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 ! !! !!