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Evaluation of early administration of simvastatin in the prevention and treatment of delirium in critically ill patients undergoing mechanical ventilation (MoDUS): a randomised, double-blind, placebo-controlled trial. / Page, Valerie; Casarin, Annalisa; Ely, E.W; Zhao, Xiao B.; McDowell, Cliona; Murphy, Lynn ; McAuley , Daniel F. .

In: The Lancet Respiratory Medicine, Vol. 5, No. 9, 19.07.2017, p. 727-737.

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@article{0365af5a661f406b8f66760349e22cc7,
title = "Evaluation of early administration of simvastatin in the prevention and treatment of delirium in critically ill patients undergoing mechanical ventilation (MoDUS):: a randomised, double-blind, placebo-controlled trial",
abstract = "SummaryBackgroundDelirium in critically ill patients is associated with poor clinical outcomes. Neuroinflammation might be an important mechanism in the pathogenesis of delirium, and since simvastatin has anti-inflammatory properties it might reduce delirium. We aimed to establish whether early treatment with simvastatin would decrease the time that survivors of critical illness spent in delirium or coma.MethodsWe undertook this randomised, double-blind, placebo-controlled trial in a general adult intensive care unit (ICU) in Watford General Hospital (Watford, UK). We enrolled critically ill patients (≥18 years) needing mechanical ventilation within 72 h of admission. We randomly assigned patients (1:1 ratio) to receive either simvastatin 80 mg or placebo daily for up to a maximum of 28 days, irrespective of coma or delirium status. We assessed delirium using the Confusion Assessment Method for the ICU (CAM-ICU). The primary outcome was number of days alive and was assessed as delirium-free and coma-free in the first 14 days after being randomly allocated to receive treatment or placebo. ICU clinical and research staff and patients were masked to treatment. We did intention-to-treat analyses with no extrapolation. This trial is registered with the International Standard Randomised Controlled Trial Registry, number ISRCTN89079989.FindingsBetween Feb 1, 2013, and July 29, 2016, 142 patients were randomly assigned to receive simvastatin (n=71) or placebo (n=71), and were included in the final analysis. The mean number of days alive without delirium and without coma at day 14 did not differ significantly between the two groups (5·7 days [SD 5·1] with simvastatin and 6·1 days [5·2] with placebo; mean difference 0·4 days, 95% CI −1·3 to 2·1; p=0·66). The most common adverse event was an elevated creatine kinase concentration to more than ten times the upper limit of normal (eight [11%] in the simvastatin group vs three [4%] in the placebo group p=0·208). No patient had a serious adverse event related to the study drug.InterpretationThese results do not support the hypothesis that simvastatin modifies duration of delirium and coma in critically ill patients.FundingNational Institute for Health Research.",
author = "Valerie Page and Annalisa Casarin and E.W Ely and Zhao, {Xiao B.} and Cliona McDowell and Lynn Murphy and McAuley, {Daniel F.}",
note = "This document is the Accepted Manuscript version of the following article: Valerie J. Page, et al, {\textquoteleft}Evaluation of early administration of simvastatin in the prevention and treatment of delirium in critically ill patients undergoing mechanical ventilation (MoDUS): a randomised, double-blind, placebo-controlled trial{\textquoteright}, The Lancet Respiratory Medicine, Vol. 5 (9): 727-737, September 2017. Under embargo until 19 July 2018. The final, definitive version is available online at doi: https://doi.org/10.1016/S2213-2600(17)30234-5. ",
year = "2017",
month = jul,
day = "19",
doi = "10.1016/S2213-2600(17)30234-5",
language = "English",
volume = "5",
pages = "727--737",
journal = "The Lancet Respiratory Medicine",
issn = "2213-2600",
publisher = "Elsevier Ltd",
number = "9",

}

RIS

TY - JOUR

T1 - Evaluation of early administration of simvastatin in the prevention and treatment of delirium in critically ill patients undergoing mechanical ventilation (MoDUS):

T2 - a randomised, double-blind, placebo-controlled trial

AU - Page, Valerie

AU - Casarin, Annalisa

AU - Ely, E.W

AU - Zhao, Xiao B.

AU - McDowell, Cliona

AU - Murphy, Lynn

AU - McAuley , Daniel F.

N1 - This document is the Accepted Manuscript version of the following article: Valerie J. Page, et al, ‘Evaluation of early administration of simvastatin in the prevention and treatment of delirium in critically ill patients undergoing mechanical ventilation (MoDUS): a randomised, double-blind, placebo-controlled trial’, The Lancet Respiratory Medicine, Vol. 5 (9): 727-737, September 2017. Under embargo until 19 July 2018. The final, definitive version is available online at doi: https://doi.org/10.1016/S2213-2600(17)30234-5.

PY - 2017/7/19

Y1 - 2017/7/19

N2 - SummaryBackgroundDelirium in critically ill patients is associated with poor clinical outcomes. Neuroinflammation might be an important mechanism in the pathogenesis of delirium, and since simvastatin has anti-inflammatory properties it might reduce delirium. We aimed to establish whether early treatment with simvastatin would decrease the time that survivors of critical illness spent in delirium or coma.MethodsWe undertook this randomised, double-blind, placebo-controlled trial in a general adult intensive care unit (ICU) in Watford General Hospital (Watford, UK). We enrolled critically ill patients (≥18 years) needing mechanical ventilation within 72 h of admission. We randomly assigned patients (1:1 ratio) to receive either simvastatin 80 mg or placebo daily for up to a maximum of 28 days, irrespective of coma or delirium status. We assessed delirium using the Confusion Assessment Method for the ICU (CAM-ICU). The primary outcome was number of days alive and was assessed as delirium-free and coma-free in the first 14 days after being randomly allocated to receive treatment or placebo. ICU clinical and research staff and patients were masked to treatment. We did intention-to-treat analyses with no extrapolation. This trial is registered with the International Standard Randomised Controlled Trial Registry, number ISRCTN89079989.FindingsBetween Feb 1, 2013, and July 29, 2016, 142 patients were randomly assigned to receive simvastatin (n=71) or placebo (n=71), and were included in the final analysis. The mean number of days alive without delirium and without coma at day 14 did not differ significantly between the two groups (5·7 days [SD 5·1] with simvastatin and 6·1 days [5·2] with placebo; mean difference 0·4 days, 95% CI −1·3 to 2·1; p=0·66). The most common adverse event was an elevated creatine kinase concentration to more than ten times the upper limit of normal (eight [11%] in the simvastatin group vs three [4%] in the placebo group p=0·208). No patient had a serious adverse event related to the study drug.InterpretationThese results do not support the hypothesis that simvastatin modifies duration of delirium and coma in critically ill patients.FundingNational Institute for Health Research.

AB - SummaryBackgroundDelirium in critically ill patients is associated with poor clinical outcomes. Neuroinflammation might be an important mechanism in the pathogenesis of delirium, and since simvastatin has anti-inflammatory properties it might reduce delirium. We aimed to establish whether early treatment with simvastatin would decrease the time that survivors of critical illness spent in delirium or coma.MethodsWe undertook this randomised, double-blind, placebo-controlled trial in a general adult intensive care unit (ICU) in Watford General Hospital (Watford, UK). We enrolled critically ill patients (≥18 years) needing mechanical ventilation within 72 h of admission. We randomly assigned patients (1:1 ratio) to receive either simvastatin 80 mg or placebo daily for up to a maximum of 28 days, irrespective of coma or delirium status. We assessed delirium using the Confusion Assessment Method for the ICU (CAM-ICU). The primary outcome was number of days alive and was assessed as delirium-free and coma-free in the first 14 days after being randomly allocated to receive treatment or placebo. ICU clinical and research staff and patients were masked to treatment. We did intention-to-treat analyses with no extrapolation. This trial is registered with the International Standard Randomised Controlled Trial Registry, number ISRCTN89079989.FindingsBetween Feb 1, 2013, and July 29, 2016, 142 patients were randomly assigned to receive simvastatin (n=71) or placebo (n=71), and were included in the final analysis. The mean number of days alive without delirium and without coma at day 14 did not differ significantly between the two groups (5·7 days [SD 5·1] with simvastatin and 6·1 days [5·2] with placebo; mean difference 0·4 days, 95% CI −1·3 to 2·1; p=0·66). The most common adverse event was an elevated creatine kinase concentration to more than ten times the upper limit of normal (eight [11%] in the simvastatin group vs three [4%] in the placebo group p=0·208). No patient had a serious adverse event related to the study drug.InterpretationThese results do not support the hypothesis that simvastatin modifies duration of delirium and coma in critically ill patients.FundingNational Institute for Health Research.

U2 - 10.1016/S2213-2600(17)30234-5

DO - 10.1016/S2213-2600(17)30234-5

M3 - Article

VL - 5

SP - 727

EP - 737

JO - The Lancet Respiratory Medicine

JF - The Lancet Respiratory Medicine

SN - 2213-2600

IS - 9

ER -