Early sedation with dexmedetomidine in critically ill patients

Yahya Shehabi, Belinda D. Howe, Rinaldo Bellomo, Yaseen M. Arabi, Michael Bailey, Frances E. Bass, Suhaini Bin Kadiman, Colin J. McArthur, Lynnette Murray, Michael C. Reade, Ian M. Seppelt, Jukka Takala, Matt P. Wise, Steven A. Webb

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Abstract

BACKGROUND: Dexmedetomidine produces sedation while maintaining a degree of arousability and may reduce the duration of mechanical ventilation and delirium among patients in the intensive care unit (ICU). The use of dexmedetomidine as the sole or primary sedative agent in patients undergoing mechanical ventilation has not been extensively studied. METHODS: In an open-label, randomized trial, we enrolled critically ill adults who had been undergoing ventilation for less than 12 hours in the ICU and were expected to continue to receive ventilatory support for longer than the next calendar day to receive dexmedetomidine as the sole or primary sedative or to receive usual care (propofol, midazolam, or other sedatives). The target range of sedation-scores on the Richmond Agitation and Sedation Scale (which is scored from −5 [unresponsive] to +4 [combative]) was −2 to +1 (lightly sedated to restless). The primary outcome was the rate of death from any cause at 90 days. RESULTS: We enrolled 4000 patients at a median interval of 4.6 hours between eligibility and randomization. In a modified intention-to-treat analysis involving 3904 patients, the primary outcome event occurred in 566 of 1948 (29.1%) in the dexmedetomidine group and in 569 of 1956 (29.1%) in the usual-care group (adjusted risk difference, 0.0 percentage points; 95% confidence interval, −2.9 to 2.8). An ancillary finding was that to achieve the prescribed level of sedation, patients in the dexmedetomidine group received supplemental propofol (64% of patients), midazolam (3%), or both (7%) during the first 2 days after randomization; in the usual-care group, these drugs were administered as primary sedatives in 60%, 12%, and 20% of the patients, respectively. Bradycardia and hypotension were more common in the dexmedetomidine group. CONCLUSIONS: Among patients undergoing mechanical ventilation in the ICU, those who received early dexmedetomidine for sedation had a rate of death at 90 days similar to that in the usual-care group and required supplemental sedatives to achieve the prescribed level of sedation. More adverse events were reported in the dexmedetomidine group than in the usual-care group.

Original languageEnglish
Pages (from-to)2506-2517
Number of pages12
JournalNew England Journal of Medicine
Volume380
Issue number26
DOIs
Publication statusPublished - 27 Jun 2019

Cite this

Shehabi, Yahya ; Howe, Belinda D. ; Bellomo, Rinaldo ; Arabi, Yaseen M. ; Bailey, Michael ; Bass, Frances E. ; Bin Kadiman, Suhaini ; McArthur, Colin J. ; Murray, Lynnette ; Reade, Michael C. ; Seppelt, Ian M. ; Takala, Jukka ; Wise, Matt P. ; Webb, Steven A. / Early sedation with dexmedetomidine in critically ill patients. In: New England Journal of Medicine. 2019 ; Vol. 380, No. 26. pp. 2506-2517.
@article{76199b87963a41b789d0f0080e244ee0,
title = "Early sedation with dexmedetomidine in critically ill patients",
abstract = "BACKGROUND: Dexmedetomidine produces sedation while maintaining a degree of arousability and may reduce the duration of mechanical ventilation and delirium among patients in the intensive care unit (ICU). The use of dexmedetomidine as the sole or primary sedative agent in patients undergoing mechanical ventilation has not been extensively studied. METHODS: In an open-label, randomized trial, we enrolled critically ill adults who had been undergoing ventilation for less than 12 hours in the ICU and were expected to continue to receive ventilatory support for longer than the next calendar day to receive dexmedetomidine as the sole or primary sedative or to receive usual care (propofol, midazolam, or other sedatives). The target range of sedation-scores on the Richmond Agitation and Sedation Scale (which is scored from −5 [unresponsive] to +4 [combative]) was −2 to +1 (lightly sedated to restless). The primary outcome was the rate of death from any cause at 90 days. RESULTS: We enrolled 4000 patients at a median interval of 4.6 hours between eligibility and randomization. In a modified intention-to-treat analysis involving 3904 patients, the primary outcome event occurred in 566 of 1948 (29.1{\%}) in the dexmedetomidine group and in 569 of 1956 (29.1{\%}) in the usual-care group (adjusted risk difference, 0.0 percentage points; 95{\%} confidence interval, −2.9 to 2.8). An ancillary finding was that to achieve the prescribed level of sedation, patients in the dexmedetomidine group received supplemental propofol (64{\%} of patients), midazolam (3{\%}), or both (7{\%}) during the first 2 days after randomization; in the usual-care group, these drugs were administered as primary sedatives in 60{\%}, 12{\%}, and 20{\%} of the patients, respectively. Bradycardia and hypotension were more common in the dexmedetomidine group. CONCLUSIONS: Among patients undergoing mechanical ventilation in the ICU, those who received early dexmedetomidine for sedation had a rate of death at 90 days similar to that in the usual-care group and required supplemental sedatives to achieve the prescribed level of sedation. More adverse events were reported in the dexmedetomidine group than in the usual-care group.",
author = "Yahya Shehabi and Howe, {Belinda D.} and Rinaldo Bellomo and Arabi, {Yaseen M.} and Michael Bailey and Bass, {Frances E.} and {Bin Kadiman}, Suhaini and McArthur, {Colin J.} and Lynnette Murray and Reade, {Michael C.} and Seppelt, {Ian M.} and Jukka Takala and Wise, {Matt P.} and Webb, {Steven A.}",
year = "2019",
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language = "English",
volume = "380",
pages = "2506--2517",
journal = "New England Journal of Medicine",
issn = "0028-4793",
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number = "26",

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Early sedation with dexmedetomidine in critically ill patients. / Shehabi, Yahya; Howe, Belinda D.; Bellomo, Rinaldo; Arabi, Yaseen M.; Bailey, Michael; Bass, Frances E.; Bin Kadiman, Suhaini; McArthur, Colin J.; Murray, Lynnette; Reade, Michael C.; Seppelt, Ian M.; Takala, Jukka; Wise, Matt P.; Webb, Steven A.

In: New England Journal of Medicine, Vol. 380, No. 26, 27.06.2019, p. 2506-2517.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Early sedation with dexmedetomidine in critically ill patients

AU - Shehabi, Yahya

AU - Howe, Belinda D.

AU - Bellomo, Rinaldo

AU - Arabi, Yaseen M.

AU - Bailey, Michael

AU - Bass, Frances E.

AU - Bin Kadiman, Suhaini

AU - McArthur, Colin J.

AU - Murray, Lynnette

AU - Reade, Michael C.

AU - Seppelt, Ian M.

AU - Takala, Jukka

AU - Wise, Matt P.

AU - Webb, Steven A.

PY - 2019/6/27

Y1 - 2019/6/27

N2 - BACKGROUND: Dexmedetomidine produces sedation while maintaining a degree of arousability and may reduce the duration of mechanical ventilation and delirium among patients in the intensive care unit (ICU). The use of dexmedetomidine as the sole or primary sedative agent in patients undergoing mechanical ventilation has not been extensively studied. METHODS: In an open-label, randomized trial, we enrolled critically ill adults who had been undergoing ventilation for less than 12 hours in the ICU and were expected to continue to receive ventilatory support for longer than the next calendar day to receive dexmedetomidine as the sole or primary sedative or to receive usual care (propofol, midazolam, or other sedatives). The target range of sedation-scores on the Richmond Agitation and Sedation Scale (which is scored from −5 [unresponsive] to +4 [combative]) was −2 to +1 (lightly sedated to restless). The primary outcome was the rate of death from any cause at 90 days. RESULTS: We enrolled 4000 patients at a median interval of 4.6 hours between eligibility and randomization. In a modified intention-to-treat analysis involving 3904 patients, the primary outcome event occurred in 566 of 1948 (29.1%) in the dexmedetomidine group and in 569 of 1956 (29.1%) in the usual-care group (adjusted risk difference, 0.0 percentage points; 95% confidence interval, −2.9 to 2.8). An ancillary finding was that to achieve the prescribed level of sedation, patients in the dexmedetomidine group received supplemental propofol (64% of patients), midazolam (3%), or both (7%) during the first 2 days after randomization; in the usual-care group, these drugs were administered as primary sedatives in 60%, 12%, and 20% of the patients, respectively. Bradycardia and hypotension were more common in the dexmedetomidine group. CONCLUSIONS: Among patients undergoing mechanical ventilation in the ICU, those who received early dexmedetomidine for sedation had a rate of death at 90 days similar to that in the usual-care group and required supplemental sedatives to achieve the prescribed level of sedation. More adverse events were reported in the dexmedetomidine group than in the usual-care group.

AB - BACKGROUND: Dexmedetomidine produces sedation while maintaining a degree of arousability and may reduce the duration of mechanical ventilation and delirium among patients in the intensive care unit (ICU). The use of dexmedetomidine as the sole or primary sedative agent in patients undergoing mechanical ventilation has not been extensively studied. METHODS: In an open-label, randomized trial, we enrolled critically ill adults who had been undergoing ventilation for less than 12 hours in the ICU and were expected to continue to receive ventilatory support for longer than the next calendar day to receive dexmedetomidine as the sole or primary sedative or to receive usual care (propofol, midazolam, or other sedatives). The target range of sedation-scores on the Richmond Agitation and Sedation Scale (which is scored from −5 [unresponsive] to +4 [combative]) was −2 to +1 (lightly sedated to restless). The primary outcome was the rate of death from any cause at 90 days. RESULTS: We enrolled 4000 patients at a median interval of 4.6 hours between eligibility and randomization. In a modified intention-to-treat analysis involving 3904 patients, the primary outcome event occurred in 566 of 1948 (29.1%) in the dexmedetomidine group and in 569 of 1956 (29.1%) in the usual-care group (adjusted risk difference, 0.0 percentage points; 95% confidence interval, −2.9 to 2.8). An ancillary finding was that to achieve the prescribed level of sedation, patients in the dexmedetomidine group received supplemental propofol (64% of patients), midazolam (3%), or both (7%) during the first 2 days after randomization; in the usual-care group, these drugs were administered as primary sedatives in 60%, 12%, and 20% of the patients, respectively. Bradycardia and hypotension were more common in the dexmedetomidine group. CONCLUSIONS: Among patients undergoing mechanical ventilation in the ICU, those who received early dexmedetomidine for sedation had a rate of death at 90 days similar to that in the usual-care group and required supplemental sedatives to achieve the prescribed level of sedation. More adverse events were reported in the dexmedetomidine group than in the usual-care group.

UR - http://www.scopus.com/inward/record.url?scp=85068214170&partnerID=8YFLogxK

U2 - 10.1056/NEJMoa1904710

DO - 10.1056/NEJMoa1904710

M3 - Article

VL - 380

SP - 2506

EP - 2517

JO - New England Journal of Medicine

JF - New England Journal of Medicine

SN - 0028-4793

IS - 26

ER -