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NCT Number: NCT02009722

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

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.

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Key information

Age range

18 year and older

Sex eligibility

Female

Study type

Interventional

Phase

Phase 4

Primary location

Rochester Methodist Hospital, Mayo Clinic

Rochester, Minnesota, 55902, United States

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Morphine

Drug

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

Other names: Duramorph

Hydromorphone

Drug

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

Other names: Dilaudid

Primary outcomes

  1. 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

Secondary outcomes

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. Treatment for Nausea

    Time frame: First 24 hours

    number of patients needing medication treatment for nausea in first 24 hours

  9. 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

Sponsors and collaborators

Lead sponsor

Mayo Clinic

Other

Registry information

Important dates

Study start
2014
Primary completion
2014
Study completion
2015
First posted
Dec 12, 2013
Registry last updated
Jul 25, 2016

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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