Spinal Morphine vs. Hydromorphone for Pain Control After Cesarean Delivery

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, 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.

Inclusion:

1. ASA physical status II-III women presenting for elective cesarean delivery

2. Term gestation (37-42 weeks)

3. Desire to have a spinal anesthesia technique for cesarean delivery

Exclusion:

1. Any contraindication to the administration of a spinal technique for anesthesia

2. History of intolerance or adverse reaction to opioid medications

3. Chronic pain syndrome or current opioid use >30 oral morphine equivalents/day

4. Allergy or intolerance to acetaminophen, ketorolac, ibuprofen, or oxycodone

5. Current BMI > 50