Paracetamol in children

This one is paracetamol as it is used in children: the doses and where they differ, the specific errors that keep recurring, what to do about an overdose, and the pharmacology underneath it. Almost everything here is more interesting than the drug's reputation suggests.

Four things, if you take nothing else

1. It is the most useful drug on the ward and the most casually prescribed. Regular paracetamol reduces opioid requirement, works, and is almost free. It is also written up without a weight, continued for a fortnight, and duplicated inside a combination product. The harm it does is almost never from a single wrong dose.
2. The child at risk in your unit is not the overdose. It is the child on regular therapeutic paracetamol who has stopped eating, is vomiting, is septic, or is on an enzyme inducer. Prolonged fasting and malnutrition deplete glutathione and shift metabolism towards the toxic pathway. The dose did not change; the child did.
3. Two strengths of the intravenous formulation, one concentration, and a recurring tenfold error. Intravenous paracetamol is 10 mg/mL, supplied as 500 mg in 50 mL and 1,000 mg in 100 mL. Confusing milligrams with millilitres gives exactly ten times the intended dose, and this has killed infants. Over two hundred inadvertent overdoses were reported to the UK national reporting system in one period.
4. A child under 10 kg is not just a smaller child. The product information specifies a lower intravenous dose below 10 kg — 7.5 mg/kg rather than 15 — and a lower daily maximum. Writing the standard dose for a 9 kg infant is a doubling, not a rounding.

The practical part

Situation	Dose	Notes
Oral or rectal child	15 mg/kg every four to six hours maximum 60 mg/kg/day	Round to a sensible volume of the strength you actually have. Rectal absorption is slower and less predictable than oral, so it is a fallback rather than an equivalent.
Intravenous over 10 kg	15 mg/kg every six hours maximum 60 mg/kg/day	Solution is 10 mg/mL. Always prescribe in milligrams, never millilitres.
Intravenous 10 kg or less	7.5 mg/kg every six hours maximum 30 mg/kg/day	A different dose and a different ceiling. This is the one people get wrong.
Duration at maximum dose	Review by 48 to 72 hours	Particularly in the small, unwell, fasting or malnourished child. Maximum dosing was never intended to be open-ended.

Every one of these must be checked against your own formulary and local guideline before use. They are here to be recognised, not copied.

When it is an overdose

This is the commonest deliberate ingestion at school age and in adolescence, and it is also the most forgiving if you catch it. Accidental liquid ingestion in the younger child is common and rarely needs treatment.

• The threshold that mattersAn acute ingestion of 200 mg/kg or 10 g, whichever is less, is potentially toxic. Above 500 mg/kg or 30 g is a massive overdose, where absorption may continue for up to twenty-four hours and increased acetylcysteine doses are used.
• Take the level at four hours, not beforeEarlier concentrations may not have peaked and cannot be plotted. The nomogram applies only to acute immediate-release ingestions with a known time.
• The nomogram does not cover everythingRepeated supratherapeutic ingestion, modified-release preparations, staggered overdoses and unknown timing all need different rules and a call to the poisons centre.
• Acetylcysteine, two bags200 mg/kg over four hours, then 100 mg/kg over sixteen. The dose is the same in children as in adults; what changes is the dilution volume, which is reduced to avoid fluid overload. Getting that wrong is how a child ends up hyponatraemic.
• Ring somebodyThe Poisons Information Centre is 13 11 26 in Australia. Massive ingestions, intravenous paracetamol overdose, and any transaminase above about a thousand warrant a conversation rather than a protocol.

The pharmacology

What it does, and the honest answer. Nobody is entirely sure. It is an analgesic and antipyretic with almost no peripheral anti-inflammatory action, which is why it is not classed as a non-steroidal anti-inflammatory. The leading explanations are central cyclo-oxygenase inhibition in an environment of low peroxide tone, an active metabolite acting on vanilloid and cannabinoid receptors, and augmentation of descending serotonergic inhibition. Being asked to explain a mechanism that is not settled is itself a fair exam question.

Kinetics. Oral bioavailability is good but incomplete, with peak concentrations in roughly thirty to sixty minutes for a liquid and longer for tablets. Volume of distribution is close to total body water, protein binding is low, and the elimination half-life is two to three hours — prolonged in overdose and in liver failure, where a rising half-life is a bad sign.

Metabolism, which is the whole of the toxicology. About ninety per cent is conjugated to inactive glucuronide and sulfate and excreted. A small fraction is oxidised by cytochrome P450, chiefly CYP2E1, to NAPQI — which is rapidly conjugated by glutathione and rendered harmless.

In overdose, or in a child whose glutathione is already depleted, that last step fails. Free NAPQI binds covalently to hepatocyte proteins and produces centrilobular necrosis. Acetylcysteine works by replenishing glutathione, which is why it is effective early and progressively less so late.

Adverse effects. At therapeutic doses, remarkably few — which is most of why it is prescribed so casually. Hepatotoxicity is the one that matters. Rare severe cutaneous reactions are described. The reported association with childhood asthma is confounded by indication and should be treated as unresolved rather than as established.

Interactions worth knowing. Enzyme inducers — carbamazepine, phenytoin, rifampicin, isoniazid, and chronic alcohol — increase flux through the oxidative pathway and lower the threshold for harm. Regular therapeutic paracetamol raises the INR in a patient on warfarin, which surprises people every time.