Drug Overdose and Toxicology
Drug overdose and poisoning are common emergency presentations. Knowledge of specific antidotes, risk assessment tools, and management protocols is essential for safe clinical practice.
Key Facts
- Paracetamol overdose is the commonest cause of acute liver failure in the UK - use the treatment nomogram and give N-acetylcysteine (NAC)
- TOXBASE (National Poisons Information Service) is the UK's primary clinical toxicology database for management guidance
- Activated charcoal (50g PO) is effective if given within 1 hour of ingestion of most toxins
- Opioid overdose: Pinpoint pupils, respiratory depression → naloxone 400mcg IV/IM, repeat as needed
- Tricyclic antidepressant overdose: Broad QRS, seizures, arrhythmias → sodium bicarbonate 8.4% (1-2 mEq/kg IV)
- Benzodiazepine overdose: Rarely fatal in isolation → flumazenil (use cautiously - seizure risk in mixed overdose/chronic use)
- Salicylate (aspirin) overdose: Tinnitus, mixed respiratory alkalosis + metabolic acidosis → alkaline diuresis, haemodialysis if severe
- Staggered paracetamol overdoses are highest risk - always treat with NAC if >75mg/kg over 24 hours
Overview
Key Facts
Poisoning accounts for over 170,000 hospital presentations per year in England. It is the leading cause of death in young adults (15-35 years) and is frequently associated with mental health conditions and substance misuse.
Epidemiology
- >100,000 ED attendances for self-poisoning per year in England
- Paracetamol is involved in ~50% of poisoning presentations
- ~5,000 deaths from poisoning per year in the UK (including drug misuse deaths)
- Self-poisoning accounts for ~80% of self-harm hospital presentations
Aetiology
- Intentional self-harm: ~80% of poisoning presentations (impulsive in many)
- Accidental ingestion: Especially in children under 5 years
- Recreational drug use: MDMA, cocaine, novel psychoactive substances
- Iatrogenic: Medication errors, drug interactions
Pathophysiology
Mechanisms of toxicity depend on the agent:
- Paracetamol: NAPQI (toxic metabolite) depletes glutathione → hepatocyte necrosis
- Opioids: Mu-receptor agonism → respiratory depression
- Tricyclics: Sodium channel blockade (broad QRS), anticholinergic effects, alpha-blockade
- Salicylates: Uncoupling of oxidative phosphorylation, direct CNS stimulation
- Organophosphates: Irreversible acetylcholinesterase inhibition
Clinical Presentation
Toxidromes
- Sympathomimetic (cocaine, amphetamines): Tachycardia, hypertension, hyperthermia, mydriasis, agitation
- Anticholinergic (TCAs, antihistamines): 'Hot as a hare, blind as a bat, dry as a bone, red as a beet, mad as a hatter'
- Cholinergic (organophosphates): SLUDGE - Salivation, Lacrimation, Urination, Defaecation, GI distress, Emesis
- Opioid: Pinpoint pupils, respiratory depression, reduced consciousness
- Serotonin syndrome: Clonus, agitation, hyperthermia, hyperreflexia
Red Flags
- Altered consciousness (GCS <8 - protect airway)
- Respiratory rate <12 or >25
- Seizures
- Cardiac arrhythmias (prolonged QRS >120ms or QTc >500ms)
- Metabolic acidosis (pH <7.30)
- Liver failure features (coagulopathy, encephalopathy) in paracetamol overdose
Differential Diagnosis
| Diagnosis | Key Features | Investigation |
|---|---|---|
| Paracetamol overdose | Asymptomatic early, RUQ pain later, liver failure | Paracetamol level (4h+), LFTs, INR |
| Opioid overdose | Pinpoint pupils, bradypnoea | Response to naloxone, urine toxicology |
| TCA overdose | Anticholinergic features, seizures, broad QRS | ECG (QRS >100ms), blood levels |
| Salicylate overdose | Tinnitus, hyperventilation | Salicylate level, ABG |
| Benzodiazepine overdose | Drowsiness, rarely respiratory depression alone | Clinical response to flumazenil (if safe) |
| Carbon monoxide poisoning | Headache, cherry-red skin (late), confusion | Carboxyhaemoglobin level |
| Alcohol intoxication | Altered behaviour, ataxia, reduced GCS | Blood alcohol level, exclude head injury |
Diagnosis / Investigation
Bedside
- A-E assessment: ABCDE approach, ensure airway protection
- ECG: QRS duration (TCA), QTc (many drugs), ST changes
- Blood glucose: Hypoglycaemia (insulin, sulfonylureas, alcohol)
- Temperature: Hyperthermia (serotonin syndrome, NMS, sympathomimetics)
Bloods
- Paracetamol level: At 4 hours post-ingestion (or ASAP if staggered)
- Salicylate level: If suspected
- ABG/VBG: Acid-base status, lactate, carboxyhaemoglobin
- U&Es: Renal function, potassium
- LFTs and INR: Hepatotoxicity assessment
- FBC, glucose, CRP: Baseline
Imaging
- CXR: Aspiration pneumonitis, pulmonary oedema
- CT head: If reduced consciousness and diagnosis uncertain, or suspected head injury
Special Tests
- Urine drug screen: Cocaine, opioids, benzodiazepines, amphetamines
- TOXBASE consultation: For specific agent guidance
- Carboxyhaemoglobin: CO poisoning (take sample before O2 therapy if possible)
Management
Non-pharmacological
- Airway protection: Intubation if GCS <8
- Activated charcoal: 50g PO within 1 hour of ingestion (most toxins)
- Whole bowel irrigation: Sustained-release preparations, body packers
Pharmacological
Specific antidotes:
- Paracetamol → N-acetylcysteine (NAC): 150mg/kg in 200mL 5% dextrose over 1h, then 50mg/kg over 4h, then 100mg/kg over 16h
- Opioids → Naloxone: 400mcg IV, repeat every 2-3 min (max 10mg); consider infusion (short half-life)
- Benzodiazepines → Flumazenil: 200mcg IV, then 100mcg every 60s (max 2mg) - caution in chronic use/mixed OD
- TCAs → Sodium bicarbonate 8.4%: 50mL IV if QRS >120ms or arrhythmias
- Beta-blockers → Glucagon: 2-10mg IV bolus, then infusion
- Organophosphates → Atropine (high dose) + pralidoxime
- Digoxin → DigiFab: Digoxin-specific antibody fragments
- Iron → Desferrioxamine: 15mg/kg/h IV
- Methanol/ethylene glycol → Fomepizole (or ethanol infusion) + haemodialysis
Surgical/Interventional
- Haemodialysis: Lithium, salicylates, methanol, ethylene glycol, theophylline
- Intralipid (lipid emulsion): Local anaesthetic toxicity, lipophilic drug overdose
Referral Criteria
- All intentional self-harm → psychiatric assessment before discharge
- Severe poisoning → ICU/toxicology
- Paracetamol with high-risk features → liver unit (King's College criteria)
- National Poisons Information Service (NPIS): 0344 892 0111
Prognosis
- Paracetamol overdose: Mortality <1% if NAC given within 8 hours; ~5% mortality with established liver failure
- Opioid overdose: Excellent prognosis with timely naloxone administration
- TCA overdose: Mortality 2-5% in severe cases; most deaths from arrhythmias
- Overall poisoning mortality in hospital: <1% with appropriate management
- Risk of repeat self-harm within 1 year: ~25%; suicide risk ~3% over 5 years
Other Relevant Information
Key Antidotes Summary
| Toxin | Antidote | Key Notes |
|---|---|---|
| Paracetamol | N-acetylcysteine (NAC) | Use nomogram; treat staggered OD |
| Opioids | Naloxone | Short t½ - may need infusion |
| Benzodiazepines | Flumazenil | Avoid in chronic use/mixed OD |
| TCAs | Sodium bicarbonate | Target QRS narrowing |
| Warfarin | Vitamin K / PCC | PCC for major bleeding |
| Heparin | Protamine | 1mg per 100 units heparin |
| Beta-blockers | Glucagon | Bypasses beta receptor |
| Calcium channel blockers | Calcium chloride/gluconate + high-dose insulin | HDI with dextrose |
| Digoxin | DigiFab | Number of vials = digoxin level × weight / 100 |
| Iron | Desferrioxamine | If serum iron >90 µmol/L |
King's College Criteria for Liver Transplant (Paracetamol)
| Criteria |
|---|
| Arterial pH <7.30 after resuscitation |
| OR all three of: INR >6.5, creatinine >300 µmol/L, grade III-IV encephalopathy |