Intrathecal Opioids for Pain Control After Cesarean Delivery: Determining the Optimal Dose

June 23, 2016 updated by: Hans P. Sviggum, M.D., Mayo Clinic
Both hydromorphone and morphine are administered as part of spinal anesthesia to help improve pain control after cesarean delivery. In this study, the investigators are going to determine the doses of each of those medicines that provides optimal pain control to women undergoing cesarean delivery while limiting side effects related to those medicines. The investigators hypothesize that the doses of hydromorphone and morphine that provide optimal pain control without significant side effects will be 100 micrograms and 150 micrograms, respectively. The investigators further hypothesize that at each respective optimal dose, side effects will be less in the hydromorphone group.

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 along with a local anesthetic during spinal anesthesia for Cesarean delivery to provide postoperative analgesia. The effectiveness of intrathecal morphine for post-Cesarean pain control is well established, but the effectiveness of intrathecal hydromorphone in this patient population is limited to case reports and small retrospective studies. No prospective studies have been conducted to establish the effectiveness of intrathecal hydromorphone for post-Cesarean pain.

Hydromorphone has been studied extensively as a substitute for intrathecal morphine in patients with chronic noncancer pain. In fact, a recent consensus article placed hydromorphone as a first line therapy along with morphine for intrathecal pain management. Its ability to treat post-Cesarean pain when administered in the epidural space has been known for quite some time, but its effects in the intrathecal space are less established. In patients undergoing Cesarean delivery, intrathecal doses of 40 to 100 micrograms have been reported to provide good pain scores postoperatively with only minimal side effects. Doses of up to 300 micrograms have been used, leading to excellent pain control without out respiratory depression, but with significant pruritus and nausea.

Although 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 33%. While hydromorphone is similar chemically to morphine, it is metabolized differently. Differences in pharmacokinetics may allow for differences in side effect profiles. Hydromorphone is more lipid soluble than morphine. 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. 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.

The optimal dose of intrathecal morphine for analgesia following Cesarean delivery is still debated and the efficacy of intrathecal hydromorphone has not been studied extensively in this patient population. The investigators aim to identify the dose of each medication that provides good pain relief without causing significant side effects. The investigators will then perform a comparative analysis of each drug at their optimal dose.

Study Type

Interventional

Enrollment (Actual)

84

Phase

  • Phase 4

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, 55902
        • Rochester Methodist Hospital, Mayo Clinic

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

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  • Women presenting for elective cesarean delivery with no major co-morbidities, including pregnancy induced co-morbidities (e.g. pre-eclampsia)
  • Singleton gestation at term (37-42 weeks)
  • Desire to have a spinal anesthesia technique for cesarean delivery

Exclusion Criteria:

  • Current or historical evidence of clinically significant medical disease or condition
  • Any contraindication to the administration of a spinal technique for anesthesia
  • History of hypersensitivity or idiosyncratic reaction to opioid medications
  • Chronic pain syndrome or current regular opioid use
  • Evidence of anticipated fetal anomalies
  • Allergy or intolerance to Tylenol, ketorolac, ibuprofen, or oxycodone
  • BMI > 40

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 intrathecal hydromorphone or intrathecal morphine as part of their spinal anesthesia. The starting dose of intrathecal hydromorphone will be 40 micrograms. This will be adjusted in subsequent patients based on the previous patient's success or failure according to an up-and-down methodology utilizing a biased coin design.
Drug: Hydromorphone
Hydromorphone (Dilaudid) is administered in the intrathecal space for post-operative pain control
Other Names:
  • Dilaudid
Active Comparator: Intrathecal morphine
Patients will be randomized to receive a one-time dose of intrathecal hydromorphone or intrathecal morphine as part of their spinal anesthesia. The starting dose of intrathecal morphine will be 100 micrograms. This will be adjusted in subsequent patients based on the previous patient's success or failure according to an up-and-down methodology utilizing a biased coin design.
Drug: Morphine
Duramorph 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
Dose of IT Morphine and IT Hydromorphone for Adequate Analgesia (Pain Score Less Than or Equal to 3) in 90% of Patients
Time Frame: 12 hours after administration of spinal anesthesia
Each patient will be interviewed by a member of the study team 12 hours after receiving their spinal anesthetic (which will include either hydromorphone or morphine). Patients will be asked to rate their current level of pain on a scale of 0 (no pain) to 10 (worst pain imaginable). A pain score <4 will be considered a success. The up-down sequential allocation method will be used to determine the dose (mcg) of IT hydromorphone and IT morphine for subsequent patients
12 hours after administration of spinal anesthesia

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Side Effects: Pruritus
Time Frame: 6 hours after spinal administration
Patients will be evaluated by a member of the study team at 6 hours after spinal administration. The number of patients with moderate or severe pruritus will be recorded.
6 hours after spinal administration
Side Effects: Nausea
Time Frame: 6 hours after spinal
Patients will be evaluated by a member of the study team at 6 hours after spinal administration. Patients with moderate or severe nausea will be recorded.
6 hours after spinal
Side Effects: Sedation
Time Frame: 6, 12, and 24 hours after spinal administration
Patients will be evaluated by a member of the study team at 6, 12, and 24 hours after spinal administration. The presence of sedation will be graded by the Richmond Agitation Sedation Scale. Patients with a score of (-)2 or lower on the Richmond were classified as being positive for sedation.
6, 12, and 24 hours after spinal administration
Pruritus
Time Frame: 12 hours after spinal
Patients will be evaluated by a member of the study team at 12 hours after spinal administration. The number of patients with moderate or severe pruritus will be recorded.
12 hours after spinal
Pruritus
Time Frame: 24 hours after spinal
Patients will be evaluated by a member of the study team at 24 hours after spinal administration. The number of patients with moderate or severe pruritus will be recorded.
24 hours after spinal
Nausea
Time Frame: 12 hours after spinal
Patients will be evaluated by a member of the study team at 12 hours after spinal administration. The number of patients with moderate or severe nausea will be recorded.
12 hours after spinal
Nausea
Time Frame: 24 hours after spinal
Patients will be evaluated by a member of the study team at 24 hours after spinal administration. The number of patients with moderate or severe nausea will be recorded.
24 hours after spinal
Treatment for Nausea
Time Frame: First 24 hours
number of patients needing medication treatment for nausea in first 24 hours
First 24 hours
Treatment for Pruritus
Time Frame: First 24 hours after spinal
The number of patients needing medical treatment for pruritus in first 24 hours after surgery
First 24 hours after spinal

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, M.D., 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

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

January 1, 2014

Primary Completion (Actual)

December 1, 2014

Study Completion (Actual)

April 1, 2015

Study Registration Dates

First Submitted

December 9, 2013

First Submitted That Met QC Criteria

December 11, 2013

First Posted (Estimate)

December 12, 2013

Study Record Updates

Last Update Posted (Estimate)

July 25, 2016

Last Update Submitted That Met QC Criteria

June 23, 2016

Last Verified

June 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 13-008490

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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