Toxic alcohols

Question 1

Discuss risk assessment for ETOH intoxication

Answer 1

ETOH ingestion causes rapid dose dependent CNS depression with a high degree of inter-individual variability

Dose may be estimated if the number os standard drinks is known (10g ethanol in a standard drink)

Co-ingestion of other CNS depressants increases the risk of respiratory depression

Question 2

Discuss Toxicokinetics of ETOH

Answer 2

Rapidly absorbed following oral administration - distributes readily to total body water (VD 0.6Lkg)

ETOH is oxidised by cytosolic and microsomal alcohol dehydrogenases to form acetaldehyde which in turn is metablised by aldehyde dehydrogenase to acetate. Both steps incolve the reduction of NAD to NADH

It is metabolised by zero order kinetics – in most cases decrease by approximatly 4mmol/l/hour

The production of NADH decreases conversion of lactate to pyruvate and inhibits gluconeogenesis and fatty acid oxidation

Question 3

Discuss sources of ethylene glycol and risk assessment of same

Answer 3

Used for two main purposes as a raw material in the manufacture of polyester fibers and for antifreeze formulations.

Ingestion of >1ml/kg is potentially lethal
-all deliberate self poisoning are assumed to be potentially lethal
-Unintenional infegestion of less than a mouthful is benign and dose not require hosptial evaluation
-Coingestion can complicate risk assessment
Demral and inhalation exposures does not lead to EG intoxication

Question 4

Discuss toxic mechanisms of ethylene glycol

Answer 4

Causes CNS effects similar to those seen with ETOH – the more important toxic effects are due to metabolites rather that the parent compound

Severe HAGMA develops secondary to accumulation of glycolic acid and lactate

Calcium oxalate crystals form in tissues including the renal tubules, myocardium, muscles and brain. Hypoglycaemai follows due to increase in NADH

ACute oliguric renal failure occurs secodnary to the nephrotoxic effects of both glycolic acid and clacium oxalate

Question 5

Discuss toxicokinetics of EG

Answer 5

Rapidly absorbed following ingestions - peak concentrations occur within 1-2 hours
VD across the total body water with rapid CNS penetration

It is metabolised subsequently by alcohol dehydrogenase and aldehyde dehydrogenase into glycoaldehyde and glycoclic acid which in turn is converted into glyoxylic acid and oxalic acid

In the absence of ethanol or fomepizole the elimination half life is 3-9 hours. In the present of ethanol which competitively inhibits ADH elimination half life is extended to 14-17 hours

EG is eliminated exclusively by the kidney

Question 6

Discuss clinical features of EG intoxications

Answer 6

Clinical course is often described in three stages (CNS, cardiopulmonary and renal) but these are artificial descriptions of a rapid clinical course

-Initial clinical features develop within the first 1-2 hours and are similar to those of ETOH intoxication

Progressively severe features develop over the subsequent 4-12 hours
-dysponoea , tachypnoea, tachycardia, hypternsion and decreased LOC progressing to shock coma, seizure and death
Flank pain and oliguira indicate acute renal failure
Late cranial neuropathies involving CN 2,5,7,8,9,10 and 12 are described up to 5-20 days later

Question 7

Discuss invesitgations in EG

Answer 7

ECG, BGL and paracetamol level

EUC, serum lactate, serum osmolalatiy, arterial blood gases and CMP are all needed

• Elevated osmolar gap , HAGMA and hyperlactaemia are all indicators of intoxication
• HAGAM with lactaemia, +- osmolar gap and hypocalcaemia is pathognomic of EG intoxication
• Elevated serum lactate must be interpreted with care as some lab assays do not differentiate between glycol ate and lactae

Urine microscopy - presence of oxalate crystals in the urine is pathognomonic of ethylene glycol intoxication

Question 8

Discuss Resus of EG intoxications

Answer 8

ABCD

• If patient requiring intubation attention needs to be taken to ensure adequate respiratory rate is maintained as these patient are often significantly acidotic and require ventilatory compensation
• Can consider bicarb bolus if concerned acidosis is worsening n

Detect and correct hypoglycaemia, hyperkalaemia and hypomagnesaemia - only correct hypocalcaemia if there is refractory seizures or prolonged QT

Question 9

Discuss DEAD of EG intoxications

Answer 9

D - GIT decontamination is not idnicated

E: - HD is the definitive magnement of EG intoxication - during HD elimination halflife is reduced to 2.4-3.5 hours
-lactate free dialysates with added bicarb may assist correction of acidaemia
-Indications for HD
—History of large EG infestion with osmlolar gap >10
—Acidaemai with pH<7.3
—Ethylene glycol level >8 mmol/L
End points
- correction of acidosis
-osmolar gap <10
-ethylene glycol level <3.2mmol/l

A- ETOH and fomepizole are used in the treatment of supspected or confirmed EG as a temporising measure while awaiting HD

Question 10

Discuss Disposition and follow-up

Answer 10

Children who remain well after suspected unintentional ignestion and have a normal venous bicarb level at 4 or more hours post ingestion may be discharged

Adutls who remain clinically well after accidental ingfestion and have a normal venous bicarb level at 4 hours are fit for discharge

All symptomatic patients and those with deliberate ingestion are assumed ot have potentially lethal intoxication and are admitted to hospital for further evaluation

Normal osmolar gap dose not exlcude intoxication, absence of symptoms dose not exclude signifiacnt ingestion
-Care if ADH is blocked by ETOH symptoms may be delayed in onset

Question 11

Discuss sources of and risk assessment of isopropanol (isopropyl alcohol)

Answer 11

Sources: hand sanitisers, disinfectants, solvents window cleaners and perfumes.

Risk assessment

• Causes dose related CNS depression
• As little as 1ml/kg of a 70% solution causes symptoms of inebriation and more than 4ml/kg may cause coma and respiratory depression
• Children - minor ingestions such as a taste or a lick do not require evaluation unless symptoms develop >3ml are associated with symptoms and should be monitored. Significant toxicity has been reported from dermal absorption following application of rubbing lacohol to small children as an antipyretic measure

Question 12

Discuss toxic mechanisms of isoprolyl alcohol

Answer 12

Augmentation of the GABAa receptor complex is thoguht to be central to effects. Production of acetone and severe ketonaemia may contribute to CNS depression

Severe HAGMA is not a feature of isopropanol intoxication as acetone is not further metabolised to any great extent

It is a GIT irritant and causes dose-dependant CVS depression

Question 13

Discuss toxicokinetics of isopropanol

Answer 13

Rapidly and well absorebed following ingestion, dermal contact or inhalation.
VD to total body water 0.6L/Kg
40% of the absorbed dose is excreted unchanged by the kidney and lungs, the remainder is metabolised by hepatic ADH to form acetone. Acetone is excreted mostly unchagned by the lungs and less extent kidneys
Affinity of ADH for isopropyl alcohol is much less compared to ETOH and elimination Half life is correspondingly much slower if coingestion occurs

Question 14

Discuss clinical features of isoproyl alcohol

Answer 14

Intoxication syndrome indentical to ethanol develops
The duration of inebriation is longer than following ethanol
Ketosis may be indicated by the breath odour of acetone

Question 15

Discuss invesitgations of isoproyl alcohol

Answer 15

ECG, paracetmaol, BSL

Osmolar gap in the absence of significant HAGMA indicates isopropyl alcohol intoxication

Question 16

Discuss management

Answer 16

ABCD

DEAD is not indicated
– HD very effective but supportive care adequate

Question 17

Discuss source and risk assessment of methanol

Answer 17

Source

• Carburettor cleaning lfuid
• Chemical applications in industry
• Solvent in thinners, varnishes paints and enamels
• Model aeorplane and car fuel
• Feul additive
• Dyes and stains
• Wood alcohol and spirits

Ingestion of >0.5ml/kg of 100% methanol is potentially lehal
Dermal or inhalational exposures is unlikley to led to methanol intoxication although it sis reported in the context of inhalational solvent abuse

Question 18

Discuss toxic mechanisms of methanol

Answer 18

Production and accumulation of formic acid produces a severe anion gap acidosis and direct cellular toxicity due to inhibition of cytochrome oxidase. Retinal injury and edema leads to blindness
In the brain subcortical white matter haemorrhages and putamenal oedema classicaly occur

Late Hyperlactataemia occurs due to inhibitoin of cellular oxidative metabolism

Question 19

Discuss toxicokinetics of methanol

Answer 19

Rapidly absorbed with peak levels occuring within 30-60minutes.
Rapid distribution across total body water
Metabolised in the liver by alcohol dehydrogenase to formaldehyde which in turn is metbaolsed to formic acid

Elimination hlaf life is 24 hours
ETOH concentration of 22mmool/l competitievily inhibts ADH so that mehtanol cannot be metabolised to formaldehyde

Methanol elimination half life increases to 48 hours as methanol is exclusively eliminated via the kidney and pulmonary routes

Question 20

Discuss clinical features of methanol intoxication

Answer 20

Mild CNS intoxication is evident within 1 hour of ingestion - nausea vomitng and abdominal pain may ocur

Following a latent period of 12-24 hours symtpoms of headahce, dizziness, vertigo, dyspnoea, blurred vision and photophobia develop
Sever intoxication include tachypnoea, drowsiness and blindness
Progressive obtundation leading to coma and seizures heralds the onset of cerebral oedema - papilloedema is characteristic with progressive demyeliniation and up to 1/3 of patient suffer irreversible visual complicaitons

Question 21

Discuss investigation for methanol intoxications

Answer 21

HAGMA, hyperlactaemia and elevated osmolar gap are surrogate markers of itnxociation
CT scan demonstrates characteristic ischaemic or haemorrhagic injury ot the basal ganglia in patient with permanent neurogloical sequalae

+ the same as the other toxic alcohols

Question 22

Discuss resus of severe methanol intoxications

Answer 22

A: - if indicated need to set adeqaute resp rate to maintain compensation for HAGMA
-reduced PH below 7.30 augments formic acid inhibition of cytochrom oxidase – if below 7.3 administer 50mmol aliquots of bicarb to raise the ph

Treat seizures, hypoglycaemia
Folic acid is given at 50mg IV 6 hourly and continued until poisoning is definitively treated

Question 23

Discuss DEAD of methanol intoxication

Answer 23

D: -not indicated

E- HD is the definitive management of methanol intoxication
-indication same as for ethylene glycol

Antidoes - ETOH and fomepiazole

Question 24

Discuss risk assessment of hydrocarbons

Answer 24

Hydrocarbons include (petroleum, toluene, essential oils, kerosene)

Whether ingested or inhaled can cause rapid onset of CNS depression, seizures and cardiac dysrhythmias
-Aspiration can lead to chemical pneumonitis

THe major risk following acute ingestion are early CNS depression and seizures. For most petroleum distillates more than 1-2ml/kg is required to cause signicicant systemic toxicity

Ingestion of as little as 10mls of eucalyptus oil or other essential oil may lead to CNS depression and seizures always wihtin 1-2 hours.

High viscosity compounds (motor oil, petroleum jelly) have very low risk of systemic toxicity or chemical pneumonitis

CHildren
-ingestion of 5mls of eucalyptus oil or other essential oils is associated with rapid onset of coma

Question 25

Discuss TM and TK of hydrocarbon ingestion

Answer 25

TM: disruption of lung surfactant produces a chemical pneumonitis. The mechanisms of CNS depression is unclear. Dysrythmias are secondary to myocardial sensitisation to endogenous catecholamines.

TK: Absorption followin inhalational exposure is determined by concentration duration and minute ventilation. Absorption following ingestion is inversely related to the molecular weight of the hydrocarbon. Distribution to the CNS is determined by lipid solubility. Most hydrocarbons are eliminated unchanged through expired air

Question 26

Discuss clinical features of hydrocarbons

Answer 26

Resp

• immediate coughing and gagging indicates aspiration
• the development of chemical pneumonitis is heralded by wheeze, tachypnoea, hypoxia, haemoptysis and pulmonary oedea. In mild cases pulmonary sigs may be delayed - feature typically worsen over 24-72 hours and resolve over 5-7 days

CVS
-dysrhtymias occur early in poisoning

CNS

• Profound CNS depression coma and seizure may occur with massive acute exposure, onset is wihtin2 hours
• chronic toluene abuse resutl in ataxiam dementia and peripehral neuropathy

GIT
-nasuea and vomiting

Other

• chemical phlebitis and local tissue injury occur following SC or IV injeciton
• high pressure injection injurues can produce extensive tissue injury involving tendons and deep sturctures
• hepatic and renal injury occur in cabron tetrachloride

Question 27

Discuss management of hydrocabon toxicity

Answer 27

ABCD
A: secure if signicant CNS depression
C: in the even of ventricular dysrhytmia
-commence ALS
-intubate and hyperventilate and correct hypoxia
-admin propanolol 1mg IV or metoprolol 5mg IV
-correct k and MG
-withold catecholamines inotropes if possible
D:- manage seizure as per toxic seizure management

D: - remove patient from the exposure, remove clothing and wash skin
-activated charcoal does not bind hydrocarbons
-GIT decontamination of any kind is contraindicated becuase of indcution of vomting increasing risk of hydrocabon aspiration
E: nil
A: nil
D: 6 hour observtion

Question 28

Describe calculation of osmolar gap

Answer 28

Osmalarity-Osmalality

Osmalarity = 2xNA + glucose + urea
Osmalality is measured
Normal <10