Multimodal Pain Management for Cesarean Delivery
Condition: Pain
Study type: Interventional
Phase: Phase 4

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.
    

Intervention name(s): Intravenous acetominophen; Ketorolac, intramuscular; Bupivacaine, subcutaneous; Normal saline
Intervention type(s): Drug; Drug; Drug; Drug
Intervention description(s): One dose if 1 gram intravenous to be given pre-surgery; One dose of 60 mg Intramuscular to be given at time of skin closure; Inject 20 mL of 0.25% bupivacaine at the site of anticipated skin incision.; 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.
Other intervention name(s): Ofirmev; Toradol
Intervention MeSH terms: Acetaminophen; Ketorolac; Bupivacaine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Cesarean delivery; Multimodal pain management