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.
|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|
- 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.
- 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))
|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)|
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.
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.
Duramorph is administered as part of spinal anesthesia for post-operative pain relief.
Other Name: Duramorph
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT02009722
|Contact: Hans P Sviggum, M.D.||firstname.lastname@example.org|
|United States, Minnesota|
|Rochester Methodist Hospital, Mayo Clinic||Recruiting|
|Rochester, Minnesota, United States, 55902|
|Contact: Hans P Sviggum, M.D. 507-266-2049 email@example.com|
|Principal Investigator: Hans P Sviggum, M.D.|
|Principal Investigator:||Hans P Sviggum, M.D.||Mayo Clinic|