Cortisol levels and adrenal response in severe community-acquired pneumonia: A systematic review of the literature

Intensive Care Unit and Postgraduate Program, Instituto Nacional de Câncer, Rio de Janeiro, Brazil.
Journal of critical care (Impact Factor: 2). 09/2010; 25(3):541.e1-8. DOI: 10.1016/j.jcrc.2010.03.004
Source: PubMed


Our aim was to review the literature on the prevalence and impact of critical-illness related corticosteroid insufficiency (CIRCI) on the outcomes of patients with severe community-acquired pneumonia (CAP).
We reviewed Cochrane, Medline, and CINAHL databases (through July 2008) to identify studies evaluating the adrenal function in severe CAP. Main data collected were prevalence of CIRCI and its mortality.
We screened 152 articles and identified 7 valid studies. Evaluation of adrenal function varied, and most studies used baseline total cortisol levels. The prevalence of CIRCI in severe CAP ranged from 0% to 48%. Among 533 patients, 56 (10.7%) had cortisol levels of 10 μg/dL or less and 121 patients (21.2%) had cortisol levels of 15 μg/dL or less. In a raw analysis, there was no significant difference in mortality when patients with cortisol levels less than 10 μg/dL (8.6 vs 15.5%; P = .55) or less than 15 μg/dL (12.4 vs 16%; P = .38) were compared with those with cortisol above these levels. In the meta-analysis, relative risk for mortality were 0.81 (confidence interval, 0.39-1.7; P = .59; χ(2) = 1.04) for cortisol levels less than 10 μg/dL and relative risk was 0.67 (confidence interval, 0.4-1.14; P = .84; χ(2) = 1.4) for cortisol levels less than 15 μg/dL.
A significant proportion of patients with severe CAP fulfilled criteria for CIRCI. However, CIRCI does not seem to affect the outcomes. Noteworthy, the presence of elevated cortisol levels is associated with increased mortality and may be useful as a prognostic marker in patients with severe CAP.

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Available from: Fernando A Bozza, Dec 23, 2013
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    • "Interestingly, case 2 had higher cortisol level and lower DHEAS levels than case 1, but had lower cellular immune function. One meta-analysis also has demonstrated the association between high cortisol levels and mortality, which made cortisol an useful biomarker for assessing prognosis in patients with severe community-acquired pneumonia (CAP) [2]. Glucocorticoids influence the traffic of circulating leukocytes and inhibit many functions of leukocytes and immune accessory cells [3]. "
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    ABSTRACT: The immunoneuroendocrine axis plays a major role in the regulation of the host's response to infection, but its role in severe H7N9 pneumonia is still unknown. Therefore, this study is carried out to explore the relationship between the immunoneuroendocrine axis and severe H7N9 pneumonia.Case presentantion: The study included two H7N9 pneumonia patients. Endocrine response and cellular immune function in prolonged phase of these two severe H7N9 pneumonia cases were reported and analyzed. A 57-year-old male patient (case 1) and a 68-year-old male patient (case 2) were admitted because of cough, fever and dyspnea. Moist rales were present in both lungs. The rest of the examination was reportedly normal. The laboratory test showed that (1) The patients had loss of cortisol rhythm and elevated cortisol level at 4 pm. (2) The patients showed decline of cellular immune function. (3) The patients showed vitamin D insufficiency. (4) Case 2 had higher cortisol level but lower DHEAS, serum phosphorus and vitamin D level as well as cellular immune function than case 1. (5) The thyroid axis, gonadal and lactotropic axis were normal, so were the level of FT3, FT4, STSH and LH, FSH, T, E2 as well as PRL in these two cases. Chest CT revealed inflammation of both lungs especially in right lung. Real time RT-PCR by Centers for Disease Control and Prevention (CDC) confirmed H7N9 infection. Immunoneuroendocrine axis dysfunction may play an important role in severe H7N9 pneumonia. We need pay more attention to hypophosphatemia and vitamin D insufficiency in H7N9 pneumonia.
    Full-text · Article · Jan 2014 · BMC Infectious Diseases
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    • "According to IDSA/ATS consensus guideline, CIRCI should be screened in all patients at risk for severe CAP [29]. In a systematic review, Salluh et al. [30] showed that the prevalence of CIRCI in severe CAP ranged from 0% to 48%. Cortisol is a major regulator in the immune system and inflammation. "
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    ABSTRACT: The benefit of corticosteroids in community-acquired pneumonia (CAP) remains controversial. We did a meta-analysis to include all the randomized controlled trials (RCTs) which used corticosteroids as adjunctive therapy, to examine the benefits and risks of corticosteroids in the treatment of CAP in adults. Databases including Pubmed, EMBASE, the Cochrane controlled trials register, and Google Scholar were searched to find relevant trials. Randomized and quasi-randomized trials of corticosteroids treatment in adult patients with CAP were included. Effects on primary outcome (mortality) and secondary outcomes (adverse events) were accessed in this meta-analysis. Nine trials involving 1001 patients were included. Use of corticosteroids did not significantly reduce mortality (Peto odds ratio [OR] 0.62, 95% confidence interval [CI] 0.37-1.04; P = 0.07). In the subgroup analysis by the severity, a survival benefit was found among severe CAP patients (Peto OR 0.26, 95% CI 0.11-0.64; P = 0.003). In subgroup analysis by duration of corticosteroids treatment, significant reduced mortality was found among patients with prolonged corticosteroids treatment (Peto OR 0.51, 95% CI 0.26-0.97; P = 0.04; I(2) = 37%). Corticosteroids increased the risk of hyperglycemia (Peto OR 2.64, 95% CI 1.68-4.15; P<0.0001), but without increasing the risk of gastroduodenal bleeding (Peto OR 1.67, 95% CI 0.41-6.80; P = 0.47) and superinfection (Peto OR 1.36, 95% CI 0.65-2.84; P = 0.41). Results from this meta-analysis did not suggest a benefit for corticosteroids treatment in patients with CAP. However, the use of corticosteroids was associated with improved mortality in severe CAP. In addition, prolonged corticosteroids therapy suggested a beneficial effect on mortality. These results should be confirmed by future adequately powered randomized trials.
    Preview · Article · Oct 2012 · PLoS ONE
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    • "The inclusion criteria of patients, with more severe disease (all patients with ICU admission and 74% requiring mechanical ventilation) differed markedly from the current cohort. In this setting, Salluh et al.[24]reported that most patients with severe CAP admitted to the ICU had adrenal insufficiency caused by a disregulation of the hypothalamic-pituitaryadrenal axis. Clearly, the presence of underlying adrenal insufficiency could explain the favourable results obtained among some of the patients with severe pneumonia. "
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    ABSTRACT: The benefit of corticosteroids as adjunctive treatment in patients with severe community-acquired pneumonia (CAP) requiring hospital admission remains unclear. This study aimed to evaluate the impact of corticosteroid treatment on outcomes in patients with CAP. This was a prospective, double-blind and randomized study. All patients received treatment with ceftriaxone plus levofloxacin and methyl-prednisolone (MPDN) administered randomly and blindly as an initial bolus, followed by a tapering regimen, or placebo. Of the 56 patients included in the study, 28 (50%) were treated with concomitant corticosteroids. Patients included in the MPDN group show a more favourable evolution of the pO2/FiO2 ratio and faster decrease of fever, as well as greater radiological improvement at seven days. The time to resolution of morbidity was also significantly shorter in this group. Six patients met the criteria for mechanical ventilation (MV): five in the placebo group (22.7%) and one in the MPDN group (4.3%). The duration of MV was 13 days (interquartile range 7 to 26 days) for the placebo group and three days for the only case in the MPDN group. The differences did not reach statistical significance. Interleukin (IL)-6 and C-reactive protein (CRP) showed a significantly quicker decrease after 24 h of treatment among patients treated with MPDN. No differences in mortality were found among groups. MPDN treatment, in combination with antibiotics, improves respiratory failure and accelerates the timing of clinical resolution of severe CAP needing hospital admission. International Standard Randomized Controlled Trials Register, ISRCTN22426306.
    Full-text · Article · Mar 2011 · Critical care (London, England)
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