Corticosteroids

Placebo

Mortality

Systematic Review

Randomized Control Trial

Last 10 Years

I: corticosteroids

C: placebo

O: mortality

Controlled Trials: 29

Primary Research: 14

corticosteroids

antibiotic

corticosteroids

antibiotic

Research

corticosteroids

antibiotic

Review Articles

Open Access

Published online 2017 Dec 13. doi: 10.1002/14651858.CD007720.pub3

Corticosteroids for pneumonia

Anat Stern, Keren Skalsky, Tomer Avni, Elena Carrara, Leonard Leibovici, and Mical Paul

Article: Corticosteroids-for-pnuemonia.pdf

Background

Pneumonia is a common and potentially serious illness. Corticosteroids have been suggested for the treatment of different types of infection, however their role in the treatment of pneumonia remains unclear. This is an update of a review published in 2011.

Objectives

To assess the efficacy and safety of corticosteroids in the treatment of pneumonia.

Search methods

We searched the Cochrane Acute Respiratory Infections Group’s Specialised Register, CENTRAL, MEDLINE, Embase, and LILACS on 3 March 2017, together with relevant conference proceedings and references of identified trials. We also searched three trials registers for ongoing and unpublished trials.

Selection criteria

We included randomized controlled trials (RCTs) that assessed systemic corticosteroid therapy, given as adjunct to antibiotic treatment, versus placebo or no corticosteroids for adults and children with pneumonia.

Data collection and analysis

We used standard methodological procedures expected by Cochrane. Two review authors independently assessed risk of bias and extracted data. We contacted study authors for additional information. We estimated risk ratios (RR) with 95% confidence intervals (CI) and pooled data using the Mantel–Haenszel fixed‐effect model when possible.

Main results

We included 17 RCTs comprising a total of 2264 participants; 13 RCTs included 1954 adult participants, and four RCTs included 310 children. This update included 12 new studies, excluded one previously included study, and excluded five new trials. One trial awaits classification.

All trials limited inclusion to inpatients with community‐acquired pneumonia (CAP), with or without healthcare‐associated pneumonia (HCAP). We assessed the risk of selection bias and attrition bias as low or unclear overall. We assessed performance bias risk as low for nine trials, unclear for one trial, and high for seven trials. We assessed reporting bias risk as low for three trials and high for the remaining 14 trials.

Corticosteroids significantly reduced mortality in adults with severe pneumonia (RR 0.58, 95% CI 0.40 to 0.84; moderate‐quality evidence), but not in adults with non‐severe pneumonia (RR 0.95, 95% CI 0.45 to 2.00). Early clinical failure rates (defined as death from any cause, radiographic progression, or clinical instability at day 5 to 8) were significantly reduced with corticosteroids in people with severe and non‐severe pneumonia (RR 0.32, 95% CI 0.15 to 0.7; and RR 0.68, 95% CI 0.56 to 0.83, respectively; high‐quality evidence). Corstocosteroids reduced time to clinical cure, length of hospital and intensive care unit stays, development of respiratory failure or shock not present at pneumonia onset, and rates of pneumonia complications.

Among children with bacterial pneumonia, corticosteroids reduced early clinical failure rates (defined as for adults, RR 0.41, 95% CI 0.24 to 0.70; high‐quality evidence) based on two small, clinically heterogeneous trials, and reduced time to clinical cure.

Hyperglycaemia was significantly more common in adults treated with corticosteroids (RR 1.72, 95% CI 1.38 to 2.14). There were no significant differences between corticosteroid‐treated people and controls for other adverse events or secondary infections (RR 1.19, 95% CI 0.73 to 1.93).

Authors’ conclusions

Corticosteroid therapy reduced mortality and morbidity in adults with severe CAP; the number needed to treat for an additional beneficial outcome was 18 patients (95% CI 12 to 49) to prevent one death. Corticosteroid therapy reduced morbidity, but not mortality, for adults and children with non‐severe CAP. Corticosteroid therapy was associated with more adverse events, especially hyperglycaemia, but the harms did not seem to outweigh the benefits.

Ming Cheng  ¹ , Zhi-Yong Pan, Jiong Yang, Ya-Dong Gao

Article: CorticosteroidtherapyforsevereCAP.Meta-analysis.pdf

Background: The debate about the efficacy of corticosteroids in the treatment of severe community-acquired pneumonia (CAP) is still a longstanding dilemma. We performed a meta-analysis including 4 randomized controlled trials (RCTs) to evaluate the effect of corticosteroids on the treatment of severe CAP in adults.

Methods: We performed a systematic review of published and unpublished clinical trials. Databases, including PubMed, Embase, CINAHL, and Cochrane (from their establishment to July 2013), were searched for relevant articles. Only RCTs of corticosteroids as adjunctive therapy in adult patients with severe CAP were selected.

Results: Four trials enrolling 264 patients with severe CAP were included. Use of corticosteroids significantly reduced hospital mortality compared with conventional therapy and placebo (Peto odds ratio = 0.39, 95% CI 0.17-0.90). The quality of the evidence underlying the pooled estimate of effect on hospital mortality was low, downgraded for inconsistency and imprecision.

Conclusions: On the basis of the current limited evidence, we suggest that, although corticosteroid therapy may reduce mortality and improve the prognosis of adult patients with severe CAP, the results should be interpreted with caution due to the instability of pooled estimates. Reliable treatment recommendations will be raised only when large sufficiently powered multi-center RCTs are conducted.

Published online 2019 Jun 28. doi: 10.1097/MD.0000000000016239

Efficacy and safety of glucocorticoids in the treatment of severe community-acquired pneumonia. A meta-analysis

Shan Jiang, MD,^a Tiecheng Liu, PhD,^b Yuxin Hu, PhD,^a Ranwei Li, PhD,^c Xin Di, PhD,^d Xin Jin, PhD,^d Yanqiao Wang, MD,^a and Ke Wang, PhD^a,∗

Article: Efficacyandsafetyofglucocorticoid.pdf

Background:

Recent clinical trials have shown that adjunctive glucocorticoids is associated with inhibiting excessive inflammatory response and modulating cytokines release offering several advantages over conventional therapy on relieving clinical symptoms, reducing mortality, and improving prognosis. However, given the severe complications triggered by glucocorticosteroid, whether similar benefits may be achieved by patients undergoing glucocorticosteroid intervention remains controversial. Our meta-analysis aimed to investigate the efficacy and safety of adjunctive glucocorticoids in the treatment of severe community acquired pneumonia.

Methods:

A search of PubMed, EMBASE, Cochrane Library, EBASO, Medline, Google Scholar, Science Dicet, CBM, and CNKI databases was performed to analyze all relevant randomized controlled trials (RCTs) of corticosteroids in patients with severe community acquired pneumonia (CAP) up to January 2018. All-cause mortality, C-reactive protein (CRP) level, incidence of septic shock, and requirement of mechanical ventilation were selected as efficacy outcomes. Major adverse events involving super infection, upper gastrointestinal bleeding, and hyperglycemia were safety outcomes. Meta-analysis was conducted with RevMan 5.3 software.

Results:

A total of 10 RCTs comprising 665 patients were included for analysis. Regarding efficacy outcomes, adjunctive corticosteroid seemed to be superior compared with conventional treatment in terms of all-cause mortality (relative risk [RR]: 0.47, 95% confidence interval [CI], 0.3–0.74, P = .001), CRP level on day 8 after administration (standard mean difference [SMD]: −0.8, 95% CI, −1.11 to −0.5, P < .001), incidence of septic shock (odds ratio [OR] 0.15, 95% CI, 0.07–0.29, P < .001) and requirement for mechanical ventilation (OR: 0.32, 95% CI, 0.20–0.52, P < .001). Meanwhile, we found that low dose (≤86 mg) (RR: 0.41, 95% CI, 0.21–0.82, P = .01) and prolonged (>5 days) (RR: 0.35, 95% CI, 0.15–0.81, P = .01) use of corticosteroids in dosage modus of a maintenance dose after a bolus (RR: 0.28, 95% CI, 0.14–0.55, P = .002) obtained better results in death through subgroup analysis. Regarding safety outcomes, no difference was observed between 2 groups in terms of upper gastrointestinal bleeding (OR: 0.83, 95% CI, 0.27–2.52, P = .74), hyperglycemia (OR: 1.3, 95% CI, 0.68–2.49, P = .42), and super infection (OR: 1.11, 95% CI, 0.14–9.13, P = .92).

Conclusion:

Adjunctive corticosteroid yielded favorable outcomes in the treatment of severe community acquired pneumonia (SCAP) as evidenced by decreased all-cause mortality, incidence of septic shock, and requirement for mechanical ventilation without increasing risk of adverse events. Low dose (≤86 mg/d), prolonged use (>5 days) of corticosteroid in dosage modus of a maintenance dose after a bolus can be recommended as preferred regimen to guard against SCAP.

Effect of Corticosteroids on Treatment Failure Among Hospitalized Patients With Severe Community-Acquired Pneumonia and High Inflammatory Response: A Randomized Clinical Trial

Antoni Torres  ¹ , Oriol Sibila  ² , Miquel Ferrer  ³ , Eva Polverino  ³ , Rosario Menendez  ⁴ , Josep Mensa  ⁵ , Albert Gabarrús  ³ , Jacobo Sellarés  ³ , Marcos I Restrepo  ⁶ , Antonio Anzueto  ⁷ , Michael S Niederman  ⁸ , Carles Agustí 

Article: joi150004.pdf

Importance: In patients with severe community-acquired pneumonia, treatment failure is associated with excessive inflammatory response and worse outcomes. Corticosteroids may modulate cytokine release in these patients, but the benefit of this adjunctive therapy remains controversial.

Objective: To assess the effect of corticosteroids in patients with severe community-acquired pneumonia and high associated inflammatory response.

Design, setting, and participants: Multicenter, randomized, double-blind, placebo-controlled trial conducted in 3 Spanish teaching hospitals involving patients with both severe community-acquired pneumonia and a high inflammatory response, which was defined as a level of C-reactive protein greater than 150 mg/L at admission. Patients were recruited and followed up from June 2004 through February 2012.

Interventions: Patients were randomized to receive either an intravenous bolus of 0.5 mg/kg per 12 hours of methylprednisolone (n = 61) or placebo (n = 59) for 5 days started within 36 hours of hospital admission.

Main outcomes and measures: The primary outcome was treatment failure (composite outcome of early treatment failure defined as [1] clinical deterioration indicated by development of shock, [2] need for invasive mechanical ventilation not present at baseline, or [3] death within 72 hours of treatment; or composite outcome of late treatment failure defined as [1] radiographic progression, [2] persistence of severe respiratory failure, [3] development of shock, [4] need for invasive mechanical ventilation not present at baseline, or [5] death between 72 hours and 120 hours after treatment initiation; or both early and late treatment failure). In-hospital mortality was a secondary outcome and adverse events were assessed.

Results: There was less treatment failure among patients from the methylprednisolone group (8 patients [13%]) compared with the placebo group (18 patients [31%]) (P = .02), with a difference between groups of 18% (95% CI, 3% to 32%). Corticosteroid treatment reduced the risk of treatment failure (odds ratio, 0.34 [95% CI, 0.14 to 0.87]; P = .02). In-hospital mortality did not differ between the 2 groups (6 patients [10%] in the methylprednisolone group vs 9 patients [15%] in the placebo group; P = .37); the difference between groups was 5% (95% CI, -6% to 17%). Hyperglycemia occurred in 11 patients (18%) in the methylprednisolone group and in 7 patients (12%) in the placebo group (P = .34).

Conclusions and relevance: Among patients with severe community-acquired pneumonia and high initial inflammatory response, the acute use of methylprednisolone compared with placebo decreased treatment failure. If replicated, these findings would support the use of corticosteroids as adjunctive treatment in this clinical population.

(# of subjects/ studies, cohort definition etc. )

– Inclusion Criteria:

Included randomized controlled trials (RCTs) comparing corticosteroid to placebo or no treatment. All included trials limited inclusion to participants with CAP, with or without HCAP, who were treated as inpatients.

-17 randomized control trials with n=2264 participants were included.

(2) Early clinical failure

3) Time to clinical failure

4) Development of respiratory failure

5) development of shock

6) Transfer to ICU

7) Duration of Hospital/ICU Stay

8)Complications or secondary infections.

Also, mortality, although reflecting the severity of pneumonia, may be influenced by other parameters such as the antibiotic regimens used or the standard of medical care given in the specific centre.

PubMed, Embase, CINAHL, and Cochrane (from their establishment to July 2013),

– Four trials enrolling 264 patients with severe CAP were included.

Inclusion Criteria:

(1) only studies designed as RCTs,(2) adult patients with severe CAP as participants, (3)intervention with corticosteroids used as adjunctive therapy for patients with severe CAP, (4) control intervention with placebo (normal saline solution or drugs with a physical appearance similar to corticosteroids), and (5) hospital mortality as the primary outcome

– Secondary outcomes were length of hospital stay, length of ICU stay, duration of MV, days off MV, and adverse effects

(2 Second, this study lacked the power to test publication bias because of the limited number of trials included. In the study by Confalonieri et al, 7 patients died in the control group, but none died in the intervention group, which may generate high publication bias. (3)Importantly, the small sample size, a common problem in 4 studies, may have biased their results.

(4)Moreover this meta-analysis lacked pooled effect to detect potentially significant harmful effects because of a relatively small number of included trials. (5) Finally, various types of dosages, and durations of corticosteroids were used in the 4 trials. In addition, the diagnosis criteria of severe pneumonia were not exactly the same in these trials

.

– Inclusion Criteria:

Clinical randomized controlled trials published at home and abroad in English and Chinese which compared antimicrobial therapy and adjunctive systematic glucocorticoids therapy with antimicrobial therapy alone in patients with severe community acquired pneumonia.

– A total of 10 RCTs comprising 665 patients were included for analysis.

(3)Third, it is underpowered to assess the risk of death as demonstrated by analysis because of a lack of long-term follow-up data.

(4) Fourth, the sample size of the included literatures and studies is small, which has a significant impact on the reliability of the results.

Interventions  Patients were randomized to receive either an intravenous bolus of 0.5 mg/kg per 12 hours of methylprednisolone (n = 61) or placebo (n = 59) for 5 days started within 36 hours of hospital admission.

(3)Third, it is underpowered to assess the risk of death as demonstrated by analysis because of a lack of long-term follow-up data.

(4) Fourth, the sample size of the included literatures and studies is small, which has a significant impact on the reliability of the results.