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: [email protected]
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