Clinical trial NCT02009722: Intrathecal Opioids for Pain Control After Cesarean Delivery: Determining the Optimal Dose
Official title: Intrathecal Opioids for Pain Control After Cesarean Delivery: Determining the Optimal Dose
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Analgesia, Obstetrical
Cesarean Section
Keywords: Cesarean Delivery
Intrathecal Morphine
Intrathecal Hydromorphone
Obstetrical Analgesia
Spinal Anesthesia
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
First posted: 2013-12-12
Enrollment: 84
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

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 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.

Eligibility criteria: 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

Primary outcomes:
measure: Dose of IT Morphine and IT Hydromorphone for Adequate Analgesia (Pain Score Less Than or Equal to 3) in 90% of Patients
timeFrame: 12 hours after administration of spinal anesthesia
Secondary outcomes:
measure: Side Effects: Pruritus
timeFrame: 6 hours after spinal administration
measure: Side Effects: Nausea
timeFrame: 6 hours after spinal
measure: Side Effects: Sedation
timeFrame: 6, 12, and 24 hours after spinal administration
measure: Pruritus
timeFrame: 12 hours after spinal
measure: Pruritus
timeFrame: 24 hours after spinal
measure: Nausea
timeFrame: 12 hours after spinal
measure: Nausea
timeFrame: 24 hours after spinal
measure: Treatment for Nausea
timeFrame: First 24 hours
measure: Treatment for Pruritus
timeFrame: First 24 hours after spinal
Other outcomes:
Locations:
city: Rochester
country: United States
facility: Rochester Methodist Hospital, Mayo Clinic
state: Minnesota
Study officials:
affiliation: Mayo Clinic
name: Hans P Sviggum, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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):379-383. doi: 10.1016/j.jclinane.2013.01.014. Epub 2013 Aug 17.
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: Rauch E. Intrathecal hydromorphone for postoperative analgesia after cesarean delivery: a retrospective study. AANA J. 2012 Aug;80(4 Suppl):S25-32.
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.
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. doi: 10.1272/jnms.70.327.
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. doi: 10.1111/j.1365-2044.2008.05817.x.
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.
citation: Pace NL, Stylianou MP. Advances in and limitations of up-and-down methodology: a precis of clinical use, study design, and dose estimation in anesthesia research. Anesthesiology. 2007 Jul;107(1):144-52. doi: 10.1097/01.anes.0000267514.42592.2a.
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. doi: 10.1097/00000539-199902000-00023.