Effect of Prolonged Methylprednisolone Therapy in Unresolving Acute Respiratory Distress Syndrome: a Randomized Controlled Trial

Meduri, Umberto G.; Headley, Stacey; Golden, Emmel; Carson, Stephanie; Umberger, Reba; Kelso, Tiffany M.; Tolley, Elizabeth A.

doi:10.1097/00132586-199906000-00015

Cited by 268 publications

(470 citation statements)

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“…Failed or delayed recognition of nosocomial infections in the presence of a blunted febrile response represents a serious threat and may be more common than initially suspected. In the two randomised trials that incorporated infection surveillance [30,42], nosocomial infections were frequently (56%) identified in the absence of fever.…”

Section: Role Of Glucocorticosteroids In Severe Pneumoniamentioning

confidence: 99%

Corticosteroids in severe pneumonia

Sibila¹,

Agustı́²,

Torres³

2008

European Respiratory Journal

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The mortality rate in severe community-or hospital-acquired pneumonia is very high, ranging 20-50%. Despite advances in antimicrobial therapy and supportive measures, this rate has not changed in recent years, suggesting that other factors are also responsible for the poor outcome. An abnormal increase in the local and systemic inflammatory response is associated with poor outcome, and this occurs despite adequate antibiotic therapy.There is evidence that acute administration of corticosteroids decreases the inflammatory response and might decrease mortality in severe pneumonia. This has been shown in one small randomised controlled study, terminated prematurely due to 0% mortality in the intervention arm. In addition, an experimental study showed that glucocorticosteroids decrease lung inflammatory response and lung bacterial burden, confirming the results obtained through in vitro investigations.Although these results are promising and suggest a novel role of glucocorticosteroids in pneumonia, the inherent risks and potential side-effects of these drugs require further controlled clinical trials in order to better define the target population before their general use in clinical practice. Specifically, dosage, period of administration, titration, tapering and side-effects are some of the key questions that need to be investigated.

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Section: Role Of Glucocorticosteroids In Severe Pneumoniamentioning

confidence: 99%

Corticosteroids in severe pneumonia

Sibila¹,

Agustı́²,

Torres³

2008

European Respiratory Journal

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“…Development of clinical practice guidelines, summarized in Table 1, has been challenged by contradictory results of clinical trials. [1][2][3][4][5][6][7][8][9][10] One expert panel recommended corticosteroids for patients with acute respiratory distress syndrome (ARDS) and for septic shock; 11 however, perceived indications and contraindications for corticosteroid therapy often coexist in critically ill patients. This phenomenon may explain why only half the patients received corticosteroids in recent sepsis and ARDS studies where no protocol was established for their use.…”

mentioning

confidence: 99%

Corticosteroid use in the intensive care unit: a survey of intensivists

Lamontagne

Martinez

Adhikari

et al. 2013

Can J Anesth/J Can Anesth

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Objective The efficacy of systemic corticosteroids in many critical illnesses remains uncertain. Our primary objective was to survey intensivists in North America about their perceived use of corticosteroids in clinical practice. Design Self-administered paper survey.Population Intensivists in academic hospitals with clinical trial expertise in critical illness. Measurements We generated questionnaire items in focus groups and refined them after assessments of clinical sensibility and test-retest reliability and pilot testing. We administered the survey to experienced intensivists practicing in selected -013-9929-3 North American centres actively enrolling patients in the multicentre Oscillation for ARDS Treated Early (OSCILLATE) Trial (ISRCTN87124254). Respondents used a four-point scale to grade how frequently they would administer corticosteroids in 14 clinical settings. They also reported their opinions on 16 potential near-absolute indications or contraindications for the use of corticosteroids. Main results Our response rate was 82% (103/125). Respondents were general internists (50%), respirologists (22%), anesthesiologists (21%), and surgeons (7%) who practiced in mixed medical-surgical units. A majority of respondents reported almost always prescribing corticosteroids in the setting of significant bronchospasm in a mechanically ventilated patient (94%), recent corticosteroid use and low blood pressure (93%), and vasopressorrefractory septic shock (52%). Although more than half of respondents stated they would almost never prescribe corticosteroids in severe community-acquired pneumonia (81%), acute lung injury (ALI, 76%), acute respiratory distress syndrome (ARDS, 65%), and severe ARDS (51%), variability increased with severity of acute lung injury. Near-absolute indications selected by most respondents included known adrenal insufficiency (99%) and suspicion of cryptogenic organizing pneumonia (89%), connective tissue disease (85%), or other potentially corticosteroidresponsive illnesses (85%). Conclusions Respondents reported rarely prescribing corticosteroids for ALI, but accepted them for bronchospasm, suspected adrenal insufficiency due to previous corticosteroid use, and vasopressor-refractory septic shock. These competing indications will complicate the design and interpretation of any future large-scale trial of corticosteroids in critical illness.123 Can J Anesth/J Can Anesth (2013) 60:652-659 DOI 10.1007/s12630 RésuméObjectif L'efficacite´des corticoste´roı¨des syste´miques demeure incertaine pour plusieurs maladies graves. Notre objectif primaire e´tait d'obtenir l'opinion des intensivistes en Ame´rique du Nord concernant leur perception de l'utilisation des corticoste´roı¨des dans la pratique clinique. Méthodologie Sondage auto-administre´sur papier. Population Intensivistes dans des hôpitaux universitaires ayant une expertise en matie`re d'e´tudes cliniques sur les maladies graves. Mesures Les e´le´ments du questionnaire ont e´te´cre´e´s dans des groupes de discussion; nous les ...

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“…[112][113][114][115]. In a small trial of steroids in late-stage ARDS, there was improvement in mortality [116]. Re-examination of this issue with a larger patient population revealed that patients receiving methylprednisolone had improved oxygenation and lung compliance, and were able to be liberated from mechanical ventilation sooner, but had a higher rate of recurrent respiratory failure and no difference in mortality [111].…”

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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

113

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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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Effect of Prolonged Methylprednisolone Therapy in Unresolving Acute Respiratory Distress Syndrome: a Randomized Controlled Trial

Cited by 268 publications

References 0 publications

Corticosteroids in severe pneumonia

Corticosteroids in severe pneumonia

Corticosteroid use in the intensive care unit: a survey of intensivists

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

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