Table 5 - uploaded by Gyu Rak Chon
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Peak norepinephrine (NE) equivalent doses and duration of NE in the corticosteroid and noncorticosteroid groups
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We evaluated the clinical data in patients who required mechanical ventilation for severe community-acquired pneumonia (CAP) and compared survival with and without the use of systemic corticosteroids. This retrospective study examined 97 patients with severe CAP in the MICU of the Asan Medical Center in Korea between January 2002 and November 2006....
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Citations
... A recent meta-analysis indicated that corticosteroid therapy of CAP may be associated with inhibition of excessive inflammatory response, and modulating cytokines release offers advantages over conventional therapy for relieving clinical symptoms, reducing mortality, and improving prognosis (16). However, most previous studies were retrospective cohort studies with substantial heterogeneity with an inability to determine the etiology of cases of pneumonia, as well as phenotype and pathology (17)(18)(19). Thus, we conducted a cohort study with a large sample size to evaluate the effects of adjunctive low-dose corticosteroid treatment for children with MPP, stratified by severe pneumonia, refractory pneumonia, Abbreviations: MP, Mycoplasma pneumoniae; MPP, Mycoplasma pneumoniae pneumonia; CAP, community acquired pneumonia; RCT, randomized controlled trial; MRMP, macrolide-resistant Mycoplasma pneumoniae; CRP, C-reactive protein; LDH, lactic dehydrogenase; IL, interleukin; OR, odds ratio; CI, confidence interval; ICU, intensive care unit; MSMP, macrolide-sensitive Mycoplasma pneumoniae. ...
Background: The clinical value of corticosteroid treatment in Mycoplasma pneumoniae pneumonia (MPP) has been controversial. Our study aimed to identify the effects of low-dose corticosteroids on the recovery of children with MPP.
Methods: In this retrospective cohort study, pediatric inpatients with MPP were included from the Shanghai Children's Mycoplasma pneumoniae pneumonia cohort study between August 2014 and July 2019. The multivariable logistic regression and propensity-score matching were used to investigate the effects of low-dose corticosteroid treatment on fever duration after admission, total fever duration, length of hospital stay, C-reactive protein recovery time, and imaging recovery time with the stratification of severe pneumonia, refractory pneumonia, inflammatory biomarkers, pulmonary images, and timing of corticosteroids.
Results: There were 548 patients in the corticosteroid group and 337 in the no-corticosteroid group. The corticosteroid group showed severe clinical parameters such as more severe and refractory cases, higher laboratory values, and more abnormal imaging manifestations. The corticosteroid group also showed longer fever duration after admission [odds ratio (OR) = 1.9 (95% CI, 1.2–3.1), P = 0.008], longer total fever duration [OR = 1.6 (95% CI, 1.1–2.3), P = 0.011], longer hospital stay [OR = 2.8 (95% CI, 1.9–4.0), P < 0.001], and longer C-reactive protein (CRP) recovery time [OR = 2.1 (95% CI, 1.1–3.9), P = 0.021] in the regression model after the adjustment for severity. Although low-dose corticosteroids were associated with shortened imaging recovery time in patients with high level laboratory values, pulmonary imaging could be completely recovered in both groups. The trend of these results was consistent even after stratifications and a propensity scores matching analysis.
Conclusions: Low-dose corticosteroids may not be beneficial in children inpatients with MPP, and further studies on proper treatment modality are needed in the MRMP era.
... Corticosteroids can be useful in the combination of СAP with bronchial obstruction, there is uncertainty in the use of glucocorticoids in patients with CAP [1]. Although glucocorticoids have not been shown to be associated with a reduction in 28-day and 3-month mortality through a retrospective observational study, a randomized controlled trial demonstrated that methylprednisolone compared with placebo reduced the incidence of treatment failure [18]. Given the findings of the above studies, there is an excessive inflammatory response leading to treatment failure and mortality in CAP [2], and the fact that steroids inhibit the expression of many cytokines involved in the inflammatory response associated with pneumonia, glucocorticoids may play a significant role in management of patients with CAP [11,[19][20][21], however, corticosteroids suppresses the protective functions of the immune system. ...
... Blum et al. [50] randomized 785 CAP patients to either prednisone or placebo and found a non-significant trend to higher mortality in the steroid group (OR 1.24, 95%CI 0.59 to 2.62, p = 0.57). Even in patients with severe CAP and high inflammatory response (defined as a level of CRP greater than 150 mg/L at admission) [40] and in a group of patients with a higher prevalence of CIRCI at admission [65], steroids did not show a survival benefit. Tagami et al. [66] accessed a Japanese nationwide administrative database to retrospectively analyze 6925 patients diagnosed with severe CAP who received mechanical ventilation between July 2010 to March 2013. ...
Community-acquired pneumonia (CAP) is a leading cause of morbidity and mortality despite adequate antibiotic therapy. It is the single most common cause of infection-related mortality in the United States. An exaggerated host inflammatory response can potentially be harmful to both the lung and host, and has been associated with treatment failure and mortality. Modulation of inflammatory response may therefore be theoretically beneficial. The anti-inflammatory and immunosuppressive effects of steroids seem an attractive therapeutic option in severe CAP patients. Available data point to overall shorter time to clinical stability and decreased length-of-stay in CAP patients, with a potential mortality benefit in severe CAP. The level of evidence is, however, low to moderate regarding mortality due to high heterogeneity and insufficient power of data. Furthermore, steroids were deleterious in influenza pneumonia and in patients with pneumococcal pneumonia data suggest lack of efficacy and potential harm. Both European and American guidelines recommend not using corticosteroids in CAP. Patients who might benefit and those that can be harmed from steroids remain to be clearly identified, as does the ideal steroid for CAP patients, based on pharmacokinetic and pharmacodynamic properties. It is essential for future studies to avoid the same methodological bias present in the available data so that high-quality evidence on the true role of steroids in CAP can be provided.
... There is some evidence that corticosteroids may enhance recovery in CAP and reduce mortality (125,126), however these trials enrolled very few patients who were in ICU or required mechanical ventilation. Concerns have been raised about the use of steroids to treat severe CAP in ICU (127), with the few observational studies which focus on this group suggesting steroids are associated with a prolonged length of stay (128) and increased mortality (129). In patients with A/H1N1 pandemic influenza, use of steroids was associated with increased mortality and an increase rate of subsequent HAP (130). ...
Emergence and spread of MDR pathogens have become a major leading cause of death worldwide and a major problem in ICU patients . ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Escherichia coli/Enterobacter cloacae) reflect the strongest challenge today. The increasing prevalence of MDR bacteria is associated with increased 3rd generation cephalosporins-resistant K. pneumoniae and cephalosporins-resistant E. coli which lead to more frequent use of carbapenems and to the emergence of XDR and/
or PDR Enterobacteriaceae. The emergence of carbapenemase producing K. pneumoniae [carbapenemase-producing Enterobacterales (CPE)] is of particular concern in Italy and Greece, the prevalence of vancomycin-resistant Enterococcus (VRE) has also increased, ceftazidime-resistant P. aeruginosa remains stable while a decrease of methicillin-resistant Staphylococcus aureus (MRSA) was observed. These differences vary according to the bacterial species and geographical region. The unsafety of intensivists against a probable infection lead to a massive consumption of antibiotics (up 50% of ICU patients
under empirical antibiotic therapy have no confirmed infection) while de-escalation and shortened treatment duration are considered insufficiently in those with documented infection, promoting substantial ecological side effects and dissemination of MDR pathogens.
... Three articles were included independently from the search engines ( Figure 1). The papers were divided into two groups: those evaluating ARF in CAP but not its ventilatory management (n = 12) [10,[20][21][22][23][24][25][26][27][28][29][30] and those evaluating ventilatory management of ARF in CAP (n = 17) [11,[31][32][33][34][35][36][37][38][39][40][41][42][43][44][45][46] (Tables S1 and S2). ARF: acute respiratory failure. ...
... Two papers evaluated the administration of steroids in severe pneumonia: Chon showed that steroids were not associated with a reduction in 28-day and 3-month mortality, whereas Torres demonstrated that they could decrease the treatment failure rates [20,21]. ...
... Another important finding is the uncertainty of the use of glucocorticoids in CAP patients. While glucocorticoids were shown not to be associated with a reduction of 28-day and 3-month mortality by a retrospective observational study [20], a randomized control trial demonstrated that the acute use of methylprednisolone compared with the placebo decreased the treatment failure rates [21]. Although not included in this systematic review, it is also worth noting that the randomized controlled trial by Annane and collaborators showed a significant benefit of hydrocortisone plus fludrocortisone on 90-day all-cause mortality in patients with septic shock [55]. ...
Community-acquired pneumonia (CAP) is a leading cause of mortality worldwide. CAP mortality is driven by the development of sepsis and acute respiratory failure (ARF). We performed a systematic review of the available English literature published in the period 1 January 1997 to 31 August 2017 and focused on ARF in CAP. The database searches identified 189 articles—of these, only 29 were retained for data extraction. Of these 29 articles, 12 addressed ARF in CAP without discussing its ventilatory management, while 17 evaluated the ventilatory management of ARF in CAP. In the studies assessing the ventilatory management, the specific treatments addressed were: high-flow nasal cannula (HFNC) (n = 1), continuous positive airway pressure (n = 2), non-invasive ventilation (n = 9), and invasive mechanical ventilation (n = 5). When analyzed, non-invasive ventilation (NIV) success rates ranged from 20% to 76% and they strongly predicted survival, while NIV failure led to an increased risk of adverse outcome. In conclusion, ARF in CAP patients may require both ventilatory and non-ventilatory management. Further research is needed to better evaluate the use of NIV and HFNC in those patients. Alongside the prompt administration of antimicrobials, the potential use of steroids and the implementation of severity scores should also be considered.
... Chon, 2011 21 Garcia-Vidal, 2007 23 Polverino, 2013 20 Salluh, 2011 22 Tagami, 2015 3 Ugajin, 2013 19 Subtotal (95% CI) ...
Background:
Corticosteroids are an option in the treatment of community-acquired pneumonia (CAP). However, the benefits and adverse effects of corticosteroids, especially in severe CAP, have not been well assessed.
Methods:
Pubmed, Embase, and Cochrane library databases from inception to May 2015 were searched. Randomized controlled trials (RCTs) and cohort studies that evaluated use of corticosteroids in adult patients with CAP were included. The quality of outcomes was evaluated using GRADE methodology. The Mantel-Haenszel method with random-effects modeling was used to calculate pooled relative risks (RRs) and 95% confidence intervals(CIs).
Results:
Nine eligible RCTs (1667 patients) and six cohort studies(4095 patients), were identified. The mean corticosteroid dose and treatment duration were 30 mg/day methylprednisolone for 7 days. Corticosteroids did not have a statistically significant effect on mortality (RR, 0.72; 95% CI: 0.43-1.21; evidence rank: low) in CAP patients, and severe CAP patients (RCTs; RR, 0.72; 95% CI: 0.43-1.21; evidence rank: low; cohort studies; RR, 1.00; 95% CI, 0.86-1.17 ). Corticosteroids treatment was associated with an decreased risk of adult respiratory distress syndrome (RR, 0.21; 95% CI, 0.08-0.59), and may reduce the lengths of hospital and intensive care unit stay, the duration of intravenous antibiotic treatment, and the time to clinical stability. Corticosteroid were not associated with increased rates of adverse events.
Conclusions:
Short-term treatment with corticosteroids is safe, and may reduce the risk of adult respiratory distress syndrome, shorten the length of the disease in CAP patients.
... The Italian trial al- most certainly overestimated the effect size: the mortality rate was higher than expected in the placebo group, and the trial was stopped early for benefit without predefined stopping crite- ria. 30,31 Nonetheless, the successful trial encour- aged other studies, [21][22][23][24][25][26][27][28][29][32][33][34] with most showing benefits (TABLE 1). ...
A strong inflammatory response to community-acquired pneumonia (CAP) is associated with excess morbidity and mortality. There is growing interest in corticosteroids as an adjunctive treatment for patients hospitalized with CAP. We review recent randomized trials addressing the use of corticosteroids across the full range of CAP patients. Thirteen randomized controlled trials including 2,005 patients have addressed the impact of short-term (single dose to ten days) corticosteroid administration in patients with CAP. Results consistently show shorter time to clinical stability, and shorter length of hospital stay on the order of one day. Some studies also suggest a possible reduction in mortality. Adverse effects, primarily hyperglycaemia and neuropsychiatric symptoms, are uncommon, and neither serious nor prolonged. Results raise the possibility that steroid administration should become a standard of care for patients with CAP.
... Recent meta-analyses of randomised controlled trials found that even though low-dose corticosteroid use may not be beneficial to the overall population of patients with CAP, it may have a beneficial effect on mortality in patients with severe CAP and/or acute respiratory distress [13,[21][22][23]. However, recent small observational studies that focused on patients with severe CAP reported conflicting results [24][25][26]. Therefore, the effect of low-dose corticosteroid use on mortality in critically ill patients with severe CAP remains unclear. ...
... Additionally, we performed stratified analyses of patients with and without shock. We believe that this stratification is important when investigating patients with severe CAP who receive corticosteroids, because shock is an important contributing factor to 28-day mortality, and may respond to corticosteroid use [10,23,26]. The propensity score-matched approach is a powerful tool that attempts to construct a randomised experiment-like situation by comparing groups with similar observed characteristics, without specifying the relationships between confounders and outcomes. ...
The relationship between low-dose corticosteroid use and mortality in patients with severe community-acquired pneumonia (CAP) remains unclear.
6925 patients with severe CAP who received mechanical ventilation with or without shock (defined as use of catecholamines) at 983 hospitals were identified using a Japanese nationwide administrative database. The main outcome measure was 28-day mortality.
2524 patients with severe CAP who received catecholamines were divided into corticosteroid (n=631) and control (n=1893) groups. The 28-day mortality was significantly different between corticosteroid and control groups (unmatched: 24.6% versus 36.3%, p<0.001; propensity score-matched: 25.3% versus 32.6%, p=0.01; inverse probability-weighted: 27.5% versus 34.2%, p<0.001). 4401 patients with severe CAP who did not receive catecholamines were also divided into corticosteroid (n=1112) and control (n=3289) groups. The 28-day mortality was not significantly different between corticosteroid and control groups in propensity score-matched analyses (unmatched: 16.0% versus 19.4%, p=0.01; propensity score-matched: 17.7% versus 15.6%, p=0.22; inverse probability-weighted: 18.8% versus 18.2%, p=0.44).
Low-dose corticosteroid use may be associated with reduced 28-day mortality in patients with septic shock complicating CAP.
... También hay que considerar que en los estudios recientes de uso de esteroides en pacientes con neumonía grave y durante la reciente epidemia de influenza H1N1, muchos de cuyos pacientes cumplían con los criterios de SDRA primario (23,25,(34)(35)(36), el uso de esteroides se asoció con aumento de la mortalidad (37,38). ...
Introducción: el síndrome de dificultad respiratoria aguda (SDRA) es secundario a inflamación originada en una enfermedad pulmonar primaria o una afección extrínseca al pulmón. Es frecuente en cuidado intensivo y conlleva alta mortalidad. Objetivos: determinar la eficacia y seguridad de los glucocorticoides en dosis bajas en personas mayores de 18 años con SDRA, en términos de mortalidad, días libres de ventilación mecánica, incidencia de infecciones nosocomiales, neuromiopatía y sangrado digestivo. Metodología: se hizo una búsqueda sistemática de ensayos clínicos controlados que compararon glucocorticoides con placebo, en adultos con SDRA en los desenlaces descritos. También, búsqueda secundaria de ensayos clínicos referenciados en los artículos primarios. Resultados: se encontraron siete ensayos clínicos. Se demostró disminución de la mortalidad hospitalaria al día 28 (OR: 0,56 [0,38-0,81], ganancia de 3,5 días libres de ventilación mecánica, disminución en la incidencia de infecciones nosocomiales y neumonía adquirida en el hospital. No hubo diferencias en la neuromiopatía asociada con esteroides, pero sí una tendencia, no significativa, al aumento del sangrado digestivo. Conclusión: los esteroides en dosis bajas disminuyen la mortalidad al día 28 de los adultos con SDRA y aumentan los días libres de ventilación mecánica sin aumentar los efectos adversos significativos.
Community-acquired pneumonia (CAP) is a leading cause of hospitalization, morbidity, and mortality. Despite advances in antibiotic treatments, mortality among patients with CAP is still high. For this reason, interest has been focused on nonantibiotic therapeutic measures directed to the host response rather than the microorganism. The development of an efficacious adjunctive treatment has important implications for reducing mortality in CAP. Some clinical studies performed in the last decade have shown a clinically beneficial effect of corticosteroids, possibly by diminishing local and systemic inflammatory host response. Recent meta-analyses showed faster resolution of symptoms, shorter time to clinically stability, reduction of mechanical ventilation needed, and reduction of mortality in the most severe population, although some methodological limitations must be taken into account. In addition, some studies using statins also suggested improved outcomes due to its anti-inflammatory effect in CAP, although this requires further research. Other adjunctive therapies such as immunoglobulins and stem cells are being explored, but are not yet in the stage of clinical trials. In summary, the use of corticosteroids and other adjuvant treatments are promising in CAP, but more studies are needed to determine their impact on mortality. © Thieme Medical Publishers333 Seventh Avenue, New York, NY 10001, USA.
