Pharmacological interventions for preventing rocuronium-induced pain responses and rocuronium-induced withdrawal responses: a systematic review and network meta-analysis

Study objective: Rocuronium is widely used during the induction of general anesthesia. However, it is associated with rocuronium-induced pain response, which can appear as a rocuronium-induced withdrawal response. The purpose of this study was to compare the effectiveness of pharmacological interventions in preventing rocuronium-induced pain response and rocuronium-induced withdrawal response using a network meta-analysis. Design: Systematic review and network meta-analysis (NMA) of RCTs. Setting: Pharmacological interventions to prevent rocuronium-induced pain response and rocuronium-induced pain response and rocuronium-induced withdrawal. Data sources: MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), Google Scholar were systematically searched from its inception until Mar 2020. Methods: We searched multiple databases and extracted randomized controlled trials that compared two or more pharmacological interventions to prevent rocuronium-induced pain response and rocuronium-induced withdrawal response in adult patients who received rocuronium injections for general anesthesia. We conducted network meta-analysis and used surface under the cumulative ranking curve values and rankograms to present the hierarchy of the pharmacological interventions evaluated. Results: In total, 43 studies (5,291 patients) were included in this network meta-analysis and 31 pharmacological interventions were evaluated. The rankogram and cumulative ranking plot showed that oxycodone followed by a combination of lidocaine and sodium bicarbonate (NaHCO3), esmolol, alfentanil, and rocuronium mixed with NaHCO3 had the lowest frequency of rocuronium-induced withdrawal response. In terms of rocuronium-induced pain response, NaHCO3 mixed with rocuronium showed the lowest frequency, followed by a combination of lidocaine and NaHCO3, a combination of lidocaine and nitrous oxide, rocuronium mixed with lidocaine, and lidocaine. Conclusions: Lidocaine administration has been shown to reduce the incidence of rocuronium-induced pain response regardless of the method of injection or drug combination. The combination of lidocaine and NaHCO3 or mixing NaHCO3 with rocuronium was effective at reducing rocuronium-induced withdrawal response. In particular, oxycodone was shown to be more effective than the other opioids evaluated and esmolol was also found to be effective at reducing rocuronium-induced withdrawal response.