Dose and Response of Intrathecal Hydromorphone in Patients Undergoing Cesarean Section at Virginia Commonwealth University Health System

In the United States the incidence of cesarean deliveries have increased over the last several decades and is currently approximately 30% nationwide. The anesthesia and analgesia for elective c-sections vary between institutions.

Parturients present a unique challenge for the anesthesiologist as the mother has to care not only for herself, but also for the newborn postpartum. While intrathecal opioids provide adequate pain relief, they do so at the cost of bothersome side effects for patients, such as pruritus and nausea/vomiting.

Intrathecal hydromorphone has started to be explored as a new option for intrathecal analgesia. A study done by Beatty et al. showed in a retrospective review that 40 mcg of intrathecal dilaudid was safe and effective as compared to intrathecal morphine for analgesia after cesarean delivery. Additionally they showed no difference in side effect profiles of the two medications. Mhyre et al. investigated the use of 100 mcg of intrathecal dilaudid with hyperbaric bupivacaine in varying dosages for labor analgesia. The results were inconclusive, but the dosage of hydromorphone was reported to be without adverse effects.

Virginia Commonwealth University Health Systems has successfully instituted the use of intrathecal morphine with superior analgesia but with undesired side effects, most notably pruritus. Recent drug shortages of duramorph have prompted investigators to seek alternative options for post cesarean section analgesia. The investigators are interested in determining the dose, efficacy, and side effect profile of intrathecal hydromorphone. Although our institution has never utilized intrathecal hydromorphone for our patient population, it has been studied at various other institutions where it has been found to be safe and efficacious with an acceptable side effect profile.

Study Overview

• Status: Terminated
• Conditions: Cesarean Section; Obstetric Anesthesia
• Intervention / Treatment: Drug: Intrathecal hydromorphone

• Study Type: Interventional
• Enrollment (Actual): 14
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Virginia
    • Richmond, Virginia, United States, 23298
      • Virginia Commonwealth University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• American Society of Anesthesiologists physical status classification less than or equal to 3 Elective cesarean section Able to obtain a signed consent in English Patients who are 18 years or older

Exclusion Criteria:

• ASA greater than 3 or major medical comorbidities that are not optimized Patient refusal or contraindications to neuraxial/study drugs. Allergy to study drugs Conversion to general anesthesia Any patient who does not receive any multimodal regimen (PO acetaminophen, +/- PO ibuprofen/IV ketorolac) Any patient who is taking PO/IV opioids or buprenorphine during the current pregnancy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: HEALTH_SERVICES_RESEARCH
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

EXPERIMENTAL: Intrathecal Dilaudid; This will be a prospective up/down dosage study. After obtaining informed consent, eligible participants will be part of an up/down dose titration study. This first phase of our study will be conducted using intrathecal (spinal) hydromorphone to determine an appropriate dose range for our study population. Study drug dose will initially be 40 mcg. The only deviation from the current standard of care will be that patients will be given hydromorphone intrathecally instead of morphine. The rest of the care provided will be standard of care and per current practices at VCU labor and delivery floor.

Drug: Intrathecal hydromorphone; Intrathecal hydromorphone will be administered in an up/down dosage fashion. A successful dose will be defined as a patient not requiring additional narcotic pain medication outside of the standard VCU order set, which includes PRN oxycodone 5 and 10 mg every 4 hours and a one time PRN 1 mg hydromorphone IV. Failure of a dose will be if patient requires additional narcotic pain medication outside of these parameters

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Narcotic Pain Medication	Dose failure defined as requiring more than oxycodone 5 or 10 mg q 4 hours and a 1x PRN of IV hydromorphone	12 hours post administration of intrathecal hydromorphone

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Nausea	Rated on Numerical rating scale 0 -10 and by amount of anti-emetic medication required (ondansetron)	4, 8, 12, 18 and 24 hours after placement of intrathecal hydromorphone
Pruritus	Rated on numerical rating scale 0 - 10, and by amount of anti-pruritic medication required (nalbuphine, benadryl)	4, 8, 12, 18 and 24 hours after placement of intrathecal hydromorphone
Sedation	Richmond Agitation and Sedation Score at above time points	4, 8, 12, 18 and 24 hours after placement of intrathecal hydromorphone
Pain	Pain score on numeric rating scale, 0 - 10 at above time points, total amount of narcotic pain medication required	4, 8, 12, 18 and 24 hours after placement of intrathecal hydromorphone
Infant Outcome	Infant APGAR scores at 1, 5 and 10 minutes post delivery	up to 10 minutes

Collaborators and Investigators

• Sponsor: Virginia Commonwealth University
• Investigators: Principal Investigator: Shilen Thakrar, MD, Virginia Commonwealth University

Study record dates

Study Major Dates

• Study Start: April 1, 2016
• Primary Completion (ACTUAL): December 31, 2017
• Study Completion (ACTUAL): December 31, 2017

Study Registration Dates

• First Submitted: May 26, 2016
• First Submitted That Met QC Criteria: May 31, 2016
• First Posted (ESTIMATE): June 1, 2016

Study Record Updates

• Last Update Posted (ACTUAL): April 24, 2018
• Last Update Submitted That Met QC Criteria: April 20, 2018
• Last Verified: April 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Opioid; Narcotics; Hydromorphone
• Other Study ID Numbers: HM20005584

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No