Occupational Toxic Encephalopathy

Occupational toxic encephalopathy is diffuse brain dysfunction caused by workplace chemical exposure. It presents as acute confusion, depressed consciousness or seizures, or as chronic cognitive, psychiatric and movement disorders.

Causes. Solvents (toluene, xylene, trichloroethylene, n-hexane), carbon monoxide, hydrogen sulphide, cyanide, organophosphates, carbon disulphide, methyl bromide, and metals (lead, mercury, manganese, organic tin, arsenic, thallium).

Acute and chronic forms. Acute toxic encephalopathy follows heavy exposure over minutes to days. Chronic disease follows repeated exposure over years and may be preceded by an acute event. Delayed neuropsychiatric syndrome can follow carbon monoxide poisoning after 2 to 40 days.

Epidemiology. Underdiagnosed because cognitive complaints are non-specific. Confined space work, poor ventilation, accidental release and illicit or unregulated work increase the risk.

Prognosis. Acute forms often recover when the cause is removed and treated. Chronic and metal related forms may leave persistent deficits.

Pathophysiology.

Mechanisms include hypoxia (carbon monoxide, cyanide, hydrogen sulphide, methaemoglobin formers), membrane and myelin disruption by lipophilic solvents, enzyme inhibition (organophosphates), and metal specific neuronal injury in vulnerable regions such as the basal ganglia, cerebellum and white matter.

Secondary injury follows hypoxia, oedema, excitotoxicity and oxidative stress.

• Acute: headache, confusion, agitation, delirium, drowsiness, ataxia, seizures and coma, with toxidrome features of the specific agent.
• Chronic: fatigue, poor memory and concentration, mood change, personality change, tremor and ataxia, sometimes with neuropathy.
• Symptoms often relate to workplace timing, and co-workers may be affected.

Red flags.

• Reduced consciousness, seizures or focal signs.
• Cherry red skin, lactic acidosis or smoke inhalation (carbon monoxide or cyanide).
• Rapid progression, cardiac arrhythmia or marked hypoxaemia.

• Exposure history: agents, containers, confined spaces, alarms, co-worker illness and timing. Request safety data sheets.
• Bedside: glucose, oxygen saturation (pulse oximetry can be falsely normal in carbon monoxide poisoning), arterial gas and lactate with co-oximetry (carboxyhaemoglobin, methaemoglobin), ECG, electrolytes, renal and liver function, creatine kinase, osmolar gap and toxicology screen.
• Metals in blood and urine as directed by history: lead, mercury, arsenic, thallium, manganese.
• MRI brain (basal ganglia, white matter and cortical change), EEG and lumbar puncture when infection or other causes remain possible.
• Neuropsychological testing for chronic cases, interpreted against premorbid function.

Differential diagnosis. Sepsis and central nervous system infection, metabolic and endocrine encephalopathy, hepatic encephalopathy, stroke, drug or alcohol intoxication or withdrawal, hypoglycaemia, primary psychiatric illness, degenerative dementia, Wernicke encephalopathy.

• Remove from exposure and decontaminate; protect rescuers; airway, breathing and circulation; correct hypoglycaemia.
• Carbon monoxide: 100% oxygen by a tight fitting non-rebreather mask at 15 litres/minute for at least 6 hours, until carboxyhaemoglobin is under 3 to 5% and symptoms have resolved. Consider hyperbaric oxygen for loss of consciousness, neurological deficit, ischaemic cardiac features, pregnancy or carboxyhaemoglobin over 25%. Monitor ECG, troponin, neurological state and pulse co-oximetry.
• Cyanide (smoke inhalation, nitrile or cyanide salt exposure): hydroxocobalamin 5 g intravenously over 15 minutes in adults, with a second 5 g dose over 15 minutes to 2 hours if needed. Maximum 10 g. Children: 70 mg/kg to a maximum of 5 g. Monitor blood pressure (transient hypertension), and expect red skin and urine and interference with colorimetric laboratory tests. Caution in known allergy; no renal adjustment.
• Organophosphate poisoning: atropine and oximes by toxicology direction.
• Seizures: lorazepam 4 mg intravenously over 2 minutes, repeated once after 10 minutes if seizures continue. Maximum 8 mg. Monitor breathing and blood pressure; caution in respiratory depression and hepatic impairment; no renal adjustment.
• Heavy metal poisoning: chelation by toxicology direction after confirmation.
• Chronic disease: no drug reverses solvent or metal related deficits; cognitive rehabilitation, sleep and mood treatment, and permanent removal from exposure.
• Treat comorbid depression: sertraline 50 mg orally once daily, increased after at least 1 week in steps of 50 mg to 100 to 200 mg daily if needed. Maximum 200 mg daily. Review at 4 to 6 weeks. Monitor sodium, bleeding risk with anticoagulants or NSAIDs, and suicidal thoughts in people under 25 years. Reduce dose in hepatic impairment; no renal adjustment.

Monitoring. Neurological observation hourly during acute illness; neuropsychological testing at 3 to 6 months and yearly; follow up for delayed neuropsychiatric syndrome for 6 weeks after carbon monoxide poisoning.

Referral and escalation. Toxicology and neurology; intensive care for coma or respiratory failure; hyperbaric centre for carbon monoxide; occupational physician for workplace investigation and co-worker screening; notification and compensation where required.