2nd Journal Reading

Impact and indication of early systemic corticosteroids for very severe communityacquired pneumonia

RIKO JUMATTULLAH
Department of Internal Medicine M. Djamil Hospital/ Medical Faculty of Andalas University 2013 1

Introduction

Community Acquired Pneumonia (CAP)

a serious and a major cause of death

Former studies have shown that in patients with CAP systemic inflammatory responses lead to poor clinical outcomes

Corticosteroids are well-known as anti inflammatory agents and act at genomic level

However, in CAP, the efficacy of systemic corticosteroids added to antibiotic therapy has not yet been confirmed
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In a retrospective study
Garcia et al reported the administration of systemic corticosteroids contributed to the reduction of mortality in severe CAP

In contrast, the randomized, double blind, placebo controlled study produced by Snijder et al showed no beneficial effects of adjunctive corticosteroids in hospitalized CAP patients

In this single center, prospective, and observational study

This Study investigated the clinical features of patients treated with early adjunctive systemic corticosteroids and impact of early adjunctive systemic corticosteroids on clinical outcomes in very severe CAP 7

Materials and methods

Consecutive patients admitted to the IchinomiyaNishi hospital because of CAP, from August 2010 through February 2013, who had a pneumonia severity index (PSI) of >130 points (class 5) Patients aged >18 years who were admitted from the community/nursing home Patients had not been hospitalized in the 90 days before the start of the study Patients did not have any antibiotic exposure during the 14 days prior to enrollment

Patients
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CAP was diagnosed in;

Presented with a new radiographic infiltrate Patients who showed at least two compatible clinical symptoms (body temperature >38C, productive cough, chest pain, shortness of breath, or crackles on auscultation)
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Patients were excluded chronically immunosuppressed (chemotherapy, human immunodeficiency virus infection, therapy with corticosteroids, or other immunosuppressive agents)

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Methods and endpoints

Calculation of PSI, collection of venous blood samples, arterial blood gas analysis, microbiological sputum examination, and urinary antigen tests for Streptococcus pneumoniae and Legionella pneumophila serogroup 1

performed on admission for all CAP patients

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Measurements of blood counts and levels of serum biochemical markers (C-reactive protein [CRP], blood urea nitrogen, albumin, glucose, sodium, and creatinine) were performed immediately after blood sampling
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Causative pathogens finding of 3+ growth in the sputum culture or the presence of antigen in urine Heart failure DM Cerebrovascular diseases Neoplastic diseases Co-existing CKD illnesses Advanced liver diseases COPD and other lung diseases
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Performance status according to the European Cooperative Oncology Group score

Grade 0 = fully active, able to carry on all predisease performance without restriction

Grade 1 = restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature

Grade 2 = ambulatory and capable of all self-care but unable to carry out any work activity, up and about more than 50% of working hours

Grade 3 = capable of only limited self-care, confined to bed or chair more than 50% of working hours

Grade 4 = completely disabled, cannot carry on any selfcare, totally confined to bed or chair

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The choice of antibiotic regimen was made according to the national guidelines proposed by the Japanese Respiratory Society Treatment with early adjunctive systemic corticosteroids was defined as administration of dosages equivalent to prednisone of 20 mg/day as a stress dose of systemic corticosteroids for pneumonia added to the initial intravenous antibiotic medication
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The primary endpoint mortality within 28 days of admission. The secondary endpoints requirement for intensive care and occurrence of adverse events.

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Statistical analysis
The differences between the two groups were tested using the nonparametric MannWhitney U test for continuous variables and Fishers exact test for categorical variables Survival curves from admission were plotted using the KaplanMeier method, and the comparison between two curves was performed using the logrank test

The results were expressed as hazard ratio (HR) and 95% confidence interval (CI) A two-tailed probability value 0.05 was considered to be statistically significant

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Result

Patient population 101 patients having >130 points of PSI on admission were enrolled in this study (Figure 1)

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The baseline characteristics of enrolled patients are shown in Table 1.

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Causative pathogens were detected in Table 2.

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The characteristics of patients treated with and without early adjunctive systemic corticosteroids are shown in Table 4.

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The adverse events of patients treated with and without early adjunctive systemic corticosteroids are shown in Table 5.

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A comparison of the characteristics of deceased and surviving patients is shown in Table 6.

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The KaplanMeier survival curves for mortality within 28 days of admission did not differ significantly between the patients treated with and without early adjunctive systemic corticosteroids (Figure 2).

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The results of multivariate analysis for mortality are shown in Table 7.

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Discussion

The present study in very severe CAP:

(1) the addition of systemic corticosteroids to initial antibiotics was more frequently observed in patients having alteration of mental status, serious respiratory failure or underlying lung diseases, and receiving fluoroquinolones as initial antibiotics (2) the dosage of additional (to initial antibiotics) systemic corticosteroids was less than 60 mg/day of an equivalent to prednisone by bolus intravenous infusion for a period shorter than 8 days in most patients

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(3) the occurrence of adverse events did not differ between the patients treated with and without early adjunctive systemic corticosteroids (4) the early adjunctive systemic corticosteroid was an independent protective factor for mortality

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Systemic inflammatory responses brought about by severe pneumonia cause critical conditions, such as respiratory failure and hypotension. Corticosteroids inhibit the expression and action of many cytokines involved in inflammatory responses systemic corticosteroids can suppress inflammatory responses

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However, not many CAP studies have shown that adjunctive systemic corticosteroids reduce the risk of mortality

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In order to assess the influence of adjunctive systemic corticosteroids on mortality, it is necessary to study critically ill CAP patients However, most of the earlier CAP studies included patients with a mild to moderate severity of illness.

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In the present study, we confined our study cohort to critically ill patients, as per PSI, which is regarded as a reliable severity indicator of CAP throughout the world. This may be one of the reasons why our study showed favorable efficacy of systemic corticosteroids in reducing the risk of mortality in CAP patients.

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Systemic corticosteroids have several undesirable clinical effects, such as immunosuppression, hyperglycemia, and changes of mental condition In the present CAP study, the early adjunctive systemic corticosteroids did not bring more adverse events compared with the therapy without early corticosteroids In this study treatment can be associated with safety of adjunctive systemic corticosteroids in patients with CAP
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This current study has several limitations:

1. This was not a placebo-controlled interventional study 2. This study cohort included a limited number of patients because it was a single-center observational study 3. Adrenocortical function was not evaluated in this study

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In conclusion, early adjunctive systemic corticosteroids may be expected to have the efficacy to reduce the mortality in very severe CAP We can consider the administration of systemic corticosteroids simultaneously with initial antibiotic medication in cases of very severe CAP, although a larger-scale prospective study is necessary
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The question ( PICO ) of the study P ( Population/problem) : Patients CAP with PSI> 130 point I ( Intervention ) : Early systemic corticosteroids usage on patients CAP with PSI>130 point C ( Compare ) : Patients CAP treated with and without early systemic corticosteroid O (Outcome ) : Efficacy of early systemic corticosteroid on Patients CAP with PSI >130 point
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Critical Appraisal Evidence Based Medicine Prognostic Aspect I.Are the results of this prognosis study valid? 1. Was a defined, representative sample of patients assembled at a common (usually early) point in the course of their disease?

Yes, all of patient were representative at common point in the course of their disease

2. Was patient follow up sufficiently long and complete?

Yes, the patients were follow up sufficiently long and complete

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3. Were objective outcome criteria aplied in a blind fashion?

No, this research use double blind method

4. If subgroup with defined prognoses are identified was there adjusment for important prognostic factors?

No sub group in this study

5. Was there validation in a independent group of patients?

No independent group in this study

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If we calculate CI of prognostic aspect

Clinical Measurement SE CI Calculation

If p = 30/101=0,29=(or 29%) n = 101

Proportion :
Number of pat = n Patient proportion of outcome =p {p x (1-p)/n}

SE = ( 0,29 x( 1 0,29) / 101

= 0,045 = 4,5% 95% CI = 50% 1,96 x 4,5% = 50 % 8,82% = 41,18 % - 58,82%

Calculation : n = 101 SE P = 30/101=0,29 CI 95 % 41,18 % - 58,82% : 4,5 %

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II. Are the valid results of prognosis study important? 1.How likely are the outcomes over time?

n = 101 P = 30/101=0,29 SE : 4,5 % CI 95 % = 41,18 % - 58,82%

2.How precise are the prognostic estimates?

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III. Can we applied the evidence of these valid and important prognostic aspect to our patients? Does patient on this study look like our patient?

Yes

Does evidence will have important Influence clinically toward our conclusion about what we should offer or tell to our patients?

Yes

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Pneumonia Severity Index

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Stratification of Risk Score

Risk Risk Class Score Mortality

Low

Based on algorithm

0.1%

Outpatient treatment

Low

II

<= 70

0.6%

Low

III

71-90

0.9%

Moderate

IV

91-130

9.3%

Hospital admission

High

>130

27.0%

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