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

NCT ID: NCT02009722

Last Updated: 2016-07-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 84 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-01-31
• Study Completion Date: 2015-04-30

Brief Summary

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.

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.

Conditions

Analgesia, Obstetrical; Cesarean Section

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

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.

Group Type: ACTIVE_COMPARATOR

Hydromorphone

Intervention Type: DRUG

Hydromorphone (Dilaudid) is administered in the intrathecal space for post-operative pain control

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.

Group Type: ACTIVE_COMPARATOR

Morphine

Intervention Type: DRUG

Duramorph is administered as part of spinal anesthesia for post-operative pain relief.

Interventions

Morphine

Duramorph is administered as part of spinal anesthesia for post-operative pain relief.

Intervention Type: DRUG

Hydromorphone

Hydromorphone (Dilaudid) is administered in the intrathecal space for post-operative pain control

Intervention Type: DRUG

Other Intervention Names

Duramorph; Dilaudid

Eligibility 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Mayo Clinic

OTHER

Sponsor Role: lead

Responsible Party

Hans P. Sviggum, M.D.

Assistant Professor of Anesthesiology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Hans P Sviggum, M.D.

Role: PRINCIPAL_INVESTIGATOR

Mayo Clinic

Locations

Rochester Methodist Hospital, Mayo Clinic

Rochester, Minnesota, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 23965210 (View on PubMed)

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Reference Type: BACKGROUND

PMID: 9952150 (View on PubMed)

Rauch E. Intrathecal hydromorphone for postoperative analgesia after cesarean delivery: a retrospective study. AANA J. 2012 Aug;80(4 Suppl):S25-32.

Reference Type: BACKGROUND

PMID: 23248827 (View on PubMed)

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Reference Type: BACKGROUND

PMID: 23256273 (View on PubMed)

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Reference Type: BACKGROUND

PMID: 12928713 (View on PubMed)

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. doi: 10.1111/j.1365-2044.2008.05817.x.

Reference Type: BACKGROUND

PMID: 19462494 (View on PubMed)

Dougherty TB, Baysinger CL, Henenberger JC, Gooding DJ. Epidural hydromorphone with and without epinephrine for post-operative analgesia after cesarean delivery. Anesth Analg. 1989 Mar;68(3):318-22.

Reference Type: BACKGROUND

PMID: 2465709 (View on PubMed)

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Reference Type: BACKGROUND

PMID: 17585226 (View on PubMed)

Gerancher JC, Floyd H, Eisenach J. Determination of an effective dose of intrathecal morphine for pain relief after cesarean delivery. Anesth Analg. 1999 Feb;88(2):346-51. doi: 10.1097/00000539-199902000-00023.

Reference Type: BACKGROUND

PMID: 9972754 (View on PubMed)

Other Identifiers

13-008490

Identifier Type: -

Identifier Source: org_study_id