Pain, Postpartum Depression
Conditions
Keywords
Cesarean Delivery
Brief summary
The purpose of this study is to identify pharmacokinetics of postpartum ketamine infusion. This study will assess ketamine kinetics and metabolism in this setting. Ketamine is expected to exert different kinetics during the physiologic state of post-pregnancy. The goal in conducting this study is to better understand the pharmacokinetics and pharmacodynamics of postpartum ketamine infusion. A secondary goal is to compare these kinetics to reproductive age matched controls and to assess sex differences in ketamine pharmacokinetics. The peripartum group of this study will receive ketamine after cesarean delivery, while the control group will consist of non-pregnant female subjects and male subjects receiving the same infusion protocol.
Detailed description
A lack of data on new pain treatments in pregnancy puts 1.2 million US women having cesarean delivery (CD) every year at risk for poor pain control, depressed mood, and poor recovery. Evidence of successful post-surgical pain management and rapid reduction of depressive symptoms render ketamine a great candidate for post-CD pain management and potential reduction of postpartum depression (PPD) symptomology. Knowledge gaps in ketamine pharmacokinetics (PK) in the postpartum period limit an informed approach to its use for postpartum analgesia and PPD mitigation strategies. Similarly, knowledge gaps about sex differences in ketamine PK limit understandings about potential heterogeneity of treatment effects. This study aims to better understand the pharmacokinetics and pharmacodynamics of ketamine in postpartum women. Secondarily, it will assess key differences in postpartum ketamine PK compared to non-pregnant female controls. Secondarily it will assess key sex differences in ketamine metabolism between male and female subjects. Peripartum females undergoing cesarean delivery will receive a ketamine infusion for 12 hours after cord clamping. Samples will be taken to characterize ketamine PK (primary objective). Healthy volunteer control females and males will receive the same ketamine infusion dosing schematic. Comparisons will be made between peripartum females and non-pregnant female controls, and between female and male controls (secondary objectives).
Interventions
Loading Dose: 0.18 mg/kg/hr x 1 hour; Maintenance Dose 0.05 mg/kg/hr x 11 hours
Sponsors
University of Utah
National Institute of Mental Health (NIMH)
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
NONE
Intervention model description
20 subjects will be cesarean delivery population 30 subjects will be Healthy Control population (N=15 nonpregnant female, N=15 male) Both groups will receive same intervention
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
Peripartum Participants: Inclusion Criteria * Cesarean delivery * Adults 18 years and older * Term delivery ≥ 37 weeks gestation anticipated at time of delivery * ASA PS 2 or 3 * Able to provide informed consent * One of the following must be met for inclusion: Not planning to breastfeed OR ketamine use indicated for pain management plan.
Exclusion criteria
* Patient going under general anesthesia for cesarean delivery * Allergy to study medication (ketamine) * ASA PS 4 + * Contraindications to neuraxial anesthesia * Preterm delivery (\<37 weeks gestation) * Anticipated fetal-neonatal complex care plan as indicated in the patient's chart * Patient history of ketamine or PCP abuse * Patient history of schizophrenia or psychosis * Patient history of liver or renal insufficiency * Patient history of uncontrolled hypertension, chest pain, arrhythmia, head trauma, or intracranial hypertension, uncontrolled hyperthyroidism, or other contraindications to ketamine * Participating in another pain or depression intervention trial * Undergoing hormonal or gender affirming therapies * Pre-eclampsia with severe features * Hemodynamic instability * Inability to participate in study procedures for any reason * Contraindicated medications use: oral antihypertensive medications (exclusion: hypertensive disorders of pregnancy), intravenous magnesium (exclusion: pre-eclampsia with severe features), ketamine/phencyclidine/psilocybins/any other psychedelics (exclusion: ketamine or PCP abuse), lithium/valproate/carbamazepine/lamotrigine/haloperidol/chlorpromazine/fluphenazine/aripiprazole/clozapine/other typical or atypical antipsychotic medications (exclusion: schizophrenia or psychosis) Control Participants Inclusion Criteria * Age 18 years and older * Sex: Male or Female * Able to provide informed consent * ASA PS 1, 2, or 3
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maternal ketamine area under the curve (AUC) | 0 to 24 hours from initiation of ketamine infusion | Ketamine area under the plasma concentration-time curve (AUC 0-∞) (AUC, mcg\*min/mL), which reflects the actual body exposure to ketamine after administration of ketamine. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Patient reported acceptability of any reported side effects | 0 to 24 hours after initiation of ketamine infusion | Proportion (%) of patient cohort reporting acceptability of ketamine infusion |
| Pain area under the curve (AUC) | 0 to 24 hours after initiation of ketamine infusion | Pain score area under the curve (AUC) where pain scores are measured from 0 (no pain) to 10 (worst imaginable pain), for the duration of epidural analgesia. |
| Depression scores (Peripartum) | Baseline to week 12 post-infusion | Depression scores as defined by the Edinburgh Postnatal Depression Scale (Peripartum Group), scale 0-30, measured among the peripartum cohort. |
| Depression Scores (control) | Baseline to week 12 post-infusion | Depression scores as defined by the Patient Health Questionnaire (PHQ-9) (Control Group), scale 0-27, measured among the control nonperipartum cohort. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORGrace Lim, MD, MSc
University of Utah
Outcome results
None listed