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Oxygen: Can You Get Too Much of a Good Thing?

Oxygen: Can You Get Too Much of a Good Thing?. Robert E. Rosenthal, MD Section of Hyperbaric Medicine R Adams Cowley Shock Trauma Center. Clinical Case Study. 46 year old CA victim Successful ED resuscitation Remains comatose Intubated, controlled ventilation Initial ABG: 7.28/51/465.

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Oxygen: Can You Get Too Much of a Good Thing?

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  1. Oxygen: Can You Get Too Much of a Good Thing? Robert E. Rosenthal, MD Section of Hyperbaric Medicine R Adams Cowley Shock Trauma Center

  2. Clinical Case Study • 46 year old CA victim • Successful ED resuscitation • Remains comatose • Intubated, controlled ventilation • Initial ABG: 7.28/51/465

  3. Initial Hyperoxia • 108 Patients Underwent ED Airway Control • 40/108 (37%) survived to ED discharge • 23/40 (58%) were hyperoxic on initial post-resuscitative ABG (pO2=365+/-142; range 181-681 mm Hg)

  4. Correction of Hyperoxia • 2nd ABG recorded 4.5+/-4.3 hours after 1st ABG (0.8-20 hr) • 16/23 patients (70%) remained hyperoxic (349+/-146 mm Hg; range 166-610) at the time of 2nd ABG. • Normoxic (pO2<150) ABG’s were recorded in 19 patients an average of 19+/-27 (0.8-120) hr following initial ABG

  5. CA/ROSC: Brain Lipid Oxidation * * * Relative Total Peak Area *

  6. HYPEROXIC RESUSCITATION INCREASES BRAIN LIPID OXIDATION Relative HPLC Peak Area Control Normox Hyperox

  7. M49 Non-Ichemic M59 Hyperoxic M61 Normoxic HYPEROXIC RESUSCITATION EXACERBATES PROTEIN OXIDATION FOLLOWING CA AND RESUSCITATION

  8. PYRUVATE DEHYDROGENASE: THE BRIDGE BETWEEN ANAEROBIC AND AEROBIC METABOLISM Glucose ATP Pyruvate Lactate PDH AcetylCoA E T C NAD+ TCA CYCLE ATP NADH

  9. LOSS OF PYRUVATE DEHYDROGENASE IMMUNOSTAINING IN LAYER V PYRAMIDAL NEURONS DURING CA/ROSC Control 10 Min CA 2 Hr ROSC 24 Hr ROSC

  10. HIPPOCAMPAL PDHC E1 QUANTIFICATION Control Hyperoxic Normoxic

  11. GLUCOSE METABOLISM IN THE BRAIN: ANAEROBIC CONDITIONS Glucose ATP Lactate Pyruvate PDH AcetylCoA E T C NAD+ TCA CYCLE ATP NADH

  12. CA/ROSC: Cortical Lactate umol Lactate/gm wet weigt

  13. HYPEROXIA EXACERBATES HIPPOCAMPAL NEURONAL DEATH AFTER CANINE CARDIAC ARREST Non-Ischemic Hyperoxic Normoxic

  14. Neuro Outcome: Hyperoxic ROSC Hyperoxia Normoxia Brain Dead Normal 58.6+/-3.5 45.0+/-4.0

  15. Hyperoxic Resuscitation: Clinical Implications? • Stroke • Cardiac Arrest • Hypovolemic Shock • Cardiopulmonary Bypass • TBI • Others

  16. Stroke: Clinical HyperoxiaRonning OM: Stroke 1999;30:2033 • All stroke patients admitted within 24 hr • ½ Supplemental Oxygen (3 L NC) for 24 hr • Main outcomes: Survival (1 year, SSS, Barthel Index • No differences in survival between groups • Mild Stroke Victims: 91% survival Control; 82% Oxygen (p = 0.023) • Supplemental oxygen not recommended for non-hypoxic stroke victims

  17. NEWBORN RESUSCITATION: RESAIR STUDIES • Asphyxiated newborns, > 1000 g resuscitated with either 100% oxygen or ambient air • Ambient air as efficient as oxygen for newborn resuscitation. • 1st breath and cry, nl breathing pattern established more rapidly with 21% O2 resuscitation • Significantly higher oxidative stress one mo following resuscitation with 100% O2 • Neonatal mortality trends towards lower values in infants resuscitated with ambient air. • No differences in somatic growth or neurologic handicap at 18 – 24 mo

  18. INJURED SHAM HYPEROXIC NORMOXIC anti-nitrotyrosine (1:500) Ni-DAB

  19. Human TBI: Hyperoxia • 24 patients with severe head injury, all with ICP and O2 monitoring and microdialysis • 12 patient cohort given FIO2 100% over six hours vs 12 patient control cohort given standard respiratory therapy • In hyperoxic patients: mean PaO2 441(vs 136.4); brain PO2 levels increased up to 359%; lactate levels decreased by 40% (p<0.05). Menzel M, Doppenberg EM, Zauner A, Soukap J, Reinert MM, Bullock R. J Neurosurg91: 1-10, 1999

  20. HYPEROXIC RESUSCITATION • Hyperoxia worsens clinical neurologic outcome following experimental cardiac arrest/reperfusion. • Hyperoxia worsens oxidation of brain proteins following experimental TBI. • Clinical implications of these experimental data remain unclear. • Long-term outcome studies are needed.

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