Quando la NIV non basta. Andrea Vianello Fisiopatologia e Terapia Intensiva Respiratoria Ospedale-Università di Padova

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Quando la NIV non basta Andrea Vianello Fisiopatologia e Terapia Intensiva Respiratoria Ospedale-Università di Padova

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

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.

Acute respiratory failure-associated diagnosis Changing etiologies of ARF among patients receiving NIV

20% of patients without a COPD diagnosis who received NIV IMV; 13.4% of patients with COPD who received NIV IMV; Patients experiencing NIV failure before transition to IMV had greater hospital mortality than those initially on IMV.

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

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

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

NIV reasons for failure ACPE COPD Non COPD ALI/ARDS Hypoxemia + + +++ Hypercapnia + ++ + Leak/Mask + + ++ ++ intol Secretion + + + Mentation + + + + Agitation + ++ Progression + +++ Failure Rate 18% 24% 37% 60% Schettino G. Crit Care Med 2008; 36:441-7

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, 2011-2014) 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)

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

NIV reasons for failure ACPE COPD Non COPD ALI/ARDS Hypoxemia + + +++ Hypercapnia + ++ + Leak/Mask intol + + ++ ++ Secretion + + + Mentation + + + + Agitation + ++ Progression + +++ Failure Rate 18% 24% 37% 60% Schettino G. Crit Care Med 2008; 36:441-7

A requirement to effectively counteract hypercapnia!

Gas containing little or no CO2 Diffusion

The membrane lung

The pump Membrane lung Membrane lung Membrane lung Three configurations of extracorporeal blood flow (a) single-site double lumen veno-venous (VV), (b) two-site VV, and (c) arterio-venous

Greater diffusibility of CO2 compared to O2 across extracorporeal membranes because of higher solubility.

Steep slope in the CO2 dissociation curve in the physiologic range of dissolved CO2

Potential application of ECCO2R technology ECCO 2 R for patients on IMV: to enable lung protective ventilation to treat refractory hypercapnic RF to support weaning and facilitate extubation ECCO 2 R for patients on NIV: to avoid endotracheal intubation

Clinical use of ECCO 2 R in patients on NIV Chronic Obstructive Pulmonary Disease A bridge to Lung Transplant Other conditions

ECCO 2 R in COPD patients with hypercapnic ARF Vianello et al, Minerva Pneumol 2015

Objectives: To assess efficacy and safety of NIV plus ECCO 2 R in comparison to NIV-only to prevent ETI in patients with exacerbated AECOPD Design: Matched cohort study with historical control. Methods: Primary endpoint: cumulative prevalence of ETI. 25 pts included in the study group. 21 patients selected for the control group Results: Risk of being intubated 3 times higher in patients treated with NIV-only (hazard ratio, 0.27). Intubation rate in NIVplus- ECCO 2 R 12% and in NIV-only 33% (not statistically different). CCM, 2015

Limitations of the study: High number of pts who refused to give consent to NIV-plus-ECCO 2 R lack of clinical equipoise; Non-randomized design of the study; Decision to use ECCO 2 R made in an unblinded manner; Patients not representative of those commonly admitted to the ICU for treatment with NIV. CCM, 2015

Conclusions: data provide the rationale for future RCT that are required to validate ECCO 2 R in patients with hypercapnic respiratory failure nonresponsive to NIV.

Removing extra CO 2 in AECOPD patients Reported studies are limited in size; Insufficient information regarding when ECCO 2 R should ideally be implemented; However, the ability to increase avoidance of IMV and trends in reduced hospital LOS need for prospective, randomized, controlled studies. Lund, Curr Respir Care Rep 2012

A bridge to Lung Transplant Undergoing IMV before LT is an independent predictor of a longer time on MV and in the ICU during the posttransplantation period; Growing interest in the use of ECCO2R as a bridge to LT for patients with severe, hypercapnic RF in the attempt to avoid or limit IMV.

ECCO 2 R in patients on waiting list for LT Study details N of patients Bridged to LT Comments Fisher, 2006 12 10 A-V system (8 still alive at the 1yr follow-up) Ricci, 2010 12 3 Mean time on ECCO 2 R: 13.5 days 8 died on the device, 1 recovered Bartosik, 2011 2 1 1 recovered Schellongowski, 2014 20 19 2 systems (A-V and V-V) (4 switched to ECMO) Complications in 6 pts

Removing extra CO 2 in patients on Waiting List Bridging to LT with ECCO 2 R is feasible and associated with high successful transplantation and survival rates.

Sporadic case reports on the utilization of ECCO 2 R Near-fatal pediatric and adult asthma (Conrad 2007, Elliot 2007, Jung 2011) Intracranial bleeding (Mallick 2007) Influenza infection (Twigg 2008) Chest/abdominal/head trauma (McKinlay 2008) Bronchopleural fistulae (Bombino 2011) Acute exacerbation of IPF (Vianello 2016)

Conclusions The boundaries for the use of NIV continue to expand; however, the risk of NIV failure is still present; Transitioning to IMV after NIV failure may not be in the interest of some categories of patients, including those with AECOPD; The future management of patients with COPD will routinely include respiratory dyalisis : only a fascinating hypothesis?