Ketamine to Improve Recovery After Cesarean Delivery - Part 1
Condition: Obstetric Pain; Postpartum Depression; Breastfeeding; Pain, Acute; Pain, Chronic; Obstetric Anesthesia Problems; Drug Effect; Opioid Use
MeSH terms: Depression, Postpartum; Acute Pain; Chronic Pain; Labor Pain
Intervention: Ketamine
Intervention description: Subjects in the intervention arm will receive infusion dosing as noted in arm/group descriptions at the time of cord clamping. Duration of infusion will be 12 hours. Concentrations of ketamine and ketamine metabolites (nor-ketamine, NKET; and dehydro-nor-ketamine, DHNK) are measured in maternal plasma and urine as well as breastmilk. Maternal side effects, adverse events, and efficacy endpoints will be measured over the 12 hour infusion and over 15 hours after infusion discontinuation.
Intervention MeSH terms: Ketamine
Phase: Phase 2
Study type: Interventional
Primary purpose: Prevention
Intervention model: Single Group Assignment
Intervention model description: Prospective observational open-label trial (Part 1)
Masking: None (Open Label)
Enrollment: 8.0
Sex: Female
Minimum age: 18 Years
Maximum age: 99 Years
Healthy volunteers: Accepts Healthy Volunteers

Summary:

      The objective of this study is evaluate the breastmilk transfer and pharmacokinetics (Part 1)
      and effectiveness (Part 2) of a post-cesarean delivery intravenous ketamine
      bolus-and-infusion strategy, as a preventive analgesic modality to reduce pain and opioid
      requirements.

      In Part 1, physiochemical analysis of pharmacokinetic/pharmacodynamic (PK/PD) and breastmilk
      transfer of ketamine and its metabolites will be assessed. Additionally calculated
      estimations for neonatal and infant exposure will be assessed.

      In Part 2, PK/PD assessments will continue in a larger cohort; endpoints will also include
      postpartum pain, depression scores, central sensitization measures, patient-reported
      postpartum recovery scores, breastfeeding, and parent-infant bonding, assessed in the acute
      post-cesarean period and up to 12 weeks postpartum in a randomized controlled trial.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Adult female patients (i.e., ≥18 years of age) and able to provide informed consent

          -  Cesarean Delivery, Scheduled or Non-Emergent (delivery within 15 minutes not
             necessary), or female weaning off of breastfeeding

          -  Cesarean cohort: ASA PS 2 or 3, with or without E designation (delivery within 15
             minutes not necessary), Scheduled or Non-Emergent

          -  Spinal anesthesia with intrathecal morphine if Cesarean Delivery, Scheduled or
             Non-Emergent

          -  Multimodal postop analgesia with IV ketorolac, PO NSAID, and PO APAP if Cesarean
             Delivery, Scheduled or Non-Emergent

          -  Women who do not plan to breastfeed or who want to temporarily withhold breastfeeding
             or who are weaning off of breastfeeding (Part 1)

        Exclusion Criteria:

          -  Cesarean Delivery under General Anesthesia

          -  Allergies to study medications

          -  ASA PS 4 or 4E

          -  ASA PS with E designation because delivery within 15 minutes required

          -  ASA PS greater than 4 (moribund patients)

          -  Contraindications to spinal anesthesia

          -  Contraindications to NSAIDs (gastric bypass, etc.)

          -  Contraindication to any other multimodal analgesia medicine

          -  Significant psychiatric history (depression and anxiety NOT exclusion criteria),
             uncontrolled hyperthyroidism, cardiac disease, fever, hypertension

          -  Adverse occurrence during caesarean section such as hemorrhage, need for transfusion,
             hemodynamic instability

          -  Placenta accreta spectrum or previa with large anticipated blood loss

          -  History of hallucinations, alcohol or illicit substance use/abuse, chronic opioid
             therapy, or chronic pain (chronic pain - defined by any condition requiring consistent
             follow up with pain specialist or daily administration of pain medications that could
             augment sedative effects)

          -  Pre-eclampsia with severe features