Poisoning and Overdose

Emergency management

Poisoning or overdose (OD) may be intentional or unintentional. It can occur via ingestion, injection, or inhalation, and rarely by transdermal or other routes. It may be obvious from the history and presentation, but a high index of suspicion may also be required.

The emergency management of poisoning involves:

Initial resuscitation.
Identification, where possible, of likely agent.
Specific treatments or antidotes.
General supportive measures.

Causes

Common poisoning agents include:

Pharmaceutical products including ‘over-the-counter medications’:
- E.g. paracetamol (and paracetamol-containing products), aspirin (and other analgesics/NSAIDs), opiates/opioids, benzodiazepines and ‘Z-drugs’ (e.g. zopiclone), antidepressants (including SSRIs and tricyclics), and barbiturates
Recreational drugs (including alcohol, the most common drug to be co-ingested either with recreational drugs or as part of self-poisoning):
- E.g. opiates/opioids, cocaine, amphetamines, ecstasy, gammahydroxybutyric acid (GHB), hallucinogenics (e.g. LSD), glues or volatile chemicals
Industrial chemicals, household chemicals, and environmental toxins including inhaled poisons (e.g. carbon monoxide and cyanide):
- E.g. organophosphates, paraquat, methanol, ethylene glycol, household products (e.g. batteries, cleaning agents and detergents)
Animal, fish, and insect bites/stings.

Presentation and assessment

A history of attempted suicide, psychiatric illness, or substance abuse.
Airway or respiratory signs and symptoms:
- Respiratory depression
- Aspiration, pneumonitis, or bronchospasm
- Oropharyngeal burns
Cardiovascular:
- Hypotension, hypertension, cardiovascular collapse, cardiac arrest
- ECG: tricyclics and antidepressants, amongst other drugs, cause conduction defects and arrhythmias, which may be resistant to treatment
Neurological:
- Agitation, confusion, or hallucinations
- Unexplained unconsciousness, especially if associated with compartment syndrome or prolonged contact burns
- Convulsions
- Profound weakness, or conversely muscle rigidity or dystonia
- Ataxia or nystagmus
GI: vomiting or diarrhoea; liver failure.
Renal: renal failure, rhabdomyolysis.

Other features that may be associated with poisoning include:

Hypo- or hyperthermia.
Self-harm injuries.
Trauma, burns, drowning, and head injuries.
Electrolyte imbalance, especially sodium, potassium, or glucose.
Metabolic acidosis, especially with a raised osmolar or anion gap (see p.205).

Individual signs and symptoms are associated with certain poisons (Tables 14.1, 14.2, 14.3, 14.4). Clusters of symptoms may occur together when poisoning with certain agents has occurred; these are commonly referred to as ‘toxidromes’ (Table 14.5).

Investigations

The investigations required will be dictated by the patient’s severity of illness, and the most likely causative agent(s), but may include:

ABGs (hypoxia, hypercapnia, metabolic acidosis, raised anion gap).
FBC, coagulation studies (coagulation may be deranged).
Blood methaemaglobin concentration (see p.453).
RBC cholinesterase activity (in organophosphate poisoning).
U&Es, LFTs.
Serum calcium (in ethylene glycol poisoning) and phosphate.
Serum CK (raised in rhabdomyolysis).
Serum glucose.
Blood alcohol levels (or expired air levels if possible).
Paracetamol and salicylate levels (important to check timings).
Specific drug serum levels may be indicated for other substances (e.g. ethylene glycol, digoxin, valproic acid, phenytoin, theophylline, iron, lithium, carbamazepine).
Carboxyhaemoglobin (by co-oximetry).
Urine for myoglobin.
Consider taking blood, urine, and gastric aspirate samples for toxicology, or for storage in case later analysis is required.
12-lead ECG (may show ischaemia, evidence of hyperkalaemia or QT prolongation).
CXR (if aspiration suspected or prior to hyperbaric oxygen therapy).
AXR may be useful if ingestion of radiopaque substances is suspected (chloral hydrate, heavy metals, iron, enteric coated or sustained release preparations, ‘body packing’).
Consider head CT or LP to exclude other causes of unconsciousness.

Differential diagnoses

Conditions causing altered consciousness, altered behaviour, or respiratory depression (e.g. head injuries, meningitis/encephalitis, hypoglycaemia and post-ictal state).
Conditions causing cardiovascular collapse (e.g. anaphylaxis).
Conditions causing muscle weakness (e.g. Guillain-Barré and botulism)
Conditions causing non-specific symptoms such as vomiting or hypothermia (e.g. infections/sepsis, neurological injury/SAH).

Table 14.1 Cardiorespiratory changes and associated poisons

Signs and symptoms	Potential poisons
Respiratory depression; hypoventilation	Alcohols, barbiturates, benzodiazepines, botulinum toxin, neuromuscular blocking agents, opioids, sedatives, strychnine, tranquillizers, tricyclic antidepressants
Tachypnoea	Ethylene glycol, isoniazid, methanol, pentachlorophenol, salicylates
Pulmonary oedema	Cocaine, chlorophenoxy herbicides, ethylene glycol, hydrocarbons, irritant gases, organic solvents, opioids, paraquat, phosgene, salicylates
Pneumothorax	Cocaine
Bradycardia	β-blockers, calcium-channel antagonists, carbamates, cholinergics, clonidine, digoxin, lithium, metoclopramide, opioids, organophosphates, phenylpropanolamine, physostigmine, propoxyphene, quinidine
Tachycardia	Amphetamines, anticholinergics, antihistamines, caffeine, carbon monoxide, cocaine, cyanide, hydralazine, hydrogen sulphide, phencyclidine, phenothiazines, sympathomimetics, theophylline, thyroxine, tricyclic antidepressants
Arrhythmias	β-blockers, chloroquine, cyanide, digoxin, phenothiazines, quinidine, theophylline, tricyclic antidepressants
Hypotension	β-blockers, calcium channel antagonists, ethanol, opioids, sedatives, tranquillizers
Hypertension	Anticholinergics, sympathomimetics

Table 14.2 Temperature, skin, and oral changes

Signs and symptoms	Potential poisons
Hyperthermia	Anticholinergics, amphetamines, antihistamines, cocaine, dinitrophenols, hydroxybenzonitriles, LSD, MAOIs, phencyclidine, phenothiazines, pentochlorophenols, procainamide, quinidine, salicylates, tricyclic antidepressants
Hypothermia	Barbiturates, carbon monoxide, colchicine, ethanol, lithium, opioids, phenothiazines, sedatives, tricyclic antidepressants
Excess salivation	Cholinesterase inhibitors, strychnine
Dry mouth	Anticholinergics, opioids, tricyclic antidepressants, phenothiazines
Sweating	Cholinergics, hypoglycaemics, sympathomimetics
Dry skin	Anticholinergics
Hair loss	Thallium
Acne	Bromide, organochlorine

Table 14.3 Neurological and eye changes

Signs and symptoms	Potential poisons
Coma, ↓consciousness	Alcohols, benzodiazepines, barbiturates, bethanechol, carbamates, clonidine, GHB, hypoglycaemic agents, lithium, nicotine, opioids, organophosphates, physostigmine, pilocarpine, salicylates, tranquillizers tricyclic antidepressants
Convulsions	Amphetamines, anticholinergics, antihistamines, antipsychotics, caffeine, camphor, carbamates, carbon monoxide, chlorinated hydrocarbons, cocaine, ethylene glycol, isoniazid, lead, lidocaine, lindane, lithium, methanol, nicotine, organophosphates, orphenadrine, phencyclidine, propranolol, salicylates, strychnine, theophylline, tricyclic antidepressants
Paraesthesia	Thallium
Ataxia/nystagmus	Antihistamines, bromides, barbiturates, carbamazepine, carbon monoxide, diphenylhydantoin, ethanol, phenytoin, piperazine, sedatives, thallium
Miosis	Barbiturates, carbamates, cholinergics, clonidine, ethanol, isopropyl alcohol, organophosphates, opioids, phencyclidine, phenothiazines, physostigmine, pilocarpine
Mydriasis	Amphetamines, anticholinergics, antihistamines, cocaine, dopamine, glutethimide, LSD, MAOIs, phencyclidine, tricyclic antidepressants
Blindness	Quinine, methanol

Table 14.4 Gastrointestinal and renal changes

Signs and symptoms	Potential poisons
Vomiting	Aspirin, iron, fluoride, theophylline
GI bleed	Anticoagulants, corrosive compounds, NSAIDs, salicylates
Liver failure	Carbon tetrachloride, paracetamol
Diarrhoea	Arsenic, cholinesterase inhibitors
Constipation	Lead, opioids, thallium
Urinary retention	Atropine, opioids, tricyclic antidepressants
Incontinence	Carbamates, organophosphates
Crystals in urine	Ethylene glycol, primidone
Renal failure	Amanita toxin, aminoglycosides, cadmium, carbon tetrachloride, ethylene glycol, oxalates, paracetamol, polymyxin, mercury, methanol.

Table 14.5 Toxidromes and combinations of symptoms and the likely associated poisons

Toxidromes	Constellation of signs and symptoms	Possible toxins
Anticholinergic activity	Agitation, delirium, diminished consciousness, mydriasis hyperthermia, dry skin and mucosal membranes, flushing, tachycardia, bowel stasis, urinary retention	Anticholinergic alkaloids (e.g. in plants such as belladonna), antihistamines, antiparkinsonian drugs, atropine, baclofen, cyclopentolate, phenothiazines, propantheline, scopolamine, tricyclic antidepressants
Cholinergic activity (muscarinic and/or nicotinic effects)	Miosis or mydriasis, blurred vision, sweating, excess salivation, lacrimation or bronchial secretions, wheezing or dyspnoea, tachycardia or bradycardia, hypertension, vomiting and diarrhoea, abdominal cramps, urinary and faecal incontinence, muscle weakness, fasciculations, paralysis	Acetylcholinesterase inhibitors: carbamates, neostigmine, organophosphates (pesticides or agents such as sarin), physostigmine, pyridostigmine
Cholinergic activity (muscarinic and/or nicotinic effects)		Acetylcholine agonists: carbachol, choline, metacholine, pilocarpine
Sympathetic hyperactivity α and β-adrenergic activity	Agitation, mydriasis, sweating, flushing, pyrexia, tachycardia, hypertension	Amphetamines, cocaine, ecstasy, ephedrine, PCP, phencyclidine, pseudoephedrine
If predominantly β-adrenergic	Tremor, tachycardia, hypotension	Caffeine, salbutamol, terbutaline, theophylline
If predominantly α-adrenergic	Bradycardia, hypertension	Phenylephrine, phenylpropanolamine
Extrapyramidal	Cog-wheel rigidity, tremor, trismus, hyper-reflexia, dyskinesia, dystonia, posturing, opisthotonos, choreoathetosis	Haloperidol, olanzapine, phenothiazines, risperidone
Hallucinogenic	Agitation, psychosis, hallucinations, mydriasis, hyperthermia	Amphetamines, cannabinoids, cocaine, LSD
Narcotic	Decreased consciousness, miosis, bradypnoea, bradycardia, hypotension, hypothermia, bowel stasis	Clonidine, dextromethorphan, opiates, pentazocine, propoxyphene
Sedative	Confusion, slurred speech, ↓consciousness, normal or reduced respiratory rate, normotension, normocardia	Anticonvulsants, antipsychotics, barbiturates, benzodiazepines, ethanol, GHB, meprobamate
Volatile inhalation	Euphoria, confusion, slurred speech, headache, restlessness, ataxia, seizures, respiratory depression, arrhythmias	Acetone, chlorinated hydrocarbons, fluorocarbons, hydrocarbons (petrol, butane, propane), nitrites (isobutyl, amyl, butyl), toluene
Serotonin	Agitation, confusion, mydriasis, flushing, sweating, tremor, hyperreflexia, clonus, myoclonus, trismus, hyperthermia, tachypnoea, tachycardia, hypertension	Amphetamine, ecstasy, MAOIs, serotonin re-uptake inhibitors
Chemical pneumonitis	Cough, dyspnoea, wheeze, respiratory distress, cyanosis, fever Can occur without aspiration or loss of consciousness	Essential oils, petroleum distillates, turpentine, white spirit
Methaemaglobinaemia	Headache, diminished consciousness, dyspnoea, tachypnoea, severe hypoxia, tachycardia, chocolate coloured blood	Alanine dyes, benzocaine, chlorates, chloroquine, dapsone, nitrates and nitrites, nitrobenzene, nitrophenol, phenacetin, phenazopyridine, primaquine, sodium nitroprusside

Immediate management

Rapid simultaneous assessment of the patient, and of the likely agent(s) involved, may aid management.

Details of which agent(s), how much, and how long ago should be actively sought; the following may help:

History from patient, family, other witnesses, or paramedics.
History of repeat prescriptions from GP.
Examination of patient for signs associated with certain drugs.
Examination of pill bottles or tablets; a pill identification system such as the computer-aided tablet and capsule identification program (TICTAC) may be required.

Resuscitation

Give O₂ and support airway, breathing, and circulation as required.

Airway support

Endotracheal intubation may be required if the following is present:
- Hypoxia
- Diminished consciousnes (GCS ≤9, or rapidly deteriorating)
- The patient is at risk of aspiration
- The patient is agitated, or combative and not mentally competent
- Any corrosive substances have been ingested

Breathing support

Ensure ventilation is adequate, use mechanical ventilation if necessary:
- Respiratory stimulants are unhelpful
- In conditions where there is extreme acidosis it may be appropriate to hyperventilate the patient for a short period

Circulatory support

Fluid loading may be required to treat hypotension:
- Tachypnoea, sweating, and prolonged unconsciousness can lead to fluid depletion
- Inotropes are occasionally required, but may interact with overdoses of cardiovascular drugs; where there is doubt discuss their use with an expert in poisonings
Hypotension may be the result of arrhythmias requiring treatment; treat any cardiac arrhythmias and conduction defects which may compromise the circulation (see p.132 and 138).
- Correction of hypoxia, acidosis (both metabolic and respiratory), and electrolytes will be required
- Where tricyclic antidepressants are involved a bolus of 50-100 ml sodium bicarbonate 8.4% IV may help
- Where drugs have prolonged the QT interval resulting in torsade de pointes, it may be treated with magnesium sulphate 8 mmol (2 g) in 100 ml 5% glucose IV over 2-5 minutes followed by an infusion of 2-4 mmol/hour (0.5-1 g/hour) (10 mmol) and potassium supplementation (40 mmol in 100 ml 5% dextrose over 1-4 hours via a central line aiming for a plasma concentration of 4.5-5.0 mmol/L)
Profound bradycardia may be caused by certain agents, and may be unresponsive to drug therapy, requiring:
- Early transvenous or transcutaneous pacing
- Chemical pacing with adrenaline or isoprenaline
- β-blocker toxicity may require treatment with glucagon 2-10 mg IV/IM, and calcium channel antagonist toxicity may require calcium chloride 10 ml 10% IV; additional treatment for bradycardia and/or hypotension may also be necessary (see pp.104 and 132)
- In digoxin overdose treatment with Fab fragments may help
Hypertension can occur with some drugs, particularly amphetamines and cocaine- hypotensive agents may be required.

Neurological support

Convulsions are mostly brief and non-sustained; where status epilepticus occurs first-line treatment is with a short-acting benzodiazepine such as lorazepam 4 mg IV (see p.160):
- Be aware that many patients will have taken benzodiazepines as part of their overdose ‘cocktail’
Dystonic reactions can occur and may require treatment with procyclidine 5-10 mg IV.

Prevention of absorption

Activated charcoal

50-100 g PO of activated charcoal can be used if patients have ingested a potentially toxic dose of a poison within the past 1 hour:
- Activated charcoal is contraindicated in patients at risk of aspiration, e.g. patients with ↓consciousness or after hydrocarbon ingestion; it is also relatively contraindicated in patients at risk of GI bleeding or perforation
- In patients with diminished consciousness, charcoal can be safely delivered via a NGT if the airway is protected by cuffed ETT and the NGT position has been positively confirmed
- It is ineffective against alcohols, solvents, metal salts (e.g. iron and lithium), petroleum distillates, DDT, and malathion
- Do not give alongside an oral antidote
Multiple-dose activated charcoal may be used for certain drugs, (phenobarbital, carbamazepine, dapsone, quinine, and theophylline) at a rate not less than 12.5 g/hour.

Gastric lavage

Gastric lavage is not routinely recommended. It should only ever be considered in case of extreme risk from recent ingestion (<1 hour) of very toxic substances:
- It is contraindicated in patients at risk of aspiration, and if corrosive substances or hydrocarbons (e.g. petrol) have been ingested due to the risk of gut perforation or pneumonitis

Forced emesis

Forced emesis (e.g. with ipecacuanha) is no longer recommended.

Further management

Specific information on how to manage poisonings can be obtained from databases (e.g. Toxbase). Complex cases can be discussed with staff from a specialist poisons unit.

Agitation

Look for and treat causes of agitation, e.g. hypoxia or full bladder.
Sedation may be required in profoundly agitated patients, but may provoke a drop in consciousness requiring endotracheal intubation; sedation may also worsen any hypotension.
Antipsychotics are sometimes used to treat agitation, but may lower the seizure threshold.

Coma

If opioids or benzodiazepines are suspected of contributing to ↓level of consciousness naloxone (0.6-1.2 mg IV) or flumazenil (0.5 mg IV) may be administered as a diagnostic challenge:
- Flumazenil may lower the seizure threshold, and can provoke arrhythmias (avoid in suspected tricyclic overdose)

Hypothermia

Hypothermia is common following prolonged unconsciousness; or it can occur as a result of certain drugs (classically barbiturates).
Hypothermia may be profound and require rewarming ( p.250); there may be an associated bradycardia ( p.132).

Hyperthermia

Hyperthermia is associated with stimulants, neuroleptic and antimuscarinic drugs; cooling and specific antihyperthermic therapy may be required ( p.248).

Other

Catheterization and urine output measurements may be required.
Regular blood sugar measurements may be required in order to monitor/treat any hypoglycaemia.
Invasive monitoring and continuous ECG monitoring are required for many poisonings and overdoses.

Active removal of drugs and poisons

Haemodialysis or haemoperfusion may be useful in the removal of certain toxins (see p.457).
Urinary alkalinization (often known as forced alkaline diuresis) using sodium bicarbonate can be used to encourage the renal excretion of specific acidic drugs (moderately severe aspirin/salicylate overdoses not requiring haemodialysis; 2,4-dichlorophenoxyacetic acid and chlorphenoxy herbicides; mecoprop):
- Different regimens exist for achieving urinary alkalinization, an example is the infusion of 1000 ml 1.4% sodium bicarbonate in
  water solution over 2.5 hours; urine should be tested to ensure a pH of 7.8-8.5
- Urinary alkalinization may also be of benefit in methotrexate, fluoride, or diflunisal poisoning, although the evidence for this is not clear
- It is not recommended for phenobarbital (multiple-dose activated charcoal is superior), or chlorpropamide (supportive care with glucose infusion mostly adequate)
- It is associated with hypokalaemia and alkalotic tetany (electrolytes should be monitored and replaced)
- It is relatively contraindicated in patients with incipient renal failure or significant pre-existing heart disease
Urinary acidification has previously been considered for drugs such as amphetamines, quinine, and phencyclidine, but is generally not recommended because of associated complications.
Whole bowel irrigation using balanced polyethylene glycol electrolyte solution (1500-2000 ml/hour NG) to promote bowel transit and liquefy stool has only limited evidence of effectiveness, but has been used in the following circumstances:
- For sustained release drug preparations, and drugs not absorbed by charcoal (e.g. iron and lithium)
- For ‘body-packers’ (drug couriers who have ingested packages/condoms filled with drugs)
- Contraindications include: unprotected airway; bowel perforation, obstruction, or haemorrhage; haemodynamic instability

Table 14.6 Specific antidotes and treatments

Drug or chemical	Antidote(s)
Anticholinergics	Physostigmine
β-blockers¹	Glucagon
Benzodiazepines	Flumazenil
Calcium channel antagonists¹	Calcium chloride/gluconate
Cyanide	Sodium-nitrate with sodium-thiosulphate Dicobalt edetate Hydroxycobalamin
Digoxin	Fab fragments
Ethylene glycol/methanol	Ethanol or fomepizole
Heavy metal poisoning	Sodium calcium edetate Penicillamine Dimercaprol DMSA/DMPS
Insulin/hypoglycaemics	Glucose, glucagon
Iron	Desferrioxamine
Isoniazid	Pyridoxine
Methaemoglobinaemia	Methylene blue
Opiates/opioids	Naloxone
Organophosphates/nerve agents	Atropine or pralidoxime
Paracetamol	Acetylcysteine or methionine
Rocuronium/vecuronium	Sugammadex
Snake bites	Antivenom (antivenin/antivenene)
Warfarin	Prothrombin complex Vitamin K
¹β-blocker and calcium channel antagonist toxicity have also been successfully treated with high-dose insulin therapy. This therapy should only be used where there is an established protocol for its use.
NB Local anaesthetic agent toxicity has been successfully treated with IV lipid therapy (see p.493). This treatment is also being investigated for use with for other lipid-soluble drugs.

Pitfalls/difficult situations

If a deliberate release of toxic agents, or a mass poisoning event, is suspected follow the guidelines on p.496.
Accidental or deliberate self-poisoning is commonly associated with other injuries, including trauma.
The use of multiple agents is common in self-poisoning, and signs and symptoms are often a mixture of those caused by various drugs.
The combination of stimulant and sedatives (particularly GHB) taken together can result in profound fluctuations in consciousness.
Where there is any doubt as to the aetiology of ↓consciousness or seizures a CT scan is indicated:
- Alcohol is associated with head trauma and intracranial bleeding
Paracetamol and salicylate are extremely common ingredients in overdose ‘cocktails’, check plasma levels for these agents in cases of self-poisoning, even if there is no evidence of ingestion.
Prior to blood levels being available, or where no blood tests exist, treatment can be based upon the calculated maximum dose (e.g. if all the available pill bottles were full at the time of ingestion).
Blood levels of toxins taken soon after ingestion may be falsely low.
Identification of tablets, plants, or snakes brought in to hospital is often wrong, expert advice may be required either via direct contact or via programs such as TICTAC.
Activated charcoal may sometimes be of use in cases where ingestion took place >1 hour prior to admission, or where the timing of ingestion is unknown; where there is doubt discuss the case with a poisons expert.
‘Body-packers’ (drug couriers who have ingested packages filled with drugs), require a surgical referral, treatment will depend upon the risks posed by the drug(s) involved and their position within the GI tract.
Self-poisoning requires appropriate evaluation of any future suicide risk; ideally this should be arranged prior to ICU discharge.

Legal pitfalls

Deaths from poisoning should be reported to the coroner.
Most patients will cooperate with treatment though some, particularly those who have attempted suicide, may refuse it:
- Patients who are mentally competent have the right to refuse any, and all, treatment, even if they risk death in doing so
- Mental competency requires the ability to understand, retain, believe and evaluate information
Life-saving treatments may be administered to patients against their will only if they are not mentally competent and have no legally binding advance directive.
When in doubt ask for senior advice or psychiatric advice early.
Carefully document any refusal of treatment, or any treatment against a patient’s wishes.

¹The elimination of many more drugs can be enhanced by extracorporeal techniques, but in many cases the clinical benefit is unknown, or there are more effective treatments (e.g. digoxin and fab fragments)

²CVVH is unlikely to be of benefit.

³Haemodialysis can also be used but is considered to be less effective.

Further reading

Brooks DE, et al. Toxicology in the ICU. Part 2: Specific toxins. Chest 2011; 140(4): 1072-85.

Joint Formulary Committee. Emergency treatment of poisoning In British national formulary. London: BMJ Group and Pharmaceutical Press, latest edn September 2012.

Position paper on urine alkalinization. Clin Toxicol 2004; 42(1): 1-26.

Position paper: gastric lavage. Clin Toxicol 2004; 42(7): 933-43.

Position paper: whole bowel irrigation. Clin Toxicol 2004; 42(6): 843-54.

Position paper: single-dose activated charcoal. Clinical Toxicol 2005; 43: 61-87.

Position statement and practice guidelines on the use of multi-dose activated charcoal in the treatment of acute poisoning. Clin Toxicol 1999; 37(6): 731-51.

Mental Capacity Act 2005. London: HMSO, 2005.

Levine M, et al. Toxicology in the ICU. Part 1: general overview and approach to treatment. Chest 2011; 140(3): 795-80.

Levine M, et al. Toxicology in the ICU. Part 3: natural toxins. Chest 2011; 140(5): 1357-70.

TICTAC tablet identification system:

<http://tictac.vhn.net/home/>.

TOXBASE—web-based database of the National Poisons Information Service available to registered users (i.e. A&E departments):

<http://www.spib.axl.co.uk/>.

Analgesics

! Paracetamol poisoning

Paracetamol (acetaminophen) is a common hepatotoxic agent in deliberate overdose. It is found in many over-the-counter medications.

Causes

Paracetamol poisoning occurs when healthy individuals take moderate to large overdoses (10 g/20 tablets or 150 mg/kg within 24 hours).
Certain patients have depleted stores of glutathione and are susceptible to hepatotoxicity at much lower doses, including:
- Malnourished: anorexia, alcoholism, HIV
- Taking enzyme inducing drugs: carbamazepine, phenobarbital, phenytoin, primidone, rifampicin, St John’s wort
In rare cases in high-risk individuals, poisoning may occur at normal doses administered over a prolonged time.

Presentation and assessment

Initial presentation is mostly asymptomatic unless other agents are also involved, although nausea and vomiting may occur.
In exceptionally high overdoses (>5000 µmol/L or 800 mg/L) acute deterioration in GCS may occur accompanied by lactic acidosis.
Delayed presentation (12 hours-4 days) can be accompanied by RUQ pain with liver and/or renal failure.
Liver damage is maximal at 4 days after the overdose, and may result in encephalopathy, cerebral oedema, haemorrhage, and hypoglycaemia.

Investigations

(See also

p.449.)

ABGs, if compromised (acidaemia).
FBC and coagulation studies (deranged INR).
U&Es, LFTs (raised transaminases).
Serum glucose (hypoglycaemia may occur).
Serum paracetamol levels (at 4 hours post ingestion if possible).

Immediate management

(See also

p.454.)

Give O₂ and support airway, breathing, and circulation as required.
Treatment is guided by plasma levels taken >4 hours after ingestion, levels (earlier levels are misleading); high-risk patients require treatment at lower plasma levels (see Fig. 14.1).
If history is suggestive of an overdose in the past 36 hours requiring treatment then commence IV N-acetylcysteine whilst awaiting levels.
Methionine can be given if poisoning is <12 hours with no vomiting
IV N-acetylcysteine (best started <8 hours after ingestion):
- 150 mg/kg IV (diluted in 5% glucose) over 15 minutes, then
- 50 mg/kg IV (diluted in 5% glucose) over 4 hours, then
- 100 mg/kg IV (diluted in 5% glucose) over 16 hours
Discontinue if overdose occurred <8 hours ago and serum paracetamol levels are under treatment levels, or
- Overdose occurred >8 hours ago (or was staggered), serum paracetamol levels are under treatment levels, and AST normal.

Fig. 14.1 Paracetamol poisoning nomogram. Patients whose plasma-paracetamol concentrations are above the normal treatment line should be treated with acetylcysteine by IV infusion (or, if acetylcysteine cannot be used, with methionine by mouth, provided the overdose has been taken within 10-12 hours and the patient is not vomiting).

Patients at high-risk of liver damage, and who should be treated if their plasma concentration is above the high-risk treatment line, include:

Those taking liver-enzyme-inducing drugs (e.g. carbamazepine, phenobarbital, phenytoin, primidone, rifampicin, efavirenz, nevirapine, alcohol, St John’s wort).
Those who are malnourished (e.g. anorexia or bulimia, cystic fibrosis, hepatitis C, in alcoholism, or those who are HIV positive); or who have not eaten for a few days.

The prognostic accuracy after 15 hours is uncertain but a plasmaparacetamol concentration above the relevant treatment line should be regarded as carrying a serious risk of liver damage. Graph reproduced with permission from Professor PA Routledge, All Wales Therapeutics and Toxicology Centre, Cardiff and Vale University Health Board. Text adapted from the British National Formulary.

Further management

(See also

p.456.)

Monitor for hepatotoxicity using serial PT/INR and bilirubin measurements; LFT changes often occur late; renal failure may also occur.
Discuss impending hepatic failure with a specialist liver centre: INR >3, oliguria, raised creatinine, hypoglycaemia, acidosis and encephalopathy.

Pitfalls/difficult situations

Medications may contain co-drugs needing treatment, in particular co-proxamol (available but no longer licensed).

Aspirin/salicylate and NSAID poisoning

Most NSAIDs are benign in overdose, but salicylate overdoses can produce life-threatening, difficult-to-manage, complex clinical pictures.

Causes

NSAIDs are available as prescription and over-the-counter medicines and are commonly involved in multiple-drug overdoses. Salicylates overdoses have become less common than other NSAIDs but are far more toxic Salicylate (mild to moderate toxicity 150-200 mg/kg) is found in: