Efficacy and Safety of Corticosteroids for Persistent Acute Respiratory Distress Syndrome

Steinberg, Kenneth P.; Hudson, Leonard D.; Goodman, Richard B.; Hough, Catherine L.; Lanken, Paul N.; Hyzy, Robert C.; Thompson, B. Taylor; Ancukiewicz, Marek

doi:10.1056/nejmoa051693

Cited by 1,244 publications

(344 citation statements)

References 36 publications

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“…In follow up, the NIH NHLBI ARDS Network conducted a multicenter randomized controlled trial of patients meeting ARDS criteria for at least 7 days, with continuous mechanical ventilation and persistent infiltrates on chest radiograph at study entry 47 . Patients meeting ARDS criteria for longer than 28 days were excluded.…”

Section: Clinical Trials Of Steroids In Prevention and Treatment Of Ardsmentioning

confidence: 99%

“…It has been suggested that tapering methylprednisolone early after liberation from the ventilator led to recrudescence of lung inflammation and fibroproliferation, deteriorating compliance and oxygenation, increased work of breathing, and subsequent need for mechanical ventilation 47,48 . Perhaps a protocol that continued treatment with steroids well beyond liberation from mechanical ventilation would prevent this mechanism of recurrent respiratory failure.…”

Section: Clinical Trials Of Steroids In Prevention and Treatment Of Ardsmentioning

confidence: 99%

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Steroids for Acute Respiratory Distress Syndrome?

Hough

2014

Clinics in Chest Medicine

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The development and severity of ARDS are closely related to dysregulated inflammation, and the duration of ARDS and eventual outcomes are related to persistent inflammation and abnormal fibroproliferation. Corticosteroids are potent modulators of inflammation and inhibitors of fibrosis that have been used since the description of the acute respiratory distress syndrome in attempts to improve outcomes. Randomized controlled trials of steroids for ARDS have answered some, but not all, questions regarding efficacy for prevention and treatment. First, there is no evidence that corticosteroids prevent the development of ARDS among patients at risk. Second, high dose and short course treatment with steroids does not improve the outcomes of patients with ARDS. And third, while there is compelling data that low dose and prolonged treatment with steroids improves pulmonary physiology in patients with ARDS, additional studies are needed to recommend treatment with steroids for ARDS.

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Section: Clinical Trials Of Steroids In Prevention and Treatment Of Ardsmentioning

confidence: 99%

Section: Clinical Trials Of Steroids In Prevention and Treatment Of Ardsmentioning

confidence: 99%

Steroids for Acute Respiratory Distress Syndrome?

Hough

2014

Clinics in Chest Medicine

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“…13–19 Results of a large multicenter trial suggest systemic corticosteroids are biologically active in acute lung injury (ALI) but may have negative systemic effects. 18 Clinical trials of the inhaled corticosteroids (ICS) in ALI are lacking. However, in animal models of ALI, ICS have demonstrated consistent attenuation in surrogate measures of ALI severity.…”

Section: Introductionmentioning

confidence: 99%

Prehospital use of inhaled steroids and incidence of acute lung injury among patients at risk

Festić

Ortiz-Diaz

Lee

et al. 2013

Journal of Critical Care

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Purpose Inhaled corticosteroids (ICS) attenuated lung injury in animal studies. We investigated the association between pre-hospital ICS and incidence of acute lung injury (ALI) among patients at-risk. Methods In this ancillary analysis of the large multicenter Lung Injury Prediction Study (LIPS) cohort, we developed a propensity score for pre-hospital ICS use followed by matching, for all patients and for a subgroup of patients with at least one risk factor for direct pulmonary injury. The primary outcome was ALI, secondary outcomes included ARDS, need for invasive mechanical ventilation and hospital mortality. Results Of the 5126 patients, 401 (8%) were using ICS. ALI developed in 343 (7%). The unadjusted incidence of ALI was 4.7% vs. 6.9% (p=0.12) among those in ICS compared to non-ICS group. In the “direct” lung injury subgroup, the unadjusted incidence of ALI was 4.1% vs. 10.6% (p=0.006). After propensity matching, the estimated effect for ALI in the whole cohort was 0.69 (95% CI 0.39–1.2; p=0.18) and in the “direct” subgroup was 0.56 (95% CI 0.22–1.46; p=0.24). Conclusions Pre-admission use of ICS in a hospitalized population of patients at-risk for ALI was not significantly associated with a lower incidence of ALI once controlled by comprehensive propensity matched analysis.

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“…For example, the use of β2-adrenoceptor agonists or glucocorticoids has shown some efficacy in experimental ALI using rodents 113, 114 , but such agents have failed to show protective results in clinical trials in humans 28, 30, 115 . These observations may suggest the existence of considerable discrepancies in the molecular pathophysiology of experimental ALI in small animals as compared to ALI/ARDS in humans.…”

Section: Expert Opinionmentioning

confidence: 99%

“…Protein-based strategies have tested the administration of recombinant human proteins such as activated protein C (drotrecogin α), granulocyte macrophage colony stimulating factor (GM-CSF) and surfactant protein C based agents to ALI/ARDS patients 24-26 . Additional trials have used methylprednisolone, nitric oxide, β2-adrenergic receptor agonists (albuterol, salbutamol), and antioxidants (N-acetylcysteine) 7, 27-30 . All of these pharmacologic interventions were unable to demonstrate significant clinical efficacy (Table 1).…”

Section: Introducing the Problemmentioning

confidence: 99%

Protein-based therapies for acute lung injury: targeting neutrophil extracellular traps

Bosmann

Ward

2014

Expert Opinion on Therapeutic Targets

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Introduction Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are the acute onset of non-cardiac respiratory insufficiency associated with bilateral lung infiltrations. During the past decade, mechanical ventilation strategies using low tidal volumes have reduced the mortality of ALI/ARDS to around 20-40%. However, ALI/ARDS continues to be a major factor in global burden of diseases, with no pharmacologic agents currently available. Areas covered In this review we discuss several inflammatory proteins involved in the molecular pathogenesis of ALI/ARDS. The complement cleavage product, C5a, is a peptide acting as a potent anaphylatoxin. C5a may trigger the formation of neutrophil extracellular traps (NETs) and release of histone proteins to the extracellular compartment during ALI/ARDS.NETs may activate platelets to release TGFβ which is involved in tissue remodeling during the later phases of ALI/ARDS. Interception of C5a signaling or blockade of extracellular histones has recently shown promising beneficial effects in small animal models of ALI/ARDS. Expert opinion Novel protein-based strategies for the treatment of ALI/ARDS may inspire the hopes of scientists, clinicians and patients. While neutralization of extracellular histones / NETs, C5a and TGFβ is effective in experimental models of ALI/ARDS, controlled clinical trials will be necessary for further evaluation in future.

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Efficacy and Safety of Corticosteroids for Persistent Acute Respiratory Distress Syndrome

Cited by 1,244 publications

References 36 publications

Steroids for Acute Respiratory Distress Syndrome?

Steroids for Acute Respiratory Distress Syndrome?

Prehospital use of inhaled steroids and incidence of acute lung injury among patients at risk

Protein-based therapies for acute lung injury: targeting neutrophil extracellular traps

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