Intrathecal Hydromorphone for Post-cesarean Delivery Pain - a Dose Finding Study

May 22, 2017 updated by: Dirk Varelmann, MD, Brigham and Women's Hospital

Pain relief after cesarean delivery can be provided in a few ways. Most commonly, certain medications called opioids, such as morphine, are given through the vein or into the muscle. However, a more effective way to give pain relief with fewer side effects (such as nausea and slowing your breathing) is to give opioids in the spinal space as part of the medications given for a cesarean delivery.

For many years, the opioid of choice was morphine due to its long anesthetic effect and acceptable side effect profile. A nation-wide disruption in the supply of preservative-free morphine has made it necessary to look for alternatives. Many institutions worldwide have used another opioid, called hydromorphone, in the spinal space for over a decade. This drug has a very good safety and side effect profile and has been used at the investigators' institution for more than a year. Of interest, while a number of different doses of hydromorphone have been used, there have been very few studies to evaluate the best dose for providing good pain relief with minimal side effects. The goal of this study is to find the best dose of spinal hydromorphone for women undergoing cesarean delivery.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

Intrathecal opioids in have been shown to produce analgesia. Lipid solubility and effect on specific mu opioid receptors in the dorsal horn of the spinal cord primarily determine the analgesic effect of intrathecally injected opioids. Rostral spread of intrathecal opioids causes some of the side effects like pruritus, respiratory depression, nausea and vomiting.

In the investigators' institute, during cesarean delivery under spinal anesthesia is usually performed with 1.6-1.8 ml of 0.75% bupivacaine with dextrose (hyperbaric solution) with 10-20mcg of fentanyl. Preservative free intrathecal (IT) morphine100 to 200 mcg is injected at the time of initiation of spinal block for postoperative pain relief. Multiple studies have shown excellent postoperative pain relief following cesarean delivery up to 18hrs with this dosing regimen.

However, there has been a national shortage of preservative free morphine since August 2012. Based on the pharmacokinetic and pharmacodynamic profile, intrathecal (IT) preservative free hydromorphone 100 mcg has been used as a substitute. Anecdotal experience during the past 8 months suggest that patients have comparable post partum pain relief, with a similar side-effect profile to IT morphine.

There is no published data on the optimal dose of IT hydromorphone for post cesarean analgesia. There are case reports and retrospective case study of use of 100mcg IT hydromorphone. One randomized controlled trial for knee arthroscopy used 2.5-5-10 mcg of IT hydromorphone for postoperative analgesia.

Hence it is important to determine the optimal dose of IT hydromorphone for post operative pain management following cesarean delivery in terms of analgesic efficacy, incidence of side effects and the need for treatment interventions

This study will aim to determine the optimal dose of intrathecal hydromorphone that would provide adequate postoperative analgesia with minimal side effects.

Study Type

Interventional

Enrollment (Actual)

29

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
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Brigham and Women's Hospital

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 to 40 years (Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  • Healthy at-term parturients undergoing elective cesarean delivery under spinal anesthesia

Exclusion Criteria:

  • Emergency cesarean delivery
  • Respiratory disease
  • significant comorbidities: preeclampsia, insulin-dependent diabetes mellitus
  • obstructive sleep apnea
  • body mass index > 35kg/m2
  • <18yrs
  • documented intolerance or allergy to systemic or neuraxial opioids
  • patient with a history of chronic opioid or current use of opioids

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: Other
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Hydromorphone 25mcg
The arm will receive 25mcg intrathecal hydromorphone to supplement the spinal anesthesia
Drug: Hydromorphone 25mcg
Intrathecal Hydromorphone 25mcg
Other Names:
  • HM25
Drug: spinal anesthesia
bupivacaine 0.75% 1.6 mL (12mg)
Active Comparator: Hydromorphone 50mcg
The arm will receive 50mcg intrathecal hydromorphone to supplement the spinal anesthesia
Drug: spinal anesthesia
bupivacaine 0.75% 1.6 mL (12mg)
Drug: Hydromorphone 50mcg
Intrathecal Hydromorphone 50mcg
Other Names:
  • HM50
Active Comparator: Hydromorphone 100mcg
The arm will receive 100mcg intrathecal hydromorphone to supplement the spinal anesthesia
Drug: spinal anesthesia
bupivacaine 0.75% 1.6 mL (12mg)
Drug: Hydromorphone 100mcg
Intrathecal Hydromorphone 100mcg
Other Names:
  • HM100

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
24hr Post-partum IV Opioid Requirement
Time Frame: 24hrs after administration of intrathecal hydromorphone
Intrathecal (IT) hydromorphone added to intrathecally administered local anesthetics for spinal anesthesia increases patient comfort by decreasing post-operative pain. This leads to a decrease in the post-operative intravenous hydromorphone requirements.
24hrs after administration of intrathecal hydromorphone

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Oxygen Saturation, Need for Supplemental Oxygen
Time Frame: 24hrs post administration of IT hydromorphone
Intravenously, and to a lesser extent, intrathecally administered opioids can lead to respiratory depressions. Therefore the subjects' oxygen saturation is measured (standard clinical practice).
24hrs post administration of IT hydromorphone
Patients With Nausea and Vomiting Requiring Rescue Medication
Time Frame: 24hrs post administration of IT hydromorphone
IV and IT opioids can induce nausea and vomiting. Outcome measure is reported as percentage of patients with nausea and vomiting requiring rescue medication.
24hrs post administration of IT hydromorphone
Number of Patients With Hypothermia (Body Temperature < 95F/35C)
Time Frame: 24hrs post administration of IT hydromorphone
intrathecally administered opioids can cause hypothermia (body temperature <95F/35C)
24hrs post administration of IT hydromorphone
Number of Patients With Visual Disturbances
Time Frame: 24hrs post administration of IT hydromorphone
IT/IV opioids can create visual disturbances. The number of patients with visual disturbances are reported.
24hrs post administration of IT hydromorphone
Number of Patients With Pruritus
Time Frame: 24hrs post administration of IT hydromorphone
IT opioids can cause pruritus. Persistent pruritus requiring treatment will be recorded.
24hrs post administration of IT hydromorphone
Intraoperative Vasopressor Use: Ephedrine Equivalents
Time Frame: Intraoperatively (at time of operation)
IT (intrathecal) applied local anesthetics and opioids can cause arterial and venous vasodilation leading to a decrease in afterload as well as preload. This is typically treated with volume replacement and vasopressors (acutely). Total intraoperative vasopressor use will be reported for ephedrine equivalents.
Intraoperatively (at time of operation)
Intraoperative Vasopressor Use: Phenylephrine Equivalents
Time Frame: Intraoperatively (at time of operation)

IT (intrathecal ) applied local anesthetics and opioids can cause arterial and venous vasodilation leading to a decrease in afterload as well as preload. This is typically treated with volume replacement and vasopressors (acutely).

Total intraoperative vasopressor use will be reported for phenylephrine equivalents.
Intraoperatively (at time of operation)

Collaborators and Investigators

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

Sponsor

Brigham and Women's Hospital

Investigators

  • Principal Investigator: Dirk J Varelmann, MD, Brigham and Women's Hospital

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 (Actual)

December 1, 2014

Primary Completion (Actual)

July 1, 2016

Study Completion (Actual)

August 1, 2016

Study Registration Dates

First Submitted

September 12, 2013

First Submitted That Met QC Criteria

September 12, 2013

First Posted (Estimate)

September 17, 2013

Study Record Updates

Last Update Posted (Actual)

June 19, 2017

Last Update Submitted That Met QC Criteria

May 22, 2017

Last Verified

May 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2013P001850
  • Hydromorphone_IT (Other Identifier: BrighamHospital)

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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