Dexmedetomidine Sedation With Third Molar Surgery

This study has been terminated.
(Protocol proved to be ineffective for adequate sedation for third molar surgery.)
Sponsor:
Information provided by (Responsible Party):
University of North Carolina, Chapel Hill
ClinicalTrials.gov Identifier:
NCT01017237
First received: August 14, 2009
Last updated: May 7, 2013
Last verified: April 2012
  Purpose

Intravenous sedation is used frequently for the relief of pain and anxiety associated with oral surgical procedures performed under local anesthesia. The purpose of this study is to learn about patient and surgeon satisfaction with sedation using Dexmedetomidine in combination with midazolam alone or with midazolam plus low dose ketamine while having wisdom teeth removed.

The sedation produced by dexmedetomidine is unique in that it mimics natural sleep, a unique quality not shared by other drugs. Dexmedetomidine is often used in anesthesia in hospital operating rooms and has been approved by the US Food and Drug Administration for the use planned in this study.


Condition Intervention Phase
Anesthesia
Drug: Dexmedetomidine
Drug: Midazolam
Drug: Ketamine
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Comparison of the Effectiveness of Sedation With i.v. Dexmedetomidine in Combination With Midazolam Alone or Midazolam and Low Dose Ketamine for Extraction of Third Molars.

Resource links provided by NLM:


Further study details as provided by University of North Carolina, Chapel Hill:

Primary Outcome Measures:
  • Amnesia: Lack of Picture Recall Shown Prior to Sedation. [ Time Frame: Day of surgery prior to discharge ] [ Designated as safety issue: No ]
    Subjects were shown pictures of familiar objects prior to sedation, after the bolus dose of dexmedetomidine was administered, at 15 minutes and 30 minutes into the surgery and at the end of surgery. Subjects were shown a page containing multiple pictures to evaluate whether they could remember any of them. No recall demonstrating the presence of amnesia during that portion of the procedure. This process was repeated the day following surgery

  • Amnesia: Lack of Recall One Day After Surgery of The Picture That Was Shown Prior to Sedation. [ Time Frame: One day after surgery ] [ Designated as safety issue: No ]
    Lack of recall of picture shown indicates presence of amnesia the day following surgery.

  • Amnesia: Lack of Picture Recall Following Dexmedetomidine Infusion Plus Midazolam. [ Time Frame: Day of Surgery prior to discharge ] [ Designated as safety issue: No ]
    Percentage of patients unable to recall picture

  • Amnesia: Lack of Recall One Day After Surgery of The Picture That Was Shown Following Dexmedetomidine Infusion Plus Midazolam. [ Time Frame: One day after surgery ] [ Designated as safety issue: No ]
    Inability to recall picture shown at this time indicates presence of amnesia on the day following surgery.

  • Amnesia: Lack of Picture Recall Shown 15 Minutes Into Surgery [ Time Frame: Day of Surgery prior to discharge ] [ Designated as safety issue: No ]
    Lack of recall of picture shown at this time indicates presence of amnesia

  • Amnesia: Lack of Recall One Day After Surgery of The Picture That Was Shown 15 Minutes Into Surgery. [ Time Frame: One day after surgery ] [ Designated as safety issue: No ]
    Lack of recall of picture demonstrates presence of amnesia on day following surgery

  • Amnesia: Lack of Picture Recall Shown 30 Minutes Into Surgery [ Time Frame: Day of Surgery prior to discharge ] [ Designated as safety issue: No ]
    Lack of recall of picture shown indicates presence of amnesia

  • Primary Title: Amnesia: Lack of Recall One Day After Surgery of The Picture That Was Shown 30 Minutes Into Surgery. [ Time Frame: One day after surgery ] [ Designated as safety issue: No ]
    Lack of recall of picture shown indicates presence of amnesia on day following surgery.

  • Amnesia: Lack of Picture Recall at Surgery End Time. [ Time Frame: Day of surgery prior to discharge ] [ Designated as safety issue: No ]
    Lack of recall of picture shown indicates presence of amnesia

  • Amnesia: Lack of Recall One Day After Surgery of The Picture That Was Shown at Surgery End Time. [ Time Frame: One day after surgery ] [ Designated as safety issue: No ]
    Lack of recall of picture shown indicates presence of amnesia on day following surgery.


Secondary Outcome Measures:
  • Respiratory Parameters: Respiratory Rate [ Time Frame: Immediately prior to sedation ] [ Designated as safety issue: Yes ]
    Respirations per minute

  • Respiratory Parameters: Respiratory Rate [ Time Frame: During surgical procedure ] [ Designated as safety issue: Yes ]
    Rate of respirations

  • Respiratory Parameters: Oxyhemoglobin Saturation [ Time Frame: Immediately prior to surgery ] [ Designated as safety issue: Yes ]
    Oxyhemoglobin saturation per pule oximeter

  • Respiratory Parameters: Oxyhemoglobin Saturation [ Time Frame: During surgical procedure ] [ Designated as safety issue: Yes ]
    Oxyhemoglobin saturation per pulse oximetry

  • Respiratory Parameters: End-tidal Carbon Dioxide [ Time Frame: Immediately prior to sedation ] [ Designated as safety issue: Yes ]
    Measured via capnography at nares

  • Respiratory Parameters: End-tidal Carbon Dioxide [ Time Frame: Duration of surgery ] [ Designated as safety issue: Yes ]
    Measured by capnography at nares

  • Mean Arterial Blood Pressure [ Time Frame: Immediately prior to surgery ] [ Designated as safety issue: Yes ]
    Blood pressure per automated monitor

  • Mean Arterial Blood Pressure [ Time Frame: During duration of surgery ] [ Designated as safety issue: Yes ]
    Measured using automated blood pressure monitor

  • Heart Rate [ Time Frame: Prior to sedation ] [ Designated as safety issue: Yes ]
    Heart rate per EKG monitor

  • Heart Rate [ Time Frame: Duration of surgery ] [ Designated as safety issue: Yes ]
    Per EKG monitor

  • Surgeon Satisfaction With Sedation Technique [ Time Frame: After surgery completed: day of surgery, within 15 minutes ] [ Designated as safety issue: No ]
    Numerical value on scale of 1-5 from Very dissatisfied (1) to Extremely satisfied (5)

  • Patient Satisfaction With Sedation Technique [ Time Frame: after completion of surgery (within 15 minutes) ] [ Designated as safety issue: No ]
    Rating of how satisfied the patient was with their sedation on a scale of 1-5 with 1 being very dissatisfied and 5 being extremely satisfied

  • Ramsey Sedation Scale Score [ Time Frame: During surgical procedure ] [ Designated as safety issue: No ]
    Rating of depth of sedation by sedationist. Scale 1 - 6, 1 being widw awake and 6 being non-responsive

  • Bispectral Index Score (BIS) [ Time Frame: During surgery duration. ] [ Designated as safety issue: No ]
    Bispectral Index (BIS) measures level of consciousness by algorithmic analysis of the patient's electroencephalogram (EEG) during anesthesia and sedation. The BIS can range from 0 (equivalent to EEG silence) to 100 (equivalent to fully awake and alert). A BIS value of 40-60 indicates an adequate general anesthesia state.


Enrollment: 18
Study Start Date: July 2009
Study Completion Date: December 2011
Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Dex plus midazolam
Dexmedetomidine loading dose of 0.4 mcg/kg followed by an infusion of 0.5 mcg/kg/hr plus midazolam 0.04 mg/kg i.v.
Drug: Dexmedetomidine
Dexmedetomidine will be infused at a rate of 6 mcg/kg/hr for four minutes; resulting in a loading dose of 0.4 mcg/kg, Followed by an infusion of 0.5 mcg/kg/hr will be initiated and continued until the completion of surgery.
Other Name: Precedex
Drug: Midazolam
Midazolam 0.04 mg/kg i.v. administered after dexmedetomidine loading dose.
Other Name: Versed
Active Comparator: Dex plus midazolam and ketamine
Dexmedetomidine loading dose of 0.4 mcg/kg followed by an infusion of 0.5 mcg/kg/hr plus midazolam 0.04 mg/kg and 0.25 mg/kg ketamine i.v.
Drug: Dexmedetomidine
Dexmedetomidine will be infused at a rate of 6 mcg/kg/hr for four minutes; resulting in a loading dose of 0.4 mcg/kg, Followed by an infusion of 0.5 mcg/kg/hr will be initiated and continued until the completion of surgery.
Other Name: Precedex
Drug: Midazolam
Midazolam 0.04 mg/kg i.v. administered after dexmedetomidine loading dose.
Other Name: Versed
Drug: Ketamine
Ketamine 0.25 mg/ml administered i.v. following the dexmedetomidine loading dose and the midazolam.
Other Name: Ketalar

Detailed Description:

Subjects who have been screened medically and are scheduled for third molar surgery in the University of North Carolina (UNC)Oral and Maxillofacial Surgery (OMFS) clinic will be asked to volunteer for the study by the evaluating OMFS resident or attending physician. No additional x-rays will be taken other than those usually indicated for 3rd molar surgery. Informed consent will be obtained by study investigators.

Subjects will be instructed to fast for at least 8 hours prior to their appointment. Surgery will be performed in the Oral & Maxillofacial Surgery operating/sedation clinic where all monitoring equipment as well as emergency equipment is readily available, including the ability to ventilate the patient with oxygen (bag-mask), the ability to intubate, resuscitation drugs and equipment including a defibrillator. Patients will be positioned in a semi-reclining position in the dental chair and all monitors applied. A 20 gauge i.v. catheter will be placed and normal saline infusion attached. Supplemental oxygen will be administered via nasal cannula at 3 liters per minute. A picture will then be shown for recall testing. Pulse rate, arterial oxygen saturation (SpO2), respiratory rate, blood pressure, end-tidal CO2 (ETCO2), Ramsey Sedation Score (RSS sedation score) and Bispectral Index Scale (BIS) value will be recorded as a baseline and at 5 minute intervals during the procedure. Any SpO2 values below 90% as well as any episodes of apnea greater than 20 seconds will be recorded. Monitoring and recording of all data will be done by one of the investigators. Data will be recorded on pre-printed data forms. The surgical procedure will be performed by an oral and maxillofacial surgery resident physician.

Following the administration of 0.12 mg/kg of dexamethasone , dexmedetomidine will be infused at a rate of 6 mcg/kg/hr for four minutes; resulting in a loading dose of 0.4 mcg/kg. All of the above parameters will again be obtained and recorded. Patients will be randomly assigned by block randomization to receive either midazolam 0.04 mg/kg i.v. (50 patients), or midazolam 0.04 mg/kg plus 0.25 mg/kg of ketamine (50 patients). The operating surgeon and the patient will be blinded as to which protocol is being used. A dexmedetomidine infusion of 0.5 mcg/kg/hr will be initiated and continued until the completion of surgery. At this point local anesthesia will be administered in all four quadrants. Pain reaction during injections will be recorded. When efficacy of local anesthesia has been confirmed, surgery will commence. The surgery will be interrupted at 15 and 30 minutes to show a picture for recall testing by an investigator. If at any point the patient is deemed to be uncomfortable or uncooperative due to inadequate sedation, the protocol will be broken and additional sedation administered as per usual standards. The rescue therapy may include additional midazolam, ketamine, narcotic or propofol at the discretion of the anesthetist/sedationist. At the conclusion of surgery the dexmedetomidine infusion will be discontinued and the patient will be attended by a recovery nurse for collection of postoperative data. During recovery the physiologic parameters will be recorded at 10 minute intervals. When the patient achieves a recovery Aldrete score of >9, they will be asked by an investigator to recall pictures for amnesia assessment, and asked to assess patient satisfaction before leaving with an escort. The patient will be contacted on the day following surgery by phone or e-mail by one of the investigators to test for recall of pictures shown (amnesia testing) and patient satisfaction

  Eligibility

Ages Eligible for Study:   18 Years to 30 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • American Society of Anesthesiology (ASA) physical status I and II
  • Four asymptomatic third molars indicated for removal

Exclusion Criteria:

  • Clinical history or ECG evidence of:

    • cardiac dysrhythmia or heart block
    • ischemic heart disease
    • asthma
    • sleep apnea
    • impaired liver, renal, or mental function
  • chronic sedative or analgesic use
  • allergies to any of the study drugs
  • history of pericoronal infection with third molars
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01017237

Locations
United States, North Carolina
University of North Carolina School of Dentistry
Chapel Hill, North Carolina, United States, 27599
Sponsors and Collaborators
University of North Carolina, Chapel Hill
Investigators
Principal Investigator: Jay A Anderson, DDS, MD UNC Chapel Hill
  More Information

No publications provided

Responsible Party: University of North Carolina, Chapel Hill
ClinicalTrials.gov Identifier: NCT01017237     History of Changes
Other Study ID Numbers: 08-2157
Study First Received: August 14, 2009
Results First Received: January 31, 2013
Last Updated: May 7, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by University of North Carolina, Chapel Hill:
Dexmedetomidine sedation
Oral surgery sedation
Dexmedetomidine amnesia

Additional relevant MeSH terms:
Dexmedetomidine
Ketamine
Midazolam
Adjuvants, Anesthesia
Adrenergic Agents
Adrenergic Agonists
Adrenergic alpha-2 Receptor Agonists
Adrenergic alpha-Agonists
Analgesics
Analgesics, Non-Narcotic
Anesthetics
Anesthetics, Dissociative
Anesthetics, General
Anesthetics, Intravenous
Anti-Anxiety Agents
Central Nervous System Agents
Central Nervous System Depressants
Excitatory Amino Acid Agents
Excitatory Amino Acid Antagonists
GABA Agents
GABA Modulators
Hypnotics and Sedatives
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Psychotropic Drugs
Sensory System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014