Propofol and Dexmedetomidine Versus a Propofol Only Regimen for Sedation During Colonoscopy

Comparing Time to Readiness for Discharge After Colonoscopy: Propofol and Dexmedetomidine vs Propofol Only Sedation

An ideal sedative for colonoscopy should have properties that include: rapid onset and offset of action, provide cardiopulmonary stability, have minimal adverse effects, and allow for smooth recovery, and early discharge. Propofol is often used solely because of its rapid onset and short duration of action---a property which is ideal for a fast recovery and early discharge in the ambulatory setting. However, the use of propofol has been associated with undesirable effects such as hypotension, hypoventilation and apnea requiring assisted ventilation.

Balanced anesthesia, using a combination of medications with different mechanisms of action can reduce the total amount of each sedative agent used and minimize their side effects while achieving the desired level of sedation. Dexmedetomidine is one agent that has been used either alone or in combination with propofol for sedation during colonoscopy. While there are many advantages to using dexmedetomidine, there is concern that the use of this agent for sedation during colonoscopy may prolong post-operative recovery time and readiness for discharge home.

No study has definitively assessed whether the use of dexmedetomidine in combination with propofol during ambulatory colonoscopy prolongs post-operative recovery time as determined by the Modified Post Anesthesia Discharge Scoring System (MPADSS).

Study Overview

• Status: Completed
• Conditions: Colonoscopy
• Intervention / Treatment: Drug: Dexmedetomidine; Drug: Propofol; Other: Saline placebo

Detailed Description

In this study, investigators plan to prospectively compare in a randomized, controlled, double-blind trial, the sedation technique for colonoscopy between two groups. Group 1: sedation with dexmedetomidine and propopfol versus group 2: sedation with saline placebo and propofol.

The study will have the following outcome measures for each group.

Primary outcome measure:

Readiness-for-discharge (RFD) at 10, 20 and 30 minutes after the colonoscopic procedure. Ready-for-discharge is defined as attainment of MPADSS score of 9-10.

Secondary outcome measures:

1. Total propofol consumption in mg/kg/duration of procedure in minutes;

2. Side effects:

   1. lowest intraoperative percent (%) drop in mean arterial pressure (MAP) from baseline,
   2. incidence of sustained bradycardic episodes (HR<50 for at least 5 minutes) intraoperatively,
   3. incidence of apneic episodes intraoperatively requiring positive pressure ventilation.

Methods:

One hundred patients will be recruited and randomized into two groups. For sedation, Group 1 will receive intravenous dexmedetomidine 0.3 ug/kg bolused at the onset of the procedure followed by titrated doses of propofol. Group 2 will receive a saline placebo bolus at the onset of the procedure followed by titrated doses of propofol. A hospital research pharmacist, based on a randomization table, will allocate to the anesthesia provider giving the sedation, the bolus syringe labelled dexmedetomidine/or saline study agent. The anesthesia provider, gastroenterologist, nurses as well as the subject will be blinded as to the syringe's actual content. A Bispectral Index (BIS) Monitor will be used during sedation. All subjects will be targeted to maintain a BIS score between 60-70. Outcome measures will be evaluated for statistical significance in a non-inferiority assessment.

Investigators hypothesize that there will be no difference in the time to discharge between the two treatment groups.

• Study Type: Interventional
• Enrollment (Actual): 122
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • New York
    • Brooklyn, New York, United States, 11203
      • SUNY downstate Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• patients scheduled to undergo colonoscopy at SUNY Downstate Medical Center.

Exclusion Criteria:

• < 18 years old
• > 75 years old
• Cognitively Impaired patients (Cognitively impaired patients are excluded from the study because our primary outcome involves a very strict discharge criteria that requires the patient to respond to and perform tasks on our pre-existing discharge scale checklist. These may be impossible to assess or will be difficult to standardize for patients whom are Cognitively Impaired.)
• Pregnant patients
• Patients who use a wheelchair or ambulates with crutches (Patients using a wheelchair are excluded from the study because our primary outcome involves a very strict discharge criteria that requires the patient to respond to and perform tasks on our pre-existing discharge scale checklist. These may be impossible to assess or will be difficult to standardize for patients whom who use a wheel-chair).
• Limited exercise tolerance (as this could represent active coronary disease)
• Total body weight greater than 105 kg (due to maximal dose of drug available in randomized syringes containing study drug)
• Propofol, soy, glycerol or dexmedetomidine allergy
• Significant renal impairment
• Significant hepatic impairment
• Inability to read or write in English

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dexmedetomidine and propofol; Intravenous dexmedetomidine 0.3 ug/kg followed by propofol. Titrated doses of propofol will be given at the discretion of the anesthesiologist based on a target BIS range between 60-70.	Drug: Dexmedetomidine; Dexmedetomidine 0.3 ug/kg intravenous bolus; Other Names: Precedex; Dex; Drug: Propofol; Propofol titrated intravenous boluses; Other Names: Diprivan
Placebo Comparator: Saline placebo and propofol; Intravenous saline placebo followed by propofol. Titrated doses of propofol will be given at the discretion of the anesthesiologist based on a target BIS range between 60-70.	Drug: Propofol; Propofol titrated intravenous boluses; Other Names: Diprivan; Other: Saline placebo; Intravenous saline/placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Subjects Ready for Discharge in Each Group at 30 Minutes Post Procedure	Each subject was assessed for readiness for discharge at 10, 20 and 30 minutes after the procedure, using the Modified Post-Anesthesia Discharge Scoring System (MPADSS). A subject getting an MPADS score of 9-10 is deemed ready for discharge. The percentage of subjects ready for discharge in each group at 10, 20 and 30 minutes will be measured as primary outcome.	30 minutes

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Average Total Propofol Consumption Per Group	Total propofol consumption per subject was measured as μg/kg/min of procedure in minutes. The average propofol consumption in each group will be measured as secondary outcome.	between 7 and 57 minutes (median 19 min)
Number of Participants With Sustained Bradycardic Episodes	Incidence of sustained bradycardic episodes (HR<50 for at least 5 minutes) intraoperatively in each group	30 minutes
Lowest Intraoperative % Change in MAP From Baseline	Lowest intraoperative percent (%) change in mean arterial pressure (MAP) from baseline (average in each group)	30 minutes
Number of Participants With Apneic Episodes Intraoperatively Requiring Positive Pressure Ventilation	Incidence of apneic episodes intraoperatively requiring positive pressure ventilation in each group	30 minutes

Collaborators and Investigators

• Sponsor: State University of New York - Downstate Medical Center
• Investigators: Principal Investigator: Dennis Dimaculangan, MD, SUNY Downstate Medical Center Department of Anesthesiology

Publications and helpful links

General Publications

• Arain SR, Ebert TJ. The efficacy, side effects, and recovery characteristics of dexmedetomidine versus propofol when used for intraoperative sedation. Anesth Analg. 2002 Aug;95(2):461-6, table of contents. doi: 10.1097/00000539-200208000-00042.
• Vicari JJ. Sedation and analgesia. Gastrointest Endosc Clin N Am. 2002 Apr;12(2):297-311, viii. doi: 10.1016/s1052-5157(01)00011-3.
• Faigel DO, Baron TH, Goldstein JL, Hirota WK, Jacobson BC, Johanson JF, Leighton JA, Mallery JS, Peterson KA, Waring JP, Fanelli RD, Wheeler-Harbaugh J; Standards Practice Committe, American Society for Gastrointestinal Endoscopy. Guidelines for the use of deep sedation and anesthesia for GI endoscopy. Gastrointest Endosc. 2002 Nov;56(5):613-7. doi: 10.1016/s0016-5107(02)70104-1. No abstract available.
• Waring JP, Baron TH, Hirota WK, Goldstein JL, Jacobson BC, Leighton JA, Mallery JS, Faigel DO; American Society for Gastrointestinal Endoscopy, Standards of Practice Committee. Guidelines for conscious sedation and monitoring during gastrointestinal endoscopy. Gastrointest Endosc. 2003 Sep;58(3):317-22. doi: 10.1067/s0016-5107(03)00001-4.
• Akarsu Ayazoglu T, Polat E, Bolat C, Yasar NF, Duman U, Akbulut S, Yol S. Comparison of propofol-based sedation regimens administered during colonoscopy. Rev Med Chil. 2013 Apr;141(4):477-85. doi: 10.4067/S0034-98872013000400009.
• Tuncali B, Pekcan YO, Celebi A, Zeyneloglu P. Addition of low-dose ketamine to midazolam-fentanyl-propofol-based sedation for colonoscopy: a randomized, double-blind, controlled trial. J Clin Anesth. 2015 Jun;27(4):301-6. doi: 10.1016/j.jclinane.2015.03.017. Epub 2015 Mar 20.
• Kamibayashi T, Maze M. Clinical uses of alpha2 -adrenergic agonists. Anesthesiology. 2000 Nov;93(5):1345-9. doi: 10.1097/00000542-200011000-00030. No abstract available.
• Taittonen MT, Kirvela OA, Aantaa R, Kanto JH. Effect of clonidine and dexmedetomidine premedication on perioperative oxygen consumption and haemodynamic state. Br J Anaesth. 1997 Apr;78(4):400-6. doi: 10.1093/bja/78.4.400.
• Jalowiecki P, Rudner R, Gonciarz M, Kawecki P, Petelenz M, Dziurdzik P. Sole use of dexmedetomidine has limited utility for conscious sedation during outpatient colonoscopy. Anesthesiology. 2005 Aug;103(2):269-73. doi: 10.1097/00000542-200508000-00009.
• Dere K, Sucullu I, Budak ET, Yeyen S, Filiz AI, Ozkan S, Dagli G. A comparison of dexmedetomidine versus midazolam for sedation, pain and hemodynamic control, during colonoscopy under conscious sedation. Eur J Anaesthesiol. 2010 Jul;27(7):648-52. doi: 10.1097/EJA.0b013e3283347bfe.
• Palumbo P, Tellan G, Perotti B, Pacile MA, Vietri F, Illuminati G. Modified PADSS (Post Anaesthetic Discharge Scoring System) for monitoring outpatients discharge. Ann Ital Chir. 2013 Nov-Dec;84(6):661-5.
• Aldrete JA, Kroulik D. A postanesthetic recovery score. Anesth Analg. 1970 Nov-Dec;49(6):924-34. No abstract available.

Study record dates

Study Major Dates

• Study Start (Actual): May 5, 2017
• Primary Completion (Actual): May 4, 2018
• Study Completion (Actual): July 19, 2018

Study Registration Dates

• First Submitted: April 24, 2017
• First Submitted That Met QC Criteria: May 2, 2017
• First Posted (Actual): May 3, 2017

Study Record Updates

• Last Update Posted (Actual): July 29, 2019
• Last Update Submitted That Met QC Criteria: July 15, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• 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, Intravenous; Anesthetics, General; Anesthetics; Analgesics, Non-Narcotic; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Hypnotics and Sedatives; Propofol; Dexmedetomidine
• Other Study ID Numbers: IRB: 932304

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No