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Emerg Med J. 2007 May; 24(5): 1–2.
PMCID: PMC2658515 PubMed articles by these
authors
doi: 10.1136/emj.2006.043216
Copyright ©2007 Emergency Medicine Journal.
 Bourdeaux, C.
Death from paracetamol overdose
despite appropriate treatment
with N‐acetylcysteine
Chris Bourdeaux and Jeremy Bewley

Bewley, J.
PubMed related articles

ReviewParacetamol poisoning:
the action line and the timing of
Chris Bourdeaux, Jeremy Bewley, Department of
acetylcysteine therapy.
Anaesthesia, Bristol Royal Infirmary, Bristol, UK
[Ir
Med J. 1996]
Correspondence to: Dr C Bourdeaux
Department of Anaesthesia, Level 7, Queens Building, Bristol
 Shorter duration of oral NRoyal Infirmary, Bristol BS2 8HW, UK;
acetylcysteine therapy for
chrisbourdeaux@googlemail.com
Accepted October 5, 2006.
acute acetaminophen
This article has been cited by other articles in PMC.
overdose.
Abstract
[Ann Emerg Med. 2000]

The administration of N-
A case of death from severe paracetamol poisoning acetylcysteine causes a
decrease in prothrombin time in
which presented early and received appropriate
patients with paracetamol
treatment according to evidence‐based guidelines
overdose but without evidence
is presented here. It is very rare for patients to die
of liver impairment.
from paracetamol poisoning when they receive
[Eur J Gastroenterol Hepatol.
N‐acetylcysteine (NAC) within 8 h of ingestion. The 2005]
patient had a marked lactic acidosis on
 [Risk of acute hepatic
insufficiency in children due to
presentation to hospital. This case demonstrates
chronic accidental overdose of
that a patient can die from paracetamol poisoning
paracetamol (acetaminophen)].
despite early and appropriate treatment, and raises
[Ned Tijdschr Geneeskd. 2007]
the question whether lactic acidosis in a patient  ReviewParacetamol overdose in
following paracetamol overdose should prompt the a preterm neonate.
[Arch Dis Child Fetal Neonatal
initiation of NAC treatment while awaiting
Ed. 2001]
paracetamol levels.

» See reviews... | » See all...
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Other Sections▼
Paracetamol is the most common drug taken in
overdose in the UK. Management of paracetamol
overdose presented to hospital within a few hours
of ingestion is often thought of as straightforward.
We present a fatal case of paracetamol overdose
that presented early and received appropriate
treatment according to available evidence.

Other Sections▼
Case history
A previously well 55‐year‐old man presented to the
emergency department 2 h after taking 50 g of

paracetamol, 3.15 g of aspirin and 1.125 g of

cinnarizine. His 4 h paracetamol level was 534
mg/l. He was not identified as at high risk for
paracetamol poisoning for the purposes of the
N‐acetylcysteine (NAC) nomogram.
The notable blood results on admission were
creatinine 109 μmol/l, alanine aminotransferase
(ALT) 15 U/l, prothrombin time (PT) 9.8 s and
lactate 15.54 mmol/l. Arterial blood gases at 8 h
after ingestion showed a marked compensated
lactic acidosis despite adequate fluid resuscitation,
pH 7.35, partial pressure of carbon dioxide 22.2,
partial pressure of oxygen 118.7, BE‐13.5,
bicarbonate 11.0, lactate 12.76 mmol/l and glucose
20.6 mmol/l. Salicylate levels were not significantly
raised on immediate and later testing.
Infusion of NAC was commenced at 6 h after
ingestion after obtaining the 4‐h paracetamol level.
This was in accordance with evidence‐based
guidelines for patients not at high risk for

Death from paracetamol
overdose despite
appropriate treatment with
n‐acetylcysteine

paracetamol overdose
trea...(869)

paracetamol overdose(1053)

Management of acute
paracetamol
(acetaminophen) toxicity: a
standardised proforma
improves...

paracetamol
poisoning(3618)
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Compound
PubMed
Substance
paracetamol poisoning.1 At 8 h after ingestion, the
patient developed signs of agitation, confusion and
a falling conscious level. He was admitted to the
intensive care unit, and was intubated and
ventilated for airway protection.
Over the next 48 h, he developed non‐oliguric
acute renal failure with creatinine peaking at 283
μmol/l, and continuous renal replacement treatment
was commenced at an early stage. Interestingly,
his liver function tests did not become grossly
abnormal. International normalised ratio at 48 h had
risen to 2.0 and ALT was 138 U/l. The NAC infusion
was continued.
In the 24 h that followed, his condition deteriorated
rapidly. A vasodilatory state of shock developed,
and he required high doses of vasopressors to
maintain adequate mean arterial pressure guided
by invasive cardiac output monitoring. Oxygenation
became problematic and chest x ray showed
four‐quadrant alveolar shadowing consistent with
acute respiratory distress syndrome.
The international normalised ratio peaked at 2.5 at
72 h after ingestion, ALT remained only moderately
increased at 145 U/l and bilirubin never rose above
25 μmol/l. The patient became hypoglycaemic,
requiring a 50% dextrose infusion to maintain
acceptable blood glucose levels. His cardiovascular
status continued to deteriorate and he died at 84 h
after ingestion. His condition was discussed at
regular intervals with a tertiary liver unit, and they
did not recommend transfer at any point.
A postmortem examination showed a
normal‐looking liver with no evidence of cirrhosis.
Liver histology was not performed. Appearance of
the lung was consistent with severe acute
respiratory distress syndrome. Causes of death
were recorded as multi‐organ failure and
paracetamol toxicity.

Other Sections▼
Discussion
Deaths from paracetamol overdose are extremely
rare when NAC is administered within 8 h of
ingestion. A study by Prescott et al2 identified only
one case of liver damage among 62 patients
treated with NAC within 10 h of ingestion and
described optimal results from NAC if the infusion is
commenced within 8 h.
This patient gave a history of massive paracetamol
overdose 2 h before presenting to the emergency
department, and was managed according to the
guidelines for early presentation. An intravenous
NAC infusion was commenced 4 h after
presentation to hospital as soon as the result of the
4 h paracetamol level was obtained. The
paracetamol level was extremely high, indicating
that this was a substantial overdose.
It is unusual for death to occur after paracetamol
poisoning without the patient showing obvious
signs of liver damage that may indicate a poor
prognosis. PT has been suggested as a reliable
predictor of poor outcome.3 The peak PT on day 4
in our patient was 25 s, well below the levels
associated with poor outcome. He never became
jaundiced, and the rise in ALT was only moderate.
The very high initial lactate value in this case might
have alerted us sooner to the severity of the
overdose. Lactate values >3.5 mmol/l on
presentation and >3.0 mmol/l after fluid
resuscitation have been found to predict a poor
outcome in paracetamol overdose.4 This case
highlights the importance of measuring lactate
levels on admission to hospital in cases where
significant overdose of paracetamol is suspected,
and raises the question of whether lactic acidosis in
a patient following paracetamol overdose should
prompt the initiation of NAC treatment while
awaiting paracetamol levels. It is important to note
that a patient can die from paracetamol poisoning
despite early and appropriate treatment.
Abbreviations
ALT - alanine aminotransferase
NAC - N‐acetylcysteine
PT - prothrombin time
Footnotes
Competing interests: None declared.
Informed consent was obtained for publication of the person's
details in this report.
References
1. Wallace C I, Dargan P I, Jones A L. Paracetamol poisoning:
an evidence‐based flowchart to guide management. Emerg Med
J 2002. 19202–205.205. [PMC free article] [PubMed]
2. Prescott L F, Illingworth R N, Critchley J A. et al Intravenous
N‐acetylcysteine: the treatment of choice for paracetamol
poisoning. BMJ 1979. 21097–1100.1100. [PMC free
article] [PubMed]
3. Harrison P M, O'Grady J G, Keays R T. et al Serial
prothrombin time as a prognostic indicator in paracetamol
induced fulminant hepatic failure. BMJ 1990. 301964–
966.966. [PMC free article][PubMed]
4. Bernal W, Donaldson N, Wyncoll D. et al Blood lactate as an
early predictor of outcome in paracetamol induced acute liver
failure: a cohort study. Lancet 2002. 359558–563.563. [PubMed]
Articles from Emergency Medicine Journal : EMJ are
provided here courtesy of
BMJ Group

Paracetamol overdose: an evidence based flowchart to guide management.[Emerg Med J. 2002]

Intravenous N-acetylcystine: the treatment of choice for paracetamol poisoning.[Br Med J. 1979]

Serial prothrombin time as prognostic indicator in paracetamol induced fulminant hepatic
failure.[BMJ. 1990]

Blood lactate as an early predictor of outcome in paracetamol-induced acute liver failure: a cohort
study.[Lancet. 2002]
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