Ketamine Tolerated Dose for Postpartum Depression and Pain After Cesarean Delivery

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to identify a tolerable dose for postpartum ketamine infusion using a maximum tolerated dose (MTD) 3+3 design. A loading dose over 1 hour will be the MTD variable to be tested, as our data suggest that ketamine side effects occur with the loading dose. The investigators hypothesize that subanesthetic ketamine dose will be well tolerated and any noted side effects will be rated acceptable by postpartum women following cesarean delivery.

Detailed Description
-----------------
Pain management for women having a cesarean delivery is rather limited and risks poor pain control, depressed mood, and poor recovery following the cesarean delivery. Current cesarean pain management treatments ignore the multidimensionality of pain, including the influence of mood on pain. Recent evidence suggests that ketamine may provide successful post-surgical pain management, opioid reduction, and rapid reduction of depressive symptoms. The current study aims to identify an appropriate dose of ketamine for post-cesarean pain management while minimizing potential dose-dependent side effects in women following childbirth.

Official Title
-----------------
Ketamine Tolerated Dose for Postpartum Depression and Pain After Cesarean Delivery (PREPARE1)

Conditions
-----------------
Pain, Postoperative, Depression, Postpartum

Intervention / Treatment
-----------------
* Drug: Ketamine (Ketalar) Dose Level 1
* Drug: Ketamine (Ketalar) Dose Level 2
* Drug: Ketamine (Ketalar) Dose Level 3
* Drug: Ketamine (Ketalar) Dose Level 4


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Adults 18 years and older Cesarean Delivery American Society of Anesthesiologists Physical Status of 2 or 3 Neuraxial anesthesia with neuraxial morphine Term delivery ≥37 weeks gestation Either planning not to breastfeed, OR receiving ketamine as part of routine clinical care Exclusion Criteria: General anesthesia Allergy to study medications ASA PS 4 or higher Contraindications to neuraxial anesthesia Preterm delivery (<37 weeks gestation) Anticipated fetal-neonatal complex care plan Participating in another pain intervention trial Hypertensive disorder of pregnancy Pre-eclampsia with severe features Hemodynamic instability Medical History exclusions: ketamine or PCP (phencyclidine) abuse, schizophrenia or psychosis, liver or renal insufficiency, uncontrolled hypertension, chest pain, arrhythmia, head trauma, or intracranial hypertension, uncontrolled thyroid disease, or other contraindications to ketamine

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Other
Intervention Model: Sequential Assignment
Interventional Model Description: MTD 3+3 design
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Loading dose Ketamine<br>Loading dose of ketamine in 3+3 MTD for 1 hour followed by maintenance 0.05mg/kg/hr ketamine 11-hour infusion. | Drug: Ketamine (Ketalar) Dose Level 1<br>* Loading Dose: 0.05 mg/kg/hr X 1 hour; Maintenance Dose 0.05 mg/kg/hr x 12 hours<br>* Other names: 0.05 mg/kg/1hr loading dose Ketamine;Drug: Ketamine (Ketalar) Dose Level 2<br>* Loading Dose: 0.08 mg/kg/hr X 1 hour; Maintenance Dose 0.05 mg/kg/hr x 12 hours<br>* Other names: 0.08 mg/kg/1hr loading dose Ketamine;Drug: Ketamine (Ketalar) Dose Level 3<br>* Loading Dose: 0.12 mg/kg/hr X 1 hour; Maintenance Dose 0.05 mg/kg/hr x 12 hours<br>* Other names: 0.12 mg/kg/1hr loading dose Ketamine;Drug: Ketamine (Ketalar) Dose Level 4<br>* Loading Dose: 0.18 mg/kg/hr X 1 hour; Maintenance Dose 0.05 mg/kg/hr x 12 hours<br>* Other names: 0.18 mg/kg/1hr loading dose Ketamine;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Tolerated Dose of ketamine | Dose that fewer than 33% of patients experience intolerability | Between 0 to 24 hours postpartum | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patient reported acceptability of any reported side effects | Proportion (%) of patient cohort reporting acceptability at each ketamine dose | Between 0 to 24-hours postpartum | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Cesarean Delivery