Toxic Alcohols (Murray)

Question 1

What is the toxic mechanism of alcohol?

Answer 1

Exact mechanism is unsure, augmentation of GABA-A receptor complex results in CNS depressant effects. Glycine, NMDA, serotonin, adenosine, L-type calcium channels are also involved. Dose-dependent CV depression, impairs gluconeogenesis –> hypoglycaemia

Question 2

Discuss the toxicokinetics of alcohol.

Answer 2

Rapidly absorbed, distributes readily across total body water (VoD of 0.6 L/kg). Oxidised by cytosolic and microsomal alcohol dehydrogenases to form acetaldehyde –> metabolised by aldehyde dehydrogenase to acetate. Above [ETOH] > 4 mmol/L zero order kinetics applies. The production of NADH decreases lactate to pyruvate metabolism, inhibits gluconeogenesis and fatty acid oxidation.

Question 3

What is the lethal dose of ethylene glycol?

Answer 3

> 1ml/kg (1g/kg) is usually lethal

Question 4

Discuss the toxicity of ethylene glycol.

Answer 4

Toxic effects from metabolites. Severe anion gap metabolic acidosis due to glycolic acid and lactate. Calcium oxalate crystals form - renal tubules, myocardium, muscles, brain leading to hypocalcaemia. Oliguric renal failure due to glycolic acid and calcium oxalate.

Question 5

Discuss ethanol and ethylene glycol.

Answer 5

Ethanol in serum (50-100 mg/dL) competitively inhibits ADH (alcohol dehydrogenase) prevting EG from being metabolised.

Question 6

What are two drugs that can be given that can force EG elimination to be only by the kidneys?

Answer 6

Fomepizole and ethanol

Question 7

Describe the clinical features of EG intoxication.

Answer 7

Three stages (CNS, cardiopulm and renal) do not clearly exist. Instead: (1) 1-2 hours: euphoria, drowsy, nystagmus, nausea/vomiting, (2) 4-12 hours: dyspnoea, tachypnoea, tachycardia, hypertension, ALOC, shock, coma, seizures, death. Flank pain + oliguria –> ARF. Cranial neuropathies may occur 5-20 days later.

Question 8

Describe the blood test results pathognomonic of EG intoxication.

Answer 8

Anion gap acidosis + elevated lactate (+/- elevated osmolar gap), hypocalcaemia, rising creatinine. OR: presence of calcium oxalate crystals in the urine.

Question 9

You have just intubated a patient with EG toxicity, what two measures can you take to ensure their acidaemia does not worsen post-intubation? If they fail?

Answer 9

Keep hyperventilating them on the ventilator and consider a bolus of IV sodium bicarbonate 1-2 mmol/kg. If those measures fail –> dialysis.

Question 10

What should you think about with electrolyte management in EG toxicity?

Answer 10

Detect/correct hypoglycaemia, hyperkalaemia and hypomagnasaemia but only correct hypocalcaemia IF the QT is prolonged or the patient is having protracted seizures.

Question 11

What are the indications for dialysis with EG intoxication?

Answer 11

(1) Hx of large ingestion with osmolar gap >10, (2) Acidaemia with pH < 7.3, (3) Acute renal failure, (4) EG level > 8 mmol/L

Question 12

What is important to remember with patients who have had both ethanol and EG?

Answer 12

Coingestion results in delays in the onset of EG intoxication/clincal features

Question 13

What are sources of ethylene glycol?

Answer 13

Radiator coolants, antifreeze, de-icing solutions, solvents, brake fluids

Question 14

Discuss isopropanol (isopropyl alcohol) intoxication.

Answer 14

CNS intoxications syndrome identical to ethanol but more potent and longer in duration. GI irritation + ketosis without acidosis. Supportive management.

Question 15

What amount of methanol ingestion is potentially lethal?

Answer 15

> 0.5 ml/kg of 100% methanol; in children even >0.25 ml/kg could cause singificant toxicity

Question 16

What is the mechanism of toxicity with methanol?

Answer 16

Production and accumulation of formic acid –> severe anion gap acidosis and direct cellular toxicity due to inhibition of cytochrome oxidase. Hyperlactataemia, retinal injury and CNS haemorrhages/oedema result.

Question 17

Describe the toxicokinetics of methanol.

Answer 17

Rapidly absorbed, VoD of 0.7 L/kg. Metabolised by alcohol dehydrogenase to form formic acid (via formaldehyde). Coningestion with alcohol prevents formaldehyde formation and therefore stops formic acid formation too. Elimination by the kidney and pulmonary route.

Question 18

Describe the clinical featuers of methanol intoxication.

Answer 18

Similar to ethanol - mild CNS depression, abdo pain, nausea/vomiting initially. After approx 12-24 hours: headaches, dizziness, dyspnoea, blurred vision, photophobia, drowsiness, blindness. Progressive obtundation –> coma _ seizures (secondary to cerebral oedema). Papilloedema, demyelination progress. One-third of patients may have irreversible visual complications.

Question 19

What are the typical CT brain findings in methanol intoxication?

Answer 19

Ischaemic/haemorrhagic injury to the basal ganglia.

Question 20

What is an important physiological consequence of acidosis in patients with methanol intoxication?

Answer 20

If the pH < 7.3, it enhances formic acid inhibition of cytochrome oxidase. So ensure that bicarbonate is given in 50 mmol aliquotes if the pH is <7.3

Question 21

What drug can be given in methanol intoxication?

Answer 21

Cofactor therapy - folinic/folic acid 50 mg IV every 6 hours until poisoining is definitively treated

Question 22

What are the indications for dialysis with methanol intoxication?

Answer 22

Any patient that fulfils the criteria for ADH blockade, acidaemia with pH < 7.3, visual symptoms, renal failure, deterioration of vital signs/electrolyte status despite supportive care, methanol level > 16 if available

Question 23

If a child has a suspected unintentional methanol ingestion, when may they be discharged?

Answer 23

If they have a normal venous bicarb level at 8+ hours post-ingestion

Question 24

If an adult has a suspected unintentional methanol ingestion, when may they be discharged?

Answer 24

Normal venous bicarbonate level at 8 hours post-ingestion + normal ETOH level at same time

Question 25

Provide several examples of sources of methanol.

Answer 25

Methylated spirits in Australia do not contain methanol. However, dyes, stains, racing car fuel, solvent in thinners/paints, carburettor cleaning fluid, wood alcohol,

Question 26

In what contexts is propylene glycol toxicity often a problem?

Answer 26

It is a dilutent in drug preparations; associated with sudden cardiovascular collapse

Question 27

With what toxic alcohol ingestions can symptoms of toxicity be delayed by up to 48 hours?

Answer 27

EGBE, EGME

Question 28

List some treatment options with toxic alcohol ingestion.

Answer 28

Haemodialysis, IV sodium bicarbonate, ethanol and fomepizole

Question 29

What are the metabolic changes you would expect to find with toxic alcohol intoxication?

Answer 29

Acidosis, bicarb <20 with an osmolar gap >10