Long-term Dexmedetomidine versus Midazolam in Patients Under Mechanical Ventilation: A Double-blinded Randomized Clinical Trial:

Background: Dexmedetomidine has been approved for short-term analgesia and sedation of patients in the intensive care unit (ICU). Longer duration of sedation with Dexmedetomidine is off-label and its safety has not yet been tested. This study aims to examine the safety profile for long-term use of Dexmedetomidine and compare it to midazolam (MID) based sedation in the ICU. Methods: One hundred and one patients on mechanical ventilation were randomized to receive either Dexmedetomidine 0.2-1.0 µg/kg/h or MID 20- 40 µg/kg/h in a double-blinded fashion to reach the target of -2 to 1 on the Richmond Agitation-Sedation Scale (RASS). Duration of mechanical ventilation was the primary endpoint; secondary endpoints included the occurrences of composite cardiac adverse event (CCAE), bradycardia, hypotension, significant dysrhythmias, heart failure myocardial infarction or death within 28 days, ICU length of stay, need for additive analgesic, time spent at target sedation, and delirium. Results: The duration of mechanical ventilation and ICU stay were almost 2 days shorter in the DEXMEDETOMIDINE group (P= 0.002 and 0.001, respectively), but regarding CCAE, sinus bradycardia occurred more frequently (P= 0.399 ) and mortality was similar in both groups (P=0.378). Conclusion: Our results confirmed the results of previous trials showing that long-term Dexmedetomidine was comparable to benzodiazepines for the frequency of major complications in critically ill patients. Although Dexmedetomidine is capable to reduce the duration of mechanical ventilation and ICU stay, physicians should weigh these benefits against the occurrence of significant bradycardia and hypotension.