This chapter is related to the aims of Section F10(ii) from the 2017 CICM Primary Syllabus, which expects the exam candidate to "explain the physiological effects of ...hypoxaemia".  There is no mention of the causes of hypoxaemia in the syllabus, but it is clearly a learning objective, as some of the past paper questions have asked about it. Overall, hypoxia and hypoxemia questions in the past papers have been distributed as follows:

  • Question 14 from the second paper of 2018 (detection and response)
  • Question 1 from the first paper of 2012 (detection and response)
  • Question 1 from the second paper of 2010 (cause of early post-op hypoxaemia)
  • Question 11 from the second paper of 2007 (acid-base changes in acute hypoxemia)

As the reflexes which control the respiratory responses to hypoxemia are discussed elsewhere, this chapter will gloss over the "detection and response" areas and mainly focus on the classification of causes, and on the physiological consequences of hypoxemia.

In brief:

The following are physiological consequences of hypoxaemia:

  • Airway reflexes (especially cough) are depressed
  • Ventilatory drive increases due to activation of carotid chemoreceptors
  • Respiratory oxygen exchange becomes less efficient due to decrease in concentration gradients and hypoxic alveolar damage
  • Afterload increases in the pulmonary circulation
  • Regional systemic arteriolar beds dilate in response to local hypoxia
  • Systemically, hypoxia produces a sympathetic-driven hypertension and tachycardia
  • Cerebral blood flow increases
  • A respiratory alkalosis and a metabolic acidosis develop, owing to the increased clearance of CO2 and increased production of lactate
  • There is a decrease in diuresis and natriuresis
  • The liver decreases its oxygen consumption and releases increased amounts of  glucose to compensate for increased demand (anaerobic metabolism requires more glucose)
  • Renal release of erythropoietin increases, stimulating the production of erythrocytes
  • Release of hypoxia-induceable factors (HIFs) stimulates immune cells to produce (mainly, proinflammatory) cytokines

As far as published peer-reviewed evidence goes, no one single source contains enough information to cover this entire topic, and one must by necessity trawl through multiple papers and book chapters. The bibliography at the end of this article is representative, but far from comprehensive. 

Hypoxia and hypoxemia

"For a good mark it was expected that candidates define hypoxaemia", the examiners crowed gleefully in their comments to the poorly-performing Question 1 from the second paper of 2010, where 67% of the candidates were unable to "discuss the physiological causes of early post operative hypoxaemia". Indeed, it sounds like something worth defining, where one intends to write extensively on the subject. 

In brief:

Hypoxaemia is an abnormally low concentration of oxygen in arterial blood

Hypoxia is the failure of tissue oxygenation

To illustrate the distinction:

  • A patient may be hypoxaemic, but not hypoxic (eg. where the high haematocrit and vigorous circulation maintain the tissue oxygenation of a healthy young climber at the summit of Everest)
  • A patient may be hypoxic, but not hypoxaemic (eg. where a patient with cardiogenic shock has excellent arterial oxygenation but minimal oxygen delivery to the tissues)

These examples definitely stray far from the way these terms are used in colloquial lunchroom conversations (i.e. interchangeably) and this whole thing might seem like the indulgent pedantry of curmudgeonly professors, but in fact there is some relevance to it, at least from an exam perspective. "Factors leading to tissue hypoxia, such as anaemia or low 2,3-DPG were not given marks", said the examiners in the response to Question 1 from the second paper of 2010. "Candidates may have done so because they confused “hypoxaemia” with “hypoxia”". In short, those curmudgeonly professors will be marking your papers, and so it is probably important to retrain one's mind to use these terms correctly. 

Where did they come from? Difficult to say. In 1973, when the International Union of Physiological Sciences Committee on Nomenclature compiled their Glossary on respiration and gas exchange, the terms were already so ancient that the committee incorporated them unquestioningly and without offering any references or explanations: 

HYPOXEMIA: Hypoxémie (F); Hypoxämie (G). A state in which the oxygen pressure and/or concentration in arterial and/or venous blood is lower than its normal value at sea level. 

HYPOXIA: Hypoxie (F); Hypoxie (G). Any state in which the oxygen in the lung, blood, and/or tissues is abnormally low compared with that of normal resting man breathing air at sea level. If the PO2 is low in the environment, whether because of decreased barometric pressure or decreased fractional concentration of O2, the condition is termed environmental hypoxia. Hypoxia when referring to the blood is terrned hypoxemia. Tissues are said to be hypoxic when their PO2 is low, even if there is no arterial hypoxemia, as in “stagnant hypoxia” which occurs when the local circulation is low compared to the local metabolism.

So, these terms have been around for a very long time. It appears at first the term anoxyémie was coined by Denis Jourdanet, a Parisian physician whose research deal with mountain sickness, and who used it to describe the reduction of the oxygen content in arterial blood which occurred at altitude (Jourdanet, 1861). Subsequently, work by Paul Bert (1833–1886) popularised the use of this terminology along with the then-revolutionary idea that low arterial oxygen concentration made people sick (Kellogg, 1978). 

Anyway. It is perhaps best to organise one's mind for the discussion of hypoxia into some familiar system. There being many systems with nothing to scientifically discriminate between them, the author will choose one of his liking, which is not necessarily the best one. 

Effects of hypoxia on airway reflexes

One might expect, in the course of increasing becoming more and more hypoxic, that eventually one would become unconscious and lose one's ability to maintain a patient airway in the supine position. That's probably true in some nightmarish perimortem depths of poor oxygenation, i.e. a phenomenon you would see and measure just before the heart stops. With moderate hypoxia, however, upper airway reflexes do not seem affected. Eckert et al (2008) were able to asphyxiate healthy male volunteers down to sats of 85% in their sleep, and discovered that their genioglossus EMG remained essentially unchanged. The same author also demonstrated that in contrast, cough reflex is significantly depressed by sustained hypoxia, as hypoxic subjects required much more capsaicin to provoke the same cough response (Eckert et al, 2006). These were healthy young people breathing 9% FiO2, with an average SpO2 of something like 80-82%, which is a rather plausible ICU-like scenario. In summary, a patient with an SpO2 in their boots may have some cough suppression develop during their hypoxic episode, but their upper airway reflexes should remain intact over the survivable range of oxygen saturation values.

Respiratory effects of hypoxaemia

Effect on respiratory drive: As the relationship of arterial oxygen and alveolar ventilation is detailed elsewhere, this chapter will not digress extensively on the ventilatory response to hypoxemia, only to say that:

  • Decreasing PaO2 causes an increase in minute ventilation.
    • Sensors: peripheral chemoreceptors at the carotid glomus and aortic arch
    • Afferents: vagus nerve and glossopharyngeal nerve
    • Controller: central medullary and pontine respiratory control centres
    • Efferents: phrenic nerve and spinal innervation of respiratory skeletal muscles
    • Effectors: diaphragm, intercostal muscles, scalenes and abdominal muscles 
  • The relationship between oxygen tension and minute volume can be described as a hyperbolic curve
  • The inflexion point for this relationship is approximately a PaO2 of 50-60 mmHg; beyond this threshold value the minute volume increases steeply.

Effect on gas exchange: There are two mechanisms by which hypoxia affects gas exchange. One is a brutally stupid effect related to the difference in partial pressures between the capillary blood and the alveolar content. Low partial pressure of oxygen in the alveolus causes a decrease in the diffusion rate of oxygen purely because the concentration gradient between the alveolus and the capillary is smaller. Consider a preposterous thought experiment where the venous PO2 is 40 mmHg, and the alveolar PO2 is also suddenly made 40 mmHg. Clearly, no diffusion of any sort is going to take place.

The other mechanism is somewhat more subtle. In short, alveolar hypoxia damages alveolar cells, and begets further hypoxia. Alveolar pulmonary cells derive most of their oxygenation from the ambient alveolar air mixture. When the ambient air mixture is deprived of oxygen, so are they. And without oxygen, these cells will not feel very inclined to perform various important duties of theirs, such as secreting surfactant and acting as a good blood-gas barrier. Hypoxic alveolar cells degrade nonessential proteins (like NA+/K+ ATPase), redirect their efforts to focus on their own survival, and to hell with the rest of the organism. What ensues resembles ARDS, or high altitude pulmonary oedema. Jain & Sznajder (2005) have produced an excellent summary of the details.

Beyond these effects, hypoxia also influences the function of the pulmonary vessels, which is a whole separate kettle of fish.

Cardiovascular effects of hypoxaemia

Cardiovascular effects of hypoxaemia should probably be separated into "cardiac" and "vascular".  Both are explored with excellent attention to detail in  Almirall & Hedenstierna (1991).

In summary:

  • Hypoxic vasoconstriction in the pulmonary circulation
  • Regional hypoxic vasodilatation in the systemic circulation:
    • Cerebral arterial vasodilation
    • Coronary arterial vasodilation
  • but...
    • Systemic hypoxic vasoconstriction and hypertension, due to sympathetic overactivity driven by activated carotid and aortic chemoreceptors 
  • With profound hypoxia, cardiovascular collapse and fall in cardiac output 

The pulmonary circulation really only has this one mechanism of autoregulating the blood flow to differently ventilated lung region, and that is hypoxic pulmonary vasoconstriction. The normal value for pulmonary vascular resistance (PVR) is 100-200 dynes/sec/cm-5, or  255 - 285 dynes-sec/cm–5/m2 for PRVI (indexed to boy surface area).  With hypoxia, this value increases by about 100% over the course of about 5 minutes (Talbot et al, 2005)

Systemic arteries, taken as an isolated series of muscular tubes, vasodilate in response to hypoxia. This is a mechanism best known for its local effects in tissues which are experiencing an increased metabolic load. Being unable to control the cardiac output, the local circulatory beds only have their own resistance to manipulate, when it comes to controlling flow. As resistance drops, so the flow increases, and the delivery of oxygen regionally improves. 

The coronary circulation also vasodilates in response to hypoxia. The level of hypoxia required for this seems to be quite significant, requiring a PaO2 in the order of 35-40 mmHg. Vance et al (1971) found that coronary blood flow increased by about 50% below that threshold. 

However, the systemic circulation, taken as a complex system with multiple neurohormonal controls, actually reacts quite differently to severe hypoxia. Below a PaO2 of around 70 mmHg, carotid and aortic chemoreceptors produce enough sympathetic stimulus to markedly increase peripheral vascular resistance cardiac output and blood pressure. This was demonstrated  in a series of experiments by Pelletier et al (1972); as the years were unkind to the photocopied paper, the original graph from the paper required some retouching, but the shape and scale of the data remain unchanged:

systemic sympathetic vasoconstriction in response to hypoxiaAs one can see, there was some vasoconstrictor stimulus even with a relatively normal SpO2 70 mmHg, which increases dramatically with the severity of hypoxaemia. The pressures measured in the abovedemonstrated dog's hind limb reached preposterously high values (almost 300 mmHg!) with a PaO2 of 35 mmHg.

The cardiac effects are somewhat more complex. The range of hypoxaemia which would be tolerated by the heart is surprisingly broad. For ICU people, that is probably worth knowing. We are known to walk into scenes where the patient is grey in colour and the oxygen saturation monitor is alarming with an implausibly low value.  These people will probably continue to have some cardiac output for a few more seconds, before they succumb to hypoxic bradycardia and finally asystole. To explore this shadowy territory at the edges of death, Hobler & Carey (1973) killed ten dogs with hypoxia (that's 180kg of dog in total) while continuously measuring their cardiac output and lactate. The diagram below is essentially identical to those in the original paper, except crudely doctored to include some of the original measured values.

cardiovascular collapse in response to profound hypoxia

As one can make out from these data, cardiac output in these dogs was well maintained over a fairly large range of values. However, at a PaO2 of around 36 mmHg (corresponding to sats of around 65%) lactate begins to rise, suggesting that there is some impairment of tissue oxygen delivery. Beyond this point, at a PaO2 of around 25 mmHg, cardiac output drops dramatically. Most of the dogs in this study had cardiac arrests around PaO2 of 15 mmHg. Of course, these findings do not mean that a PaO2 of 36 is safe indefinitely, but they do demonstrate the surprising resilience of the heart against hypoxia.

Central nervous system effects of hypoxaemia

The cerebral circulation responds to arterial hypoxaemia by attempting to increase cerebral blood flow, which seems like a logical step. If the oxygen content of blood is insufficient, the only way of maintaining the same rate of oxygen delivery would be to increase the blood flow rate. The vessels of the brain accomplish this by dilating. In fact, the vasodilation is quite marked. As seen in the graph below,   Kontos et al (1978) were able to demonstrate a change in vessel diameter of up to 140% of control values in a bunch of urethane-anaesthetised cats, at a PaO2 of around 25 mmHg (i.e. sats of slightly under 50%). 

cerebral vasodilation in response to hypoxia from Kontos et al (1978)

This seems to be a smooth muscle response under local control, rather than a reflex, because denervated cerebral vessels seem to retain the capacity to dilate and constrict (Heistad et al, 1980). However, bruised inflamed cerebral vessels seem to lose some their regulatory abilities. Lewelt et al (1982) were able to demonstrate this in a cruel-sounding fluid percussion injury model ("cerebral trauma was produced by the release of a weighted pendulum, which impounded a saline-filled Plexiglas column"). Cats whose brains were pummelled in this fashion had trouble increasing their cerebral blood flow in response to severe hypoxia (PaO2 30mmHg).

The neurological effects of acute hypoxia are fairly predictable. The brain is an avid metaboliser of oxygen and has a very high oxygen extraction ratio, with jugular venous saturation often in the 50s. From that, it follows that hypoxia should produce dysfunction of the more oxygen-hungry regions (hippocampus, frontal lobes, etc), which should manifest as an unsubtle slide into coma and seizures. This was investigated by Rossen et al (1943) by means of the cruel-sounding Kabat-Rossen-Anderson apparatus, a device for producing rapid occlusion of both carotids. The anoxic subjects remained alert for five or six seconds. Before loss of consciousness, "many subjects experienced rapid narrowing of the field of vision, blurring of vision, with the field of vision becoming gray, and, finally, complete loss of vision". Then the eyes became fixed, consciousness was lost, and seizures ensued. This neurological deterioration appears to be something of a spectrum, which starts with some decrease in cognitive function. Goodall et al (2014) looked at EEG slowing and found that it became established at a PaO2 of around 40mmHg, which corresponds to a SpO2 of around 75%.

Chronic hypoxia is also not exactly benign, even though it can be tolerated for years. The chronically hypoxic elderly from a study by Stuss et al (2008) were found to have "a relatively focused pattern of impairment in measures of memory function and tasks requiring attention allocation", probably related to the slow degeneration of metabolically active limbic regions which are supposed to be responsible for explicit memory. The investigators were surprised to find to overt dementia in their group, and performance across many domains of cognitive function (language abilities, perceptual-motor functioning, simple attention) was completely unrelated to their blood gas results.

Acid-base changes associated with hypoxaemia

This was the topic of Question 11 from the second paper of 2007, which was passed by 14% of the candidates (i.e. by one person). Fortunately, the college examiners left us with a small window into their thinking. In short, there are two main effects:

  • Respiratory alkalosis, at mild hypoxaemia
  • Metabolic acidosis, with severe hypoxaemia

How does this work? Well:

  • Acute hypoxaemia (low partial pressure of oxygen at the carotid chemoreceptors) is a potent respiratory stimulant
  • At a PaO2 around 60 mmHg, "hypoxic drive" becomes an important influence on the respiratory control centre, producing an increase in the respiratory rate and tidal volume
  • This increase in minute volume produces an increase in the clearance of PaCO2 
  • The decrease in PaCO2 changes the chemical equilibrium of bicarbonate and carbonic acid, decreasing the concentration of carbonic acid and increasing the pH
  • Alkalosis ensues.

However, with severe hypoxaemia:

  • The oxygen concentration the blood is insufficient to support aerobic metabolism
  • Cellular metabolism switches to anaerobic metabolism and generates lactate
  • Lactate dissociates fully at physiological pH, widening the anion gap and generating hydrogen ions
  • The presence of excess hydrogen ions decreases the pH
  • This decreased pH serves to further stimulate the respiratory centre

Renal function and electrolytes

Electrolyte composition: Hypoxia has no effect whatsoever on the electrolyte composition of body fluids. Hypoxic animals in a study by Sapir et al (1967) had unchanged electrolytes over a whole week of being at a PO2 of 50%.

Renal function is unsurprisingly affected by hypoxia, as the kidneys are a high oxygen extraction organ and already use most of the oxygen delivered to them under normal conditions. Specifically, the renal medulla operates under conditions of extreme hypoxia even when the rest of the organism is normoxic. Brezis et al (1994) shoved a bunch of Clark electrode microprobes into the kidneys of anaesthetised rats and demonstrated an average medullary PO2 of 16 mmHg under normal operating conditions. One can imagine what would happen if systemic oxygenation were to drop. These hypoxic medullary regions clearly represent a watershed area and end up being injured by hypotension and hypoxia even while the relatively well-oxygenated cortices survive. As the medulla is where you keep your tubules, one might expect hypoxia to produce some degree of tubular injury. Acute tubular necrosis, to be precise.

Everybody knows what ATN looks like, and in any case one could not really describe this as a physiological response to hypoxia What uninjured tubules do when stressed with hypoxia is less clear. Most investigators seem to report decreased urine production and solute clearance, but not everybody agrees what this is due to, or what happens to renal electrolyte handling. Tubular function appears to be well-preserved even in severely hypoxic dogs (breathing about 6% FiOwith Axelrod & Pitts, 1952). But then Neylon et al (1997) demonstrated some hypoxia-associated decrease in diuresis and natriuresis in a rat model, and attributed this to hypotension. In contrast, Pauli et al (1968) modelled hypoxia by using carbon monoxide, and found an increase in natriuresis. 

Hepatic function during hypoxaemia

The liver, in response to a drop in its oxygenation, reacts in a very rational and productive way. Its own oxygen consumption decreases (i.e. some metabolic processes are curtailed in order to conserve oxygen), and it begins to issue glucose, probably in order to facilitate the (highly inefficient) anaerobic metabolism which the rest of the organism will need to survive. This makes perfect sense because one gets much less ATP per glucose molecule when there is not enough oxygen around; ergo more glucose will be needed to supply the same amount of ATP. This information was derived from a foetal lamb model (Bristow et al, 1983) and may not be perfectly generalisable to humans, but it is probably close enough for government work.

Even though hypoxia calls for a more economical use of oxygen, metabolic liver function appears to be otherwise relatively unaffected, as it continues to extract more and more oxygen from the arterial and portal venous blood. This carries on until the hepatic oxygen extraction ratio is essentially 100%, i.e. the blood emerging from the hepatic vein has an SvO2 of 0%.  According to a cat study by Larsen et al (1976), this tends to happen when the oxygen tension of the perfusing blood drops to something like 5-10 mmHg. After that point, the liver gives up on trying to metabolise things, and itself becomes a source of lactate. The rest of the organism of course does not care by that stage, as it is probably dead.

Haematological response to hypoxaemia

As the organ responsible for maintaining the oxygen content of blood, the bone marrow logically responds to hypoxaemia by upregulating its rate of erythropoiesis. More correctly, the kidneys do this, by increasing the rate of erythropoietin synthesis. This mechanism is responsible for the compensatory polycythaemia seen in mountain dwellers (Rodriguez et al, 2000). 

Immune response to hypoxaemia

Immune cells function very well in even extremely hypoxic environments (eg. the inside of an abscess) and so their function is not particularly impaired in the face of systemically low oxygen. However, there are various immune phenomena which take place in the hypoxic patient, detailed by Krzywinska & Stockmann(2018). In summary, hypoxia-inducible factors (HIFs, "transcriptional activators that function as master regulators of oxygen homeostasis in all metazoan species") induce a variety of changes in immune cell function, including:

  • Increased pro-inflammatory cytokine production
  • Increased chemotaxis
  •  IL-8 and TNF-α production
  • Stimulation of VEGF

Causes of hypoxaemia and hypoxia

It is not inconceivable that at some stage some exam candidate somewhere will be directly asked to produce a list of causes for hypoxaemia, which will need to be produced quickly, and with a structure. However, directly is not how CICM likes to ask about this topic.  In Question 11 from the second paper of 2007, "physiological causes of hypoxaemia" was one of the main points expected for a pass, even though the question really sounds like it was all about lactic acidosis and anaerobic metabolism ("describe the acid-base changes that occur in acute hypoxaemia"). In contrast, "no marks were awarded for discussing the causes" in Question 14 from the second paper of 2018, where "the detection and response to hypoxaemia" were the main topics.  In short, the trainees should probably just make a habit of inserting this into every written answer, as it might surprise them by scoring some marks in questions where it otherwise seems irrelevant.

Anyway. The best published non-blog resource for this answer is probably this BMJ article from 1998 by Treacher & Leach, and the snarky response to it by an R.P Howard, Consultant Anaesthetist. The combination of these sources was chopped and lightly fried to create this list (remembering that these are causes of hypoxaemia; i.e. these account for a low blood oxygen content).

  • Decreased alveolar oxygen
    • Alveolar hypoventilation with hypercapnia (eg. opiates, COPD)
    • Decreased atmospheric oxygen tension (eg. high altitude)
  • Decreased oxygen diffusion through the blood-gas barrier
    • Decreased blood-gas barrier surface area (eg. ARDS)
    • Decreased blood-gas barrier permeability (eg. pulmonary fibrosis)
  • Decreased perfusion of gas exchange surfaces
    • V/Q mismatch, eg. pneumonia
    • Shunt (eg. intracardiac right to left shunt)
    • Massively increased dead space (eg. massive PE)
  • Decreased mixed venous oxygen content 
    • Increased O2 consumption (i.e. a relative deficit), due to:
      • an increased metabolic rate, eg. malignant hyperthermia
      • a decreased cardiac output, i.e. increased oxygen extraction ratio

Even though the standard definition of hypoxaemia (low oxygen concentration in the blood) potentially allows for causes such as anaemia, because the concentration of haemoglobin is an essential component of total oxygen concentration in the blood, in fact it appears that CICM (and in fact most authors) limit the definition of hypoxaemia to only causes of low oxygen tension. In other words, oxygen carried on haemoglobin is not factored into this definition.  For example in their answer to Question 1 from the second paper of 2010, the college were insistent that factors which decreased the oxygen-carrying capacity of the blood (such as anaemia and an altered oxygen-haemoglobin dissociation relationship) would not score marks, because they were "factors leading to tissue hypoxia" and therefore a sign that people "may have ... confused “hypoxaemia” with “hypoxia”".

Anyway. A slightly different list could be generated if one is more interested in the causes of hypoxia instead of hypoxaemia.  Again, for every article on this subject there is at least one new way of classifying hypoxia and presenting the same information. The reader is invited to create their own, because that what everybody else seems to have done. A representative example is this system from Part One:

  • Hypoxaemic hypoxia (otherwise known as hypoxaemia?)
    • Decreased alveolar oxygen
      • Alveolar hypoventilation with hypercapnia (eg. opiates, COPD)
      • Decreased atmospheric oxygen tension (eg. high altitude)
    • Decreased oxygen diffusion through the blood-gas barrier
      • Decreased blood-gas barrier surface area (eg. ARDS)
      • Decreased blood-gas barrier permeability (eg. pulmonary fibrosis)
    • Decreased perfusion of gas exchange surfaces
      • V/Q mismatch, eg. pneumonia
      • Shunt (eg. intracardiac right to left shunt)
      • Massively increased dead space (eg. massive PE)
    • Decreased mixed venous oxygen content
      (increased O2 consumption) due to:
      • a decreased cardiac output, i.e. increased oxygen extraction ratio
      • an increased metabolic rate, eg. malignant hyperthermia
  • Anaemic hypoxia
    • Decreased oxygen-carrying capacity of the blood
      • Insufficient effective haemoglobin (eg. anaemia, methaemoglobinaemia, carbon monoxide poisoning)
      • Inappropriate change in oxygen-haemoglobin affinity (eg. severe acidosis)
  • Ischaemic hypoxia
    • Decreased delivery of otherwise well-oxygenated blood to the tissues, eg. sepsis or cardiogenic shock
  • Histotoxic hypoxia (also known as cytotoxic hypoxia)
    • Failure to utilise oxygen at the cellular or mitochondrial level, eg. due to cyanide toxicity

Causes of specifically postoperative hypoxemia

Mainly because the college were interested in this topic, it will have the most attention here, even though postoperative hypoxemia is no more important than medical nonoperative hypoxemia. Jones et al (1990) covered this in some detail. In summary, what follows is just the abovementioned list of causes for hypoxaemia, except this time seasoned with some perioperative flavour. The attentive reader will notice that only the examples were changed.

  • Decreased alveolar oxygen
    • Alveolar hypoventilation, due to
      • Opiate analgesia
      • Residual anaesthetic agent
      • Incomplete reversal of NMJ blocker
  • Decreased perfusion of gas exchange surfaces
    • V/Q mismatch
      • atelectasis due to decreased FRC (supine position, anaesthesia)
      • atelectasis due to increased closing capacity
      • atelectasis due to the use of supplemental oxygen ("absorption atelectasis")
    • Increased dead space (due to positive pressure ventilation)
  • Decreased mixed venous oxygen content 
    • Increased O2 consumption, due to:
      • an increased metabolic rate, eg. malignant hyperthermia
      • a decreased cardiac output, i.e. increased oxygen extraction ratio, due to the cardiotoxic effects of anaesthetic drugs

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