Spinal Morphine vs. Hydromorphone for Pain Control After Cesarean Delivery

April 24, 2019 updated by: Hans P. Sviggum, M.D., Mayo Clinic

Intrathecal Morphine Versus Intrathecal Hydromorphone for Analgesia Following Cesarean Delivery

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed 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.

Study Type

Interventional

Enrollment (Actual)

134

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Mayo Clinic in Rochester

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Intrathecal hydromorphone
Patients will be randomized to receive a one time dose of 75 mcg intrathecal hydromorphone as part of their spinal anesthesia.
Drug: Hydromorphone
Hydromorphone is administered as part of spinal anesthesia for post-operative pain relief.
Other Names:
  • Dilaudid
Active Comparator: Intrathecal morphine
Patients will be randomized to receive a one time dose of 150 mcg intrathecal morphine as part of their spinal anesthesia.
Drug: Morphine
Morphine is administered as part of spinal anesthesia for post-operative pain relief.
Other Names:
  • Duramorph

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
NRS Score for Pain (0-10) With Movement 24 Hours After Spinal Administration
Time Frame: 24 hours after administration of spinal anesthesia
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Nausea
Time Frame: 24 hours after administration of spinal anesthesia
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
Pruritus
Time Frame: 24 hours after administration of spinal anesthesia
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Mayo Clinic

Investigators

  • Principal Investigator: Hans P Sviggum, Mayo Clinic

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2016

Primary Completion (Actual)

September 1, 2017

Study Completion (Actual)

March 15, 2018

Study Registration Dates

First Submitted

May 31, 2016

First Submitted That Met QC Criteria

May 31, 2016

First Posted (Estimate)

June 3, 2016

Study Record Updates

Last Update Posted (Actual)

April 25, 2019

Last Update Submitted That Met QC Criteria

April 24, 2019

Last Verified

March 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 15-009421

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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