Risk Prediction of Dexmedetomidine-associated Hemodynamic Instability (DEXSEDATION)

Risk Prediction and Consequences of Dexmedetomidine-associated Hemodynamic Instability in Intubated Mechanically Ventilated Intensive Care Unit Patients

Hypotension and bradycardia have been commonly associated with dexmedetomidine therapy, occurring in 13% to 68% and 1% to 42% of patients, respectively. The variability in reported incidence may be partially attributed to inconsistent definitions and study populations. The significance of this hemodynamic instability is not only highlighted by its high incidence but also the need for corrective interventions. In one study, hemodynamic instability requiring clinical intervention occurred in nearly one third of ICU patients receiving dexmedetomidine. Moreover, patients who experienced dexmedetomidine-associated hypotension had a higher mortality rate than those who did not.

Study Overview

• Status: Suspended
• Conditions: Sedation
• Intervention / Treatment: Drug: DEX 0.2 μg/kg/h.

Detailed Description

Dexmedetomidine is specific for the α-2a receptor, especially at lower concentrations, resulting in both vasodilation and a blunting of the sympathetic response. Due to these mechanistic considerations, patients who are dependent upon adrenergic tone to maintain blood pressure are more prone to its' hemodynamic instability. This is especially true in those who are receiving dexmedetomidine in the settings of hypovolemia, traumatic spinal cord injury, or general anesthetic administration. The use of dexmedetomidine in these patient populations may explain the high rate of hypotension reported in a recent study in trauma patients where almost 50% of patients had a spinal cord injury.

Although hemodynamic instability may negatively impact outcomes in the ICU, specific risk factors for the development of clinically significant hemodynamic instability in patients receiving dexmedetomidine are poorly characterized in the current literature. Although previous studies in focused populations have implicated dexmedetomidine dosing strategies, including initial loading infusions and titration frequency, the degree to which alternative patient-specific factors or concurrent interventions impact the risk of hemodynamic instability remains incompletely understood.

The aim of this study will be to determine the risk factors of dexmedetomidine-associated hemodynamic instability in critically ill trauma patients and the effect of this hemodynamic instability on different body systems.

• Study Type: Interventional
• Enrollment (Anticipated): 250
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Egypt
  • Assiut Governorate
    • Assiut, Assiut Governorate, Egypt, 715715
      • Assiut university main hospital, Trauma ICU

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adult patients (18-65 years old)
• admitted to Intensive care units in Assiut university Hospital
• requiring endotracheal intubation, mechanical ventilation and light to moderate sedation
• of an estimated duration not less than 24h.

Exclusion Criteria:

• History of coronary care unit admission.
• Severe traumatic brain injury.
• Low baseline arterial blood pressure defined as SBP <100 mm Hg or mean arterial blood pressure (MAP) <70 mm Hg in the 60 minutes preceding dexmedetomidine initiation.
• Slow baseline heart rate was <70 bpm in the 60 minutes preceding dexmedetomidine initiation.
• Spinal cord injury.
• Patients who have a cardiac pacemaker or automatic implantable cardioverter defibrillator.
• Patients who are admitted with a primary diagnosis of substance withdrawal.
• Pregnant females.
• Patients who are incarcerated.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: DEX 0.2 μg/kg/h; Patients will receive dexmedetomidine for sedation with initial maintenance dose rate of 0.2 μg/kg/h. The dose will be increased in 0.1 μg/kg/h increments to achieve target Richmond Agitation Sedation Scale (RASS) levels of -2 to zero and with a maximum dose of 1.4 μg/kg/h for 24 hours.	Drug: DEX 0.2 μg/kg/h.; DEX 0.2 μg/kg/h. The dose will be increased in 0.1 μg/kg/h increments to achieve target Richmond Agitation Sedation Scale (RASS) levels of -2 to zero and with a maximum dose of 1.4 μg/kg/h for 24 hours.; Other Names: Precedex

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of hemodynamic instability events during dexmedetomidine	The primary end point will be the occurrence of at least 1 episode of clinically significant hemodynamic instability during dexmedetomidine therapy defined as systolic blood pressure (SBP) < 80 mm Hg, diastolic blood pressure (DBP) <50 mm Hg, or heart rate <50 beats per minute (bpm) To qualify as an event, the hemodynamic variable had to remain below the specified threshold for at least 2 consecutive readings (≥30 minutes of recorded hemodynamic instability). The cumulative incidence of hemodynamic instability events during dexmedetomidine sedation will be plotted and Cox proportional hazards models will be constructed to determine hazard ratios (HRs) and 95% confidence intervals (CIs) for the risk factors of hemodynamic instability during dexmedetomidine therapy.	24 hours

Collaborators and Investigators

• Sponsor: Assiut University
• Investigators: Principal Investigator: Hala S Abdelghaffar, MD, Professor of anesthesia, faculty of medicine, Assiut university, Egypt; Principal Investigator: Hala S Abdelghaffar, MD, Professor of anesthesia, faculty of medicine, Assiut university, Assiut, Egypy

Study record dates

Study Major Dates

• Study Start (Anticipated): June 1, 2021
• Primary Completion (Anticipated): August 1, 2022
• Study Completion (Anticipated): August 1, 2022

Study Registration Dates

• First Submitted: September 14, 2017
• First Submitted That Met QC Criteria: September 14, 2017
• First Posted (Actual): September 15, 2017

Study Record Updates

• Last Update Posted (Actual): January 14, 2021
• Last Update Submitted That Met QC Criteria: January 12, 2021
• Last Verified: January 1, 2021

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; Analgesics, Non-Narcotic; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Hypnotics and Sedatives; Dexmedetomidine
• Other Study ID Numbers: 17200062

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