Conflicts of Interest

1. NPPV in Adult and Pediatric PatientsGiorgio Conti MDIntensive Care and Anesthesia DeptCatholic University of Rome

2. Conflicts of Interest • Medical advisor of Nihon Kohden Orangemed • Research fundings to the Anesthesia Dept of the Catholic University of Rome from Orionpharma (Finland)

3. Noninvasive Ventilation definition: - NIV can be defined as a form of assisted ventilation without an artificial airway Transition from Invasive Ventilation to NIV to HFNC (O2) Therapy) NKV-550 Ventilator

4. NPPV: PHYSIOLOGIC TARGETS • Decrease in diaphragmatic activity • Decrease PaC02 • Increase pH • Improve PaO2 • Offset the PEEPi level • Decrease WOB • Prevent ETI

5. NPPV advantages: • Avoid local trauma due to ETT • No interference with speech or swallowing • No interference with airway clearance • More patient comfort • Offset additional WOB due the ET • Possibility of intermittent use !

6. NPPV in Patients with COPD exacerbation

7. Early Established Resolving Post-extubation 1 2 4 3 COPD: Timing of NPPV Application • 1. Early: to prevent intubation • 2. Established: as alternative to intubation • 3. Resolving: to wean from ventilation • 4. Post-extubation: to prevent re-intubation Conventional MV with ETI ?

8. NONINVASIVE VENTILATION FOR ACUTE EXACERBATION OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE Brochard L,Mancebo J,Wysocki M,Lofaso F, Conti G. et al : The New England Journal of Medicine 1995,333,817-22

9. ET intubation Length of stay Mortality NIV – PSV ( n=43 ) 26 % 23 ± 17 days 9 % O2( n=42 ) 74 % 35 ± 33 days 29 % NIV in COPD exacerbations Physiological effects Brochard L et al. NEJM 1995; 333: 817

10. Early use of NIV for acute exacerbations of COPD on general respiratory wards: a multicentre RCT 236 randomized 118 standard therapy 118 NIV 32 met criteria for intubation 86 treated successfully 18 met criteria for intubation 100 treated successfully 24 died 94 survived 12 died 106 survived PK Plant et al: The Lancet vol 355 June 3, 2000

11. Need for intubation and in hospital mortality PK Plant et al: The Lancet vol 355 June 3, 2000

13. Early Established Resolving Post-extubation 1 2 4 3 COPD: Timing of NPPV Application • 1.Early: to prevent intubation • 2. Established: as alternative to intubation • 3. Resolving: to wean from ventilation • 4. Post-extubation: to prevent re-intubation Conventional MV with ETI ?

14. Aim of the study: To compare NIV and CMV with ETI in Pts failing to respond standard medical treatment and who required ventilatory support NIV vs. conventional MV in COPD patients after failure of medical treatment in the ward: a RCT G. Conti et al. Intensive Care Med 2002,1701-1707

15. Assessed for eligibility (n=94) for AGE, SEX, SAPS, KELLY,WBC, Excluded (n=45) Not meeting inclusion criteria (n=45) * Enrollment ICU admission • COPD exacerbation, *Randomised (n=49) • pH < 7.20 • SO < 90% 2 +(2 or more): RR > 35 • Kelly score > 3 Allocated to NPPV (n=23)Received allocated intervention (n=23) Allocated to conventional MV (n=26)Received allocated intevention (n=26) Allocation Lost to follow up (n=0)Discontinued intervention (n=12) (intubation required) Lost follow up (n=0)Discontinued intervention (n=0) Follow up Analysed (n=23)Excluded from analysis (n=0) Analysed (n=26)Excluded from analysis (n=0) Analysis

16. Changes in PaCO2 and pH over time:

17. RESULTS: • 12 /23 (52%) failed NIV • ICU survival similar (NIV 78% vs Conv 85%) • Hospital mortalitysimilar (26% vs 19%) • Similar ICU Lenght of Stay & Complications

20. Conclusions In the subgroup of COPD pts in whichintubationwasavoided, survival wasincreased, and ICU LOS, length of ventilatory support and no. of early and late complicationswerereduced.

21. Early Established Resolving Post-extubation 1 2 4 3 COPD: Timing of NPPV Application • 1.Early: to prevent intubation • 2. Established: as alternative to intubation • 3. Resolving: to wean from ventilation • 4. Post-extubation: to prevent re-intubation Conventional MV with ETI ?

22. NPPV as a weaning tool in COPD Intubated COPD patients (50 Pts) T-piece trial within 48 h after ET intubation Patients tolerate: Extubation Patients do not tolerate Standard weaning: ET tube + PSV Extubation + continuous NPPV Nava S et al. Ann Intern Med 1998;128:721-8

23. From Nava S et al . Ann Intern Med 1998

24. NPPV during persistent weaning failure Invasive MV ³3 d (77% chronic respiratory diseases) T-piece trial failure during 3 consecutive days Standard weaning: daily T-piece trial (n=22) Extubation + continuous NPPV (n=21) Ferrer M: NIV during persistent weaning failure: a RCT Am J Respir Crit Care Med 2003,168: 70-76

25. NPPV during persistent weaning failure ICU Survival Tracheotomy Re-intubation p=NS p<0.001 p=0.045 30 100 n=19 n=13 n=6 60 80 50 n=13 20 40 60 % n=3 30 40 10 20 n=1 20 10 0 0 0 NPPV Control NPPV Control NPPV Control Ferrer M: NIV during persistent weaning failure: a RCT Am J Respir Crit Care Med 2003,168: 70-76

26. Use of NIV in COPD exacerbations Effect: mortality We recommend bilevel NIV for patients with ARF leading to acute or acute-on-chronic respiratory acidosis (pH ⩽7.35) due to COPD exacerbation. (Strong recommendation, high certainty of evidence) Rochwerg B, et al. Eur Respir J 2017;50:1602426

27. NPPV in hypoxemic ARF patients

28. 354 consecutive patients with hypoxemic ARF • in 7 Centers (Europe and USA): • PaO2/FiO2 < 200 breathing O2 (Venturi) • RR>30, AC accessory muscles or paradoxical abd. Mot. • COPD excluded 86 ARDS (P/F < 200, bil. Pulm.infiltrates, absence of LVF) • 108 (30%) failure • 264 (70%)success Antonelli, Conti et al. Intensive Care Med, nov. 2001

29. Physiologic Effects of Noninvasive Ventilation during ALIErwan L’Her, et AL, AJRCCM 2005; 172:1112-1118

30. Antonelli,Conti et al NEJM 1998;339;429-435 • To compare FM NPPV with ETI+ MV for hypoxemic ARF in pts requiring MV • prospective randomized study • single center • 64 patients with ARF: (PaO2/FiO2 < 200) breathing 50% O2 (Venturi) RR>35, accessory muscles or paradoxical abd. Mot. • 32 randomized to NPPV and 32 to ETI+MV • COPD excluded

31. Antonelli, Conti et al NEJM 1998;339:429-35 (RCT) • In Survivors shorter MV duration (3±3 vs 6±5 days, P=0.006) • Los in ICU (6.6±6 vs 14±13 days, P=0.002) • PN & sinusitis lower in NIV group [1(3%) vs 10(31%), P=0.003] • Mortality not different (28% vs 47%) 31% P=0.003 3%

32. Noninvasive Ventilation in Severe HypoxemicRespiratory Failure: A Randomized Clinical TrialMiquel Ferrer, AJRCCM 2003;168: 1438–1444 46/51(91%)of NIV pts had pulmonary infiltrates and ALI/ARDS

34. NPPV in immunocompromised patients with ARF

35. Antonelli,Conti et Al JAMA 2000;283:235-241 (P/F < 200, RR 35b/min, Active Contraction of AM or PAM, severe dyspnea) COPD excluded NIV vs Venturi+MT to prevent ETI in 40 pts with hypoxemic ARF, after Solid Organ transplant (L,L,K) 20 Pts NIV, 20 Venturi NIV associated with less ETI (20% vs 70%, P=.05), sepsis and SS (including VAP) (20% vs 50%, P=0.047)

37. DoesNIV allows the prognostic improvement of immunocompromised pts. admitted to the ICU with PULMONARY INFILTRATES + Fever + ARF ? G. Hilbert, N ENGL J MED 2001 METHODS 52 pts with HEMATOLOGICAL MALIGNANCIES, NEUTROPENIA IMMUNOCOMPROMISED, AIDS PULMONARY INFILTRATES - FEVER - Dyspea, RR > 30/min - PaO2/FiO2 < 200 26 PTS NPPV Random assignment 26 PTS O2

38. RESULTS II NIV Standard RR Treatment p (95% CI) Intubation - no./no.total (%) 12/26 (46) 20/26 (77) 0.03 0.60 (0.38-0.96) Hematological malignancies 8/15 (53) 14/15 (93) 0.02 0.57 (0.35-0.93) Immunosuppressor 3/9 (33) 5/9 (56) 0.32 0.60 (0.20-1.79) AIDS 1/2 (50) 1/2 (50) 0.83 Ventilation (D) Total 6  3 6  5 0.59 Ventilation (D) Survivors 5  2 3 5 0.12 LoS in the ICU (D) Total 7  3 9 4 0.11 LoS in the ICU (D) Survivor 7  3 10 4 0.06 Complications- no. (%)13 (50) 21 (81) 0.02 Complications  death 10 (38) 18 (69) 0.03 V.A.P. and/or Sinusitis -no. (%) 3 (12) 9 (35) 0.05

40. NIV O2

42. Use of NIV in immunocompromised patients Effect: mortality We suggest early NIV for immunocompromised patients with ARF. (Conditional recommendation, moderate certainty of evidence) Rochwerg B, et al. Eur Respir J 2017;50:1602426

49. NIV in patients with ARDS: the LUNG-SAFE analysis 459 ICUs 50 Countries Bellani G et al. Am J Resp Crit Care Med 2016;10.1164/rccm.201606-1306OC (18-October-2016)