Question 10.1

Highest mark

8.75

A 58-year-old farmer with a history of depression was found collapsed in his shed. On arrival at the Emergency Department, his Glasgow Coma Scale score was 10 (E2, V3, M5), respiratory rate was 23 breaths per minute, and mouth ulceration was noted with a green coloured substance staining his lips, hands and clothes.

His arterial blood gas and biochemistry on admission were as follows:

Parameter	Patient Value	Normal Adult Range
FiO2	0.5
pH	7.29*	7.35 – 7.45
PCO2	35 mmHg (4.6 kPa)	35 – 45 (4.6 – 6.0)
PaO2	68 mmHg	(9.0 kPa)
HCO3	16 mmol/L*	24 – 28
Base Excess	-9.0 mmol/L*	-2.0 – +2.0
Sodium	140 mmol/L	135 – 145
Potassium	4.3 mmol/L	3.5 – 5.0
Chloride	111 mmol/L*	95 – 105
Glucose	7.2 mmol/L*	4.0 – 6.0
Lactate	5.2 mmo/L*	< 2.5
Haemoglobin	162 g/L*	130 – 160
Creatinine	230 µmol/L*	60 – 120

a) Characterise the acid-base and blood gas abnormalities.

b) What is the likely diagnosis?

c) List the important principles of management specific to this condition.

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College Answer

a) Characterise the acid-base and blood gas abnormalities.

Combined high anion gap and normal anion gap metabolic acidosis with inadequate respiratory compensation (respiratory acidosis)
A-aDO2 = 245

b) What is the likely diagnosis?
Paraquat ingestion

c) List the important principles of management specific to this condition.

Risk assessment based on estimate of quantity of Paraquat ingested
Gastrointestinal decontamination with diatomaceous earths, activated charcoal or sodium resonium

Monitoring for organ dysfunction (respiratory, CVS, renal, GIT, adrenal, hepatic, CNS)

Avoid high FiO2

Discussion

a)

This data set is identical to that of Question 14.1 from the first paper of 2008.

Firstly, what we have here is a hypoxia with a widened A-a gradient.
The PAO2 should be (0.5 x 713) - (35 x 1.25), or 311mmHg - so the gradient is a whopping 246.
Next, we have a metabolic acidosis (the BE is -9)
This disorder is inadequately compensated by ventilation. No matter which equation you use, the CO2 should be lower. If you apply the "7.xx" rule, the CO₂ shold be the last two digits of the pH - 29. If you apply Winter's Formula, the CO₂ should be around 32. Thus, a mild respiratory acidosis also exists.
The anion gap is only slightly raised, 17.3 (140+4.3 - 111 - 16)
The delta ratio is therefore 0.66 (5.3 / 8) -if we take the normal anion gap to be 12.
The metabolic acidosis is therefore a mixed disorder.
The serum osmolality and urea are not provided, so we cannot calculate an osmolar gap.

b)

The findings suggest paraquat toxicity:

Mild overdose:

Nausea and vomiting
Diarrhoea
Intestinal hemorrhage
Haemoptysis
Oliguria
Minimal renal dysfunction

Moderate overdose:

Renal failure (ATN within 12-24hours)
Pulmonary oedema
Hepatotoxicity
Pulmonary haemorrhage
Shock
Pulmonary fibrosis

Massive overdose:

multi-organ system failure
rapidly fatal

The toxicity (at least in moderate doses) emerges in several discrete phases:

Phase I: corrosion; mucosal linings ulcerate and swell; there may be haematamesis.This is the first two days.
Phase II: organ failure; between the second and fifth days following ingestion, renal failure and hepatocellular necrosis develop. Most patients with severe overdose will die during this phase.
Phase III: pulmonary fibrosis; death after many days/weeks of hypoxia.

c)

Management of paraquat overdose follows the following pattern:

Decontamination

Fuller's Earth: calcium montmorillonite, or bentonite - a absorbent aluminium phyllosilicate, formed from the weathering of volcanic ash.
Activated charcoal may have equal efficacy, and is more widely available
Cation exchange resins (eg. resonium) may be of use
The “window of opportunity” is very narrow, only a few hours at most. Absorption from the gut is very rapid.
Remove contaminated clothes
Wash skin with soap and water to prevent transdermal absorption

Enhancement of elimination

Charcoal haemoperfusion works very well, but contributes little to the overall prognosis because the drug is rapidly cleared from the plasma anyway, and the pulmonary reserve is trapped there (it is not available for removal).
Dialysis is probably going to be useless, as paraquat is rapidly eliminated and by the time you get the circuit set up most of it will have gone already. The alveolar and renal damage will have been done by then, so you have nothing to gain (other than a more rapid control of the acid-base disturbance).

Specific antidotes

None exist. Among previously trialled antioxidants, we can find Vitamin E, Vitamin C, desferrioxamine, N-acetylcysteine, methylene blue, etc. Thus far, nothing satisfying has been found.

Supportive management

Intubation to protect the rapidly swelling airway after corrosive ingestion
Avoidance of hyperoxia: it has been demonstrated to exacerbate the oxidative toxicity of paraquat.
Circulatory support (there will be shock from myocardial necrosis and third space losses
Analgesia and sedation which is almost palliative in its intent - many of these people will die in spite of everything you do.
Specifically, propofol seems to have some sort of unique scavenging effect.

References

Gawarammana, Indika B., and Nicholas A. Buckley. "Medical management of paraquat ingestion." British journal of clinical pharmacology 72.5 (2011): 745-757.

Clark, D. G. "Inhibition of the absorption of paraquat from the gastrointestinal tract by adsorbents." British journal of industrial medicine 28.2 (1971): 186-188.

Kehrer, James P., Wanda M. Haschek, and Hanspeter Witschi. "The influence of hyperoxia on the acute toxicity of paraquat and diquat." Drug and chemical toxicology 2.4 (1979): 397-408.

Dinis-Oliveira, R. J., et al. "Paraquat poisonings: mechanisms of lung toxicity, clinical features, and treatment." Critical reviews in toxicology 38.1 (2008): 13-71.

Sirker, A. A., et al. "Acid− base physiology: the ‘traditional’and the ‘modern’approaches." Anaesthesia 57.4 (2002): 348-356

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