Paracetamol poisoning admissions to the Poison Treatment Center in New York have increased in recent years. Paracetamol is rapidly absorbed and causes liver damage through a toxic metabolite. Treatment involves assessing ingestion amount and time to determine if acetylcysteine (NAC) is needed. NAC treatment is most effective when started within 8 hours and involves a 3-stage infusion or oral dosing. While reactions can occur, NAC is the antidote for paracetamol overdose and aims to prevent liver injury.

1. PARACETAMOL ( ACETAMINIOPHAN )
POISONING
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2. Paracetamol poison cases admitted to
Poison Treatment Center NYGH
Year Male Female Total
2015 22 70 92
2016 21 88 109
2017 13 78 91
2018
(Jan to Apr)
9 32 41
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3. Causes severe hepatocellular necrosis and
less commonly acute tubular necrosis.
Rapidly absorbed from the small intestine.
Peak serum concentrations occur
within 1–2 hours for standard tablet or capsule
formulations and
within 30 minutes for liquid preparations.
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4. 85% Conjugation
NAPQI
Glutathione
Paracetamol Mechanism
N-acetyl-p-benzoquinonamine
Hepatotoxicity
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5. Adults and children > 6 years of age Children aged 0–6 years
Acute
single
ingestion
> 200 mg/kg or 10 g (whichever is
less) over a period of less than
8 hours
≥ 200 mg/kg over a period of
less than 8 hours
Repeated
supra-
therapeutic
ingestion
> 200 mg/kg or 10 g (whichever is
less) over a single 24-hour period
> 150 mg/kg or 6 g (whichever is
less) per 24-hour period for the
preceding 48 hours
> 100 mg/kg or 4 g/day (whichever
is less) in patients with predisposing
risk factors
≥ 200 mg/kg over a single 24-
hour period
≥ 150 mg/kg per 24-hour period
for the preceding 48 hours
≥ 100 mg/kg per 24-hour period
for the preceding 72 hours
Paracetamol dosing that may be associated with hepatic injury
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6. High risk persons ( lower margin of safety )
Those taking enzyme inducing drugs
( eg. anticonvulsants, rifampicin )
Chronic alcoholics
Malnourished patients,
Fasting state
HIV positive patients.
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7. The key factors to consider
The ingested dose and serum paracetamol
concentration (early)
Clinical and laboratory features suggesting liver
damage (late).
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8. The best surrogate marker indicating the
potential for injury is a timed serum
paracetamol level plotted on a nomogram.
The nomogram cannot be applied for
repeated or staggered doses, or if the time of
ingestion cannot be determined with
confidence by the treating clinician.
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9. The most important risk factor for liver
damage and death after acute paracetamol
ingestion is the extent of delay beyond 8 hours
until treatment with NAC commences.
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10. Clinical Features-
Early after acute overdose, there are usually no symptoms other
than nausea and vomiting.
Clinical evidence of end-organ toxicity often does not manifest until
24-48 hours after an acute ingestion
After 24-48 hours, ALT and AST begin to rise(hepatic necrosis)
Acute renal failure occurs occasionally.
Liver damage is maximal 3-4 days after ingestion
Despite a lack of significant symptoms, patients should be referred
to hospital.
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11. Time after ingestion
TEST 1-8 hr 8-24 hr > 24 hr
Paracetamol
level
At 4 hours or as
soon thereafter
as possible
On admission On admission
GOT/GPT On admission
AND at end of
NAC infusion
On admission
PT/ INR On admission
Urea/ Creat On admission
Glucose On admission
ABG On admission
Recommended investigations
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12. • Transaminase X Paracetamol product
<10,000
– At the time treatment starts and again
at 12 hours
– Lifethreatening toxicity is unlikely
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16. Three-stage N-acetylcysteine infusion
Initial
infusion
150 mg/kg of NAC diluted in 200 mL of 5%
glucose and infused over 15 to 60 minutes
Second
infusion
Followed by a continuous infusion of
50 mg/kg of NAC in 500 mL of 5% glucose
over the next 4 hours
Third
infusion
followed by a continuous infusion of
100 mg/kg of NAC in 1000 mL of 5%
glucose over the next 16 hours
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17. Anaphylactoid reactions ( 10-50% of patients during
first two NAC infusion)
Rash, wheeze or mild hypotension
Severe life-threatening reactions are very rare, but may
occur in predisposed individuals, such as patients with
asthma.
Management
Supportive, with temporary halting or slowing of the
infusion, and administration of antihistamines.
The occurrence of an anaphylactoid reaction does not
preclude the use of NAC on another occasion if
indicated.8/27/2018 17

18. Oral NAC ( available as mucolytic agent )
140 mg/kg stat
followed by
70mg/kg 4 hourly for 17 doses
with anti-emetic to prevent vomiting.
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19. The 2006 Cochrane review of several case series concluded there was no clear
difference in efficacy (in terms of hepatoxicity and mortality rates) between
intravenous and oral routes.
Oral NAC has been used for 30 years in the USA with similar efficacy and safety
Oral and Intravenous Acetylcysteine for Treatment of
Acetaminophen Toxicity:
A Systematic Review and Meta-analysis
(Green JL et. al. West J Emerg Med. 2013 May; 14(3): 218–226)
5164 patients in 16 articles
The overall rate of hepatotoxicity for the oral and IV routes were
12.6% and 13.2%, respectively.
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20. Don’t underestimate paracetamol poisoning
Stated timing and dose are often unreliable
and this needs to be taken into
consideration.
NAC is a safe and effective antidote.
Time to NAC is crucial.
May be asymptomatic in first 24 hours
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