1. Immunosuppressed ARF 40 patient RCT of NIV(20) vs standard therapy(20)
Solid organ transplant patients
Respiratory distress
Intermittent NIV
NIV group
Inc P/F ratio at 1 hr
Dec intubation rate
Dec rate of severe sepsis
Dec ICU mortality
Hospital mortality: same
Antonelli M, et al. JAMA 2000; 283: 235

2. Timing of Endotracheal Intubation in the 2 Groups
Changes in the Ratio of PaO2 to Fraction of Inspired Oxygen (FIO2) and PaCO2 Over Time
Timing of Endotracheal Intubation in the 2 Groups
Antonelli, M. et al. JAMA 2000;283:

3. Immunosuppressed ARF
52 patient RCT of NIV (26) vs standard therapy (26)
Pulmonary infiltrate, fever and hypoxemic ARF
Neutropenia, immunosuppressive drugs, post-transplant, ARDS
NIV group
Dec intubation rate
Dec serious complications
Dec ICU mortality
Dec hospital mortality
Hilbert G, et al. NEJM 2001; 344: 481

4. Hilbert G, et al. NEJM 2001; 344: 481

5. Immunosuppressed: Use NIV
Hilbert G, et al. NEJM 2001; 344: 481

6. ALI/ARDS 123 patient RCT of NIV vs standard NIV group
55% pneumonia
17% cardiogenic APO
NIV group
Inc 1 hr oxygenation
Same intubation rate
Same hospital mortality
Same ICU LOS
Inc adverse events
4 pts had cardiac arrest (3 at time of intubation)
4 pts had stress ulcers
Delclaux C, et al. JAMA 2000; 284: 2352

7. ARDS: avoid NIV
Delclaux C, et al. JAMA 2000; 284: 2352

8. Post-op hypoxemia Multi-centre RCT from Italy 209 patients
CPAP 7.5 vs oxygen
Trial ceased early
CPAP had lower
Intubation rate
Pneumonia
Sepsis
ICU LOS (1.4 vs 2.6)
Same hospital LOS and few deaths
Squadrone V, et al. JAMA 2005; 293: 509

9. Squadrone V, et al. JAMA 2005; 293: 509

10. Post-op ARF: Use NIV

11. Asthma

12. Asthma Singel centre RCT from Israel 30 patients in ED BiPAP vs sham
Nasal IPAP 8 – 15
EPAP 3 – 5
For 3 hours
NIV increased FEV1 and reduced hospitalisation
Soroksky A, et al. Chest 2003; 123: 1018

15. Asthma: more trials

16. Chest trauma 69 patient RCT of CPAP vs ETI/MV CPAP >3 rib fractures
Insufficient cough
Epidural analgesia in CPAP group
CPAP
Reduced ICU LOS
Reduced hospital LOS
Reduced pneumonia
Bolliger CT, et al. Chest 1990; 97: 943

17. Chest trauma: more trials
52 patient RCT of CPAP vs ETI/MV
PCA in CPAP group
CPAP
Reduced nosocomial infection
Reduced mortality
Lower PaO2 in first 2 days
Same duration of ICU stay
Chest trauma: more trials
Gunduz M, et al. Emerg Med J. 2003; 22: 325

18. Post-extubation ARF: NIV to treat?
221 patient RCT of NIV vs standard
Same
Reintubation rate
But NIV increased
Mortality
Reintubation delay
12 hours vs 2.5 hours (p=0.02)
Esteban A, et al. NEJM 2004; 350: 24

19. Esteban A, et al. NEJM 2004; 350: 24

20. Post-extubation ARF – NIV to prevent?
97 patient RCT of NIV vs standard when at increased risk of post-op ARF
> 8 hours NIV for 48 hours
NIV lowered
Reintubation rate
Multivariate analysis
NIV reduced ICU mortality
Nava S, et al. CCM 2005; 33: 246S

21. Post-extubation ARF – NIV to prevent?
162 patient RCT of NIV vs standard when at increased risk of post-op ARF (24 hours of NIV)
If no signs of spontaneous breathing failure appeared after 30 to 120 min of a T-piece trial, patients were extubated and randomly allocated,
received NIV (NIV group) or
those who underwent conventional management (control group).
Ferrer M, et al. AJRCCM 2006; 173: 164

22. Ferrer M, et al. AJRCCM 2006; 173: 164

23. Post-extubation ARF: may be to prevent
Ferrer M, et al. AJRCCM 2006; 173: 164

24. Early weaning from MV - COPD
50 patient RCT of NIV vs MV
48 hrs after intubation, if failed a T-piece trial, received either NIV vs continued MV
NIV lead to reduced
Duration of MV
ICU LOS
Mortality (D60 survival rates 92% for NIV and 72% for MV; P = 0.009).
Pneumonia
Nava S, et al. Ann Intern Med 1998; 128: 721

27. Nava, S. et. al. Ann Intern Med 1998;128:721-728
Kaplan-Meier curves for COPD patients who could not be weaned from mechanical ventilation (defined as weaning failure or death linked to mechanical ventilation) in the two groups
NIV
Nava, S. et. al. Ann Intern Med 1998;128:

28. Early weaning from MV - ARF
43 patient RCT of NIV vs MV
If failed a T-piece trial 3 consecutive days
Study stopped at interim analysis
NIV lead to reduced
Duration of MV
ICU and hospital LOS
Tracheostomy rate
Pneumonia
Septic shock
ICU and 90 day mortality
Ferrer M, et al. AJRCCM 2003; 168: 70

29. Ferrer M, et al. AJRCCM 2003; 168: 70

30. Ferrer M, et al. AJRCCM 2003; 168: 70

31. Weaning from MV: Use NIV (esp COPD)
NPPV as a weaning strategy for intubated adults with respiratory failure: metaanalysis.
MEDLINE (January 1966 to July 2003) and EMBASE (January 1980 to July 2003)
Early extubation with immediate application of NPPV vs IPPV weaning in intubated adults with respiratory failure.
11 RCT trials, of which five were included, 171 participants (predominantly COPD)
Compared to the IPPV strategy, the NPPV strategy
decreased mortality
the incidence of ventilator associated pneumonia
intensive care unit length of stay
hospital length of stay
total duration of mechanical support
duration of endotracheal mechanical ventilation
Conclusion: use of NPPV to facilitate weaning in mechanically ventilated patients with predominantly COPD is associated with promising, although insufficient, evidence of net clinical benefit.
Weaning from MV: Use NIV (esp COPD)
Burns, K, et al. Cochrane Database of Systematic Reviews. 1, 2006.

32. Severe acute respiratory syndrome (SARS)
A triphasic disease
Fever
Myalgia
Headache
Other systemic symptoms
Oxygen desaturation
Progressive CXR abnormalitis
ADRS
Lung destruction
Lung fibrosis
IgG
Viral load
Viral replication phase & cytololysis
Immunopathological phase
Immunoparesis & lung destruction phase (or recovery)
Peiris et al. Lancet 2003

33. Ref: Peiris et al 2003. Lancet.

34. Ref: Peiris et al 2003. Lancet.

35. Exhaled aerosol dispersal pattern during high-flow oxygen administration with a conventional, noninvasive face mask
Ref: Fowler RA, NEJM 2004

36. Author
Pts no
Results
Chen H 2003 25
Non-survivors had higher RR & lower SpO2 within 24 hrs of support, 48% having had NIV died
Li H 2003 24
NIV could dec chance of MV, 5% of the entire cohort of 104 cases died, 16.7% subcutaneous emphysema
Liu XQ 2003 33
CPAP: Improved oxygenation & RR within 1 hr
Luo D NA
CPAP/BIPAP: IPAP 6 – 10 cmH2O
Xiao Z 2003
9% of the entire cohort of 78 cases died
Wu W 2003 9
9 on BIPAP in 9.4% of 96 patients, one (1.0%) died
Zhao Z 2003 62
11 out of the entire cohort of 190 died (5.8%). Patients using different pharmacological treatment were compared (best outcome with high dose steroid + CPAP: zero mortality in 60 patients)
Cheung 2004*
Lau 2004 20
Intubation avoided in 70%, 15% patients on NIV died; 3.5% of the total 90 patients died
Han F 2004* 28
One intolerant, Inc PaO2, SpO2, PaO2/FiO2, dec RR within 1 hr. 66.7% could wean off NIV; fatality rate 6.7% in entire cohort of 120 patients; intubated avoid in 2/3 of patients (N = 120)
Vu HT 2004 6
Not specifically mentioned
Yang L 2004 27
Pneumothorax and mediastinal emphysema (25.9%), incidence was significantly higher than in cases of SARS without receiving MV and NIV

37. Progress on NIV
Cheung et al. CHEST 2004

38. Non-invasive versus invasive mechanical ventilation for respiratory failure in severe acute respiratory syndrome
Yam LYC et al. Chinese Med J 2005

39. Lab findings and resp status

40. Compared with IMV hospitals:
1. NIV hospitals had lower need for IMV (21.4% vs 41.2%), p = 0.012
2. Death (9.5% vs 25.1%), p =

41. Time from symptom onset to intervention
Time to invasive mechanical ventilation can be delayed to D21 (vs D11), at a time when the patient has less viral excretion

42. Infection risk to HCW
Nurses caring for 6 NIV patients “may be at an increased risk” (RR 2.33, p = 0.5); but still advised against use of NIV by the authors – Fowler et al. AJRCCM 2003
105 medical and nursing staff involved with care of 20 patients with NIV, none acquired clinical SARS, none had positive serology – Cheung et al. Chest 2004
None of the HCW contracted SARS during the care of 28 patients receiving NPPV – Han F et al. Sleep Breath 2004

43. Summary of possible benefits of NIV
For patients:
Early application could rapidly improve vital signs, oxygenation and tachypnoea (So 2003, Cheung 2004, Liu 2003)
Avoid intubation in up to two-thirds of patients (Zhao 2003, Zhong 2003, Cheung, Yam 2005)
Reduce chance of ventilator-associated complications: pneumonia and barotrauma (combination of pneumothorax, pneumomediastinum, subcutaneous emphysema in 20 – 30%) (Fowler 2003, Lew 2003, Gomersall 2004, Buckley 2004)
Buys time for immunomodulatory agents to work

44. Summary of possible benefits of NIV
For HCW:
Reduces need for high flow oxygen, and the resulting aerosol
Jet of exhaled gas is downwards
Reduces chance of HCW infection during high-risk intubation (reduce the need of intubation
Delays the time to intubation to a time when the patient is less infectious
For the outbreak:
Limited availability of positive-pressure ventilation (Chinese Thoracic Society 2003)

45. Infection control Mandatory Provisions CDC Recommendations
“Guidelines for Environmental Infection Control in Health-Care Facilities, June 2003”
Uni-directional airflow from clean to dirty area.
Negative pressure patient rooms.
Pressure gradient not so steep as to create air turbulence (2.5 Pa).
High level supply/Low level exhaust.
12 air changes per hour.
Door to be provided to all ward cubicles.
Air-tight patient room construction.

46. Mandatory Provisions Operational Considerations
Air supply adjustable between 100% fresh air and 30% fresh air with 70% recirculation.
HEPA-filtered return air to staff/non-patient areas.
Temperature 20-22ºC, relative humidity 50-60%.
Air-lock at ward entrance.
Wash-hand basins with auto-taps.
Staff facilities – gowning / de-gowning areas, toilets, showers etc.

47. Infection control for NIV
Strict environmental control measure
Zero staff infection from one reported series, provided excellent environmental ventilation (> 8-12 ACH) and appropriate PPE are ensured. Cheung et al. CHEST 2004
Viral filter between mask and expiratory port
Expiratory port: round-the-tube outflow (Whisper-swivel II, Respironics Inc).
Independent inspiratory & expiratory tubings with viral filters by using conventional ventilator to deliver NIV.
Use AIRMATE in the health care worker who needs to come into close contact with patient on NIV

48. Viral filters Between patient and machine
Between patient and pressure transducer

49. Expiratory port with round-the-tube outflow (Whisper-swivel II, Respironics Inc)
Facial mask
Expiratory port

50. Things to avoid
? Facial mask better than nasal mask

51. Test strip to detect airflow direction

52. ICU/HDU setup

58. SARS: Use NIV, only under strict infection control

59. Summary (1) SARS COPD Use NIV Acute cardiogenic pulmonary edema (CPE)
Use CPAP
Hypoxemic respiratory failure (ARF)
Use NIV, individualize
Pneumonia
More trials
Immunosuppressed with ARF
ALI/ARDS
Avoid NIV
Post-operative ARF
Asthma
Chest trauma
Post-extubation ARF
Maybe to prevent
Weaning from mechanical ventilation
SARS
Use NIV, only if adequate infection control
SARS

60. Summary (2)
Use NIV for
COPD
Acute CPE
Hypoxemic ARF
Immunosuppressed pts with ARF
Post-op hypoxemia
Weaning from MV
SARS, if and only if good infection control measures are observed
More trials required for pnemonia, asthma, chest trauma and prevention of post-op ARF
Avoid NIV for established ALI/ARDS

61. Caveats regarding NIV studies
Few studies have been blinded
Many patients have been excluded from these trials
Resp arrest
Severe hemodynamic instability
Encephalopathy
Poor cough
>2 organ failure
Severe resp acidosis
Equipment and settings have varied widely
Often NIV has been (and should still be) a “try early and bail out” strategy

62. Predicting NIV failure

63. COPD: Nasal mechanical ventilation for hypercapnic respiratory failure in chronic obstructive pulmonary disease: determinants of success and failure.
Success (7)
Failure (7)
APAPCHE II 15 21
Teeth Y N
Pneumonia
43%
Excess secretions
Mouth leaks, ml
100
314
Poor coordination
After 1 hr: dec PaCO2 > 10, RR, inc pH >0.05
Soo Hoo et al. CCM 1994

64. COPD: Predicting the Result of Noninvasive Ventilation in Severe Acute Exacerbations of Patients With Chronic Airflow Limitation episodes with face mask NIV
Success (34)
Failure (10)
APACHE II 19 20
FEV1 (%) 27 38
Level Conscious
(1-4)
2.4 to 1.6
(improved)
2.8 to 3
(worsened)
PaCO2
(baseline to 1 hr)
81 to 68
81 to 84 pH
7.27 to 7.34
7.28 to 7.28
Anton et al. Chest 2000

65. COPD: A chart of failure risk for noninvasive ventilation in patients with COPD exacerbation.
Two risk charts were designed (at admission and after 2 h of NPPV) that included pH, RR APACHE, GCS derived from a population representing the patients seen routinely in clinical practice
Risk stratification of NPPV failure was assessed in 1,033 consecutive patients
Following patients have a predicted risk failure > 70%
Glasgow Coma Score <11
acute physiology and chronic health evaluation (APACHE) II > or =29
respiratory rate > or =30 breaths x min(-1)
pH at admission <7.25
A pH <7.25 after 2 h greatly increases the risk (>90%)
To identify patients with a probability of failure >50%
sensitivity and specificity were 33% and 96.7% on admission
52.9% and 94.1% after 2 h of NPPV, respectively.
Confalonieri et al. ERJ 2005

66. Condition Adjusted OR ARDS or CAP 3.75 PaO2/FiO2 ≤ 146 2.51
Acute hypoxemic RF: Predictors of failure of noninvasive positive pressure ventilation in patients with acute hypoxemic respiratory failure: a multi-center study.
N= 354, Italian multicenter study, 30% failed
highest in ARDS and CAP – 50%
lowest in cardiogenic pulmonary edema - 10%
Condition
Adjusted OR
ARDS or CAP
3.75
PaO2/FiO2 ≤ 146
2.51
SAPS II ≥ 35
1.81
Age > 40
1.72
Antonelli et al. Int Care Med 2001

67. Objectives To know about the practical aspects of NIV
Literature review of the application and efficacy of NIV in various acute clinical conditions, including SARS
Predictors of NIV failure in general

68. Thank you.