Comparison of the efficacy and safety of remifentanil versus different pharmacological approaches on prevention of etomidate-induced myoclonus: a meta-analysis of randomized controlled trials

Bingchen Lang, Lingli Zhang, Fengshan Li, Yunzhu Lin, Wensheng Zhang, Chunsong Yang, Bingchen Lang, Lingli Zhang, Fengshan Li, Yunzhu Lin, Wensheng Zhang, Chunsong Yang

Abstract

Objective: Myoclonus was considered as one conundrum in etomidate induction, which led to multiple risks during clinical anesthesia. The present study was conducted to compare the efficacy of pretreatment with remifentanil to different pharmacological approaches on reducing etomidate-induced myoclonus. Methods: We searched PubMed, Embase, Cochrane Library, and China National Knowledge Infrastructure from the inception to October 2018. Randomized controlled trials comparing remifentanil versus other pharmacological approaches in reducing etomidate-induced myoclonus were eligible to be analyzed. Results: Overall, 13 trials with 1,392 patients met with the inclusion criteria. 1) Pretreatment with remifentanil could reduce the incidence of etomidate-induced myoclonus compared to placebo and fentanyl; few differences were found between the use of remifentanil and the use of midazolam: (incidence of myoclonus: 5.56% with remifentanil vs 71.65% with saline, RR=0.08, with 95% CI [0.05, 0.12], P<0.0001; 3.80% with remifentanil vs 13.33% with fentanyl, RR with 95% 0.31 [0.11, 0.86], P=0.02; 46.00% with remifentanil vs 55.45% with midazolam, RR=0.82, with 95% CI [0.64, 1.06], P=0.13). 2) Compared with placebo, pretreatment with remifentanil could reduce the incidence of mild, moderate, and severe myoclonus; compared with midazolam, patients receiving remifentanil experienced lower occurrence of severe myoclonus; compared with fentanyl, pretreatment with remifentanil associated with significant low occurrence of moderate and severe myoclonus. 3) The outcomes also indicated that pretreatment with remifentanil could prevent excessive hemodynamic changes after endotracheal intubation compared to fentanyl. Conclusions: Pretreatment with remifentanil could be considered as one operative option to reduce both incidence and severity of etomidate-induced myoclonus. Compared with fentanyl, it also provides efficacy in preventing excessive hemodynamic changes after endotracheal intubation. However, the best treatment and the proper prophylactic dosage calls for more high quality evidence with large sample size.

Keywords: etomidate; fentanyl; meta-analysis; midazolam; myoclonus; remifentanil.

Conflict of interest statement

The authors report no conflicts of interest in this work.

Figures

Figure 1
Figure 1
Flow chart of literature screening and the selection process. Abbreviations: CNKI, China National Knowledge Infrastructure; RCT, randomized controlled trial.
Figure 2
Figure 2
Risk of bias assessment of included studies. Green + dot, low risk of bias; yellow ? dot, unclear risk of bias; red - dot, high risk of bias.
Figure 3
Figure 3
Forest plot of incidence of etomidate-induced myoclonus.Notes: (A) remifentanil vs saline; (B) remifentanil versus midazolam; (C) remifentanil vs fentanyl; (D) remifentanil 2 ng/ml (TCI) vs remifentanil 4 ng/ml (TCI). Abbreviations: RR, risk ratio.; TCI, target controlled infusion.
Figure 4
Figure 4
Forest plot of severity of etomidate-induced myoclonus: remifentanil vs saline.Notes: (A) incidence of etomidate-induced mild myoclonus; (B) incidence of etomidate-induced moderate myoclonus; (C) incidence of etomidate-induced severe myoclonus.
Figure 5
Figure 5
Forest plot of severity of etomidate-induced myoclonus: remifentanil vs midazolam.Notes: (A) incidence of etomidate-induced mild myoclonus; (B) incidence of etomidate-induced moderate myoclonus; (C) incidence of etomidate-induced severe myoclonus.
Figure 6
Figure 6
Forest plot of severity of etomidate-induced myoclonus: remifentanil vs fentanyl.Notes: (A) incidence of etomidate-induced mild myoclonus; (B) incidence of etomidate-induced moderate myoclonus.
Figure 7
Figure 7
Forest plot of severity of etomidate-induced myoclonus: remifentanil 2 ng/ml (TCI) vs remifentanil 4 ng/ml (TCI).Notes: (A) incidence of etomidate-induced mild myoclonus; (B) incidence of etomidate-induced moderate myoclonus. Abbreviation: TCI, target controlled infusion.
Figure 8
Figure 8
Forest plot of the numbers of patients that experienced great hemodynamic changes: remifentanil vs fentanyl. Notes: (A) numbers of patients that experienced great systolic blood pressure changes; (B) numbers of patients that experienced great heart rate changes.
Figure 9
Figure 9
Funnel plots of effect estimates for various clinical outcomes.Notes: (A) incidence of etomidate-induced myoclonus: remifentanil vs saline (Begg’s test, P=0.029; Egger’s test, P=0.001); (B) incidence of etomidate-induced mild myoclonus: remifentanil vs saline (Begg’s test, P=0.062; Egger’s test, P=0.002); (C) incidence of etomidate-induced moderate myoclonus: remifentanil vs saline (Begg’s test, P=0.484; Egger’s test, P=0.022); (D) incidence of etomidate-induced severe myoclonus: remifentanil vs saline (Begg’s test, P=0.312; Egger’s test, P=0.941).Abbreviations: RR, risk ratio; SE, standard error.

References

    1. Forman SA. Clinical and molecular pharmacology of etomidate. Anesthesiology. 2011;114(3):695–707. doi: 10.1097/ALN.0b013e3181ff72b5.
    1. Holdcroft A, Morgan M, Whitwam JG, Lumley J. Effect of dose and premedication on induction complications with etomidate. Br J Anaesth. 1976;48:199–205. doi:10.1093/bja/48.3.199
    1. Nyman Y, Von Hofsten K, Palm C, Eksborg S, Lönnqvist PA. Etomidate-lipuro is associated with considerably less injection pain in children compared with propofol with added lidocaine. Br J Anaesth. 2006;97(4):536–539. doi:10.1093/bja/ael187
    1. Cotten JF, Husain SS, Forman SA, et al. Methoxycarbonyl-etomidate: a novel rapidly metabolized and ultra-short-acting etomidate analogue that does not produce prolonged adrenocortical suppression. Anesthesiology. 2009;111(2):240–249. doi:10.1097/ALN.0b013e3181ae63d1
    1. Hueter L, Schwarzkopf K, Simon M, Bredle D, Fritz H. Pretreatment with sufentanil reduces myoclonus after etomidate. Acta Anaesthesiol Scand. 2003;47(4):482–484. doi:10.1034/j.1399-6576.2003.00081.x
    1. Hüter L, Schreiber T, Gugel M, Schwarzkopf K. Low-dose intravenous midazolam reduces etomidate-induced myoclonus: a prospective, randomized study in patients undergoing elective cardioversion. Anesth Analg. 2007;105(5):1298–1302. doi:10.1213/01.ane.0000287248.25610.c0
    1. Choi JM, Choi IC, Jeong YB, Kim TH, Hahm KD. Pretreatment of rocuronium reduces the frequency and severity of etomidate-induced myoclonus. J Clin Anesth. 2008;20(8):601–604. doi:10.1016/j.jclinane.2008.06.010
    1. Gultop F, Akkaya T, Bedirli N, Gumus H. Lidocaine pretreatment reduces the frequency and severity of myoclonus induced by etomidate. J Anesth. 2010;24(2):300–302. doi:10.1007/s00540-010-0869-6
    1. Glass PS, Hardman D, Kamiyama Y, et al. Preliminary pharmacokinetics and pharmacodynamics of an ultra-short-acting opioid: remifentanil (GI87084B). Anesth Analg. 1993;77:1031–1040. doi:10.1213/00000539-199311000-00028
    1. Kelsaka E, Karakaya D, Sarihasan B, Baris S. Remifentanil pretreatment reduces myoclonus after etomidate. J Clin Anesth. 2006;18(2):83–86. doi:10.1016/j.jclinane.2005.05.004
    1. Ri HS, Shin SW, Kim TK, Baik SW, Yoon JU, Byeon GJ. The proper effect site concentration of remifentanil for prevention of myoclonus after etomidate injection. Korean J Anesthesiol. 2011;61(2):127–132. doi:10.4097/kjae.2011.61.2.127
    1. Ko BJ, Oh JN, Lee JH, Choi SR, Lee SC, Chung CJ. Comparison of effects of fentanyl and remifentanil on hemodynamic response to endotracheal intubation and myoclonus in elderly patients with etomidate induction. Korean J Anesthesiol. 2013;64(1):12–18.
    1. Moher D, Liberati A, Tetzlaff J, Altman DG; PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. BMJ. 2009;339:b2535.
    1. Higgins JP, Altman DG, Gøtzsche PC, et al.; Cochrane Statistical Methods Group. The Cochrane collaboration’s tool for assessing risk of bias in randomised trials. BMJ. 343;2011:d5928. doi:10.1136/bmj.d5928
    1. Higgins JP, Altman DG, Sterne JA, editors. Chapter 8: Assessing risk of bias in included studies. Cochrane Handbook for Systematic Reviews of Interventions. London: The Cochrane Collaboration; 2008:187–241.
    1. Lee SW, Gill HJ, Park SC, et al. The effect of remifentanil for reducing myoclonus during induction of anesthesia with etomidate. Korean J Anesthesiol. 2009;57(4):438–443. doi:10.4097/kjae.2009.57.4.438
    1. Zou L, Yuan H, Wang HY, Geng ZY, Xu L, Sun L. [Role of target controlled infusion of remifentanil for the prevention of etomidate induced myoclonus during general anesthesia]. Acta Acad Med Sin. 2013;35(1):112–115. Chinese.
    1. Zhao XH, Li JB, Deng XM. [Remifentanil pretreatment reduces myoclonus after etomidate]. J Clin Anesthesiol. 2008;24:482–483. Chinese.
    1. Sun ZC, Huang XL, Zhang RJ, Qi C. Gao L. [Reducing etomidate injection induced myoclonus symptom by remifentanil target control infusion]. J Trop Med. 2012;12(11):1367–1369. Chinese.
    1. Yuan LL, Wen XB, Zhou W, Xu DP. [Effects of remifentanil on myoclonus induced by etomidate]. Clin J Med Offic. 2012;40(2):298–299. Chinese.
    1. Hwang JY, Kim JH, Oh AY, Do SH, Jeon YT, Han SH. A comparison of midazolam with remifentanil for the prevention of myoclonic movements following etomidate injection. J Int Med Res. 2008;36(1):17–22. doi:10.1177/147323000803600103
    1. Chen Y, Wang GL, Yu YH. [Effects of different opioids on myoclonus and bispectral index during etomidate induction]. Tianjin Med J. 2009;37(5):368–370. Chinese.
    1. Song ZG, Zhang ZP, Fang NN, Li X, Sun GH. [Comparison of effects of fentanyl，remifentanil and sufentanil on hemodynamic response to endotracheal intubation and myoclonus in elderly patients with etomidate induction]. Pract Pharm Clin Remedies. 2014;17(10):1262–1265. Chinese.
    1. Xie YF, Song DD, Zhou J, Liu GL. [Preventive effect of fentanyl and remifentanil on myoclonus induced by etomidate in elderly patients]. Pract Pharm Clin Remedies. 2016;19(2):187–189. Chinese.
    1. Sedighinejad A, Naderi Nabi B, Haghighi M, et al. Comparison of the effects of low-dose midazolam, magnesium sulfate, remifentanil and low-dose etomidate on prevention of etomidate-induced myoclonus in orthopedic surgeries. Anesth Pain Med. 2016;6(2):e35333. doi:10.5812/aapm.35333
    1. Doenicke AW, Roizen MF, Kugler J, Kroll H, Foss J, Ostwald P. Reducing myoclonus after etomidate. Anesthesiology. 1999;90(1):113–119. doi:10.1097/00000542-199901000-00017
    1. Guarracino F, Lapolla F, Cariello C, et al. Target controlled infusion: TCI. Minerva Anestesiol. 2005;71(6):335–337.
    1. Nauta J, Stanley TH, de Lange S, Koopman D, Spierdijk J, van Kleef J. Anaesthetic induction with alfentanil: comparison with thiopental, midazolam, and etomidate. Can Anaesth Soc J. 1983;30:53–60. doi:10.1007/BF03007717
    1. Giese JL, Stockham RJ, Stanley TH, Pace NL, Nelissen RH. Etomidate versus thiopental for induction of anesthesia. Anesth Analg. 1985;64:871–876. doi:10.1213/00000539-198509000-00006
    1. Safavi M, Honarmand A, Zolfaghari S. Comparing the effect of sodium thiopental, magnesium sulfate, midazolam, prime etomidate, and remifentanil on myoclonus incidence and pain induced by anesthesia with etomidate. J Isfahan Med Sch. 2018;35(453):1515–1520.

Source: PubMed

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