Intrathecal Opioids for Pain Control After Cesarean Delivery: Determining the Optimal Dose

Cesarean Section Clinical Trial

Official title:

Intrathecal Opioids for Pain Control After Cesarean Delivery: Determining the Optimal Dose

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02009722
• Other study ID #: 13-008490
• Status: Completed
• Phase: Phase 4
• First received: December 9, 2013
• Last updated: May 20, 2015
• Start date: January 2014
• Est. completion date: April 2015

Study information

• Verified date: May 2015
• Source: Mayo Clinic
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review BoardUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

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 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 80
• Est. completion date: April 2015
• Est. primary completion date: December 2014
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Women presenting for elective cesarean delivery with no major co-morbidities, including pregnancy induced co-morbidities (e.g. pre-eclampsia)

• Singleton gestation at term (37-42 weeks)

• Desire to have a spinal anesthesia technique for cesarean delivery

Exclusion Criteria:

• Current or historical evidence of clinically significant medical disease or condition

• Any contraindication to the administration of a spinal technique for anesthesia

• History of hypersensitivity or idiosyncratic reaction to opioid medications

• Chronic pain syndrome or current regular opioid use

• Evidence of anticipated fetal anomalies

• Allergy or intolerance to Tylenol, ketorolac, ibuprofen, or oxycodone

• BMI > 40

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Analgesia, Obstetrical
• Cesarean Section

Intervention

Drug:
• Morphine
Duramorph is administered as part of spinal anesthesia for post-operative pain relief.
• Hydromorphone
Hydromorphone (Dilaudid) is administered in the intrathecal space for post-operative pain control

Locations

Country	Name	City	State
United States	Rochester Methodist Hospital, Mayo Clinic	Rochester	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
Mayo Clinic

Country where clinical trial is conducted

United States, 

References & Publications (9)

Beatty NC, Arendt KW, Niesen AD, Wittwer ED, Jacob AK. Analgesia after Cesarean delivery: a retrospective comparison of intrathecal hydromorphone and morphine. J Clin Anesth. 2013 Aug;25(5):379-83. doi: 10.1016/j.jclinane.2013.01.014. Epub 2013 Aug 17. — View Citation

Dougherty TB, Baysinger CL, Henenberger JC, Gooding DJ. Epidural hydromorphone with and without epinephrine for post-operative analgesia after cesarean delivery. Anesth Analg. 1989 Mar;68(3):318-22. — View Citation

Gehling M, Tryba M. Risks and side-effects of intrathecal morphine combined with spinal anaesthesia: a meta-analysis. Anaesthesia. 2009 Jun;64(6):643-51. Review. — View Citation

Gerancher JC, Floyd H, Eisenach J. Determination of an effective dose of intrathecal morphine for pain relief after cesarean delivery. Anesth Analg. 1999 Feb;88(2):346-51. — View Citation

Pace NL, Stylianou MP. Advances in and limitations of up-and-down methodology: a précis of clinical use, study design, and dose estimation in anesthesia research. Anesthesiology. 2007 Jul;107(1):144-52. Review. — 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

Rauch E. Intrathecal hydromorphone for cesarean delivery: in search of improved postoperative pain management: a case report. AANA J. 2011 Oct;79(5):427-32. — View Citation

Rauch E. Intrathecal hydromorphone for postoperative analgesia after cesarean delivery: a retrospective study. AANA J. 2012 Aug;80(4 Suppl):S25-32. — View Citation

Terajima K, Onodera H, Kobayashi M, Yamanaka H, Ohno T, Konuma S, Ogawa R. Efficacy of intrathecal morphine for analgesia following elective cesarean section: comparison with previous delivery. J Nippon Med Sch. 2003 Aug;70(4):327-33. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Visual analog pain score following spinal anesthesia administration	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.	12 hours after administration of spinal anesthesia	No
Secondary	Total opioid medication consumption	Total amount of opioids administered to patients in the first 24 hours after spinal administration will be recorded in terms of morphine equivalents.	24 hours following spinal administration	No
Secondary	Visual analog pain score following administration of spinal anesthesia	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).	6 hours and 24 hours after spinal administration	No
Secondary	Side effects: Pruritus	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)	6, 12, and 24 hours after spinal administration	No
Secondary	Side effects: Nausea	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)	6, 12, and 24 hours after spinal administration	No
Secondary	Side effects: Sedation	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))	6, 12, and 24 hours after spinal administration	Yes