Dexmedetomidine Sedation With Third Molar Surgery

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.

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.

Study Overview

• Status: Terminated
• Conditions: Anesthesia
• Intervention / Treatment: Drug: Dexmedetomidine; Drug: Midazolam; Drug: Ketamine

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

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • University of North Carolina School of Dentistry

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 30 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

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
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 Names: Precedex; Drug: Midazolam; Midazolam 0.04 mg/kg i.v. administered after dexmedetomidine loading dose.; Other Names: 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 Names: Precedex; Drug: Midazolam; Midazolam 0.04 mg/kg i.v. administered after dexmedetomidine loading dose.; Other Names: Versed; Drug: Ketamine; Ketamine 0.25 mg/ml administered i.v. following the dexmedetomidine loading dose and the midazolam.; Other Names: Ketalar

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Amnesia: Lack of Picture Recall Shown Prior to Sedation.	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	Day of surgery prior to discharge
Amnesia: Lack of Recall One Day After Surgery of The Picture That Was Shown Prior to Sedation.	Lack of recall of picture shown indicates presence of amnesia the day following surgery.	One day after surgery
Amnesia: Lack of Picture Recall Following Dexmedetomidine Infusion Plus Midazolam.	Percentage of patients unable to recall picture	Day of Surgery prior to discharge
Amnesia: Lack of Recall One Day After Surgery of The Picture That Was Shown Following Dexmedetomidine Infusion Plus Midazolam.	Inability to recall picture shown at this time indicates presence of amnesia on the day following surgery.	One day after surgery
Amnesia: Lack of Picture Recall Shown 15 Minutes Into Surgery	Lack of recall of picture shown at this time indicates presence of amnesia	Day of Surgery prior to discharge
Amnesia: Lack of Recall One Day After Surgery of The Picture That Was Shown 15 Minutes Into Surgery.	Lack of recall of picture demonstrates presence of amnesia on day following surgery	One day after surgery
Amnesia: Lack of Picture Recall Shown 30 Minutes Into Surgery	Lack of recall of picture shown indicates presence of amnesia	Day of Surgery prior to discharge
Primary Title: Amnesia: Lack of Recall One Day After Surgery of The Picture That Was Shown 30 Minutes Into Surgery.	Lack of recall of picture shown indicates presence of amnesia on day following surgery.	One day after surgery
Amnesia: Lack of Picture Recall at Surgery End Time.	Lack of recall of picture shown indicates presence of amnesia	Day of surgery prior to discharge
Amnesia: Lack of Recall One Day After Surgery of The Picture That Was Shown at Surgery End Time.	Lack of recall of picture shown indicates presence of amnesia on day following surgery.	One day after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Respiratory Parameters: Respiratory Rate	Respirations per minute	Immediately prior to sedation
Respiratory Parameters: Respiratory Rate	Rate of respirations	During surgical procedure
Respiratory Parameters: Oxyhemoglobin Saturation	Oxyhemoglobin saturation per pule oximeter	Immediately prior to surgery
Respiratory Parameters: Oxyhemoglobin Saturation	Oxyhemoglobin saturation per pulse oximetry	During surgical procedure
Respiratory Parameters: End-tidal Carbon Dioxide	Measured via capnography at nares	Immediately prior to sedation
Respiratory Parameters: End-tidal Carbon Dioxide	Measured by capnography at nares	Duration of surgery
Mean Arterial Blood Pressure	Blood pressure per automated monitor	Immediately prior to surgery
Mean Arterial Blood Pressure	Measured using automated blood pressure monitor	During duration of surgery
Heart Rate	Heart rate per EKG monitor	Prior to sedation
Heart Rate	Per EKG monitor	Duration of surgery
Surgeon Satisfaction With Sedation Technique	Numerical value on scale of 1-5 from Very dissatisfied (1) to Extremely satisfied (5)	After surgery completed: day of surgery, within 15 minutes
Patient Satisfaction With Sedation Technique	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	after completion of surgery (within 15 minutes)
Ramsey Sedation Scale Score	Rating of depth of sedation by sedationist. Scale 1 - 6, 1 being widw awake and 6 being non-responsive	During surgical procedure
Bispectral Index Score (BIS)	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.	During surgery duration.

Collaborators and Investigators

• Sponsor: University of North Carolina, Chapel Hill
• Investigators: Principal Investigator: Jay A Anderson, DDS, MD, UNC Chapel Hill

Study record dates

Study Major Dates

• Study Start: July 1, 2009
• Primary Completion (Actual): December 1, 2011
• Study Completion (Actual): December 1, 2011

Study Registration Dates

• First Submitted: August 14, 2009
• First Submitted That Met QC Criteria: November 19, 2009
• First Posted (Estimate): November 20, 2009

Study Record Updates

• Last Update Posted (Estimate): June 17, 2013
• Last Update Submitted That Met QC Criteria: May 7, 2013
• Last Verified: April 1, 2012

More Information

Terms related to this study

• Keywords: Dexmedetomidine sedation; Oral surgery sedation; Dexmedetomidine amnesia
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Adrenergic Agents; 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, Non-Narcotic; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Tranquilizing Agents; Psychotropic Drugs; Hypnotics and Sedatives; Adjuvants, Anesthesia; Anti-Anxiety Agents; GABA Modulators; GABA Agents; Ketamine; Midazolam; Dexmedetomidine
• Other Study ID Numbers: 08-2157