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

NCT ID: NCT06867068

Last Updated: 2025-03-10

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

73 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-10-04

Study Completion Date

2024-06-10

Brief Summary

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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

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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.

Conditions

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Anesthesia Tooth Extraction

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

SUPPORTIVE_CARE

Blinding Strategy

DOUBLE

Participants Caregivers
For purposes of safety the anesthesiologist was not blinded.

Study Groups

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Ketamine Group

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.

Group Type ACTIVE_COMPARATOR

Midazolam Hydrochloride

Intervention Type DRUG

Short-acting sedative. Benzodiazepine. Gamma-aminobutyric acid (GABA) inhibitor

Fentanyl

Intervention Type DRUG

Synthetic opioid drug used as an analgesic.

Ketamine

Intervention Type DRUG

General Anesthetic. N-methyl-D-aspartate (NMDA) receptor agonist

Nitrous oxide

Intervention Type DRUG

Modulates a wide range of ligand-gated ion channels and inhibits NMDA receptor-mediated currents

Propofol Group

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.

Group Type ACTIVE_COMPARATOR

Midazolam Hydrochloride

Intervention Type DRUG

Short-acting sedative. Benzodiazepine. Gamma-aminobutyric acid (GABA) inhibitor

Fentanyl

Intervention Type DRUG

Synthetic opioid drug used as an analgesic.

Propofol injection

Intervention Type DRUG

General Anesthetic. GABA receptor modulator and calcium channel blocker

Nitrous oxide

Intervention Type DRUG

Modulates a wide range of ligand-gated ion channels and inhibits NMDA receptor-mediated currents

Interventions

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Midazolam Hydrochloride

Short-acting sedative. Benzodiazepine. Gamma-aminobutyric acid (GABA) inhibitor

Intervention Type DRUG

Fentanyl

Synthetic opioid drug used as an analgesic.

Intervention Type DRUG

Ketamine

General Anesthetic. N-methyl-D-aspartate (NMDA) receptor agonist

Intervention Type DRUG

Propofol injection

General Anesthetic. GABA receptor modulator and calcium channel blocker

Intervention Type DRUG

Nitrous oxide

Modulates a wide range of ligand-gated ion channels and inhibits NMDA receptor-mediated currents

Intervention Type DRUG

Other Intervention Names

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Versed (N-phenyl-N-[1-(2-phenylethyl)-4piperidinyl]propanamide); Sublimaze, Actiq, Duragesic, Abstral, Subsys, and Ionsys Ketalar 2,6-diisopropylphenol; Diprivan Nitrous, laughing gas

Eligibility Criteria

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Inclusion Criteria

* American Society of Anesthesiologists (ASA) health class I or II
* Existing clinical population
Minimum Eligible Age

16 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Albert Einstein College of Medicine

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Stephen S Gelfman, MD, DDS

Role: PRINCIPAL_INVESTIGATOR

New York City Health and Hospitals (NYCHHC)

Locations

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NYCHHC - Jacobi Medical Center and North Central Bronx Hospital

The Bronx, New York, United States

Site Status

Countries

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United States

References

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American Association of Oral and Maxillofacial Surgeons Parameters of Care: Clinical Practice Guidelines. 2012.

Reference Type BACKGROUND

Peskin RM. Contemporary intravenous anesthetic agents and delivery systems: propofol. Anesth Prog. 1992;39(4-5):178-84. No abstract available.

Reference Type BACKGROUND
PMID: 1344020 (View on PubMed)

Braidy HF, Singh P, Ziccardi VB. Safety of deep sedation in an urban oral and maxillofacial surgery training program. J Oral Maxillofac Surg. 2011 Aug;69(8):2112-9. doi: 10.1016/j.joms.2011.04.017.

Reference Type BACKGROUND
PMID: 21783001 (View on PubMed)

Craig DC, Wildsmith JA; Royal College of Anaesthetists; Royal College of Surgeons of England. Conscious sedation for dentistry: an update. Br Dent J. 2007 Dec 8;203(11):629-31. doi: 10.1038/bdj.2007.1105.

Reference Type BACKGROUND
PMID: 18065980 (View on PubMed)

Goktay O, Satilmis T, Garip H, Gonul O, Goker K. A comparison of the effects of midazolam/fentanyl and midazolam/tramadol for conscious intravenous sedation during third molar extraction. J Oral Maxillofac Surg. 2011 Jun;69(6):1594-9. doi: 10.1016/j.joms.2010.09.005. Epub 2011 Feb 1.

Reference Type BACKGROUND
PMID: 21277062 (View on PubMed)

Sims PG, Kates CH, Moyer DJ, Rollert MK, Todd DW. Anesthesia in outpatient facilities. J Oral Maxillofac Surg. 2012 Nov;70(11 Suppl 3):e31-49. doi: 10.1016/j.joms.2012.07.030. No abstract available.

Reference Type BACKGROUND
PMID: 23128005 (View on PubMed)

Ulmer BJ, Hansen JJ, Overley CA, Symms MR, Chadalawada V, Liangpunsakul S, Strahl E, Mendel AM, Rex DK. Propofol versus midazolam/fentanyl for outpatient colonoscopy: administration by nurses supervised by endoscopists. Clin Gastroenterol Hepatol. 2003 Nov;1(6):425-32. doi: 10.1016/s1542-3565(03)00226-x.

Reference Type BACKGROUND
PMID: 15017641 (View on PubMed)

Personal Communication. Oral and Maxillofacial Surgery National Insurance Company. 2013.

Reference Type BACKGROUND

Blankstein KC. Low-dose intravenous ketamine: an effective adjunct to conventional deep conscious sedation. J Oral Maxillofac Surg. 2006 Apr;64(4):691-2. doi: 10.1016/j.joms.2005.11.038. No abstract available.

Reference Type BACKGROUND
PMID: 16546650 (View on PubMed)

Casagrande AM. Propofol for office oral and maxillofacial anesthesia: the case against low-dose ketamine. J Oral Maxillofac Surg. 2006 Apr;64(4):693-5. doi: 10.1016/j.joms.2005.11.039. No abstract available.

Reference Type BACKGROUND
PMID: 16546651 (View on PubMed)

Cillo JE Jr. Analysis of propofol and low-dose ketamine admixtures for adult outpatient dentoalveolar surgery: a prospective, randomized, positive-controlled clinical trial. J Oral Maxillofac Surg. 2012 Mar;70(3):537-46. doi: 10.1016/j.joms.2011.08.036. Epub 2011 Dec 16.

Reference Type BACKGROUND
PMID: 22177821 (View on PubMed)

Driscoll EJ, Gelfman SS, Sweet JB, Butler DP, Wirdzck PR, Medlin T. Thrombophlebitis after intravenous use of anesthesia and sedation: its incidence and natural history. J Oral Surg. 1979 Nov;37(11):809-15.

Reference Type BACKGROUND
PMID: 290773 (View on PubMed)

Haas DA, Harper DG. Ketamine: a review of its pharmacologic properties and use in ambulatory anesthesia. Anesth Prog. 1992;39(3):61-8.

Reference Type BACKGROUND
PMID: 1308374 (View on PubMed)

Idvall J, Ahlgren I, Aronsen KR, Stenberg P. Ketamine infusions: pharmacokinetics and clinical effects. Br J Anaesth. 1979 Dec;51(12):1167-73. doi: 10.1093/bja/51.12.1167.

Reference Type BACKGROUND
PMID: 526385 (View on PubMed)

Kramer KJ, Ganzberg S, Prior S, Rashid RG. Comparison of propofol-remifentanil versus propofol-ketamine deep sedation for third molar surgery. Anesth Prog. 2012 Fall;59(3):107-17. doi: 10.2344/12-00001.1.

Reference Type BACKGROUND
PMID: 23050750 (View on PubMed)

Senel AC, Altintas NY, Senel FC, Pampu A, Tosun E, Ungor C, Dayisoylu EH, Tuzuner T. Evaluation of sedation in oral and maxillofacial surgery in ambulatory patients: failure and complications. Oral Surg Oral Med Oral Pathol Oral Radiol. 2012 Nov;114(5):592-6. doi: 10.1016/j.oooo.2012.03.008. Epub 2012 Aug 15.

Reference Type BACKGROUND
PMID: 22901639 (View on PubMed)

Gelfman SS, Gracely RH, Driscoll EJ, Wirdzek PR, Butler DP, Sweet JB. Comparison of recovery tests after intravenous sedation with diazepam-methohexital and diazepam-methohexital and fentanyl. J Oral Surg. 1979 Jun;37(6):391-7.

Reference Type BACKGROUND
PMID: 286027 (View on PubMed)

Gelfman SS, Gracely RH, Driscoll EJ, Butler D, Sweet JB, Wirdzek PR. Recovery following intravenous sedation during dental surgery performed under local anesthesia. Anesth Analg. 1980 Oct;59(10):775-81.

Reference Type BACKGROUND
PMID: 7191651 (View on PubMed)

Lepere AJ, Slack-Smith LM. Average recovery time from a standardized intravenous sedation protocol and standardized discharge criteria in the general dental practice setting. Anesth Prog. 2002 Summer;49(3):77-81.

Reference Type BACKGROUND
PMID: 15384295 (View on PubMed)

Takarada T, Kawahara M, Irifune M, Endo C, Shimizu Y, Maeoka K, Tanaka C, Katayama S. Clinical recovery time from conscious sedation for dental outpatients. Anesth Prog. 2002 Winter;49(4):124-7.

Reference Type BACKGROUND
PMID: 12779113 (View on PubMed)

Becker DE. Pharmacokinetic considerations for moderate and deep sedation. Anesth Prog. 2011 Fall;58(4):166-72; quiz 173. doi: 10.2344/0003-3006-58.4.166.

Reference Type BACKGROUND
PMID: 22168806 (View on PubMed)

Gelfman SS, Gracely RH, Driscoll EJ, Wirdzek PR, Sweet JB, Butler DP. Conscious sedation with intravenous drugs: a study of amnesia. J Oral Surg. 1978 Mar;36(3):191-7.

Reference Type BACKGROUND
PMID: 272450 (View on PubMed)

Miller RI, Bullard DE, Patrissi GA. Duration of amnesia associated with midazolam/fentanyl intravenous sedation. J Oral Maxillofac Surg. 1989 Feb;47(2):155-8. doi: 10.1016/s0278-2391(89)80108-9.

Reference Type BACKGROUND
PMID: 2913250 (View on PubMed)

Bennett J, Peterson T, Burleson JA. Capnography and ventilatory assessment during ambulatory dentoalveolar surgery. J Oral Maxillofac Surg. 1997 Sep;55(9):921-5;discussion 925-6. doi: 10.1016/s0278-2391(97)90058-6.

Reference Type BACKGROUND
PMID: 9294499 (View on PubMed)

Dionne RA, Driscoll EJ, Gelfman SS, Sweet JB, Butler DP, Wirdzek PR. Cardiovascular and respiratory response to intravenous diazepam, fentanyl, and methohexital in dental outpatients. J Oral Surg. 1981 May;39(5):343-9.

Reference Type BACKGROUND
PMID: 6938649 (View on PubMed)

Provided Documents

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Document Type: Informed Consent Form

View Document

Other Identifiers

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2014-3556

Identifier Type: -

Identifier Source: org_study_id

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