Permissive hypoxaemia. Mervyn Singer Bloomsbury Institute of Intensive Care Medicine University College London, UK

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1 Permissive hypoxaemia Mervyn Singer Bloomsbury Institute of Intensive Care Medicine University College London, UK

2 Is mechanical ventilation such a good idea? ventilator-induced lung injury (short- & long-term) systemic effects --> immune activation, cardiovascular effects need for sedation --> immunosuppression, cardiovascular effects ventilator-associated pneumonia

3 Recent paradigms ALI ARDS IR-PCV.. permissive hypercapnia prone positi0ning... mode variants, posture... NO, surfactant fluorocarbon bad ARDS Permissive hypoxaemia HFO Novolung ECMO ECCO 2 R..

4

5 .. but what about complications? What s the long-term morbidity? stroke? leg amputation? neurocognitive disturbances?...

6 I never inhaled... OXYGEN ENEMATA AS A REMEDY IN CERTAIN DISEASES OF THE LIVER AND INTESTINAL TRACT Kellogg JH, JAMA, 1888 THE INTRAVENOUS INJECTION OF OXYGEN GAS AS A THERAPEUTIC MEASURE Tunnicliffe, FW, Stebbing GF. Lancet 1916 (ii) 321-3

7

8 SMV O2 content Mixed venous O2 content Arterial O2 content Artif Organs 2000; 24: FiO2 0.14

9 What about permissive hypoxaemia??

10 Case history (i) 23 y.o. male overdose of anti-epileptics Rx: activated charcoal in local hospital ER ---> aspirated charcoal ---> severe lung injury after 10d ---> UCLH ICU with ARDS and multiple bronchopleural fistulae PC ventilation ( PEEP), FiO2 1.0 SaO2 88%, PaO2 7 kpa, PaCO kpa also requiring norepinephrine

11 Early May

12 Late May PC ventilation ( PEEP) FiO2 1.0 SaO2 73% PaO2 4.7 kpa PaCO2 14 kpa surgeons not interested off inotropes Kidneys OK 12

13 Late June weaning!

14 Late July extubated!

15 Case history (ii) 35 y.o. female collapse, SOB during epidural pre-caesarean section urgent intubation for severe hypoxaemia CXR: ARDS Rx: high FiO2, PEEP, IR-PCV improved by Day 3: FiO2 0.6, PaO2 8 kpa plateau d for 4 days, then gradual decline

16 Day 13: FiO2 1.0 PEEP 14 IR-PCV (PAP 45 cm H2O) prone positioning PaO2 3.8 kpa, SaO2 66% pneumothorax ---> referred to UCLH

17 On arrival: SaO2 68% yet all other organ systems working CO 8 l/min, BP 110/60 P.U. ing ml/hr liver function tests normal base excess +5.4, PaCO2 8.3 kpa

18 transferred without problem slow but steady improvement day 35: discharged ICU day 48: discharged home last seen pushing 3 kids round supermarket

19 Have they both acclimatised???

20 Effects of altitude (low PaO2) on performance altitude (x 10 3 ft) coma within minutes at rest death weakness unreliable coma on exertion poor learning PO 2 (kpa) 5 0

21

22

23 Hypoxia response systems * carotid body O 2 sensors --> hypoxic ventilatory response (HVR) * pulmonary vascular O 2 sensors --> hypoxic pulmonary vasoconstriction * peripheral O 2 sensors --> hypoxic vasodilation (via NO, nitrite...) --> expression of VEGF (+ receptors)->angiogenesis * O 2 sensors in kidney/liver --> erythropoietin ----> increased RBC mass * tissue-specific O 2 sensing & signal transduction pathways --> altered expression of hypoxia-sensitive genes for metabolic enzymes & transporters

24 critical illness Adaptation to altitude circulatory response: * global changes * regional changes (flow and pressure) cellular response: * myoglobin * mitochondrial density * resp y enzyme activities * metabolic changes * phenotype changes (e.g. fast -->slow twitch fibres) respiratory response: * minute ventilation * V-Q vascular response: * polycythaemia * tissue capillarity * oxyhb curve shift

25 Adaptation to exercise lactate acute hypoxia LOWLANDERS acclimatisation normoxia HIGHLANDERS (Himalayas/Andes) Hochachka PNAS 1998; 95: power

26 Arterial-mitochondrial PO2 gradient oxygen tension (kpa) artery capillary interstitium cell mitochondria (0.1-1)

27 We cope, we adapt mountaineers altitude dwellers pearl fishers Type II chronic bronchitics congenital cyanotic heart disease.. how about sepsis & ARDS???

28 Conclusions consider permissive hypoxaemia for severe ARDS as a better (??) alternative to driving ventilation, mechanical supports, etc.. allow time (1-2 weeks???) to acclimatise slowly carefully monitor adequacy of organ perfusion

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