Efficacy and Safety of Early Dexmedetomidine During Noninvasive Ventilation for Patients With Acute Respiratory Failure

Background: Successful application of noninvasive ventilation (NIV) for acute respiratory failure (ARF) requires patient cooperation and comfort. The efficacy and safety of early IV dexmedetomidine when added to protocolized, as-needed IV midazolam and fentanyl remain unclear. Methods: Adults with ARF and within 8 h of starting NIV were randomized to receive IV dexmedetomidine (0.2 mu g/kg/h titrated every 30 min to 0.7 mu g/kg/h to maintain a Sedation-Agitation Scale [SAS] score of 3 to 4) or placebo in a double-blind fashion up to 72 h, until NIV was stopped for > 2 h, or until intubation. Patients with agitation (SAS > 5) or pain (visual analog scale >= 5 of 10 cm) 15 min after each dexmedetomidine and placebo increase could receive IV midazolam 0.5 to 1.0 mg or IV fentanyl 25 to 50 m g, respectively, at a minimum interval of every 3 h. Results: The dexmedetomidine (n 5 16) and placebo (n 5 17) groups were similar at baseline. Use of early dexmedetomidine did not improve NIV tolerance (score, 1 of 4; OR, 1.44; 95% CI, 0.44-4.70; P =.54) nor, vs placebo, led to a greater median (interquartile range) percent time either tolerating NIV (99% [61%-100%] vs 67% [40%-100%], P =.56) or remaining at the desired sedation level (SAS score 5 3 or 4, 100% [86%-100%] vs 100% [100%-100%], P =.28], or fewer intubations (P =.79). Although use of dexmedetomidine was associated with a greater duration of NIV vs placebo (37 [16-72] vs 12 [4-22] h, P =.03), the total ventilation duration (NIV 1 invasive) was similar (3.3 [2-4] days vs 3.8 [2-5] days, P =.52). More patients receiving dexmedetomidine had one or more episodes of deep sedation vs placebo (SAS <= 2, 25% vs 0%, P =.04). Use of midazolam (P =.40) and episodes of either severe bradycardia (heart rate <= 50 beats/min, P =.18) or hypotension (systolic BP <= 90 mm Hg, P =.64) were similar. Conclusions: Initiating dexmedetomidine soon after NIV initiation in patients with ARF neither improves NIV tolerance nor helps to maintain sedation at a desired goal. Randomized, multicenter trials targeting patients with initial intolerance are needed to further elucidate the role for dexmedetomidine in this population.