12th March 2024

Overview of poisoning

Ethanol poisoning

Ethanol serum levels greater than 300mg/dl can induce coma, though frequent users often have high tolerances. Symptoms of poisoning include nystagmus, dysarthria, and ataxia. Treatment is supportive with special care for the airway, blood sugar level and prevention of hypothermia.

Paracetamol poisoning

Paracetamol is the most frequently involved drug in intentional overdoses. Toxicity occurs when a dose of 75mg/kg or more is consumed within a 24-hour period. The presentation can vary, with many being asymptomatic and others experiencing nausea, vomiting or abdominal pain. A build-up of the toxic metabolite N-acetyl- p-benzoquinone imine (NAPQI) can result in acute liver injury which, in turn, can lead to fulminant hepatic failure within 24-36 hours. Less commonly, it can cause nephrotoxicity and renal tubular necrosis. If a paracetamol overdose is suspected, then LFTs and INR should be measured, and a paracetamol nomogram should be used to guide management. Acute ethanol intake alongside paracetamol intake is a protective factor for paracetamol toxicity as it inhibits microsomal acetaminophen oxidation leading to reduced levels of NAPQI.

Acetylcysteine is the mainstay of treatment when hepatocellular toxicity is suspected. This agent increases glutathione synthesis which inactivates NAPQI. A liver transplant is indicated if any of the following criteria are met.

Salicylate poisoning

Symptoms can include diaphoresis, fever, tinnitus, deafness and vasodilation. In severe toxicity, mixed respiratory/metabolic acidosis and cerebral/ pulmonary oedema may occur. Clinical toxicity is not closely correlated to serum concentration. Fluid therapy and electrolyte balance are crucial to the management of these patients. Multi-dose treatment with activated charcoal and urine alkalinisation using IV sodium bicarbonate can also be effective. Regardless of symptoms, haemodialysis should be considered over the serum concentration of 700 mg/L. Levels of over 900 mg/L mean urgent haemodialysis is definitively indicated. Quinine toxicity presents similarly to salicylate poisoning, with tinnitus, impaired hearing and blurred vision. Blindness can also occur with the onset often being delayed.

Lithium poisoning

As lithium is absorbed comparatively slowly, symptoms of poisoning often do not manifest until 12 hours or more after ingestion. Symptoms range from altered mental status to weakness, fasciculations, ataxia, vomiting and diarrhoea. Severe poisoning can cause convulsions, hypotension and dehydration. Lithium is excreted renally therefore, an increase in oral or IV fluids would increase elimination. Gastric lavage and/or whole bowel irrigation can be considered if within an hour of ingestion. Haemodialysis is the treatment of choice in severe poisoning and is indicated in those with reduced GCS, cerebellar signs or convulsions, regardless of lithium concentration. Lithium poisoning often occurs in the context of an insult to the kidneys precipitating toxicity in a chronic lithium user. Examples of these insults include acute infection, progressive CKD or commencement of new medications, especially NSAIDs and diuretics.

Organophosphate poisoning

Organophosphates are used in pesticides and can be absorbed through the skin and lungs. Symptoms are caused by stimulation of muscarinic receptors (diarrhoea, urination, salivation and sweating) and nicotinic receptors (hypertension, brady/tachycardias). Atropine can alleviate muscarinic symptoms by acting as a competitive inhibitor.

Tricyclic antidepressant poisoning

Of the tricyclics, the drugs with the highest risk of toxicity are dothiepin and amitriptyline. The mechanism involves inhibition of the reuptake of norepinephrine and serotonin. In an overdose, the symptoms include anticholinergic effects (dry mouth, dilated pupils, urinary retention), cardiovascular effects (widened QRS, prolonged QT, sinus tachycardia) and CNS effects (drowsiness, convulsions, delirium). Acidosis, hypokalaemia and hypotension can be present in severe poisoning. Treatment includes IV sodium bicarbonate to alkalise the urine. Antiarrhythmic drugs should be avoided in most cases, as arrhythmias largely resolve with sodium bicarbonate and supportive care.

Theophylline poisoning

Theophylline is most commonly found in its modified release form as a treatment for COPD and asthma. Chronic overdose symptoms include tachycardia, vomiting and seizures. Acute poisoning symptoms can be similar with the addition of tremors, hypokalaemia, hypotension, and metabolic acidosis. Severe acute poisoning symptoms do not usually manifest under serum levels of 80-100mg/L. Treatment is largely supportive; beta blockers can be effective to treat ventricular and supraventricular tachycardias. Gut decontamination with repeated activated charcoal can be used in an acute overdose. Haemodialysis is indicated in patients with serum levels over 100mg/l or seizures not responding to medical management.

Iron poisoning

Iron is found in numerous over the counter vitamin supplement tablets, and as few as 10 tablets can cause severe poisoning, especially in a child. Symptoms include diarrhoea, vomiting and abdominal pain. In severe cases, hypotension and metabolic acidosis can occur. Serum iron levels can be measured and desferrioxamine mesylate provides an effective antidote by chelating excess circulating iron.

Carbon monoxide poisoning

Carbon monoxide (CO) poisoning occurs when there is poor ventilation and incomplete combustion, such as in low-quality housing with a faulty boiler. It is a colourless and odourless gas. CO binds to haemoglobin and myoglobin more readily than oxygen and causes a left shift in the oxygen dissociation curve. Hence, tissue ischaemia can occur despite a normal PaO2. CO poisoning symptoms vary from headaches, nausea and dizziness to altered mental state, weakness, seizures or ‘cherry red’ lips.

Pulse oximetry will give a falsely high reading; VBG/ABG and carboxyhaemoglobin levels are needed for diagnosis. If CO poisoning is suspected, then immediate high flow 100% oxygen is essential. Hyperbaric oxygen therapy indications include pregnancy, persistent confusion, neurological signs (not including headache), evidence of ischaemia on ECG and significant loss of consciousness.

Ethylene glycol poisoning

Ethylene glycol is found in antifreeze solution and diagnosis of poisoning can often be delayed as symptoms are similar to ethanol poisoning. Ethylene glycol poisoning can cause metabolic acidosis with a high anion and osmolar gap. The first line treatment is an alcohol dehydrogenase inhibitor, usually fomepizole. Ethanol can be used as a second line agent which also competitively inhibits alcohol dehydrogenase, thereby slowing the metabolism of ethylene glycol into its toxic metabolites. Haemodialysis can be used in refractory cases.

Cocaine poisoning

Cocaine is a recreational drug which can cause chest pain, agitation, hypertension, sinus tachycardia, narrow complex tachycardia and QT prolongation. Other neurological effects include mydriasis, hyperreflexia and convulsions. Treatment involves benzodiazepines which work by decreasing sympathetic nerve activity. When managing cocaine-induced hypertension, benzodiazepines are first line followed by agents such as sodium nitroprusside and GTN which act as vasodilators to control hypertension. Sodium bicarbonate also has a role to treat those with widened QRS >100ms.

High anion gap metabolic acidosis

The anion gap is calculated as the total number of sodium and potassium ions minus the total number of chlorine and bicarbonate ions. A normal anion gap ranges from 8-16 mEq/l. The mnemonic CAT MUDPILES is often used to remember the causes of high anion gap metabolic acidosis:

• Carbon monoxide/ cyanide
• Aminoglycosides
• Toluene (found in acrylics, glue and paint)
• Methanol
• Uraemia
• Diabetic ketoacidosis
• Paracetamol/ Propylene glycol
• Infection/Iron/Isoniazid/ Inborn errors of metabolism
• Lactic acidosis
• Ethylene glycol
• Salicylates

Table of toxins and antidotes

References

• Kent R Olson, MD (2014) Basic & Clinical Pharmacology Fourteenth Edition, Lange. Chapter 58: Management of the Poisoned Patient
• NICE/BNF, Poisoning, emergency treatment. Retrieved June 15, 2022, from https://bnf.nice.org.uk/treatment-summaries/poisoning-emergency-treatment/
• Müller D, Desel H. Common causes of poisoning: etiology, diagnosis and treatment. Dtsch Arztebl Int. 2013 Oct;110(41):690-9; quiz 700. doi: 10.3238/arztebl.2013.0690. Epub 2013 Oct 11. PMID: 24194796; PMCID: PMC3813891.
• Summers SA, Glynne PA. Acute poisoning on the medical admissions unit. Clin Med (Lond). 2007 Jun;7(3):277-9. doi: 10.7861/clinmedicine.7-3-277. PMID: 17633951; PMCID: PMC4952706.
• Rose, Jason J et al. “Carbon Monoxide Poisoning: Pathogenesis, Management, and Future Directions of Therapy.” American journal of respiratory and critical care medicine vol. 195,5 (2017): 596-606. doi:10.1164/rccm.201606-1275CI