Intrathecal Hydromorphone vs Intrathecal Morphine to Treat Post Cesarean Pain in Patients With Opioid Use Disorder Taking Buprenorphine

Summary

This is a single center, double-blind, randomized trial to compare the effects of intrathecal hydromorphone versus intrathecal morphine to treat post cesarean pain in patients with OUD taking buprenorphine. Inclusion criteria include American Society of Anesthesiologists (ASA) Physical Status II or III presenting for cesarean delivery to be done under spinal anesthesia, who have a diagnosis of OUD and are taking buprenorphine. Exclusion criteria include contraindication to spinal anesthesia, allergy/intolerance to acetaminophen or ibuprofen and laboring patients who have an epidural that will be used for anesthesia for cesarean delivery. Potential subjects will be approached about participating in the study at either their preop anesthesia visit or on the day of surgery after surgical and anesthesia consent has been obtained. Enrolled patients will be randomly allocated to receive either 200 mcg of intrathecal morphine or 100 mcg of intrathecal hydromorphone (study opioid medication). Intraoperatively, with the patient in a sitting position a spinal block will be performed with administration of 0.75% bupivacaine in 8.25% dextrose, 15 mcg fentanyl and the study opioid medication. Supplemental intraoperative analgesia/anxiolysis will be administered at the discretion of the anesthesia care team. Ultrasound-guided transversus abdominis plane blocks will be performed bilaterally at the end of the procedure with 10mL liposomal bupivacaine mixed with 10mL 0.25% bupivacaine injected on each side. Post-cesarean multimodal pain regimen will include scheduled acetaminophen 650mg every 6 hours and scheduled ibuprofen 600mg every 6 hours. Oxycodone will be ordered for breakthrough pain, starting at 5mg every 6 hours as needed. Escalation of as needed pain medication will be at the discretion of the anesthesia team. The patient will be followed for the following 36 hours postoperatively. The primary outcome is the patient's pain score with movement at 12 hours. Secondary outcomes include pain scores at rest and with movement at 6 and 24 hours, satisfaction with anesthesia, time to first opioid use, total opioid consumption in 24 and 36 hours, subjective rating of nausea and pruritis over first 24 hours , treatment for nausea or pruritis in 24 and 36 hours, Obstetric Quality of Recovery 10 (ObsQoR10) score, and Global Health Numeric Rating Scale (NRS) score.

Timeline

Start

2026-02

Primary completion

2029-01

Completion

2029-01

Publications

• Background Hirai AH, Ko JY, Owens PL, Stocks C, Patrick SW. Neonatal Abstinence Syndrome and Maternal Opioid-Related Diagnoses in the US, 2010-2017. JAMA. 2021 Jan 12;325(2):146-155. doi: 10.1001/jama.2020.24991.
• Background Lui B, Aaronson JA, Tangel V, Quincy M, Weinberg R, Abramovitz SE, White RS. Opioid use disorder and maternal outcomes following cesarean delivery: a multistate analysis, 2007-2014. J Comp Eff Res. 2020 Jul;9(10):667-677. doi: 10.2217/cer-2020-0050. Epub 2020 Jul 10.
• Background Suarez EA, Huybrechts KF, Straub L, Hernandez-Diaz S, Jones HE, Connery HS, Davis JM, Gray KJ, Lester B, Terplan M, Mogun H, Bateman BT. Buprenorphine versus Methadone for Opioid Use Disorder in Pregnancy. N Engl J Med. 2022 Dec 1;387(22):2033-2044. doi: 10.1056/NEJMoa2203318.
• Background Vilkins AL, Bagley SM, Hahn KA, Rojas-Miguez F, Wachman EM, Saia K, Alford DP. Comparison of Post-Cesarean Section Opioid Analgesic Requirements in Women With Opioid Use Disorder Treated With Methadone or Buprenorphine. J Addict Med. 2017 Sep/Oct;11(5):397-401. doi: 10.1097/ADM.0000000000000339.
• Background Mittal L, Suzuki J. Feasibility of collaborative care treatment of opioid use disorders with buprenorphine during pregnancy. Subst Abus. 2017 Jul-Sep;38(3):261-264. doi: 10.1080/08897077.2015.1129525. Epub 2015 Dec 16.
• Background Cobb J, Craig W, Richard J, Snow E, Turcotte H, Warters R, Quaye A. A Retrospective Study of Acute Postoperative Pain After Cesarean Delivery in Patients With Opioid Use Disorder Treated With Opioid Agonist Pharmacotherapy. J Addict Med. 2022 Sep-Oct 01;16(5):549-556. doi: 10.1097/ADM.0000000000000964. Epub 2022 Feb 14.
• Background Meyer M, Paranya G, Keefer Norris A, Howard D. Intrapartum and postpartum analgesia for women maintained on buprenorphine during pregnancy. Eur J Pain. 2010 Oct;14(9):939-43. doi: 10.1016/j.ejpain.2010.03.002. Epub 2010 May 4.
• Background Holland E, Gibbs L, Spence NZ, Young M, Werler MM, Guang Z, Saia K, Bateman BT, Achu R, Wachman EM. A comparison of postpartum opioid consumption and opioid discharge prescriptions among opioid-naive patients and those with opioid use disorder. Am J Obstet Gynecol MFM. 2023 Aug;5(8):101025. doi: 10.1016/j.ajogmf.2023.101025. Epub 2023 May 19.
• Background O'Connor AB, Smith J, O'Brien LM, Lamarche K, Byers N, Nichols SD. Peripartum and Postpartum Analgesia and Pain in Women Prescribed Buprenorphine for Opioid Use Disorder Who Deliver by Cesarean Section. Subst Abuse. 2022 Jun 21;16:11782218221107936. doi: 10.1177/11782218221107936. eCollection 2022.
• Background Reno JL, Kushelev M, Coffman JH, Prasad MR, Meyer AM, Carpenter KM, Palettas MS, Coffman JC. Post-Cesarean Delivery Analgesic Outcomes in Patients Maintained on Methadone and Buprenorphine: A Retrospective Investigation. J Pain Res. 2020 Dec 30;13:3513-3524. doi: 10.2147/JPR.S284874. eCollection 2020.
• Background Lim G, Soens M, Wanaselja A, Chyan A, Carvalho B, Landau R, George RB, Klem ML, Osmundson SS, Krans EE, Terplan M, Bateman BT. A Systematic Scoping Review of Peridelivery Pain Management for Pregnant People With Opioid Use Disorder: From the Society for Obstetric Anesthesia and Perinatology and Society for Maternal Fetal Medicine. Anesth Analg. 2022 Nov 1;135(5):912-925. doi: 10.1213/ANE.0000000000006167. Epub 2022 Sep 22.
• Background Stanislaus MA, Reno JL, Small RH, Coffman JH, Prasad M, Meyer AM, Carpenter KM, Coffman JC. Continuous Epidural Hydromorphone Infusion for Post-Cesarean Delivery Analgesia in a Patient on Methadone Maintenance Therapy: A Case Report. J Pain Res. 2020 Apr 28;13:837-842. doi: 10.2147/JPR.S242271. eCollection 2020.
• Background Cobb J, Craig W, Richard J, Snow E, Turcotte H, Warters R, Quaye A. Low-dose ketamine infusion for post-cesarean delivery analgesia in patients with opioid use disorder. Int J Obstet Anesth. 2021 Aug;47:103170. doi: 10.1016/j.ijoa.2021.103170. Epub 2021 May 2. No abstract available.
• Background Cook MI, Kushelev M, Coffman JH, Coffman JC. Analgesic Outcomes in Opioid Use Disorder Patients Receiving Spinal Anesthesia with or without Intrathecal Clonidine for Cesarean Delivery: A Retrospective Investigation. J Pain Res. 2022 Apr 21;15:1191-1201. doi: 10.2147/JPR.S358045. eCollection 2022.
• Background Volpe DA, McMahon Tobin GA, Mellon RD, Katki AG, Parker RJ, Colatsky T, Kropp TJ, Verbois SL. Uniform assessment and ranking of opioid mu receptor binding constants for selected opioid drugs. Regul Toxicol Pharmacol. 2011 Apr;59(3):385-90. doi: 10.1016/j.yrtph.2010.12.007. Epub 2011 Jan 6.
• Background Kohan L, Potru S, Barreveld AM, Sprintz M, Lane O, Aryal A, Emerick T, Dopp A, Chhay S, Viscusi E. Buprenorphine management in the perioperative period: educational review and recommendations from a multisociety expert panel. Reg Anesth Pain Med. 2021 Oct;46(10):840-859. doi: 10.1136/rapm-2021-103007. Epub 2021 Aug 12.
• Background Beatty NC, Arendt KW, Niesen AD, Wittwer ED, Jacob AK. Analgesia after Cesarean delivery: a retrospective comparison of intrathecal hydromorphone and morphine. J Clin Anesth. 2013 Aug;25(5):379-383. doi: 10.1016/j.jclinane.2013.01.014. Epub 2013 Aug 17.
• Background Marroquin B, Feng C, Balofsky A, Edwards K, Iqbal A, Kanel J, Jackson M, Newton M, Rothstein D, Wong E, Wissler R. Neuraxial opioids for post-cesarean delivery analgesia: can hydromorphone replace morphine? A retrospective study. Int J Obstet Anesth. 2017 May;30:16-22. doi: 10.1016/j.ijoa.2016.12.008. Epub 2016 Dec 30.
• Background Sharpe EE, Molitor RJ, Arendt KW, Torbenson VE, Olsen DA, Johnson RL, Schroeder DR, Jacob AK, Niesen AD, Sviggum HP. Intrathecal Morphine versus Intrathecal Hydromorphone for Analgesia after Cesarean Delivery: A Randomized Clinical Trial. Anesthesiology. 2020 Jun;132(6):1382-1391. doi: 10.1097/ALN.0000000000003283.
• Background Sultan P, Kormendy F, Nishimura S, Carvalho B, Guo N, Papageorgiou C. Comparison of spontaneous versus operative vaginal delivery using Obstetric Quality of Recovery-10 (ObsQoR-10): An observational cohort study. J Clin Anesth. 2020 Aug;63:109781. doi: 10.1016/j.jclinane.2020.109781. Epub 2020 Mar 20.

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