Question 24.1

College answer

Not available.

Discussion

In detail:

• The A-a gradient is slightly increased (713 × 1.0) - (192 / 0.8) - 400 = 73 mmHg.
  However, the patient is not hypoxemic (far from it). 
• The patient is profoundly acidaemic
• The CO₂ is wildly elevated. This can only be an acute change, as nobody walks around in the community with a CO₂ of 200, so the formula that applies is 1:10, i.e. for every 10mmHg rise in CO₂ above 40, the bicarbonate should increase by 1. In this case, that would make the expected HCO₃^- = 24 + (190-40)/10 =  39. Thus:
• There is a metabolic acidosis. The SBE is not provided, but the bicarbonate is only 11, which is far below what you would normally expect for this CO₂ value.
• The anion gap is (147 - 109 - 11) = 27, i.e. it is elevated. 
• The lactate is raised, which is surely contributing to the anion gap elevation. 
• If one accepts 12 as the ideal normal AG, the delta ratio is therefore (27-12)/(24-11) = 1.2, which suggests that this is a purely high anion gap metabolic acidosis. The magnitude of the lactate rise and the magnitude of the change in the anion gap are not entirely proportionate, but close enough, i.e. you could legitimately blame the lactate for the anion gap
• The patient is profoundly hypoglycaemic, with a BSL of 1.3 mmol/L, which is not compatible with normal brain function.
• Creatinine is elevated, and its presence in the blood gas suggests that it was put there to widen the range of differentials.

Three possibilities for how this could have happened? The PaCO₂ is much higher than anything you might expect from a normal cardiac arrest scenario, suggesting that either the patient's ventilatory drive has been suppressed for some time, or there has been some barrier to normal ventilation. Moreover clearly something very easily reversible (like airway obstruction) must have been the cause of cardiac arrest, given the relative ease with which the circulation was restored. Without cheating by looking at the next set of results in Question 24.2, the possibilities include:

• Acute fulminant liver failure with cerebral oedema and decreased level of consciousness would give biochemistry broken in exactly this way, with respiratory acidosis, a raised lactate, hypoglycaemia and acute kidney injury. The possible causes include:
  • Paracetamol overdose with late presentation
  • Amanita phalloides mushroom ingestion
  • A solvent of some sort (xylene, chloroform, trichloroethylene, carbon tetrachloride)
  • Recreational drugs, for example MDMA, cocaine, etc
• Insulin overdose would lead to a decreased level of consciousness and hypercapnia respiratory failure, with the lactate accounted for by the cardiac arrest; but then why the renal failure?
• Severe asthma (fits with the patient's youth but does not fully explain the renal failure, and can't be reconciled with the hypoglycaemia, nor would this have been easy to fix with just a couple of cycles of CPR and an LMA)
• Metformin toxicity, perhaps due to its accumulation in renal failure, with the CO₂ then having to be attributed purely to the cardiac arrest (but then the renal failure remains unexplained)
• Ethylene glycol overdose could also cause this picture, as it can lead to a decreased level of consciousness by its CNS depressant effect (producing hypercapnia), would produce a spuriously elevated lactate level, and would damage the kidneys. However the hypoglycaemia would remain unexplained.

A reader (thank you Dev) opened a tantalising opportunity by asking whether this massive CO₂ could actually represent a hypermetabolic state; in short, could this be a state of increased CO₂ production that is markedly unmatched by ventilation? This is a good hypothesis; but the exam candidates are reminded that not a single word of the exam paper is wasted, and examiners do not usually just randomly insert details like "A laryngeal mask (LMA) was placed en route to hospital" without expecting something to develop from it. In this scenario, it is pretty clear that the answers are being guided  towards the direction of ventilation problems. However, it is also true that valid off-rubric responses would be graded, and this answer does open the door for such responses because the prehospital time is not stated. As such, the CO₂ could have risen over two hours of aeromedical retrieval in a patient with slightly increased metabolism and carelessly chosen ventilator settings; or over twenty minutes of extreme metabolic stress. 

Though the author still feels shame about wasting the reader's time in the exam answers, no such shame exists in the deepest back ends of long meandering chapters, and so naturally an extensive digression into this area followed, which can be summarised as follows:

• Heat stroke could definitely be a differential, and patients with a temperature in excess of 39ºC seem to have up to 50% more CO₂ production, which produces a net increase of ~2mmHg/min. Under these conditions, assuming we start from a normal baseline, the time to achieve a PaCO₂ of 192 would have been about 70-80 minutes (a realistic retrieval timeframe for the geographically cursed continent of Australia, where a cardiac arrest patient may be 500km away from the nearest cath lab)
• Sympathomimetics generally, and sympathetically angry states like hyperthyroidism  sepsis or trauma, do produce an increased rate of CO₂ production, but it is modest- in the order of 10-30% if temperature is controlled for - and the rate of CO₂ rise is proportionally slower, i.e a conventionally septic patient would have to have their ventilator settings thoroughly ignored for at least two hours before their hypercapnia becomes as bad as this SAQ stem.
• Extreme muscular exertion could absolutely lead to hypercapnia. This could come in the form of malignant hyperthermia or status epilepticus. Of the former, small case series suggest that an increase in CO2 production of 5 to 10-fold is common. The result would be a rate of rise of CO₂ by 8mmHg/min, i.e. a CO₂ of nearly 200 within about 20-30 minutes.  Malignant hyperthermia would be a highly plausible option here if there was no mention of the LMA, because then we could all assume the patient was intubated with a rapid sequence induction and therefore had a reasonable chance of getting a dose of suxamethonium to trigger a hyperthermic crisis. Status epilepticus could theoretically produce even more CO₂, as muscle exertion is the way our sports heroes increase their VCO₂ production, but it is unlikely that this patient is being transported  from the scene of their arrest without the use of muscle relaxant, which somewhat limits the reach of this hypothesis.

In short, of the possible ways to add these to the answer, one would want to probably limit oneself to sux-induced MH and heat stroke with prolonged transfer, but the marks were surely mostly concentrated in ventilation-related areas, and for 15% (1.5 marks, ninety seconds of writing) the average candidate cannot afford to get too academic about any of this.  Consider, from your own viewpoint, observing a senior colleague who receives an admission like this, and immediately starts shouting about dantrolene. Common things are common, one might retort in that scenario; the likelihood that the seal is poor and the ventilation substandard greatly outweighs the possibility of a rare drug reaction or a thyrotoxic crisis underlying this presentation.