Clinical Drug Investigation

, Volume 36, Issue 4, pp 243–253 | Cite as

5-HT3 Receptor Antagonists for Propofol Injection Pain: A Meta-Analysis of Randomized Controlled Trials

  • Wen Wang
  • Liang Zhou
  • Lin-Xin Wu
  • Tong Wang
  • Chao-Bing Zhang
  • Li Sun
Systematic Review
First Online:

Abstract

Background and Objectives

5-hydroxytryptamine3 (5-HT3) receptor antagonists have been commonly used to reduce propofol injection pain. The aim of this meta-analysis was to evaluate the efficacy and safety of 5-HT3 receptor antagonists in decreasing the incidence and intensity of propofol injection pain.

Methods

Online databases of Pubmed, Embase and the Cochrane Central Register of Controlled Trials were searched as well as reference lists of included studies and recent reviews. Eligible randomized controlled trials (RCTs) assessing the efficacy and safety of 5-HT3 receptor antagonists for propofol injection pain were identified. The outcomes included the incidence and intensity of propofol injection pain and adverse effects. We calculated risk ratios (RR) with 95 % confidence intervals (CIs) for dichotomous data and adopted fixed or random-effects model when proper.

Results

A total of eight RCTs were included in the final analysis. Compared with the control group, 5-HT3 receptor antagonists were related to a decreasing incidence of propofol injection pain (RR 0.43, 95 % CI 0.33–0.56, P < 0.05). Besides, they also effectively alleviated the severity of propofol injection pain. They significantly reduced the number of patients with moderate (RR 0.21, 95 % CI 0.15–0.30, P < 0.05) and severe pain (RR 0.16, 95 % CI 0.10–0.25, P < 0.05) during propofol injection. 5-HT3 receptor antagonists and lidocaine were equally effective in preventing propofol injection pain. Moreover, only one article mentioned the adverse effects of 5-HT3 receptor antagonists in two patients.

Conclusion

Our meta-analysis indicates that 5-HT3 receptor antagonists can effectively reduce the incidence and severity of propofol injection pain. Additionally, 5-HT3 receptor antagonists may become the alternatives to lidocaine in attenuating propofol injection pain. However, evidence is still limited for the safety of 5-HT3 receptor antagonists on propofol injection pain.

Keywords

Lidocaine Risk Ratio Ondansetron Granisetron Palonosetron 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
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References

  1. 1.
    Bateman BT, Kesselheim AS. Propofol as a transformative drug in anesthesia: insights from key early investigators. Drug Discov Today. 2015;20:1012–7.CrossRefPubMedGoogle Scholar
  2. 2.
    Macario A, Weinger M, Truong P, et al. Which clinical anesthesia outcomes are both common and important to avoid? The perspective of a panel of expert anesthesiologists. Anesth Analg. 1999;88:1085–91.PubMedGoogle Scholar
  3. 3.
    Jalota L, Kalira V, George E, et al. Prevention of pain on injection of propofol: systematic review and meta-analysis. BMJ. 2011;342:d1110.CrossRefPubMedGoogle Scholar
  4. 4.
    Hanci V, Ayoglu H, Yilmaz M, et al. Effect of menstrual cycle on the injection pain due to propofol. Eur J Anaesthesiol. 2010;27:425–7.CrossRefPubMedGoogle Scholar
  5. 5.
    Fletcher GC, Gillespie JA, Davidson JA. The effect of temperature upon pain during injection of propofol. Anaesthesia. 1996;51:498–9.CrossRefPubMedGoogle Scholar
  6. 6.
    Huang CL, Wang YP, Cheng YJ, et al. The effect of carrier intravenous fluid speed on the injection pain of propofol. Anesth Analg. 1995;81:1087–8.PubMedGoogle Scholar
  7. 7.
    Davies AF, Vadodaria B, Hopwood B, et al. Efficacy of microfiltration in decreasing propofol-induced pain. Anaesthesia. 2002;57:557–61.CrossRefPubMedGoogle Scholar
  8. 8.
    Soltesz S, Diekmann M, Mitrenga-Theusinger A, et al. Reduced pain on injection with a 0.5 % propofol emulsion during induction of anesthesia. Eur J Anaesthesiol. 2012;29:162–3.CrossRefPubMedGoogle Scholar
  9. 9.
    Fahringer DL, Goodwin SR, Warde MK, et al. The effect of a 3: 1 volume mixture of propofol 1 % and thiopental 2.5 % in reducing the pain on injection of propofol in children. Paediatr Anaesth. 2010;20:545–52.CrossRefPubMedGoogle Scholar
  10. 10.
    Kim K, Sung Kim Y, Lee DK, et al. Reducing the pain of microemulsion propofol injections: a double-blind, randomized study of three methods of tourniquet and lidocaine. Clin Ther. 2013;35:1734–43.Google Scholar
  11. 11.
    Machu TK. Therapeutics of 5-HT3 receptor antagonists: Current uses and future directions. Pharmacol Ther. 2011;130:338–47.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Higgins JP, Altman DG, Gotzsche PC, et al. The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. BMJ. 2011;343:d5928.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Cho YH, Kim CK, Heo KH, et al. Acupuncture for acute postoperative pain after back surgery: a systematic review and meta-analysis of randomized controlled trials. Pain Pract. 2015;15:279–91.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Begg CB, Mazumdar M. Operating characteristics of a rank correlation test for publication bias. Biometrics. 1994;50:1088–101.CrossRefPubMedGoogle Scholar
  15. 15.
    Egger M, Davey Smith G, Schneider M, et al. Bias in meta-analysis detected by a simple, graphical test. BMJ (Clinical researched). 1997;315:629–34.CrossRefGoogle Scholar
  16. 16.
    Rahimzadeh P, Faiz SH, Nikoobakht N, et al. Which one is more efficient on propofol 2 % injection pain? Magnesium sulfate or ondansetron: a randomized clinical trial. Adv Biomed Res. 2015;4:56.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Singh DK, Jindal P, Singh G. Comparative study of attenuation of the pain caused by propofol intravenous injection, by granisetron, magnesium sulfate and nitroglycerine. Saudi J Anaesth. 2011;5:50–4.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    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.CrossRefPubMedGoogle Scholar
  19. 19.
    Memis D, Turan A, Karamanlioglu B, et al. The prevention of propofol injection pain by tramadol or ondansetron. Eur J Anaesthesiol. 2002;19:47–51.Google Scholar
  20. 20.
    Lee KH, Rim SK, Lee JY, et al. Effects of pretreatment with intravenous palonosetron for propofol-remifentanil-based anesthesia in breast and thyroid cancer surgery: A double-blind, randomized, controlled study. Korean J Anesthesiol. 2014;67:13–9.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Ryu HB, Kim SJ. Analgesic effects of palonosetron in the intravenous propofol injection. Korean J Anesthesiol. 2014;66:99–104.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Singh D, Jagannath S, Priye S, et al. Prevention of propofol injection pain: comparison between lidocaine and ramosetron. J Anaesthesiol Clin Pharmacol. 2014;30:213–6.CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Lee HY, Kim SH, So KY. Prevention of microemulsion propofol injection pain: A comparison of a combination of lidocaine and ramosetron with lidocaine or ramosetron alone. Korean J Anesthesiol. 2011;61:30–4.CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Ahmed A, Sengupta S, Das T, et al. Pre-treatment with intravenous granisetron to alleviate pain on propofol injection: A double-blind, randomized, controlled trial. Indian J Anaesth. 2012;56:135–8.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Dubey PK, Prasad SS. Pain on injection of propofol: The effect of granisetron pretreatment. Clin J Pain. 2003;19:121–4.CrossRefPubMedGoogle Scholar
  26. 26.
    Alipour M, Tabari M, Alipour M. Paracetamol, ondansetron, granisetron, magnesium sulfate and lidocaine and reduced propofol injection pain. Iran Red Crescent Med J. 2014;16:e16086.PubMedPubMedCentralGoogle Scholar
  27. 27.
    Zahedi H, Maleki A, Rostami G. Ondansetron pretreatment reduces pain on injection of propofol. Acta Med Iran. 2012;50:239–43.PubMedGoogle Scholar
  28. 28.
    Ambesh SP, Dubey PK, Sinha PK. Ondansetron pretreatment to alleviate pain on propofol injection: a randomized, controlled, double-blinded study. Anesth Analg. 1999;89:197–9.PubMedGoogle Scholar
  29. 29.
    Moher D, Liberati A, Tetzlaff J, et al. Reprint–preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Phys Ther. 2009;89:873–80.PubMedGoogle Scholar
  30. 30.
    McCrirrick A, Hunter S. Pain on injection of propofol: the effect of injectate temperature. Anaesthesia. 1990;45:443–4.CrossRefPubMedGoogle Scholar
  31. 31.
    Shimizu T, Inomata S, Tanaka M. Rapid injection of propofol reduces vascular pain and facilitates Laryngeal Mask Airway insertion. J Clin Anesth. 2011;23:540–3.CrossRefPubMedGoogle Scholar
  32. 32.
    Dedic A, Adam S, Gommers D, et al. Propofol injection pain: is it still an issue? The effect of premedication. Minerva Anestesiol. 2010;76:720–4.PubMedGoogle Scholar
  33. 33.
    Stokes DN, Robson N, Hutton P. Effect of diluting propofol on the incidence of pain on injection and venous sequelae. Br J Anaesth. 1989;62:202–3.CrossRefPubMedGoogle Scholar
  34. 34.
    King SY, Davis FM, Wells JE, et al. Lidocaine for the prevention of pain due to injection of propofol. Anesth Analg. 1992;74:246–9.CrossRefPubMedGoogle Scholar
  35. 35.
    Fujii Y, Itakura M. Efficacy of the lidocaine/flurbiprofen axetil combination for reducing pain during the injection of propofol. Minerva Anestesiol. 2011;77:693–7.PubMedGoogle Scholar
  36. 36.
    Gehan G, Karoubi P, Quinet F, et al. Optimal dose of lignocaine for preventing pain on injection of propofol. Br J Anaesth. 1991;66:324–6.CrossRefPubMedGoogle Scholar
  37. 37.
    Borazan H, Erdem TB, Kececioglu M, et al. Prevention of pain on injection of propofol: a comparison of lidocaine with different doses of paracetamol. Eur J Anaesthesiol. 2010;27:253–7.CrossRefPubMedGoogle Scholar
  38. 38.
    Kazemi-Kjellberg F, Henzi I, Tramer MR. Treatment of established postoperative nausea and vomiting: a quantitative systematic review. BMC Anesthesiol. 2001;1:2.CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Ye JH, Mui WC, Ren J, et al. Ondansetron exhibits the properties of a local anesthetic. Anesth Analg. 1997;85:1116–21.PubMedGoogle Scholar
  40. 40.
    Gregory RE, Ettinger DS. 5-HT3 receptor antagonists for the prevention of chemotherapy-induced nausea and vomiting. A comparison of their pharmacology and clinical efficacy. Drugs. 1998;55:173–189.Google Scholar
  41. 41.
    Farouk S. Ondansetron added to lidocaine for intravenous regional anaesthesia. Eur J Anaesthesiol. 2009;26:1032–6.CrossRefPubMedGoogle Scholar
  42. 42.
    Honarmand A, Safavi M, Adineh-Mehr L. Effect of adding 8 milligrams ondansetron to lidocaine for Bier’s block on post-operative pain. Adv Biomed Res. 2013;2:52.CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    Azimaraghi O, Aghajani Y, Molaghadimi M, et al. Ondansetron reducing pain on injection of etomidate: a controlled randomized study. Braz J Anesthesiol. 2014;64:169–72.CrossRefGoogle Scholar
  44. 44.
    Salvo N, Doble B, Khan L, et al. Prophylaxis of radiation-induced nausea and vomiting using 5-hydroxytryptamine-3 serotonin receptor antagonists: a systematic review of randomized trials. Int J Radiat Oncol Biol Phys. 2012;82:408–17.CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  • Wen Wang
    • 1
  • Liang Zhou
    • 1
  • Lin-Xin Wu
    • 1
  • Tong Wang
    • 2
  • Chao-Bing Zhang
    • 1
  • Li Sun
    • 1
  1. 1.Department of Anesthesiology, Cancer Institute and Hospital, National Cancer CenterChinese Academy of Medical Sciences, Peking Union Medical CollegeBeijingChina
  2. 2.Institute for Hospital ManagementTsinghua UniversityBeijingChina

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