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384  |  Acad Emerg Med. 2022;29:384–386.wileyonlinelibrary.com/journal/acem
Received: 5 July 2021  | Revised: 2 August 2021  | Accepted: 5 August 2021
DOI: 10.1111/acem.14368 
T H E B R A S S T A C K S : C O N C I S E R E V I E W S 
O F P U B L I S H E D E V I D E N C E
Dexmedetomidine in critically ill adults requiring noninvasive 
ventilation
Brit Long MD1  | Michael Gottlieb MD2
1Department of Emergency Medicine, Brooke Army Medical Center, Fort Sam Houston, Texas, USA
2Department of Emergency Medicine, Rush University Medical Center, Chicago, Illinois, USA
Correspondence
Brit Long, MD, Brooke Army Medical Center, 3841 Roger Brooke Drive, Fort Sam Houston, TX 78234, USA.
Email: brit.long@yahoo.com
Supervising Editor: Shahriar Zehtabchi, MD.
Keywords: analgesia, critical care, dexmedetomidine, sedation
NNT color recommendation Yellow (unclear if benefits)
Abstract heading Possibly reduces the need 
for intubation, delirium, 
intensive care unit (ICU) 
length of stay, and 
pneumonia but increases 
the risk of bradycardia and 
hypotension
Benefits in NNT 1 in 6 were helped (lower risk of 
intubation)
1 in 6 were helped (lower risk of 
delirium)
1 in 6 were helped (lower risk of 
pneumonia)
Benefits in percentages 
(absolute risk reduction)
17% lower risk of intubation 
requirement
19% lower risk of delirium
2.4 fewer ICU days
17% lower risk of pneumonia
Harms in NNT (NNH) 1 in 4 were harmed (bradycardia)
1 in 5 were harmed 
(hypotension)
Harms in percentages 23% higher risk of bradycardia
18% higher risk of hypotension
Efficacy endpoints Need for intubation, delirium, 
ICU length of stay, 
pneumonia, mortality
Harm endpoints Bradycardia, hypotension
Who was in the studies 738 critically ill patients 
requiring noninvasive 
ventilation
NARR ATIVE
Noninvasive ventilation (NIV) is an effective therapy for hypercap-
nic and hypoxemic respiratory failure and can reduce the need for 
intubation and mechanical ventilation.1 It may also reduce intensive 
care unit (ICU) length of stay, pneumonia, and mortality.2– 6 However, 
NIV can be uncomfortable for patients due to the mask interface 
and respiratory pressures delivered, and over one- third of patients 
placed on NIV will experience agitation.7,8 Intolerance to NIV typi-
cally requires intubation. A variety of interventions can be utilized 
to improve compliance with NIV, including medications such as dex-
medetomidine, an α- 2 agonist with sedative and analgesic effects.9 
Current guidelines recommend the use of a nonbenzodiazepine 
sedative such as propofol or dexmedetomidine in critically ill, me-
chanically ventilated adults, because these medications may reduce 
delirium, ICU length of stay, and duration of mechanical ventila-
tion.10 The systematic review summarized here included randomized 
trials (RCTs) of adults ≥ 18 years admitted to the ICU with acute res-
piratory failure treated with NIV.11 The authors included studies in 
which the intervention group received dexmedetomidine in the ICU 
(any dose, initiation day, route, frequency, formulation, administra-
tion, and duration) and the control group received a different form 
of pharmacologic sedation or placebo. Studies of patients treated 
chronically at home with NIV who were admitted to the ICU, pa-
tients supported with NIV for postextubation respiratory failure, 
and patients with alcohol withdrawal were excluded. Outcomes in-
cluded need for intubation and mechanical ventilation, delirium, ICU 
length of stay, mortality, duration of NIV, pneumonia, bradycardia, 
and hypotension.
The authors of the meta- analysis identified 12 RCTs compris-
ing 738 ICU patients.11 The mean age was 61.5 years and 36% of 
Editor’s Note: Brass Tacks are concise reviews of published evidence. This series is a 
result of collaboration between Academic Emergency Medicine and the evidence- based 
medicine website, www.TheNNT.com. For inquiries please contact the section editor, 
Shahriar Zehtabchi, MD (Shahriar.zehtabchi@downstate.edu). 
© 2021 Society for Academic Emergency Medicine.
mailto:
https://orcid.org/0000-0003-4770-8869
https://orcid.org/0000-0003-3276-8375
mailto:brit.long@yahoo.com
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    | 385DEXMEDETOMIDINE IN CRITICALLY ILL ADULTS REQUIRING NONINVASIVE VENTILATION
patients were women. Four trials included 200 patients with base-
line agitation or delirium. Four trials provided an intravenous (IV) 
loading dose of dexmedetomidine, two trials did not report a load-
ing dose, and six trials used IV infusion only. Most studies used a 
dosing range of 0.2– 0.7 μg/kg/h IV, although three trials used a 
wider range of dosing (0.2– 2 μg/kg/h). Six RCTs used placebo as 
the comparator, while two used haloperidol, three used midazolam, 
one used propofol, and one utilized sedation according to the ICU 
team.
Dexmedetomidine reduced the need for intubation and me-
chanical ventilation (relative risk [RR] = 0.54, 95% confidence in-
terval [CI] = 0.41 to 0.71, absolute risk difference [ARD] = 17%, 
number needed to treat [NNT] = 6; moderate certainty), delirium 
(RR = 0.34, 95% CI = 0.22 to 0.54, ARD = 19%, NNT = 6; moderate 
certainty), ICU length of stay (mean difference [MD] = 2.40 days 
fewer ICU days, 95% CI = 3.51 to 1.29; low certainty), and 
pneumonia (RR = 0.30, 95% CI = 0.17 to 0.52, ARR = 16.7%, 
NNT = 6; moderate certainty). Dexmedetomidine did not impact 
survival (low certainty). However, it increased the risk of brady-
cardia (RR = 2.80, 95% CI = 1.92 to 4.07, ARD = 23%, number 
needed to harm [NNH] = 4; moderate certainty) and hypotension 
(RR = 1.98, 95% CI = 1.32 to 2.98, ARD = 18%, NNH = 5; mod-
erate certainty).11
C AVE ATS
While 12 RCTs were included, not all trials reported all the outcomes. 
In particular, the data pertaining to mortality were limited. The low 
number of patients who died in the ICU resulted in imprecision in 
reporting this outcome. Second, due to the relatively small popula-
tion of 738 patients, results may be associated with a type I or type 
II error due to overestimation or underestimation of the statistical 
significance of the results, respectively. Third, the authors were un-
able to complete analysis of several prespecified outcomes such as 
hypertension and subgroup analyses by age and dose of dexmedeto-
midine due to limited patient- level data. This also limited subgroup 
analyses including patients with and without agitation or delirium 
at the time of enrollment. Fourth, the systematic review was not 
able to generate a funnel plot for publication bias due to the small 
number of trials. Of note, dexmedetomidine was associated with an 
increased risk of bradycardia and hypotension. Overall, bradycardia 
occurred in 78 of 236 patients and hypotension in 75 of 232 patients 
receiving dexmedetomidine. However, treatment for bradycardia 
and hypotension varied significantly in the included studies, includ-
ing decreased dexmedetomidine infusion, vasopressor or inotrope 
infusion, or no intervention, with not all studies reporting treat-
ment for bradycardia and hypotension. Finally, there was significant 
statistical heterogeneity concerning ICU length of stay as well as 
clinical heterogeneity concerning the other outcomes. While the 
other outcomes demonstrated little to no statistical heterogeneity, 
the underlying etiology requiring the use of NIV differed in the in-
cluded studies, raising concerns of significant clinical heterogeneity 
and threatening the validity of the results.
Based on the presented evidence, we have assigned a color rec-
ommendation of yellow (data inadequate) for use of dexmedeto-
midine in critically ill patients undergoing NIV. Further data from 
larger trials are needed to provide a more accurate effect size and 
to evaluate the ideal dosing as well as studies comparing dexmede-
tomidine with other agents. Additional research is also needed to 
assess the effects on important subgroupssuch as patients with 
preexisting delirium or agitation, elderly patients, and those sep-
arated by etiology of acute respiratory failure (e.g., hypoxemic, 
hypercarbic).
CONFLIC T OF INTERE S T
The authors have no potential conflicts to disclose.
ORCID
Brit Long https://orcid.org/0000-0003-4770-8869 
Michael Gottlieb https://orcid.org/0000-0003-3276-8375 
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How to cite this article: Long B, Gottlieb M. Dexmedetomidine 
in critically ill adults requiring noninvasive ventilation. Acad 
Emerg Med. 2022;29:384– 386. https://doi.org/10.1111/
acem.14368
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iley O
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ibrary for rules of use; O
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icense
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https://doi.org/10.1111/acem.14368