Clinical trial NCT01943565: Intrathecal Hydromorphone for Post-cesarean Delivery Pain - a Dose Finding Study
Official title: Intrathecal Hydromorphone for Post-cesarean Delivery Pain - a Dose Finding Study
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Healthy
Pain
Pregnancy
Keywords: Pregnancy
Healthy
Intrathecal
Opioids
Spinal
Anesthesia
Pain
Cesarean
Delivery
Human
Lead sponsor: Brigham and Women's Hospital
Sponsor class: OTHER
First posted: 2013-09-17
Enrollment: 29
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: Pain relief after cesarean delivery can be provided in a few ways. Most commonly, certain medications called opioids, such as morphine, are given through the vein or into the muscle. However, a more effective way to give pain relief with fewer side effects (such as nausea and slowing your breathing) is to give opioids in the spinal space as part of the medications given for a cesarean delivery.

For many years, the opioid of choice was morphine due to its long anesthetic effect and acceptable side effect profile. A nation-wide disruption in the supply of preservative-free morphine has made it necessary to look for alternatives. Many institutions worldwide have used another opioid, called hydromorphone, in the spinal space for over a decade. This drug has a very good safety and side effect profile and has been used at the investigators' institution for more than a year. Of interest, while a number of different doses of hydromorphone have been used, there have been very few studies to evaluate the best dose for providing good pain relief with minimal side effects. The goal of this study is to find the best dose of spinal hydromorphone for women undergoing cesarean delivery.

Detailed description: Intrathecal opioids in have been shown to produce analgesia. Lipid solubility and effect on specific mu opioid receptors in the dorsal horn of the spinal cord primarily determine the analgesic effect of intrathecally injected opioids. Rostral spread of intrathecal opioids causes some of the side effects like pruritus, respiratory depression, nausea and vomiting.

In the investigators' institute, during cesarean delivery under spinal anesthesia is usually performed with 1.6-1.8 ml of 0.75% bupivacaine with dextrose (hyperbaric solution) with 10-20mcg of fentanyl. Preservative free intrathecal (IT) morphine100 to 200 mcg is injected at the time of initiation of spinal block for postoperative pain relief. Multiple studies have shown excellent postoperative pain relief following cesarean delivery up to 18hrs with this dosing regimen.

However, there has been a national shortage of preservative free morphine since August 2012. Based on the pharmacokinetic and pharmacodynamic profile, intrathecal (IT) preservative free hydromorphone 100 mcg has been used as a substitute. Anecdotal experience during the past 8 months suggest that patients have comparable post partum pain relief, with a similar side-effect profile to IT morphine.

There is no published data on the optimal dose of IT hydromorphone for post cesarean analgesia. There are case reports and retrospective case study of use of 100mcg IT hydromorphone. One randomized controlled trial for knee arthroscopy used 2.5-5-10 mcg of IT hydromorphone for postoperative analgesia.

Hence it is important to determine the optimal dose of IT hydromorphone for post operative pain management following cesarean delivery in terms of analgesic efficacy, incidence of side effects and the need for treatment interventions

This study will aim to determine the optimal dose of intrathecal hydromorphone that would provide adequate postoperative analgesia with minimal side effects.

Eligibility criteria: Inclusion Criteria:

* Healthy at-term parturients undergoing elective cesarean delivery under spinal anesthesia

Exclusion Criteria:

* Emergency cesarean delivery
* Respiratory disease
* significant comorbidities: preeclampsia, insulin-dependent diabetes mellitus
* obstructive sleep apnea
* body mass index \> 35kg/m2
* \<18yrs
* documented intolerance or allergy to systemic or neuraxial opioids
* patient with a history of chronic opioid or current use of opioids

Primary outcomes:
measure: 24hr Post-partum IV Opioid Requirement
timeFrame: 24hrs after administration of intrathecal hydromorphone
Secondary outcomes:
measure: Oxygen Saturation, Need for Supplemental Oxygen
timeFrame: 24hrs post administration of IT hydromorphone
measure: Patients With Nausea and Vomiting Requiring Rescue Medication
timeFrame: 24hrs post administration of IT hydromorphone
measure: Number of Patients With Hypothermia (Body Temperature < 95F/35C)
timeFrame: 24hrs post administration of IT hydromorphone
measure: Number of Patients With Visual Disturbances
timeFrame: 24hrs post administration of IT hydromorphone
measure: Number of Patients With Pruritus
timeFrame: 24hrs post administration of IT hydromorphone
measure: Intraoperative Vasopressor Use: Ephedrine Equivalents
timeFrame: Intraoperatively (at time of operation)
measure: Intraoperative Vasopressor Use: Phenylephrine Equivalents
timeFrame: Intraoperatively (at time of operation)
Other outcomes:
Locations:
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
Study officials:
affiliation: Brigham and Women's Hospital
name: Dirk J Varelmann, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Wang JK, Nauss LA, Thomas JE. Pain relief by intrathecally applied morphine in man. Anesthesiology. 1979 Feb;50(2):149-51. doi: 10.1097/00000542-197902000-00013. No abstract available.
citation: Ross BK, Hughes SC. Epidural and spinal narcotic analgesia. Clin Obstet Gynecol. 1987 Sep;30(3):552-65. doi: 10.1097/00003081-198709000-00010. No abstract available.
citation: Palmer CM, Emerson S, Volgoropolous D, Alves D. Dose-response relationship of intrathecal morphine for postcesarean analgesia. Anesthesiology. 1999 Feb;90(2):437-44. doi: 10.1097/00000542-199902000-00018.
citation: Milner AR, Bogod DG, Harwood RJ. Intrathecal administration of morphine for elective Caesarean section. A comparison between 0.1 mg and 0.2 mg. Anaesthesia. 1996 Sep;51(9):871-3. doi: 10.1111/j.1365-2044.1996.tb12622.x.
citation: Lee YS, Park YC, Kim JH, Kim WY, Yoon SZ, Moon MG, Min TJ. Intrathecal hydromorphone added to hyperbaric bupivacaine for postoperative pain relief after knee arthroscopic surgery: a prospective, randomised, controlled trial. Eur J Anaesthesiol. 2012 Jan;29(1):17-21. doi: 10.1097/EJA.0b013e3283476055.