Skip to main content
NCBI home page
Current Therapeutic Research, Clinical and Experimental logoLink to Current Therapeutic Research, Clinical and Experimental
. 2010 Oct;71(5):298–308. doi: 10.1016/j.curtheres.2010.10.005

Antiemetic effects of midazolam added to fentanyl-ropivacaine patient-controlled epidural analgesia after subtotal gastrectomy: A prospective, randomized, double-blind, controlled trial

Sioh Kim 1, Jeongwon Seo 1, Younghoon Jeon 2,*
PMCID: PMC3969600  PMID: 24688151

Abstract

Background: Nausea and vomiting are frequent adverse effects of patient-controlled epidural analgesia (PCEA) with opioids.

Objective: This study was designed to assess the antiemetic effect of midazolam added to fentanyl—ropivacaine PCEA.

Methods: In a prospective, randomized, double-blind, controlled trial, smoking patients with gastric cancer undergoing elective subtotal gastrectomy were evenly allocated to 1 of 2 treatment groups to manage postoperative pain: 0.2% ropivacaine mixed with fentanyl 4 μg/mL and midazolam 0.2 mg/mL (test group) or 0.2% ropivacaine mixed with fentanyl 4 μg/mL (control group). The PCEA infusion was set to deliver 4 μL/h of the study solution, with a bolus of 2 mL per demand and a 15-minute lockout time. The incidence of postoperative nausea and vomiting (PONV), pain intensity, sedation score, usage of rescue analgesia and rescue antiemetic, respiratory depression, urinary retention, and pruritus were recorded at 2, 6, 12, 24, 48, and 72 hours after surgery. Total infused volume of PCEA at 72 hours after surgery was measured.

Results: A total of 60 patients were approached and randomized to treatment. No patients were excluded by exclusion criteria and all enrolled patients completed this study. Incidence of nausea (7% vs 33%; P = 0.02) in the test group was significantly lower than in the control group. The overall frequency of PONV in the test group was significantly less than that of the control group (7% vs 40%; P = 0.006). In addition, the mean (SD) infused volume of PCEA in the test group was significantly lower than that in the control group (392.3 [68.9] vs 351.2 [49.8] mL; P = 0.01). However, there were no significant differences in pain intensity, usage of rescue antiemetics and rescue analgesics, and mild pruritus between groups. No patient reported moderate or severe sedation, respiratory depression, or hypoxemia. In addition, there were no severe adverse events.

Conclusions: Midazolam added to fentanyl-ropivacaine PCEA was associated with a significant reduction in the incidence of PONV compared with fentanyl-ropivacaine alone, and a significant decrease in the amount of PCEA administered without a significant increase in adverse events in these patients who underwent subtotal gastrectomy.

Key words: fentanyl, midazolam, nausea and vomiting, epidural analgesia

Full Text

The Full Text of this article is available as a PDF (652.5 KB).

References

  • 1.Scott DA, Beilby DS, McClymont C. Postoperative analgesia using epidural infusions of fentanyl with bupivacaine. A prospective analysis of 1014 patients. Anesthesiology. 1995;83:727–737. doi: 10.1097/00000542-199510000-00012. [DOI] [PubMed] [Google Scholar]
  • 2.Chaney MA. Side effects of intrathecal and epidural opioids. Can J Anaesth. 1995;42:891–903. doi: 10.1007/BF03011037. [DOI] [PubMed] [Google Scholar]
  • 3.Golembiewski J, Chernin E, Chopra T. Prevention and treatment of postoperative nausea and vomiting. Am J Health Syst Pharm. 2005;62:1247–1260. doi: 10.1093/ajhp/62.12.1247. [DOI] [PubMed] [Google Scholar]; Golembiewski J, Chernin E, Chopra T. Prevention and treatment of postoperative nausea and vomiting. Am J Health Syst Pharm. 2005;62:1261–1262. doi: 10.1093/ajhp/62.12.1247. quiz. [DOI] [PubMed] [Google Scholar]
  • 4.Klahsen AJ, O’Reilly D, McBride J. Reduction of post-operative nausea and vomiting with the combination of morphine and droperidol in patient-controlled analgesia. Can J Anaesth. 1996;43:1100–1107. doi: 10.1007/BF03011835. [DOI] [PubMed] [Google Scholar]
  • 5.Lee IH, Lee IO. Antipruritic and antiemetic effect of epidural droperidol: Comparative study between single and continuous epidural injection. Eur J Anaesthesiol. 2006;23:213–218. doi: 10.1017/S0265021505002218. [DOI] [PubMed] [Google Scholar]
  • 6.Choi JH, Lee J, Choi JH, Bishop MJ. Epidural naloxone reduces pruritus and nausea without affecting analgesia by epidural morphine in bupivacaine. Can J Anaesth. 2000;47:33–37. doi: 10.1007/BF03020728. [DOI] [PubMed] [Google Scholar]
  • 7.Bauer KP, Dom PM, Ramirez AM, O’Flaherty JE. Preoperative intravenous midazolam: Benefits beyond anxiolysis. J Clin Anesth. 2004;16:177–183. doi: 10.1016/j.jclinane.2003.07.003. [DOI] [PubMed] [Google Scholar]
  • 8.Di Florio T, Goucke CR. The effect of midazolam on persistent postoperative nausea and vomiting. Anaesth Intensive Care. 1999;27:38–40. doi: 10.1177/0310057X9902700107. [DOI] [PubMed] [Google Scholar]
  • 9.Sanjay OP, Tauro DI. Midazolam: An effective antiemetic after cardiac surgery—a clinical trial. Anesth Analg. 2004;99:339–343. doi: 10.1213/01.ANE.0000121772.29181.71. [DOI] [PubMed] [Google Scholar]
  • 10.Splinter WM, MacNeill HB, Menard EA. Midazolam reduces vomiting after tonsillectomy in children. Can J Anaesth. 1995;42:201–203. doi: 10.1007/BF03010676. [DOI] [PubMed] [Google Scholar]
  • 11.Unlugenc H, Guler T, Gunes Y, Isik G. Comparative study of the antiemetic efficacy of ondansetron, propofol and midazolam in the early postoperative period. Eur J Anaesthesiol. 2003;20:668–673. doi: 10.1017/s026502150300108x. [DOI] [PubMed] [Google Scholar]
  • 12.Tucker AP, Lai C, Nadeson R, Goodchild CS. Intrathecal midazolam I: A cohort study investigating safety. Anesth Analg. 2004;98:1512–1520. doi: 10.1213/01.ANE.0000087075.14589.F5. [DOI] [PubMed] [Google Scholar]
  • 13.Tucker AP, Mezzatesta J, Nadeson R, Goodchild CS. Intrathecal midazolam II: Combination with intrathecal fentanyl for labor pain. Anesth Analg. 2004;98:1521–1527. doi: 10.1213/01.ANE.0000112434.68702.E4. [DOI] [PubMed] [Google Scholar]
  • 14.Ho KM, Ismail H. Use of intrathecal midazolam to improve perioperative analgesia: A meta-analysis. Anaesth Intensive Care. 2008;36:365–373. doi: 10.1177/0310057X0803600307. [DOI] [PubMed] [Google Scholar]
  • 15.Kumar P, Rudra A, Pan AK, Acharya A. Caudal additives in pediatrics: A comparison among midazolam, ketamine, and neostigmine coadministered with bupivacaine. Anesth Analg. 2005;101:69–73. doi: 10.1213/01.ANE.0000153862.95153.2E. [DOI] [PubMed] [Google Scholar]
  • 16.Nishiyama T, Matsukawa T, Hanaoka K. Continuous epidural administration of midazolam and bupivacaine for postoperative analgesia. Acta Anaesthesiol Scand. 1999;43:568–572. doi: 10.1034/j.1399-6576.1999.430514.x. [DOI] [PubMed] [Google Scholar]
  • 17.Nishiyama T, Matsukawa T, Hanaoka K. Effects of adding midazolam on the postoperative epidural analgesia with two different doses of bupivacaine. J Clin Anesth. 2002;14:92–97. doi: 10.1016/s0952-8180(01)00347-6. [DOI] [PubMed] [Google Scholar]
  • 18.Huh BK, Jung S, White W, Jeon Y. Anti-emetic effect of midazolam added to morphine patient-controlled analgesia after total abdominal hysterectomy. Anaesth Intensive Care. 2010;38:481–485. doi: 10.1177/0310057X1003800311. [DOI] [PubMed] [Google Scholar]
  • 19.Reves JG, Glass PSA, Lubarsky DA, McEvoy MD. Intravenous nonopioid anesthetics. In: Miller RD, editor. Miller's Anesthesia. 6th ed. Elsevier/Churchill Livingstone; New York, NY: 2005. pp. 317–378. [Google Scholar]
  • 20.Reid M, Herrera-Marschitz M, Hökfelt T. Differential modulation of striatal dopamine release by intranigral injection of gamma-aminobutyric acid (GABA), dynorphin A and substance P. Eur J Pharmacol. 1988;147:411–420. doi: 10.1016/0014-2999(88)90176-8. [DOI] [PubMed] [Google Scholar]
  • 21.Phillis JW, Bender AS, Wu PH. Benzodiazepines inhibit adenosine uptake into rat brain synaptosomes. Brain Res. 1980;195:494–498. doi: 10.1016/0006-8993(80)90087-6. [DOI] [PubMed] [Google Scholar]
  • 22.Serrao JM, Stubbs SC, Goodchild CS, Gent JP. Intrathecal midazolam and fentanyl in the rat: Evidence for different spinal antinociceptive effects [published correction appears in Anesthesiology. 1989;71:482] Anesthesiology. 1989;70:780–786. doi: 10.1097/00000542-198905000-00013. [DOI] [PubMed] [Google Scholar]
  • 23.Nishiyama T, Hanaoka K. Midazolam can potentiate the analgesic effects of intrathecal bupivacaine on acute thermal- or inflammatory-induced pain. Anesth Analg. 2003;96:1386–1391. doi: 10.1213/01.ANE.0000057606.82135.7D. [DOI] [PubMed] [Google Scholar]
  • 24.Goodchild CS, Guo Z, Musgreave A, Gent JP. Antinociception by intrathecal midazolam involves endogenous neurotransmitters acting at spinal cord delta opioid receprors. Br J Anaesth. 1996;77:758–763. doi: 10.1093/bja/77.6.758. [DOI] [PubMed] [Google Scholar]
  • 25.Malinovsky JM, Cozian A, Lepage JY. Ketamine and midazolam neurotoxicity in the rabbit. Anesthesiology. 1991;75:91–97. doi: 10.1097/00000542-199107000-00015. [DOI] [PubMed] [Google Scholar]
  • 26.Schwieger IM, Jorge-Costa M, Pizzolato GP. Intrathecal midazolam reduces isoflurane MAC and increases the apnoeic threshold in rats. Can J Anaesth. 1994;41:144–148. doi: 10.1007/BF03009809. [DOI] [PubMed] [Google Scholar]
  • 27.Nishiyama T, Matsukawa T, Hanaoka K. Acute phase histopathological study of spinally administered midazolam in cats. Anestb Analg. 1999;89:717–720. doi: 10.1097/00000539-199909000-00035. [DOI] [PubMed] [Google Scholar]
  • 28.Aguilar JL, Espachs P, Roca G. Difficult management of pain following sacrococcygeal chordoma: 13 Months of subarachnoid infusion. Pain. 1994;59:317–320. doi: 10.1016/0304-3959(94)90085-X. [DOI] [PubMed] [Google Scholar]
  • 29.Borg PA, Krijnen HJ. Long-term intrathecal administration of midazolam and Clonidine. Clin J Pain. 1996;12:63–68. doi: 10.1097/00002508-199603000-00012. [DOI] [PubMed] [Google Scholar]

Articles from Current Therapeutic Research, Clinical and Experimental are provided here courtesy of Elsevier

RESOURCES