Clinical trial NCT03285087: Risk Prediction of Dexmedetomidine-associated Hemodynamic Instability
Official title: Risk Prediction and Consequences of Dexmedetomidine-associated Hemodynamic Instability in Intubated Mechanically Ventilated Intensive Care Unit Patients
Study type: INTERVENTIONAL
Overall status: SUSPENDED
Phase: PHASE2
PHASE3
Conditions: Sedation
Lead sponsor: Assiut University
Sponsor class: OTHER
First posted: 2017-09-15
Enrollment: 250
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: 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.
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Incidence of hemodynamic instability events during dexmedetomidine
timeFrame: 24 hours
Secondary outcomes:
Other outcomes:
Locations:
city: Assiut
country: Egypt
facility: Assiut university main hospital, Trauma ICU
state: Assiut Governorate
Study officials:
affiliation: Professor of anesthesia, faculty of medicine, Assiut university, Egypt
name: Hala S Abdelghaffar, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Professor of anesthesia, faculty of medicine, Assiut university, Assiut, Egypy
name: Hala S Abdelghaffar, MD
role: PRINCIPAL_INVESTIGATOR
References: