TC02 Obese Women Using It Morphine vs PCA IV Hydromorphone for Post-Cesarean Analgesia

Randomized Controlled Trial Evaluating the Transcutaneous Carbon Dioxide Measurements in Obese Women Using Intrathecal Morphine Versus Patient-Controlled Intravenous Hydromorphone for Post-Cesarean Analgesia

Cesarean deliveries are the most commonly performed surgery in the United States and account for 32.9% of all births.8,9 The ASA recommends the use of neuraxial opioids of post-cesarean analgesia partly because respiratory depression in the obstetric population, as measured by intermittent respiratory rate and pulse oximetry, is reported to be low (0-1.2%).10,11 Respiratory depression lacks a standard definition,12 but the most sensitive means of detecting respiratory depression is hypercapnia.1,3 Two recent studies using continuous hypercapnia (>50mmHg PaCO2) monitoring demonstrated higher rates of respiratory depression (17.8-37%) in healthy, non-obese women receiving intrathecal opioids for post-cesarean analgesia.13,14 In addition, supplemental opioids are required in the majority of women receiving intrathecal morphine and may increase the risk of respiratory depression.11,14 Anesthesiologists debate whether neuraxial opioids or intravenous patient controlled opioid analgesia (PCA) are the safest practice for postoperative analgesia in obese parturients following cesarean delivery. The ASA recommendations to employ neuraxial analgesia post-cesarean delivery does not differentiate between non-obese and obese women who now make up 30.3% in US women of child-bearing age.2 Obesity has been described as a risk factor for respiratory depression in those receiving opioids via any route of opioid administration,11,15, 17 but whether obesity itself is the risk factor or associated co-morbidities such as sleep apnea is debated.

Studies are conflicting whether intrathecal opioids or patient controlled intravenous opioids cause more respiratory depression. Several studies have documented the incidence of respiratory depression with IV PCA; the rates range from 0.19% to 5.2%, which are equivalent or higher than those reported for intrathecal opioids. (Hagle 16). Dalchow et al. demonstrated higher rates of hypercapnia in patients receiving intrathecal opioid compared with those receiving intravenous opioid via patient controlled analgesia in nonobese women following cesarean delivery. (Dalchow)

The Topological Oscillation Search with Kinematical Analysis (TOSCA) monitor allows a noninvasive method to measure transcutaneous carbon dioxide levels, with relative accuracy compared to arterial carbon dioxide monitoring.4-7 No studies have examined transcutaneous carbon dioxide levels in obese women following cesarean delivery using any form of postoperative analgesia. The investigators propose a randomized controlled trial using continuous transcutaneous carbon dioxide monitoring to evaluate the degree of respiratory depression in obese women receiving neuraxial opioid compared to intravenous opioid via PCA for post-cesarean analgesia.

Two studies have demonstrated high rates of hypercapnia in non-obese women following administration of intrathecal morphine for cesarean delivery in the postpartum period. (Dalchow, Bauchat) Dalchow et al. demonstrated higher rates of hypercapnia in women receiving intrathecal diamorphine than intravenous morphine delivered via patient controlled analgesia. It is unclear whether intrathecal morphine causes more or less respiratory depression than intravenous opioid delivered via patient-controlled analgesia in obese women.

This study will add to the understanding of respiratory function in the immediate postpartum period in obese women using opioids via intrathecal or intravenous routes. This study will better inform guidelines for the postpartum analgesic route of choice in the obese obstetric population and allow the investigators to make recommendations for the detection and prevention of respiratory depression after opioid administration in the obstetric population.

Objective is to examine the transcutaneous carbon dioxide levels in obese women using either intrathecal morphine or intravenous patient-controlled hydromorphone for post-cesarean analgesia.

The hypothesis is carbon dioxide levels will be significantly higher in obese women receiving intrathecal morphine versus obese women receiving intravenous patient controlled intravenous hydromorphone.

Study Overview

• Status: Withdrawn
• Conditions: Obesity; Pain, Postoperative; Respiratory Insufficiency
• Intervention / Treatment: Drug: Intrathecal Morphine; Drug: Intravenous hydromorphone

• Study Type: Interventional
• Phase: Phase 4

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Term (≥37 week's gestation)
• Healthy
• ASA class 2-3
• BMI ≥40kg/m2 scheduled for elective cesarean section whose anesthetic plan is for neuraxial anesthesia (spinal or combined-spinal epidural technique)

Exclusion Criteria:

• Women with ASA >3,
• BMI <40 kg/m2
• Allergy to any of the medications used for pain control
• Contraindication to the spinal anesthetic technique
• Known sleep apnea or other sleep disordered breathing
• Regular use of other medications that cause respiratory depression (ie. benzodiazepines).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Intrathecal Morphine; Administration of 100µg intrathecal morphine to be given in the operative area.	Drug: Intrathecal Morphine; Intrathecal Morphine administered in the operating room.
Active Comparator: Intravenous Hydromorphone; Administration of intravenous hydromorphone give IV pca in the post operative area.	Drug: Intravenous hydromorphone; Intravenous hydromorphone administered via IV in the post operative area.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of hypercapnia	Incidence of hypercapnia (transcutaneous CO2 levels >50mmHg) in the intrathecal morphine versus patient controlled intravenous morphine groups	24 hours post delivery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Opioid consumption	Amount of opioids used during the time from delivery to 24 hours post delivery	24 hours post delivery
NSAID consumption	Amount of NSAID's used during the time from delivery to 24 hours post delivery.	24 hours post delivery
Respiratory rate	Hourly respiratory rates for the first 12 hours then every 2 hours for the next 12 hours.	24 hours post delivery
Sedation scores	Sedation scores as scored on the Richmond Agitation and Sedation Scale at 2 hours, 6 hour and 12 hours post delivery.	delivery to 12 hours post delivery
Pain Scores	Pain scores on a scale of 0 (low)-10 (high) will be documented every hour for the first 24 hours after delivery.	24 hours
Pulse oximetry	Pulse oximetry will be collected using the transcutaneous Co2 monitor for 24 hours after deliuvery.	24 hours post delivery

Collaborators and Investigators

• Sponsor: Northwestern University
• Investigators: Principal Investigator: Feyce Peralta, MD, Northwestern University

Publications and helpful links

General Publications

• Lee LA, Caplan RA, Stephens LS, Posner KL, Terman GW, Voepel-Lewis T, Domino KB. Postoperative opioid-induced respiratory depression: a closed claims analysis. Anesthesiology. 2015 Mar;122(3):659-65. doi: 10.1097/ALN.0000000000000564.
• Ogden CL, Carroll MD, Kit BK, Flegal KM. Prevalence of childhood and adult obesity in the United States, 2011-2012. JAMA. 2014 Feb 26;311(8):806-14. doi: 10.1001/jama.2014.732.
• Practice Guidelines for the Prevention, Detection, and Management of Respiratory Depression Associated with Neuraxial Opioid Administration: An Updated Report by the American Society of Anesthesiologists Task Force on Neuraxial Opioids and the American Society of Regional Anesthesia and Pain Medicine. Anesthesiology. 2016 Mar;124(3):535-52. doi: 10.1097/ALN.0000000000000975. No abstract available.
• McCormack JG, Kelly KP, Wedgwood J, Lyon R. The effects of different analgesic regimens on transcutaneous CO2 after major surgery. Anaesthesia. 2008 Aug;63(8):814-21. doi: 10.1111/j.1365-2044.2008.05487.x.

Study record dates

Study Major Dates

• Study Start (Anticipated): August 1, 2019
• Primary Completion (Anticipated): December 1, 2021
• Study Completion (Anticipated): December 1, 2021

Study Registration Dates

• First Submitted: September 12, 2017
• First Submitted That Met QC Criteria: September 12, 2017
• First Posted (Actual): September 14, 2017

Study Record Updates

• Last Update Posted (Actual): May 6, 2022
• Last Update Submitted That Met QC Criteria: May 5, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Keywords: Pregnancy; Cesarean Section; Pulse Oximetry; Hypoxemia; Postoperative pain control; Hypercarbia; Transcutaneous Carbon Dioxide Monitoring; High BMI
• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Respiration Disorders; Postoperative Complications; Pain; Neurologic Manifestations; Pain, Postoperative; Respiratory Insufficiency; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Opioid; Narcotics; Morphine; Hydromorphone
• Other Study ID Numbers: STU00203985

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