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Does a Single Intravenous Dose of Ketamine Reduce the Need for Supplemental Opioids in Post-Cesarean Section Patients?

Primary Purpose

Ketamine Adverse Reaction, Effects of; Anesthesia, Spinal and Epidural, in Pregnancy, Complication of Labor and/or Delivery

Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Ketamine
Placebo
Sponsored by
Northwestern University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Ketamine Adverse Reaction focused on measuring Ketamine, Spinal Anesthesia, C-section

Eligibility Criteria

18 Years - 60 Years (Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria:

  • Eligible women are at term (≥37 week gestation),
  • Healthy,
  • ASA class 1-2,
  • Scheduled for elective cesarean section whose anesthetic plan is for spinal anesthesia with intrathecal morphine and intravenous ketorolac analgesia for post operative analgesia

Exclusion Criteria:

  • Women with American Society of Anesthesiologists physical status >2,
  • Body mass index ≥40 kg/m2,
  • Known allergy to any of the study medications,
  • Contraindication to the spinal anesthesia,
  • History of substance abuse,
  • History of hallucinations,
  • Chronic opioid therapy,
  • Chronic pain.

Sites / Locations

  • Northwestern University

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Ketamine

Placebo

Arm Description

Subjects receive IV ketamine 10 mg 5 minutes after infant delivery.

Subjects receive IV Saline 20 mL 5 minutes after infant delivery

Outcomes

Primary Outcome Measures

Number of Subjects Requiring Supplemental Analgesia in the First 24 Hours Following Cesarean Delivery
Request for oral hydrocodone/acetaminophen for pain not controlled by around the clock non-steroidal antiflammatory drugs in the first 24 hours following cesarean delivery.

Secondary Outcome Measures

Verbal Pain Scores (0 to 10) at First Analgesia Request
Numeric rating of pain scores (NRS) scale (0 to 10) at time of supplemental analgesia request. Zero is no pain and 10 is worst pain imaginable.
Cumulative Hydrocodone/Acetaminophen for Supplemental Analgesia to Treat Breakthrough Pain
Cumulative hydrocodone/acetaminophen for supplemental analgesia to treat breakthrough pain for 72 hours following cesarean delivery
Postoperative Nausea
Number of subjects reporting nausea in first 24 hours following cesarean delivery
Postoperative Vomiting
Number of subjects that vomited in the first 24 hours following cesarean delivery
Postperative Pruritus
Number of subjects with pruritus in the first 24 hours following cesarean delivery
Disturbing Dreams
Number of subject reporting disturbing dreams at 72 hours post cesarean delivery

Full Information

First Posted
June 13, 2007
Last Updated
March 17, 2014
Sponsor
Northwestern University
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1. Study Identification

Unique Protocol Identification Number
NCT00486902
Brief Title
Does a Single Intravenous Dose of Ketamine Reduce the Need for Supplemental Opioids in Post-Cesarean Section Patients?
Official Title
Does a Single Intravenous Dose of Ketamine Reduce the Need for Supplemental Opioids in Post-Cesarean Section Patients?
Study Type
Interventional

2. Study Status

Record Verification Date
March 2014
Overall Recruitment Status
Completed
Study Start Date
July 2006 (undefined)
Primary Completion Date
October 2008 (Actual)
Study Completion Date
October 2008 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Northwestern University

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
Pain control after cesarean delivery is associated with improved breastfeeding and infant rooming-in times. In addition, inadequate analgesia leads to elevated plasma catecholamine concentrations, which negatively affect every organ system. There is growing evidence that ketamine, N-methyl-D-aspartate receptor antagonist, is efficacious when used as an adjuvant in postoperative pain control. A 2006 Cochrane Collaboration systemic review and meta-analysis concluded, "Ketamine in subanesthetic doses….is effective in reducing morphine requirements in the first 24 hours after surgery." Ketamine's prolonged analgesic effect, despite its short half-life and its use in low doses, is theorized to be due to blockade of spinal cord central sensitization. Central sensitization is a phenomenon whereby repeated painful stimulus leads to more severe pain perception over time despite no change in the intensity of the painful stimulus.Ketamine may also prevent the development of acute opioid tolerance. Ketamine's analgesic effects have also demonstrated in the obstetric population. Post-cesarean delivery morphine requirements in women who received ketamine as part of a general anesthesia technique were decreased. Similary, low-dose ketamine in conjunction with bupivacaine-only spinal anesthesia reduced postoperative analgesic requirements compared to bupivacaine-only spinal anesthesia and bupivacaine-fentanyl spinal anesthesia. In the United States, healthy women scheduled for elective cesarean delivery commonly receive spinal anesthesia with bupivacaine-fentanyl-morphine. To our knowledge, IV ketamine has not been studied as an adjuvant to this regimen in the analgesic management in post-cesarean delivery patients. Multimodal therapy for postoperative pain control is widely practiced due to the advantage it provides in blocking multiple pain pathways while minimizing side effects of each individual pain medication. We hypothesize that low dose intravenous ketamine will improve multi-modal post-cesarean analgesia compared to placebo. The purpose of this study is to evaluate this hypothesis and study the possible side effects of this regimen in combination with bupivacaine-fentanyl-morphine spinal anesthesia.
Detailed Description
Eligible women for elective cesarean section admitted to the Labor and Delivery Unit of Prentice Women's Hospital will be approached for study participation immediately after the routine preanesthetic evaluation. This occurs shortly after admission to the Labor and Delivery Unit. Women who agree to participate will give written, informed consent at this time. Subjects will be prepared preoperatively in the usual fashion with intravenous (IV) access, aspiration prophylaxis and intraoperative monitoring. Preincision antibiotics will be given and uterotonic medications will be used as per usual practice after delivery. The anesthesiologist will perform a spinal anesthetic per routine with the subject in the sitting position using sterile technique at the L3-4 interspace (± one vertebral interspace). The spinal anesthetic will consist of 12 mg of hyperbaric bupivacaine + 15 μg fentanyl + 150 μg of morphine. The subject will be placed supine with left lateral tilt to alleviate aortocaval compression. Cesarean section will commence after adequate anesthesia is assured to a T4 sensory level to pinprick. Vasopressors and IV fluids will be administered at the anesthesiologist's discretion per usual practice. At the time of delivery, subjects will be randomized to one of two groups using a computer generated random number table. Randomization will be blocked based on whether the cesarean procedure is a primary or a repeat procedure. Randomization assignments will be kept in sequentially numbered opaque envelopes. The envelope will be opened by a research nurse who will prepare a 20 mL syringe labeled "study drug". The syringe will be given to the anesthesiologist blinded to the treatment group who will subsequently administer the study drug. Subjects randomized to the treatment group will receive ketamine 10 mg (ketamine 10 mg/mL) diluted to 20 mL with 0.9% preservative free saline. Subjects randomized to the placebo group will receive 20 mL preservative free saline. The study drug will be administered into the intravenous line via an infusion pump over 10 minutes. Five minutes after placebo or drug administration, the anesthesiologist will ask the subject if she has nausea, vomiting and pruritus. Nausea and pruritus will be graded as none, mild, moderate or severe; and vomiting as present or absent. Any spontaneous complaints of psychedelic effects will be noted at this time. Sedation will be assessed via the Richmond agitation-sedation scale (RASS [see Appendix 1]). Upon completion of the cesarean section, the subject will be transported to the post anesthesia recovery unit. Patients will receive ketorolac 30 mg every 6 hours time 4 doses beginning shortly after admission to the PACU. At 1 h, 4 h, 8 h, 12 h and at 24 h after administration of the study drug, the subject's pain will be assessed using the numeric rating scale for pain NRS 0-10 (see Appendix 2). Patients may request rescue analgesia if they are experiencing discomfort. The time of first rescue analgesia request will be noted, and the NRS will be determined at the time of request for rescue analgesia. Rescue medication will consist of hydrocodone 10 mg plus acetaminophen 325 mg per os. An additional dose of hydrocodone 10 mg plus acetaminophen 325 mg will be provided after 1 hour if the pain is not relieved to the subject's satisfaction. These are routine oral analgesic medications for postoperative cesarean delivery analgesia. Standard orders will be written for monitoring sedation and respiratory rate, and treatment of side effects (nausea, vomiting, pruritus and respiratory depression). The total amount of rescue medication will be determined for each subject after 24, 48 and 72 hours. The presence of nausea, vomiting, and pruritus will be assessed at the same time intervals as the NRS for pain: 1 h, 4 h, 8 h, 12 h and 24 h after IV infusion of ketamine or placebo. The subjective psychedelic effects of ketamine and morphine will be assessed using a set of true/false questions from the LSD and morphine short form of the Addiction Research Center Inventory, ARCI (Appendix 3). These questions will be administered verbally by the anesthesiologist or researcher blinded to the treatment group upon admission to the PACU and at 4 h. The following data will be collected in addition to the primary and secondary outcome data: maternal age, height, weight, prepregnancy weight, gestational age and IV fluids administered during cesarean section. In addition, all intraoperative and postoperative medications will be recorded, including those administered for the treatment of side effects listed above. Protocol specific analgesia assessment ends 24 hours after administration of the study drug. At 72 hours the subject will be asked about her satisfaction with postoperative analgesia (100 mm scale, 0 mm = not satisfied at all, 100 mm = very satisfied). One telephone follow-up evaluation 2 weeks after delivery will again, assess for satisfaction with analgesia and average pain (NRS) since the procedure.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Ketamine Adverse Reaction, Effects of; Anesthesia, Spinal and Epidural, in Pregnancy, Complication of Labor and/or Delivery
Keywords
Ketamine, Spinal Anesthesia, C-section

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
188 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Ketamine
Arm Type
Experimental
Arm Description
Subjects receive IV ketamine 10 mg 5 minutes after infant delivery.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Subjects receive IV Saline 20 mL 5 minutes after infant delivery
Intervention Type
Drug
Intervention Name(s)
Ketamine
Other Intervention Name(s)
N-methyl-D-aspartate (NMDA)
Intervention Description
Ketamine 10 mg diluted to 20 mL delivered over 10 minutes via an infusion pump set at 2ml/minute
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
0.9% Saline
Intervention Description
Saline 20 mL IV infusion delivered over 10 minutes via an infusion pump set at 2ml/minute
Primary Outcome Measure Information:
Title
Number of Subjects Requiring Supplemental Analgesia in the First 24 Hours Following Cesarean Delivery
Description
Request for oral hydrocodone/acetaminophen for pain not controlled by around the clock non-steroidal antiflammatory drugs in the first 24 hours following cesarean delivery.
Time Frame
24 hours
Secondary Outcome Measure Information:
Title
Verbal Pain Scores (0 to 10) at First Analgesia Request
Description
Numeric rating of pain scores (NRS) scale (0 to 10) at time of supplemental analgesia request. Zero is no pain and 10 is worst pain imaginable.
Time Frame
24 hours
Title
Cumulative Hydrocodone/Acetaminophen for Supplemental Analgesia to Treat Breakthrough Pain
Description
Cumulative hydrocodone/acetaminophen for supplemental analgesia to treat breakthrough pain for 72 hours following cesarean delivery
Time Frame
72 hours
Title
Postoperative Nausea
Description
Number of subjects reporting nausea in first 24 hours following cesarean delivery
Time Frame
24 hours
Title
Postoperative Vomiting
Description
Number of subjects that vomited in the first 24 hours following cesarean delivery
Time Frame
24 hours
Title
Postperative Pruritus
Description
Number of subjects with pruritus in the first 24 hours following cesarean delivery
Time Frame
24 hours
Title
Disturbing Dreams
Description
Number of subject reporting disturbing dreams at 72 hours post cesarean delivery
Time Frame
72 hours

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Eligible women are at term (≥37 week gestation), Healthy, ASA class 1-2, Scheduled for elective cesarean section whose anesthetic plan is for spinal anesthesia with intrathecal morphine and intravenous ketorolac analgesia for post operative analgesia Exclusion Criteria: Women with American Society of Anesthesiologists physical status >2, Body mass index ≥40 kg/m2, Known allergy to any of the study medications, Contraindication to the spinal anesthesia, History of substance abuse, History of hallucinations, Chronic opioid therapy, Chronic pain.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Cynthia A Wong, M.D.
Organizational Affiliation
Northwestern University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Northwestern University
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States

12. IPD Sharing Statement

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Does a Single Intravenous Dose of Ketamine Reduce the Need for Supplemental Opioids in Post-Cesarean Section Patients?

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