Chest
Volume 145, Issue 6, June 2014, Pages 1204-1212
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Original Research
Efficacy and Safety of Early Dexmedetomidine During Noninvasive Ventilation for Patients With Acute Respiratory Failure: A Randomized, Double-Blind, Placebo-Controlled Pilot Study

https://doi.org/10.1378/chest.13-1448Get rights and content

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.

Trial registry

ClinicalTrials.gov; No: NCT00871624; URL: www.clinicaltrials.gov

Section snippets

Setting

This prospective, randomized, double-blind, placebo-controlled study was conducted at two medical centers: Tufts Medical Center, a 320-bed academic medical center in Boston, Massachusetts, and Winchester Hospital, a 200-bed community hospital in Winchester, Massachusetts. The institutional review boards at each institution approved the study (IRB #8533 and IRB #5-2008, respectively), and written informed consent was obtained from all patients prior to randomization.

Patients

From September 2008 to

Results

Sixty-one patients were evaluated for participation in the study; 25 were excluded, and 36 were randomized (Fig 1). Three patients were withdrawn from the study before dexmedetomidine (or placebo) could be administered because of consent withdrawal (n = 1), emergent intubation (n = 1), and the accidental administration of nonblinded, nonstudy dexmedetomidine (n = 1). Thirty-three patients were, therefore, included in the final intention-to-treat analysis.

Baseline characteristics were similar

Discussion

Unlike other reports that have focused solely on either evaluating the role of dexmedetomidine as treatment of acute agitation during NIV23‐26 or in patients refusing to continue NIV,27 the present randomized, double-blind study sought to determine whether the routine early initiation of dexmedetomidine after the application of NIV would improve NIV tolerance. In a population of patients of which only one-third was intolerant of NIV at baseline, we found that the addition of low-dose IV

Acknowledgments

Author contributions: Dr Devlin had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Dr Devlin: contributed to the study concept, data acquisition and interpretation, and manuscript preparation and final approval.

Dr Al-Qadheeb: contributed to the data acquisition and interpretation and manuscript preparation and final approval.

Dr Chi: contributed to the data acquisition and interpretation and manuscript

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    Part of this article has been presented in abstract form at the American Thoracic Society International Conference, May 17-22, 2013, Philadelphia, PA.

    Funding/Support: This study was supported by an unrestricted investigator-initiated grant from Hospira, Inc.

    Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.

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