jurnal reading 2 rikojumat11 - Copy.ppt

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Impact and indication ofearly systemic corticosteroids

for very severe community-

acquired pneumonia

2nd Journal Reading

RIKO JUMATTULLAH

Department of Internal Medicine M. Djamil Hospital/

Medical Faculty of Andalas University

20131



Introduction

Community Acquired Pneumonia (CAP)

a serious and a major cause of death

2



Former studies haveshown that in patientswith CAP systemic

inflammatory responseslead to poor clinical

outcomes

Corticosteroidsare well-known asanti inflammatoryagents and act at

genomic level

3



However, in CAP,the efficacy of

systemiccorticosteroids

added to antibiotic

therapy has not yetbeen confirmed

4



In a retrospective study

• Garcia et al

• reported the administrationof systemic corticosteroidscontributed to thereduction of mortality insevere CAP

5



In contrast, the randomized,double blind, placebo

controlled study producedby Snijder et al showed no

beneficial effects ofadjunctive corticosteroids in

hospitalized CAP patients

6



In this single center, prospective, andobservational study

This Study investigated the clinical

features of patients treated with early

adjunctive systemic corticosteroids andimpact of early adjunctive systemic

corticosteroids on clinical outcomes in

very severe CAP7



Materials and methods

Patients

• Consecutive patients admitted to the Ichinomiya-Nishi hospital because of CAP, from August2010 through February 2013, who had apneumonia severity index (PSI) of >130 points(class 5)

• Patients aged >18 years who were admittedfrom the community/nursing home

• Patients had not been hospitalized in the 90days before the start of the study

• Patients did not have any antibiotic exposureduring the 14 days prior to enrollment

8



CAP was diagnosed in;

• Presented with a new radiographicinfiltrate

• Patients who showed at least twocompatible clinical symptoms (body

temperature >38°C, productivecough, chest pain, shortness ofbreath, or crackles on auscultation)

9



Patients were excludedchronically

immunosuppressed(chemotherapy, humanimmunodeficiency virusinfection, therapy with

corticosteroids, or other

immunosuppressiveagents)

10



Methods and endpoints

Calculation of PSI, collection of venous bloodsamples, 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

11



Measurements of blood countsand levels of serum biochemical

markers (C-reactive protein[CRP], blood urea nitrogen,albumin, glucose, sodium, and

creatinine) were performedimmediately after blood sampling

12



Causative pathogens finding of 3+ growth in thesputum culture or the presence of antigen in urine

Heart failure

DM

Cerebrovascular diseases

Neoplastic diseases

CKD Advanced liver diseases

COPD and other lung diseases

Co-existing

illnesses

13



Performance status according tothe European Cooperative

Oncology Group score

Grade 0 = fullyactive, able to

carry on allpredisease

performancewithout

restriction

Grade 1 =restricted inphysicallystrenuousactivity butambulatoryand able to

carry out workof a light orsedentary

nature

Grade 2 =ambulatoryand capable

of all self-carebut unable tocarry out anywork activity,up and about

more than50% of

working hours

Grade 3 =capable ofonly limitedself-care,

confined tobed or chairmore than

50% ofworking hours

Grade 4 =completely

disabled,cannot carryon any self-care, totallyconfined tobed or chair

14



The choice of antibiotic regimen was madeaccording to the national guidelines proposed by

the Japanese Respiratory Society

Treatment with early adjunctive systemic

corticosteroids was defined as administration ofdosages equivalent to prednisone of ≥ 20

mg/day as a “stress dose” of systemic

corticosteroids for pneumonia

added to the initial intravenous antibiotic

medication

15



The primary endpoint mortality within 28days of admission.

The secondary endpoints requirement

for intensive care and occurrence ofadverse events.

16



Statistical analysis

The differences between the two groups were tested usingthe nonparametric Mann –Whitney U test for continuousvariables and Fisher’s exact test for categorical variables

Survival curves from admission were plotted using theKaplan−Meier 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 bestatistically significant

17



Result

Patient population 101 patients having >130 points of PSI on admission

were enrolled in this study (Figure 1)

18



19



The baseline characteristics of enrolled patients areshown in Table 1.

20



Causative pathogens were detected in Table 2.

21



The characteristics of patients treated with andwithout early adjunctive systemic corticosteroids are

shown in Table 4.

22



23



The adverse events of patients treated with and

without early adjunctive systemic corticosteroids are

shown in Table 5.

24



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

25



26



The Kaplan−Meier survival curves for mortality within28 days of admission did not differ significantly

between the patients treated with and without early

adjunctive systemic corticosteroids (Figure 2).

27



28



The results of multivariate analysis for mortality are

shown in Table 7.

29



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

30



(3) the occurrence of adverse events did notdiffer between the patients treated with and

without early adjunctive systemic

corticosteroids

(4) the early adjunctive systemic corticosteroidwas an independent protective factor for

mortality

31



Systemic inflammatory responses brought aboutby severe pneumonia cause critical conditions,

such as respiratory failure and hypotension.

Corticosteroids inhibit the expression and action

of many cytokines involved in inflammatoryresponses systemic corticosteroids can

suppress inflammatory responses

32



However, notmany CAP studieshave shown that

adjunctivesystemic

corticosteroids

reduce the risk ofmortality

33



In order to assess the influence ofadjunctive 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.

34



In the present study, we confined ourstudy cohort to critically ill patients, asper PSI, which is regarded as a reliableseverity indicator of CAP throughout theworld. This may be one of the reasons

why our study showed favorable efficacyof systemic corticosteroids in reducingthe risk of mortality in CAP patients.

35



Systemic corticosteroids have severalundesirable clinical effects, such as

immunosuppression, hyperglycemia, and

changes of mental condition

In the present CAP study, the early adjunctivesystemic 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

36



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-centerobservational study

3. Adrenocortical function was not evaluated in

this study

37



In conclusion, early adjunctive systemiccorticosteroids may be expected to have theefficacy to reduce the mortality in very severeCAP

We can consider the administration of systemiccorticosteroids simultaneously with initial

antibiotic medication in cases of very severeCAP, although a larger-scale prospective studyis necessary

38



The question ( PICO ) of the study

P ( Population/problem) :

Patient’s CAP with PSI> 130 point

I ( Intervention ) :

Early systemic corticosteroids usage on patient’s

CAP with PSI>130 point

C ( Compare ) : Patient’s CAP treated with and without early

systemic corticosteroid

O (Outcome ) :

Efficacy of early systemic corticosteroid on Patient’s

CAP with PSI >130 point

39



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 thecourse 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 andcomplete?

Yes, the patients were follow up sufficiently long and

complete

40



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 prognosticfactors?

No sub group in this study

5. Was there validation in a independent group of

patients? No independent group in this study

41



If we calculate CI of prognostic aspect

Clinical Measurement SE CI Calculation

Proportion : Number of pat = n Patient proportion of outcome

= p √ {p x (1-p)/n}

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

n = 101 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%

n = 101

P = 30/101=0,29

Calculation : SE : 4,5 %

CI 95 % 41,18 % - 58,82%

42



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 %

2.How precise are the prognostic estimates?

CI 95 % = 41,18 % - 58,82%

43



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 clinicallytoward our conclusion about what we should offer or

tell to our patients?

Yes

44



Pneumonia Severity Index

45



46



47



48



Stratification of Risk Score Risk Risk Class Score Mortality

Low I 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 V >130 27.0%

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