Efficacy and safety of early dexmedetomidine during noninvasive ventilation for patients with acute respiratory failure: a randomized, double-blind, placebo-controlled pilot study

Chest. 2014 Jun;145(6):1204-1212. doi: 10.1378/chest.13-1448.

Abstract

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 μg/kg/h titrated every 30 min to 0.7 μg/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 μg, respectively, at a minimum interval of every 3 h.

Results: The dexmedetomidine (n = 16) and placebo (n = 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 = 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 + 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.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Acute Disease
  • Administration, Intravenous
  • Aged
  • Aged, 80 and over
  • Dexmedetomidine / administration & dosage
  • Dexmedetomidine / adverse effects*
  • Dexmedetomidine / therapeutic use*
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Drug Therapy, Combination
  • Female
  • Fentanyl / administration & dosage
  • Fentanyl / therapeutic use
  • Humans
  • Hypnotics and Sedatives / administration & dosage
  • Hypnotics and Sedatives / adverse effects*
  • Hypnotics and Sedatives / therapeutic use*
  • Male
  • Midazolam / administration & dosage
  • Midazolam / therapeutic use
  • Middle Aged
  • Pilot Projects
  • Respiration, Artificial*
  • Respiratory Insufficiency / therapy*
  • Treatment Outcome

Substances

  • Hypnotics and Sedatives
  • Dexmedetomidine
  • Midazolam
  • Fentanyl