Intrathecal Hydromorphone for Post-cesarean Delivery Pain - a Dose Finding Study

Healthy Clinical Trial

Official title:

Intrathecal Hydromorphone for Post-cesarean Delivery Pain - a Dose Finding Study

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT01943565
• Other study ID #: 2013P001850
• Secondary ID: Hydromorphone_IT
• Status: Not yet recruiting
• Phase: Phase 4
• First received: September 12, 2013
• Last updated: September 12, 2013
• Start date: October 2013
• Est. completion date: July 2014

Study information

• Verified date: September 2013
• Source: Brigham and Women's Hospital
• Contact: Dirk J Varelmann, MD
• Phone: 617-732-8280
• Email: dvarelmann[@]partners.org
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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 our 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.

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 our 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 120
• Est. completion date: July 2014
• Est. primary completion date: July 2014
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 40 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator)

Related Conditions & MeSH terms

• Adult
• Healthy
• Human
• Parturient

Intervention

Drug:
• Hydromorphone 25mcg

• Hydromorphone 50mcg

• Hydromorphone 100mcg

• Hydromorphone 200mcg

Locations

Country	Name	City	State
United States	Brigham and Women's Hospital	Boston	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Brigham and Women's Hospital

Country where clinical trial is conducted

United States, 

References & Publications (5)

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. — View 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. — View 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. Erratum in: Anesthesiology 1999 Apr;90(4):1241. — View Citation

Ross BK, Hughes SC. Epidural and spinal narcotic analgesia. Clin Obstet Gynecol. 1987 Sep;30(3):552-65. Review. — View Citation

Wang JK, Nauss LA, Thomas JE. Pain relief by intrathecally applied morphine in man. Anesthesiology. 1979 Feb;50(2):149-51. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	24hr post-partum IV opioid requirement	Intrathecal (IT) hydromorphone added to intrathecally administered local anesthetics for spinal anesthesia increases patient comfort by decreasing post-operative pain. This leads to a decrease in the post-operative intravenous hydromorphone requirements.	24hrs after administration of intrathecal hydromorphone	No
Secondary	Oxygen saturation, need for supplemental oxygen	Intravenously, and to a lesser extent, intrathecally administered opioids can lead to respiratory depressions. Therefore the subjects' oxygen saturation is measured (standard clinical practice).	24hrs post administration of IT hydromorphone	No
Secondary	Nausea and vomiting requiring rescue medication	IV and IT opioids can induce nausea and vomiting	24hrs post administration of IT hydromorphone	No
Secondary	Hypothermia (body temperature < 95F/35C)	intrathecally administered opioids can cause hypothermia	24hrs post administration of IT hydromorphone	No
Secondary	Visual disturbances	IT/IV opioids can create visual disturbances	24hrs post administration of IT hydromorphone	No
Secondary	Pruritus	IT opioids can cause pruritus. Persistent pruritus requiring treatment will be recorded.	24hrs post administration of IT hydromorphone	No
Secondary	Intraoperative vasopressor use	IT applied local anesthetics and opioids can cause arterial and venous vasodilation leading to a decrease in afterload as well as preload. This is typically treated with volume replacement and vasopressors (acutely). The total intraoperative vasopressor use will be correlated with the IT hydromorphone dose.	Intraoperatively	No