Spinal Hydromorphone Versus Morphine for Post-Cesarean Delivery Analgesia

Postoperative Pain Clinical Trial

Official title:

Spinal Hydromorphone Versus Morphine for Post-Cesarean Delivery Analgesia: A Non-Inferiority Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03592992
• Other study ID #: 4357
• Status: Completed
• Phase: Phase 4
• Start date: November 11, 2020
• Est. completion date: July 28, 2022

Study information

• Verified date: March 2023
• Source: Lawson Health Research Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Morphine is usually used for pain relief after cesarean delivery. However, sometimes it is not available, the patient might be allergic to morphine or intolerant to its side effects. Hydromorphone, another drug from the same class, might be used alternatively, but we need to prove that it is not inferior to morphine.

Description:

Spinal or intrathecal (IT) morphine is the most commonly used opioid for post-cesarean delivery analgesia. Factors that contribute to its widespread use include a favorable pharmacokinetic profile with duration of action up to 24 hours, ease of administration (during spinal block for surgical anesthesia) and low cost. Most providers administer 100 to 200 mcg of IT morphine for cesarean delivery analgesia with excellent analgesic results. Nevertheless, subarachnoid use of morphine is not without adverse events. While dose-dependent respiratory depression is the most worrisome complication, other side effects such as pruritus, nausea, vomiting and urinary retention can be bothersome during early puerperium. Furthermore, shortages of preservative free morphine in the United States has led clinicians to seek a reasonable alternative.

For the last 20 years, spinal hydromorphone has been successfully used for chronic pain associated with neoplasms. Its use for post-cesarean analgesia has been successfully reported. However, data regarding its efficacy in the IT space for post-cesarean analgesia is scarce. In the past, doses of 40 to 100 mcg have been reported to provide adequate postoperative pain relief with minimal side effects. In a recent study, the Effective Dose in 90% of patients has been established for both Hydromorphone and Morphine to be 75 mcg and 150 mcg, respectively.

No prospective studies have been conducted to specifically establish non-inferiority of hydromorphone when compared to morphine for post- cesarean analgesia. In addition, while all opioids share the same side effect profile, the frequency of those events are unknown for IT hydromorphone.

The current proposal is a blinded randomized controlled trial of intrathecal hydromorphone versus morphine in term pregnant women undergoing elective cesarean deliveries under spinal anesthesia.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 126
• Est. completion date: July 28, 2022
• Est. primary completion date: July 28, 2022
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Age > 18 years; American Society of Anesthesiologist's Physical Status (ASA-PS) < 3; Term pregnancy (> 37 weeks gestational age); Elective cesarean delivery; Spinal Anesthesia;

Exclusion Criteria:

• Documented allergy or severe intolerance to opioids; Intra-operative conversion to a general anesthetic technique; Chronic pain syndrome with baseline pain levels >3 on a visual analogue scale (0-10 cm); History of opioid use during this pregnancy; Allergy or intolerance to NSAIDS or acetaminophen; Morbid obesity- Body Mass Index (BMI) >40.

Related Conditions & MeSH terms

• Pain, Postoperative
• Postoperative Pain

Intervention

Drug:
• Spinal Hydromorphone
75 mcg of hydromorphone will be prepared in a non-identifiable syringe by central hospital pharmacy. The resulting solution will then be added to the spinal anesthetic mixture(fentanyl 15 mcg and 0.75% hyperbaric bupivacaine 1.4-1.6 mcg at the discretion of the attending anesthesiologist, adjusted to height and weight)
• Spinal Morphine
150 mcg of morphine will be prepared in a non-identifiable syringe by central hospital pharmacy.The resulting solution will be added to the spinal anesthetic mixture (fentanyl 15 mcg and 0.75% hyperbaric bupivacaine 1.4-1.6 mcg at the discretion of the attending anesthesiologist, adjusted to height and weight)

Locations

Country	Name	City	State
Canada	Victoria Hospital- LHSC	London	Ontario

Sponsors (1)

Lead Sponsor	Collaborator
Lawson Health Research Institute

Country where clinical trial is conducted

Canada, 

References & Publications (15)

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. — View Citation

Ciechanowicz S, Setty T, Robson E, Sathasivam C, Chazapis M, Dick J, Carvalho B, Sultan P. Development and evaluation of an obstetric quality-of-recovery score (ObsQoR-11) after elective Caesarean delivery. Br J Anaesth. 2019 Jan;122(1):69-78. doi: 10.1016/j.bja.2018.06.011. Epub 2018 Jul 31. — View Citation

Deer TR, Smith HS, Burton AW, Pope JE, Doleys DM, Levy RM, Staats PS, Wallace MS, Webster LR, Rauck RL, Cousins M; Center For Pain Relief, Inc. Comprehensive consensus based guidelines on intrathecal drug delivery systems in the treatment of pain caused by cancer pain. Pain Physician. 2011 May-Jun;14(3):E283-312. — View Citation

Dougherty TB, Baysinger CL, Henenberger JC, Gooding DJ. Epidural hydromorphone with and without epinephrine for post-operative analgesia after cesarean delivery. Anesth Analg. 1989 Mar;68(3):318-22. — View Citation

Gerancher JC, Floyd H, Eisenach J. Determination of an effective dose of intrathecal morphine for pain relief after cesarean delivery. Anesth Analg. 1999 Feb;88(2):346-51. doi: 10.1097/00000539-199902000-00023. — View Citation

Girgin NK, Gurbet A, Turker G, Aksu H, Gulhan N. Intrathecal morphine in anesthesia for cesarean delivery: dose-response relationship for combinations of low-dose intrathecal morphine and spinal bupivacaine. J Clin Anesth. 2008 May;20(3):180-5. doi: 10.1016/j.jclinane.2007.07.010. — View Citation

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 Sep;51(9):871-3. doi: 10.1111/j.1365-2044.1996.tb12622.x. — View Citation

Palmer CM, Emerson S, Volgoropolous D, Alves D. Dose-response relationship of intrathecal morphine for postcesarean analgesia. Anesthesiology. 1999 Feb;90(2):437-44. doi: 10.1097/00000542-199902000-00018. Erratum In: Anesthesiology 1999 Apr;90(4):1241. — View Citation

Parker RK, Sawaki Y, White PF. Epidural patient-controlled analgesia: influence of bupivacaine and hydromorphone basal infusion on pain control after cesarean delivery. Anesth Analg. 1992 Nov;75(5):740-6. doi: 10.1213/00000539-199211000-00015. — View Citation

Rathmell JP, Pino CA, Taylor R, Patrin T, Viani BA. Intrathecal morphine for postoperative analgesia: a randomized, controlled, dose-ranging study after hip and knee arthroplasty. Anesth Analg. 2003 Nov;97(5):1452-1457. doi: 10.1213/01.ANE.0000083374.44039.9E. — View Citation

Rauch E. Intrathecal hydromorphone for cesarean delivery: in search of improved postoperative pain management: a case report. AANA J. 2011 Oct;79(5):427-32. — View Citation

Rauch E. Intrathecal hydromorphone for postoperative analgesia after cesarean delivery: a retrospective study. AANA J. 2012 Aug;80(4 Suppl):S25-32. — View Citation

Sviggum HP, Arendt KW, Jacob AK, Niesen AD, Johnson RL, Schroeder DR, Tien M, Mantilla CB. Intrathecal Hydromorphone and Morphine for Postcesarean Delivery Analgesia: Determination of the ED90 Using a Sequential Allocation Biased-Coin Method. Anesth Analg. 2016 Sep;123(3):690-7. doi: 10.1213/ANE.0000000000001229. — View Citation

Ventola CL. The drug shortage crisis in the United States: causes, impact, and management strategies. P T. 2011 Nov;36(11):740-57. No abstract available. — View Citation

Wong JY, Carvalho B, Riley ET. Intrathecal morphine 100 and 200 mug for post-cesarean delivery analgesia: a trade-off between analgesic efficacy and side effects. Int J Obstet Anesth. 2013 Jan;22(1):36-41. doi: 10.1016/j.ijoa.2012.09.006. Epub 2012 Nov 15. — View Citation

* Note: There are 15 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Difference in the Average Numeric Rating Score (0-10 , where 0=no pain and 10= maximum pain) during the first 24 hours.	This is defined as the between- group difference in the average pain scores on a 0-10 Numeric Rating Scale, as assessed by a nurse, anesthesia consultant or trainee 24 hours after spinal anesthesia.	24 hours after spinal anesthesia.
Secondary	Difference in NRS pain scores at specific time points in the first 24 hours.	This is defined as the between- group difference in the mean pain scores on a 0-10 Numeric Rating Scale, as assessed by a nurse, anesthesia consultant or trainee immediately after surgery (in the Post-Anesthesia Care Unit) and at 6, 12, 18 and 24 hours after spinal anesthesia.	immediately after surgery (in PACU), 6, 12 and 18 hours after spinal anesthesia is given.
Secondary	Time-to-first oral opioid analgesic request	This is defined as the length of time between spinal anesthesia and the first time the subject requested additional opioid analgesia, up to 24 hours from the spinal anesthesia.	Measured in hours from the time of spinal anesthetic until patient request for prescribed oral opioid analgesia, up to 24 hours from the spinal anesthetic .
Secondary	Nausea and/or Vomiting that required treatment.	Nausea/Vomiting episodes that required pharmacological treatment in the first 24 hours after spinal anesthesia	Absolute number of treatments required in the 24-hour time frame.
Secondary	Pruritus that required treatment.	Pruritus episodes that required pharmacological treatment in the first 24 hours after spinal anesthesia	Absolute number of treatments required in the 24-hour time frame.
Secondary	Respiratory Depression	Respiratory Rate measured in breaths/minute)	In post-anesthesia care unit (PACU), 6, 12, 18 and 24 hours after spinal anesthesia
Secondary	Apgar Scores	Neonatal Apgar scores at 1 and 5 minutes in a 1-10 interval scale	1 and 5 minutes after birth.
Secondary	Difference in Opioid Consumption in the first 24 hours	This is defined as the between-group difference in the total amount of Oral Morphine Equivalents consumed in the first 24 hours after spinal anesthesia is given.	24 hours after spinal anesthesia.
Secondary	Obstetric Quality of Recovery Score ObsQoR-11	11-item questionnaire applied to subjects 24 hours after spinal anesthesia. Measured in a 0-110 scale	24 hours after spinal anesthesia.