Basic advice

• All patients suspected of taking a deliberate overdose need a psychiatric evaluation before being discharged, if they abscond or attempt to discharge against advice seek urgent help from your senior and/or psychiatric service.
  
• Toxicology is continuously changing. In the UK, up to date and expert online support is available at Toxbase which can be accessed from NHS computers. Advice can be sought at the National Poisons Information Service. Also consult local guidelines and experts for help. Similar local and national systems exist in other countries.
  
• Most overdoses have stabilised by 12 hours; however, delayed toxicity may be seen with aspirin, paracetamol, iron, paraquat, TCAs, co-phenotrope and overdoses of modified release preparations. All need admission.
  
• Death following overdose is thankfully rare but can be further reduced with ABC management, early access to ITU if needed and airway protection, ventilatory support, arrhythmias, electrolyte, acid–base, seizure and psychosis management and sedation as needed. Some will need antidotes, bowel irrigation and dialysis. Identify these.

Determine history

Paramedics will often bring information from setting – tablets taken, how many, when, empty bottles or packets and the circumstances. Was there a suicide note, was alcohol or other drugs taken? What are patient’s co-morbidities? Does patient have capacity? Patients may abuse their own drugs or often those of others. It is sensible to always screen for paracetamol and salicylate as these are common and for paracetamol early treatment may be life saving. Patients also do not always tell the truth especially if they do want to die.

Specific clinical signs

Toxidromes

Investigations for overdose

• Expanding use for cardiac arrest due to local anaesthetics and any lipid-soluble drugs. Intravenous fat emulsion (IFE), in the form of Intralipid 20% is for life-threatening arrhythmias/cardiac arrest caused by lipid-soluble drugs, especially local anaesthetics. May be used in toxicity from CCBs, haloperidol, TCAs, lipophilic beta-blockers. Use only under senior guidance adhering to local policies.
  
• Administration. Lipid emulsion 20% at 1.5 ml/kg IV in 1 min followed by an infusion of 0.25 ml/kg/min for 30–60 min. In a 70 kg patient – take a 500 ml bag of Intralipid 20% and a 50 ml syringe, draw up 100 ml and give stat. Attach the Intralipid bag to an IV administration set (macrodrip) and run it IV over the next 15 min. Repeat 100 ml bolus if spontaneous circulation has not returned. Maximum total dose of 10 ml/kg is recommended in first 30 min, i.e. 700 ml. Continue CPR to aid circulation. Further information at www.lipidrescue.com.

• May be used for beta-blocker and calcium channel blocker toxicity. Monitored closely HIET is safe, and adverse events are predictable, uncommon, and easily managed. Insulin increases glucose and lactate uptake by myocardial cells and improves function without increased oxygen demand.
  
• Insulin promotes excitation–contraction coupling and contractility. It may be best used adjunctively with other measures such as catecholamines, for two reasons. First, insulin-mediated inotropy is not catecholamine-mediated, and is not affected by beta-blockers. Secondly, although insulin appears to improve myocardial contractility, it has no chronotropic effect and may cause vasodilation. Side-effects: hypoglycaemia, hypokalaemia, hypomagnesaemia, hypophosphataemia.
  
• Give 10% IV GLUCOSE with loading bolus of 0.5–1 U/kg INSULIN then INSULIN at 1–10 U/kg/h (higher doses may be given according to clinical response). Used in an ITU/HDU setting with close monitoring. Very large doses of insulin have been given with few side-effects as long as blood glucose and other electrolytes maintained.

• Various types: methamphetamine (‘crystal meth’ or ‘ice’) and 3,4 methylene-dioxymethamphetamine (‘ecstasy’) all cause increased presynaptic noradrenaline, dopamine. Increased serotonin release.
  
• Clinical: euphoria, psychosis, violence, dilated pupils, ↑HR, ↑BP. ↑Temp, anorexia, bruxism, sweating.
  
• Complications: seizures, cerebral oedema, DIC, liver failure, AKI and rhabdomyolysis.
  
• Investigations: FBC, U&E ↓Na (MDMA due to SIADH), LFT, Mg, Ca, ↑CK, glucose, lactate. ECG. CT head +/− LP if fever, meningism, coma, confusion, suspected cerebral oedema, infection.
  
• Management: if ingestion recent then activated CHARCOAL may be used. Huge amounts, e.g. body packing for drug trafficking, consider whole bowel irrigation. Supportive: ITU review if GCS <9. ABC, O2 as per BTS guidelines. ECG monitoring. Hyperthermia: external cooling. May consider DANTROLENE 1 mg/kg IV (max 10 mg/kg). If low BP: give IV crystalloid if normonatraemic and euvolaemic or hypovolaemic. Fluids may be delayed until results back where ecstasy-reduced SIADH may be suspected. MDMA-associated SIADH usually responds to fluid restriction. If comatose these patients should receive hypertonic saline solution to correct a portion of the metabolic imbalance rapidly. Agitation: consider DIAZEPAM 10–20 mg IV. Seizures: manage as per status epilepticus with IV LORAZEPAM 2–4 mg.

• About: widely used drugs. Competitively blocks β1 and β2 adrenoceptors.
  
• Aetiology: glucagon activates adenyl cyclase increasing cAMP. Bypasses beta adrenoceptor.
  
• Clinical: bradycardia-related low BP. Bronchospasm. Worsening LVF, shock.
  
• Investigations: FBC, U&E, LFT, Mg, Ca, glucose, lactate. ECG: heart blocks and ↓HR, QT changes.
  
• Management: supportive: ABC/O2, HDU if severe, close monitoring, IV crystalloid, telemetry. Consider gastric lavage if very early presentation. Bronchospasm – SALBUTAMOL neb. Severe bradycardia: ATROPINE 0.5–1 mg up to 3 mg IV and/or temporary pacing may be needed.
  
• If hypotension/shock then consider first line inotropes, e.g. ADRENALINE. If response poor consider GLUCAGON 2–10 mg slow IV in G5 over 10 min followed by infusion 1–5 mg/h. An alternative is insulin–glucose euglycaemic therapy: Section 14.4.
  
• Intra-aortic balloon pumping has been used for circulatory support.
  
• Intralipid therapy should be considered if fat soluble beta-blocker. Section 14.3.

References: Engebretsen et al. (2011) High-dose insulin therapy in beta-blocker and calcium channel-blocker poisoning. Clin Toxicol, 49:277. Shepherd (2006) Treatment of poisoning caused by beta-adrenergic and calcium-channel blockers. Am J Health Pharmacy, 63:1828.

• About: seen with Diazepam, Clonazepam, Temazepam. Used as sedatives and anxiolytics. Accidental overdose with IV procedural sedation. Exacerbated with alcohol or other sedatives.
  
• Clinical: drowsiness and coma. If coma (GCS <10) look for other drugs or pathology. Pupils may be partially dilated, ataxia, dysarthria. Higher risk where combined with other sedation, alcohol, underlying chest disease and elderly.
  
• Investigations: FBC, U&E, LFT, Mg, Ca, glucose, lactate. ECG. ABG if comatose or low saturations or breathless.
  
• Management: supportive: ABCs. Within 1 h activated charcoal may be given. Most overdoses are ‘slept off’. Give O2 as per BTS guidelines. Recovery position (lower leg straight, upper leg flexed) and nasopharyngeal airway if needed. IV fluids. Severe respiratory depression and GCS <9 and concerns about the airway/cough/gag reflex: FLUMAZENIL 200 mcg (0.2 mg) over 15 sec and then 100–300 mcg repeated doses (0.1–0.3 mg) might be given (max dose of 3 mg). There is a risk of lowering seizure threshold, especially in a mixed overdose with other drugs that also lower seizure threshold, e.g. alcohol, TCAs. Lone overdoses will rarely need ITU. Most are stable <24 h depending on severity of overdose.

• About: occasionally lethal so do not underestimate seriousness, admit CCU/ITU and give IV calcium. Take advice.
  
• Aetiology: CCB block Ca influx into myocardial/vascular tissues via L-type channels. Amlodipine and Nifedipine overdose cause ↑HR and ↓BP. Verapamil and Diltiazem cause ↓HR and ↓BP, ↑glucose, circulatory collapse, cardiac arrest, cardiogenic shock.
  
• Investigations: FBC, U&E, LFT, Mg, Ca, ECG:↓HR.
  
• Management: give calcium (see below), supportive: ABC, O2, ECG monitoring. Best on CCU or ITU/HDU. Give 500–1000 ml IV crystalloids. Treat ↓HR with IV ATROPINE 0.5–1 mg (max 3mg). Cardiac pacing if needed. Whole bowel irrigation with PEG and activated charcoal can reduce absorption of sustained-release verapamil.
  
• Immediate: CALCIUM GLUCONATE 10–20 ml 10% IV over 5–10 min for ↓BP. Aim for mild high Ca – monitor for 12h+ with modified release preparations. Persisting ↓BP/shock. Consider ADRENALINE 2–10 mcg/min or ISOPRENALINE 5 mcg/min or GLUCAGON 2–10 mg slow IV in G5 over 10 min followed by infusion 1–5 mg/h. If this fails consider insulin–glucose euglycaemic therapy (Section 14.4). Intra-aortic balloon pumping has been used for circulatory support. Cardiac pacing may be considered for persisting significant ↓HR-induced ↓BP.
  
• Other steps: intralipid therapy: may have a role for verapamil and diltiazem, unclear for dihydropyridines. If there is acidosis consider IV NaHCO3.

References: Engebretsen et al. (2011) High-dose insulin therapy in beta-blocker and calcium channel-blocker poisoning. Clin Toxicol, 49:277. Shepherd (2006) Treatment of poisoning caused by beta-adrenergic and calcium-channel blockers. Am J Health Pharmacy, 63:1828.

• About: commonly used and generally safe anticonvulsant. Valproate-induced hyperammonaemic encephalopathy (VIHE) may be seen without overdose.
  
• Clinical: progressive delirium and coma, hypotension, respiratory depression, increased seizure frequency (VIHE).
  
• Investigations: as for coma. FBC, U&E, LFTS, glucose, ECG, CT head, serum valproate, EEG (VIHE) shows continuous generalised slowing, theta and delta activity, triphasic waves. Blood ammonia elevated.
  
• Management: ABC, stop valproate, supportive. Multidose activated charcoal +/− WBI may be considered if early. Try NALOXONE. IV L-CARNITINE may be helpful when there is hyperammonaemia, hepatotoxicity, and coma. Treat until improves. Severe cases consider haemodialysis.

• Note: Pulse oximetry will be falsely normal and fail to report severe hypoxia. If you suspect CO you must check ABG and CO-Hb levels. CO is an odourless, colourless gas, formed by the incomplete combustion of fossil fuels such as in exhaust fumes. Accidental – poorly ventilated faulty home heating. Low dose toxicity may be subtle in its presentation, e.g. flu-like illness. Cold spell where gas/solid fuel home/water heating used, changes to home heating or ventilation.
  
• Aetiology: CO binds avidly to Hb with × 240 times more affinity than does O2. Saturation probes treat CO-Hb as O2-Hb giving a false normal SaO2. Normal CO-Hb is 3–5% with levels up to 10% in smokers. Result is tissue hypoxia and metabolic acidosis. The result is leftward shift in O2-Hb dissociation curve. Causes myocardial and cerebral hypoxia and cerebral oedema.
  
• Clinical: drowsiness, flu-like illness, headache, fatigue, breathlessness, coma and death. Pink rosy colouration.
  
• Investigations: FBC, U&E, LFT, lactate. Only an ABG will show hypoxia. Troponin. ECG. CXR. Measure CO-Hb specifically if diagnosis considered. Patients get O2 en route and so hospital CO-Hb may not represent prior levels or the extent and severity of any hypoxia. Severe when CO-Hb >10%.
  
• Differential: excess opiates, sedatives, alcohol. Stroke/SDH/SOL.
  
• Management: remove source: open windows, switch off heating/car engine. Supportive: O2 sat probe unreliable. Check ABG. Give 100% O2 via tight-fitting mask unless COPD and Type 2 RF and if so consider ventilation. 100% O2 will reduce half-life of CO from 4 h to 40 min. Give O2 12 L/min via CPAP mask for at least 6 h until CO-Hb is less than 5%; may be needed for 12–24 h.
  
• Severe cases: (when CO-Hb >10% or ECG shows ischaemia or signs of cerebral oedema) cause fitting and cardiorespiratory arrest. Prone to cerebral oedema so do neurological observations. Patients may need IV MANNITOL. Risk of long term neuropsychiatric damage, Parkinsonism and cerebellar symptoms. Indications for hyperbaric O2 (HBO) at 3.0 atm pressure for 60 min and repeated as per local protocol (reduces CO half-life to 20 min) are: CO-Hb >40%, coma, neurological or psychiatric problems, ECG changes, e.g. ST depression, T wave changes, arrhythmias, pregnancy (fetal CO-Hb is to the left of mother’s). Transporting patients to a distant hyperbaric chamber can be hazardous and difficult and the role of hyperbaric O2 is controversial. Take early expert advice.

• Always: ask about usage if considered as a factor with HTN, chest pain, stroke. It is a CNS stimulant derived from the leaves of the coca plant.
  
• Aetiology: blocks reuptake of dopamine, serotonin and noradrenaline. Chronic usage may actually accelerate atherosclerosis. Pleasure from raising dopamine levels in the mesolimbic reward centres.
  
• Administration: snorted and absorbed via well-vascularised tissues lining the nose – causes localised vasoconstriction and eventual damage to the nasal mucosa. Smoked or taken IV give a rapid response but a shorter high than snorting. Rubbed on gums or small amounts taken orally, or as a suppository. Cocaine-induced chest pain usually due to spasm and generally not treated with thrombolysis. Users often have coexisting atherosclerotic disease and so are actually more prone to spasm.
  
• Clinical: chest pain, neurology from ischaemic or haemorrhagic stroke, aortic dissection, ↑↑BP, ↑HR, ↑temp, euphoria/psychotic, mydriasis. Chronic – myocarditis, atherosclerosis.
  
• Investigations: FBC, U&E, LFT, troponin at baseline and 12 h. CXR cardiomegaly. ECG: ischaemia or look for STEMI, LVH. CT head if any neurology.
  
• Management: O2 as per BTS guidance. IV fluids. Suspected ACS with ST elevation necessitates primary PCI. Thrombolysis avoided especially where markedly hypertensive. Consider GTN 2 sprays (800 mcg) or GTN 500 mcg tablet SL. If chest pain persists then IV GTN 1–10 mg/h prior to PCI. Avoid beta-blockade, which will cause HTN due to unopposed alpha effects. Hyperthermia is a side-effect of cocaine and should be treated with fluids, cooling and DANTROLENE. Agitation: DIAZEPAM 1–5 mg PO/IV. Avoid haloperidol and phenothiazines which lower fit threshold.

• Source: usage of lidocaine, bupivacaine overdose (accidental or deliberate).
  
• Aetiology: local anaesthetics block open Na channels.
  
• Clinical: tingling lips, blurred vision, tinnitus, respiratory depression, seizure, coma, arrhythmias, hypotension, cardiac arrest.
  
• Management: ABC. Severe toxicity consider INTRALIPID therapy (Section 14.3).

• Source: inhaled smoke contains hydrogen cyanide and CO which can kill. Confirmation of cyanide poisoning is a process which currently takes days. Empiric treatment with hydroxocobalamin is central to the treatment algorithms.
  
• Aetiology: accidental exposure, e.g. chemical industry. Suicide or homicide attempt. Inhaled smoke from burning of plastics/foam. Excess nitroprusside infusion. Binds mitochondrial cytochrome a3, blocks oxidative phosphorylation.
  
• Clinical: in lethal overdoses death is usually pre-hospital. Survival to hospital bodes well. Evidence of smoke inhalation, cherry-red skin colour, breath smell of bitter almonds. Chest pain and dyspnoea, seizures, coma.
  
• Investigation: FBC, U&E, LFT, CXR, ECG. Lactate increased. ABG: metabolic acidosis, elevated venous oxygen saturation.
  
• Management: supportive: ABC and respiratory support with high flow O2. ITU if high EWS. DICOBALT EDETATE 300 mg IV over 1 min followed by 50 ml of 50% GLUCOSE, but only if severe toxicity confirmed because it is itself very toxic. Otherwise, Cyanokit – HYDROXOCOBALAMIN 5 g IV over 15 min repeated to a total of 10 g; it combines to form cyanocobalamin. Side-effects: BP rise, anaphylaxis, rash, chest tightness. Also give Sodium thiosulphate (25 ml of 50% solution), which enhances the conversion of cyanide to thiocyanate, which is renally excreted.

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