

總結

Sugammadex是用來選擇性回復術後肌肉無力的新藥：某些手術處置需要肌肉鬆弛來順利進行。假使術後無法將該作用完全回復，可能導致肌肉持續無力、呼吸問題、肺部感染、和延遲恢復。目前neostigmine和其他同家族的藥物被用來回復術後的肌肉功能。然而，這些藥物不是在所有的情況都有效、並可能造成併發症。併發症包括心肺功能改變及術後噁心嘔吐。Sugammadex是術後用來回復肌肉鬆弛藥物的新藥。在本篇文章我們回顧了18篇臨床試驗來分析sugammadex的效果和安全性。這些臨床試驗一共包含了1321位病人。Sugammadex比安慰劑或neostigmine相對安全且可更有效地回復術中肌肉神經阻斷所導致之肌肉鬆弛。不到百分之一使用sugammadex的病人發生嚴重的併發症。這篇回顧性文章的結論(特別是安全性結果)需要未來更大病人族群的臨床試驗來證實。