Prolonged glucocorticoid treatment is associated with improved ARDS outcomes: analysis of individual patients’ data from four randomized trials and trial-level meta-analysis of the updated literature

Meduri, G. Umberto; Bridges, Lisa J.; Shih, Mei‐Chiung; Marik, Paul E.; Siemieniuk, Reed; Kocak, Mehmet

doi:10.1007/s00134-015-4095-4

Cited by 232 publications

(270 citation statements)

References 40 publications

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“…These data favoured steroid treatment, with a high degree of evidence for the duration of initial assisted breathing and ventilator-free day outcomes, in particular. In the trial-level meta-analysis, glucocorticoid treatment was associated with an increase in mechanical ventilation-free and ICU-free days and with a reduced risk of in-hospital mortality (total mortality risk ratio 0.52, 95% CI 0.33-0.82) [48]. Risk of nosocomial infection did not increase with glucocorticoid treatment.…”

Section: Treatmentmentioning

confidence: 91%

“…No clear differences between early versus late treatment initiation was noted, whereas patients undergoing a rapid tapering of the study drug after the patient achieved unassisted breathing showed a greater risk of returning to mechanical ventilation. Secondary outcomes included mechanical ventilation-free days, ICU-free days, hospital mortality, time to death by hospital discharge or by day 28 and infectious complications [48]. These data favoured steroid treatment, with a high degree of evidence for the duration of initial assisted breathing and ventilator-free day outcomes, in particular.…”

Section: Treatmentmentioning

confidence: 95%

“…MEDURI et al [48] performed a meta-analysis consisting of two sets of analyses. The first was an individual patient data (IPD) analysis [45] of four RCTs which investigated prolonged (⩾7 days) methylprednisolone treatment 1-2 mg·kg −1 ·day −1 in 322 patients (early initiation within 72 h in 118 patients, and later after 5-7 days in 204 patients) with an intention-to-treat methodology.…”

Section: Treatmentmentioning

confidence: 99%

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Acute respiratory distress syndrome

2017

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Since its first description, the acute respiratory distress syndrome (ARDS) has been acknowledged to be a major clinical problem in respiratory medicine. From July 2015 to July 2016 almost 300 indexed articles were published on ARDS. This review summarises only eight of them as an arbitrary overview of clinical relevance: definition and epidemiology, risk factors, prevention and treatment. A strict application of definition criteria is crucial, but the diverse resource-setting scenarios foster geographic variability and contrasting outcome data. A large international multicentre prospective cohort study including 50 countries across five continents reported that ARDS is underdiagnosed, and there is potential for improvement in its management. Furthermore, epidemiological data from low-income countries suggest that a revision of the current definition of ARDS is needed in order to improve its recognition and global clinical outcome. In addition to the well-known risk-factors for ARDS, exposure to high ozone levels and low vitamin D plasma concentrations were found to be predisposing circumstances. Drug-based preventive strategies remain a major challenge, since two recent trials on aspirin and statins failed to reduce the incidence in atrisk patients. A new disease-modifying therapy is awaited: some recent studies promised to improve the prognosis of ARDS, but mortality and disabling complications are still high in survivors in intensive care. Definition and epidemiologySince its first description by ASHBAUGH et al. [1] in 1967, the acute respiratory distress syndrome (ARDS) has been widely recognised as a major clinical problem worldwide, carrying a high morbidity and mortality burden [2][3][4]. Although the recent Berlin definition [5] is probably much better than previous ones, there is still a high variability in both epidemiology and clinical outcomes in diverse healthcare settings [4]. In fact, the incidence of ARDS ranges from 1.5 cases per 100 000 [2] to nearly 79 cases per 100 000 [3], with European countries reporting a lower incidence than USA [6]. Moreover, studies from Brazil reported incidence rates ranging from 1.8 to 31 per 100 000 [7,8].Although the overall survival rate is improving [9,10], there is a notable difference when considering in-hospital mortality over several observational studies [2][3][4][8][9][10][11]. This may be explained by differences in risk factors, availability of diagnostics, ability to recognise ARDS and some selection biases affecting clinical trials [12]. Recently, a large international observational study (the LUNG SAFE trial) evaluated the incidence of ARDS across 459 intensive care units (ICUs) in 50 countries [13]. To assess the clinical recognition of ARDS according to the latest definition, any patient inclusion into the trial was made through a computer algorithm following the Berlin criteria [5], and then compared to the diagnosis made by the attending physicians. Among 4499 patients who developed acute hypoxaemic respiratory failure, ARDS occurred in 1...

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Section: Treatmentmentioning

confidence: 91%

Section: Treatmentmentioning

confidence: 95%

Section: Treatmentmentioning

confidence: 99%

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Acute respiratory distress syndrome

2017

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“…In this context, the current analysis by Meduri et al [5] is welcome. These authors conducted a two-part analysis-(1) individual patient data meta-analysis (IPDMA) from trials with methylprednisolone and (2) an updated trial-level metaanalysis including additional randomised controlled trials (RCTs) with hydrocortisone in early ARDS-and have reported that steroids accelerated the resolution of ARDS, leading to reduced ventilatory assistance, hospital mortality and health care utilisation [5]. However, these conclusions appear to contradict those of the ARDS Network LaSRS study [4], which contributed 56 % of the patients to the IPDMA.…”

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confidence: 86%

Steroids in ARDS: to be or not to be

2015

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“…A recent analysis of individual patient data from four randomized trials combined with a trial-level meta-analysis of the updated literature demonstrated that early and prolonged GC treatment accelerated resolution of ARDS, decreased hospital mortality and healthcare utilization without increasing the risk of infection [11]. The suggested mechanism underlying these beneficial effects is that prolonged treatment with low-dose GC may overcome ARDS-associated deficient GC-GRa activity [12].…”

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confidence: 99%

Steroids are part of rescue therapy in ARDS patients with refractory hypoxemia: yes

2016

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In recent years, three important topics have been frequently addressed in terms of scientific efforts and clinical management of the acute respiratory distress syndrome (ARDS): (1) the demand for a new definition which underlines more precisely the acute character of this syndrome [1], (2) the identification of the typical inflammatory pathways at onset of ARDS resulting in early management recommendations [2], and (3) a 'shift' from mortality as the golden standard of outcome parameter to the health-related quality of life of surviving ARDS patients [3]. The Berlin definition-despite some current critiques-enables a grading of the severity of the syndrome, i.e., severe ARDS means 'acute hypoxemic' and life-threatening, resulting in a high mortality rate. The three major causes of death in ARDS are refractory hypoxemia, multiple organ failure secondary to sepsis or hemodynamic compromise, or ventilator-induced lung injury. It has been shown that early ARDS is characterized by an overshooting systemic and pulmonary inflammatory response within 48 h triggered by various cytokines and inflammatory pathways. Furthermore there is an imbalance between excessive nuclear factor jB (NFjB) activity and deficient glucocorticoid receptor a (GCGRa) inducing resistance or insensitivity of the stressed host to endogenous corticosteroids [4]. As a result patients develop not only systemic inflammation and hemodynamic instability but also pulmonary inflammation and fibroproliferation with subsequent loss in lung function, increased mortality rate, and reduced health-related quality of life in survivors. Failure to repair tissue damage results in an ongoing and self-perpetuating inflammation: lung biopsies demonstrated fibroproliferation in 60 % of ARDS patients [5]. Typical clinical findings include persistent increased levels of inflammatory biomarkers, decreased compliance of the lungs, and reticular densities in radiographic imaging.Consequently, from recent interventional randomized studies we have learned that early therapeutic interventions in ARDS (lung [ultra-]protective strategies, adequate high PEEP, prone positioning) are critical points in setting the direction for survival: the first 48 h present the most vulnerable period in an ARDS's life! The early downregulation of inflammation is essential for reduction of the influx of neutrophils, monocytes, macrophages, and lymphocytes into the lung to restore the lung's homeostasis [6].What is the role of glucocorticoid (GC) therapy in early management of ARDS? Meduri and coworkers have impressively shown that low-dose GC have potent antiinflammatory and antifibroproliferative effects in this specific clinical setting [4]. Furthermore, the expression of high levels of type III procollagen in the immediate Intensive Care Med (2016) 42:918-920

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Prolonged glucocorticoid treatment is associated with improved ARDS outcomes: analysis of individual patients’ data from four randomized trials and trial-level meta-analysis of the updated literature

Abstract: Prolonged methylprednisolone treatment accelerates the resolution of ARDS, improving a broad spectrum of interrelated clinical outcomes and decreasing hospital mortality and healthcare utilization.

Cited by 232 publications

References 40 publications

Acute respiratory distress syndrome

Acute respiratory distress syndrome

Steroids in ARDS: to be or not to be

Steroids are part of rescue therapy in ARDS patients with refractory hypoxemia: yes

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