TSANZ meeting 01 Apr Physiology of respiratory failure in COPD & OHS. Bhajan Singh MBBS FRACP PhD

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1 TSANZ meeting 01 Apr 2015 Physiology of respiratory failure in & OHS Bhajan Singh MBBS FRACP PhD Head of Department, Pulmonary Physiology & Sleep Medicine, Sir Charles Gairdner Hospital Director, West Australian Sleep Disorders Research Institute Clinical Professor, Faculty of Science, University of Western Australia Overview Work of Breathing Respiratory muscle reserve SDB CO2 load Adequate compensation Inadequate compensation Normocapnia Hypercapnia 1

2 : work of breathing Alveolar Ventilation Respiratory muscle capacity Work of breathing Airway PEEPi END-EXPIRATION NORMAL P = 0 Alveolus P = +5cmH 2 O PEEPi accounts for >50% of the in work of breathing in exac. with ARF (Coussa et al. J Appl Physiol 1993). Loads Resistive Elastic Hyperinflation Intrinsic PEEP V/Q inequality : increased work of breathing Loring et al. J Appl Physiol 2009 Roussos and Zakynthinos Eur Respir J 1995 In, the work of breathing is markedly increased by inspiratory resistance and PEEPi 2

3 : reduced respiratory muscle reserve Alveolar Ventilation Respiratory muscle reserve Work of breathing HEALTHY Respiratory muscles inefficient muscle length mechanical disadvantage Dome Zone of apposition Effect of sleep on ventilation Mechanisms: 1. in respiratory drive 2. upper airway resistance 3. ribcage contribution to breathing 4. FRC Esp. during REM sleep. N = 19 healthy adults In ventilatory failure: Hypoventilation during sleep is common (43% of 54 subjects in O Donoghue et al. 2003) Compensatory renal retention of HCO 3 can impair ventilatory control during the day Douglas et al. Thorax 1982 O Donoghue et al. Eur Respir J

4 : sleep hypoventilation Assessment of mechanisms by which NIV reverses ventilatory failure in N = 19 patients with severe stable with hypercapnia PaCO 2 (kpa) Bicarbonate (mm/ l) Measured ABG, HCVR, lung volumes, resp. muscle strength at baseline and after nocturnal NIV for 5-8 days and at 3 months Found: - PaCO 2 & HCO D0 D5 3M 28 D0 D5 3M - ventilatory response to CO 2 - Slight decrease in TLC - No objective increase in respiratory muscle strength Limitation: mixed population? - mean BMI 35 (8), 9 had symptoms of OSA Hypercapnic ventilatory response (l/ min/ kpa) Supports idea that sleep hypoventilation is central to ventilatory failure in 3 D0 D5 3M Nickol AH et al. Int J 2008; 3(3): Factors associated with ventilatory failure Mechanism Associations with hypercapnia in Load FEV 1 (esp. <40% pred. or <0.5 L) Hyperinflation ( FRC/IC, IC/TLC) diaphragm load (diaphragm TTI) muscle reserve ratio of respiratory load to respiratory muscle reserve SDB Pattern of breathing Clinical R L Obesity History of heart failure MIP, Pplmin, Pes,max R L /MIP, R L /Pplmin, Edyn/Pplmin Duration of REM sleep Severity of sleep hypoventilation Symptoms of OSA V T, V D /V T, T I Cigarette smoking LTOT 4

5 OHS Risk factors Obesity OSA Reduced lung volumes Obesity reduces lung volumes, especially FRC & ERV. Prevalence of OHS increases with BMI patients with OSA N = 373 r 2 = 0.49 p = Mokhlesi B Respir Care 2010; 55(10): Jones & Nzekwu Chest 2006; 130: Obesity: deranged respiratory mechanics N = 61 patients without lung disease, anaesthesized & paralysed prior to surgery 51 severely obese, BMI 48.5 (8.9), age 43.8 (11.9) yrs. 10 non-obese, BMI 25.2 (2.8), age 44.7 (11.4) yrs. Measured Pes, Pg, P AO, flow, volume Alternate Ppl = threshold P AO = airway pressure required to increase lung volume from V rel (P AO-Thr ). Pes at V Rel, cmh 2 O Threshold P AO, cmh 2 O C RS, L/cmH 2 O C L, L/cmH 2 O C CW, L/cmH 2 O Normal 6.9 (3.1) 0.4 (0.2) (0.007) (0.029) (0.132) Obese 12.5 (3.9) 3.1 (3.0) (0.008) (0.016) (0.109) P < < < Behazin N et al. J Appl Physiol 2010; 108 (1);

6 OHS: increased work of breathing (20) (6) (8) (14) N = 58 WoB is increased in OHS. Lee M-Y et al. Respiration 2009;77 OHS Post-event ventilation Relationship between ventilatory response to OSA events and CO 2 load N = 14 OSA, PaCO mmhg. Measured V E and breath-by-breath FeCO 2 & FeO 2 during sleep. Calculated CO 2 load (metabolic production exhaled CO 2 ) during each event and for 10 s after the event. In 12/14, direct relationship between post-event V E & CO 2 load during preceding event (P<0.05) but slope was variable. Inverse relationship between post-event ventilatory response slope and chronic awake PaCO 2, suggesting this mechanism may be impaired in patients with OHS. Berger KI et al. J Appl Physiol 93: ,

7 OHS CO 2 sensitivity Evaluation of sleep abnormalities in patients with OHS and different CO 2 sensitivities. N = 15 OHS patients. PSG, CO 2 ventilatory response Baseline CO 2 sensitivity related to proportion of hypoventilation during REM. Chouri-Pontarollo N et al. Chest 2007; 131: OHS - CO 2 sensitivity Leptin Effect of leptin on CO 2 responsiveness in OSA N = Eucapnic OSA (13) 2. Hypercapnic OSA (16) 3. Controls matched for age, gender & BMI (12). Measured fasting leptin & HCVR Findings HCVR related to leptin level in control & eucapnic subjects (r=0.42, P<0.05) HCVR lower in hypercapnic patients than eucapnic patients in spite of similar leptin levels. Leptin resistance may contribute to OHS IGF-1 IGF-1 and IGFBG-3 lower in OHS and inversely related to PaCO 2 (D. Monneret et al. Growth Hormone & IGF Research 2010; 20: ) Makinoden K et al. Respiration 2008; 75(3):

8 Respiratory-renal interactions Evaluation of respiratory-renal interactions in the transition from acute to chronic hypercapnia. Computational model of whole body CO 2 kinetics modified by adding V E control and renal HCO 3 kinetics. 8 h of periodic breathing (OSA) and 16 h of regular V E (wakefulness) repeated for 20 d. Interventions: varying initial awake CO 2 response, rate of renal HCO3 excretion Transition from acute to chronic hypercapnia required either slowing of renal HCO 3 kinetics or reduction in ventilatory CO 2 responsiveness or both. Norman RG et al. J Appl Physiol 2006; 100: Summary OHS Work of Breathing Respiratory muscle reserve OHS PEEPi Airway resistance Lung compliance REM hypoventilation SDB OHS OSA Sleep hypoventilation Inefficient CO2 load Adequate compensation Normocapnia Pattern of breathing Inadequate compensation Reduced CO 2 sensitivity Abnormal HCO 3 kinetics Hypercapnia OHS Leptin IGF-1 8