PAPER DE LA VNI EN LA RETIRADA DE LA VENTILACIÓ INVASIVA I FRACÀS

D’EXTUBACIÓ

www.idibapsrespiratoryresearch.org

Dr. Miquel FerrerUVIIR, Servei de Pneumologia, Hospital

Clínic, IDIBAPS, CibeRes, Barcelona. E-mail: miferrer@clinic.ub.es

Barcelona, 3 de novembre de 2010

Withdrawal of mechanical ventilation

Weaning period

Esteban A. JAMA 2002; 287:345

40-50% of total duration of ventilation Longer ventilation related to higher mortality

Survival and prolonged mechanical ventilation

≈ 5,200 ventilated patients

361 ICUs Europe, North and

South America

Patients ventilated >12 h

(n=4,968)

Non-invasive ventilation

11.1%

Spontaneous breathing trial

62%

• T-piece: 71%

• Low levels PSV: 14%

Planned extubation

(n=1,649)• Prior MV: 4 days

• Weaning: 40% of total MV

Needed >1 weaning attempt

23%

Extubated after 1st weaning attempt

77%

Re-intubation rate: 12% Mode of ventilation:

• PSV: 55%

• ACV: 28%

• SIMV-PSV: 15%

• SIMV <2%

Tracheostomy: 12.5%• Median timing: 11 days

New classification of weaning

Estimated 69%

Estimated 31%

actividad de

músculos respiratorios

demandas metabólicas

(consumo O2, producción CO2)

Respuesta cardiovascular adecuada

( Aporte periférico de O2)

Patrón respiratorio rápido

y superficial

Comportamiento de la función cardio-pulmonar

en el éxito de la retirada de la VM

Ventilación mecánica (con presión positiva)

Respiración espontánea (con presión negativa)

Remodelado de factores intra y

extrapulmonares determinantes

de los gases arteriales

retorno venoso

VCVPSVSB

Respiratory Rate (min-1 )15202530Breathing Pattern***

p<0.0001p<0.0001

Respiratory rate

ACV PSV SB

10

15

20

25

30

35

*

Tidal volume (mL)

ACV PSV SB

300

400

500

600

700

800

*

• Rapid and shallow breathing pattern during

spontaneous breathing

• No changes in minute ventilation

PaO2/FiO

2

ACV PSV SB

200

210

220

230PaCO

2

ACV PSV SB

45

50

55

60

*

QT (L/min)

ACV PSV SB

4

5

6

7

8 PVO

2 (mmHg)

ACV PSV SB

34

36

38

40

42

p<0.005* *p<0.01

QT and PVO2 increased during spontaneous breathing, preventing a fall in PaO2

Mean Q

ACV PSV SB

0.3

0.4

0.5

0.6

0.7

0.8Dispersion of

blood flow

ACV PSV SB

1.2

1.3

1.4

1.5

1.6

1.7Dead space (% V

A)

ACV PSV SB

40

45

50

55

60

**

Increase of dead space and overall lung perfusion during spontaneous breathing without changes in VA/Q mismatching

Retirada de la ventilación mecánica con éxito

• Patrón ventilatorio rápido y superficial

• Mínimos cambios en los factores intrapulmonares del intercambio de gases

• Respuesta cardiovascular adecuada:

• Aumento QT, DO2 y PVO2

• No cambios en oxigenación arterial

Increased:• Breathing drive • Workload• Ventilatory demands • Left ventricular afterload

Inappropriate cardiovascular response

Pathophysiologic bases of weaning failure

Hyperinflation Reduced inspiratory muscle strength Rapid and shallow breathing

Respiratory distressHypercapnia-acidosis

Load

Capacity

Tobin MJ. Am Rev Respir Dis 1986;134:1111-8

Unsuccessful weaning in COPD patientsRapid and shallow breathing pattern

Jubran A. Am J Respir Crit Care Med 1997;155:906-15

RINSP

EDYN

PEEPI

Increased workload of respiratory muscles

Inappropriate cardiovascular response in unsuccessful weaning

• Increased venous return to right ventricle• Large negative deflections in intrathoracic pressure • Increased left ventricular afterload• Fall of PVO2 and SVO2

Jubran A. AJRCCM 1998;158:1763 Lemaire F. Anesthesiology 1988;69:171

Approaches proposed to optimize weaning

Protocol-driven weaning:• Daily screening of respiratory function

• Respiratory therapists vs physicians

• Pressure-support vs assist-control ventilation

• Daily spontaneous breathing trials

• Automated systems

20-30% patients can not be extubated after the first weaning attempt

NIV as part of a protocol-driven weaningImprovement of underlying indication for MV

DAILY SCREENING of respiratory function

Acceptable parameters

NO YES

Mechanical ventilation

and daily screening

SPONTANEOUS BREATHING TRIAL

No contraindications for NPPV

Chronic respiratory disease?

Hypercapnia?

EXTUBATION + NPPV

Adapted from Esteban A. Intensive Care Med 1998;24:999

No signs of poor tolerance

EXTUBATION

Prolonged ventilation

Consider Tracheotomy

Contraindications for NPPV

Signs of poor tolerance

GRADUAL WITHDRAWAL OF VENTILATORY SUPPORT

Difficult weaning and non-invasive ventilation

The addition of PEEP to non-invasive PSV resulted in additional decrease of the work of breathing

The improvement of respiratory blood gases is due to higher alveolar ventilation

NIV attained a more efficient breathing pattern

VA/Q relationships did not change

Non-invasive PSV in ventilator-dependent chronic respiratory patients

PTPdi/VTE

i-PSV

n-PSV

T-pieceS.B.

cm

H2O

x s

/L

0

20

40

60

* **

Vitacca M. Am J Respir Crit Care Med 2001;164:638

T-piece trial

Invasive-PSV

Spontaneous breathing

Noninvasive-PSV

Extubation

PaCO2

i-PSV

n-PSV

T-piece

mm

Hg

40

50

60

70

80

90

Prolonged weaning associated with worse outcome:• No different outcomes between simple and difficult weaning• Factors implicated in prolonged weaning no assessed

Patients ventilated >48 h

undergoing planned extubation

(n=181)

Simple weaning

(n=81)

Difficult weaning

(n=67)Prolonged weaning

(n=33)

Characteristics and outcomes from the 3 groups Predictive factors for prolonged weaning and survival

Sellares J, Ferrer M et al. Submitted

Is prolonged weaning clinically relevant?

Days0 10 20 30 40 50 60 70 80 90

%

0

50

60

70

80

90

100

Simple

p=0.019

90-day survival

Difficult

Prolonged

Hospital mortality

%

10

20

30

40

50ICU mortality

0

10

20

30

40

50

n=10 n=8

p<0.001 p=0.004

n=14

n=15n=16

n=16

Sellares J, Ferrer M et al. Intensive Care Med (1st revision)

Ventilator-associated

pneumonia

%

10

20

30

40

50

n=12n=13

p=0.018n=14

Hospital stay

20

25

30

35

40

Simple weaning

Difficult weaning

Prolonged weaning

p=0.005

The problem of hypercapnia during weaning

Days0 10 20 30 40 50 60 70 80 90

%

0

50

60

70

80

90

100

Hypercapnia

p=0.001

90-day survival

Normocapnia

Decreased 90-d survival Adj. OR 95%-CI p value

Re-intubation criteria 5.33 3.14-9.09 <0.001

PaCO2 during SBT 1.033 1.011-1.055 0.003

Independent predictors of prolonged weaning and survival

Prolonged weaning Cutoff Adj. OR 95%-CI p value

Heart rate SBT ≥105 min-1 1.060 1.029-1.091 <0.001

PaCO2 SBT ≥54 mmHg 1.071 1.027-1.118 0.001

PaCO2

Simple Difficult Prolonged

mm

Hg

40

45

50

55

60 Simple weaning

Difficult weaning

Prolonged weaning

p=0.001

Sellares J, Ferrer M et al. Intensive Care Med (1st revision)

CO2 retention and outcome of weaning

Increased CO2 retention during spontaneous breathing strongly predicts prolonged weaning and mortality

Higher PaCO2 also related with respiratory failure after extubation (OR: 1.046, p=0.004)

Increased PaCO2 is amenable of medical intervention

Detection of high levels of PaCO2 implement measures to shorten weaning and avoid re-intubation (NIV!!!)

Adapted from Noninvasive Positive Pressure Ventilation, NS Hill ed., Futura Pub 2001

“Clinical” advantages of the early removal of the ETT

Communication

Patient comfort

Effective cough

Mucociliary clearance

Sinus drainage

Sedation

Nosocomial infection/VAP

Work of breathing

When to use NIV during withdrawal of mechanical ventilation?

Respiratory failure after extubation:

Management Prevention

Early extubation

Weaning failure(difficult and prolonged)

Pneumonia

NIV Standard

%

0

10

20

30 n=23

n=18p<0.01

n=0

n=7 p<0.01

ICU survival

NIV Standard

%

0

20

40

60

80

100MV duration

NIV Standard

Day

s

0

5

10

15

20ICU stay

NIV Standard0

10

20

30

p<0.05 p<0.01

NPPV in COPD and early extubation One failed weaning attempt (within 48 h of MV) Mean PaCO2: 62-64 mmHg, mean pHa: 7.30-7.31

Nava S. Ann Intern Med 1998;128:721

60-d weaning success

NIV Standard

%

0

20

40

60

80

100p<0.01

n=22

n=17

Patients who could not be weaned from MV

Standard weaning

NIV

NPPV in ACRF and single weaning failure

Girault C. Am J Respir Crit Care Med 1999;160:86

3-day reduction of ETMV

No changes in major clinical outcomes

Small sample size

Duration of endotracheal mechanical ventilation

Single failed weaning attempt Mean PaCO2: 60-64 mmHg, mean pHa: 7.33-7.35

Ferrer M et al.

Am J Respir Crit Care Med 2003;168:70

NIV during persistent weaning failure

Duration of ventilation (days)

0 10 20 30 40 50

0

20

40

60

80

100 Successfully weaned patients

NIVControl

p=0.002

Duration of intubation

NIV Standard0

5

10

15

20

25

p=0.003

Nosocomial pneumonia

NIV Control

%

0

20

40

60

80Tracheostomy

NIV Control0

20

40

60

80p=0.042

n=5

n=13p<0.001

n=13

n=1

Control

0 10 20 30 40 50 60 70 80 90

%

0

40

60

80

100

NIV

90-day survival

p=0.044

ICU Survival

NIV Control

0

20

40

60

80

100

p=0.045n=19

n=13

Failed weaning attempts for 3 consecutive days 77% chronic respiratory (60% COPD) Mean PaCO2: 52-54 mmHg Mean pHa: 7.37-7.38

Meta-analysis of 12 RCTs Extubation with immediate

NPPV vs weaning using IPPV

BMJ. 2009 May 21;338:b1574. doi: 10.1136/bmj.b1574

NIV during difficult weaning

Primary end-point: Shortening weaning

Secondary end-points: Decreasing complications associated to prolonged MV and mortality

Currently available RCTs:

• Nearly all with chronic respiratory disorders and hypercapnia

• Frequent cardiac co-morbidity

• Limited number of patients:

• Overall 530 in 12 trials, but

• Only 3 trials in high quartile peer-review journals (126 patients)

• Future multicentre RCTs? France, ≈ 200 inclusions

Clinical relevance of extubation failure

Incidence and outcome of re-intubation

Incidence: 6-23% planned extubations

Crude mortality rate: 12-68%

Independent risk factor for:

• Nosocomial pneumonia

• Increased mortality

• Increased length of stay

Torres A. Am J Respir Crit Care Med 1995;152:137

Epstein SK. Chest 1997;112:186

Patients ventilated >12 h

(n=4,968)

Non-invasive ventilation

11.1%

Spontaneous breathing trial

62%Planned extubation

(n=1,649)• Prior MV: 4 days

• Weaning: 40% of total MV

Needed >1 weaning attempt

23%

Extubated after 1st weaning attempt

77%

Re-intubation rate: 12%

Effect of failed extubation on the outcome of mechanical ventilation

ICU stay

Day

s

0

5

10

15

20

25

Extubation success

Extubation failure

Hospital mortality

%

0

10

20

30

40

50 p<0.001

Hospital stay

0

10

20

30

40p<0.001p<0.001

Epstein SK. Chest 1997;112:186

Independent predictors of death

Time to re-ETI was an independent predictor of mortality

Time from extubation to re-ETI

%0 20 40 60 80

49-72 h

25-48 h

13-24 h

0-12 h Incidence

Mortality

Predicting extubation outcome

Better prediction

Risks derived from prolonged ventilation

Delay of extubation

Shorter duration of MV

Risks derived from re-intubation

Advance of extubation

Is there an optimal rate of post-extubation failure?

Test accuracy may be less important if NIV is effective for extubation failure

%0 20 40 60

Other

Encephalopathy

Upper airway obstruction

Aspiration-excess secretions

Heart failure

Respiratory failure

Mortality

Incidence

Causes potentially responding to NIV accounted for half of re-

intubations and had high mortality

When can NIV be used after extubation?

Respiratory failure after extubation: Management (late use) Prevention (early use

NPPV for post-extubation respiratory distress

Keenan SP. JAMA 2002;287:3238

81 patients Mixed population:

• Cardiac: 35%• Respiratory: 32%

(COPD 11%!!!!)

Methods ...... “. After the first year, patients with an acute exacerbation of COPD were excluded because the randomized trial evidence strongly supported the use of NPPV for these patients and because NPPV was therefore applied when these patients developed respiratory distress.”

Hospital survival

NPPV Standard

0

20

40

60

80

Re-IT

NPPV Standard

%

0

20

40

60

80n=28

n=27 n=29n=29

NPPV in the management of post-extubation failure

Esteban A. N Engl J Med 2004;350:2452

221 patientsMixed population: COPD 10%!!!!

ICU mortality

NIV Control

%

0

20

40

60Re-ETI

NIV Control

%

0

20

40

60

p=0.038n=55

n=30

n=51

n=15

Time to re-ETI

(hours, median)

NIV Control0

10

20

30

p=0.041

NPPV in the management of post-extubation failure

Esteban A.

N Engl J Med 2004;350:2452

Standard medical therapy … “These patients could be reintubated or crossed over to NIV if they met the predefined criteria for reintubation …..”

ICU mortality

NPPV Standard

0

10

20

30Re-IT

NPPV Standard

%

0

20

40

60

n=62 n=31

n=12

n=44p=0.12

p=0.31

When can NIV be used after extubation?

Respiratory failure after extubation: Management (late use) Prevention (early use

ICU mortality

NIV Standard

0

10

20

30Re-IT

NIV Standard

%

0

10

20

30

n=4 n=3

n=9n=12p=0.027 p=0.064

NIV independently associated to reduced risk for RF after extubation Re-IT strongly predicted mortality

ICU mortality

Re-ETINo re-ETI

%

0

20

40

60

80

n=10

n=2

p<0.001

Randomised clinical trial Successful weaning trial (33% COPD) At high-risk for RF after extubation

(Crit Care Med 2005; 33:2465–2470)

Extubation failure

NIV Control

%

0

10

20

30

40 p=0.022

n=13

n=27

Overall population

Days0 10 20 30 40 50 60 70 80 90

%

0

50

60

70

80

90

100

NIV group

p=0.397

Control group

(n=162)

Successful weaning trial (36% COPD or chronic bronchitis) Risk factors for RF after extubation

p=0.429 p=0.006

(n=113) (n=49)

No hypercapnia

Days

0 10 20 30 40 50 60 70 80 90

%

0

50

60

70

80

90

100Hypercapnia

Days

0 10 20 30 40 50 60 70 80 90

%

0

50

60

70

80

90

100

90-day survival

70% COPD or chronic bronchitis

Successful weaning trial, hypercapnia while on spontaneous breathing

Respiratory failureafter extubation

NIV Control

%

0

10

20

30

40

50 p<0.001

n=8

n=25

Days0 10 20 30 40 50 60 70 80 90

%

0

50

60

70

80

90

100

NIV groupp=0.015

Control group

90-day survival

Why?

Time from extubation (hours)

0 24 48 72

NIV group

Control group

0 24 48 72

NIV group

Control group

AJRCCM 2006

Lancet 2009

Severely obese patients

NIV 48 h after extubation, compared with historically matched controls (n=62+62)

Hosp. mortality

0

10

20

30

NIV

Control

Respiratory failure

%

0

10

20

30

n=6n=8

n=16n=15

ICU length of stay

0

10

20p=0.03p=0.17p<0.001

Hospital mortality

0

20

40

60

n=4

n=11p=0.03

Hypercapnic patients during SBT

1. Prophylactic NIV immediately after extubation

1. Therapeutic NIV after RF after extubation developed

Why such different outcomes in RF after extubation?

Keenan SP. JAMA 2002;287:3238

Esteban A. N Engl J Med 2004;350:2452

Nava S. Crit Care Med 2005;32:2465

Ferrer M. Am J Respir Crit Care Med 2006;173:164

Ferrer M. Lancet 2009;374:1082

5. Scheduled periods of NIV delivery after extubation

5. After 4-12 h, no subsequent continuous delivery of NIV

2. Higher proportions of chronic respiratory disorders (39% and 51%)

2. Lower proportions of chronic respiratory disorders (COPD: 10-11%)

3. Ventilator specifically designed for NIV with high performance

3. Ventilators with less performance or no specific ventilator

4. Long-term experience (>10 yr) in clinical use and research with NIV

4. Minimal required experience with NIV of 1 year in both studies

Studies on prevention Studies on treatment

Limitations of NIV in withdrawal of MV

Main reasons for NIV failure• Lack of co-operation, agitation • Excessive secretions• Hemodynamic instability• Decreased consciousness (not hypercapnic)

Protection of airways Tracheostomy?

NIV and respiratory failure after extubation

Hypercapnia during spontaneous breathing trial is consistently associated with poor outcome

In non-selected patients, NIV does not improve outcome of post-extubation failure and may be harmful

In selected patients at high risk of re-intubation, it helps in preventing post-extubation failure

Benefits of NIV in survival restricted to patients with hypercapnic respiratory failure