Poisoning with alcohol Dr James Dear University of Edinburgh

Clinical history 59 year old man Patient presented to hospital at 11 am. Claimed to have taken an overdose but will not disclose what has been ingested other than co-codamol. Estimated 50+ tablets. Paracetamol 49 mg/L. Other medication prescribed to the patient include a statin, adcal, amlodipine, thiamine, salbutamol, alendronic acid, frusemide, omeprazole. Blood pressure low but responding to fluid, systolic now 105 mmHg. Liver Function Tests: AST 60 U/L, raised but lower than normal (normally AST and ALT in 90s) Serum creatinine concentration 186 μmol/L on admission, now 124 μmol/L with fluids (previously 64 μmol/L ) Arterial Blood Gases (ABG's) H+ 90, pH 7.01, bicarbonate 5, lactate 25. Clinical pharmacologist asked what is making this man so acidotic?

Medicines and chemicals that cause acidosis Common toxicological causes of a high anion gap metabolic acidosis: Paracetamol Amphetamines Carbon monoxide Cocaine Toluene, benzene, formaldehyde Methanol, ethylene glycol Valporate Salicylates Paraldehyde Iron Isoniazid Ethanol Formic acid (NSAIDs, metformin, glycols) [Antiretrovirals: zidovudine, didanosine, stavudine

Clinical history continues Patient denied taking methanol or ethylene glycol but had access to toxic alcohols through work. Subsequent blood results: Measured osmolality 370, calculated 310 OSMOLAL GAP = [MEASURED OSMOLALITY- CALCULATED OSMOLALITY] Calculated osmolality = (2x[sodium]) + [potassium] + [urea] + [glucose] (All should be measured in mmol/L) The normal osmolal gap is about 10 mOsm/kg H20 A significant osmolal gap is > 10-15 mOsm/kg H20

This suggests poisoning with a toxic alcohol!

Indications for treatment with the toxic alcohol antidote fomepizole (or ethanol) High anion gap metabolic acidosis OR Osmolal gap greater than 10 mosmols/kg without there being another likely cause (e.g. ethanol intoxication)

Indications for haemodialysis Ethylene glycol concentration greater than 500 mg/L Severe metabolic acidosis Renal failure Deteriorating condition despite supportive measures Severe electrolyte imbalance A desire to shorten the duration of the poisoning Dialysis should be continued until: Plasma ethylene glycol concentration is undetectable AND Acidosis and signs of systemic toxicity have resolved

I am a clinical pharmacologist Clinical Pharmacology and Therapeutics (CPT) is one of 30 physician specialties in the medical career pathway. Consultants trained in this specialty lead on all aspects of medicines management. It is the only medical specialty in the NHS focusing on the safe, effective, and cost- effective use of medicines. Clinical pharmacologists play a crucial role in refining the use of currently available medicines, and in developing the pioneering medicines of tomorrow. Clinical pharmacologists have diverse career paths working, for example, in the NHS, regulatory bodies, clinical trials units, universities or the pharmaceutical industry.