Spinal Morphine vs. Hydromorphone for Pain Control After Cesarean Delivery

Analgesia, Obstetrical Clinical Trial

Official title:

Intrathecal Morphine Versus Intrathecal Hydromorphone for Analgesia Following Cesarean Delivery

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02789410
• Other study ID #: 15-009421
• Status: Completed
• Phase: N/A
• Start date: May 2016
• Est. completion date: March 15, 2018

Study information

• Verified date: March 2019
• Source: Mayo Clinic
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Intrathecal (IT) opioids are commonly administered with local anesthetic during spinal anesthesia for post-Cesarean delivery analgesia. Traditionally, IT morphine has been used but the use of IT hydromorphone is growing. A previous study has shown that the effective dose for postoperative analgesia in 90% patients (ED90) for both IT hydromorphone and IT morphine (NCT02009722). These doses were found to be 75 mcg for hydromorphone and 150 mcg for morphine. The current proposed study would compare the duration of analgesia of IT morphine vs IT hydromorphone after elective cesarean delivery. Additionally, the investigators will compare each drug with respect the incidence of nausea and pruritus.

Description:

Spinal anesthesia is the most common anesthetic technique used for Cesarean delivery in the United States and across the world. Intrathecal opioids are administered with a local anesthetic during spinal anesthesia post-Cesarean delivery analgesia. The effectiveness of intrathecal morphine for post-Cesarean pain control is well established, and the use of intrathecal hydromorphone in this patient population is growing. No prospective studies have been conducted to specifically compare the efficacy of intrathecal morphine versus hydromorphone for post-Cesarean analgesia.

After intrathecal administration, opioid drug disposition depends on the lipid solubility of the individual drug. Because of its hydrophilic nature, cerebrospinal fluid (CSF) concentrations of morphine decline more slowly than similar doses of lipophilic drugs. This accounts for more rostral spread, greater dermatomal analgesia, and longer duration of action when compared to highly lipophilic opioids like fentanyl and sufentanil. When used for post-cesarean analgesia, intrathecal morphine has a duration of action between 14-36 hours with wide variation between individual patients. While hydromorphone is similar chemically to morphine, it is more lipid soluble. This decreases its spread within the intrathecal space and enhances its penetration into the dorsal horn of the spinal cord where interactions with opioid receptors occur. These differences between the two medications may influence their duration of action. Theoretically, this would reduce the duration of action of intrathecal hydromorphone when compared with intrathecal morphine. Retrospective studies have shown that the analgesic benefit for intrathecal hydromorphone appears to extend at least 12 hours after cesarean delivery and may extend up to 24 hours.

Although effective in reducing pain, intrathecal opioids are associated with side effects including pruritus, nausea, and respiratory depression. A meta-analysis reviewing twenty-eight studies which investigated intrathecal morphine versus placebo demonstrated moderate increases in the incidences of pruritus, nausea and vomiting. In fact the incidence of nausea with IT morphine has been reported to be nearly 33%. The differences in pharmacokinetics between morphine and hydromorphone may also create differences in side effect profiles. Some studies have found that hydromorphone causes less nausea and pruritus than morphine, while others have not. Although opioid-induced respiratory depression is a rare event, studies evaluating intrathecal hydromorphone for post-Cesarean delivery pain have not reported any cases of respiratory depression.

In this study, the investigators aim to compare the duration of analgesia of intrathecal morphine vs. hydromorphone for analgesia after cesarean delivery. Secondarily, the investigators will compare the side effects of each drug, including nausea and pruritus. To achieve the goals of this study, it is important to study equipotent doses of these medications. Previous work by the investigators of this study found that the effective dose for postoperative analgesia in 90% of patients (ED90) is 75 micrograms for intrathecal hydromorphone and 150 micrograms for intrathecal morphine. However, it is not known if these two equipotent medication doses provide a similar duration of analgesia.

The investigators hypothesize that 150 mcg of intrathecal morphine will result in a longer duration of analgesia when compared to 75 micrograms of intrathecal hydromorphone. Additionally, the investigators hypothesize that there will be more pruritus in the intrathecal hydromorphone group early after surgery, and no difference in side effects at 24 hours after surgery.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 134
• Est. completion date: March 15, 2018
• Est. primary completion date: September 2017
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• American Society of Anesthesiologists (ASA) physical status II-III women presenting for elective cesarean delivery

• Term gestation (37-42 weeks)

• Desire to have a spinal anesthesia technique for cesarean delivery

Exclusion Criteria:

• Any contraindication to the administration of a spinal technique for anesthesia

• History of intolerance or adverse reaction to opioid medications

• Chronic pain syndrome or current opioid use >30 oral morphine equivalents/day

• Allergy or intolerance to acetaminophen, ketorolac, ibuprofen, or oxycodone

• Current BMI > 50

Related Conditions & MeSH terms

• Analgesia, Obstetrical
• Obstetric Surgical Procedures

Intervention

Drug:
• Morphine
Morphine is administered as part of spinal anesthesia for post-operative pain relief.
• Hydromorphone
Hydromorphone is administered as part of spinal anesthesia for post-operative pain relief.

Locations

Country	Name	City	State
United States	Mayo Clinic in Rochester	Rochester	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
Mayo Clinic

Country where clinical trial is conducted

United States, 

References & Publications (9)

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

Bucklin BA, Hawkins JL, Anderson JR, Ullrich FA. Obstetric anesthesia workforce survey: twenty-year update. Anesthesiology. 2005 Sep;103(3):645-53. — View Citation

Gehling M, Tryba M. Risks and side-effects of intrathecal morphine combined with spinal anaesthesia: a meta-analysis. Anaesthesia. 2009 Jun;64(6):643-51. Review. — View Citation

Nortcliffe SA, Shah J, Buggy DJ. Prevention of postoperative nausea and vomiting after spinal morphine for Caesarean section: comparison of cyclizine, dexamethasone and placebo. Br J Anaesth. 2003 May;90(5):665-70. — 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. Erratum in: Anesthesiology 1999 Apr;90(4):1241. — 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

Terajima K, Onodera H, Kobayashi M, Yamanaka H, Ohno T, Konuma S, Ogawa R. Efficacy of intrathecal morphine for analgesia following elective cesarean section: comparison with previous delivery. J Nippon Med Sch. 2003 Aug;70(4):327-33. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	NRS Score for Pain (0-10) With Movement 24 Hours After Spinal Administration	Each patient will be interviewed by a member of the study team 24 hours after receiving their spinal anesthetic. Patients will be asked to rate their current level of pain on a Numeric Rating Scale (NRS) of 0 (no pain) to 10 (worst pain imaginable).	24 hours after administration of spinal anesthesia
Secondary	Nausea	The number of subjects who experienced and self-reported nausea within the first 24 hours after administration of spinal anesthesia.	24 hours after administration of spinal anesthesia
Secondary	Pruritus	The number of subjects who experienced and self-reported pruritus within the first 24 hours after administration of spinal anesthesia.	24 hours after administration of spinal anesthesia

External Links

•   Mayo Clinic Clinical Trials