Dexmedetomidine Sedation With Third Molar Surgery

• ClinicalTrials.gov Identifier: NCT01017237
• Recruitment Status: Terminated
• First Posted: November 20, 2009
• Results First Posted: June 17, 2013
• Last Update Posted: June 17, 2013
• Sponsor: University of North Carolina, Chapel Hill
• Information provided by (Responsible Party): University of North Carolina, Chapel Hill

Tracking Information

• First Submitted Date: August 14, 2009
• First Posted Date: November 20, 2009
• Results First Submitted Date: January 31, 2013
• Results First Posted Date: June 17, 2013
• Last Update Posted Date: June 17, 2013
• Study Start Date: July 2009
• Actual Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 7, 2013)

• Amnesia: Lack of Picture Recall Shown Prior to Sedation. [ Time Frame: Day of surgery prior to discharge ]
  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 ]
  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 ]
  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 ]
  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 ]
  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 ]
  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 ]
  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 ]
  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 ]
  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 ]
  Lack of recall of picture shown indicates presence of amnesia on day following surgery.

• Original Primary Outcome Measures (submitted: November 19, 2009): Amnesia: recall of pictures shown during sedation, of local anesthetic injections, or of portions of the procedure. [ Time Frame: Recall for: pre-sedation, after dexmedetomidine load (4 minutes), during injections, and surgery (at 15 minute intervals during sedation) and immediately post surgery. Amnesia will be tested just prior to discharge and 24 hours following surgery. ]

Current Secondary Outcome Measures (submitted: May 7, 2013)

• Respiratory Parameters: Respiratory Rate [ Time Frame: Immediately prior to sedation ]
  Respirations per minute
• Respiratory Parameters: Respiratory Rate [ Time Frame: During surgical procedure ]
  Rate of respirations
• Respiratory Parameters: Oxyhemoglobin Saturation [ Time Frame: Immediately prior to surgery ]
  Oxyhemoglobin saturation per pule oximeter
• Respiratory Parameters: Oxyhemoglobin Saturation [ Time Frame: During surgical procedure ]
  Oxyhemoglobin saturation per pulse oximetry
• Respiratory Parameters: End-tidal Carbon Dioxide [ Time Frame: Immediately prior to sedation ]
  Measured via capnography at nares
• Respiratory Parameters: End-tidal Carbon Dioxide [ Time Frame: Duration of surgery ]
  Measured by capnography at nares
• Mean Arterial Blood Pressure [ Time Frame: Immediately prior to surgery ]
  Blood pressure per automated monitor
• Mean Arterial Blood Pressure [ Time Frame: During duration of surgery ]
  Measured using automated blood pressure monitor
• Heart Rate [ Time Frame: Prior to sedation ]
  Heart rate per EKG monitor
• Heart Rate [ Time Frame: Duration of surgery ]
  Per EKG monitor
• Surgeon Satisfaction With Sedation Technique [ Time Frame: After surgery completed: day of surgery, within 15 minutes ]
  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) ]
  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 ]
  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. ]
  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.

Original Secondary Outcome Measures (submitted: November 19, 2009)

• Respiratory Parameters: Respiratory rate, ETCO2, SpO2 [ Time Frame: Continuous. Recorded every 5 minutes or with any significant deviation from normal. ]
• Cardiovascular Parameters: Heart rate, blood pressure and ECG [ Time Frame: Continuous: Recorded at 5 minute intervals as well as any significant deviations from normal recorded. ]
• Surgeon Satisfaction With Sedation Technique [ Time Frame: After surgery completed: day of surgery, within 15 minutes ]
• Patient Satisfaction With Sedation Technique [ Time Frame: after completion of surgery (within 15 minutes) and the day after surgery (24 hours) ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Dexmedetomidine Sedation With Third Molar Surgery
• 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.

Brief Summary

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.

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
• Study Phase: Phase 4
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Anesthesia

Intervention

• 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

Study Arms

• 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.
  Interventions:

  • Drug: Dexmedetomidine
  • Drug: Midazolam
• 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.
  Interventions:

  • Drug: Dexmedetomidine
  • Drug: Midazolam
  • Drug: Ketamine

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: May 7, 2013): 18
• Original Estimated Enrollment (submitted: November 19, 2009): 50
• Actual Study Completion Date: December 2011
• Actual Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)

Eligibility 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 30 Years (Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01017237
• Other Study ID Numbers: 08-2157
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: University of North Carolina, Chapel Hill
• Study Sponsor: University of North Carolina, Chapel Hill
• Collaborators: Not Provided

Investigators

• Principal Investigator: Jay A Anderson, DDS, MD; UNC Chapel Hill

• PRS Account: University of North Carolina, Chapel Hill
• Verification Date: April 2012