Wolfram Windisch Lung Center Cologne University of Witten/Herdecke, Germany
Non-invasive positive pressure ventilation (NPPV) used in patients with chronic hypercapnic respiratory failure that arises from COPD is aimed at improving Hypercapnia (physiological outcome) Symptoms and quality of life (subjective outcome) Long-term survival (objective outcome)
I have morning headache I see
CO 2 : Extrapulmonary vasodilatation Reduction in precapillary tone Distal movement of the filtration equilibrium point in the capillaries I have morning headache I see Increased extravasation and loss of plasma volume; thus, effective circulating volume is reduced Stimulation of the sympathetic nervous system and the renin-angiotensin-aldosterone system Kidney response: sodium retention and intravascular volume restoration Maintenance of hypercapnia: Peripheral edema Leeuw PW. et al. Eur Respir J 2003; 22(suppl.) 46:33-44
Hypercapnic edema in COPD - Aggravation caused by diuretics - airways hypercapnia - Hypoventilation - metabolic compensation: renal bicarbonate retention limbs edema circulus vitiosus loop diuretics respiratory compensation: hypoventilation metabolic alkalosis
% Continuing NIPPV 100 80 60 40 20 N = 172 Poliomyelitis Tuberculosis Neuromuscular Kyphoscoliosis COPD 0 Bronchiectasis 0 1 2 3 4 5 Years Simonds AK. et al. Thorax 1995; 50:604-609
Wijkstra PJ. et al. Chest 2003; 124:337-343
1 year follow-up 2 years follow-up NPPV + LTOT vs. LTOT alone IPAP (cmh 2 O) EPAP (cmh 2 O) ΔPaCO 2 (mmhg) Survival Casanaova et al. Clini et al. 12 4 NPPV: +0.4 LTOT: -0.9 14 2 NPPV: -1.0 LTOT: +0.5 No benefit (1 year) No benefit (2 years) Casanova C. et al. Chest 2000; 118:1582-1590 Clini E. et al. Eur Respir J 2002; 20:529-538
McEvoy RD. et al. Thorax 2009; 64:561-566
mean adherence to NIV: 4.5 ± 3.2 hours McEvoy RD. et al. Thorax 2009; 64:561-566
McEvoy RD. et al. Thorax 2009; 64:561-566
Wolfram Windisch Windisch W. Breathe 2011; 8:114-123
At present, there is insufficient evidence to support the application of routine NIPPV in patients with stable COPD. However, higher IPAP levels, better compliance and higher baseline PaCO 2 seem to improve PaCO 2. Struik FM et al. Respir Med 2014; 108:329-337
Wolfram Windisch Windisch W. Breathe 2011; 8:114-123
Wolfram Windisch Windisch W. Breathe 2011; 8:114-123
High-intensity NPPV N = 73 Windisch W. et al. Int J Med Sci 2009; 6:72-76 Improvements blood gases breathing pattern lung function anemia, polyglobulia quality of life dyspnea exercise capacity Windisch W. et al. Respir Med 2002; 96:572-579 Windisch W. et al. Respir Med 2005; 99: 52-59 Windisch W. et al. Chest 2005; 128:657-662 Windisch W. et al. Respir Physiol Neurobiol 2006; 150:251-260 Windisch W. Eur Respir J 2008; 32:1328-1336 Windisch W. et al. Int J Med Sci 2009; 6:72-76
N = 34 NPPV (asspcv): IPAP 28 ±6 mbar; bf 21 ±3 /min 2-year survival: 86% Windisch W. et al. Chest 2005; 128:657-662
MRC = Medical Research Council: Oxygen 15 hours/day (MRC O 2 ) versus control (MRC controls) NOTT = Nocturnal Oxygen Therapy Trial: Continuous oxygen (COT) versus Nocturnal oxygen (NOT) Stoller JK. et al. Chest 2010; 138:179-187
Mortality risk Dubois P. et al. Chest 1994; 105:469-474
Lukácsovitis J. et al. Eur Respir J 2012; 39:869-875
Lukácsovitis J. et al. Eur Respir J 2012; 39:869-875
n = 20 mean ± standard deviation Age (years) 63.9 ± 10.2 BMI (kg/m 2 ) 28.7 ± 8.0 prior NPPV-initiation after 12 weeks of NPPV p- value HbA1c (%) 45.9 ± 10.4 44.5 ± 11.1 0.17 Smokers (n) 16 Pack years 37.1 ± 24.1 Trop. T (pg/ml) 0.011 (0.005 / 0.027) 0.010 (0.006 / 0.023) 0.487 FEV 1 / FVC (%) 43.1 ± 11.7 FEV 1 (%pred.) 31.4 ± 17.1 TLC (%pred.) 104.9 ± 30.0 RV (%pred.) 225.7 ± 92.0 probnp (pg/ml) 91 (47 / 930) 75 (27 / 245) 0.017 probnp mean (pg/ml) 865 ± 1620 287 ± 489 PAI-1 (ng/ml) 46.1 ± 15.7 48.7 ± 16.3 0.577 Triglyceride (md/dl) 103.5 (84.5 / 125) 97.5 (74.5 / 127) 0.196 Cholesterin (mg/dl) 196.9 ± 46.9 206.6 ± 46.3 0.163 60 difference in PaCO 2 over time 50 40 30 20 10 0 asspcv mean min / max IPAP (mbar) 22.8 16 / 30 EPAP (mbar) 4.2 4 / 11 bf (/min) 17.3 13 / 20-10 -2000-1000 0 1000 2000 3000 4000 5000 difference in BNP over time Dreher M. et al. Eur Respir J 2013; Suppl. Congress abstracts
Severe Respiratory Insufficiency Questionnaire SRI Respiratory Complaints RC Social Functioning SF SRI Well-Being WB German English French Spanish Dutch Swedish Norwegian Polish (Greek) Japanese Danish Physical Functioning PF Attendant Symptoms and Sleep AS Summary Scale SS Social Relationships SR Windisch W. et al. J Clin Epidemiol 2003; 56:752-759 Windisch W. et al. Intensive Care Med 2003; 29:615-621 Windisch W. et al. J Clin Epidemiol 2008; 61:848-853 Anxieties AX http://www.pneumologie.de/808.0.html
CCQ CRQ MRF-28 SRI Struik FM. et al. J Clin Epidemiol 2013; 66:1166-1174
N = 137 COPD Restrictive thoracic diseases Obesity- Hypoventilations-Syndrome Neuromuscular disorders Miscellaneous Windisch W. Eur Respir J 2008; 32:1328-1336
SRI-Summary Scale (SRI-SS) 65 55 45 IPAP/EPAP (mbar) 20/3 19/4 25/1 Changes in SRI-SS independent from the underlying disease MANOVA; F=0,62; P=0,65. P < 0.001 T0 T1 T12 COPD RTD NMD P < 0.001 neuromuscular P < 0.001 COPD restrictive thoracic Windisch W. Eur Respir J 2008; 32:1328-1336
high: 29 cmh 2 O; controlled ventilation low: 15 cmh 2 O; assisted ventilation Primary outcome: Nocturnal PaCO 2 Mean treatment effect: -9.2 mmhg 95%CI [-13.7, -4.6 mmhg]; P<0.001 No period effect: P=0.96 No carry over effect: P=0.87 Compliance (daily use): Mean treatment effect: 3.6 hours 95%CI [0.6, 6.7 hours]; P=0.024 Dyspnea (BDS) QoL (SRI-SS) FEV 1 (L) Lowintensity Highintensity + + + Dreher M. et al. Thorax 2010, 65:303-308
Mean IPAP: high: 29 cmh 2 O; low:14 cmh 2 O Dreher M. et al. Chest 2011; 140:939-945
Is long-term NIV capable of improving long-term survival in COPD patients with chronic hypercapnic respiratory failure? NIV aimed at reducing PaCO 2 by > 20% or at achieving normocapnia 195 patients randomized Köhnlein T. et al. Lancet Respir Med 2014; 2:698-705
Ventilator Setting - adherence: IPAP/EPAP: 21.6±4.7 / 4.8±1.6 mbar Respiratory rate: 16.1±3.6 (range 2 24) min -1 70 patients with respiratory rate 14 min -1 Mean NPPV-usage: 5.9±3.1 hours per day Köhnlein T. et al. Lancet Respir Med 2014; 2:698-705
Köhnlein T. et al. Lancet Respir Med 2014; 2:698-705
1-year-mortality 33% 12% Köhnlein T. et al. Lancet Respir Med 2014; 2:698-705
Windisch W. et al. Pneumologie 2010, 64:640-652
5 cmh 2 O 15/5 cmh 2 O Cheung APS. et al. Int J Tuberc Lung Dis 2010; 14:642 649
6-min-walking distance after 3 months 20/5 cmh 2 O N = 13 N = 13 Funk GC. et al. Respir Med 2011; 105:427-434
event = readmission for respiratory cause or death = primary endpoint Struik FM et al. et al. Thorax 2014; 69:826-834
Struik FM et al. et al. Thorax 2014; 69:826-834
Following ARF CRF Windisch W. et al. Pneumologie 2010, 64:640-652
Thank you very much!