title: Efficacy and safety of early dexmedetomidine during noninvasive ventilation for patients with acute respiratory failure: a randomized, double-blind, placebo-controlled pilot study.
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.
authors.affiliation: School of Pharmacy, Northeastern University; Division of Pulmonary, Critical Care and Sleep Medicine. Electronic address: j.devlin@neu.edu.
authors.forename: John W
authors.initials: JW
authors.lastname: Devlin
authors.affiliation: School of Pharmacy, Northeastern University.
authors.forename: Nada S
authors.initials: NS
authors.lastname: Al-Qadheeb
authors.affiliation: Division of Pulmonary, Critical Care and Sleep Medicine.
authors.forename: Amy
authors.initials: A
authors.lastname: Chi
authors.affiliation: Department of Pharmacy, Tufts Medical Center, Boston, MA.
authors.forename: Russel J
authors.initials: RJ
authors.lastname: Roberts
authors.affiliation: Division of Pulmonary, Critical Care and Sleep Medicine.
authors.forename: Imrana
authors.initials: I
authors.lastname: Qawi
authors.affiliation: Division of Pulmonary, Critical Care and Sleep Medicine.
authors.forename: Erik
authors.initials: E
authors.lastname: Garpestad
authors.affiliation: Division of Pulmonary, Critical Care and Sleep Medicine.
authors.forename: Nicholas S
authors.initials: NS
authors.lastname: Hill
mesh_terms: D000208:Acute Disease; D061605:Administration, Intravenous; D000368:Aged; D000369:Aged, 80 and over; D020927:Dexmedetomidine / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005283:Fentanyl / Q000008:administration & dosage / Q000627:therapeutic use; D006801:Humans; D006993:Hypnotics and Sedatives / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use*; D008297:Male; D008874:Midazolam / Q000008:administration & dosage / Q000627:therapeutic use; D008875:Middle Aged; D010865:Pilot Projects; D012121:Respiration, Artificial; D012131:Respiratory Insufficiency / Q000628:therapy*; D016896:Treatment Outcome
chemical_list: D006993:Hypnotics and Sedatives; D020927:Dexmedetomidine; D008874:Midazolam; D005283:Fentanyl