Insufficienza Respiratoria Andrea Vianello Fisiopatologia e Terapia Intensiva Respiratoria Ospedale – Università di Padova 1

 VE Airway narrowing & obstruction Airway Inflammation  Frictional WOB Shortened muscles curvature Auto- PEEP  Elastic WOB Gas trapping  VCO2  muscle strength  VT  VE  VA PaCO2 pH PaO2

Steroids Abx BDs Teophylline  VE usa i farmaci e bene ! Airway narrowing & obstruction Airway Inflammation Steroids  Frictional WOB Abx Shortened muscles curvature Auto- PEEP BDs  Elastic WOB Gas trapping Teophylline  VCO2  muscle strength  VT  VE  VA PaCO2 pH PaO2

Steroids Abx PEEP BDs Teophylline MV MV  VE MV usa i farmaci e bene ! Airway narrowing & obstruction Airway Inflammation Steroids  Frictional WOB Abx PEEP Shortened muscles curvature Auto- PEEP BDs  Elastic WOB Gas trapping Teophylline MV MV  VCO2  muscle strength  VT  VE MV  VA PaCO2 pH PaO2

Non-Invasive Ventilation “a form of ventilatory support that avoids airway invasion” Hill et al Crit Care Med 2007; 35:2402-7

NIV VS TRATTAMENTO STANDARD Keenan S et al

NIV VS TRATTAMENTO STANDARD Keenan S et al

NIV - Meta-analysis (n=8) NPPV resulted in decreased mortality (RR 0.41; 95% CI 0.26, 0.64), decreased need for ETI (RR 0.42; 95%CI 0.31, 0.59) Greater improvements within 1 hour in pH (WMD 0.03; 95%CI 0.02, 0.04), PaCO2 (WMD -0.40 kPa; 95%CI -0.78, -0.03), RR (WMD –3.08 bpm; 95%CI –4.26, -1.89). Complications associated with treatment (RR 0.32; 95%CI 0.18, 0.56) and length of hospital stay were also reduced with NPPV (WMD –3.24 days; 95%CI –4.42, -2.06) Lightowler, Elliott, Wedzicha & Ram BMJ 2003; 326:185

49 pazienti con IRA in BPCO dopo fallimento terapia medica, pH 7.2 Simili durata di permanenza in ICU, durata VM, complicanze generali, mortalità in ICU, e mortalità in ospedale con NIV 48% evitano ETI, sopravvivono con permanenza in ICU inferiore vs pazienti VM invasiva (P=0.02) A 1 anno: NIV inferiore riospedalizzazione (65% vs 100% P=0.016) e minor frequenza di riutilizzo supplemento di ossigeno (0% vs 36%)

Studio caso-controllo: 64 paz. con IRA trattati con NIV pH = 7.18 40/64 (62%) fallimento NIV (RR con NIV - 38%) Simili mortalità in ICU, e mortalità in ospedale; durata di permanenza in ICU e post ICU, ma: Inferiori complicanze (P=0.01) e probabilità di rimanenere in VM (P=0.056) Se NIV efficace (24/64 = 38%) migliore sopravvivenza e ridotta permanenza in ICU vs pazienti VM invasiva

NIV: Change in practice over time 1992-1996 (mean pH = 7.25+/-0.07) 1997-1999 (7.20+/-0.08; P<0.001). > 1997 - risk of failure pH <7.25 three fold lower than in 1992-1996. > 1997 ARF with a pH >7.28 were treated in Medical Ward (20% vs 60%). Daily cost per patient treated with NIV (€558+/-8 vs €470+/-14,P<0.01) Carlucci et al Intensive Care Med 2003; 3:419-25

Epidemiology Rationale: evidence supporting use of NIV varies widely for different causes of ARF. Population: 11,659,668 cases of ARF from the Nationwide Inpatient Sample during years 2000 to 2009; Objectives: To compare utilization trends and outcomes associated with NIV in patients with and without COPD.

Rationale: The patterns and outcomes of NIV use in patients hospitalized for AECOPD nationwide are unknown. Population: 7,511,267 admissions for acute AE occurred from 1998 to 2008; Objectives: To determine the prevalence and trends of NIV in AECOPD.

Use of NIPPV or IMV as first-line respiratory support in patients hospitalized with AECOPD

Joint BTS/RCP London/Intensive Care Society Guidelines. NIV in COPD Joint BTS/RCP London/Intensive Care Society Guidelines. NIV in COPD. Oct 2008

When to use Non-Invasive Ventilation

Goals of NIV can they be reached? NIV is time consuming, needs proper equipment, enough staff with sufficient expertise. time technical equipment staff expertise predict success of NIV

Eur Respir J 2002; 19: 1159–66

Definition of the three levels of care European Task Force on Respiratory Intermediate Care Survey Corrado et al, ERJ 2002;20:1343-50

Appropriatezza di utilizzo della Ventilazione Non-Invasiva in ambito pneumologico nell’assistenza ai pazienti con BroncoPneumopatia Cronica Ostruttiva in fase acuta.

Rate of NIV failure is extremely different according to study design, severity of illness and level of monitoring

Sixty-two RCTs including a total of 5870 patients Overall NIV failure: 16.3%

NIV – Real Life Evaluation of all 449 patients receiving NPPV for a 1-yr period for acute or acute on chronic RF CPE (n=97) AECOPD (n=87) non-COPD acute hypercapnic RF (n=35) postextubation RF (n=95) acute hypoxemic RF (n=144) Intubation rate was 18%, 24%, 38%, 40%, and 60%, respectively Hospital mortality for patients with acute hypoxemic RF who failed NPPV was 64% Schettino G. Crit Care Med 2008; 36:441-7 24

The percentage of patients transitioned from NIV to IMV ≈ 5% and did not increase from 1998 to 2008

Reasons for low rate of IMV use after NPPV, compared to clinical trial: End of life decision to not accept IMV Patients died before IMV could be started Good selection of appropriate patients

High mortality rate (≈30%) ;↑ over time OR for death:1.63, compared to those initially on IMV ↑hospital stay

Nearly one third of patients for whom there is the best evidence base for NIV did not receive it Admission pH < 7.26: 66% received NIV compared to 34% pH 7.26 to 7.34. Similar lowest pH Significant proportion had a metabolic acidosis Hospital mortality was 25% (270/1077) for patients receiving NIV but 39% (86/219) for those with late onset acidosis “The audit raises concerns that challenge the respiratory community to lead appropriate clinical improvements across the acute sector

Reasons for high mortality rate in patients transitioned to IMV Increased use of NIPPV in patients difficult to ventilate? Continuation of NIPPV despite a lack of early improvement?

Aetiology of NIV failure Failure to adequately ventilate/oxygenate Delayed NIV treatment Inappropriate ventilatory technique Patient’s clinical condition B. Dependence on non-invasive support Lack of improvement of acute illness C. Complications

NIV failure is predicted by: Advanced age High acuity illness on admission (i.e. SAPS-II >34) Acute respiratory distress syndrome Community-acquired pneumonia with or without sepsis Multi-organ system failure

NIV in acute COPD: correlates for success Retrospective analysis 59 episodes of ARF in 47 COPD patients NIV success: 46 NIV failure: 13 Predictors for NIV failure: Higher PaCO2 at admission Worse functional condition Reduced treatment compliance Pneumonia Ambrosino N, Thorax 1995;50:755-7

NIV complications Complication Incidence (%) Major Minor Aspiration pneumonia <5 Haemodinamyc collapse Infrequent Barotrauma Rare Minor Noise 50-10 CO2 rebreathing 50-100 Discomfort 30-50 Claustrophobia 5-20 Nasal skin lesions 2-50

Mask selection - a crucial issue! CO2 rebreathing (50-100%) Noise (50-100%) Leak/Discomfort (30-50%) Claustrophobia (5-20%) Nasal skin lesions (2-50%)

NIV should not be used in: Respiratory arrest Inability to tolerate the device, because of claustrophobia, agitation or uncooperativeness Inability to protect the airway, due to swallowing impairment Excessive secretions not sufficiently managed by clearance techniques Recent upper airway surgery 36

Transition to IMV: when is in the interest of a patient? Hospital mortality: 64% (Schettino, 2008) Mortality rate: 30%; prolonged hospitalization (Chandra, 2011) Great hospital mortality (Walkey, 2013)

Transition to IMV (personal experience, 2011-2013) Number of subjects 62 Age (mean ± SD) , yrs 65.4±19.3 Gender (males, females) 26, 36 Ineffective NIV, n (%) Severe hypercapnia Severe hypoxemia 52 (83.8) 25 (42.4) 21 (35.6) Dependence on NIV, n (%) 8 (13.3) NIV complication, n (%) 2 (3.4) Tracheotomy, n (%) 16 (28.8) Outcome , n (%) Died during hosp Discharged from hosp 41 (66.1) 21 (33.9)

Kaplan-Meier function of overall survival Median survival: 46 days (95% CI, 43 to 162) Kaplan-Meier function of overall survival

Kaplan-Meier function of survival according to baseline condition Mean survival: NM/CW = 305.58±36.9 COPD = 53.90±7.3 ILD = 31.13±7.8 ] p=0.0176 ] p<0.0001 Kaplan-Meier function of survival according to baseline condition

Kaplan-Meier function of survival for dichotomus age (50 and >50) Median survival: 50 = 380.0 d (95%CI, 15.0 to n.c.) >50 = 45.0 d (95%CI,24.0 to 54.0) ] p=0.0071 Kaplan-Meier function of survival for dichotomus age (50 and >50)

Remarks Mortality rate among patients transitioned to IMV is very high; The outcome of patients with ILD is extremely poor. Should IPF/COPD patients be excluded from IMV after failing a NIV trial?

Use of a novel veno-venous extracorporeal carbon dioxide removal system as an alternative to endotracheal intubation in a lung transplant candidate with acute respiratory failure. Submitted to Respiratory Care

NIV in AECOPD: conclusions Confirm and reinforce the routine use of NIV, however: Suggest caution with NIV among patients at high risk of failure The problem of transitioning from NIV to IMV: may not be in the interest of patients!