Multimodal Pain Management for Cesarean Delivery

NCT ID: NCT02922985

Last Updated: 2021-12-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 120 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-10-31
• Study Completion Date: 2017-07-31

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.

Detailed Description

We are proposing a double-blinded, placebo controlled, randomized trial of patients undergoing elective cesarean delivery. Participants will be randomized to either a control group or study group. This is a double-blinded study, neither participants nor the obstetric or anesthesia team are aware of study assignment. The study group, aka multimodal group, will receive 1 g of IV acetaminophen (ofirmev) within 30 minutes before starting the surgery, regional anesthesia (spinal anesthesia only) with fentanyl, duramorph (morphine) and bupivacaine will be performed as per anesthesia team, the anticipated sight of skin incision will be infiltrated with 20 mL of bupivacaine 0.25% in the subcutaneous space prior to skin incision, and 60 mg of intramuscular (IM) ketorolac (toradol) will be given at the time of fascial closure. The control group will receive a placebo drip within 30 minutes before starting the surgery, regional anesthesia (spinal anesthesia only) with fentanyl, duramorph (morphine) and bupivacaine will be performed as per anesthesia team, the anticipated sight of skin incision will be infiltrated with 20 mL of normal saline in the subcutaneous space prior to skin incision, and an IM dose of placebo at the time of fascial closure. Post-operatively both groups will be managed similarly.

Inclusion Criteria:

• 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

Exclusion Criteria:

Urgent or emergent CD Active labor Epidural or Intrathecal 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 Uncontrolled hypertension Ischemic cardiac disease Congestive heart failure Thrombocytopenia, platelet count <150,000/microliter Preeclampsia including Hemolysis Elevated Liver enzymes Low Platelets syndrome DIC or active hemorrhage before randomization Estimated blood loss > 2000 mL

Primary Outcome: The primary outcome of the study is the total opioid (hydrocodone) use in milligrams in the first 48 hours after cesarean delivery.

Conditions

Pain

Keywords

Cesarean delivery; Multimodal pain management

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Placebo Control Group

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.

Group Type: PLACEBO_COMPARATOR

Normal saline

Intervention Type: 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.

Multimodal Pain Regimen Group

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.

Group Type: ACTIVE_COMPARATOR

Intravenous acetominophen

Intervention Type: DRUG

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

Ketorolac, intramuscular

Intervention Type: DRUG

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

Bupivacaine, subcutaneous

Intervention Type: DRUG

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

Interventions

Intravenous acetominophen

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

Intervention Type: DRUG

Ketorolac, intramuscular

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

Intervention Type: DRUG

Bupivacaine, subcutaneous

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

Intervention Type: DRUG

Normal saline

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.

Intervention Type: DRUG

Other Intervention Names

Ofirmev; Toradol

Eligibility Criteria

Inclusion Criteria

• 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

Exclusion Criteria

• 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
• Uncontrolled hypertension
• Ischemic cardiac disease
• Congestive heart failure
• Thrombocytopenia, platelet count <150,000/microliter
• Preeclampsia including Hemolysis Elevated Liver enzymes Low Platelets syndrome
• Disseminated intravascular coagulation (DIC) or active hemorrhage before randomization
• Estimated blood loss > 2000 mL

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: Yes

Sponsors

The University of Texas Medical Branch, Galveston

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Emily E Hadley, MD

Role: PRINCIPAL_INVESTIGATOR

University of Texas

Locations

University of Texas Medical Branch

Galveston, Texas, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 26824844 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 25461352 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 9260006 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 17981455 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 30822800 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

IRB 16-0121

Identifier Type: -

Identifier Source: org_study_id