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.

Status

Terminated

Phases

Phase 4

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01017237

Enrollment

Registered

2009-11-20

Start date

2009-07-31

Completion date

2011-12-31

Last updated

2013-06-17

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Anesthesia

Keywords

Dexmedetomidine sedation, Oral surgery sedation, Dexmedetomidine amnesia

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

Interventions

DRUGDexmedetomidine

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.

DRUGMidazolam

Midazolam 0.04 mg/kg i.v. administered after dexmedetomidine loading dose.

DRUGKetamine

Ketamine 0.25 mg/ml administered i.v. following the dexmedetomidine loading dose and the midazolam.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

18 Years to 30 Years

Healthy volunteers

Yes

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

Design outcomes

Primary

Measure	Time frame	Description
Amnesia: Lack of Recall One Day After Surgery of The Picture That Was Shown at Surgery End Time.	One day after surgery	Lack of recall of picture shown indicates presence of amnesia on day following surgery.
Amnesia: Lack of Picture Recall Shown Prior to Sedation.	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.	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.	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.	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	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.	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	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.	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.	Day of surgery prior to discharge	Lack of recall of picture shown indicates presence of amnesia

Secondary

Measure	Time frame	Description
Respiratory Parameters: Oxyhemoglobin Saturation	Immediately prior to surgery	Oxyhemoglobin saturation per pule oximeter
Respiratory Parameters: End-tidal Carbon Dioxide	Immediately prior to sedation	Measured via capnography at nares
Mean Arterial Blood Pressure	Immediately prior to surgery	Blood pressure per automated monitor
Heart Rate	Prior to sedation	Heart rate per EKG monitor
Surgeon Satisfaction With Sedation Technique	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	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	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)	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.
Respiratory Parameters: Respiratory Rate	Immediately prior to sedation	Respirations per minute

Countries

United States

Participant flow

Recruitment details

Patients requiring extraction of third molars requiring sedation in the Oral Surgery clinic recruited.

Participants by arm

Arm	Count
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. 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. Midazolam : Midazolam 0.04 mg/kg i.v. administered after dexmedetomidine loading dose.	10
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. 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. Midazolam : Midazolam 0.04 mg/kg i.v. administered after dexmedetomidine loading dose. Ketamine : Ketamine 0.25 mg/ml administered i.v. following the dexmedetomidine loading dose and the midazolam.	8
Total	18

Baseline characteristics

Characteristic	Dex Plus Midazolam	Dex Plus Midazolam and Ketamine	Total
Age Continuous	19 years STANDARD_DEVIATION 3.6	20 years STANDARD_DEVIATION 4.1	19 years STANDARD_DEVIATION 3.8
Region of Enrollment United States	10 participants	8 participants	18 participants
Sex: Female, Male Female	7 Participants	5 Participants	12 Participants
Sex: Female, Male Male	3 Participants	3 Participants	6 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	0 / 10	0 / 8
serious Total, serious adverse events	0 / 10	0 / 8

Outcome results

Primary

Amnesia: Lack of Picture Recall at Surgery End Time.

Lack of recall of picture shown indicates presence of amnesia

Time frame: Day of surgery prior to discharge

Population: per protocol

Arm	Measure	Value (NUMBER)
Dexmedetomidine Plus Midazolam	Amnesia: Lack of Picture Recall at Surgery End Time.	83 percentage of patients
Dexmedetomidine Plus Midazolam and Ketamine	Amnesia: Lack of Picture Recall at Surgery End Time.	100 percentage of patients

Primary

Amnesia: Lack of Picture Recall Following Dexmedetomidine Infusion Plus Midazolam.

Percentage of patients unable to recall picture

Time frame: Day of Surgery prior to discharge

Population: Per protocol

Arm	Measure	Value (NUMBER)
Dexmedetomidine Plus Midazolam	Amnesia: Lack of Picture Recall Following Dexmedetomidine Infusion Plus Midazolam.	100 percentage of patients
Dexmedetomidine Plus Midazolam and Ketamine	Amnesia: Lack of Picture Recall Following Dexmedetomidine Infusion Plus Midazolam.	100 percentage of patients

Primary

Amnesia: Lack of Picture Recall Shown 15 Minutes Into Surgery

Lack of recall of picture shown at this time indicates presence of amnesia

Time frame: Day of Surgery prior to discharge

Population: per protocol

Arm	Measure	Value (NUMBER)
Dexmedetomidine Plus Midazolam	Amnesia: Lack of Picture Recall Shown 15 Minutes Into Surgery	100 percentage of patients
Dexmedetomidine Plus Midazolam and Ketamine	Amnesia: Lack of Picture Recall Shown 15 Minutes Into Surgery	100 percentage of patients

Primary

Amnesia: Lack of Picture Recall Shown 30 Minutes Into Surgery

Lack of recall of picture shown indicates presence of amnesia

Time frame: Day of Surgery prior to discharge

Population: per protocol

Arm	Measure	Value (NUMBER)
Dexmedetomidine Plus Midazolam	Amnesia: Lack of Picture Recall Shown 30 Minutes Into Surgery	83 percentage of patients
Dexmedetomidine Plus Midazolam and Ketamine	Amnesia: Lack of Picture Recall Shown 30 Minutes Into Surgery	100 percentage of patients

Primary

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

Time frame: Day of surgery prior to discharge

Population: Randomized per protocol

Arm	Measure	Value (NUMBER)
Dexmedetomidine Plus Midazolam	Amnesia: Lack of Picture Recall Shown Prior to Sedation.	0 percentage of participants
Dexmedetomidine Plus Midazolam and Ketamine	Amnesia: Lack of Picture Recall Shown Prior to Sedation.	0 percentage of participants

Primary