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Immunosuppressed ARF n 40 patient RCT of NIV(20) vs standard therapy(20) – Solid organ Immunosuppressed ARF n 40 patient RCT of NIV(20) vs standard therapy(20) – Solid organ transplant patients – Respiratory distress – Intermittent NIV n NIV group – – n 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

Timing of Endotracheal Intubation in the 2 Groups Changes in the Ratio of Pa. Timing of Endotracheal Intubation in the 2 Groups Changes in the Ratio of Pa. O 2 to Fraction of Inspired Oxygen (FIO 2) and Pa. CO 2 Over Time Antonelli, M. et al. JAMA 2000; 283: 235 -241.

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

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

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

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

Delclaux C, et al. JAMA 2000; 284: 2352 Delclaux C, et al. JAMA 2000; 284: 2352

Post-op hypoxemia n n n Multi-centre RCT from Italy 209 patients CPAP 7. 5 Post-op hypoxemia n n n 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

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

Asthma Asthma

Asthma n n n n Singel centre RCT from Israel 30 patients in ED Asthma n n n n Singel centre RCT from Israel 30 patients in ED Bi. PAP vs sham Nasal IPAP 8 – 15 EPAP 3 – 5 For 3 hours NIV increased FEV 1 and reduced hospitalisation Soroksky A, et al. Chest 2003; 123: 1018

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

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

Post-extubation ARF: NIV to treat? 221 patient RCT of NIV vs standard n Same Post-extubation ARF: NIV to treat? 221 patient RCT of NIV vs standard n Same n – Reintubation rate n But NIV increased – Mortality – Reintubation delay n 12 hours vs 2. 5 hours (p=0. 02) Esteban A, et al. NEJM 2004; 350: 24

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

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

Post-extubation ARF – NIV to prevent? n n 162 patient RCT of NIV vs Post-extubation ARF – NIV to prevent? n n 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

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

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

Early weaning from MV COPD n 50 patient RCT of NIV vs MV – Early weaning from MV COPD n 50 patient RCT of NIV vs MV – 48 hrs after intubation, if failed a T-piece trial, received either NIV vs continued MV n NIV lead to reduced – – – Duration of MV ICU LOS Mortality (D 60 survival rates 92% for NIV and 72% for MV; P = 0. 009). – Pneumonia Nava S, et al. Ann Intern Med 1998; 128: 721

Kaplan-Meier curves for COPD patients who could not be weaned from mechanical ventilation (defined 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: 721 -728

Early weaning from MV ARF n 43 patient RCT of NIV vs MV – Early weaning from MV ARF n 43 patient RCT of NIV vs MV – If failed a T-piece trial 3 consecutive days – Study stopped at interim analysis n 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

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

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

NPPV as a weaning strategy for intubated adults with respiratory failure: metaanalysis. n n NPPV as a weaning strategy for intubated adults with respiratory failure: metaanalysis. n n n 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. Burns, K, et al. Cochrane Database of Systematic Reviews. 1, 2006.

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

Ref: Peiris et al 2003. Lancet. Ref: Peiris et al 2003. Lancet.

Ref: Peiris et al 2003. Lancet. Ref: Peiris et al 2003. Lancet.

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

Author Pts no Results Chen H 2003 25 Non-survivors had higher RR & lower Author Pts no Results Chen H 2003 25 Non-survivors had higher RR & lower Sp. O 2 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 cm. H 2 O Xiao Z 2003 24 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 Pa. O 2, Sp. O 2, Pa. O 2/Fi. O 2, 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

Progress on NIV Cheung et al. CHEST 2004 Progress on NIV Cheung et al. CHEST 2004

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

Lab findings and resp status Lab findings and resp status

Compared with IMV hospitals: 1. NIV hospitals had lower need for IMV (21. 4% 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 = 0. 0003

Time from symptom onset to intervention Time to invasive mechanical ventilation can be delayed Time from symptom onset to intervention Time to invasive mechanical ventilation can be delayed to D 21 (vs D 11), at a time when the patient has less viral excretion

Infection risk to HCW n n Nurses caring for 6 NIV patients “may be Infection risk to HCW n n 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 n None of the HCW contracted SARS during the care of 28 patients receiving NPPV – Han F et al. Sleep Breath 2004

Summary of possible benefits of NIV For patients: n Early application could rapidly improve Summary of possible benefits of NIV For patients: n Early application could rapidly improve vital signs, oxygenation and tachypnoea (So 2003, Cheung 2004, Liu 2003) n Avoid intubation in up to two-thirds of patients (Zhao 2003, Zhong 2003, Cheung, Yam 2005) n 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) n Buys time for immunomodulatory agents to work

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

Infection control Mandatory Provisions CDC Recommendations “Guidelines for Environmental Infection Control in Health-Care Facilities, Infection control Mandatory Provisions CDC Recommendations “Guidelines for Environmental Infection Control in Health-Care Facilities, June 2003” 1. 2. 3. 4. 5. 6. 7. 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.

Mandatory Provisions Operational Considerations 1. 2. 3. 4. 5. 6. Air supply adjustable between Mandatory Provisions Operational Considerations 1. 2. 3. 4. 5. 6. 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.

Infection control for NIV n Strict environmental control measure – Zero staff infection from Infection control for NIV n 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 n Viral filter between mask and expiratory port n Expiratory port: round-the-tube outflow (Whisperswivel II, Respironics Inc). n Independent inspiratory & expiratory tubings with viral filters by using conventional ventilator to deliver NIV. n Use AIRMATE in the health care worker who needs to come into close contact with patient on NIV

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

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

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

Test strip to detect airflow direction Test strip to detect airflow direction

ICU/HDU setup ICU/HDU setup

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

Summary (2) n n n Use NIV for – – – – COPD Acute Summary (2) n n n 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

Caveats regarding NIV studies n n Few studies have been blinded Many patients have Caveats regarding NIV studies n n Few studies have been blinded Many patients have been excluded from these trials – – – n n 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

Predicting NIV failure Predicting NIV failure

COPD: Nasal mechanical ventilation for hypercapnic respiratory failure in chronic obstructive pulmonary disease: determinants 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 N 43% Excess secretions N Y 100 314 Poor coordination N Y After 1 hr: dec Pa. CO 2 > 10, RR, inc p. H >0. 05 Y N Mouth leaks, ml Soo Hoo et al. CCM 1994

COPD: Predicting the Result of Noninvasive Ventilation in Severe Acute Exacerbations of Patients With COPD: Predicting the Result of Noninvasive Ventilation in Severe Acute Exacerbations of Patients With Chronic Airflow Limitation - 44 episodes with face mask NIV Success (34) Failure (10) APACHE II 19 20 FEV 1 (%) 27 38 2. 4 to 1. 6 (improved) 2. 8 to 3 (worsened) Pa. CO 2 (baseline to 1 hr) 81 to 68 81 to 84 p. H (baseline to 1 hr) 7. 27 to 7. 34 7. 28 to 7. 28 Level Conscious (1 -4) Anton et al. Chest 2000

COPD: A chart of failure risk for noninvasive ventilation in patients with COPD exacerbation. COPD: A chart of failure risk for noninvasive ventilation in patients with COPD exacerbation. n n n Two risk charts were designed (at admission and after 2 h of NPPV) that included p. H, 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) p. H at admission <7. 25 n A p. H <7. 25 after 2 h greatly increases the risk (>90%) n 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

Acute hypoxemic RF: Predictors of failure of noninvasive positive pressure ventilation in patients with 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 Pa. O 2/Fi. O 2 ≤ 146 2. 51 SAPS II ≥ 35 1. 81 Age > 40 1. 72 Antonelli et al. Int Care Med 2001

Objectives 1. 2. 3. To know about the practical aspects of NIV Literature review Objectives 1. 2. 3. 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

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