OxygenPeter 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 NADwhich 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
MilkDigitalisTincture of nux vomicaMustard plasterPure brandy subcut
Increased heart function (EF)
Fall in lactate
May be better?
No benefit, but nice acronym
Increasing Hospital Admission(in the best sense)
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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 . . .
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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
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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?
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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 onmyocardial injury in ST-elevation myocardialinfarction• 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.
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Debate about harm of hyperoxia
YES
NO
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In-hospital mortality69
Poor neurological outcome
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“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”
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Although prospective data are lacking, retrospective studies and meta-analysis suggest that hyperoxia could be associated with an increased mortality
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. . . but was associated with decreased survival and worse neurological outcomes.
Elmer et al. Critical Care (2015) 19:105170 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.”
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So can we safely use less oxygen?
• Adults (age ≥18 years), • Unconscious (Glasgow Coma Scale<9) • with an advanced airway
(endotracheal tube [ETT] or supraglottic airways [SGA]) in situ and
• sustained ROSC• following an OHCA of presumed
cardiac cause, and • an initial monitored rhythm assessed
as shockable (ventricular fibrillation or pulseless ventricular tachycardia).
Randomly assigned to either • 2 L/minute (L/min) oxygen (titrated) or• >10 L/min oxygen (control) with the oxygen administered via a bag-valve reservoir (BVR), otherwise known as aself-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 randomised controlled trials enrolled 16 037 patients with sepsis, critical illness, stroke,
trauma, myocardial infarction, or cardiac arrest, and patients who had emergency surgery.
In acutely ill adults, high-quality
evidence shows that liberal
oxygen therapy increases
mortality without improving
other patient-important
outcomes. Supplemental oxygen
might become unfavourable above
an SpO₂ range of 94–96%. These
results support the conservative
administration of oxygen therapy.
15. In patients with Paraquat poisoning or bleomycin lung injury the routine use of supplemental oxygen is not recommended.
16. In patients with Paraquat poisoning or bleomycin lung injury it is recommended that oxygen administration be targeted to achieve oxygen saturation (SpO2) of 88-92%.
17. In patients who are at risk of hypercapnic respiratory failure, the routine use of supplemental oxygen is not recommended.
18. In patients who are at risk of hypercapnic respiratory failure it is recommended that oxygen administration be targeted to achieve oxygen saturation (SpO2) of 88-92%.
Patients at risk of hypercapnic respiratory failure• A small reduction in ventilation may be a contributing factor to the
rise in carbon dioxide levels during oxygen therapy in COPD. Much of the rise in carbon dioxide which occurs is due to deterioration in the matching of blood flow and gas flow in the lungs.2 This can be avoided by giving controlled lower concentration oxygen therapy to vulnerable patients.
Who is at risk?If the diagnosis is unknown, patients aged >50 years who are long-term smokers with a history of chronic breathlessness on minor exertion such as walking on level ground and no other known cause of breathlessness should be treated as if having COPD. Patients without diagnosed COPD, but at risk of hypercapnic respiratory failure include patients with:
• cystic fibrosis
• bronchiectasis
• severe kyphoscoliosis or severe ankylosing spondylitis
• severe lung scarring from old tuberculosis (especially with thoracoplasty)
• morbid obesity (body mass index >40 kg/m2)
• musculoskeletal disorders with respiratory muscle weakness (especially if on home ventilation)
• overdose of opioids, benzodiazepines or other respiratory depressant drugs.
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?
BMJ 2018;363:k4169 doi: 10.1136/bmj.k4169
The panel asked:
• In acutely ill patients, when should oxygen therapy be started?
(What is the lower limit of peripheral capillary oxygen saturation (SpO2)?)
• In acutely ill patients receiving oxygen therapy, how much oxygen should be given?
(What is the upper limit of SpO2?)
BMJ 2018;363:k4169 doi: 10.1136/bmj.k4169
BMJ 2018;363:k4169 doi: 10.1136/bmj.k4169
So they all need a pulse oximeter . . .
What about pulse oximetry???
What does the Pulse Oximeter try to measure ?• tries to measure SaO2
• assumes all patients are healthy controls with same calibration curve
• either approximate functional or fractional saturation
• 2 SD +/- 4%?
Factors affecting accuracy of oximeters
• motion artefact• newer oximeters better
• low saturation• poor validation
• overhead lights• SpO2 may be falsely elevated (sunlight) or lowered (infrared)
• heart rate unreliable
• dyshaemoglobinaemias• carboxyhaemoglobin
• viewed as if oxyhaemoglobin
• SpO2 overestimates SaO2
• methaemoglobin
• absorption ratio close to one (83-87%)
• SpO2 approaches 85% as metHb increases
Factors affecting accuracy of oximeters• dyes
• methylene blue, indigo carmine, indocyanine green
• falsely low SpO2
• nail polish• falsely low if blue/green/black/purple
• try perpendicular placement
• vasoconstriction / low flow states
• cyanide ?
• low SVR ?• Secker C et al (1997) Anaesthesia 52:127-130
Are you worried about PaO2??
And how do we give the O2 anyway?
Oxygen delivery devices: nasal and simple masks• A wide range of simple devices aim to blow oxygen at or into the air
passages.
• This oxygen is mixed with inspired air to give an inspired oxygen concentration which is a complex function of the geometry of the device, the oxygen flow rate, the patient's ventilation and whether the patient is breathing through his mouth or nose.
• The effective inspired oxygen concentration is impossible to predict and may vary within very wide limits (Leigh, 1973).
Evidence:The use of oxygen may be beneficial in emergencies with breathing and non-breathing victims [Class A; LOE Expert Consensus Opinion]. There is evidence to support the use of oxygen as part of first aid management of:• decompression illness (COSTR 2015, very low quality evidence) and for • shortness of breath (dyspnoea) in cancer patients with hypoxaemia (COSTR 2015 moderate quality
evidence) and without hypoxaemia (COSTR 2015, very low quality evidence).
3.2 Conditions where oxygen is recommended
• during cardiopulmonary resuscitation (Guideline 11.1.1, Guideline 12.2)
• bleeding (Guideline 9.1.1)
• burns (Guideline 9.1.3)
• shock (Guideline 9.1.4)
• heart attack with shortness of breath (Guideline 9.2.1)
• stroke (Guideline 9.2.2)
• asthma (Guideline 9.2.5)
• anaphylaxis (Guideline 9.2.7)
• drowning (Guideline 9.3.2)
• decompression illness (Guideline 9.3.5)
• poisoning (Guideline 9.5.1).
12. All patients with shock, major trauma, sepsis or other critical illness should be managed initially with high concentration oxygen therapy from a reservoir mask. It is recommended that oxygen administration be targeted to achieve an oxygen saturation (SpO2) of 94-98%.
13. The routine use of supplemental oxygen high-dose oxygen via a reservoir mask is recommended for a patient with carbon monoxide poisoning.
14. Patients developing symptoms of decompression sickness after diving should be treated with high flow oxygen as soon as possible.
Avoid hypoxia and hypotension?
Summary
•Oxygen is good: sometimes
•Lack of oxygen is bad: sometimes
•Why not use it in everyone? It can cause harm
• Is there actually evidence of harm? Yes, but . . .
•So what about the guidelines? Complex, but a simple message
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
Management• Basic Life Support measures should never be delayed whilst waiting for oxygen or other equipment. [Class A; LOE Expert
Consensus Opinion].
• The short-term administration of supplemental oxygen to a breathing victim will not cause harm in most circumstances.
• The administration of oxygen and use of oxygen delivery devices should only be undertaken by those who are trained
• A victim who requires supplemental oxygen in a first aid setting requires further assessment by a health care professional so an ambulance must always be called.
• Pulse oximetry, may be useful in guiding oxygen therapy.
• Victims with an oxygen saturation of 94% or above do not usually need supplemental oxygen unless there are signs of cyanosis (blue colouration of skin), shock, decompression illness or a situation suggesting carbon monoxide poisoning
All about Goldilocks
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