Den hyperkapniska triangeln Bengt Midgren Skånes Universitetssjukhus Lund Hyperkapnisk kronisk respiratorisk insufficiens OBESITAS OSA KOL Kronisk hyperkapni vid KOL • Uppträder sent i sjukdomens naturalförlopp • Beror definitionsmässigt på en alveolär hypoventilation • Men beror inte på egentlig hypoventilation = låg minutventilation! West JB. Causes of carbon dioxide retention N Engl J Med 1971; 284:1232 Hypercapnia in COPD is not due to hypoventilation, but to the patient´s inability to increase his ventilation to the extent that is necessary to maintain a normal alveolar ventilation (VA) in lungs with severe ventilation-perfusion mismatch Minutventilation Alveolär ventilation Dead-spaceventilation Normal KOL utan CO2stegring KOL med CO2stegring Ishockeykurvan klubban PCO2 Upprätthålls till priset av stigande minutventilation 25-30% FEV1 Svenska LTOT-patienter (Swedevox) 75 år FEV1 37%pred BMI 24 (17% har BMI >30) PaO2 6,5 (urvalskriterium) PaCO2 6,2 kPa PaCO2 starkt korrelerat till FEV1 BMI men inte till ålder Ishockeykurvan PCO2 * 25-30% Svenska KOL-LTOT-patienter, BMI 24, ålder 75 år FEV1 Ishockeykurvan PCO2 Svenska KOL- LTMV-patienter, BMI 28, ålder 69 år * 25-30% FEV1 Ishockeykurvan PCO2 Tyska KOL- LTMV-patienter, BMI 28, ålder 63 år * 25-30% FEV1 Hyperkapnisk kronisk respiratorisk insufficiens OBESITAS OSA KOL Kronisk hyperkapni vid obesitas • OHS definieras som hyperkapni i vakenhet vid BMI > 30 i frånvaro av andra orsaker till hypoventilation • Populationsestimat 0,3 % (Amanda Piper) • Ca 1000 svenskar behandlas med hemrespirator pga OHS = 0,01% Kronisk hyperkapni vid obesitas • 50% av hospitaliserade patienter med BMI > 50 – Nowbar et al 2004 • Men – ingen specifik BMI-”cut off” när man måste ta arteriell blodgas. PaCO2 Relationen BMI – PaCO2 BMI OHS - mekanismer • Högre andningsarbete hos OHS-patienter jämfört med lika feta eukapniska • Mer central fettfördelning hos OHS-patienter jämfört med lika feta eukapniska • OSA hos 90% av OHS-patienter • Dagsymptomen vid OHS samma som vid OSA Dagsymptom vid LTMV Epworth vid LTMV Semin Respir Crit Care Med 2009; 30: 253-261 Clinical presentation of OHS Most, but not all, patients with OHS will have some daytime respiratory complaints and some degree of excessive daytime somnolence. All the other complaints seen in the more typical eucapnic patient with OSA may also be present, including fatigue, somnolence (which can be mild or severe), mood disturbance, impaired concentration and memory, sleep disruption with snoring and choking, and morning headaches. Clinical presentation of OHS • Evidence of right ventricular dysfunction is seen in some patients with OSA uncomplicated by hypercapnia • Overt cor pulmonale is extremely uncommon in OSA in the absence of hypercapnia • Most patients with OHS (hypercapnia) will eventually show signs of circulatory congestion and cor pulmonale. Clinical presentation of OHS • The ‘‘typical’’ presentation of patients with OHS falls into two main patterns that differ primarily in the route by which the patient comes to clinical attention. • Patients either present as – part of the general OSA population or – after an episode of severe respiratory failure, often precipitating a stay in the intensive care unit (ICU). • Published series of OHS have tended to show different findings depending on which of these groups predominated. Andningsdrive vid OHS • Sänkt, men ej genetiskt – Reversibelt vid behandling • Leptin – ”smalhormonet” – Bildas i fettväv – Sänker aptiten – Stimulerar andningen • Starkt positivt samband leptin – PCO2 – Leptinresistens • analogt med insulinresistens vid DM typ II Hyperkapnisk kronisk respiratorisk insufficiens OBESITAS OSA KOL Kronisk hyperkapni vid OSA • Inte välstuderat • 10-20% av populationen vid sömnklinik?? – Äldre arbeten, selekterat material • Mina erfarenheter i oselekterat material – Synnerligen ovanligt – Om PaCO2 inte över 6,5 går det utmärkt att behandla med vanlig CPAP Kronisk hyperkapni vid OSA • Mekanismer? – Repetitiv transient hyperkapni ger resetting av pH-receptorerna i medulla oblongata • AHI korrelerar dåligt till PaCO2 – Durationen av apnéerna mer väsentlig än index? AHI 70 AHI 40 Kronisk hyperkapni vid OSA • Mekanismer? – Repetitiv transient hyperkapni ger resetting av pH-receptorerna i medulla oblongata • Aggraverande faktorer – Obesitas – Andningsdeprimerande substanser – KOL Semin Respir Crit Care Med 2009; 30: 253-261 Något missvisande titel, handlar mest om hur OSA övergår i kronisk hypoventilation How to identify the patient? • The hypercapnic patient who presents [to the sleep lab] will frequently be unrecognized initially if blood gases are not drawn • It is only on careful analysis of the sleep study that hypoventilation will be suspected from the prolonged, rather than intermittent, desaturation pattern seen during the night How to identify the patient? • Our practice is to obtain blood gases (specifically arterial PCO2) in any patient presenting with a history suggesting OSA who also has – either an elevated venous bicarbonate level – and/or associated chronic obstructive pulmonary disease (COPD) – or predisposition to respiratory depression (e.g. drugs). Therapy A review of our laboratory’s experience … in patients with chronic daytime hypercapnia … showed that 50% of hypercapnic patients with OSA required only CPAP, whereas the remainder were diagnosed with SHVS and required therapy with noninvasive bilevel ventilation in addition to CPAP. It is rarely necessary to provide supplemental O2 to keep the O2 saturation above 90%. Patofysiologi • Effects of periodic breathing on acute CO2 loading • Magnitude of compensation for CO2 accumulated during apnea/hypopnea • This is ultimately limited by the 1) duration available and 2) magnitude of ventilation during the compensatory phase between apneas Interaktion med opiater … impaired CO2 homeostasis after respiratory events (e.g., the relative shortening of the interapnea duration and the reduced postevent ventilation) may be mediated by opioids or opioid receptors because endorphin blockade changed this pattern. These observations provide a framework for understanding the facilitating effect that opiates (including methadone) may have on the development of hypercapnia in some patients with OSA. Mekanism 1 • Immediate ventilatory compensation is required after each acute hypercapnic insult (apnea/hypopnea or sustained periods of hypoventilation). • Ventilatory compensation may be compromised by either – reduced ventilatory drive (e.g. reduction in ventilatory drive or induced by drug or oxygen) or – reduced ventilatory efficiency of CO2 clearance (e.g. as in underlying lung disease or congestive heart failure). Mekanism 2 • Adequate renal bicarbonate excretion is required during wakefulness to offset the effects of uncompensated cyclical hypercapnia. • Renal compensatory mechanism may be compromised by – diuretic induced chloride deficiency and/or – by increased sodium avidity (e.g., CHF, hypoxia, or metabolic syndrome) • and contribute to the transition between acute hypercapnia and the chronic hypercapnic state. Hyperkapnisk kronisk respiratorisk insufficiens OBESITAS OSA KOL Så här tror Bengt att verkligheten ser ut Obesitas OHS E662 OSA G473 Hyperkapnisk kronisk respiratorisk insufficiens OBESITAS OSA KOL Overlap syndrome • ”… the overlap syndrome, in which obstructive sleep apnea is combined with chronic obstructive lung disease in the same patient” • DC Flenley 1985 Clin Chest Med Overlap syndrome • Prevalence and clinical feature of the "overlap syndrome", obstructive sleep apnea (OSA) and chronic obstructive pulmonary disease (COPD), in OSA population. • Rizzi et al 1997 Sleep Breath Rizzi et al. • In conclusion, an associated COPD is observed in more than 19% of OSA patients. • Overlap patients are at increased risk of developing pulmonary hypertension and show a poorer quality of sleep as compared with OSA patients. • The possibility of developing cor pulmonale should be given particular attention in the diagnosis and follow-up of Overlap patients. Concomitant COPD and OSA. Hypercapnia not inclusion criterion 18,9% 18,5% Overlap syndrome • COPD + OSA (1985) • COPD + asthma (2009) • The overlap syndrome of asthma and COPD: what are its features and how important is it? • Gibson PG, Simpson JL Thorax 2009 Hyperkapnisk kronisk respiratorisk insufficiens OBESITAS OSA KOL Alveolära gasekvationen 15 PCO2 12 PO2 + 1,25*PCO2 = 2017 Pensionärsrabatt 9 6 3 0 0 5 10 PO2 15 20 Case #1 • Smoking male, 70 years old • Regular visit to the COPD outpatient office – VC 2,9 (4,4) FEV1 1,2 (2,8) FEV% 40 – PO2 7,3 PCO2 6,5 BE +7 Case #1 • Now calling for an extra visit because of swollen legs • Unchanged blood gases • Seen by a not-COPD-doctor (me) • Questions COPD as the single cause of hypercapnia • BMI 36 Case #1 • Regular visit to the COPD outpatient office – VC 2,9 (4,4) FEV1 1,2 (2,8) FEV% 40 – PO2 7,3 PCO2 6,5 BE +7 – BMI 36 Normala relationen mellan FEV1 och PCO2 vid KOL PCO2 * 25-30% FEV1 Blodgas före behandlingsstart 7,3 + 1,25*6,5 = 15,4 15 PCO2 12 9 6 3 0 0 5 10 PO2 15 20 Blodgas efter en tids behandling 8,2 + 1,25*5,4 = 14,9 15 PCO2 12 9 6 3 0 0 5 10 PO2 15 20 Blodgas efter ytterligare ett år 10,8 + 1,25*5,0 = 17,0 15 PCO2 12 9 6 3 0 0 5 10 PO2 15 20 Alveolära gasekvationen 1. Ren hypoventilation PCO2 2. Lungfibros 3. Vanlig KOL 1 4 3 4. Hypoventilation med sekundär lungpåverkan 5,3 2 PO2 8 13 Hyperkapnisk kronisk respiratorisk insufficiens OBESITAS OSA KOL All that wheezes is not asthma … • But it may not be COPD either. • Hur skall vi handlägga en fet person med KOL och högt PaCO2? LTMV i Sverige Komorbiditet enl Swedevox • Lungsjuka: 20% bidiagnos OHS • OHS: 24% bidiagnos lungsjukdom LTMV – lungsjukas fysiologi 63 år, BMI 28 Olika fenotyper som får/behöver LTOT och LTMV? Ishockeykurvan PCO2 * 25-30% Svenska KOL-LTOT-patienter, BMI 24, ålder 75 år FEV1 Ishockeykurvan PCO2 Svenska KOL- LTMV-patienter, BMI 28, ålder 69 år * 25-30% FEV1 Ishockeykurvan PCO2 Tyska KOL- LTMV-patienter, BMI 28, ålder 63 år * 25-30% FEV1 7.1.4. Sonstige Besonderheiten • Die Einleitung einer NIV bei fortgeschrittener COPD fordert ein hohes Maß an Motivation und Mitarbeit von Seiten des Patienten und ist für das therapeutische Team eine besondere Herausforderung. • Deshalb kann die stationäre Behandlungszeit bis zum Erreichen einer stabilen Therapie eine bis zwei Wochen in Anspruch nehmen [Windisch et al, 2002c] [Windisch, 2008] [Sivasothy et al, 1998]. • Bei den oft älteren, multimorbiden Patienten ist dieser Zeitaufwand gerechtfertigt, um eine optimale Anpassung von Beatmungsmodus und Maske an die Bedürfnisse des Patienten zu er-zielen und um die langfristige Adhärenz des Patienten zu gewährleisten [Criner et al, 1999]. Hyperkapniska triangeln OBESITAS OSA KOL Multipel börda … och litet glädje? 100 kg