Trial reportCritical care medicine2019
Association of Elevated Plasma Interleukin-18 Level With Increased Mortality in a Clinical Trial of Statin Treatment for Acute Respiratory Distress Syndrome.
Trial report in Critical care medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers, 5 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
58 citing papers in PubMed, 5 syntheses or guidelines pooled it, 90 citations in OpenAlex.
- Pooled it
- Statin and outcomes of coronavirus disease 2019 (COVID-19): A systematic review, meta-analysis, and meta-regression.Nutrition, metabolism, and cardiovascular diseases : NMCD · 2021 · on this mapPooled it
- Meta-analysis of Effect of Statins in Patients with COVID-19.The American journal of cardiology · 2020Pooled it
- A systematic review of biomarkers multivariately associated with acute respiratory distress syndrome development and mortality.Critical care (London, England) · 2020Pooled it
- Statin therapy did not improve the in-hospital outcome of coronavirus disease 2019 (COVID-19) infection.Diabetes & metabolic syndrome · on this mapPooled it
- Evaluation of Plasma Biomarkers to Understand the Biology and Heterogeneity of Treatment Effect in Lower Tidal Volume Ventilation Facilitated by Extracorporeal CO2 Removal in Acute Hypoxemic Respiratory Failure: A Secondary Analysis of the REST Trial.Critical care explorations · 2025Trial
- Effect of total cholesterol and statin therapy on mortality in ARDS patients: a secondary analysis of the SAILS and HARP-2 trials.Critical care (London, England) · 2023Trial
- Baseline plasma IL-18 may predict simvastatin treatment response in patients with ARDS: a secondary analysis of the HARP-2 randomised clinical trial.Critical care (London, England) · 2022Trial
- Article
- The NLRP3 inflammasome in physiological and dysfunctional host response in human sepsis and critical illness: a narrative review.Critical care (London, England) · 2026Review
- The Statin Floor Effect: a Mechanistic Framework for Residual Cardiovascular Risk.Cardiovascular drugs and therapy · 2026Review
- Diffuse alveolar damage, acute respiratory distress syndrome (ARDS), and non-cardiogenic pulmonary edema. Part 1: ARDS endotypes, including systemic inflammatory response syndrome and sepsis, with dog and cat examples.Journal of veterinary diagnostic investigation : official publication of the American Association of Veterinary Laboratory Diagnosticians, Inc · 2026Review
- Admission Cytokine Profiling for ICU Mortality Prediction in Heterogeneous Acute Respiratory Failure: An Exploratory Cytokine Profiling Study.Diagnostics (Basel, Switzerland) · 2026Article
- An ancient retrotransposon provides species-specific tuning of IL-18 inflammatory signaling.bioRxiv : the preprint server for biology · 2026Article
- The plasma metabolite-mediated relationship between inflammatory cytokines and acute respiratory distress syndrome.Archives of medical science : AMS · 2026Article
- Exploring lipid-modifying therapies for sepsis through the modulation of circulating inflammatory cytokines: a Mendelian randomization study.World journal of emergency medicine · 2025Article
- Clinical management of sepsis-associated acute respiratory distress syndrome: current evidence and future directions.Frontiers in medicine · 2025Review
- An antibody to IL-1 receptor 7 protects mice from LPS-induced tissue and systemic inflammation.Frontiers in immunology · 2024Article
- Altered Ex Vivo NLRP3 Inflammasome Activation Is Associated with 28-Day Mortality in Septic Patients.Viruses · 2023Article
- Routine statins use is associated with less adverse outcome in patients above 70 years of age admitted to hospital with COVID-19.BMC geriatrics · 2023Article
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Authors and funding
17 authors at 6 institutions in 2 countries.
Funding
Abstract
objectiveA high plasma level of inflammasome mediator interleukin-18 was associated with mortality in observational acute respiratory distress syndrome cohorts. Statin exposure increases both inflammasome activation and lung injury in mouse models. We tested whether randomization to statin therapy correlated with increased interleukin-18 in the ARDS Network Statins for Acutely Injured Lungs from Sepsis trial.
designRetrospective analysis of randomized controlled clinical trial.
settingMulticenter North American clinical trial, the ARDS Network Statins for Acutely Injured Lungs from Sepsis. PATIENTS: Six hundred eighty-three subjects with infection-related acute respiratory distress syndrome, representing 92% of the original trial population.
interventionsRandom assignment of rosuvastatin or placebo for up to 28 days or 3 days after ICU discharge. MEASUREMENTS AND MAIN
resultsWe measured plasma interleukin-18 levels in all Statins for Acutely Injured Lungs from Sepsis patients with sample available at day 0 (baseline, n = 683) and day 3 (after randomization, n = 588). We tested the association among interleukin-18 level at baseline, rising interleukin-18, and the impact of statin therapy on 60-day mortality, adjusting for severity of illness. Baseline plasma interleukin-18 level greater than or equal to 800 pg/mL was highly associated with 60-day mortality, with a hazard of death of 2.3 (95% CI, 1.7-3.1). Rising plasma interleukin-18 was also associated with increased mortality. For each unit increase in log2 (interleukin-18) at day 3 compared with baseline, the hazard of death increased by 2.3 (95% CI, 1.5-3.5). Subjects randomized to statin were significantly more likely to experience a rise in plasma interleukin-18 levels. Subjects with acute kidney injury, shock, low baseline interleukin-18, and those not receiving systemic corticosteroids were more likely to experience rising interleukin-18. Randomization to statin therapy was associated with rising in interleukin-18 in all of those subsets, however.
conclusionsElevated baseline plasma interleukin-18 was associated with higher mortality in sepsis-induced acute respiratory distress syndrome. A rise in plasma interleukin-18 was also associated with increased mortality and was more common in subjects randomized to statin therapy in this clinical trial.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.