ArticleIntensive care medicine2008
Risk of death does not alter the efficacy of hydrocortisone therapy in a mouse E. coli pneumonia model: risk and corticosteroids in sepsis.
Article in Intensive care medicine, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 3 of them syntheses that pooled it.
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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.
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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.
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Who cites it
19 citing papers in PubMed, 3 syntheses or guidelines pooled it, 39 citations in OpenAlex.
- Corticosteroids in the treatment of community-acquired pneumonia in adults: a meta-analysis.PloS one · 2012Pooled it
- The effect of heparin administration in animal models of sepsis: a prospective study in Escherichia coli-challenged mice and a systematic review and metaregression analysis of published studies.Critical care medicine · 2011Pooled it
- The effects of steroids during sepsis depend on dose and severity of illness: an updated meta-analysis.Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases · 2009Pooled it
- S100A8/9-NLRP3-mediated chronic unresolved inflammation drives cardiac pathologies following invasive pneumococcal disease.Experimental & molecular medicine · 2025Article
- Glucocorticoid therapy in respiratory illness: bench to bedside.Journal of investigative medicine : the official publication of the American Federation for Clinical Research · 2022Review
- Effects of Glucocorticoid Therapy on Sepsis Depend Both on the Dose of Steroids and on the Severity and Phase of the Animal Sepsis Model.Life (Basel, Switzerland) · 2022Article
- Diet-Induced Obesity Mice Execute Pulmonary Cell Apoptosis via Death Receptor and ER-Stress Pathways afterOxidative medicine and cellular longevity · 2020Article
- General Adaptation in Critical Illness: Glucocorticoid Receptor-alpha Master Regulator of Homeostatic Corrections.Frontiers in endocrinology · 2020Review
- Nonantibiotic Adjunctive Therapies for Community-Acquired Pneumonia (Corticosteroids and Beyond): Where Are We with Them?Seminars in respiratory and critical care medicine · 2016Review
- Is prolonged low-dose glucocorticoid treatment beneficial in community-acquired pneumonia?Current infectious disease reports · 2013Article
- Beneficial effects of stress-dose corticosteroid therapy in canines depend on the severity of staphylococcal pneumonia.Intensive care medicine · 2012Article
- The evolving experience with therapeutic TNF inhibition in sepsis: considering the potential influence of risk of death.Expert opinion on investigational drugs · 2011Review
- Low-dose steroids for septic shock and severe sepsis: the use of Bayesian statistics to resolve clinical trial controversies.Intensive care medicine · 2011Review
- SB203580, a p38 inhibitor, improved cardiac function but worsened lung injury and survival during Escherichia coli pneumonia in mice.The Journal of trauma · 2010Article
- Magic bullets and surrogate biomarkers circa 2009.Critical care medicine · 2009Article
- Stratification is the key: inflammatory biomarkers accurately direct immunomodulatory therapy in experimental sepsis.Critical care medicine · 2009Article
- Year in review in Intensive Care Medicine, 2008: II. Experimental, acute respiratory failure and ARDS, mechanical ventilation and endotracheal intubation.Intensive care medicine · 2009Review
- Adjunctive therapies in severe sepsis and septic shock: current place of steroids.Current infectious disease reports · 2008Article
- Corticosteroids for community-acquired pneumonia: time to act!Critical care (London, England) · 2008Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 3 countries.
Funding
Abstract
backgroundRisk of death may influence the efficacy of anti-inflammatory agents in sepsis. "Physiologic" dose corticosteroids, while improving survival in earlier trials with higher control mortality rates (>50%), were not beneficial in the recent CORTICUS trial with lower control mortality (31%). We investigated whether risk of death altered the effects of hydrocortisone in a mouse pneumonia model.
methodsMice (n=637) challenged with high, medium or low intratracheal E. coli doses were randomized to receive one of three hydrocortisone doses (5, 25 or 125 mg/kg) or normal saline (NS) only (control) for 4 days. All animals were treated with similar volumes of ceftriaxone and NS support following E. coli and were observed for 168 h.
resultsDecreasing E. coli doses reduced control mortality rates (from 94 to 12%). In similar patterns (not significant) each hydrocortisone dose increased the odds ratio (OR) of survival (95% confidence interval) with each E. coli dose (ORs ranging from 1.2 [0.4, 3.7] to 6.1 [0.6, 61.0]). The effect of hydrocortisone on the OR was not related to control mortality rate (r=-0.13, p=0.29) and overall was highly significant (2.04 [1.37, 3.03], p=0.0004). In randomly selected animals 48 h after the highest E. coli dose, compared with the control, hydrocortisone (125 mg/kg) significantly decreased IL-6, INFgamma, and nitric oxide levels.
conclusionsIn this mouse model the beneficial effects of hydrocortisone were independent of risk of death. These findings suggest that factors other than risk of death may underlie the differing effects of corticosteroids in recent sepsis trials.
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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.