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 Rationale and physiology of NIV

Dr Nicolino Ambrosino
U.O. Pneumologia 2
Dipartimento Cardio-Toracico
Azienda Ospedaliera-Universitaria Pisana
Via Paradisa 2, Cisanello
26124 Pisa, Italy
n.ambrosino@ao-pisa.toscana.it

Summary
Mechanical ventilation is the most largely used supportive technique in intensive care
units. For several decades mechanically assisted intermittent positive-pressure ventilation has
been performed, initially, placing an artificial airway, the endotracheal (ET) tube, and in case
of prolonged ET intubation, later a tracheostomy. More recently non-invasive modality of
mechanical ventilation (NMV) through nasal or facial mask have been introduced. The need to
avoid ET tube associated complications, a better understanding of pathophysiologic
mechanisms of ventilatory pump failure, the development of synchronised ventilatory
modalities and algorithms able to compensate for leaks are the reasons for promoting NMV.
The primary use of NMV has been for patients with acute on chronic hypercapnic respiratory
failure due to acute exacerbations of chronic obstructive pulmonary disease. In these patients
NMV is associated with reduction in the need for ET intubation, a reduction in complication
rate, especially ventilator associated infections, a reduced hospital length of stay and a
substantial reduction in hospital mortality. One important factor of success seems to be the
early institution of NMV in the course of respiratory failure. Different locations for NMV
require careful selection of patients. It must be clear that NMV cannot replace ET intubation in
all circumstances.

Chronic Obstructive Pulmonary Disease (COPD) is a leading cause of death, a major

medical and an increasing economic problem1. Acute respiratory decompensation among
patients with COPD has many potential causes, such as bronchial infections, bronchospasm,
left ventricular failure, pneumonia, pneumothorax and thromboembolism 2. Acute
exacerbations of COPD (AECOPD) are generally defined as episodes of increased respiratory
compromise without an objectively documented cause such as pneumonia 2,3 . AECOPD
requiring hospitalization are associated with substantial mortality rate3, 4 which even increases
among those patients requiring admission to an intensive care unit (ICU).5,6 Compared to
patients who do not need admission to an ICU, these patients suffer from more severe chronic
disease with predominantly irreversible airway obstruction when in their stable condition 7,
and show a trend to progressive increase in PaCO2 in the two years preceding admission. 8

In AECOPD respiratory muscles become unable to generate adequate alveolar ventilation

despite large pressure swing because of the presence of severe abnormalities in respiratory
mechanics (intrinsic Positive End Expiratory Pressure (PEEPi), high inspiratory resistances,
increase work of breathing). Despite stimulation of the respiratory centres and large negative
intrathoracic pressure swings, these abnormalities cannot be compensated, and rapid shallow
breathing with low tidal volume and high respiratory frequency ensues, leading to hypercapnia
and respiratory acidosis, and impending respiratory muscle fatigue. Dyspnoea, right ventricular
failure, and encephalopathy characterise severe AECOPD 9,10.

9
When medical therapy (oxygen, bronchodilators, antibiotics, steroids) 3 fails, mechanical
ventilation is instituted with the aims to decrease work of breathing, to unload the respiratory
muscles, to increase alveolar ventilation and to reverse life-threatening acute progressive
respiratory acidosis 11. For several decades mechanically assisted intermittent positive-
pressure ventilation has been performed, initially, placing an artificial airway, the endotracheal
(ET) tube, and in case of prolonged ET intubation, later a tracheostomy. It exposes the patient
to a variety of complications resulting from the intubation procedure, during the course of
ventilation, after removing the tube or due to tracheostomy12 but also to non respiratory
nosocomial infections associated with invasive monitoring 13 . The recent innovations of non-
invasive methods of mechanical ventilation (NMV) in the treatment of acute on chronic
respiratory failure has led to avoid the complications of invasive mechanical ventilation,
ensuring in the same time a similar degree of efficacy. Both intermittent negative pressure
ventilation and positive pressure ventilation by face or nasal masks have been used recently to
this purpose14 . We will focus on non-invasive positive pressure ventilation trying to answer
some clinical and practical questions on the basis of available evidence based medicine
(EBM).

10
References
1. Pauwels RA, Buist AS, Calverley PMA, et al on behalf of the GOLD Scientific
Committee. Global strategy for the diagnosis , management and prevention of chronic
obstructive lung disease. NHLBI/WHO global initiative for chronic obstructive lung
disease (GOLD) workshop summary. Am J Respir Crit Care Med 2001; 163: 1256-1276
2. Derenne JP, Whitelaw WA, Similowski T. Introduction: Definition and Clinical
presentation. In Derenne JP, Whitelaw WA, Similowski T : Acute respiratory failure in
chronic obstructive pulmonary disease. New York, Marcel Dekker 1996; 1-12.
3. Bach PB, Brown C, Gelfand SE, et al. Management of acute exacerbations of chronic
obstructive pulmonary disease: a summary and appraisal of published evidence. Ann
Intern Med 2001; 134: 600-620.
4. American Thoracic Society Statement. Standards for the diagnosis and care of patients
with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1995; 152: S77-
S120.
5. Connors AF jr, Dawson NV, Thomas C, et al. Outcomes following acute exacerbations of
severe chronic obstructive lung disease. The SUPPORT investigators. Am J Respir Crit
Care Med 1996; 154:959-967.
6. Seneff MG, Wagner DP, Wagner RP, et al. Hospital and 1-year survival of patients
admitted to intensive care units with acute exacerbation of chronic obstructive pulmonary
disease. JAMA 1995; 274: 1852-1857.
7. Thurlbeck WM. Pathophysiology of chronic obstructive pulmonary disease. Clin Chest
Med 1990; 11: 389-403.
8. Vitacca M, Foglio K, Scalvini S, Marangoni S, Quadri A, Ambrosino N. Time course of
pulmonary function before admission into ICU. A two year retrospective study of COLD
patients with hypercapnia. Chest 102; 1737-1741, 1992.
9. Similowski T, Milic-Emili J, Derenne JP. Respiratory mechanics during acute respiratory
failure of chronic obstructive pulmonary disease. In Derenne JP, Whitelaw WA,
Similowski T. Acute respiratory failure in chronic obstructive pulmonary disease. New
York, Marcel Dekker 1996; 23-46.
10. Rossi A, Polese G, Brandi G, Conti G. Intrinsic positive end-expiratory pressure (PEEPi).
Intensive Care Med 1995; 21: 522-536.
11. Tobin MJ. Advances in mechanical ventilation. N Eng J Med 2001; 344: 1986-1996.
12. Pingleton S. Complications associated with mechanical ventilation. In Tobin MJ (ed):
Principles and practice of mechanical ventilation. New York, McGraw-Hill 1994; 775-792.
13. Girou E, Schortgen F, Delclaux C et al. Association of noninvasive ventilation with
nosocomial infections and survival in critically ill patients. JAMA 2000; 284; 2361-2367.
14. Ambrosino N, Corrado A. Obstructive pulmonary disease with acute respiratory failure.
In: JF Muir, AK Simonds, N. Ambrosino. Noninvasive mechanical ventilation, Eur Respir
Mon 16; 2001, 11-32.

11
Slide 1 ___________________________________
___________________________________
Physiological basis of NIV
N. Ambrosino ___________________________________
___________________________________
___________________________________
Azienda Ospedaliera-
Ospedaliera-Universitaria Pisana
Dipartimento Cardio-
Cardio-Toracico
U.O. Pneumologia 2
___________________________________
___________________________________

Slide 2 ___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________

Slide 3 ___________________________________
NPPV: definition
___________________________________
Any form of ventilatory support applied
without the use of an endotracheal tube
considered to include:
___________________________________
• CPAP with or without pressure support ___________________________________
• volume- and pressure- cycled systems
• proportional assist ventilation (PAV).
___________________________________
• AJRCCM 2001; 163:283-91
___________________________________
___________________________________

12
Slide 4 ___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________

Slide 5 ___________________________________
DOES NPPV WORK IN ___________________________________
EXACERBATIONS OF COPD?
___________________________________
___________________________________
PHYSIOLOGY
___________________________________
___________________________________
___________________________________

Slide 6 ___________________________________
DOES NPPV WORK IN
EXACERBATIONS OF COPD? ___________________________________
Physiology:
___________________________________
• Improves alveolar ventilation
___________________________________
• Unloads respiratory muscles
___________________________________
• ……BUT ……………
___________________________________
___________________________________

13
Slide 7 ___________________________________
DOES NPPV WORK IN
EXACERBATIONS OF COPD? ___________________________________
___________________________________
• …….AND IN COMPARISON
___________________________________
WITH INVASIVE?
___________________________________
___________________________________
___________________________________

Slide 8 ___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________

Slide 9 NIMV for weaning in COPD ___________________________________

EARLY EXTUBATION (n=58)
(within 48 hours)
___________________________________
T - PIECE TRIAL ___________________________________
FAILURE (n=50) SUCCESS (n=8)
Random ___________________________________
WEANED
N-PSV I-PSV ___________________________________
(n=25) (n=25)

(from Nava S. et al. Ann Intern Med 1998;128:721-728) ___________________________________

___________________________________

14
Slide 10 WEANING THROUGH NIV
___________________________________
___________________________________
___________________________________
Invasive MV ___________________________________
NIV
___________________________________
Nava et al. Ann.Intern.Med. 1998;128:721-8
___________________________________
___________________________________

Slide 11 ___________________________________
NIMV-PSV PSV ___________________________________
Length MV (d.) 10.2+6.8 16.5+11.8
(p<0.05) ___________________________________
ICU stay (d.) 15.1+5.4 24.0+13.7
(p<0.005)
60 d.survival 92% 72% ___________________________________
(p<0.01)
n.VAP 0 28% ___________________________________
From Nava et al. Ann.Intern.Med. 128:1998
___________________________________
___________________________________

Slide 12 ___________________________________
NIMV for weaning in COPD
pH PaCO22, mmHg
___________________________________
7,5 140
120
7,4
7,3
100
80
___________________________________
7,2 60
NPSV NPSV
7,1 IPSV
40
20 IPSV ___________________________________
7,0 0

___________________________________
(from Nava S. et al. Ann Intern Med 1998;128:721-728) ___________________________________
___________________________________

15
Slide 13 ___________________________________

PTPdi/min (cmH20 x s/min)

___________________________________
700
*
600 * ___________________________________
500
400
300 ___________________________________
200
100
0
___________________________________
-100
i-PSV n-PSV T-piece S.B.
___________________________________
AJRCCM 164:638-42,2001

___________________________________

Slide 14 ___________________________________
DOES NPPV WORK IN ___________________________________
EXACERBATIONS OF COPD?
___________________________________
___________________________________
CLINICAL EFFECTS
___________________________________
___________________________________
___________________________________

Slide 15 MASK VENTILATION ___________________________________

ACUTE ON CHRONIC RESPIRATORY
FAILURE
• Bott et al, Lancet 1993
___________________________________
• Kramer et al, AJRCCM 1995
• Brochard et al, NEJM 1995 ___________________________________
• Barbè et al, Eur Respir J 1996
•
•
Celikel et al, Chest 1998
Plant et al, Lancet 2000
___________________________________
Mask ventilation was successful (ability to ___________________________________
avoid endotracheal intubation and death)
from 50 to 91% of cases
___________________________________
___________________________________

16
Slide 16 ___________________________________
NPPV in acute exacerbations of COPD
___________________________________
• The early use of NPPV for mildly and
moderately acidotic patients with COPD in the
general setting leads to more rapid
___________________________________
improvement of physiologic variables, a
reduction in the need for invasive mechanical
ventilation (with objective criteria, and a
___________________________________
reduction in in-hospital mortality.
___________________________________
» Plant PK et al. The Lancet 2000; 355:1931-5

___________________________________
___________________________________

Slide 17 NIMV in corsia

___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
Plant PK ___________________________________
___________________________________

Slide 18 NPPV ritarda

Brochard et al. il trattamento invasivo? ___________________________________
LF=18%
___________________________________
LF=26%
___________________________________
___________________________________
Late failures (LF)

___________________________________
___________________________________
___________________________________

17
Slide 19
Better to have late failures...
than to fail because we are late
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________

Slide 20 ___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________

Slide 21 ___________________________________
___________________________________
___________________________________
___________________________________

Rischio fallimento
___________________________________
___________________________________
___________________________________

18
Slide 22 ___________________________________
___________________________________
___________________________________
___________________________________
Mortalità
Intubazione
___________________________________
___________________________________
___________________________________

Slide 23 ___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________

Slide 24 ___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________

19
Slide 25 ___________________________________
___________________________________
Girou et al. ___________________________________
___________________________________
___________________________________
___________________________________
___________________________________

Slide 26 ___________________________________
___________________________________
Girou et al. ___________________________________
___________________________________
___________________________________
___________________________________
___________________________________

Slide 27 ___________________________________
Plant et al. Thorax 2001; 56: 708-712
118 NPPV vs 118 SMT random; ward
Survival ___________________________________

100
___________________________________
90
80
70
60
___________________________________
50 NPPV
40
30
SMT
___________________________________
20
10
0
0 3 6 12 24
___________________________________
___________________________________

20
Slide 28 ___________________________________
30 NPPV vs 27 historical ETI
Survival
___________________________________

80
___________________________________
70
60
50
___________________________________
40 NPPV
30
20
ETI
___________________________________
10
0
Discharge 3month 1 year
___________________________________
___________________________________

Slide 29 ___________________________________
___________________________________
___________________________________
How much ? ___________________________________
___________________________________
___________________________________
___________________________________

Slide 30
HUMAN WORKLOAD in RICU
Nava et al.Chest 97;111:1631
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________

21
Slide 31 ___________________________________
pH

7.35
___________________________________
rate of NIMV success (%)
7.3
81%
___________________________________
86% 86% 91% 80%
7.25 pH

78% 81%
___________________________________
7.2 84%

7.15
___________________________________
92 93 94 95 96 97 98 99

YEARS ___________________________________
___________________________________

Slide 32 ___________________________________
___________________________________
…E NEL MONDO REALE ? ___________________________________
___________________________________
___________________________________
___________________________________
___________________________________

Slide 33 NIV vs ETI: epidemiological survey in 42 ICUs

___________________________________
___________________________________
___________________________________
___________________________________
___________________________________

(from Carlucci A. et al. AJRCCM 2001;163:874-880)

___________________________________
___________________________________

22
Slide 34 ___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________
___________________________________

Slide 35 ___________________________________
___________________________________
___________________________________
DOVE? ___________________________________
___________________________________
___________________________________
___________________________________

Slide 36 Severity Location Intervention ___________________________________

pH > 7,35 Ward Drugs+Oxygen ___________________________________
pH 7,35 -7,30 Ward NPPV

pH <7,30; Alertness IICU NPPV or INPV

___________________________________
pH < 7.25
and/or
ICU ET intubation ___________________________________
Neurologic T-Trial
Status
Fatigue or
Success Failure ___________________________________
ET indication Extubation Early extubation
MOF
Discharge NPPV
___________________________________
___________________________________

23
Slide 37 ___________________________________
Noninvasive Positive Pressure Ventilation
in Acute Respiratory Failure ___________________________________
• Reduces the rate of intubation
• Reduces the intubation-related ___________________________________
complications (e.g. pneumonia, sepsis)
• Reduces the length of ICU stay ___________________________________
⇒Reduces mortality ___________________________________
Consensus. AJRCCM 2001; 163:283-91

___________________________________
___________________________________

Slide 38 ___________________________________
CONCLUSIONS
___________________________________
In clinical practice the use of both
modalities of noninvasive mechanical ___________________________________
ventilation (mask ventilation and NPV)
can avoid endotracheal intubation in the ___________________________________
large majority of patients with chronic
respiratory disorders and acute ___________________________________
respiratory failure needing mechanical
ventilation
___________________________________
___________________________________

24