CPR 15 : how much oxygen? Serge Brimioulle PaO 2 target - routinely > 6 mmhg - ALI - ARDS 55-8 mmhg - chronic hypercapnia ~ 5 mmhg - paraquat intoxication ~ 4 mmhg (lactate) Oxygenation O 2 pressure Department of Intensive Care Erasme Hospital, Brussels, Belgium (mmhg) - atmospheric 16 - alveolar 1 - arterial 97 - capillary - muscle (rest) 4 - muscle (work) 4 - mitochondrial 1 1 75 5 25 Alv. Art. Cap. Mus. rest Mus. work Mit. - acute myoc. infarction 8-1 mmhg - acute brain injury 8-1 mmhg Cell respiration Gnaiger, AEMB 3 Wagner, ERJ 8 - at rest, PcO 2 4 mmhg (Mb sat. 1%), PmO 2 2 - at work, PcO 2 4 mmhg (Mb sat. 5%), PmO 2.3 Advantages of low PcO 2 - optimal : maximal mitoch. energy production prevents excessive ROS production - maximal RBC - cell gradient (diffusion limitation) - arteriolar vasodilation (tissue autoregulation) - HIF-stimulated VEGF and angiogenesis Oxygen is good Falkowski, Science 5 Hypoxia - HIF Smith, BJH 8 - HIF = transcription factors (hundreds of genes) - continuous HIF production and degradation normal : PHD-modified, VHL-bound, metabolized hypoxia : PHD inhibition At organ level At cell level - ventilation - energy metabolism - HPV - vasomotor regulation - erythropoiesis - angiogenesis (VEGF) - cardiac output - cell growth & apoptosis
Hypoxia West, AAS 199 Hypoxia - brain ischemia Miyamoto, Neurology - Everest 1981, Everest-II 1986 - rats, ischemia < transient MCA occlusion - blood gases: 7.65-8 - 3 and 7.56-11 - 3 - left shift of ODC, quicker pulm. oxygen loading - preserved contractility and hemodynamics - (relatively) preserved exercise capacity - impairment of cognitive function - persistence for more than 12 months Hypoxia - brain trauma Diringer, COCC 8 - mitochondrial dysfunction, low PbO2 - secondary brain injury due to ischemia - hyperbaric oxygen well-known toxicity - pulmonary, ocular, and cerebral - normobaric oxygen - animal and clinical studies - better ICP, PbO 2, microdialysis data - no clinical or PET benefit Oxygen holocaust O2 atm (%) 25 15 1 5 cyanobacteria -4-3 -2-1 time (billions years) PaO 2 % necrosis hemisph. cortex - hypoxia 46 ± 1 24 ± 5 13 ± 3 - normoxia 1 ± 4 17 ± 7 8 ± 5 - hyperoxia 214 ± 6 8 ± 2 1 ± 1 Hypoxia - stroke Singhal, IJS 6 - many animal studies, often hyperbaric - may be effective in selected conditions - 3 clinical studies on hyperbaric oxygen - Anderson, Stroke 1991 - Nighoghossian, Stroke 1995 - Rusyniak, Stroke 3 - no evident clinical benefit - questionable trials design Oxygen holocaust De Duve, 2 - anaerobic reactions and unicellular organisms - photosystem (CO 2 + H 2 S) : green & purple bacteria - photosystem (CO 2 + H 2 O) : cyanobacteria - photosynthesis by plants < chloroplasts (~ cyanob.) - sea air land poisoning by oxygen - death of most oxygen-sensitive organisms - integration of oxygen-using bacteria : mitochondrias - energy-efficient (ATP) aerobic cell respiration - multicellular animals, land invasion
Oxygen is bad Nathan, BMB 1999 Oxygen is bad Nathan, BMB 1999 - oxidative phosphorylation in mitochondrias (COX) - glucose + O 2 + ADP ==> H 2 O + CO 2 + ATP - production of ROS : O 2 -, OH, H 2 O 2 Antioxidative protective mechanisms - superoxide dismutase - GSH - glutathione peroxidase - NADPH - glutathione reductase - vitamin C - NAD(P) transhydrogenase - vitamin E ROS production Chalhoub, AAS 11 Huet, CCM 11 Surgery - 32 pts after low- and intermediate-risk surgery - perfusion of serum on endothelial cells - unchanged cytokines production - ROS production, related to surgery "magnitude" Cardiac arrest - 12 pts after cardiac arrest (vs septic shock) - ROS production, antioxidant activity - impaired mitochondrial chain activity - increased anaerobic metabolism - production of ROS : O 2 -, OH, H 2 O 2 - antioxidative protective mechanisms If imbalance - hypoxia or ischemia : "reductive" stress - hyperoxia or reperfusion : "oxidative" stress - intramitochondrial dysfunction (Ca ++, Fe ++ ) - mitochondrial permeabilization and swelling - cellular toxicity Hyperoxia - surgery Meyhoff, AA 12 - Proxi trial, n = 1386 perop 8 vs 3% O 2 - no diff. in infection - MLR predictor (OR 1.3) 1 2-yr mortality, % Hyperoxia - cardiac arrest Pilcher, Resusc 12 NO2 HO2 Hyperoxia - cardiac arrest Kuisma, Resusc 6 - extrahosp CA (Finland) witnessed, VF, ROSC, n = 28 (± hypothermia) survival / 28 - FiO2 1 vs 3% (1 hr) maintain SpO2 95% 3 1 PaO2-1' 158 ± 3 373 ± 42 PaO2-6' 19 ± 7 349 ± 47 NSE - 24h 11 ± 2 13 ± 2 NSE - 48h 14 ± 5 19 ± 5 S1-24h 21 ± 4 73 ± 3 Animal studies - hyperoxia vs normoxia - effect on mortality - suppl. O2 in 5 / 14 S1-48h 23 ± 5 49 ± 16
Hyperoxia - cardiac arrest Kilgannon, JAMA 1 Hyperoxia - cardiac arrest Bellomo, CC 11-1 US hospitals, 5 yrs - nontraumatic CA first PaO 2 in 24 h n = 6326 - hypoxia < 6 mmhg - hyperoxia > 3 mmhg 6 4 - MLR predictor (OR 1.8) Hyperoxia - cardiac arrest Ferguson, Circ 12 - PICAnet, 3-1 n = 1875 PaO 2 in 1 hr - MLR predictor (OR 1.3) 4 ICU mortality, % Hyperoxia - cardiac arrest Guerra-Wallace, PCCM 13 - PICU, 4-8 surv > 48 h, n = 74 PaO 2 in 24 hr - 125 ICUs, Aust-NZ n = 1218 worst PaO 2 in 24 h - hypoxia < 6 mmhg - hyperoxia > 3 mmhg 6 4 - MLR predictor (OR 1.2) Cox non-predictor Hyperoxia - cardiac arrest Ihle, CCR 12 - Aust-NZ, 7-11 CA < VF, n = 584 most an PaO 2 in 24 h - hypoxia < 6 mmhg - hyperoxia > 3 mmhg - MLR : no effect 6 4 6-mo mortality, % Hyperoxia - cardiac arrest Wang, Resusc 14 - hypoxia < 6 mmhg - hyperoxia > 3 mmhg - no difference 1
Hyperoxia - cardiac arrest Wang, Resusc 14 Hyperoxia - cardiac arrest Elmer, ICM 15 - Pittsburgh, 8-1 surv > 24 h, n = 184 PaO 2 exposure (h) Hyperoxia - brain trauma Rincon, JNNP 13-61 US hospitals, 5 yrs n = 12121 PaO 2 in 24 h - hypoxia < 6 mmhg - hyperoxia > 3 mmhg - MLR predictor (OR 1.5) 4 Hyperoxia - cardiac arrest Kilgannon, Circ 11-1 US hospitals, 5 yrs - same as before highest PaO 2 in 24 h n = 4459 (excl. ho2) - continuous trend - MLR indep. predictor (OR 1.24 / 1 mmhg) - hypoxia < 6 mmhg - hyperoxia > 3 mmhg - 1-hr HO2 ind. predictor of survival (OR.83) Hyperoxia - stroke Rincon, CCM 14-84 US hospitals, 5 yrs n = 2894 PaO 2 in 24 h - hypoxia < 6 mmhg - hyperoxia > 3 mmhg - MLR predictor (OR 1.2) PaO 2 target 6 4 - routinely > 6 mmhg - ALI - ARDS 55-8 mmhg - chronic hypercapnia ~ 5 mmhg - paraquat intoxication ~ 4 mmhg (lactate) - acute myoc. infarction 8-1 mmhg - acute brain injury 8-1 mmhg