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

This study is currently recruiting participants.
Verified December 2013 by Mayo Clinic
Sponsor:
Information provided by (Responsible Party):
Hans P. Sviggum, M.D., Mayo Clinic
ClinicalTrials.gov Identifier:
NCT02009722
First received: December 9, 2013
Last updated: January 14, 2014
Last verified: December 2013
  Purpose

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.


Condition Intervention Phase
Analgesia, Obstetrical
Cesarean Section
Drug: Morphine
Drug: Hydromorphone
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Intrathecal Opioids for Pain Control After Cesarean Delivery: Determining the Optimal Dose

Resource links provided by NLM:


Further study details as provided by Mayo Clinic:

Primary Outcome Measures:
  • Visual analog pain score following spinal anesthesia administration [ Time Frame: 12 hours after administration of spinal anesthesia ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Total opioid medication consumption [ Time Frame: 24 hours following spinal administration ] [ Designated as safety issue: No ]
    Total amount of opioids administered to patients in the first 24 hours after spinal administration will be recorded in terms of morphine equivalents.

  • Visual analog pain score following administration of spinal anesthesia [ Time Frame: 6 hours and 24 hours after spinal administration ] [ Designated as safety issue: No ]
    A member of the study team will interview patients at 6 and 24 hours after spinal administration. Patients will be asked to rate their current level of pain on a scale from 0 (no pain) to 10 (worst pain imaginable).

  • Side effects: Pruritus [ Time Frame: 6, 12, and 24 hours after spinal administration ] [ Designated as safety issue: No ]

    Patients will be evaluated by a member of the study team at 6, 12, and 24 hours after spinal administration. The presence and severity of pruritus will be noted by patient endorsement.

    Pruritus (graded in the following way: none, mild, moderate, severe)


  • Side effects: Nausea [ Time Frame: 6, 12, and 24 hours after spinal administration ] [ Designated as safety issue: No ]

    Patients will be evaluated by a member of the study team at 6, 12, and 24 hours after spinal administration. The presence and severity of nausea will be noted by patient endorsement.

    Nausea (graded as follows: none, minor, moderate, severe)


  • Side effects: Sedation [ Time Frame: 6, 12, and 24 hours after spinal administration ] [ Designated as safety issue: Yes ]

    Patients will be evaluated by a member of the study team at 6, 12, and 24 hours after spinal administration. The presence and severity of sedation will be graded by the Richmond Agitation Sedation Scale

    Sedation (measured as follows: integer scale from -5 (unarousable) to +4 (combative))



Estimated Enrollment: 80
Study Start Date: January 2014
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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 Name: Duramorph

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT02009722

Contacts
Contact: Hans P Sviggum, M.D. 507-266-2049 sviggum.hans@mayo.edu

Locations
United States, Minnesota
Rochester Methodist Hospital, Mayo Clinic Recruiting
Rochester, Minnesota, United States, 55902
Contact: Hans P Sviggum, M.D.    507-266-2049    sviggum.hans@mayo.edu   
Principal Investigator: Hans P Sviggum, M.D.         
Sponsors and Collaborators
Mayo Clinic
Investigators
Principal Investigator: Hans P Sviggum, M.D. Mayo Clinic
  More Information

Publications:

Responsible Party: Hans P. Sviggum, M.D., Assistant Professor of Anesthesiology, Mayo Clinic
ClinicalTrials.gov Identifier: NCT02009722     History of Changes
Other Study ID Numbers: 13-008490
Study First Received: December 9, 2013
Last Updated: January 14, 2014
Health Authority: United States: Institutional Review Board
United States: Food and Drug Administration

Keywords provided by Mayo Clinic:
Cesarean Delivery
Intrathecal Morphine
Intrathecal Hydromorphone
Obstetrical Analgesia
Spinal Anesthesia

Additional relevant MeSH terms:
Anesthetics
Hydromorphone
Morphine
Analgesics, Opioid
Central Nervous System Depressants
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Narcotics

ClinicalTrials.gov processed this record on April 22, 2014