Early Methylprednisolone Treatment for Septic Syndrome and the Adult Respiratory Distress Syndrome

Bone, Roger C.; Fisher, Charles J.; Clemmer, Terry P.; Slotman, Gus J.; Metz, Craig A.

doi:10.1378/chest.92.6.1032

Cited by 338 publications

(141 citation statements)

References 7 publications

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“…Ventilation with low tidal volumes has dramatically improved the survival in ARDS, in part by reducing stretch-induced epithelial and endothelial cell damage and the release of inflammatory mediators. Although lung-protective ventilation works in part by reducing lung inflammation, inhibition of inflammatory pathways with anti-inflammatory agents, such as steroids, has failed to demonstrate reliable improvement in outcomes [112][113][114][115]. In a small trial of steroids in late-stage ARDS, there was improvement in mortality [116].…”

Section: Five-year Viewmentioning

confidence: 99%

“…The growing field of genomics may allow us to identify individuals who are at risk for developing ALI, and understanding these individual risk factors may further elucidate the complex pathobiology of ALI and allow new molecular targets to be discovered. [112][113][114][115]. In a small trial of steroids in late-stage ARDS, there was improvement in mortality [116].…”

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confidence: 99%

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Role of the pulmonary epithelium and inflammatory signals in acute lung injury

Manicone¹

2009

Expert Review of Clinical Immunology

109

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Acute lung injury (ALI) is a clinical disease marked by respiratory failure due to disruption of the epithelial and endothelial barrier, flooding of the alveolar compartment with protein-rich fluid and recruitment of neutrophils into the alveolar space. ALI affects approximately 200,000 patients annually in the USA and results in approximately 75,000 deaths. It is associated with prolonged mechanical ventilation, intensive medical care, high morbidity and mortality, and rising healthcare costs. Owing to its impact on public health, great strides have been made towards understanding the pathobiology of ALI to affect outcome. This review will focus on the role of the epithelial cell in the pathogenesis and resolution of ALI and the role of various inflammatory mediators in ALI. Keywordsβ2-agonist; acute lung injury; acute respiratory distress syndrome; chemokine; cytokine; epithelial cell; inflammation; methylprednisolone; neutrophil; salbutamol; steroid; ventilator-induced lung injuryAcute lung injury/acute respiratory distress syndrome (ALI/ARDS) was first described in 1967 by Ashbaugh and colleagues in a group of 12 patients who shared a constellation of clinical symptoms including acute respiratory distress, hypoxemia refractory to supplemental oxygen, decreased lung compliance and diffuse pulmonary infiltrates [1]. Since this first description, the clinical criteria have evolved to include acute onset of respiratory distress, bilateral pulmonary infiltrates seen on chest radiographs, absence of left-sided heart failure and hypoxemia, with the severity of hypoxemia distinguishing ALI and ARDS (Box 1) [2]. Extrapolating from recent epidemiologic studies using these criteria, ALI affects about 200,000 patients annually in the USA and results in approximately 75,000 deaths [3]. This disease, which can be caused by common events such as pneumonia, sepsis and trauma, results in high morbidity, mortality and healthcare expenditures associated with prolonged mechanical ventilation and intensive care. Because of its impact on public health and patient outcomes, great strides have been made towards understanding the pathobiology of ALI.When defined broadly to include all processes related to defense against microbes, other environmental insults and injury, a wide variety of cell types and proteins participate in inflammation and immunity. Leukocytes are the paradigmatic inflammatory cell type, but they are not the only cells that function in defense and immunity. The epithelial lining of all tissues forms a continuous barrier to the environment and is the first line of defense against infectious agents and toxins. Though specialized to serve distinct functions among tissues, epithelial cells respond similarly to injury and infection, and regulate leukocyte influx through the production of proinflammatory cytokines, chemokines and other factors that modulate chemokine gradients and effect leukocyte migration. This review will focus on the role of the pulmonary epithelium and inflammatory mediators in ALI. More s...

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Section: Five-year Viewmentioning

confidence: 99%

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confidence: 99%

Role of the pulmonary epithelium and inflammatory signals in acute lung injury

Manicone¹

2009

Expert Review of Clinical Immunology

109

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“…In this study, methylprednisolone at a dose of 30 mg/kg every 6 hours for 2 days increased the incidence of ARDS (64% vs. 33%), as well as the rate of infections (77% vs. 43%). Similarly, Bone et al demonstrated an increased 14-day mortality in the steroid group compared with a control group (52% vs. 22%) (88).…”

Section: Adjunctive Therapymentioning

confidence: 83%

“…Multiple studies have investigated the role of steroids in the prevention of ARDS and in the treatment of its diff erent phases. Four trials have assessed the use of methylprednisolone for prevention of ARDS in a high-risk group of patients (sepsis/septic shock) (87)(88)(89)(90). Specifi cally, Weigelt et al looked at high-risk surgical ICU patients (90).…”

Section: Adjunctive Therapymentioning

confidence: 99%

The Acute Respiratory Distress Syndrome

&NA;

2001

Survey of Anesthesiology

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).bilateral infi ltrates on chest radiograph, and 3) pulmonary artery occlusion pressure < 18 mm Hg when measured by pulmonary artery catheterization, or no clinical evidence of left atrial hypertension. Th e term ALI was adopted from the lung injury score to include patients with less severe forms of the same pathological entity. Th erefore, patients with a PaO 2 /FiO 2 of 200 to 300 were included within this group.Since its description, the American and European Consensus Conference defi nition has been widely used for enrollment of ARDS patients in therapeutic clinical trials (11-15). Nevertheless, the aforementioned defi nition also presented several shortcomings. First, the reliability in reading chest radiographs was questionable. Second, the defi nition did not explicitly defi ne the time interval for "acute." Th ird, the level of PEEP utilized during ventilation was not incorporated in the defi nition. Last, the use of pulmonary artery catheters has been decreasing over the last few years, precluding measurements of pulmonary artery occlusion pressures.Based on the aforementioned limitations, and after reviewing current epidemiologic evidence and results of clinical trials, in 2011 the European Society of Intensive Care Medicine proposed the Berlin ARDS defi nition (16), which considered the factors of timing, chest imaging, origin of edema, and oxygenation:• Of note, the term ALI has been eliminated. Th e categories of mild, moderate, and severe correlate with mortalities of 27%, 32%, and 45%, respectively (16). RISK FACTORSMultiple conditions may cause ARDS (Table 1). Sepsis remains the most common cause of ARDS, with 46% of the cases triggered by pulmonary entities (2). Mortality also varies according to the cause. Particularly, mortality in patients with ARDS due to severe trauma (injury severity score > 15) is 24.1%, whereas mortality in patients with severe sepsis with a pulmonary source is 40.6% (2). Notably, certain patientrelated variables have been associated with the risk of developing ARDS and with mortality. Among these risk factors, age (2, 17-19), male gender, African American race (20), and history of alcoholism are associated with a higher incidence and mortality (21-23). Active and passive smoking exposure increases the incidence of ARDS as well (24,25). Patients with a higher body-mass index have an increased incidence of ARDS, but its association with mortality is not clearly defi ned (26-28). Both diabetes mellitus and prehospital antiplatelet therapy seem to have a protective eff ect on development of ARDS (29-31).Interestingly, the Acute Lung Injury Verifi cation of Epidemiology (ALIVE) study (32) reported that ALI occurred in 16.1% of patients who were mechanically ventilated for other reasons. Hence, several groups have investigated a variety of methods to predict ARDS. Particularly, Gajic et al described the Lung Injury Prediction Score (LIPS , Table 2) using a prospective cohort study of 5584 patients (33). A LIPS score higher than 4 was associated with risk of developing ARDS ...

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“…47 High-dose systemic corticosteroids were ineffective in preventing lung injury and were associated with worse outcomes in patients with septic shock. 48 However, accumulating evidence suggests that inhaled steroids in patients at high risk may offer a preventive benefit. 49 In response to those data, the lung injury prevention subgroup is organizing a multicenter evaluation of nebulized budesonide in patients at high risk for ALI development.…”

Section: Barrier 3: Pharmacoprevention: Organizing Multicenter Clinicmentioning

confidence: 99%

Acute Lung Injury: Prevention May Be the Best Medicine

et al. 2011

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Acute lung injury affects a subset of hospitalized patients but is not universal. This syndrome can substantially delay ventilator liberation, prolong intensive care unit (ICU) stay, and increase mortality. As with many critical illness syndromes, the available treatment options are limited in number and impact. Once a patient develops lung injury, the best known strategy is supportive care. Observational studies have identified potential risk factors and have suggested that the use and timing of certain critical care interventions may influence the likelihood of developing lung injury. These findings suggest that a well designed screening tool and the systematic application of best practices in critical care may limit the risk of lung injury. An effective prediction score may also facilitate enrollment in pharmacopreventive trials. Development of such tools is accelerated by multicenter collaboration.

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Early Methylprednisolone Treatment for Septic Syndrome and the Adult Respiratory Distress Syndrome

Cited by 338 publications

References 7 publications

Role of the pulmonary epithelium and inflammatory signals in acute lung injury

Role of the pulmonary epithelium and inflammatory signals in acute lung injury

The Acute Respiratory Distress Syndrome

Acute Lung Injury: Prevention May Be the Best Medicine

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