Poisoning and STOPP/START

1. Introduction
2. General Management of Poisoning
   • Resuscitation and Risk Assessment
   • Reducing Drug Absorption
   • Enhancing Drug Elimination
3. Antidotes
4. Specific Drug Overdoses
   • Paracetamol
   • Salicylates (Aspirin)
   • Opioids
   • Benzodiazepines
   • Tricyclic Antidepressants
   • Beta-Blockers and Calcium Channel Blockers
   • Digoxin
   • Lithium
   • Iron
   • Organophosphates
   • Methanol and Ethylene Glycol
   • Cyanide and Carbon Monoxide
5. Polypharmacy
6. STOPP-START
7. Summary
8. Quiz

• The general management of poisoning has four pillars: resuscitation, reducing further absorption, enhancing elimination, and specific antidotes where one exists. The UK reference is TOXBASE, the National Poisons Information Service database.
• Important antidotes to commit to memory (the full list is in the Antidotes section): paracetamol → N-acetylcysteine, opioids → naloxone, benzodiazepines → flumazenil (on expert advice only), warfarin → vitamin K + prothrombin complex concentrate (PCC, a concentrate of clotting factors), dabigatran → idarucizumab.
• More antidotes: beta-blockers → glucagon (unlicensed for this use, and its clinical effect is unclear, so seek National Poisons Information Service advice), digoxin → DigiFab (digoxin-specific antibody fragments), organophosphates (insecticides and nerve agents) → atropine + pralidoxime, methanol/ethylene glycol → fomepizole or ethanol, iron → desferrioxamine.
• Polypharmacy (typically five or more regular medicines) is increasingly common in older adults. It increases the risk of adverse drug reactions (harm caused by medicines).
• The STOPP-START tool is a framework for medication review in patients aged 65 and over. It was developed in Ireland and validated by a European expert panel. STOPP (Screening Tool of Older Persons' Prescriptions) identifies potentially inappropriate medicines. START (Screening Tool to Alert to the Right Treatment) identifies missed indicated medicines (medicines the patient should be taking but is not).

Introduction

Poisoning is a common reason for emergency department attendance: deliberate self-harm, accidental overdose in older patients with polypharmacy, recreational drug use, and occasional industrial or environmental exposures. The pre-clinical curriculum covers the principles of management, the major antidotes, and a small number of high-yield specific poisonings.

The companion to poisoning is the prescribing review framework STOPP-START. It is used to identify and reduce inappropriate medicines in older adults. The two topics are paired because older adults often take many regular medicines (polypharmacy), which raises the risk of adverse drug reactions (harm caused by medicines) and of accidental overdose.

General Management of Poisoning

Resuscitation and Risk Assessment

The first priority is always the patient, not the poison:

1. Airway, breathing, circulation: the standard ABCDE approach (Airway, Breathing, Circulation, Disability, Exposure). Intubation (passing a breathing tube into the windpipe) if the airway is compromised.
2. Disability: check blood glucose, pupils, Glasgow Coma Scale (GCS, the score of conscious level) and temperature.
3. Exposure: remove contaminated clothing after chemical exposure, and keep the patient warm.
4. Specific risk assessment: identify the substance, the amount, the time of exposure, and any co-ingestion (other drugs or alcohol taken at the same time).
5. Investigations: standard panel of bloods, paracetamol level in any suspected, undisclosed or mixed overdose (early toxicity is clinically silent), salicylate level if suspected, ECG, blood gas, blood glucose. Toxicology screen if relevant.
6. Get advice: TOXBASE (toxbase.org) is the UK National Poisons Information Service (NPIS) database, free at the point of use to NHS staff. The 24-hour NPIS phone line is also available for complex cases.

Reducing Drug Absorption

Several historical approaches have been abandoned because they cause more harm than good. The options, from the most useful to the abandoned:

• Activated charcoal: binds many drugs in the gut, reducing systemic absorption. Most effective within 1 hour of ingestion. The window may be longer for modified-release preparations (tablets that release the drug slowly) and for some drugs. Standard dose: 50 g orally or via a nasogastric (NG) tube (a tube passed through the nose into the stomach). Contraindications: reduced GCS without airway protection (risk of aspiration, that is, breathing charcoal or stomach contents into the lungs), corrosive ingestion (swallowed acids or alkalis) and hydrocarbons (petrol, paraffin and similar solvents).

  Charcoal does not bind: lithium, iron, ethanol, methanol, ethylene glycol, strong acids and alkalis.

• Whole bowel irrigation (flushing the gut with a large volume of fluid containing macrogol, a laxative): very occasional use for sustained-release preparations, body packers (people who swallow packets of illegal drugs to smuggle them), lithium and iron.
• Gastric lavage (stomach pumping): almost never indicated; risks of aspiration outweigh benefit.
• Induced vomiting with ipecacuanha (a drug that causes vomiting): no longer recommended.

Enhancing Drug Elimination

Several techniques can speed elimination of certain drugs:

• Urinary alkalinisation with sodium bicarbonate: raises urine pH (makes the urine more alkaline). Weak acids such as salicylate become charged in alkaline urine, so they cannot cross back out of the kidney tubule (the part of the nephron that carries urine) into the blood. This is called ion trapping. Used for salicylate overdose and other weak-acid poisons.
• Multiple-dose activated charcoal, for drugs with enterohepatic circulation (the drug passes from the bile into the gut and is absorbed again): carbamazepine, theophylline (an asthma drug), dapsone, quinine and phenobarbital.
• Haemodialysis (a machine filters the blood), for severely ill patients poisoned by drugs that typically have a small volume of distribution (they stay mostly in the blood rather than spreading into the tissues) and modest protein binding (they are not tightly stuck to blood proteins), so that dialysis can reach them. The classic candidates are lithium, salicylates, methanol, ethylene glycol, theophylline, phenobarbital (an anti-seizure drug), valproate (an epilepsy drug) and metformin (when there is severe lactic acidosis, an acid build-up from lactate).
• Lipid emulsion (Intralipid), an intravenous fat solution, for local anaesthetic systemic toxicity (especially bupivacaine). For overdoses of other highly lipophilic (fat-soluble) drugs, such as tricyclic antidepressants (TCAs), beta-blockers and calcium channel blockers, the evidence is of very low quality, so it is used only as a rescue treatment on specialist advice.

Antidotes

Most poisons have no specific antidote (a drug that blocks or reverses the poison). Supportive care (treating problems such as low blood pressure or seizures as they arise) is the rule. The exceptions are the antidotes below. They are worth learning first, because the right antidote given early can prevent serious harm:

Antidote summary: high-yield list

Paracetamol → N-acetylcysteine (NAC)
Opioids → Naloxone
Benzodiazepines → Flumazenil (on expert advice only; can be hazardous)
Warfarin → Vitamin K + prothrombin complex concentrate (PCC) or fresh frozen plasma (FFP)
Dabigatran → Idarucizumab
Apixaban or rivaroxaban (direct oral anticoagulants, DOACs) → Andexanet alfa (a protein that binds them and reverses their effect; NICE recommends it only for life-threatening or uncontrolled bleeding from the gut) or prothrombin complex concentrate
Heparin → Protamine sulfate
Beta-blockers → Glucagon (unlicensed for this use; clinical effect unclear) ± high-dose insulin with glucose
Calcium channel blockers → Calcium gluconate (or calcium chloride), then high-dose insulin with glucose in severe cases (hyperinsulinaemic euglycaemia therapy, HIET: high-dose insulin with glucose to keep the blood glucose normal); glucagon has limited evidence here
Digoxin → Digoxin-specific Fab antibodies (DigiFab)
Iron → Desferrioxamine
Lead, mercury, arsenic → a chelating agent (a drug that binds the metal), chosen on National Poisons Information Service advice: succimer (DMSA), unithiol (DMPS), sodium calcium edetate (a form of EDTA) or dimercaprol (largely superseded)
Methanol / ethylene glycol → Fomepizole (or ethanol IV)
Organophosphates / nerve agents → Atropine + pralidoxime
Cyanide → Hydroxocobalamin (Cyanokit, for smoke inhalation) or dicobalt edetate (when severe poisoning is strongly suspected); sodium nitrite then sodium thiosulfate is an alternative
Carbon monoxide → 100% oxygen (hyperbaric oxygen in severe cases: discuss with the NPIS)
Methotrexate → Folinic acid (calcium folinate)
Local anaesthetic toxicity → Intralipid

Specific Drug Overdoses

Paracetamol

Paracetamol is one of the drugs most commonly taken in deliberate overdose in the UK, and it is the most common cause of acute liver failure there. Mechanism, clinical course, and treatment with N-acetylcysteine are covered in detail in the paracetamol sections of the non-steroidal anti-inflammatory drugs (NSAIDs) article (paracetamol is not an NSAID, but the two share one page). Standard summary:

• Often asymptomatic in the first 24 hours.
• For a single acute overdose, take a paracetamol level at 4 hours or later (earlier levels cannot be interpreted). Plot it on the standard treatment nomogram (a chart of drug level against time since overdose that shows who needs treatment). Since 2012 the UK has used a single treatment line, starting at 100 mg/L at 4 hours. A staggered overdose (taken over more than 1 hour), or an overdose at an unknown time, is managed differently: the British National Formulary (BNF, the UK prescribing reference) records the advice of the UK medicines regulator (the Medicines and Healthcare products Regulatory Agency, MHRA) to give acetylcysteine without delay.
• N-acetylcysteine (NAC) restores hepatic glutathione (the liver's main antioxidant store), which neutralises NAPQI (N-acetyl-p-benzoquinone imine, the toxic breakdown product of paracetamol). NAC works best when started within 8 hours, but it should still be given later if the liver is already injured.
• Severe poisoning: apply the King's College criteria (a set of blood and clinical markers that identify patients who may need a liver transplant).

Salicylates (Aspirin)

The classic biochemistry of salicylate poisoning is worth memorising:

• Early respiratory alkalosis (the blood becomes too alkaline from over-breathing): direct stimulation of the respiratory centre.
• Late metabolic acidosis (the blood becomes too acidic): uncoupling of oxidative phosphorylation (the cell burns fuel without making ATP, releasing heat) and accumulation of lactate.
• Net result: mixed respiratory alkalosis and metabolic acidosis.
• Other features: tinnitus (ringing in the ears), raised body temperature (hyperthermia), sweating, vomiting, hyperventilation (fast, deep breathing) and agitation.

Management:

• Activated charcoal if within 1 hour.
• IV fluid resuscitation with normal saline plus correction of electrolyte abnormalities.
• Urinary alkalinisation with sodium bicarbonate (target urinary pH 7.5 to 8.5): "ion trapping" of salicylate in the kidney tubule, as described above. Correct low blood potassium (hypokalaemia) before giving the bicarbonate, because hypokalaemia may complicate alkalinisation of the urine.
• Haemodialysis in severe poisoning (level > 700 mg/L, severe acidosis, renal failure, pulmonary oedema, persistent CNS features, plasma level still rising despite treatment).

Opioids

The triad of pinpoint pupils, respiratory depression and reduced consciousness (pinpoint pupils are very small pupils) is the cardinal presentation. For management, see the Opioids page: airway support, then naloxone adjusted dose by dose (titrated) to the respiratory rate. The aim is adequate breathing, not full reversal, which can bring on sudden withdrawal. Naloxone has a short half-life (the time for the blood level to halve; 30-90 min), so patients who have taken a long-acting opioid may need a continuous naloxone infusion or repeated doses.

Benzodiazepines

Excessive sedation, occasional respiratory depression (more likely when taken with other sedatives such as opioids or alcohol), hypotension. The antidote flumazenil is a competitive antagonist at the benzodiazepine site of the GABA_A receptor (the main calming receptor in the brain). It reverses sedation rapidly, but in overdose it is used cautiously and on expert advice only. It should not be used as a diagnostic test in a patient with reduced consciousness. The risks:

• Can precipitate seizures, especially in chronic benzodiazepine users or in mixed overdose with proconvulsants (drugs that lower the seizure threshold, e.g. tricyclic antidepressants).
• Short half-life (the blood level falls quickly): flumazenil is short-acting and the benzodiazepine effects can outlast it, so re-sedation is common. Flumazenil is usually reserved for clearly iatrogenic overdose (overdose caused by medical treatment, e.g. procedural sedation).

Tricyclic Antidepressants

Tricyclic antidepressants (TCAs) are especially dangerous in overdose. Between 1993 and 2002 in England, the death rate per million prescriptions was highest for TCAs and lowest for selective serotonin re-uptake inhibitors (SSRIs, a newer type of antidepressant). TCAs act in several ways: anticholinergic effects (blocking acetylcholine, so dry mouth, fast pulse, flushing and confusion), sodium channel blockade in the heart (slows electrical conduction and can cause arrhythmia) and alpha-1 blockade (widens blood vessels, so blood pressure falls). Clinical features:

• Anticholinergic effects ("dry as a bone, hot as a hare, blind as a bat, mad as a hatter, red as a beet").
• Hypotension.
• Cardiac arrhythmia: a serious feature, along with convulsions and respiratory failure. Wide QRS (a wide QRS complex on the ECG, showing slowed conduction through the heart) and ventricular arrhythmia.
• Seizures.
• Reduced consciousness.

Management: ABC, activated charcoal if within 1 hour, IV sodium bicarbonate for QRS prolongation (alkalinisation of the blood reduces TCA cardiotoxicity, that is damage to the heart's electrical activity), benzodiazepines for seizures.

Beta-Blockers and Calcium Channel Blockers

Both produce bradycardia (slow heart rate), hypotension and shock (circulatory failure) in overdose. Calcium channel blocker overdose can additionally cause hyperglycaemia (high blood glucose), because insulin secretion is calcium-dependent in pancreatic beta-cells.

Management: ABC, IV fluids, atropine. Specific therapies:

• Glucagon: unlicensed for this use, but listed in the BNF as a treatment option for severe hypotension, heart failure or cardiogenic shock (shock from a failing heart) after beta-blocker overdose. It was traditionally used to raise cardiac cyclic AMP (a signalling molecule that makes heart muscle contract harder) independently of the beta-adrenoceptor (the receptor that beta-blockers block). Its clinical effect in poisoned patients is unclear, so do not rely on it alone. Serious beta-blocker overdose needs resuscitation and National Poisons Information Service advice. In one local protocol, a glucagon infusion is considered only if the first glucagon bolus (a single quick injection) restores a stable circulation, and high-dose insulin with glucose is another monitored treatment. See the NHS Lanarkshire guidance (a local hospital protocol based on TOXBASE) and the randomised crossover trial (each volunteer received every treatment on separate days, in random order) in 10 healthy men given esmolol (a short-acting beta-blocker). It measured the effect of glucagon on heart rate and blood pressure, but it was not done in poisoned patients.
• Calcium gluconate, for calcium channel blocker overdose.
• High-dose insulin and glucose: "hyperinsulinaemic euglycaemia therapy" (HIET, high-dose insulin with glucose to keep the blood glucose normal) supports cardiac contractility. The BNF describes it for severe cases.
• Intralipid (an intravenous fat solution) as a rescue for highly lipophilic (fat-soluble) agents, on specialist advice. The evidence is low to very low quality (see the lipid emulsion point above).
• Pacing (an electrical device that sets the heart rate) or ECMO (extracorporeal membrane oxygenation, a machine that takes over heart and lung function) in extreme cases.

Digoxin

Digoxin toxicity (covered in Cardiac Arrhythmias) presents with abnormal heart rhythms of almost any type, often slow (bradyarrhythmias), gastrointestinal (GI) upset (nausea, vomiting, anorexia), confusion, and the classic yellow-green colour vision (xanthopsia).

Management: correct low potassium (hypokalaemia); caution, because severe acute toxicity may produce high potassium (hyperkalaemia). For severe toxicity (life-threatening arrhythmia, or severe hyperkalaemia, for example a potassium (K⁺) level above 6.5 mmol/L, that does not respond to adequate rehydration and conventional treatment), digoxin-specific Fab antibody fragments (DigiFab) bind digoxin and produce rapid clinical improvement.

Lithium

Lithium has a narrow therapeutic index (a small gap between a helpful dose and a toxic dose). The usual blood range is 0.4-1.0 mmol/L. For people starting lithium, NICE advises aiming for 0.6-0.8 mmol/L (the BNF advises a lower level, 0.4-0.6 mmol/L, from the age of 65). Blood samples are taken 12 hours after the last dose. Toxicity is usually described above 1.5 mmol/L, but neurotoxic symptoms (such as ataxia, which is unsteady walking, tremor, which is shaking, and confusion) can occur at therapeutic levels. Lithium levels rise with dehydration, NSAIDs, angiotensin-converting enzyme (ACE) inhibitors, diuretics (especially thiazide diuretics) and reduced renal function.

Features:

• Mild: tremor, GI upset, fatigue.
• Moderate: confusion, ataxia (unsteady walking), hyperreflexia (brisk reflexes), myoclonus (sudden muscle jerks).
• Severe: seizures, coma, arrhythmia, renal failure.

Management: stop lithium, IV fluids (saline). Haemodialysis (a machine filters the blood). The Extracorporeal Treatments in Poisoning (EXTRIP) workgroup, an international expert group, recommends it if the level is > 4.0 mmol/L and kidney function is impaired, or at any level if there is reduced consciousness, seizures or a life-threatening arrhythmia. It suggests haemodialysis if the level is > 5.0 mmol/L, if there is significant confusion, or if the level is expected to take more than 36 hours to fall below 1.0 mmol/L. The BNF adds that levels above 2 mmol/L are usually associated with serious toxicity and may need haemodialysis if there are neurological symptoms or renal failure, and that in acute overdose much higher levels may be present without features of toxicity. Activated charcoal is ineffective (charcoal does not bind lithium).

Iron

Iron poisoning is a particular risk in children, who may swallow iron tablets because they look like sweets. It is usually accidental. There are five clinical phases:

1. 0-6 hours: GI symptoms (vomiting, haematemesis (vomiting blood), melaena (black, tarry stools)).
2. 6-24 hours: apparent improvement.
3. 12-48 hours: shock, metabolic acidosis, hepatic failure, coagulopathy (a blood clotting disorder).
4. 2-3 days: recovery or progression.
5. 2-6 weeks: late strictures (scarring that narrows the stomach outlet, causing gastric outlet obstruction).

Management: whole bowel irrigation (flushing the gut with a large volume of fluid containing macrogol, a laxative) may be considered. Charcoal does not bind iron. Desferrioxamine chelates iron (binds it so that it can be passed out in the urine) and is given for severe poisoning (level > 90 micromol/L 4 hours after ingestion, or with shock, acidosis or coma).

Organophosphates

Organophosphates (insecticides such as malathion; nerve agents like sarin and Novichok) irreversibly inhibit acetylcholinesterase (the enzyme that breaks down acetylcholine), producing massive cholinergic stimulation (overactivity of acetylcholine):

• Muscarinic features (effects at muscarinic receptors in glands, gut, airways and heart), remembered as SLUDGE: Salivation, Lacrimation, Urination, Defecation, GI upset, Emesis. Plus small pupils (miosis), airway narrowing (bronchospasm) and slow heart rate (bradycardia).
• Nicotinic features (effects at nicotinic receptors in muscle): muscle weakness, fasciculations (muscle twitching), eventual paralysis.
• CNS: confusion, seizures, coma.

Management:

• ABC, decontamination (remove clothes, wash skin), staff personal protective equipment (PPE).
• Atropine: repeat the dose until the chest is clear, the heart rate is above 80 per minute and the systolic blood pressure is above 80 mmHg (the most important end-points). The aim also includes dry skin and pupils that are no longer pinpoint (very small), but pupil widening is sometimes delayed, so pupil size is a poor guide to the first doses. Doses required can be enormous.
• Pralidoxime: reactivates acetylcholinesterase, but only before the enzyme has "aged" (become permanently blocked). The speed of ageing differs between pesticides. The benefit is uncertain: oximes (the class of drugs that includes pralidoxime) might help only patients poisoned by specific pesticides or patients with moderate poisoning.
• Benzodiazepines for seizures.

Methanol and Ethylene Glycol

Both cause severe metabolic acidosis with a high anion gap and a high osmolar gap (blood test results that point to unmeasured acids and alcohols in the blood). Toxicity comes from their metabolites (formate from methanol; glycolate and oxalate from ethylene glycol), produced by alcohol dehydrogenase (the liver enzyme that breaks down alcohol).

Management:

• Fomepizole: a competitive inhibitor of alcohol dehydrogenase (it blocks the enzyme so that toxic metabolites cannot form); preferred treatment.
• Ethanol: alternative; competes for alcohol dehydrogenase.
• Haemodialysis: removes both parent compound and toxic metabolites. Essential for severe poisoning.
• Adjuncts (extra treatments): folinic acid (for methanol), and pyridoxine (vitamin B6) with thiamine (vitamin B1) for ethylene glycol.

Cyanide and Carbon Monoxide

Both are inhaled toxins typically encountered in fires.

Cyanide binds the iron of cytochrome oxidase (the cell enzyme that uses oxygen to make energy), halting cellular oxygen use. Features: rapid onset of headache, confusion, seizures, "cherry-red" skin, and high oxygen content in venous blood (because the cells cannot use it). Antidote: hydroxocobalamin (Cyanokit, the only suitable preparation; it binds cyanide to form cyanocobalamin, vitamin B₁₂) can be considered after smoke inhalation when there are signs of significant cyanide poisoning. Dicobalt edetate is the BNF antidote of choice when severe cyanide poisoning is strongly suspected, but it is itself toxic, so it is not used as a precaution. Sodium nitrite followed by sodium thiosulfate is an alternative if dicobalt edetate is not available. Sodium nitrite can cause methaemoglobinaemia (haemoglobin that cannot carry oxygen) and vasodilation (widening of the blood vessels).

Carbon monoxide binds haemoglobin with much higher affinity than oxygen, causing functional anaemia (the blood cannot carry oxygen, as if the patient were anaemic) and tissue hypoxia. Pulse oximetry is misleadingly normal. Antidote: 100% oxygen. Referral for hyperbaric oxygen (oxygen given at high pressure in a sealed chamber) should be discussed with the National Poisons Information Service if the patient is pregnant or has severe poisoning, for example loss of consciousness, psychiatric or neurological features other than headache, myocardial ischaemia (reduced blood flow to the heart muscle) or an arrhythmia, or a carboxyhaemoglobin (haemoglobin bound to carbon monoxide) level above 20%.

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