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

Phase 4

Completed

Conditions: Cesarean Section
Analgesia, Obstetrical

Interventions: Drug: Hydromorphone
Drug: Morphine

Registration Number: NCT02009722

Lead Sponsor: Mayo Clinic

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: Female

Target Recruitment: 84

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 & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Intrathecal hydromorphone	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.
Intrathecal morphine	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.

Primary Outcome Measures

Name	Time	Method
Dose of IT Morphine and IT Hydromorphone for Adequate Analgesia (Pain Score Less Than or Equal to 3) in 90% of Patients	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 Outcome Measures

Name	Time	Method
Side Effects: Pruritus	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.
Side Effects: Nausea	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.
Side Effects: Sedation	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.
Pruritus	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.
Nausea	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.
Treatment for Nausea	First 24 hours	number of patients needing medication treatment for nausea in first 24 hours
Treatment for Pruritus	First 24 hours after spinal	The number of patients needing medical treatment for pruritus in first 24 hours after surgery