Journal of Anesthesia

, Volume 27, Issue 5, pp 742–749 | Cite as

Pharmacological prevention of rocuronium-induced injection pain or withdrawal movements: a meta-analysis

  • Hyun Jeong Kwak
  • Ji Young Kim
  • Yong Beom Kim
  • Sang Kee Min
  • Bong Ki Moon
  • Jong Yeop KimEmail author
Review Article


Rocuronium is reported to be associated with injection pain or withdrawal movement (IPWM). This meta-analysis assessed the efficacy of different pharmacological treatments used to decrease the incidence of the rocuronium-induced IPWM. We searched the Cochrane Library, Embase and PubMed for randomized controlled trials comparing a pharmacological drug with a placebo to prevent the rocuronium-induced IPWM and found 37 studies with 5,595 patients. Overall incidence of rocuronium-induced IPWM was 74 %. Pretreatment with opioids [risk ratio (RR) 0.16; 95 % confidence interval (95 % CI) 0.09—0.29], lidocaine (0.47; 0.35–0.64), and ketamine (0.41; 0.22–0.77) were effective in decreasing IPWM. Lidocaine pretreatment with venous occlusion (0.40; 0.32–0.49) and opioids pretreatment with venous occlusion (0.77; 0.61–0.96) were also effective. Mixing sodium bicarbonate (NaHCO3) with rocuronium (0.15; 0.06–0.34) was also efficacious in reducing IPWM. Indirect comparison shows that the RR of NaHCO3 admixture and pretreatment with opioids were lower than that of the other four interventions (pretreatments of ketamine or lidocaine, and lidocaine or opioids with venous occlusion). This meta-analysis suggests that opioids, lidocaine, ketamine, and NaHCO3 are effective in decreasing rocuronium-induced IPWM. Considering the efficacy and convenience, pretreatment with opioids without venous occlusion is recommended for reducing rocuronium-induced IPWM.


Anesthesia Meta-analysis Rocuronium Pain Injection Prevention 


  1. 1.
    Steegers MA, Robertson EN. Pain on injection of rocuronium bromide. Anesth Analg. 1996;83:203.PubMedGoogle Scholar
  2. 2.
    Borgeat A, Kwiatkowski D. Spontaneous movements associated with rocuronium: is pain on injection the cause? Br J Anaesth. 1997;79:382–3.PubMedCrossRefGoogle Scholar
  3. 3.
    Shevchenko Y, Jocson JC, McRae VA, Stayer SA, Schwartz RE, Rehman M, Choudhry DK. The use of lidocaine for preventing the withdrawal associated with the injection of rocuronium in children and adolescents. Anesth Analg. 1999;88:746–8.PubMedGoogle Scholar
  4. 4.
    Moorthy SS, Dierdoff SF. Pain on injection of rocuronium bromide. Anesth Analg. 1995;80:1067.PubMedGoogle Scholar
  5. 5.
    Kim JY, Kim JY, Kim YB, Kwak HJ. Pretreatment with remifentanil to prevent withdrawal after rocuronium in children. Br J Anaesth. 2007;98:120–3.PubMedCrossRefGoogle Scholar
  6. 6.
    Lui JT, Huang SJ, Yang CY, Hsu JC, Lui PW. Rocuronium-induced generalized spontaneous movements cause pulmonary aspiration. Chang Gung Med J. 2002;25:617–20.PubMedGoogle Scholar
  7. 7.
    Higgins JPT, Green S, editors. Cochrane handbook for the systematic reviews of interventions. Version 5.0.2. Cochrane Collaboration; 2009.Google Scholar
  8. 8.
    Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gøtzsche PC, Ioannidis JP, Clarke M, Devereaux PJ, Kleijnen J, Moher D. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration. BMJ. 2009;339:b2700.PubMedCrossRefGoogle Scholar
  9. 9.
    Jadad AR, Moore RA, Carroll D, Jenkinson C, Reynolds DJ, Gavaghan DJ, McQuay HJ. Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials. 1996;17:1–12.PubMedCrossRefGoogle Scholar
  10. 10.
    Viechtbauer W. Conducting meta-analyses in R with the metaphor package. J Stat Softw. 2010;36:1–48.Google Scholar
  11. 11.
    Knapp G, Hartung J. Improved tests for a random effects metaregression with a single covariate. Stat Med. 2003;22:2693–710.PubMedCrossRefGoogle Scholar
  12. 12.
    Reddy MS, Chen FG, Ng HP. Effect of ondansetron pretreatment on pain after rocuronium and propofol injection: a randomised, double-blind controlled comparison with lidocaine. Anaesthesia. 2001;56:902–5.PubMedCrossRefGoogle Scholar
  13. 13.
    Memiş D, Turan A, Karamanlioğlu B, Süt N, Pamukçu Z. The prevention of pain from injection of rocuronium by ondansetron, lidocaine, tramadol, and fentanyl. Anesth Analg. 2002;94:1517–20.PubMedCrossRefGoogle Scholar
  14. 14.
    Jeon Y, Baek SU, Park SS, Kim SO, Baek WY, Yeo JS. Effect of pretreatment with acetaminophen on withdrawal movements associated with injection of rocuronium: a prospective, randomized, double-blind, placebo controlled study. Korean J Anesthesiol. 2010;59:13–6.PubMedCrossRefGoogle Scholar
  15. 15.
    Turan A, Memis D, Karamanlioglu B, Sut N, Pamukcu Z. The prevention of pain from injection of rocuronium by magnesium sulphate, lignocaine, sodium bicarbonate and alfentanil. Anaesth Intensive Care. 2003;31:277–81.PubMedGoogle Scholar
  16. 16.
    Ertugrul F. A comparison of the efficacies of different pre-treatment drugs in resolving the injection pain of rocuronium. J Int Med Res. 2006;34:665–70.PubMedCrossRefGoogle Scholar
  17. 17.
    Ayoğlu H, Altunkaya H, Ozer Y, Yapakçi O, Cukdar G, Ozkoçak I. Does dexmedetomidine reduce the injection pain due to propofol and rocuronium? Eur J Anaesthesiol. 2007;24:541–5.PubMedCrossRefGoogle Scholar
  18. 18.
    Singh M, Chauhan H, Rath GP, Prabhakar H, Bithal PK, Dash HH. Effect of narcotic pretreatment on pain after rocuronium injection: a randomized, double-blind controlled comparison with lidocaine. J Anesth. 2007;21:510–2.PubMedCrossRefGoogle Scholar
  19. 19.
    Yoon JR, Jeon Y, Yoo Y, Shin HJ, Ahn JH, Lim CH. The analgesic effect of remifentanil on prevention of withdrawal response associated with the injection of rocuronium in children: no evidence for a peripheral action. J Int Med Res. 2010;38:1795–800.PubMedCrossRefGoogle Scholar
  20. 20.
    Park JT, Choi JC, Yoo YS, Lee YB, Kim SY, Lim HK. The effect of pretreatment with thiopental on reducing pain induced by rocuronium injection. Yonsei Med J. 2005;46:765–8.PubMedCrossRefGoogle Scholar
  21. 21.
    Kim YH, Go YK, Lee JU, Chung WS, Shin YS, Han KC, Shin JE, Lee SH. Pretreatment with nafamostat mesilate, a kallikrein inhibitor, to decrease withdrawal response associated with rocuronium. J Anesth. 2010;24:549–52.PubMedCrossRefGoogle Scholar
  22. 22.
    Oh AY, Seo KS, Goo EK, Park YO, Kim SJ, Kim JH. Prevention of withdrawal movement associated with injection of rocuronium in children: comparison of remifentanil, alfentanil and fentanyl. Acta Anaesthesiol Scand. 2007;51:1190–3.PubMedGoogle Scholar
  23. 23.
    Kim JY, Kwak HJ, Kim JY, Park KS, Song JS. Prevention of rocuronium-induced withdrawal movement in children: a comparison of remifentanil with alfentanil. Paediatr Anaesth. 2008;18:245–50.PubMedCrossRefGoogle Scholar
  24. 24.
    Kim JH, Kim JH, Han SH, Hwang JW, Oh AY. Alfentanil is comparable to remifentanil in preventing withdrawal movement following rocuronium injection. J Clin Anesth. 2009;21:9–12.PubMedCrossRefGoogle Scholar
  25. 25.
    Choi BI, Choi SH, Shin YS, Lee SJ, Yoon KB, Shin SK, Lee KY. Remifentanil prevents withdrawal movements caused by intravenous injection of rocuronium. Yonsei Med J. 2008;49:211–6.PubMedCrossRefGoogle Scholar
  26. 26.
    Ahmad N, Choy CY, Aris EA, Balan S. Preventing the withdrawal response associated with rocuronium injection: a comparison of fentanyl with lidocaine. Anesth Analg. 2005;100:987–90.PubMedCrossRefGoogle Scholar
  27. 27.
    Borgeat A, Kwiatkowski D, Ruetsch YA. Spontaneous movements associated with rocuronium injection: the effects of prior administration of fentanyl. J Clin Anesth. 1997;9:650–2.PubMedCrossRefGoogle Scholar
  28. 28.
    Asida SM, Megalla SA, Korany A. Effect of fentanyl, lidocaine or, ketorolac on the prevention of pain during rocuronium injection. Egypt J Anaesth. 2009;25:31–40.Google Scholar
  29. 29.
    Kim SK, Kwon MA, Park JS. The amount of 8.4% sodium bicarbonate needed to neutralize the acidity of rocuronium so as to prevent injection pain. J Clin Anesth. 2008;20:629–30.PubMedCrossRefGoogle Scholar
  30. 30.
    Cheong KF, Wong WH. Pain on injection of rocuronium: influence of two doses of lidocaine pretreatment. Br J Anaesth. 2000;84:106–7.PubMedCrossRefGoogle Scholar
  31. 31.
    Akkaya T, Toygar P, Bedirli N, Yazicioğlu D, Gümüş H. Effects of pretreatment with lidocaine or ketamine on injection pain and withdrawal movements of rocuronium. Turk J Med Sci. 2008;38:577–82.Google Scholar
  32. 32.
    Liou JT, Hsu JC, Liu FC, Ching-Wah Sum D, Lui PW. Pretreatment with small-dose ketamine reduces withdrawal movements associated with injection of rocuronium in pediatric patients. Anesth Analg. 2003;97:1294–7.PubMedCrossRefGoogle Scholar
  33. 33.
    Mahajan R, Batra YK, Kumar S. Pain on injection of rocuronium: influence of ketamine pretreatment. Can J Anaesth. 2005;52:111–2.PubMedCrossRefGoogle Scholar
  34. 34.
    Memis D, Turan A, Kaya G, Karamanlioglu B, Seker S. Preventing pain on injection of rocuronium: two doses of dexmedetomidine. Can J Anaesth. 2005;52:437–8.PubMedGoogle Scholar
  35. 35.
    Shin YH, Choi SJ, Jeong HY, Kim MH. Evaluation of dose effects of magnesium sulfate on rocuronium injection pain and hemodynamic changes by laryngoscopy and endotracheal intubation. Korean J Anesthesiol. 2011;60:329–33.PubMedCrossRefGoogle Scholar
  36. 36.
    Yavascaoglu B, Kaya FN, Ozcan B. Esmolol pretreatment reduces the frequency and severity of pain on injection of rocuronium. J Clin Anesth. 2007;19:413–7.PubMedCrossRefGoogle Scholar
  37. 37.
    Yoon JS, Jeon HJ, Cho SS, Lee JD, Kang KO, Ryu SW, Ko HS. Effect of pretreatment with gabapentin on withdrawal movement associated with intravenous rocuronium injection. Korean J Anesthesiol. 2011;61:367–71.PubMedCrossRefGoogle Scholar
  38. 38.
    Lee HJ, Han SJ, Kim H, Lee IO, Kong MH, Kim NS, Lim SH, Lee MK. Antihistamine pretreatment to reduce incidence of withdrawal movement after rocuronium injection. J Korean Med Sci. 2009;24:879–82.PubMedCrossRefGoogle Scholar
  39. 39.
    Sharma S, Sharma D, Jain A, Jain A. Effect of nitrous oxide on pain due to rocuronium injection: a randomised, double-blind, controlled clinical trial. Indian J Anaesth. 2010;54:142–6.PubMedCrossRefGoogle Scholar
  40. 40.
    Kim KS, Kim YS, Jeon WJ, Yeom JH. Prevention of withdrawal associated with the injection of rocuronium in adults and children. J Clin Anesth. 2006;18:334–8.PubMedCrossRefGoogle Scholar
  41. 41.
    Chiarella AB, Jolly DT, Huston CM, Clanachan AS. Comparison of four strategies to reduce the pain associated with intravenous administration of rocuronium. Br J Anaesth. 2003;90:377–9.PubMedCrossRefGoogle Scholar
  42. 42.
    Han DW, Koo BN, Choi SH, Lee JS, Shin YS, Sharma M, Kim KJ. Neutralized rocuronium (pH 7.4) before administration prevents injection pain in awake patients: a randomized prospective trial. J Clin Anesth. 2007;19:418–23.PubMedCrossRefGoogle Scholar
  43. 43.
    Lee SH, Lee CJ, Kim TH, Shin BS, Lee SY, Joo EY, Sim WS. Novel use of hydromorphone as a pretreatment agent: a double-blind, randomized, controlled study in adult Korean surgical patients. Curr Ther Res Clin Exp. 2011;72:36–48.CrossRefGoogle Scholar
  44. 44.
    Lee YC, Jang YH, Kim JM, Lee SG. Rapid injection of rocuronium reduces withdrawal movement on injection. J Clin Anesth. 2009;21:427–30.PubMedCrossRefGoogle Scholar
  45. 45.
    Abduşoğlu MN, Özkoçak I, Yurtlu BS, Hancı V, Okyay RD, Ayoğlu H. A subhypnotic dose of ketamine reduces pain associated with injection of propofol and rocuronium. Eur J Anaesthesiol. 2011;28:229–30.PubMedGoogle Scholar
  46. 46.
    Prasanna M, Priya V, Divatia JV, Sareen R. Comparison between different strategies to reduce pain on intravenous injection of rocuronium. J Anaesth Clin Pharmacol. 2005;21:59–61.Google Scholar
  47. 47.
    Tuncali B, Karci A, Tuncali BE, Mavioglu O, Olguner CG, Ayhan S, Elar Z. Dilution of rocuronium to 0.5 mg/mL with 0.9% NaCl eliminates the pain during intravenous injection in awake patients. Anesth Analg. 2004;99:740–3.PubMedCrossRefGoogle Scholar
  48. 48.
    Lee HJ, Kim KS, Yeon JT, Suh JK, Sung IH, Shin IC. Potency and recovery characteristics of rocuronium mixed with sodium bicarbonate. Anaesthesia. 2010;65:899–903.PubMedCrossRefGoogle Scholar
  49. 49.
    Moher D, Pham B, Klassen TP, Schulz KF, Berlin JA, Jadad AR, Liberati A. What contributions do languages other than English make on the results of meta-analyses? J Clin Epidemiol. 2000;53:64–72.CrossRefGoogle Scholar

Copyright information

© Japanese Society of Anesthesiologists 2013

Authors and Affiliations

  • Hyun Jeong Kwak
    • 1
  • Ji Young Kim
    • 2
  • Yong Beom Kim
    • 1
  • Sang Kee Min
    • 3
  • Bong Ki Moon
    • 3
  • Jong Yeop Kim
    • 3
    Email author
  1. 1.Department of Anesthesiology and Pain MedicineGachon University Gil Medical CenterIncheonKorea
  2. 2.Department of Anesthesiology and Pain Medicine, Anesthesia and Pain Research InstituteYonsei University College of MedicineSeoulKorea
  3. 3.Department of Anesthesiology and Pain MedicineAjou University School of MedicineSuwonKorea

Personalised recommendations