Ketamine Versus Fentanyl for Surgical Abortions

Ketamine Versus Fentanyl for Surgical Abortions: A Randomized Controlled Noninferiority Trial

Ketamine is commonly used for procedural sedation and analgesia. It is widely used for trauma cases in the emergency department and is considered a superior agent in the outpatient setting due to its lack of respiratory and cardiovascular depression. In chronic opioid users, ketamine decreases acute pain and reduces postoperative opioid consumption. Few studies have examined the use of ketamine for surgical abortions. Previous studies found significant rates of emergence phenomena; however, this can be prevented if a benzodiazepine is given at the same time. Ketamine deserves further study to determine whether it is an acceptable alternative to a standard opioid-based regimen for surgical abortion. Our primary objective is to compare patient satisfaction after surgical abortion among patients receiving IV ketamine versus IV fentanyl for procedural sedation. Our secondary objectives include postoperative pain, additional pain medication used, and postoperative opioid use after the procedure. Our hypothesis is that ketamine will provide similar patient satisfaction and reduce postoperative opioid use. This will be a randomized controlled noninferiority clinical trial of 84 women receiving either IV ketamine with IV midazolam or IV fentanyl with IV midazolam for outpatient one day surgical abortions up to 13, 6/7 weeks gestation. Both groups will receive a standardized paracervical block and additional pain medication as needed. Our study has the potential to introduce IV ketamine as a satisfactory medication for outpatient surgical abortions. Ketamine may decrease the need for IV fentanyl, reduce postoperative opioid use, and may prove to be a superior analgesic for chronic opioid users.

Study Overview

• Status: Completed
• Conditions: Abortion in First Trimester; Pain, Procedural; Opioid Use
• Intervention / Treatment: Drug: Ketamine; Drug: Fentanyl

Detailed Description

First-trimester surgical abortions are one of the most common outpatient procedures worldwide. Although abortion is a quick procedure, most patients still report at least moderate pain.1 Most providers use a paracervical block plus intravenous (IV) moderate sedation with fentanyl (38%) or oral medication (33%). A recent trial comparing IV fentanyl to placebo among participants who also received the paracervical block found a 1-point difference in pain on an 11-point scale. The authors questioned the benefit of this reduction in pain in light of fentanyl's various side effects including nausea and drowsiness, the requirement for additional monitoring and resuscitative equipment, and need for naloxone in case of overdose.

Due to our nation's opioid crisis, there has been growing interest in identifying a non-opioid medication to provide safe, short term, satisfactory pain control during first trimester outpatient surgical abortions. Ketamine is commonly used for procedural sedation and analgesia, and it also reduces postoperative pain. It acts primarily as an N-methyl-D-aspartate receptor antagonist but has some opioid receptor activity. It is widely used for trauma cases and acute pain crises, and is considered a superior agent in the outpatient setting due to its lack of respiratory and cardiovascular depression. Few studies have examined ketamine for surgical abortions. Most studies found improvement when compared to the paracervical block or remifentanil. Our study's primary outcome was to determine if ketamine was noninferior in terms of patient satisfaction with anesthesia to fentanyl for procedural sedation for outpatient first trimester surgical abortions.

• Study Type: Interventional
• Enrollment (Actual): 110
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Washington
    • Renton, Washington, United States, 98057
      • Cedar River Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Aged 14 years or older
• Voluntarily requesting surgical pregnancy termination
• Intrauterine pregnancy up to 13 weeks 6 days by transabdominal or transvaginal ultrasound performed on day of procedure
• Eligible for suction curettage
• English or Spanish speaking
• Able and willing to give informed consent and agree to terms of the study

Exclusion Criteria:

• Age less than 14 years
• Reaspiration procedure or failed medication abortion
• Early pregnancy loss
• Alcohol use disorder or acute alcohol intoxication
• Currently incarcerated
• Gestational age 14 weeks or more
• Requesting a specific pain regimen
• Premedication with misoprostol
• Contraindications or allergies to ketamine or fentanyl

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ketamine; Participant will receive 2mg IV midazolam and 0.2-0.5mg/kg IV ketamine over 2 minutes, which can be repeated q5 minutes until appropriate analgesia is achieved.	Drug: Ketamine; IV ketamine
Active Comparator: Fentanyl; Participant will receive 2mg IV midazolam and 0.5-1mcg/kg IV fentanyl over 2 minutes, which can be repeated q5m until appropriate analgesia is achieved.	Drug: Fentanyl; IV fentanyl

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Satisfaction With Anesthesia Assessed by the ISAS	After the procedure, either at time of discharge (if less than 30 minutes) or at 30 minutes (if not yet discharged), research personnel will assess the participant's satisfaction with anesthesia using the Iowa Satisfaction with Anesthesia Scale. This is a validated perioperative anesthesia satisfaction scale with a minimum score of -3 and a maximum score of +3 with higher scores indicating higher satisfaction.	At discharge or 30 minutes after the procedure

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Provider Satisfaction With Anesthesia Assessed by the VAS	After the procedure, research personnel will assess provider's satisfaction with patient's anesthesia on a 100mm visual analog scale. The minimum score is 0mm and the maximum score if 100mm, with higher scores indicating higher satisfaction.	Immediately postoperatively
Number of Participants Administered Additional Pain Medications	After the procedure, research personnel will ask anesthetist what medications, if any, they gave outside of the study protocol	Immediately postoperatively
Postoperative Pain Assessed by the VAS	Patients will complete 2 followup surveys asking about their postoperative pain after discharge. This will be assessed on a 100mm visual analog scale. The minimum score is 0mm and the maximum score if 100mm, with higher scores indicating higher pain levels.	24 hours postoperatively and 7 days postoperatively

Collaborators and Investigators

• Sponsor: University of Washington
• Collaborators: Society of Family Planning
• Investigators: Principal Investigator: Jennifer Chin, MD, Fellow

Publications and helpful links

General Publications

• Chin J, McGrath M, Lokken E, Upegui CD, Prager S, Micks E. Ketamine Compared With Fentanyl for Surgical Abortion: A Randomized Controlled Trial. Obstet Gynecol. 2022 Sep 1;140(3):461-469. doi: 10.1097/AOG.0000000000004903. Epub 2022 Aug 3.

Study record dates

Study Major Dates

• Study Start (Actual): April 27, 2021
• Primary Completion (Actual): October 14, 2021
• Study Completion (Actual): October 14, 2021

Study Registration Dates

• First Submitted: April 26, 2021
• First Submitted That Met QC Criteria: April 28, 2021
• First Posted (Actual): May 4, 2021

Study Record Updates

• Last Update Posted (Actual): March 24, 2022
• Last Update Submitted That Met QC Criteria: March 22, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Pain, Procedural; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Dissociative; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Analgesics, Opioid; Narcotics; Adjuvants, Anesthesia; Ketamine; Fentanyl
• Other Study ID Numbers: STUDY00012218

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No