One-year outcomes of rosuvastatin versus placebo in sepsis-associated acute respiratory distress syndrome: prospective follow-up of SAILS randomised trial

Victor D Dinglas; Ramona O Hopkins; Amy W Wozniak; Catherine L Hough; Peter E Morris; James C Jackson; Pedro A Mendez-Tellez; O Joseph Bienvenu; E Wesley Ely; Elizabeth Colantuoni; Dale M Needham

doi:10.1136/thoraxjnl-2015-208017

One-year outcomes of rosuvastatin versus placebo in sepsis-associated acute respiratory distress syndrome: prospective follow-up of SAILS randomised trial

Thorax. 2016 May;71(5):401-10. doi: 10.1136/thoraxjnl-2015-208017. Epub 2016 Mar 2.

Authors

Affiliations

¹ Outcomes after Critical Illness and Surgery (OACIS) Group, Johns Hopkins University, Baltimore, Maryland, USA Division of Pulmonary and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
² Pulmonary and Critical Care Division, Department of Medicine, Intermountain Medical Center, Murray, Utah, USA Psychology Department and Neuroscience Center, Brigham Young University, Provo, Utah, USA Center for Humanizing Critical Care, Intermountain Health Care, Murray, Utah, USA.
³ Outcomes after Critical Illness and Surgery (OACIS) Group, Johns Hopkins University, Baltimore, Maryland, USA Department of Biostatistics, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA.
⁴ Division of Pulmonary and Critical Care Medicine, Harborview Medical Center, University of Washington, Seattle, Washington, USA.
⁵ Division of Pulmonary, Critical Care & Sleep Medicine, University of Kentucky, Lexington, Kentucky, USA.
⁶ Division of Allergy, Pulmonary, and Critical Care Medicine, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
⁷ Outcomes after Critical Illness and Surgery (OACIS) Group, Johns Hopkins University, Baltimore, Maryland, USA Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
⁸ Outcomes after Critical Illness and Surgery (OACIS) Group, Johns Hopkins University, Baltimore, Maryland, USA Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
⁹ Division of Allergy, Pulmonary, and Critical Care Medicine, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, USA Geriatric Research, Education and Clinical Center Service, Department of Veterans Affairs Medical Center, Tennessee Valley Healthcare System, Nashville, Tennessee, USA.
¹⁰ Outcomes after Critical Illness and Surgery (OACIS) Group, Johns Hopkins University, Baltimore, Maryland, USA Division of Pulmonary and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA Department of Physical Medicine and Rehabilitation, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

Abstract

Background: Prior randomised trials have evaluated statins in patients with sepsis and acute respiratory distress syndrome (ARDS), but there has been no comprehensive evaluation of long-term effects, despite potential neuromuscular and mental health adverse effects of these drugs.

Aim: To evaluate the effect of rosuvastatin versus placebo on survival, physical function and performance, and mental health outcomes in patients with sepsis-associated ARDS.

Methods: Prospective follow-up evaluation of the ARDS Clinical Trials Network Statins for Acutely Injured Lungs from Sepsis trial of rosuvastatin versus placebo in 568 mechanically ventilated patients with sepsis-associated ARDS, with blinded 6-month outcome assessment performed in the 272 eligible survivors for age-adjusted and sex-adjusted 36-Item Short Form Health Survey (SF-36) physical function and mental health domains, and in 84 eligible survivors for the 6 min walk test, along with secondary outcomes evaluations of survival, and additional patient-reported and performance-based measures at 6-month and 12-month follow-up.

Results: Over 1-year follow-up, there was no significant difference in cumulative survival in the rosuvastatin versus placebo groups (58% vs 61%; p=0.377), with survivors demonstrating substantial impairments in physical function and mental health. Rosuvastatin versus placebo had no effect (mean treatment effect (95% CI)) on SF-36 physical function (0 (-7 to 8), p=0.939) or mental health (-6 (-12 to 1) p=0.085) domains, 6 min walk distance (per cent predicted: 2 (-9 to 14), p=0.679) or the vast majority of secondary outcomes.

Conclusions: Over 1-year follow-up, patients with sepsis-associated ARDS had high cumulative mortality, with survivors commonly experiencing impairments in physical functioning and performance, and mental health. Randomisation to rosuvastatin had no effect on these outcomes.

Trial registration number: NCT00979121 and NCT00719446.

Keywords: ARDS.

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Publication types

Multicenter Study
Randomized Controlled Trial
Research Support, N.I.H., Extramural

MeSH terms

Body Mass Index
Diabetes Complications / complications
Exercise Test*
Female
Follow-Up Studies
Humans
Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use*
Kaplan-Meier Estimate
Male
Middle Aged
Prospective Studies
Quality of Life
Respiratory Distress Syndrome / complications*
Respiratory Distress Syndrome / drug therapy*
Respiratory Distress Syndrome / mortality
Risk Factors
Rosuvastatin Calcium / therapeutic use*
Sepsis / complications*
Single-Blind Method
Treatment Outcome
United States
Walking

One-year outcomes of rosuvastatin versus placebo in sepsis-associated acute respiratory distress syndrome: prospective follow-up of SAILS randomised trial

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Abstract

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