Analgesia, Obstetrical, Obstetric Surgical Procedures
Conditions
Keywords
Cesarean delivery, Analgesia, Intrathecal opioids
Brief summary
Intrathecal (IT) opioids are commonly administered with local anesthetic during spinal anesthesia for post-Cesarean delivery analgesia. Traditionally, IT morphine has been used but the use of IT hydromorphone is growing. A previous study has shown that the effective dose for postoperative analgesia in 90% patients (ED90) for both IT hydromorphone and IT morphine (NCT02009722). These doses were found to be 75 mcg for hydromorphone and 150 mcg for morphine. The current proposed study would compare the duration of analgesia of IT morphine vs IT hydromorphone after elective cesarean delivery. Additionally, the investigators will compare each drug with respect the incidence of nausea and pruritus.
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 with a local anesthetic during spinal anesthesia post-Cesarean delivery analgesia. The effectiveness of intrathecal morphine for post-Cesarean pain control is well established, and the use of intrathecal hydromorphone in this patient population is growing. No prospective studies have been conducted to specifically compare the efficacy of intrathecal morphine versus hydromorphone for post-Cesarean analgesia. After intrathecal administration, opioid drug disposition depends on the lipid solubility of the individual drug. Because of its hydrophilic nature, cerebrospinal fluid (CSF) concentrations of morphine decline more slowly than similar doses of lipophilic drugs. This accounts for more rostral spread, greater dermatomal analgesia, and longer duration of action when compared to highly lipophilic opioids like fentanyl and sufentanil. When used for post-cesarean analgesia, intrathecal morphine has a duration of action between 14-36 hours with wide variation between individual patients. While hydromorphone is similar chemically to morphine, it is more lipid soluble. 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. These differences between the two medications may influence their duration of action. Theoretically, this would reduce the duration of action of intrathecal hydromorphone when compared with intrathecal morphine. Retrospective studies have shown that the analgesic benefit for intrathecal hydromorphone appears to extend at least 12 hours after cesarean delivery and may extend up to 24 hours. Although effective in 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 nearly 33%. The differences in pharmacokinetics between morphine and hydromorphone may also create differences in side effect profiles. 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. In this study, the investigators aim to compare the duration of analgesia of intrathecal morphine vs. hydromorphone for analgesia after cesarean delivery. Secondarily, the investigators will compare the side effects of each drug, including nausea and pruritus. To achieve the goals of this study, it is important to study equipotent doses of these medications. Previous work by the investigators of this study found that the effective dose for postoperative analgesia in 90% of patients (ED90) is 75 micrograms for intrathecal hydromorphone and 150 micrograms for intrathecal morphine. However, it is not known if these two equipotent medication doses provide a similar duration of analgesia. The investigators hypothesize that 150 mcg of intrathecal morphine will result in a longer duration of analgesia when compared to 75 micrograms of intrathecal hydromorphone. Additionally, the investigators hypothesize that there will be more pruritus in the intrathecal hydromorphone group early after surgery, and no difference in side effects at 24 hours after surgery.
Interventions
DRUGMorphine
Morphine is administered as part of spinal anesthesia for post-operative pain relief.
DRUGHydromorphone
Hydromorphone is administered as part of spinal anesthesia for post-operative pain relief.
Sponsors
Mayo Clinic
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* American Society of Anesthesiologists (ASA) physical status II-III women presenting for elective cesarean delivery * Term gestation (37-42 weeks) * Desire to have a spinal anesthesia technique for cesarean delivery
Exclusion criteria
* Any contraindication to the administration of a spinal technique for anesthesia * History of intolerance or adverse reaction to opioid medications * Chronic pain syndrome or current opioid use \>30 oral morphine equivalents/day * Allergy or intolerance to acetaminophen, ketorolac, ibuprofen, or oxycodone * Current BMI \> 50
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| NRS Score for Pain (0-10) With Movement 24 Hours After Spinal Administration | 24 hours after administration of spinal anesthesia | Each patient will be interviewed by a member of the study team 24 hours after receiving their spinal anesthetic. Patients will be asked to rate their current level of pain on a Numeric Rating Scale (NRS) of 0 (no pain) to 10 (worst pain imaginable). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Nausea | 24 hours after administration of spinal anesthesia | The number of subjects who experienced and self-reported nausea within the first 24 hours after administration of spinal anesthesia. |
| Pruritus | 24 hours after administration of spinal anesthesia | The number of subjects who experienced and self-reported pruritus within the first 24 hours after administration of spinal anesthesia. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Intrathecal Hydromorphone Patients will be randomized to receive a one time dose of 75 mcg intrathecal hydromorphone as part of their spinal anesthesia.
Hydromorphone: Hydromorphone is administered as part of spinal anesthesia for post-operative pain relief. | 66 |
| Intrathecal Morphine Patients will be randomized to receive a one time dose of 150 mcg intrathecal morphine as part of their spinal anesthesia.
Morphine: Morphine is administered as part of spinal anesthesia for post-operative pain relief. | 68 |
| Total | 134 |
Baseline characteristics
| Characteristic | Intrathecal Morphine | Total | Intrathecal Hydromorphone |
|---|---|---|---|
| Age, Continuous | 31.9 years STANDARD_DEVIATION 4.3 | 31.5 years STANDARD_DEVIATION 4.3 | 31.2 years STANDARD_DEVIATION 4.4 |
| Race and Ethnicity Not Collected | — | 0 Participants | — |
| Region of Enrollment United States | 68 participants | 134 participants | 66 participants |
| Sex: Female, Male Female | 68 Participants | 134 Participants | 66 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 66 | 0 / 68 |
| other Total, other adverse events | 0 / 66 | 0 / 68 |
| serious Total, serious adverse events | 0 / 66 | 0 / 68 |
Outcome results
Primary
NRS Score for Pain (0-10) With Movement 24 Hours After Spinal Administration
Each patient will be interviewed by a member of the study team 24 hours after receiving their spinal anesthetic. Patients will be asked to rate their current level of pain on a Numeric Rating Scale (NRS) of 0 (no pain) to 10 (worst pain imaginable).
Time frame: 24 hours after administration of spinal anesthesia
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Intrathecal Hydromorphone | NRS Score for Pain (0-10) With Movement 24 Hours After Spinal Administration | 4 score on a scale |
| Intrathecal Morphine | NRS Score for Pain (0-10) With Movement 24 Hours After Spinal Administration | 3 score on a scale |
p-value: 0.132Wilcoxon (Mann-Whitney)
Secondary
Nausea
The number of subjects who experienced and self-reported nausea within the first 24 hours after administration of spinal anesthesia.
Time frame: 24 hours after administration of spinal anesthesia
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Intrathecal Hydromorphone | Nausea | 28 Participants |
| Intrathecal Morphine | Nausea | 32 Participants |
p-value: 0.59Wilcoxon (Mann-Whitney)
Secondary
Pruritus
The number of subjects who experienced and self-reported pruritus within the first 24 hours after administration of spinal anesthesia.
Time frame: 24 hours after administration of spinal anesthesia
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Intrathecal Hydromorphone | Pruritus | 27 Participants |
| Intrathecal Morphine | Pruritus | 28 Participants |
p-value: 0.971Wilcoxon (Mann-Whitney)