Perioperative analgesia after intrathecal fentanyl and morphine or morphine alone for cesarean section: A randomized controlled study

Wojciech Weigl, Andrzej Bieryło, Monika Wielgus, Świetlana Krzemień-Wiczyńska, Marcin Kołacz, Michał J Dąbrowski, Wojciech Weigl, Andrzej Bieryło, Monika Wielgus, Świetlana Krzemień-Wiczyńska, Marcin Kołacz, Michał J Dąbrowski

Abstract

Objectives: Intrathecal morphine is used in the postoperative management of pain after caesarean section (CS), but might not be optimal for intraoperative analgesia. We hypothesized that intrathecal fentanyl could supplement intraoperative analgesia when added to a local anesthetic and morphine without affecting management of postoperative pain.

Methods: This prospective, randomized, double-blind, parallel-group study included 60 parturients scheduled for elective CS. Spinal anesthesia consisted of bupivacaine with either morphine 100 μg (M group), or fentanyl 25 μg and morphine 100 μg (FM group). The frequency of intraoperative pain and pethidine consumption in the 24 hours postoperatively was recorded.

Results: Fewer patients in the FM group required additional intraoperative analgesia (P < .01, relative risk 0.06, 95% confidence interval [CI] 0.004-1.04). The FM group was noninferior to the M group for 24-hour opioid consumption (95% CI -10.0 mg to 45.7 mg, which was below the prespecified boundary of 50 mg). Pethidine consumption in postoperative hours 1 to 12 was significantly higher in the FM group (P = .02). Postoperative nausea and vomiting (PONV) were more common in the FM group (P = .01). Visual analog scale scores, effective analgesia, Apgar scores, and rates of pruritus and respiratory depression were similar between the groups.

Conclusions: Intrathecal combination of fentanyl and morphine may provide better perioperative analgesia than morphine alone in CS and could be useful when the time from anesthesia to skin incision is short. However, an increase in PONV and possible acute spinal opioid tolerance after addition of intrathecal fentanyl warrants further investigation using lower doses of fentanyl.

Conflict of interest statement

The authors declare no conflict of interests.

Figures

Figure 1
Figure 1
CONSORT study flow chart. CONSORT = consolidated standards of reporting trials.
Figure 2
Figure 2
Difference in means and 95% CI of 24-hour pethidine consumption between MF and M groups in milligrams. The shaded area represents the noninferiority region; d indicates the prespecified noninferiority margin. CI = confidence interval.
Figure 3
Figure 3
Mean postoperative patient-controlled pethidine consumption (A) and visual analog pain scores (B). Hourly opioid consumption was accumulated into 3-hour intervals to obtain a clear picture of postoperative patient-controlled analgesia requirements and for comparison with the placebo (no intrathecal opioid) group in our previous study[13] (a collation of the results from the present and previous study is provided in Supplementary Fig. 1).

References

    1. Khezri MB, Nasseh N, Soltanian G. The comparative preemptive analgesic efficacy of addition of vitamin B complex to gabapentin versus gabapentin alone in women undergoing cesarean section under spinal anesthesia: a prospective randomized double-blind study. Medicine 2017;96:e6545.
    1. Goma HM, Flores-Carrillo JC, Whizar-Lugo V. Spinal additives in subarachnoid anaesthesia for cesarean section. In: Whizar-Lugo VM, ed. Topics in Spinal Anaesthesia. InTech; 2014.
    1. Sawi W, Choy YC. A comparative study of post operative analgesia, side effects profile and patient satisfaction using intrathecal fentanyl with and without morphine 0.1 mg in caesarean section. Middle East J Anaesthesiol 2013;22:21–6.
    1. Baraka A, Noueihid R, Hajj S. Intrathecal injection of morphine for obstetric analgesia. Anesthesiology 1981;54:136–40.
    1. Braga AA, Frias JA, Braga FS, et al. Spinal anesthesia for cesarean section. Use of hyperbaric bupivacaine (10 mg) combined with different adjuvants. Rev Bras Anestesiol 2012;62:775–87.
    1. Carvalho B, Drover DR, Ginosar Y, et al. Intrathecal fentanyl added to bupivacaine and morphine for cesarean delivery may induce a subtle acute opioid tolerance. Int J Obstet Anesth 2012;21:29–34.
    1. Biswas BN, RA, Bose BK, et al. Intrathecal fentanyl with hyperbaric bupivacaine improves analgesia during caesarean delivery and in early post-operative period. Indian J Anaesth 2002;46:469–72.
    1. Hunt CO, Naulty JS, Bader AM, et al. Perioperative analgesia with subarachnoid fentanyl-bupivacaine for cesarean delivery. Anesthesiology 1989;71:535–40.
    1. Chung CJ, Yun SH, Hwang GB, et al. Intrathecal fentanyl added to hyperbaric ropivacaine for cesarean delivery. Reg Anesth Pain Med 2002;27:600–3.
    1. Sibilla C, Albertazz P, Zatelli R, et al. Perioperative analgesia for caesarean section: comparison of intrathecal morphine and fentanyl alone or in combination. Int J Obstet Anesth 1997;6:43–8.
    1. Abouleish E, Rawal N, Fallon K, et al. Combined intrathecal morphine and bupivacaine for cesarean section. Anesth Analg 1988;67:370–4.
    1. Kiran S, Singal NK. A comparative study of three different doses of 0.5% hyperbaric bupivacaine for spinal anaesthesia in elective caesarean section. Int J Obstet Anesth 2002;11:185–9.
    1. Weigl W, Bierylo A, Wielgus M, et al. Analgesic efficacy of intrathecal fentanyl during the period of highest analgesic demand after cesarean section: a randomized controlled study. Medicine 2016;95:e3827.
    1. Hess PE, Vasudevan A, Snowman C, et al. Small dose bupivacaine-fentanyl spinal analgesia combined with morphine for labor. Anesth Analg 2003;97:247–52.
    1. Hein A, Gillis-Haegerstrand C, Jakobsson JG. Neuraxial opioids as analgesia in labour, caesarean section and hysterectomy: a questionnaire survey in Sweden. F1000Res 2017;6:133.
    1. Hein A, Rosblad P, Norman M, et al. Addition of low-dose morphine to intrathecal bupivacaine/sufentanil labour analgesia: a randomised controlled study. Int J Obstet Anesth 2010;19:384–9.
    1. Angle PJ, Halpern SH, Leighton BL, et al. A randomized controlled trial examining the effect of naproxen on analgesia during the second day after cesarean delivery. Anesth Analg 2002;95:741–5.
    1. Liu Y, Wang X, Zou L, et al. An analysis of variations of indications and maternal-fetal prognosis for caesarean section in a tertiary hospital of Beijing: a population-based retrospective cohort study. Medicine 2017;96:e5509.
    1. Hamber EA, Viscomi CM. Intrathecal lipophilic opioids as adjuncts to surgical spinal anesthesia. Reg Anesth Pain Med 1999;24:255–63.
    1. Uchiyama A, Nakano S, Ueyama H, et al. Low dose intrathecal morphine and pain relief following caesarean section. Int J Obstet Anesth 1994;3:87–91.
    1. Palmer CM, Emerson S, Volgoropolous D, et al. Dose-response relationship of intrathecal morphine for postcesarean analgesia. Anesthesiology 1999;90:437–44.
    1. Girgin NK, Gurbet A, Turker G, et al. Intrathecal morphine in anesthesia for cesarean delivery: dose-response relationship for combinations of low-dose intrathecal morphine and spinal bupivacaine. J Clin Anesth 2008;20:180–5.
    1. Sultan P, Halpern SH, Pushpanathan E, et al. The effect of intrathecal morphine dose on outcomes after elective cesarean delivery: a meta-analysis. Anesth Analg 2016;123:154–64.
    1. Dahl JB, Jeppesen IS, Jorgensen H, et al. Intraoperative and postoperative analgesic efficacy and adverse effects of intrathecal opioids in patients undergoing cesarean section with spinal anesthesia: a qualitative and quantitative systematic review of randomized controlled trials. Anesthesiology 1999;91:1919–27.
    1. Connelly NR, Dunn SM, Ingold V, et al. The use of fentanyl added to morphine-lidocaine-epinephrine spinal solution in patients undergoing cesarean section. Anesth Analg 1994;78:918–20.
    1. Barkshire K, Russell R, Burry J, et al. A comparison of bupivacaine-fentanyl-morphine with bupivacaine-fentanyl-diamorphine for caesarean section under spinal anaesthesia. Int J Obstet Anesth 2001;10:4–10.
    1. Karaman S, Gunusen I, Uyar M, et al. The effects of morphine and fentanyl alone or in combination added to intrathecal bupivacaine in spinal anesthesia for cesarean section. Agri 2011;23:57–63.
    1. Thornton P, Hanumanthaiah D, O’Leary RA, et al. Effects of fentanyl added to a mixture of intrathecal bupivacaine and morphine for spinal anaesthesia in elective caesearean section. Rom J Anaesth Intensive Care 2015;22:97–102.
    1. Cohen SE, Desai JB, Ratner EF, et al. Ketorolac and spinal morphine for postcesarean analgesia. Int J Obstet Anesth 1996;5:14–8.
    1. Turk DC, Dworkin RH, McDermott MP, et al. Analyzing multiple endpoints in clinical trials of pain treatments: IMMPACT recommendations. Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials. Pain 2008;139:485–93.
    1. Culebras X, Gaggero G, Zatloukal J, et al. Advantages of intrathecal nalbuphine, compared with intrathecal morphine, after cesarean delivery: an evaluation of postoperative analgesia and adverse effects. Anesth Analg 2000;91:601–5.
    1. Fournier R, Van Gessel E, Macksay M, et al. Onset and offset of intrathecal morphine versus nalbuphine for postoperative pain relief after total hip replacement. Acta Anaesthesiol Scand 2000;44:940–5.
    1. Shende D, Cooper GM, Bowden MI. The influence of intrathecal fentanyl on the characteristics of subarachnoid block for caesarean section. Anaesthesia 1998;53:706–10.
    1. Jayaram A, Carp H. Progesterone-mediated potentiation of spinal sufentanil in rats. Anesth Analg 1993;76:745–50.
    1. Bogra J, Arora N, Srivastava P. Synergistic effect of intrathecal fentanyl and bupivacaine in spinal anesthesia for cesarean section. BMC Anesthesiol 2005;5:5.
    1. Chu CC, Shu SS, Lin SM, et al. The effect of intrathecal bupivacaine with combined fentanyl in cesarean section. Acta Anaesthesiol Sin 1995;33:149–54.
    1. Cooper DW, Lindsay SL, Ryall DM, et al. Does intrathecal fentanyl produce acute cross-tolerance to i.v. morphine? Br J Anaesth 1997;78:311–3.
    1. Caranza R, Jeyapalan I, Buggy DJ. Central neuraxial opioid analgesia after caesarean section: comparison of epidural diamorphine and intrathecal morphine. Int J Obstet Anesth 1999;8:90–3.
    1. Abboud TK, Dror A, Mosaad P, et al. Mini-dose intrathecal morphine for the relief of post-cesarean section pain: safety, efficacy, and ventilatory responses to carbon dioxide. Anesth Analg 1988;67:137–43.
    1. Milner AR, Bogod DG, Harwood RJ. Intrathecal administration of morphine for elective caesarean section. A comparison between 0.1 mg and 0.2 mg. Anaesthesia 1996;51:871–3.
    1. Weigl W, Bierylo A, Krzemien-Wiczynska S, et al. [Comparative study of postoperative analgesia after intrathecal administration of bupivacaine with fentanyl or morphine for elective Caesarean section]. Anestezjol Intens Ter 2009;41:28–32. [Polish].
    1. Swart M, Sewell J, Thomas D. Intrathecal morphine for caesarean section: an assessment of pain relief, satisfaction and side-effects. Anaesthesia 1997;52:373–7.
    1. Siti Salmah G, Choy YC. Comparison of morphine with fentanyl added to intrathecal 0.5% hyperbaric bupivacaine for analgesia after caesarean section. Med J Malaysia 2009;64:71–4.
    1. Raffaeli W, Marconi G, Fanelli G, et al. Opioid-related side-effects after intrathecal morphine: a prospective, randomized, double-blind dose-response study. Eur J Anaesthesiol 2006;23:605–10.
    1. Sarvela PJ, Halonen PM, Soikkeli AI, et al. Ondansetron and tropisetron do not prevent intraspinal morphine- and fentanyl-induced pruritus in elective cesarean delivery. Acta Anaesthesiol Scand 2006;50:239–44.
    1. Carvalho B. Respiratory depression after neuraxial opioids in the obstetric setting. Anesth Analg 2008;107:956–61.
    1. Kato R, Shimamoto H, Terui K, et al. Delayed respiratory depression associated with 0.15 mg intrathecal morphine for cesarean section: a review of 1915 cases. J Anesth 2008;22:112–6.
    1. Sinatra RS, Lodge K, Sibert K, et al. A comparison of morphine, meperidine, and oxymorphone as utilized in patient-controlled analgesia following cesarean delivery. Anesthesiology 1989;70:585–90.
    1. Ismail S, Afshan G, Monem A, et al. Postoperative analgesia following caesarean section: intravenous patient controlled analgesia versus conventional continuous infusion. Open J Anesthesiol 2012;2:120–6.
    1. Onishi E, Murakami M, Hashimoto K, et al. Optimal intrathecal hyperbaric bupivacaine dose with opioids for cesarean delivery: a prospective double-blinded randomized trial. Int J Obstet Anesth 2017;31:68–73.

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