This document provides an outline and overview of non-invasive positive pressure ventilation (NPPV). It begins with a brief history of ventilation techniques and then discusses the rationale for using NPPV to avoid complications of endotracheal intubation. The document reviews several important clinical studies on the use of NPPV in conditions such as COPD exacerbation, acute cardiogenic pulmonary edema, hypoxic respiratory failure, post-operative settings, and extubation failure. It finds that NPPV can reduce intubation rates, complications, and mortality in some of these situations compared to standard care. The document concludes by discussing factors that determine the success of NPPV.

1. Non-invasive Positive Pressure
Ventilation (NPPV)
Bach Mai Hospital
Sean M. Caples
College of Medicine
Mayo Clinic

2. Outline
 “NPPV” = BiLevel and/or CPAP
 Historical Overview
 Rationale for use of NPPV, physiology

3.  Review of important studies in selected
clinical situations
 COPD exacerbation
 Acute cardiogenic pulmonary edema
 Hypoxic resp. failure/ARDS/lung injury
 Post-operative setting
 Extubation failure
 Proposed Algorithm
Outline

4. History
 Negative pressure ventilation (Iron Lung)
 Invasive ventilation with polio epidemic
 IPPB-intermittent positive pressure breathing by
mouthpiece to deliver aerosol medications
 Sullivan-CPAP for obstructive sleep apnea 1981

5. Why Use NPPV ?
Avoid the complications of endotracheal
intubation:
1. Acute placement of the tube: trauma, aspiration,
hypotension
2. Nosocomial infection: VAP-ventilator associated
pneumonia, sinusitis
3. Post-extubation: hoarseness, tracheal stenosis, vocal
cord dysfunction
4. Patient Factors: Allows swallowing and speech

6. NPPV for Acute Respiratory
Failure at Mayo Clinic
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From Peter Gay, MD

9. NPPV: Mechanisms of Action in
Acute Respiratory Failure
 Respiratory Muscle Unloading resulting in:
 Decrease PaCO2
 Increase PaO2
 Decrease respiratory rate

10. NPPV for Acute Exacerbation of
COPD- A randomized trial
Brochard et al, NEJM 1995;333:817-22
 Randomized, 5 European Centers
 Usual Care (UC) vs. NPPV
 Inclusion Criteria = RR>30, PaCO2>45, pH<7.30
 Exclusion Criteria = Need For ETT, Extreme Dyspnea
 NPPV group:
 Less intubation (26 vs 74%)
 Less complications (16 vs 48%)
 Shorter hospital stay (23+17 vs 35+33 days)
 Lower mortality (9 vs 29%)

11. Largest Trial-14 UK Hospitals
Conducted on the Wards (not ICU)
•Physiologic improvements of similar magnitude, but occur earlier with NPPV
•26 mins average nursing care burden/day on the wards
•Still, a high rate of death with NIV if more acidotic (? Better in the ICU)

12. Meta-Analysis
NPPV in COPD Exacerbations
Keenan S, Ann Intern Med, 2003
•NPPV best for severe exacerbations of COPD
(hypercapnia)
•Little evidence to support use of NPPV in milder
Exacerbations (PaCO2 < 45)

13.  Expertise of available resources
 Fewer complicating illnesses (esp. pneumonia)
 Hypercapnic Acidosis (pH  7.30)
 Prompt initiation of treatment with rapid
improvement in gas exchange and respiratory rate
 Many questions remain-
 Sedation- what’s the right amount?
 Patient cooperation- how much do you need?
NPPV for Acute Exacerbation of
COPD- Determinants of success
Mehta S, Hill NS, State of the Art: Noninvasive Ventilation. AJRCCM 163:540-77, 2001

14. NPPV (CPAP or Bi-Level) for
Acute Cardiogenic Pulmonary
Edema

15. Mechanisms of Action
 Opens flooded/collapsed alveoli
 (↑ functional residual capacity, improves gas
exchange)
 Decreases cardiac preload
 Decreases cardiac afterload
 Overcomes resistance related to upper airway
edema

16. CPAP unloads the left ventricle and inspiratory
muscles of patients with CHF…
Naughton et al. Circ 1995

17. CPAP May Reduce Ventricular Volumes
Mehta, AJRCCM, 2000

18.  Bi-Level may more effectively unload respiratory
muscles Chadda, et al. Crit Care Med, 2002
 Bi-Level may improve physiologic indices more
rapidly Mehta, et al. Crit Care Med, 1997
BiLevel
CPAP

19. Enthusiasm for Bi-Level
tempered in 1997
p = 0.06
•More patients with chest pain were
randomized to the Bilevel group
•Higher intrathoracic pressures may occur
with BiPAP, particularly with increasing resp.
rates
•Hemodynamic effects could be exaggerated

20. Subsequent Trials have not
replicated such problems with Bi-
Level
 ER based, 38 pts (Levitt M, J Emerg Med 21(4): 2001)
 Lower intubation for BiPAP= 23.8% vs. O2= 41.2%
 No difference in ABGs, pH, and AMI rate was 19% in
the BiPAP and 29.4% for O2 (NS)
 CHF & hypercapnia AJRCCM 2003 Vol 168
 More rapid relief of distress, better gas exchange, and
reduced intubation rate but no mortality change

21. Lancet, 2006

23. Effect of NPPV on
Mortality
Number needed
to treat (NNT)
with CPAP to save
one life: 10

25. Effect of NIPPV on the
need for invasive
mechanical ventilation
NNT = 6
NNT = 7

27. NPPV in Hypoxemic
Respiratory Failure
A heterogeneous group
1. ARDS / Acute lung injury
2. Pneumonia
3. Trauma

28. L’Her, AJRCCM 2005

29.  How does NPPV compare with
conventional mechanical ventilation in
hypoxemic respiratory failure
 Design- Randomized 64 pts. to Bi-Level
NPPV or endotracheal intubation
 Non-COPD pts with Hypoxic ARF
Comparison of NPPV & Conventional
Mechanical Ventilation in Pts with ARF
Antonelli M, NEJM; 339: 429-435, 1998

31. ETT NPPV p<
% ICU Mortality 47 28 0.19
ICU Stay (days) 16+17 9+7 0.04
%Serious complications 66 38 0.02
%ETT rel. pneum/sinus 31 3 0.003
RESULTS
Comparison of NPPV & Conventional
Mechanical Ventilation in Pts with ARF
Antonelli M, NEJM; 339: 429-435, 1998

32.  Conclusions-
 ICU stay and ventilator complications reduced in
pts. with ARF who initially try NPPV
 10/32 pts. failed NPPV- age 47 vs. 66 (p<.006)
 Overall gas exchange improvement similar
 If ETT is avoided, pneumonia is rare
 High mortality if NPPV then ETT(90%)
Comparison of NPPV & Conventional
Mechanical Ventilation in Pts with ARF
Antonelli M, NEJM; 339: 429-435, 1998

33.  Do those without chronic lung disease and free of
hypercapnia respond to CPAP?
 123 Patients with acute lung injury (Pneumonia 50%)
stratified for cardiac disease Mean PaO2/FiO2~ 145
 CPAP 5 to 10 vs. high flow oxygen
 After 1 hr, sig responses greater with CPAP:
 Subjective responses e.g. dyspnea (P<.001)
 PaO2/FiO2= 203 vs. 151 mmHg (P= .02)
Treatment of Hypoxemic, Non-hypercapnic ARF
with CPAP- Randomized Controlled Trial
Delclaux C; (Brochard group) JAMA 284:2352-2360 2000

34.  But, higher overall number of serious adverse events occurred
with CPAP= 18 vs 6 (P= .01)
 Results- No differences in CPAP vs. Std Care:
 Intubation rate= 34% vs. 39% (P= .53)
 Hospital mortality= 31% vs. 30% (P= .89)
 ICU length of stay= 6.5 vs 6.0 days (P= .43)
 Conclusion- Despite early physiologic improvements, CPAP did
not improve outcomes in patients with hypoxia alone
Treatment of Hypoxemic, Non-hypercapnic ARF with
CPAP- Randomized Controlled Trial
Delclaux C; JAMA 284:2352-2360 2000

36. Failure of non-invasive ventilation in patients with
acute lung injury: observational cohort study
Rana S, Gay P, Buck C, Hubmayr R, Gajic O, Crit Care. 2006
 Design:
 Observational cohort study of 79 cons pts with ALI
initially treated with NIPPV- 25 excluded (23 DNR).
 Results:
 54 pts, 38 (70.3%) failed NIPPV, including all 19 pts that
had shock
 Successful pts had:
 Lower Apache III scores (55.5 vs 81.5; p<0.01)
 Less metabolic acidosis (base deficit: 0.52 vs -4.01;
p=0.02) or
 Severe hypoxemia (PaO2/FIO2: 147 vs 112; p= 0.02)

37. Post-operative Use of
NPPV

38. CPAP for Treatment of
Postoperative Hypoxemia
Squadrone, JAMA 2005;293:589-595.
Randomize 209 subjects
Post-Abdominal Surgery
(Cancer and non-cancer)
Probably reverses atelectasis

39. Auriant, AJRCCM, 2001
Bi-Level NPPV to attain
tidal volume of
8 to 10 ml/kg

40.  Randomized 40 solid organ transplant pts
 NPPV pts had better gas exchange and:
 Lower intubation rate (20% vs. 70%; p=0.002)
 Less fatal complications (20% vs. 50%; p= 0.05)
 Lower ICU mortality (20% vs. 50%; p= 0.05), but
hospital mortality same
 Consider NPPV use in these types of patient
NPPV Post-op failure
with Organ Transplantation
Antonelli M, JAMA; 283: 235-241, 2000

41.  Fever, lung infiltrates and early hypoxemic
respiratory failure
 26 NPPV vs. 26 standard-treatment (oxygen)
 NPPV group:
 Reduced intubation (12 vs. 20, p=0.03)
 Less serious complications (13 vs. 21, p=0.02),
 Fewer ICU (10 vs. 18, p=0.03) or hospital deaths (13
vs. 21, p=0.02)
NPPV with Immunosuppression
Hilbert G, NEJM 344: 481-487, 2001

42. NPPV following extubation
from conventional ventilator
(ET tube)
 When to apply NPPV after extubation
 ? Routinely- resource intensive
 ? Wait for respiratory distress—it may be too late
 ? Prevention in selected high risk patients
 Adjunct to weaning: Early extubation for
prolonged weaning failure

43. NPPV for Post-extubation Respiratory
Distress: Randomized Controlled Trial
Keenan SP, JAMA 287:3238-3244, 2002
 Patients- Single Center in Canada
 Mixed Medical and Surgical ICU
 Patients intubated for ≥ 48 hrs, extubated by
standard criteria (n=81)
 Randomization to standard medical therapy
alone vs. NPPV (Bi-level ST) by face mask when
respiratory distress develops:
RR > 30, or > than 50% from baseline, or use
of accessory muscles of respiration or abdominal paradox

44. NPPV for Post-extubation Respiratory
Distress: Randomized Controlled Trial
Keenan SP, JAMA 287:3238-3244, 2002
 Results- No difference
 Rate of reintubation (72% vs 69%)
 Hospital mortality (31% for both)
 Duration of MV (8.4 vs 17.5 days; p=0.11)
 Length of ICU (11.9 vs 10.8 days)
 Hospital stay (32.2 vs 29.8 days)
 Conclusions- NPPV no benefit in unselected
patients with respiratory distress <48 hours
after planned extubation

45. NPPV for Post-extubation Respiratory
Distress
Keenan et al, JAMA 2002
COMMENTS-
 Excluded COPD pts
after first yr
 Used I/E 9/4 cm
H20
 Single center
 Selection bias
 Probably “too little
too late”
0
10
20
30
40
50
60
70
80
90
Reintubated ICU surv Hosp surv Pneumonia
NIV
Control
% pts

46. NPPV with Early Signs of Extubation
Failure
Esteban et al, NEJM 2004; 350:2452
 37 ICUs, 8 countries, N = 993 MV>48h
 228 dev resp distress within 48h of extubation
 Separate randomization for COPD
 Randomization (within 48h of extubation) if:
 Hypercapnia (PaCO2>45 or >20% from pre-extubation)
 Clinical signs of resp muscle fatigue or increased WOB
 Resp rate >25 (for 2 hours)
 Resp acidosis: pH < 7.30 with PaCO2 > 50
 Hypoxemia: SpO2 < 90% or PaO2 < 80 on FiO2 > 0.50

47. NPPV with Early Signs of Extubation
Failure
No diff in age, SAPS II, duration of vent (10 v 11d),
initial cause for RF or pre-extub resp variables
0
5
10
15
20
25
30
35
40
45
50
Reintub ICU LOS d ICU mort Hosp mort Vent Time
Control
NIV
* *
Esteban et al, NEJM 2004; 350:2452

48. Higher Mortality in NPPV Failure
Average time to intubation following failure:
NPPV: 12 hours
Standard: 2.5 hours

49. May NPPV Be Detrimental?
 Very few COPD patients (13%)
 Relatively mild respiratory failure at time of
randomization: RR 29, pH 7.39, PaCO2 46,
PaO2 79
 Delay in definitive treatment (whether NPPV or
intubation) may be costly

50. NPPV to Prevent Respiratory
Failure after Extubation

51.  Hypothesis: Identify “at-risk” patients before
extubation and apply NPPV prophylactically
(age > 65, cardiogenic edema, high Apache)
 Upon extubation: Supplemental oxygen or
immediate BiPAP for 24 hrs
 No more than 4 hrs of NPPV use if signs of
failure and need for re-intubation
Early NIV Averts Extubation Failure
in Pts at Risk
M Ferrer, AJRCCM Vol 173: 164-170, (2006)

52. Early NIV Averts Extubation Failure
in Pts at Risk
M Ferrer, AJRCCM Vol 173: 164-170, (2006).

56. NPPV to Prevent Extubation Failure:
Recommendations
•Routine (self-extubated)- No
•Overt, severe post-extubation failure;
unstable cardiac/other medical problems- No
•In Post-operative patients or Selected High
Risk Patients - Possibly
Delay of reintubation, if needed, beyond 2 – 4
hours may be detrimental

57. Proposed
Mayo
NPPV
Algorithm

58. SUMMARY
NPPV for ARF
 NPPV benefit for COPD exacerbation, CHF
 NPPV vs endotracheal intubation:
 Reduces complications, especially nosocomial
pneumonia for many causes of ARF
 Absolute efficacy for hypoxic ARF or CAP
without COPD is less clear
 NPPV probably beneficial for selected patients
for failed extubation