Perioperative Use of Oxygen: What is the Right Amount?

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1 Perioperative Use of Oxygen: What is the Right Amount? Walid Habre, MD, PhD Anesthesiological Investigations Unit & Pediatric Anesthesia Unit Geneva University Hospitals and University of Geneva

2 Disclosure I have no conflicts of interest to disclose Except that I breath 21% of O 2

3 Normal oxidative metabolism of the cells controlled by cytochrome oxidase system in the mitochondria generates free electrons that are captured by O 2 Incomplete reduction of O 2! Reactive oxygen metabolites (Hydrogen peroxyde, hydroxyl radical, superoxyde anion) Lushchak VI et al. Chem Biol Interact 2014; 224:

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5 DNA damage $ cell death (oncosis, apoptosis)! proliferation Signaling Transcription factor activation! NO signaling"# angiogenesis neuroexcitotoxicity ROMs Protein oxidation! enzymatic functions Growth factor inhibition Lipid peroxidation Prostanoids "inflammation Lipid chain reaction "radical formation

6 Dual nature of Oxygen Hypoxia - ROMs +

7 PHYSIOLOGICAL ASPECTS

8 Beneficial Physiological aspects Optimisation of gas exchange! antimicrobial and proinflammatory responses in alveolar macrophages! Tissue oxygenation and Potential «+» effect on the immune system

9 Oxygen in a mixture of air : perfect carrier gas : Absolutely inert with respect to metabolism/environment PaO 2 PaO 2 /FiO 2 ratio Baseline Final Baseline Final FiO 2 40% in air 94.3 ± ± ± ± 46.6* FiO 2 40% in N 2 O 94.4 ± ± ± ± 33.9 FiO 2 100% 95.5 ± ± ± ± 22.9 Prevents from hypoxic gas Improves gas exchange Improves patient safety Potential effect on wound infection? Agarwal A. et al. Can J Anaesth 2002; 49:

10 Time to hemoglobin desaturation with initial F A O 2 of 87%!depends on FRC Benumof J et al. Anesthesiology 1997; 87:

11 Hypoxia will occur much quicker in neonates and infants independent of pre-oxygenation Hardman, J. G. et al. Br. J. Anaesth :

12 Supplemental Intraoperative Oxygen Enhances Antimicrobial and Proinflammatory Responses of Alveolar Macrophages! 100% O 2 30% O 2 Kotani N et al. Anesthesiology 2000; 93:15-25

13 Detrimental Physiological aspects Ventilation defects O 2 -absorption Airway smooth muscle Circulatory defects! PVR " SVR! Oxygen transport

14 100% FiO 2! Pressure gradient Intraalveolar-capillaries Rapid diffusion of O 2 across alveolar-capillary barrier Loss in alveolar distending pressure

15 The kinetic of O 2 -absorption atelectasis is determined by the alveolar concentration Edmark L et al. Anesthesiology 2003; 98: 28-33

16 The effect of gas composition on the recurrence of atelectasis after re-expansion 100% O 2 After RM, 40% FiO 2 :! delays significantly the recurrence of atelectasis (at least 40 )! " V/Q! # relative perfusion to poorly ventilated lung units Rothen H. et al. Anesthesiology 1995; 82(4):

17 Hyperoxia-induced lung injury is mediated by the decrease in NO production Impair relaxation Impair alveolarization Impair angiogenesis Firth A L, and Yuan J X - Am J Physiol Lung Cell Mol Physiol 2008;295:L976-L978

18 Increasing O 2 leads to proliferation of fasm cells until 50% then it drops because of apoptosis Hartman W R et al. Am J Physiol Lung Cell Mol Physiol 2012;303:L711-L719

19 Mitochondrial fragmentation in fasm cells with increasing concentration of oxygen > 50% FiO 2 Mitochodrial fragmentation Apoptosis Hartman W R et al. Am J Physiol Lung Cell Mol Physiol 2012;303:L711-L719

20 Potential mechanisms of the cardio-vascular harmful effects of oxygen Shuvy M et al. Eur Heart J 2013;34:

21 Hyperoxia, ROMs and the brain!inflammation!oligodendrocyte apoptosis!inos!cerebral vascular resistance " Cerebral blood flow Frontal cortex & thalamus microglial and astrocyte injury Gerstner B et al. J Neuroscience 2008; 28: 1236 Hoehn T et al. Pediatr Res 2003; 54: Niijima S et al. Arch Dis Child :1126

22 2 min of 100% O 2 ventilation led to pronounced responses in autonomic and hormonal control areas: hypothalamus, insula, and hippocampus 14 children 8-15yrs Alteration of hypothalamus-mediated sympathetic & hormonal outflow Macey PM, et al. PLoS Med 2007; 4(5): e173

23 CO 2 modulates hyperoxia physiological responses Hypercapnia counteracts hyperoxia-mediated vasoconstriction Hypocapnia worsens hyperoxia-mediated effects

24 Clinical aspects

25 Change in practice for neonatal resuscitation with 21% FiO 2 at start of resuscitation Resuscitation with 100% O 2!mortality NNH = Berger T et al Eur J Anaesthesiol 2012; 29(8):

26 10 th, 25 th, 50 th, 75t h, & 90 th SpO 2 percentiles from term infants ( 37 weeks) with no medical intervention after birth Initiation of neonatal resuscitation with 21% O 2 followed by variable FIO 2 to target SpO 2 at 50 th percentile: 90-95% (NEVER > 95%) Dawson JA et al. The Journal of Pediatrics ,

27 ! hazard ratio of death in the lower Sat O 2 group 1.28 (95% CI, ) ROP BPD death, cerebral palsy, PDA, PVR and apnoea SUPPORT Study (Neonatal network) N Engl J Med ; 362:

28 The+role+of+hyperoxia in+the+ pathogenesis+of+experimental+bpd Buczynski BW+et+al.+Semin Perinat :+69>78

29 Optimal oxygenation at birth and in the neonatal period : Avoid FLUCTUATIONS Concept of burden of hypoxia and hyperoxia and regional tissue haemoglobin oxygen saturation Hyttel-Sorensen S et al. BMJ. 2015; 5:350; g7635.

30 Specificity of neonatal and infant lung: Decrease in FRC!FRC

31 100% FiO 2 in infants leads rapidely to! FRC 30 P < P = FRC$[ml/kg] FRC/kg,1,CTRFRC/kg,2,CTRFRC/Kg,1,PEEP FRC/kg,2,PEEP F i O 2 0.3$ $ 1.0 Group PEEP$ ZEEP PEEP$ 3$cmH 2 O 6$cmH 2 O prevents von Ungern Sternberg et al. Anestth Analg 2007; 104: 6

32 Ventilatory strategy during anaesthesia from start of preoxygenation to emergence, including the oxygen level during transport and completion of CT A: Start preoxygenation B: Intubation C: Controlled ventilation F: Start emergence G: Extubation H: End mask ventilation Auner U et al. Upsala J of Med Sci 2014, 119,

33 Area of postoperative atelectasis Auner U et al. Upsala J of Med Sci 2014, 119,

34 Hyperoxia Is Associated With Poor Outcomes in Pediatric Cardiac Patients Supported on Venoarterial ECMO Infants Neonates PaO 2 < 190 mmhg Neonates(+(Norwood( (systemic(to(pulmonary(artery(shunt) Sznycer(Taub N.et.al.Ped Crit Care.Med.2016;.17(4):350(358

35 There is no strong evidence for the usefulness of high FiO 2 in the perioperative period There is good evidence for high risk of using high FiO 2 in the perioperative period in children

36 How to prevent intraoperative hypoxaemia? How to titrate intraoperative FiO 2?

37 ETT or circuit disconnection Ventilator impairment Anaesthetics Low minute ventilation LMA misplacement Oxygen-absorption Hypoventilation Decreased FRC Atelectasis Airway obstruction Laryngospasm Bronchospasm ALVEOLAR HYOVENTILATION HYPOXIA V/Q MISMATCH SHUNT Patent ductus PHT/CHD Atelectasis Pulmonary oedema DIFFUSION IMPAIRMENT Hypoxemia is multifactorial

38 The most plausible cause is airway closure Restore FRC Improve gas exchange Recrute the lung Apply PEEP TLC maneuver: Inflate slowly the lungs three times to P ao of 30 cm H 2 O for at least 5-10 sec

39 High FiO 2 may mask the presence of V/Q mismatch, hypoventilation Recruitment before! FiO 2

40 Strategies to improve gas exchange Recruitment maneuver Adjustement of PEEP Haemodynamic optimization Restore FRC Increase PBF Lung volume and CO participating in gas exchange

41 Hemodynamic coherence between the macro and the microcirculation Intravascular volume Blood Pressure Cardiac output O 2!oxygen delivery index optimize oxygen transport Hb CO 2

42 Relationship between O 2 delivery & consumption Vali P et al. Children 2017, 4(8), 67;

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44 Lack of evidence for a positive effect of high FiO 2 on SSI Trial sequential analysis (TSA) of high FiO 2 (60% to 90%) vs (30% to 40%) in surgical site infection for all trials of surgical participants within 14 to 30 days of follow-up: RR 0.87, 95% CI 0.65 to 1.17 Wetterslev J et al. Cochrane Database Syst Rev 2015 Jun 25;(6):CD008884

45 RISK BENEFIT BPD ductus arteriosus patency SVR atelectasis T i s s u e o x y g e n a t i o n cerebral blood flow FRC oligodendrocyte apoptosis cerebral vascular ischemia H y p o x i a t o l e r a n c e alveolar macrophage function SSI PONV coronary arterial flow ischaemic injury carotid body chemoreceptor sensitivity lung damage contractile function of the diaphragm airway inflammation in COPD POCD neurodegenerative disorders risk for stroke exacerbation Neonates Infants Children Middle age Elderly Target FiO 2 21% 30% 40% 50% 60% 50% 40% 30% Habre W et al. Br J Anaesth. 2014;113 Suppl 2:ii26-3

46 Preterm SaO % FiO 2 80% Infants and children FiO % FiO 2 80% Infants SaO 2 95% Children SaO 2 >95% Induction Maintenance Recovery Postoperative care