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Prognostic Factors in Severe Community Acquired Pneumonia Antonio Anzueto MD University of Texas Health Science Center San Antonio


IDSA-ATS, ALAT, CIDS-CTS

CAP Outpatient

Inpatient Ward

ICU


Severe CAP  Severely ill patients – Around 10 % of hospitalizations require ICU admission – High mortality rate 30-50 % – Risk score assessment vs. Severity assessment • Pneumonia severity of illness score – pneumonia Patient Outcome Research Team (PORT) study • Severely ill patients - ATS


CAP Mortality and place of care ICU 30 25 20 15

War d

10 5 0

Home Low

Intermediate

Risk of death due to CAP

High


Mortality: ICU vrs Non-ICU

Angus et al AJRCCM 166:717, 2002


CAP Clinical outcomes: Ward and ICU services

Clinical outcomes Mortality at 30 days Mortality at 90 days Length of stay (mean days +/- SD) PSI (mean +/- SD)

Ward n= 631 N (%)

ICU n= 156 N (%)

P-value

36 (5.7)

36 (23.1)

<0.001

63 (10.0)

44 (28.1)

<0.001

6.55 +/- 16.0

11.9 +/- 10.1

0.04

85.5 +/- 32.1

114.4 +/- 36.2

0.05

Restrepo et al Chest 2009


Early vs Late ICU admission

Restrepo et al Chest 2009


SCAP: Prognostic Factors

â&#x20AC;˘Severity of illness predictors â&#x20AC;˘Prognostic factors


SCAP: Prognostic Factors

â&#x20AC;˘Severity of illness predictors â&#x20AC;˘Prognostic factors


Are clinicians aware of SCAP severity of illness predictors ?


SCAP:Severity Criteria  American Thoracic Society – 1993 (9 criteria) – 2001 (major and minor criteria  British Thoracic Society – CURB criteria – CURB-65

 Pneumonia severity index score – Classes IV or V,  Apache II or III  SAPS I or II Restrepo et al Chest 2009


Aware and Use it!! 100

Percentage

80 60

50

40

28

27

20 0 ATS 2001

APACHE

PSI class V Restrepo et al Chest 2009


Aware and DO NOT Use it!! 100

Percentage

80

74

68

67

60 40 20 0 SAPS

ATS 1993 Restrepo et al Chest 2009

APACHE


NOT Aware and DO NOT Use it!! 100

Percentage

80

77

74

60 45 40 20 0 CURB

CURB-65 Restrepo et al Chest 2009

BTS


Pisco Sour

Ingredientes :

3 tazas de pisco 1 taza de jugo de limón 1 taza de jarabe de goma 2 claras de huevo 12 cubos de hielo Gotas de Amargo de Angosturo    Preparación:


Pneumonia PORT Prediction Rule for Mortality Risk Assessment STEP 1

STEP 2

Is the patient >50 years of age? No Does the patient have any of the following coexisting conditions?: Neoplastic disease; congestive heart failure; cerebrovascular disease; renal disease; liver disease No Does the patient have any of the following abnormalities?:Altered mental status; pulse ≥125/min; respiratory rate ≥30/min; systolic blood pressure <90 mmHg; temperature <35ºC or ≥40ºC

Yes

Assign points for: Demographic variables

Yes

Comorbid conditions Physical observations

Laboratory and radiographic Yes findings

Class II (≤70 points) Class III (71–90 points) Class IV (91–130 points) Class V (>130 points)

Class I No

Fine MJ, et al. NEJM 1997;336:243-250


Severe CAP Criteria MAJOR

 Mechanical ventilation  Multilobar or increase

infiltrates > 50% in 48h  Septic Shock or need for vasopressors > 4h  Acute renal failure

1 of 2 major criteria

MINOR  SBP < 90 mm Hg • •

DBP < 60 mm Hg ** RR > 30/min **  PaO2/FiO2 < 250

 Bilateral or multilobar infiltrates  ** Confusion

2 of 3 minor criteria ATS guidelines. AJRCCM. 2001;163:1730-1754 BTS guidelines. Thorax 2001;56:Supl


Defining Pneumonia Severity: CURB-65  Three prospective inpatient CAP studies, 1068

patients

– 80% as derivation cohort, 20% validation  Mortality predictors (p <0.001): – Confusion, – BUN > 7 mmol/L, – R > 30/min – SBP < 90 or DBP < 60 mm Hg), – Age > 65, fever < 37 C, albumin < 30 g/ dL Lim et al: Thorax 58: 377-382, 2003


Validation Severity Criteria PORT - database Validation Rule

ATS

BTS

Sensitivity – Sn (%)

70.7

39.6

Specificity – Sp (%)

72.4

78.2

PPV (%)

26.4

20.2

NPV (%)

94.7

90.3

0.68 (0.57-0.65)

0.58 (0.53-0.63)

ROC (95% CI)

Angus et al AJRCCM 166:717, 2002


CAP Severity score: Patients wrongly classified as non-severe

PSI: identified patients that do not hospitalization

Loke et al Thorax 2010


CAP Severity score: Patients wrongly classified as severe

Loke et al Thorax 2010


Independent Predictors of ICU Admission  Multivariate regression model  Factors:

– – – – –

Mechanical ventilation before admission Respiratory failure Tachypnea Renal failure Vasopressor requirement

Angus et al AJRCCM 166:717, 2002


CURB-65: Cumulative proportion of death

Ewin et al Thorax 2009:64:1062


SCAP: Prognostic Factors

â&#x20AC;˘Severity of illness predictors â&#x20AC;˘Prognostic factors


Severe CAP Criteria MAJOR

 Mechanical ventilation  Multilobar or increase

infiltrates > 50% in 48h  Septic Shock or need for vasopressors > 4h  Acute renal failure

1 of 2 major criteria

MINOR  SBP < 90 mm Hg • •

DBP < 60 mm Hg ** RR > 30/min **  PaO2/FiO2 < 250

 Bilateral or multilobar infiltrates  ** Confusion

2 of 3 minor criteria ATS guidelines. AJRCCM. 2001;163:1730-1754 BTS guidelines. Thorax 2001;56:Supl


SCAP Survival: Direct vs Delay ICU admission Direct

Delayed

All patients had ATS/IDSA criteria SCAP

Phua et al 2010; 36:826


SCAP: Predictors of Hospital Mortality in patients without ATS/IDSA major criteria

Phua et al 2010; 36:826


SCAP ICU admission  Factors that impact improved outcome direct

admission – Emergency Department care: • More volume resuscitation • Consistent use of antibiotics

 Delayed group - rapid deterioration of pt’s

condition in the wards: – 36/49 pt required vasopressors and/or MV.

Phua et al 2010; 36:826


Predictors of Mortality Reference

n

Design

Predictors of mortality

Moine et al., 1995 (France)

132

Prospective

• SAPS > 12 • Neutrophils < 3500/mm3 • Delayed mechanical ventilation •Ineffective initial antimicrobial therapy

Torres et al., 1991 (Spain)

92

Prospective

• Septic shock • SAPS > 13 • Streptococcus pneumoniae • Enterobacteriaceae sp

Leroy et al., 1996 (France)

335

Prospective

• Radiographic spread of pneumonia • Septic shock


Risk factors for early clinical failure: Severe CAP  Gram-negative pneumonia 3.15 (1.39-7.13, p 0.01)  Altered mental status 3.79 (2.03-7.08, p <0.001)  Art. PH < 7.35 4.46 (1.57-12.70, p 0.01)  Heart failure 0.32 (0.10-1.03, p 0.06)  Art. PO2 < 60 1.77 (0.97-3.21, p 0.06)

Hoogewerf M, et al CID 2005


Mortality in non-responding CAP patients Prob Infe c

90

Non-Infe c Non-diag

80

Primary Infe c

70

Mixe d Pe rsis Infe ct

60

%

Noso Infe ct

50 40 30

Overall mortality: 43%

20 10 0

Arancibia et al Am J Respir Crit Care Med 2000

Prognosis factors: APACHE II >14; RR:9 NOSOCOMIAL INFECTION; RR: 17


Risk factors for Septic shock for pneumococcal CAP

Garcia Vidal Thorax 2010; 65:77


Factors associated with early failures in hospitalised patients with CAP • •

Observational analysis of 1335 hospitalised adults Multivariate analysis on risk factors associated with early failure     

PSI risk class IV or V Multilobar pneumonia Legionella pneumonia Gram-negative pneumonia Discordant antibiotic therapy

OR, 2.75 (1.60 – 4.84) OR, 1.81 (1.12 – 2.92) OR, 2.71 (1.37 – 5.34) OR, 4.34 (1.04 – 18.00) OR, 2.51 (1.61 – 3.94)

(i.e. not covering the causative organism)

Therapy with appropriate, broad spectrum antibiotic is required for the empiric treatment of hospitalised CAP patients Roson B et al. Arch Intern Med 2004; 164: 502-508


Factors evaluated for Mortality in 360 Patients Receiving Antibiotic Monotherapy in Multivariate Analysis

Factor Critical illness* Discordant therapy Cefuroxime Penicillin Ceftriaxone/cefotaxime

*Pitt bacteremia score >4

P 0.0001

0.017 NS NS

Yu V et al. CID 2003;37:230


Distribution of Non-respiratory Organ Failure

Angus et al AJRCCM 166:717, 2002


Genetic Influence on CAP Severity 20 18 16

% Septic 14 Shock 12

P=0.01 AA vs no AA

10 8 6 4 2 0 AA

GA

Waterer et al. Am J Respir Crit Care Med 2001

GG

Lt alpha + 250 Genotype


Impact Sepsis protocol: Survival

Gurnani et al Clin Therap 2010; 32:1285


Conclusions  Revisited ATS rule has the best power to predict

the need for ICU admission.  3 or more minor criteria should be admitted to the ICU.  Prognostic factors of poor outcome: – Pathogens: S. pneumoniae serotypes, gram negative, Legionella sp. – Treatment: fluids, antibiotics etc. – ? genetics


Muc h Grac as ias ! !! !!

011_medb_04_AntonioAnzueto_SevereCAP_prognostic_ALATLima2010  

Prognostic Factors in Severe Community Acquired Pneumonia Antonio Anzueto MD University of Texas Health Science Center San Antonio Outpatien...

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