Ketamine Versus Fentanyl for Surgical Abortions

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Abortion in First Trimester, Pain, Procedural, Opioid Use

Intervention / Treatment
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* Drug: Ketamine
* Drug: Fentanyl


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 14 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ketamine<br>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<br>* IV ketamine<br>|
| Active Comparator: Fentanyl<br>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<br>* IV fentanyl<br>|

What is the study measuring?
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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 |