Much of this is derived from the PACT module 'major intoxication'. See ESICM website.

General considerations

Incidence: Paracetamol > ibuprofen > aspirin > SSRIs > tricyclics.
An acute overdose less than 10 times a single therapeutic dose seldom causes life-threatening symptoms apart from overdose with narcotics, paracetamol, lithium, digoxin and warfarin.

Symptoms within a few hours.
Life threatening features in 6.
Arrythmias up to 24h if slow release preparation.
Paracetamol 1-2 days.

Slow – opiates, benzos.
Fast – acidosis.
Weak – organophosphates.
Myocardial depression – tricyclics, b blockers, Ca blockers.
Vasodilatation – hypnotics.
Hypertension – symp, antichol, MAOIs.
Arrythmias – symp, antichol, MAOIs.
Reflexes down in CNS depressants; up in anticholinergics and sympathomimetics.
Convulsions – antichol, symp, CO, lithium, tricyclics, neuroleptics, alcohol withdrawal.
Coma unlikely in salicylates or paracetamol (unless liver failure).

  • Small - Opiates, organophosphates, other cholinergics
  • Big - Alcohol, ecstasy, amphetamines, anticholinergics, ß-blockers

ABC approach

As often no specific antidotes need to:
  • Reduce absorption
  • Increase elimination
  • Treat end-organ failure
Gastric lavage
Gastric lavage may instead increase the severity of poisoning by dissolving the substance and enhancing its absorption.
Gastric lavage should only be considered within one hour of ingestion of an agent causing severe toxicity.
CI in petroleum distillates and corrosives.

Activated charcoal
1-2g/kg up to 4h post ingestion.
Does not absorb alcohol, lithium, cyanide, strong acids/alkalis, iron.

Alkalinisation of blood - for any Na channel blockers eg tricyclics, class 1s (phenytoin, lignocaine, quinidine etc).
Aim for blood pH of 7.5.
Alkalinisation of urine and for any drugs that ionise in an alkaline environment - weak acids such as aspirin, barbiturates and herbicides.
Urinary pH 7.5-8.5.
Forced alkaline diuresis does not work as v.difficult to keep urine alkaline.
Drugs with LMW (<500 Da), low protein binding, low VD, high water solubility
Recommended in
  • Methanol, ethylene glycol, theophylline, lithium and salicylates

Routine blood and urine toxicology not useful or practical.
Qualitative urine tests detect a limited no of drugs.
Quantitative serum samples more useful but only in patients where treatment with an antidote may be life-saving and where treatment is guided by laboratory values (e.g. paracetamol, salicylate, lithium, digoxin, iron, methanol, ethylene glycol, theophylline and carbon monoxide poisoning).
Take and store venous blood sample from anyone admitted with coma
Only mandatory test in everyone is paracetamol.

ABG (SID, SIG, BE - must albumin correct - see acid base).
Osmolar gap effectively same thing as SIG - anions that increase SIG also increase osmolar gap.

Osmolar gap = measured osmolality − calculated osmolality

Calculated osmolality = 2[Na+]+[urea]+[glucose]+[ethanol]

Specific poisons

0844 892 0111 (NPIS)


Toxic dose 150mg/kg (around 7g in an adult).
Asymptomatic until end-organ damage occurs 48 hours or more from ingestion.
Paracetamol is metabolised by conjugation in the liver to non-toxic agents .
In OD normal metabolic pathways saturated at which point metab in liver via P450 system to toxic metabolite, N-acetyl-p-benzoquinone imine (NAPQI), which normally binds to glutathione, rendering it inactive and allowing renal excretion.
In OD this pathway can be overwhelmed
systemic release of NAPQI, which is toxic to the liver and kidneys by covalent binding to proteins thus causing ARF and ALF - hepatocellular death and centrilobular liver necrosis.
Patients with induced cytochrome P450 systems from chronic alcohol excess or regular medications (including the anti-epileptics) are at higher risk because they produce more NAPQI.
Those who are glutathione depleted (anorexics, the malnourished or those with terminal malignancy) are also at high risk
Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) concentrations begin to rise within 24 hours post-ingestion and peak at 48-72 hours as does total bilirubin and prothombin time. Severe toxicity can be defined as AST or ALT greater than 1000 IU/l.
Activated charcoal works well in 1
st few hours.
A serum paracetamol level should be taken 4 hours after the ingestion and compared with the appropriate line on the Prescott nomogram to ascertain if treatment is required.
If the level is deemed treatable, the glutathione donor N-acetylcysteine should be commenced.

N-acetylcysteine 150 mg/Kg in 200 ml 5% glucose IV for 15 minutes; then
50 mg/Kg in 500 ml 0.5% glucose for 4 hours; then
100 mg/Kg in 1000 ml for 16 hours

Regularly check LFTs and INR


Antimuscarinic effects
Cardiac Na channel blockade & K rectifier
ɑ1 rec blockade

Antimuscarinic – tachycardia, pupil dilatation, sedation or restlessness, smooth muscle relaxation
Resp arrest
ECG - wide QRS, prolonged PR, QT, arrythmias
Metabolic acidosis
Rhabdomyolysis if unconscious long time

NG charcoal in 1st 2-4 hrs.
Sodium Bicarb 50mls 8.4% (50mmol) if PH <7.4 (don’t go >7.55 as >7.65 fatal), arrhythmias, wide QRS, hypotension unresponsive to fluid.
Do not shock VT (unless pulseless). O2, bicarb, MgSO4.
Lorazepam for fits (not phenytoin).
Noradrenaline or glucagon (1mg IV every 3mins) for hypotension.

The sodium channel blockade is mitigated by larger concentrations of extracellular sodium (competitive blockade) and alkalaemia whereas acidaemia increases toxicity.
Increasing plasma pH from 7.38 to 7.5 decreases the free fraction of TCA by ~21%
Avoid class 1 drugs (eg phenytoin and lignocaine) as worsen Na channel blockade.


The two main toxic effects of salicylate overdose are a direct central stimulation of the respiratory centres and an uncoupling of oxidative phosphorylation inhibiting ATP-dependent reactions.
Initially, a respiratory alkalosis develops secondary to the direct stimulation of the respiratory centres.

Hyperventilation, non-cardiogenic pulmonary oedema, respiratory arrest and aspiration pneumonitis can occur
Tinnitus, deafness
Tachycardia, hypotension, arrythmias
Confusion, seizures, coma
Severe acidosis
GI bleeding, N&V

<50 minimal toxicity
50-100 moderate
>100 severe

Bicarb for acidosis or levels >35mg/dl.
RRT if severe symptoms, acidosis, levels >50 if chronic OD, >100 acute OD
Give glucose (can benefit conscious level, even if measured glucose is normal)
Alkalinization of the plasma (aim pH 7.50–7.55) and urine (aim pH 8.0) using IV sodium bicarbonate increases ionisation and excretion.
Adequate K has to be present for excretion of ionised salicylate.


Supportive care.
In mixed OD are protective from tricyclic effects so don’t give flumazenil.


Anticholinergic effects and α-blockade with postural hypotension and tachycardia.
Conduction blocks and prolongation of the QRS and QT intervals on the ECG.
Extrapyramidal effects such as acute dystonic reactions may occur.
Patients at risk of rapid deterioration with coma, seizures, hypotension, or dysrhythmias.
Usually somnolent, sedated and hypoactive.
May require intubation if large OD.
Alterations in thermoregulation with hypothermia or hyperthermia (rarely evolving into the neuroleptic malignant syndrome).
Supportive care with fluids, noradrenaline, bicarb and Mg.


The serotonin syndrome can be caused by a single agent or two or more drugs that increase serotonin levels, such as SSRIs and MAOIs.
Characterised by altered mental status, autonomic dysfunction and neuromuscular abnormalities such as rigidity or myoclonus.
More info

Calcium channel and β-blockers

Activated charcoal up to 4h.
Supportive care.
Not removed by RRT.
Pacemakers, intra-aortic balloon pump and cardiopulmonary bypass may be considered in patients not responding to pharmacological therapy
Drug treatment includes the use of atropine, calcium, glucagon, insulin and catecholamines:

Increases the concentration gradient across the cell membrane. Infusion doses and targeted calcium level have not been established. Aim to increase the ionized calcium to 2-5 x the patient's baseline. Calcium can reverse the hypotensive effects of β-blocker toxicity.
Glucagon raises intracellular cyclic adenosine monophosphate (cAMP) concentrations that in turn regulate ion channels (including calcium channels) through non-adrenergic pathways.
Insulin infusions can be used in verapamil, diltiazem and β-blocker toxicity. The optimal dose of insulin is unclear. The mechanism of action is thought to be inotropy secondary to increased myocardial glucose utilisation.
Role unclear. Both adrenaline and noradrenaline have been used with mixed success. Catecholamines may provoke or worsen pulmonary oedema, ischaemic vascular disease and renal failure.
Sodium bicarbonate
Recently been advocated in the management of calcium channel blocker toxicity in patients with prolonged QRS (>100 ms), acidosis, or persistent hypotension despite the above methods.

Stimulants (cocaine, ecstasy, amphetamines)

Activated charcoal if oral intake.
Cool if hyperthermia above 40 °C.
Monitor U&Es, LFTs, CK.
Use benzodiazepine if seizures, hypertension or agitation.
Can use haloperidol if inadequate response to benzo.
Cocaine may cause hypertensive emergency through CNS stimulation and its peripheral α-agonist effects.
Benzodiazepines and nitrates are first-line agents in cocaine-induced hypertension and acute coronary syndromes.
Vasoconstriction may also be reversed by phentolamine.