Effect of dexmedetomidine added to standard care on ventilator-free time in patients with agitated delirium

A randomized clinical trial

Michael C. Reade, Glenn M. Eastwood, Rinaldo Bellomo, Michael Bailey, Andrew Bersten, Benjamin Cheung, Andrew Davies, Anthony Delaney, Angaj Ghosh, Frank Van Haren, Nerina Harley, David Knight, Shay McGuiness, John Mulder, Steve O'Donoghue, Nicholas Simpson, Paul Young, DahLIA Investigators, Australian and New Zealand Intensive Care Society Clinical Trials Group

Research output: Contribution to journalArticleResearchpeer-review

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Abstract

IMPORTANCE: Effective therapy has not been established for patients with agitated delirium receiving mechanical ventilation. OBJECTIVE: To determine the effectiveness of dexmedetomidine when added to standard care in patients with agitated delirium receiving mechanical ventilation. DESIGN, SETTING, AND PARTICIPANTS: The Dexmedetomidine to Lessen ICU Agitation (DahLIA) study was a double-blind, placebo-controlled, parallel-group randomized clinical trial involving 74 adult patients in whom extubation was considered inappropriate because of the severity of agitation and delirium. The study was conducted at 15 intensive care units in Australia and New Zealand from May 2011 until December 2013. Patients with advanced dementia or traumatic brain injury were excluded. INTERVENTIONS: Bedside nursing staff administered dexmedetomidine (or placebo) initially at a rate of 0.5 μg/kg/h and then titrated to rates between 0 and 1.5 μg/kg/h to achieve physician-prescribed sedation goals. The study drug or placebo was continued until no longer required or up to 7 days. All other care was at the discretion of the treating physician. MAIN OUTCOMES AND MEASURES: Ventilator-free hours in the 7 days following randomization. There were 21 reported secondary outcomes that were defined a priori. RESULTS: Of the 74 randomized patients (median age, 57 years; 18 [24%] women), 2 withdrew consent later and 1 was found to have been randomized incorrectly, leaving 39 patients in the dexmedetomidine group and 32 patients in the placebo group for analysis. Dexmedetomidine increased ventilator-free hours at 7 days compared with placebo (median, 144.8 hours vs 127.5 hours, respectively; median difference between groups, 17.0 hours [95% CI, 4.0 to 33.2 hours]; P =.01). Among the 21 a priori secondary outcomes, none were significantly worse with dexmedetomidine, and several showed statistically significant benefit, including reduced time to extubation (median, 21.9 hours vs 44.3 hours with placebo; median difference between groups, 19.5 hours [95% CI, 5.3 to 31.1 hours]; P <.001) and accelerated resolution of delirium (median, 23.3 hours vs 40.0 hours; median difference between groups, 16.0 hours [95% CI, 3.0 to 28.0 hours]; P =.01). Using hierarchical Cox modeling to adjust for imbalanced baseline characteristics, allocation to dexmedetomidine was significantly associated with earlier extubation (hazard ratio, 0.47 [95% CI, 0.27-0.82]; P =.007). CONCLUSIONS AND RELEVANCE: Among patients with agitated delirium receiving mechanical ventilation in the intensive care unit, the addition of dexmedetomidine to standard care compared with standard care alone (placebo) resulted in more ventilator-free hours at 7 days. The findings support the use of dexmedetomidine in patients such as these.

Original languageEnglish
Pages (from-to)1460-1468
Number of pages9
JournalJAMA
Volume315
Issue number14
DOIs
Publication statusPublished - 12 Apr 2016

Cite this

Reade, Michael C. ; Eastwood, Glenn M. ; Bellomo, Rinaldo ; Bailey, Michael ; Bersten, Andrew ; Cheung, Benjamin ; Davies, Andrew ; Delaney, Anthony ; Ghosh, Angaj ; Van Haren, Frank ; Harley, Nerina ; Knight, David ; McGuiness, Shay ; Mulder, John ; O'Donoghue, Steve ; Simpson, Nicholas ; Young, Paul ; DahLIA Investigators ; Australian and New Zealand Intensive Care Society Clinical Trials Group. / Effect of dexmedetomidine added to standard care on ventilator-free time in patients with agitated delirium : A randomized clinical trial. In: JAMA. 2016 ; Vol. 315, No. 14. pp. 1460-1468.
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title = "Effect of dexmedetomidine added to standard care on ventilator-free time in patients with agitated delirium: A randomized clinical trial",
abstract = "IMPORTANCE: Effective therapy has not been established for patients with agitated delirium receiving mechanical ventilation. OBJECTIVE: To determine the effectiveness of dexmedetomidine when added to standard care in patients with agitated delirium receiving mechanical ventilation. DESIGN, SETTING, AND PARTICIPANTS: The Dexmedetomidine to Lessen ICU Agitation (DahLIA) study was a double-blind, placebo-controlled, parallel-group randomized clinical trial involving 74 adult patients in whom extubation was considered inappropriate because of the severity of agitation and delirium. The study was conducted at 15 intensive care units in Australia and New Zealand from May 2011 until December 2013. Patients with advanced dementia or traumatic brain injury were excluded. INTERVENTIONS: Bedside nursing staff administered dexmedetomidine (or placebo) initially at a rate of 0.5 μg/kg/h and then titrated to rates between 0 and 1.5 μg/kg/h to achieve physician-prescribed sedation goals. The study drug or placebo was continued until no longer required or up to 7 days. All other care was at the discretion of the treating physician. MAIN OUTCOMES AND MEASURES: Ventilator-free hours in the 7 days following randomization. There were 21 reported secondary outcomes that were defined a priori. RESULTS: Of the 74 randomized patients (median age, 57 years; 18 [24{\%}] women), 2 withdrew consent later and 1 was found to have been randomized incorrectly, leaving 39 patients in the dexmedetomidine group and 32 patients in the placebo group for analysis. Dexmedetomidine increased ventilator-free hours at 7 days compared with placebo (median, 144.8 hours vs 127.5 hours, respectively; median difference between groups, 17.0 hours [95{\%} CI, 4.0 to 33.2 hours]; P =.01). Among the 21 a priori secondary outcomes, none were significantly worse with dexmedetomidine, and several showed statistically significant benefit, including reduced time to extubation (median, 21.9 hours vs 44.3 hours with placebo; median difference between groups, 19.5 hours [95{\%} CI, 5.3 to 31.1 hours]; P <.001) and accelerated resolution of delirium (median, 23.3 hours vs 40.0 hours; median difference between groups, 16.0 hours [95{\%} CI, 3.0 to 28.0 hours]; P =.01). Using hierarchical Cox modeling to adjust for imbalanced baseline characteristics, allocation to dexmedetomidine was significantly associated with earlier extubation (hazard ratio, 0.47 [95{\%} CI, 0.27-0.82]; P =.007). CONCLUSIONS AND RELEVANCE: Among patients with agitated delirium receiving mechanical ventilation in the intensive care unit, the addition of dexmedetomidine to standard care compared with standard care alone (placebo) resulted in more ventilator-free hours at 7 days. The findings support the use of dexmedetomidine in patients such as these.",
author = "Reade, {Michael C.} and Eastwood, {Glenn M.} and Rinaldo Bellomo and Michael Bailey and Andrew Bersten and Benjamin Cheung and Andrew Davies and Anthony Delaney and Angaj Ghosh and {Van Haren}, Frank and Nerina Harley and David Knight and Shay McGuiness and John Mulder and Steve O'Donoghue and Nicholas Simpson and Paul Young and {DahLIA Investigators} and {Australian and New Zealand Intensive Care Society Clinical Trials Group}",
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Reade, MC, Eastwood, GM, Bellomo, R, Bailey, M, Bersten, A, Cheung, B, Davies, A, Delaney, A, Ghosh, A, Van Haren, F, Harley, N, Knight, D, McGuiness, S, Mulder, J, O'Donoghue, S, Simpson, N, Young, P, DahLIA Investigators & Australian and New Zealand Intensive Care Society Clinical Trials Group 2016, 'Effect of dexmedetomidine added to standard care on ventilator-free time in patients with agitated delirium: A randomized clinical trial', JAMA, vol. 315, no. 14, pp. 1460-1468. https://doi.org/10.1001/jama.2016.2707

Effect of dexmedetomidine added to standard care on ventilator-free time in patients with agitated delirium : A randomized clinical trial. / Reade, Michael C.; Eastwood, Glenn M.; Bellomo, Rinaldo; Bailey, Michael; Bersten, Andrew; Cheung, Benjamin; Davies, Andrew; Delaney, Anthony; Ghosh, Angaj; Van Haren, Frank; Harley, Nerina; Knight, David; McGuiness, Shay; Mulder, John; O'Donoghue, Steve; Simpson, Nicholas; Young, Paul; DahLIA Investigators; Australian and New Zealand Intensive Care Society Clinical Trials Group.

In: JAMA, Vol. 315, No. 14, 12.04.2016, p. 1460-1468.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Effect of dexmedetomidine added to standard care on ventilator-free time in patients with agitated delirium

T2 - A randomized clinical trial

AU - Reade, Michael C.

AU - Eastwood, Glenn M.

AU - Bellomo, Rinaldo

AU - Bailey, Michael

AU - Bersten, Andrew

AU - Cheung, Benjamin

AU - Davies, Andrew

AU - Delaney, Anthony

AU - Ghosh, Angaj

AU - Van Haren, Frank

AU - Harley, Nerina

AU - Knight, David

AU - McGuiness, Shay

AU - Mulder, John

AU - O'Donoghue, Steve

AU - Simpson, Nicholas

AU - Young, Paul

AU - DahLIA Investigators

AU - Australian and New Zealand Intensive Care Society Clinical Trials Group

PY - 2016/4/12

Y1 - 2016/4/12

N2 - IMPORTANCE: Effective therapy has not been established for patients with agitated delirium receiving mechanical ventilation. OBJECTIVE: To determine the effectiveness of dexmedetomidine when added to standard care in patients with agitated delirium receiving mechanical ventilation. DESIGN, SETTING, AND PARTICIPANTS: The Dexmedetomidine to Lessen ICU Agitation (DahLIA) study was a double-blind, placebo-controlled, parallel-group randomized clinical trial involving 74 adult patients in whom extubation was considered inappropriate because of the severity of agitation and delirium. The study was conducted at 15 intensive care units in Australia and New Zealand from May 2011 until December 2013. Patients with advanced dementia or traumatic brain injury were excluded. INTERVENTIONS: Bedside nursing staff administered dexmedetomidine (or placebo) initially at a rate of 0.5 μg/kg/h and then titrated to rates between 0 and 1.5 μg/kg/h to achieve physician-prescribed sedation goals. The study drug or placebo was continued until no longer required or up to 7 days. All other care was at the discretion of the treating physician. MAIN OUTCOMES AND MEASURES: Ventilator-free hours in the 7 days following randomization. There were 21 reported secondary outcomes that were defined a priori. RESULTS: Of the 74 randomized patients (median age, 57 years; 18 [24%] women), 2 withdrew consent later and 1 was found to have been randomized incorrectly, leaving 39 patients in the dexmedetomidine group and 32 patients in the placebo group for analysis. Dexmedetomidine increased ventilator-free hours at 7 days compared with placebo (median, 144.8 hours vs 127.5 hours, respectively; median difference between groups, 17.0 hours [95% CI, 4.0 to 33.2 hours]; P =.01). Among the 21 a priori secondary outcomes, none were significantly worse with dexmedetomidine, and several showed statistically significant benefit, including reduced time to extubation (median, 21.9 hours vs 44.3 hours with placebo; median difference between groups, 19.5 hours [95% CI, 5.3 to 31.1 hours]; P <.001) and accelerated resolution of delirium (median, 23.3 hours vs 40.0 hours; median difference between groups, 16.0 hours [95% CI, 3.0 to 28.0 hours]; P =.01). Using hierarchical Cox modeling to adjust for imbalanced baseline characteristics, allocation to dexmedetomidine was significantly associated with earlier extubation (hazard ratio, 0.47 [95% CI, 0.27-0.82]; P =.007). CONCLUSIONS AND RELEVANCE: Among patients with agitated delirium receiving mechanical ventilation in the intensive care unit, the addition of dexmedetomidine to standard care compared with standard care alone (placebo) resulted in more ventilator-free hours at 7 days. The findings support the use of dexmedetomidine in patients such as these.

AB - IMPORTANCE: Effective therapy has not been established for patients with agitated delirium receiving mechanical ventilation. OBJECTIVE: To determine the effectiveness of dexmedetomidine when added to standard care in patients with agitated delirium receiving mechanical ventilation. DESIGN, SETTING, AND PARTICIPANTS: The Dexmedetomidine to Lessen ICU Agitation (DahLIA) study was a double-blind, placebo-controlled, parallel-group randomized clinical trial involving 74 adult patients in whom extubation was considered inappropriate because of the severity of agitation and delirium. The study was conducted at 15 intensive care units in Australia and New Zealand from May 2011 until December 2013. Patients with advanced dementia or traumatic brain injury were excluded. INTERVENTIONS: Bedside nursing staff administered dexmedetomidine (or placebo) initially at a rate of 0.5 μg/kg/h and then titrated to rates between 0 and 1.5 μg/kg/h to achieve physician-prescribed sedation goals. The study drug or placebo was continued until no longer required or up to 7 days. All other care was at the discretion of the treating physician. MAIN OUTCOMES AND MEASURES: Ventilator-free hours in the 7 days following randomization. There were 21 reported secondary outcomes that were defined a priori. RESULTS: Of the 74 randomized patients (median age, 57 years; 18 [24%] women), 2 withdrew consent later and 1 was found to have been randomized incorrectly, leaving 39 patients in the dexmedetomidine group and 32 patients in the placebo group for analysis. Dexmedetomidine increased ventilator-free hours at 7 days compared with placebo (median, 144.8 hours vs 127.5 hours, respectively; median difference between groups, 17.0 hours [95% CI, 4.0 to 33.2 hours]; P =.01). Among the 21 a priori secondary outcomes, none were significantly worse with dexmedetomidine, and several showed statistically significant benefit, including reduced time to extubation (median, 21.9 hours vs 44.3 hours with placebo; median difference between groups, 19.5 hours [95% CI, 5.3 to 31.1 hours]; P <.001) and accelerated resolution of delirium (median, 23.3 hours vs 40.0 hours; median difference between groups, 16.0 hours [95% CI, 3.0 to 28.0 hours]; P =.01). Using hierarchical Cox modeling to adjust for imbalanced baseline characteristics, allocation to dexmedetomidine was significantly associated with earlier extubation (hazard ratio, 0.47 [95% CI, 0.27-0.82]; P =.007). CONCLUSIONS AND RELEVANCE: Among patients with agitated delirium receiving mechanical ventilation in the intensive care unit, the addition of dexmedetomidine to standard care compared with standard care alone (placebo) resulted in more ventilator-free hours at 7 days. The findings support the use of dexmedetomidine in patients such as these.

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