Multimodal Pain Management for Cesarean Delivery

NCT02922985 | Completed Phase 4 Results

• 1 other identifier: IRB 16-0121
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

Brief Summary

Opioid use and abuse has become a major medical problem in the United States. Over prescription of opioid medications is a major contributor to this growing problem. Cesarean delivery (CD) is the most commonly performed surgery in the US and women are generally given opioid medications for postoperative pain management. This is not a common practice in other developed countries. We believe that a multimodal pain management strategy is superior to current practices for control of postoperative pain after CD and will lead to a decrease in the use of opioid medications. This will have beneficial effects on patients' recovery and bonding with their newborns, as well as societal effects in reducing the burden of opioid abuse in the US. Our objective is to investigate the use of a multimodal pain regimen in pregnant patients undergoing CD. This is a randomized double-blinded, placebo controlled trial. The multimodal intervention consists of a pre-operative dose of IV acetaminophen (Ofirmev), infiltration of subcutaneous bupivacaine prior to skin incision, and a dose of IM ketorolac at time of fascial closure. These study medications are currently used in our patient population but not in a standardized fashion, not in every patient, and not always in combination with each other. The control group will receive placebo IV infusion preoperatively and an IM injection at fascial closure, and subcutaneous infiltration with normal saline before skin incision. Both groups will receive spinal regional anesthesia as per anesthesia team and then postoperatively, both groups will receive the current standard of care, which consists postoperative hydrocodone/acetaminophen and ibuprofen as needed depending on pain score. Our primary outcome of interest will be the total opioid intake in the first 48 hours after surgery. Secondary outcomes include time to first opioid given, pain scores at 6-12, 24 and 48 hours post op, and total number of opioid tablets left after discharge on post op day number 7. We will also evaluate patient satisfaction scores and total length of hospital stay. We will evaluate neonatal outcomes including Apgar scores, cord blood gases, immediate newborn complications in the first 48 hours after birth, and any infant adverse outcomes related to maternal opioid use up to 4 weeks of life. Our hypothesis is that our multimodal pain regimen will decrease the total opioid requirement in the first 48 hours after surgery.

Conditions

Pain

Keywords

Cesarean delivery; Multimodal pain management

Outcome Measures

Primary Outcomes (1)

• Total Opioid Intake in Morphine Milligram Equivalents in the First 48 Hours After Cesarean Delivery (CD)

  Every opioid intake by the patient in the first 48 hours after CD will be recorded and quantified in morphine milligram equivalents

  48 hours post cesarean delivery

Secondary Outcomes (9)

• Time to First Administration of Opioid Pain Medication Post Operatively

  48 hours post cesarean delivery

• Pain Score at 6-12 Hours Post Operatively

  6-12 hours post-operatively

• Number of Opioid Pain Tablets Remaining on Post-operative Day #7 From the Discharge Prescription.

  7 days post delivery

• Hospital Length of Stay

  From time of hospital admission to time of discharge home up to 168 hours.

• Pain Score at 24 Hours Post-operatively

  24 hours post-operatively

Study Arms (2)

Placebo Control Group

PLACEBO COMPARATOR

Patients will receive a placebo dose of all three study medications: Patients will receive the pre-operative dose of IV normal saline placebo within 30 minutes of going to the OR for CD. The patient will receive the subcutaneous infiltration of 20 mL of subcutaneous normal saline placebo after positioning and preparation but prior to skin incision. At the time of fascial closure, the patient will receive an IM dose of normal saline placebo.

Drug: Normal saline

Multimodal Pain Regimen Group

ACTIVE COMPARATOR

Patients will receive the actual study medication for all three study medications: Patients will receive the pre-operative dose of IV acetaminophen 1 g within 30 minutes of going to the OR for CD. The patient will receive the subcutaneous infiltration of either 20 mL of bupivacaine 0.25% after positioning and preparation but prior to skin incision. At the time of fascial closure, the patient will receive 60 mg of IM ketorolac.

Drug: Intravenous acetominophen; Drug: Ketorolac, intramuscular; Drug: Bupivacaine, subcutaneous

Interventions

Intravenous acetominophen DRUG

One dose if 1 gram intravenous to be given pre-surgery

Also known as: Ofirmev

Multimodal Pain Regimen Group

Ketorolac, intramuscular DRUG

One dose of 60 mg Intramuscular to be given at time of skin closure

Also known as: Toradol

Multimodal Pain Regimen Group

Bupivacaine, subcutaneous DRUG

Inject 20 mL of 0.25% bupivacaine at the site of anticipated skin incision.

Multimodal Pain Regimen Group

Normal saline DRUG

Normal saline will be given intravenously, intra-muscularly, and subcutaneously in the same volume as the study drugs for the patients in the placebo group.

Placebo Control Group

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Women who are 18 - 45 years of age at the time of cesarean delivery with the ability to give informed consent
• Elective cesarean delivery
• Gestational age ≥ 34 weeks
• Fluent in either English or Spanish
• Spinal anesthesia

You may not qualify if:

• Urgent or emergent CD
• Epidural or combined spinal epidural regional anesthesia
• General anesthesia
• Patients with a contraindication for regional anesthesia
• Acute or chronic hepatic disease
• Acute or chronic renal disease
• Active asthma
• Gastrointestinal ulceration
• Inflammatory bowel disease
• Allergy to ketorolac, acetaminophen, hydrocodone, codeine, ibuprofen or bupivacaine
• Opioid dependence
• Non reassuring fetal or maternal status requiring immediate delivery
• Placenta previa or accreta
• Acute or chronic pain disorder
• Maternal weight \<50 kilograms

Sponsors & Collaborators

• The University of Texas Medical Branch, Galveston: lead

Study Sites (1)

University of Texas Medical Branch

Galveston, Texas, 77555, United States

Location

Related Publications (5)

• Bartels K, Mayes LM, Dingmann C, Bullard KJ, Hopfer CJ, Binswanger IA. Opioid Use and Storage Patterns by Patients after Hospital Discharge following Surgery. PLoS One. 2016 Jan 29;11(1):e0147972. doi: 10.1371/journal.pone.0147972. eCollection 2016.

  PMID: 26824844 BACKGROUND

• Santoso JT, Ulm MA, Jennings PW, Wan JY. Multimodal pain control is associated with reduced hospital stay following open abdominal hysterectomy. Eur J Obstet Gynecol Reprod Biol. 2014 Dec;183:48-51. doi: 10.1016/j.ejogrb.2014.10.007. Epub 2014 Oct 14.

  PMID: 25461352 BACKGROUND

• Rosaeg OP, Lui AC, Cicutti NJ, Bragg PR, Crossan ML, Krepski B. Peri-operative multimodal pain therapy for caesarean section: analgesia and fitness for discharge. Can J Anaesth. 1997 Aug;44(8):803-9. doi: 10.1007/BF03013154.

  PMID: 9260006 BACKGROUND

• Munishankar B, Fettes P, Moore C, McLeod GA. A double-blind randomised controlled trial of paracetamol, diclofenac or the combination for pain relief after caesarean section. Int J Obstet Anesth. 2008 Jan;17(1):9-14. doi: 10.1016/j.ijoa.2007.06.006. Epub 2007 Nov 5.

  PMID: 17981455 BACKGROUND

• Hadley EE, Monsivais L, Pacheco L, Babazade R, Chiossi G, Ramirez Y, Ellis V, Simon M, Saade GR, Costantine M. Multimodal Pain Management for Cesarean Delivery: A Double-Blinded, Placebo-Controlled, Randomized Clinical Trial. Am J Perinatol. 2019 Sep;36(11):1097-1105. doi: 10.1055/s-0039-1681096. Epub 2019 Mar 1.

  PMID: 30822800 DERIVED

MeSH Terms

Conditions

Pain

Interventions

Acetaminophen; Ketorolac; Injections, Intramuscular; Ketorolac Tromethamine; Bupivacaine; Injections, Subcutaneous; Saline Solution

Condition Hierarchy (Ancestors)

Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Acetanilides; Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Indomethacin; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Injections; Drug Administration Routes; Drug Therapy; Therapeutics; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Results Point of Contact

• Title: Emily Hadley
• Organization: University of Texas Medical Branch

ehadley15@gmail.com

4022028626

Study Officials

• Emily E Hadley, MD

  University of Texas

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 29, 2016
• First Posted: October 4, 2016
• Study Start: October 1, 2016
• Primary Completion: June 1, 2017
• Study Completion: July 1, 2017
• Last Updated: December 6, 2021
• Results First Posted: July 24, 2018

Record last verified: 2017-10

Locations

US (1)