Corticosteroids In Severe Community-acquired Pneumonia Research Articles

When should we use corticosteroids in severe community-acquired pneumonia?

This review aims to evaluate the evidence and recommendations for the prescription of corticosteroids as adjunctive therapy in patients with severe community-acquired pneumonia. Corticosteroids have been prescribed with the objective to attenuate the marked and persistent activation of the immune system. However, some causes of community-acquired pneumonia, namely viral, are associated with unexpected low levels of cytokines and depressed cellular immunity. As a result, several recent randomized controlled trials and large prospective observational studies repeatedly showed that corticosteroids had no impact on survival, and in some types of pneumonia like influenza, its use was associated with potential harmful effects like invasive aspergillosis. Apart from this, adverse effects, namely hyperglycemia, superinfections and increased length-of-stay, were frequent findings in the corticosteroid-treated patients. According to the current evidence, corticosteroids are recommended in Pneumocystis jiroveci pneumonia in HIV-infected patients and recommendations are against its use in influenza. In all other forms of severe community-acquired pneumonia, with the exclusion of SARS-CoV-2 pneumonia, the strength of the evidence does not support the safe and widespread use of corticosteroids as adjunctive therapy. Further studies are needed to identify subgroups of severe community-acquired pneumonia that can benefit or not from corticosteroids.

Embedding a COVID-19 group sequential clinical trial within an ongoing trial: lessons from an unusual experience

The Cape-Covid trial is an embedded clinical trial within the ongoing Cape-Cod trial. The Covid-19 pandemic appeared while we were conducting a randomized trial assessing the effectiveness of corticosteroids in severe community-acquired pneumonia. We took advantage of this ongoing trial to embed a sub-trial assessing hydrocortisone in SARS-CoV-2 infected patients. In this manuscript, we wish to share our experience when we needed to make fast and robust methodological decisions during the Covid-19 pandemic in a two weeks period of time.

Efficacy and Safety of Adjunctive Corticosteroids Therapy for Severe Community-Acquired Pneumonia in Adults: An Updated Systematic Review and Meta-Analysis.

BackgroundAdjunctive corticosteroids therapy is an attractive option for community-acquired pneumonia (CAP) treatment. However, the effectiveness of adjunctive corticosteroids on mortality of CAP remains inconsistent, especially in severe CAP. We performed a meta-analysis to evaluate the efficacy and safety of adjunctive corticosteroids in severe CAP patients.MethodsThree databases of PubMed, EMBASE and Cochrane Library were searched for related studies published in English up to December, 2015. Randomized controlled trials (RCTs) of corticosteroids in hospitalized adults with severe CAP were included. Meta-analysis was performed by a random-effect model with STATA 11.0 software. We estimated the summary risk ratios (RRs) or effect size (ES) with its corresponding 95% confidence interval (95%CI) to assess the outcomes.ResultsWe included 8 RCTs enrolling 528 severe CAP patients. Adjunctive corticosteroids significantly reduced all-cause mortality (RR = 0.46, 95%CI: 0.28 to 0.77, p = 0.003), risk of adult respiratory distress syndrome (ARDS) (RR = 0.23, 95%CI: 0.07 to 0.80, p = 0.02) and need for mechanical ventilation (RR = 0.50, 95%CI: 0.27 to 0.92, p = 0.026). Adjunctive corticosteroids did not increase frequency of hyperglycemia requiring treatment (RR = 1.03, 95%CI: 0.61 to 1.72, p = 0.91) or gastrointestinal hemorrhage (RR = 0.66, 95%CI: 0.19 to 2.31, p = 0.52). In subgroup analysis by duration of corticosteroids, we found that prolonged corticosteroids therapy significantly reduced all-cause mortality (RR = 0.41, 95%CI: 0.20 to 0.83, p = 0.01) and length of hospital stay (−4.76 days, 95% CI:-8.13 to -1.40, p = 0.006).ConclusionsResults from this meta-analysis suggested that adjunctive corticosteroids therapy was safe and beneficial for severe CAP. In addition, prolonged corticosteroids therapy was more effective. These results should be confirmed by adequately powered studies in the future.

Corticosteroids for severe community-acquired pneumonia

Corticosteroids for severe community-acquired pneumonia

Corticosteroids for Severe Community-Acquired Pneumonia: Time to Change Clinical Practice

This issue contains a systematic review and meta-analysis of 13 randomized, controlled trials of adjunctive therapy with systemic corticosteroids versus placebo for patients hospitalized with commu...

Corticosteroids in the treatment of severe community-acquired pneumonia.

Controversy surrounds the use of adjunctive corticosteroids in severe community acquired pneumonia (CAP) as current guidelines either do not address or discourage their use. Double-blind, placebo-controlled, randomized controlled trials examining systemic corticosteroids in the treatment of severe CAP were summarized and their impacts on patient-important outcomes assessed. Four trials describing systemic corticosteroid use in adults with severe CAP were identified. One trial had a significant mortality difference favoring corticosteroids. However, this may be the result of a CAP severity imbalance within the trial and the mortality benefit was not confirmed in a larger trial conducted in a similar critical care setting. Pneumonia severity, mortality assessment timing, comorbidities, corticosteroid and antibiotic choice and timing in the CAP disease course, and bias risks varied across the four trials. Because of the clinical heterogeneity of available studies and the unknowns pertaining to clinical efficacy and safety, we do not recommend the use of adjunctive corticosteroids in severe CAP.

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

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. Self-administered paper survey. Intensivists in academic hospitals with clinical trial expertise in critical illness. 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 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. 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 vasopressor-refractory 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 corticosteroid-responsive illnesses (85%). 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.

Corticosteroids in severe community-acquired pneumonia: the path we choose depends on where we want to get

Severe community-acquired pneumonia is a major cause of admission to intensive care units and its mortality rates remain exceedingly high. In the search for adjunctive therapies, clinicians who were encouraged by available, though limited, evidence prescribed steroids in most patients with severe sepsis or septic shock, including those with community-acquired pneumonia. Current evidence demonstrates that, whereas corticosteroids should not be routinely employed as adjuvant therapy for severe community-acquired pneumonia, there is sufficient equipoise to continue studying the use of corticosteroids.

Corticosteroids for H1N1 associated acute lung injury: is it just wishful thinking?

Dear editor: When challenged by a potentially life-threatening infection, intensivists are frequently inclined to prescribe adjunctive therapies with so called immunomodulating effects. However, the story of anti-inflammatory therapies in severe infections has been so far a story of disenchantment. Most of it may be ascribed to an incomplete knowledge of immune and acute phase responses. Corticosteroids have recently been caught in the midst of a huge controversy regarding their indication for severe sepsis. Despite clear evidence of anti-inflammatory effects and of clinical benefit in small single center trials, the alleged survival benefits were not subsequently confirmed by the CORTICUS study. In a paper published in Intensive Care Medicine, Dr Quispe-Laime et al. [1] report their findings regarding the use of corticosteroids in patients with H1N1 influenza A virus-associated acute lung injury. The authors found significant improvement in oxygenation and a relatively low mortality rate. However, we have several concerns regarding the study’s rationale, methodology, results and conclusions. Recent systematic reviews do not support the use of corticosteroids for severe community-acquired pneumonia. Recent experimental data showed no beneficial effect on acute respiratory distress syndrome caused by the H5N1 infection [2]. A review evaluating the effects of adjunctive therapies in SARS patients concluded that among 29 trials of systemic corticosteroids, 25 were inconclusive and four were associated with harm [3]. Also, the recent WHO guidelines disapprove the use of corticosteroids as they are ‘‘of unproven benefit and potentially harmful’’ for patients with H1N1 infection. Therefore, the use of corticosteroid as adjunctive therapy for patients with severe H1N1 infection should be viewed as experimental and with extreme caution. Therefore, we believe that according to the current rules from the International Committee of Medical Journal Editors, patients included in an evaluation of the potential benefits of corticosteroids as adjunctive therapy in H1N1 influenza A virus-associated acute lung injury should have been asked to give written informed-consent [1]. Even in the event of the use of corticosteroids as a rescue therapy for refractory or persistent ARDS, close supervision to identify potential harms frequently associated with corticosteroids should have been implemented. The present study has additional methodological shortcomings, namely a very small sample size of proven H1N1 infection; only eight patients! The small sample size and the lack of a control group (not treated with corticosteroids) preclude any sound conclusion on the hypothetical benefits of this therapy in H1N1 infection. Moreover, although the authors state that their mortality rate was low (15%), it is actually similar to the rates reported by the Canadian [4] and ANZICS [5] cohorts, where barely half of the patients received corticosteroids. In conclusion, we believe that data from this small case series from Quispe-Laime et al. [1] is, at best, a hypothesis-generating one and should not be translated into clinical practice. The assessment of the hypothetical beneficial role of corticosteroids in H1N1 infection should be done with a more careful methodology. This will avoid unnecessary risk and harm to highly susceptible patients.

The role of corticosteroids in severe community-acquired pneumonia: a systematic review

Competing interests The author(s) declare that they have no competing interests. Reference 1. Salluh JI, Povoa P, Soares M, Castro-Faria-Neto HC, Bozza FA, Bozza PT: The role of corticosteroids in severe communityacquired pneumonia: a systematic review. Crit Care 2008, 12: R76. Correction Correction: The role of corticosteroids in severe community-acquired pneumonia: a systematic review Jorge IF Salluh1,2, Pedro Povoa3, Marcio Soares1, Hugo C Castro-Faria-Neto2, Fernando A Bozza4 and Patricia T Bozza2

The role of corticosteroids in severe community-acquired pneumonia: a systematic review

IntroductionThe purpose of this review was to evaluate the impact of corticosteroids on the outcomes of patients with severe community-acquired pneumonia (CAP).MethodsWe performed a systematic MEDLINE, Cochrane database, and CINAHL search (1966 to November 2007) to identify full-text publications that evaluated the use of corticosteroids in CAP.ResultsAn initial literature search yielded 109 articles, and 105 studies were excluded after the first analysis. We found four studies eligible for analysis. On the basis of their results, the use of corticosteroids as adjunctive therapy in severe CAP should be categorized as a weak recommendation (two studies) and a strong recommendation (two studies) with either low- or moderate-quality evidence. However, no evidence of adverse outcomes or harm is present in the evaluated studies.ConclusionAccording to the GRADE system, available studies do not support the recommendation of corticosteroids as a standard of care for patients with severe CAP. Further randomized controlled trials with this aim should enroll a larger number of severely ill patients. However, in patients needing corticosteroids, it may be reasonable to conclude that corticosteroid administration is safe in patients with severe infections receiving antimicrobial therapy.

Corticosteroid Treatment of Severe Community-Acquired Pneumonia

To assess the evidence for adjunctive corticosteroids for severe community-acquired pneumonia (CAP). MEDLINE (1966-February 2007) and EMBASE (1980-February 2007) were searched to identify English- and French-language publications that evaluated the use of corticosteroids for CAP in adults. Major search terms included community-acquired pneumonia, intensive care unit, steroids, glucocorticoids, and adrenal cortex hormones. Clinical studies that evaluated the use of corticosteroids for CAP in adults were included. Clinical and surrogate markers of pneumonia were evaluated. Severe CAP is associated with an increase in pulmonary and circulatory cytokines such as interleukin-6 and tumor necrosis factor-alpha that may be associated with higher mortality. Corticosteroids suppress inflammatory reactions and prevent migration of inflammatory cells from the circulation to tissues by suppressing the synthesis of chemokines and cytokines. One observational comparative study and 2 randomized, controlled studies examined the effects of corticosteroid therapy at various doses on endpoints of pulmonary and systemic inflammation and clinical outcomes. One small observational pilot study revealed that methylprednisolone blunted some of the pulmonary and systemic markers of inflammation. One small, randomized, placebo-controlled study revealed that hydrocortisone had no significant effects on markers of pulmonary and systemic inflammation or clinical outcomes. Another small, randomized, placebo-controlled preliminary study with methodological limitations revealed improvements in oxygenation, organ dysfunction score, and markers of inflammation favoring hydrocortisone over placebo. Given the lack of proven benefit on clinically meaningful endpoints and adverse events, corticosteroids cannot be recommended for adjunctive treatment of severe CAP.