The Synergistic Effect of Dexmedetomidine on Propofol for Sedation for Pediatric Endoscopy

The primary aim of this study is to compare the propofol requirements of children who receive propofol with that of children who receive dexmedetomidine prior to propofol, for sedation for upper and lower endoscopic procedures.

Study Overview

• Status: Completed
• Conditions: Anesthesia
• Intervention / Treatment: Drug: Propofol (Group P); Drug: Propofol (Group DP); Drug: Dexmedetomidine

Detailed Description

Both propofol and dexmedetomidine may be used to achieve adequate sedation conditions. Propofol has been described to produce successful conditions for completion of the intended study in almost 99% of the patients. However, in a study that reviewed outcomes when using propofol for almost 50,000 pediatric procedures, propofol was associated with stridor, laryngospasm, airway obstruction, wheezing or central apnea at a rate of 1 in 65 sedations. The need for airway and ventilation interventions which include oral/nasal airway placement, positive pressure mask ventilation and tracheal intubation occurred at a rate of 1 in 70 sedations. Hemodynamic and respiratory fluctuations of a minimum of 30% fluctuations in heart rate, blood pressure or respiratory rate occurred at a rate of 1 in 165 sedations. Another recent study cited similar incidences of hemodynamic variability with propofol as well as inhalational anesthesia in the outpatient pediatric setting.

Until 2015, dexmedetomidine had been one of the standard drugs administered for sedation in children who require radiologic diagnostic imaging studies (MRI, CT and Nuclear Medicine) in the Department of Radiology at Boston Children's Hospital (BCH). Over 17,000 infants, children and developmentally compromised young adults had been sedated with dexmedetomidine in BCH without a cardiac or respiratory arrest, or a need to provide positive pressure assisted ventilation.

This study will determine if administration of dexmedetomidine with propofol administration will result in lower doses of the latter, which may mean safer outcomes in sedation for upper and lower endoscopic procedures.

• Study Type: Interventional
• Enrollment (Actual): 39
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Boston Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 7 years to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Ages 7-18 years who are scheduled for upper or lower endoscopic procedures at Boston Children's Hospital and meets criteria to receive dexmedetomidine or propofol sedation for upper and lower endoscopic procedures
• Provides written consent to participate in the research study
• For females of childbearing age, pregnancy test is negative

Exclusion Criteria:

• Do not meet established sedation criteria
• Refuses administration of study medication prior to sedation
• History of allergy, intolerance, or reaction to dexmedetomidine or propofol or hypersensitivity
• Current, repaired or risk of Moya-Moya disease
• Recent stroke (cerebrovascular accident) within past 6 months
• Uncontrolled hypertension
• Concomitant use of opioids, beta antagonist, alpha 2 agonist or calcium channel blocker
• Egg, soy or lecithin allergy
• BMI greater than 30 or weight above 110th percentile
• Refuses insertion of intravenous catheter while awake
• Currently receiving pharmacologic agents for hypertension or cardiac disease
• Currently receiving or has received digoxin within the past 3 months
• Active, uncontrolled gastroesophageal reflux - an aspiration risk
• Current (or within past 3 months) history of apnea requiring an apnea monitor
• Unstable cardiac status (life threatening arrhythmias, abnormal cardiac anatomy, significant cardiac dysfunction)
• Craniofacial anomaly, which could make it difficult to effectively establish a mask airway for positive pressure ventilation if needed
• Active, current respiratory issues that are different from the baseline status (pneumonia, exacerbation of asthma, bronchiolitis, respiratory syncytial virus)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Propofol (Group P); Propofol only	Drug: Propofol (Group P); Patients in Group P will receive intravenous propofol in bolus increments (2.0 mg/kg bolus over one minute then 0.5 mg/kg bolus q 1 minute titrated to a BIS of 40-50). These patients will be maintained with a continuous intravenous infusion of propofol starting at 200 mcg/kg/min and will be titrated to an endpoint of maintaining a BIS level of 40-50.
Active Comparator: Propofol with Dexmedetomidine (Group DP); Propofol with Dexmedetomidine	Drug: Propofol (Group DP); Patients in Group DP will receive 0.5 mcg/kg DEX administered over 1 minute followed by an infusion of 0.15 mcg/kg/hr. Following the 0.5 mcg/kg DEX bolus, propofol will be administered with the identical protocol (with same endpoint of BIS 40-50) of the P Group. Propofol infusion will be started at 200 mcg/kg/min and will be titrated throughout the procedure to maintain a BIS 40-50. Propofol may be administered prn in 10-20 mg increments for any abrupt patient movement which may compromise the continuity of the procedure.; Drug: Dexmedetomidine; Patients in Group DP will receive 0.5 mcg/kg Dexmedetomidine (DEX) administered over 1 minute followed by an infusion of 0.15 mcg/kg/hr. Following the 0.5 mcg/kg DEX bolus, propofol will be administered with the identical protocol (with same endpoint of Bispectral Index (BIS) 40-50) of the P Group. Propofol infusion will be started at 200 mcg/kg/min and will be titrated throughout the procedure to maintain a BIS 40-50. Propofol may be administered prn in 10-20 mg increments for any abrupt patient movement which may compromise the continuity of the procedure.; Other Names: Precedex

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Propofol Requirements With Pre-treatment of Dexmedetomidine With Children Who do Not Receive Dexmedetomidine.	Compare the total propofol requirements (in mg/kg/min) of children who receive intravenous propofol with pre-treatment of dexmedetomidine with the propofol requirements in children who do not receive dexmedetomidine.	up to 3 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Frequency of Adverse Events and the Need for Airway Interventions	To compare propofol to dexmedetomidine with respect to the frequency of adverse events and the need for airway interventions	1 day
Time Required to Achieve Sedation	To compare propofol to dexmedetomidine with respect to the time required to receive sedation	up to 30 minutes
Time Required to Meet Discharge Criteria From Recovery Room	To compare the propofol-only group to dexmedetomidine-propofol group with respect to the time required to meet discharge criteria from recovery room	up to 4 hours
Adverse Events	To compare the propofol-only group to dexmedetomidine-propofol group with respect to adverse events	3 days
Number of Unplanned Airway Interventions According to the World Society of Intravenous Anaesthesia (SIVA) Adverse Sedation Event Reporting Tool	To compare the propofol-only group to dexmedetomidine-propofol group with respect to the need for unplanned airway interventions	up to 3 hours
Emergence Delirium	To compare the propofol-only group to dexmedetomidine-propofol group with respect to the Pediatric Anesthesia Emergence Delirium (PAED) score. The PAED is a scale that measures emergence delirium in children and adolescence as they wake up from anesthesia. The lowest achievable score is 0 and is consistent with no emergence delirium (best outcome). The highest achievable score is 20 and is consistent with emergence delirium (worse outcome).	up to 4 hours
Time to BIS Score	To compare the propofol-only group to dexmedetomidine-propofol group with respect to time (in minutes) of return of BIS score to baseline (pre-sedation level) in recovery room	up to 6 hours
Duration of Sedation	To compare the propofol-only group to dexmedetomidine-propofol group with respect to the duration of sedation	up to 3 hours

Collaborators and Investigators

• Sponsor: Keira Mason
• Investigators: Principal Investigator: Keira Mason, MD, Boston Children's Hospital

Publications and helpful links

General Publications

• Mason KP, Park RS, Sullivan CA, Lukovits K, Halpin EM, Imbrescia ST, Cavanaugh D, Prescilla R, Fox VL. The synergistic effect of dexmedetomidine on propofol for paediatric deep sedation: A randomised trial. Eur J Anaesthesiol. 2021 May 1;38(5):541-547. doi: 10.1097/EJA.0000000000001350.

Study record dates

Study Major Dates

• Study Start (Actual): May 11, 2018
• Primary Completion (Actual): September 11, 2019
• Study Completion (Actual): September 12, 2019

Study Registration Dates

• First Submitted: March 14, 2016
• First Submitted That Met QC Criteria: October 31, 2016
• First Posted (Estimated): November 2, 2016

Study Record Updates

• Last Update Posted (Actual): May 10, 2024
• Last Update Submitted That Met QC Criteria: May 6, 2024
• Last Verified: May 1, 2024

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: P00020516

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