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  • Oxygen Peter Morley

    Royal Melbourne Hospital

    University of Melbourne

  • Conflict of Interest

  • Oxygen: some facts

    • OK-si-jen

    • named by Antoine Lavoisier (mistakenly) from the Greek words oxys and genes, which mean "acid forming”

    • “Discovered” in 1774 by • Joseph Priestley “dephlogisticated air” • Carl Wilhelm Scheele “fire air”

    • the third most abundant element in the universe • nearly 21% of the earth's atmosphere • nearly half of the mass of the earth's crust, • two thirds of the mass of the human body • nine tenths of the mass of water

  • Rule number 1

    Avoid hypoxia and hypotension?

  • So you are called to see a man who is severely short of breath

    Obviously you grab an oxygen cylinder and a face mask, perhaps a non- rebreather, or some nasal prongs, and just sit and wait till he settles

  • Summary

    •Oxygen is good

    •Lack of oxygen is bad

    •Why not use it in everyone?

    •Is there actually evidence of harm?

    •So what about the guidelines?

  • Summary

    •Oxygen is good

    •Lack of oxygen is bad

    •Why not use it in everyone?

    •Is there actually evidence of harm?

    •So what about the guidelines?

  • Figure 10.1 Diagrammatic representation of oxidation within the mitochondrion. The substrate diffuses from the cytoplasm into the mitochondrion where hydrogen is removed under the influence of the appropriate dehydrogenase enzyme. The hydrogen is carried by intramitochondrial NAD to the first of the chain of hydrogen carriers which are attached to the cristae of the mitochondria. When the hydrogen reaches the cytochromes, ionization occurs; the proton passes into the lumen of the mitochondrion while the electron is passed along the cytochromes where it converts ferric iron to the ferrous form. The final stage is at cytochrome a3 where the proton and the electron combine with oxygen to form water. Three molecules of ADP are converted to ATP at the stages shown in the diagram. ADP and ATP can cross the mitochondrial membrane freely while there are separate pools of intra- and extramitochondrial NAD which cannot interchange

    Nunn, J. F., and John F. Nunn. Applied Respiratory

    Physiology, Elsevier Science & Technology, 1987.

    Cytochrome c oxidase system which is responsible for about 90 per cent of the total oxygen consumption of the body.

  • 1890

    Milk Digitalis Tincture of nux vomica Mustard plaster Pure brandy subcut

  • Increased heart function (EF)

  • Fall in lactate

  • May be better?

  • No benefit, but nice acronym

  • Increasing Hospital Admission (in the best sense)

  • 19

    167 adults with IHCA. Higher intra-arrest PaO2 is independently associated with higher rates of survival to discharge. Journal of Intensive Care Medicine 2016: 1-8

  • So really . . .

  • 22

  • RCTs

    Other evidence

  • Evidence?

    Observational studies

    Randomised controlled trials

    Support my opinion “see, I told you” “see, I told you”

    Contradict my opinion “Poor quality;

    need RCTs” “Poor quality; not relevant to my patients”

  • The Tony Smith modification • Level one – randomised trials that support my own opinion

    • Level two – expert opinions that support my own opinion

    • Level three – all other forms of evidence that support my own opinion

    • Level four – any form of evidence that does not support my own opinion

    • Level five – uninformed opinion of morons

    • Level six – media reports of the opinion of helicopter pilots

  • Summary

    •Oxygen is good

    •Lack of oxygen is bad

    •Why not use it in everyone?

    •Is there actually evidence of harm?

    •So what about the guidelines?

  • Oxygen

    Can’t live without it!

  • Nunn’s Applied Respiratory Physiology

    • Circulatory arrest. When the circulation is arrested, hypoxia supervenes as soon as the oxygen in the tissues and stagnant capillaries has been exhausted. • In the case of the brain, with its high rate of oxygen consumption, there is only

    about 10 seconds before consciousness is lost.

    • Exposure to a barometric pressure of less than 6.3 kPa (47 mmHg): the Po2 rapidly falls to zero and consciousness is lost within one circulation time, which is of the order of 15 seconds (Ernsting and McHardy, 1960).

    • Generally speaking, after breathing air, 90 seconds of apnoea results in a substantial fall of PO2 to a level which threatens the subject with loss of consciousness.

  • Nunn, J. F., and John F. Nunn. Applied Respiratory

    Physiology, Elsevier Science & Technology, 1987.

  • Hypoxia (asphyxia) is an animal model for cardiac arrest

  • 34

  • Summary

    •Oxygen is good

    •Lack of oxygen is bad

    •Why not use it in everyone?

    •Is there actually evidence of harm?

    •So what about the guidelines?

  • Oxygen may be harmful

  • Oxygen larger infarct size?

  • Summary

    •Oxygen is good

    •Lack of oxygen is bad

    •Why not use it in everyone?

    •Is there actually evidence of harm?

    •So what about the guidelines?

  • So what’s wrong with Oxygen?

  • 44

  • 48

  • For a heart attack?

  • 2009: may increase infarct size

  • 2010

    3 times as many people died in the oxygen group!

  • Nehme Z, et al. Heart 2016;102:444–451. doi:10.1136/heartjnl-2015-308636

  • Effect of supplemental oxygen exposure on myocardial injury in ST-elevation myocardial infarction • Multicentre, prospective, randomised, controlled trial of 441 patients with STEMI

    randomised to supplemental oxygen therapy or room air breathing.

    • The primary endpoint was myocardial infarct size as assessed by cardiac biomarkers, troponin (cTnI) and creatine kinase (CK).

    • Oxygen therapy was commenced by paramedics, and continued for up to 12 h postintervention in hospital.

    • In this study, supplemental oxygen administered in the first 12 h after STEMI was associated with a dose-dependent increase in cTnI and CK release.

    • Our findings suggest that a typical patient receiving supplemental oxygen exposure in the first 12 h after STEMI would experience an approximate 20% increase in myocardial infarct size.

  • No difference in mortality (with suspected or confirmed MI) or size of infarct

  • There was more hypoxia in the air group!

  • After cardiac arrest?

  • The administration of 100% oxygen therapy is associated with worse neurological outcome than lower oxygen concentrations in animal models of cardiac arrest.

    66

  • Debate about harm of hyperoxia

    YES

    NO

    67

  • 68

  • In-hospital mortality 69

  • Poor neurological outcome

    70

  • “However, because of the great heterogeneity among (these

    observational) studies, this conclusion should be interpreted with caution. The timing and duration of exposure to hyperoxia were not controlled in

    each study”

    71

  • 72

    Although prospective data are lacking, retrospective studies and meta-analysis suggest that hyperoxia could be associated with an increased mortality

  • 74

    . . . but was associated with decreased survival and worse neurological outcomes.

  • Elmer et al. Critical Care (2015) 19:105 170 post-arrest patients

    • “Our results reflect that oxygen exposure was increased in those with the worst early cardiopulmonary dysfunction, which one would expect if oxygen were being titrated based on the clinical assessment of the patient.”

    • “we observed what appears to be a threshold effect where toxicity accrued only after FiO2 exceeded an average of 0.75 over 24 h.”

    75

  • So can we safely use less oxygen?

  • • Adults (age ≥18 years), • Unconscious (Glasgow Coma Scale10 L/min oxygen (control) with the oxygen administered via a bag-valve reservoir (BVR), otherwise known as a self-inflating bag.

  • • Presumed cardiac OHCA cases who achieve a return of spontaneous circulation will be eligible if they are comatose, with an advanced airway and have an oxygen saturation (SpO2) 95% on >10 L/min (or 100% oxygen).

    • Paramedics will randomise 1416 eligible cases to receive oxygen therapy targeting an SpO2 of 90–94% (intervention) or 98–100% (control).

    • Study treatment will continue until admission to an intensive care unit or hospital ward.

  • So what about oxygen use in other “sick” patients?

  • 25 rand