Comparison of Two Intravenous Drug Combinations for Ambulatory Oral & Maxillofacial Surgery

Phase 1

Completed

• Conditions: Anesthesia; Tooth Extraction
• Interventions: Drug: Midazolam Hydrochloride; Drug: Fentanyl; Drug: Ketamine; Drug: Propofol injection; Drug: Nitrous oxide

• Registration Number: NCT06867068
• Lead Sponsor: Albert Einstein College of Medicine

Brief Summary

The purpose of this pilot study was to compare two commonly employed intravenous drug combinations; I) nitrous oxide, midazolam, fentanyl, and ketamine and II) the same combination with substitution of propofol for ketamine, for use during wisdom teeth extraction. Measures of recovery, amnesia testing 20 minutes after induction and after completion of recovery tests, patient satisfaction, and surgeon satisfaction will be evaluated. The data from this pilot study will be used to obtain preliminary estimates of effect sizes and to select primary and secondary endpoints for the design of a larger scale and more definitive trial of the two anesthetic approaches.

Detailed Description

The widespread application of various ambulatory anesthetic techniques has paralleled the rapid rise of ambulatory surgery. It has been estimated that over half of all elective surgery is performed in an ambulatory setting. In addition, well over 3,000,000 intravenous sedations are administered in dental offices annually where local anesthesia is obtainable to control intraoperative pain. These intravenous sedation techniques have historically been an integral part of pain and anxiety control in the dental setting and have now gained widespread application in all of ambulatory surgery. A number of intravenous anesthetic techniques have been developed to achieve sedation levels ranging from conscious sedation where patients respond purposefully to verbal commands to deep sedation where patients cannot be easily aroused and protective reflexes may be altered. The goal of all of these techniques is to create a comfortable environment for the patient and a cooperative patient for the surgeon. Ideal technique should pose minimal physiologic challenge to the patient while providing amnesia for the procedure. Most of the intravenous sedation techniques in widespread use include a combination of drugs. These combinations function in an additive if not synergistic way. The pharmacological properties of their constituents achieve this ideal. The most frequently used drug when used alone and the most common to the various combinations is midazolam, a benzodiazepine. Midazolam has been shown to provide safe sedation with reliable anterograde amnesia. The duration of these effects is dose dependent. A short acting narcotic, usually fentanyl, is often times included to increase sedation levels and to add a modicum of analgesia. Other short acting agents can also be included to deepen the sedation level. These agents are usually added in incremental doses as the surgical setting requires. Both propofol and ketamine can induce general anesthesia but in significantly smaller doses provide additional sedation. These two agents come from different drug classes. Proponents of each cite advantages and disadvantages. Nitrous oxide is also commonly used in the dental setting.

Study Timeline

• Study Start: 2016-10-04
• Primary Completion: 2024-06-10
• Study Completion: 2024-06-10
• Status Verified: 2025-03
• Study First Submitted: 2025-03-05
• Study First Submitted QC: 2025-03-05
• Last Update Submitted: 2025-03-05
• Study First Posted: 2025-03-10
• Last Update Posted: 2025-03-10

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 73

Inclusion Criteria

• American Society of Anesthesiologists (ASA) health class I or II
• Existing clinical population

Exclusion Criteria

• Do not meet the Inclusion Criteria

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Ketamine Group	Midazolam Hydrochloride	1. Midazolam 0.05 mg/kg - rounded to closest ½ mg 2. Fentanyl 50 micrograms (mcg) for patients less than or equal to 70kg and 75 mcg for those over 70 kg 3. Ketamine 0.3 mg/kg - rounded to closest 5 mg (i.e., 70 kg patient - 3.5mg Midazolam, 50 mcg Fentanyl, 20 mg Ketamine) 4. Additional intermittent dosage of Ketamine - 15 mg per surgeon's request All patients receive 40% nitrous oxide/oxygen, as per standard clinical care. All of the drugs are being used per label.
Ketamine Group	Fentanyl	1. Midazolam 0.05 mg/kg - rounded to closest ½ mg 2. Fentanyl 50 micrograms (mcg) for patients less than or equal to 70kg and 75 mcg for those over 70 kg 3. Ketamine 0.3 mg/kg - rounded to closest 5 mg (i.e., 70 kg patient - 3.5mg Midazolam, 50 mcg Fentanyl, 20 mg Ketamine) 4. Additional intermittent dosage of Ketamine - 15 mg per surgeon's request All patients receive 40% nitrous oxide/oxygen, as per standard clinical care. All of the drugs are being used per label.
Ketamine Group	Ketamine	1. Midazolam 0.05 mg/kg - rounded to closest ½ mg 2. Fentanyl 50 micrograms (mcg) for patients less than or equal to 70kg and 75 mcg for those over 70 kg 3. Ketamine 0.3 mg/kg - rounded to closest 5 mg (i.e., 70 kg patient - 3.5mg Midazolam, 50 mcg Fentanyl, 20 mg Ketamine) 4. Additional intermittent dosage of Ketamine - 15 mg per surgeon's request All patients receive 40% nitrous oxide/oxygen, as per standard clinical care. All of the drugs are being used per label.
Ketamine Group	Nitrous oxide	1. Midazolam 0.05 mg/kg - rounded to closest ½ mg 2. Fentanyl 50 micrograms (mcg) for patients less than or equal to 70kg and 75 mcg for those over 70 kg 3. Ketamine 0.3 mg/kg - rounded to closest 5 mg (i.e., 70 kg patient - 3.5mg Midazolam, 50 mcg Fentanyl, 20 mg Ketamine) 4. Additional intermittent dosage of Ketamine - 15 mg per surgeon's request All patients receive 40% nitrous oxide/oxygen, as per standard clinical care. All of the drugs are being used per label.
Propofol Group	Midazolam Hydrochloride	1. Midazolam 0.05 mg/kg - rounded to closest ½ mg 2. Fentanyl 50 mcg for patients less than or equal to 70 kg and 75 mcg for those over 70 kg 3. Propofol 0.3 mg/kg - rounded to closest 5 mg (i.e., 70 kg patient - 3.5 mg Midazolam, 50 micrograms Fentanyl, 20 mg Propofol) 4. Additional intermittent dosage of Propofol - 15 mg per surgeon's request All patients receive 40% nitrous oxide/oxygen, as per standard clinical care. All of the drugs are being used per label.
Propofol Group	Fentanyl	1. Midazolam 0.05 mg/kg - rounded to closest ½ mg 2. Fentanyl 50 mcg for patients less than or equal to 70 kg and 75 mcg for those over 70 kg 3. Propofol 0.3 mg/kg - rounded to closest 5 mg (i.e., 70 kg patient - 3.5 mg Midazolam, 50 micrograms Fentanyl, 20 mg Propofol) 4. Additional intermittent dosage of Propofol - 15 mg per surgeon's request All patients receive 40% nitrous oxide/oxygen, as per standard clinical care. All of the drugs are being used per label.
Propofol Group	Propofol injection	1. Midazolam 0.05 mg/kg - rounded to closest ½ mg 2. Fentanyl 50 mcg for patients less than or equal to 70 kg and 75 mcg for those over 70 kg 3. Propofol 0.3 mg/kg - rounded to closest 5 mg (i.e., 70 kg patient - 3.5 mg Midazolam, 50 micrograms Fentanyl, 20 mg Propofol) 4. Additional intermittent dosage of Propofol - 15 mg per surgeon's request All patients receive 40% nitrous oxide/oxygen, as per standard clinical care. All of the drugs are being used per label.
Propofol Group	Nitrous oxide	1. Midazolam 0.05 mg/kg - rounded to closest ½ mg 2. Fentanyl 50 mcg for patients less than or equal to 70 kg and 75 mcg for those over 70 kg 3. Propofol 0.3 mg/kg - rounded to closest 5 mg (i.e., 70 kg patient - 3.5 mg Midazolam, 50 micrograms Fentanyl, 20 mg Propofol) 4. Additional intermittent dosage of Propofol - 15 mg per surgeon's request All patients receive 40% nitrous oxide/oxygen, as per standard clinical care. All of the drugs are being used per label.

Primary Outcome Measures

Name	Time	Method
Surgeon Satisfaction	Postoperatively, approximately 1 hour	Surgeon satisfaction will be assessed by a surgeon's satisfaction survey administered following the procedure. The survey consisted of 3 questions which asked the surgeon to assess their level of satisfaction with the sedation regimen during local anesthesia, during the surgery, and overall satisfaction. Each of the three were rated as 1 ("Poor"), 2 ("Adequate"), or 3 ("Excellent") for an overall possible scoring range of 3-9. Higher scores are associated with increased surgeon satisfaction. Surgeon satisfaction scores will be summarized by study arm.
Recovery - Paper Test	Change from preoperatively to postoperatively, approximately 2-3 hours total on day of procedure	Recovery will be assessed using a simple repeated measure paper and pencil test (PS Form 9a). This test presented participants with 25 rows of numbers. Each row consisted of a circled number at the beginning of the string of numbers. Patients were asked to cross out each number in a row that is like the circled number. The number of successfully completed rows were tabulated for each patient and change from baseline was summarized by study arm.
Amnesia - Tactile Stimuli	Intraoperatively and postoperatively, up to 1-2 hours on day of procedure	Amnesia will be evaluated by interrupting the procedure momentarily at specific intervals (approximately 20 minutes after induction and after completion of recovery test). Amnesia for tactile stimuli will be assessed by touching the patient with a pin on one of their four limbs and asking for recall. Recall of tactile stimuli will be summarized by study arm using basic descriptive statistics.
Patient Satisfaction	Postoperatively, approximately 1 hour on day of procedure	Patient satisfaction was assessed using a patient evaluation survey administered following the procedure just prior to discharge. The survey consisted of 3 questions, 1 categorical and 2 ordinal. For purposes of this study, the 2 ordinal measures: "How do you feel now?" and "I would recommend this type of intravenous sedation to my family/friends" will be scored from 1-3 and 1-4, respectively for an overall possible scoring range of 2-7. Higher scores are associated with increased patient satisfaction. Satisfaction scores will be summarized by study arm.
Recovery - One Leg Standing Test	Change from preoperatively to postoperatively, approximately 2-3 hours total on day of procedure	Recovery will also be assessed by way of a 30 second one leg standing test administered prior to and following induction of anesthesia. The percentage of participants who are able to stand for at least 30 seconds will be summarized by study arm.
Amnesia - Visual Stimuli	Intraoperatively and postoperatively, up to 1-2 hours on day of procedure	Amnesia will be evaluated by interrupting the procedure momentarily at specific intervals (approximately 20 minutes after induction and after completion of recovery test). Amnesia for visual stimuli will be assessed by having the patient verbally identify common objects (i.e., cup, pen, tape, and keys) presented during surgery. Patients will be asked to recall the items postoperatively. Recall of visual stimuli will be summarized by study arm using basic descriptive statistics.

Trial Locations

Locations (1)

NYCHHC - Jacobi Medical Center and North Central Bronx Hospital; 🇺🇸 Bronx, New York, United States