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Did my patient have VAP?.

Dr. Andrés Esteban
Servicio de Cuidados Intensivos y Grandes Quemados
84 patients with more than 72 h. of MV
suspected of having nosocomial pneumonia.
Definitive bacterial pneumonia

● Positive pleural fluid culture (n=4)
● Rapid cavitation of lung infiltrates (n=4)
● Histopathologic demonstration (n=9)
27 patients with ultimately pneumonia
J. Y. Fagon, J. Chastre, et al
Chest 1993;103:547
Patients
without
Pneumonia

Patients
with
Pneumonia

9±7

9±6

Temperature

38.3 ± 0.8

38.4 ± 1.1

Change in temperature

+ 0.1 ± 1.0

+0.5 ± 1.0

Blood Leukocytes (103)

15.2 ± 5.8

14.5 ± 5.4

Change in Leukocytes

+2.0 ± 7.0

+2.0 ± 5.6

Radiologic score

6±2

6±2

Change in Radiologic score

+2 ± 1

+2 ± 2

Duration prior ventilation

J. Y. Fagon, J. Chastre, et al
Chest 1993;103:547
The reliability coefficient (Kappa)
among the four pathologists
was ……………… 0.916
The 6 months later resulted in
reclassification of 3 patients

S. H. Kirtland,D.E.Corley et al.
Chest 1997;112:458
39 patients died after a mean 14 d. M.V.
Mechanical ventilation

14 d. (mean)

Airspace disease (Chest radiograph) 36 / 39
Antimicrobial treatment

38 / 39

With Pneumonia (Hist)

9 / 39

Without Pneumonia (Hist)

30 / 39

S.H. Kirtland, D. Corley, et al
Chest 1997;112:445
Correlation (Kappa) with Clinical Findings
(during the 48 h. prior to death)
Histologic
diagnosis of
Pneumonia

Temperature >38.5 ºC

0.15

WBC count ≥ 15,000

-0.03

Bacterial or fungal on
sputun cultive

-0.06

Chest Radiograph

0.04

Decrease PaO2/FiO2

0.11
S.H. Kirtland, D. Corley, et al
Chest 1997;112:445
25 patients with MV >72 h.

16 biopsy speciement per patient

N. Fabregas, S. Ewing et al.
Thorax 1999;54:867
Sensitivity

Specificity

PPV

NPV

Chest
radiography

0.92

0.33

0.60

0.80

Leukocytosis

0.77

0.58

0.67

0.70

Fever

0.46

0.42

0.46

0.42

Purulent
secretions

0.69

0.42

0.56

0.56

Johanson 2/3

0.69

0.75

0.75

0.69

Johanson 3/3

0.23

0.92

0.75

0.52

Pugin
score >6

0.77

0.42

0.67

0.42

N. Fabregas, S. Ewing et al.
Thorax 1999;54:867
9906
Patients admitted to ICU
1633 (16.5 %)
Died

497 (35 %)
Obtained consent and
Performed a clinical autopsy

253
Patients included
(VM >48 h.)

120
Organ donor
101
Patients with legally
mandated autopsies

30
Lost information

A.Esteban,F.Frutos,et al. (submitted)
253 patients with autopsy

> 48 hours of MV

Following during the preceding
14 days of death
Clinical suspicion of pneumonia according
to the LOOSE DEFINITION

Infiltrate on the chest radiograph and
at least two of the folloving
● Leucocytosis >12 x 109/ml
● Fever >38.5 ºC
● Presence of purulent tracheobronquial
secretions
Clinical suspicion of pneumonia according
to the RIGOROUS DEFINITION
Infiltrate on the chest radiograph and
all three of the folloving
● Leucocytosis >12 x 109/ml
● Fever >38.5 ºC
● Presence of purulent tracheobronquial
secretions
Clinical Pulmonary Infection Score (CPIS)
Clinical suspicion of pneumonia in the presence
of a positive score at different cut offs (1-12 points)
which include the following variables.
● Body temperature

● Blood leucocyte count and number of band forms
● Tracheobronchial secretions (purulen or not and
quanty)
● Microscopic examination of bronchial secretions
(Gram and semiquantitative culture)

● PaO2/FiO2
● Chest radiograph
n = 253 patients
Age, mean ± SD
66.2 ± 13.5
157 (62.1 %), 96 (37.9 %)
Sex (Male and female), n %
SAPS II, mean ± SD
49.5 ± 15.8
Length of ICU stay d. mean ± SD
16.7 ± 17.9
Cause of ICU admission, n (%)
● Medical
142 (56.1 %)
● Surgical
88 (34.8 %)
● Coronary
23 (9.1 %)
Temperature (ºC), mean ± SD
37.63 ± 1.13
Leucocytes (x 109/L) mean ± SD
16.16 ± 12.21
PaO2 / FiO2, mean ± SD
182.86 ± 85.94
Chest x-ray findings, n (%)
● No infiltrates
● Localizated

8 (3.2 %)
76 (30 %)
The Kappa statistict
agreement between the two
intensivist in the chest
radiographies was 0.382
Chest Radiography

76 / 253 (30 %)
169 / 253 (66.8 %)

Localized infiltrates
Diffuse infiltrates
Sensibility

Specificity

(%, CI 95%)

(%, CI 95%)

Loose
Definition

64.8
(56.6–72.2)

Rigurous
Definition

Definition

CPIS

LR (+)

LR (-)

36
(27.7-45.3)

1.01
(0.84-1.22)

0.98
(0.72-1.32)

15.5
(10.5-22.3)

91
(84.2-95)

1.72
(0.85-3.48)

0.93
(0.82-1.06)

45.8
(37.8-54)

60.4
(51.1-69)

1.15
(0.86-1.54)

0.90
(0.72-1.11)

A.Esteban,F.Frutos,et al. (submitted)
N. Fabregas
Thorax 1999
(n= 25)
Definition

A. Esteban
(n = 253)

Sensibility

Specificity

Sensibility

Specificity

Johanson 2/3

0.69

0.75

0.65

0.46

Johanson 3/3

0.23

0.92

0.15

0.91

CPIS

0.77

0.42

0.46

0.61
Sensitivity

Specificity

LR (+)

LR (-)

(%, CI 95 %)

(%, CI 95 %)

(CI 95 %)

(CI 95 %)

Loose

64.9
(56.5 – 72.2)

36
(27.7 – 45.3)

1.01
(0.84– 1.22)

0.98
(0.72 – 1.32)

Loose
+ localized
infitrates

11.3
(7.1 – 17.5)

91.9
(85.3 – 95.7)

1.39
(0.64 – 3.03)

0.97
(0.85 – 1.1)

Rigorous

15.5
(10.5 – 23.6)

91
(84.2 – 95)

1.72
(0.85 – 3.48)

0.93
(0.82 – 1.06)

2.1
(0.7 – 6)

100
(96.7 – 100)

-

0.98
(0.96 – 1.0)

45.8
(37.8 – 54)

60.4
(51.1 – 69)

1.15
(0.86– 1.54)

0.90
(0.72 – 1.11)

Definition

Rigorous
+ localized
infiltrates

CPIS

A.Esteban,F.Frutos,et al. (submitted)
OVERALL
GROUP

PPV
NPV
Sensitivity
Specificity
Likelihood
(+)
Likelihood
(-)

RISK
FACTOR

PULMON.
RISK
FACTOR

EXTRAPU
L. RISK
FACTOR

75 %
84 %
66 %
89 %
6.02

76 %
75 %
66 %
83 %
3.85

61 %
69 %
59 %
72 %
2.07

85 %
78 %
70 %
90 %
6.83

0.38

0.41

0.58

0.55

A.Esteban,P.Fdez-Segoviano,F.Frutos,et al.
Ann Intern Med 2004;141:440
Decisions based on clinical criteria
resulted in inappropriate treatment
of many patients without pneumonia

J. Y. Fagon, J. Chastre, et al
Chest 1993;103:547
Early diagnosis
Fast cultures
(microarray based(-4h)detection of
ten significant bacterial species)

Procalcitonin (High NPV)
s-TREM-1( in BAL or in plasma)

Early treatments
Lipopolysacharide
Late proinflam . Mediators
Complements cascade
Apoptosis
Inducible NO synthasa
● Clinical criteria may lead to underdiagnosis, which
result an increase risk of death in patients with
ventilator-associated pneumonia not receiving
antibiotic treatment.

● Also the clinical criteria may lead to overdiagnosis
which result in overuse of antibiotics that favour
colonization with potentially resistant pathogenic
microorganisms and superinfection.
MANUEL

JULIO

DATE

376

1999

DIAGNOSIS

Craneal
Stab wound

Craneal
Stab wound

TREATMENT

Catholic Church
Bishop

University Hospital
ICU

OUTCOME

Saint Manuel
Altar of the Church

Neurosurgery bill
ICU bill
Chart number
124123
Psychiatric Nursery
Did my patient have VAP?

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Did my patient have VAP?

  • 1. Did my patient have VAP?. Dr. Andrés Esteban Servicio de Cuidados Intensivos y Grandes Quemados
  • 2.
  • 3.
  • 4. 84 patients with more than 72 h. of MV suspected of having nosocomial pneumonia. Definitive bacterial pneumonia ● Positive pleural fluid culture (n=4) ● Rapid cavitation of lung infiltrates (n=4) ● Histopathologic demonstration (n=9) 27 patients with ultimately pneumonia J. Y. Fagon, J. Chastre, et al Chest 1993;103:547
  • 5. Patients without Pneumonia Patients with Pneumonia 9±7 9±6 Temperature 38.3 ± 0.8 38.4 ± 1.1 Change in temperature + 0.1 ± 1.0 +0.5 ± 1.0 Blood Leukocytes (103) 15.2 ± 5.8 14.5 ± 5.4 Change in Leukocytes +2.0 ± 7.0 +2.0 ± 5.6 Radiologic score 6±2 6±2 Change in Radiologic score +2 ± 1 +2 ± 2 Duration prior ventilation J. Y. Fagon, J. Chastre, et al Chest 1993;103:547
  • 6.
  • 7. The reliability coefficient (Kappa) among the four pathologists was ……………… 0.916 The 6 months later resulted in reclassification of 3 patients S. H. Kirtland,D.E.Corley et al. Chest 1997;112:458
  • 8. 39 patients died after a mean 14 d. M.V. Mechanical ventilation 14 d. (mean) Airspace disease (Chest radiograph) 36 / 39 Antimicrobial treatment 38 / 39 With Pneumonia (Hist) 9 / 39 Without Pneumonia (Hist) 30 / 39 S.H. Kirtland, D. Corley, et al Chest 1997;112:445
  • 9. Correlation (Kappa) with Clinical Findings (during the 48 h. prior to death) Histologic diagnosis of Pneumonia Temperature >38.5 ºC 0.15 WBC count ≥ 15,000 -0.03 Bacterial or fungal on sputun cultive -0.06 Chest Radiograph 0.04 Decrease PaO2/FiO2 0.11 S.H. Kirtland, D. Corley, et al Chest 1997;112:445
  • 10. 25 patients with MV >72 h. 16 biopsy speciement per patient N. Fabregas, S. Ewing et al. Thorax 1999;54:867
  • 12. 9906 Patients admitted to ICU 1633 (16.5 %) Died 497 (35 %) Obtained consent and Performed a clinical autopsy 253 Patients included (VM >48 h.) 120 Organ donor 101 Patients with legally mandated autopsies 30 Lost information A.Esteban,F.Frutos,et al. (submitted)
  • 13. 253 patients with autopsy > 48 hours of MV Following during the preceding 14 days of death
  • 14. Clinical suspicion of pneumonia according to the LOOSE DEFINITION Infiltrate on the chest radiograph and at least two of the folloving ● Leucocytosis >12 x 109/ml ● Fever >38.5 ºC ● Presence of purulent tracheobronquial secretions
  • 15. Clinical suspicion of pneumonia according to the RIGOROUS DEFINITION Infiltrate on the chest radiograph and all three of the folloving ● Leucocytosis >12 x 109/ml ● Fever >38.5 ºC ● Presence of purulent tracheobronquial secretions
  • 16. Clinical Pulmonary Infection Score (CPIS) Clinical suspicion of pneumonia in the presence of a positive score at different cut offs (1-12 points) which include the following variables. ● Body temperature ● Blood leucocyte count and number of band forms ● Tracheobronchial secretions (purulen or not and quanty) ● Microscopic examination of bronchial secretions (Gram and semiquantitative culture) ● PaO2/FiO2 ● Chest radiograph
  • 17. n = 253 patients Age, mean ± SD 66.2 ± 13.5 157 (62.1 %), 96 (37.9 %) Sex (Male and female), n % SAPS II, mean ± SD 49.5 ± 15.8 Length of ICU stay d. mean ± SD 16.7 ± 17.9 Cause of ICU admission, n (%) ● Medical 142 (56.1 %) ● Surgical 88 (34.8 %) ● Coronary 23 (9.1 %) Temperature (ºC), mean ± SD 37.63 ± 1.13 Leucocytes (x 109/L) mean ± SD 16.16 ± 12.21 PaO2 / FiO2, mean ± SD 182.86 ± 85.94 Chest x-ray findings, n (%) ● No infiltrates ● Localizated 8 (3.2 %) 76 (30 %)
  • 18. The Kappa statistict agreement between the two intensivist in the chest radiographies was 0.382
  • 19.
  • 20.
  • 21.
  • 22. Chest Radiography 76 / 253 (30 %) 169 / 253 (66.8 %) Localized infiltrates Diffuse infiltrates
  • 23. Sensibility Specificity (%, CI 95%) (%, CI 95%) Loose Definition 64.8 (56.6–72.2) Rigurous Definition Definition CPIS LR (+) LR (-) 36 (27.7-45.3) 1.01 (0.84-1.22) 0.98 (0.72-1.32) 15.5 (10.5-22.3) 91 (84.2-95) 1.72 (0.85-3.48) 0.93 (0.82-1.06) 45.8 (37.8-54) 60.4 (51.1-69) 1.15 (0.86-1.54) 0.90 (0.72-1.11) A.Esteban,F.Frutos,et al. (submitted)
  • 24. N. Fabregas Thorax 1999 (n= 25) Definition A. Esteban (n = 253) Sensibility Specificity Sensibility Specificity Johanson 2/3 0.69 0.75 0.65 0.46 Johanson 3/3 0.23 0.92 0.15 0.91 CPIS 0.77 0.42 0.46 0.61
  • 25. Sensitivity Specificity LR (+) LR (-) (%, CI 95 %) (%, CI 95 %) (CI 95 %) (CI 95 %) Loose 64.9 (56.5 – 72.2) 36 (27.7 – 45.3) 1.01 (0.84– 1.22) 0.98 (0.72 – 1.32) Loose + localized infitrates 11.3 (7.1 – 17.5) 91.9 (85.3 – 95.7) 1.39 (0.64 – 3.03) 0.97 (0.85 – 1.1) Rigorous 15.5 (10.5 – 23.6) 91 (84.2 – 95) 1.72 (0.85 – 3.48) 0.93 (0.82 – 1.06) 2.1 (0.7 – 6) 100 (96.7 – 100) - 0.98 (0.96 – 1.0) 45.8 (37.8 – 54) 60.4 (51.1 – 69) 1.15 (0.86– 1.54) 0.90 (0.72 – 1.11) Definition Rigorous + localized infiltrates CPIS A.Esteban,F.Frutos,et al. (submitted)
  • 26. OVERALL GROUP PPV NPV Sensitivity Specificity Likelihood (+) Likelihood (-) RISK FACTOR PULMON. RISK FACTOR EXTRAPU L. RISK FACTOR 75 % 84 % 66 % 89 % 6.02 76 % 75 % 66 % 83 % 3.85 61 % 69 % 59 % 72 % 2.07 85 % 78 % 70 % 90 % 6.83 0.38 0.41 0.58 0.55 A.Esteban,P.Fdez-Segoviano,F.Frutos,et al. Ann Intern Med 2004;141:440
  • 27. Decisions based on clinical criteria resulted in inappropriate treatment of many patients without pneumonia J. Y. Fagon, J. Chastre, et al Chest 1993;103:547
  • 28. Early diagnosis Fast cultures (microarray based(-4h)detection of ten significant bacterial species) Procalcitonin (High NPV) s-TREM-1( in BAL or in plasma) Early treatments Lipopolysacharide Late proinflam . Mediators Complements cascade Apoptosis Inducible NO synthasa
  • 29. ● Clinical criteria may lead to underdiagnosis, which result an increase risk of death in patients with ventilator-associated pneumonia not receiving antibiotic treatment. ● Also the clinical criteria may lead to overdiagnosis which result in overuse of antibiotics that favour colonization with potentially resistant pathogenic microorganisms and superinfection.
  • 30.
  • 31.
  • 32.
  • 33.
  • 34. MANUEL JULIO DATE 376 1999 DIAGNOSIS Craneal Stab wound Craneal Stab wound TREATMENT Catholic Church Bishop University Hospital ICU OUTCOME Saint Manuel Altar of the Church Neurosurgery bill ICU bill Chart number 124123 Psychiatric Nursery