A 34-year-old British woman presented to the emergency department 30 minutes after ingesting approximately 100 acetaminophen tablets with alcohol in a suspected suicide attempt. She was treated with activated charcoal and intravenous N-acetylcysteine. On the first day of admission she developed abdominal pain and vomiting. Her liver function tests remained normal during her 3-day admission before she discharged herself against medical advice to return to the UK. Paracetamol overdose is commonly seen and requires prompt treatment with N-acetylcysteine to prevent liver damage from toxic metabolite accumulation if ingestion exceeds toxic thresholds.

1. Paracetamol overdose
By
Dr. opeoluwa folorunsho

2. Case
• EP a 34 year old British national
• presented to the accident and emergency
• 30 minutes after ingestion of approximately
100 tablets of acetimophen tablets
• EP admitted to taking medication with
alcoholic wine

3. Case
• had only been in Barbados for 2 days prior to
ingestion
• suspicion of infidelity on the part of her
boyfriend of 3 months who resides in the
island.

4. • one episode of clear colour vomitus
• she denied :
• abdominal pain
• Headache
• bleeding from any orifice
• visual or auditory disturbances

5. • it was her second attempt to terminate her
life
• 1st attempt was 15 years ago (medication)
• recently started seeing a psychologist for
depression
• Currently not on any medication

6. • As regards this episode
• Felt disappointed that she was unsuccessful
• Was not planning to do it again
• She didn’t write a suicide note
• called her boyfriend after ingesting the tablets

7. Vitals on arrival
• Temperature………………….36.2 degree celcius
• Blood pressure …………………..133/77 mmHg
• Pulse …………………………….138 beats/min
• Respiratory rate …………………22 cycles/ min
• Oxygen saturation …….98 percent on room air

8. examination
• young lady now in no apparent cardiovascular
or respiratory distress
• Her membranes were pink and moist
• she was anicteric and acyanosed
• equal chest rise on inspection
• vesicular breath sounds with no added sounds

9. examination
• Her jugular venous pressure was not elevated
and no distended neck veins observed
• Her pulse rate was 104 and regular with good
volume
• First and second heart sounds noted with no
murmurs or additional sounds appreciated
• Apex was at the 5th intercostal space mid
clavicular line

10. examination
• . Examination of the abdomen revealed a flat
soft abdomen that moved with respiration
• No previous surgical scars or hernia cough
impulse observed
• Liver was not enlarged or tender and there
were no palpably enlarged organs
• Her bowel sounds were normal

11. • No focal deficits observed and patient had
equal and reactive pupils
• the rest of her central nervous system
examination was essentially normal
• Her mood was “sad” and affect was downcast
and tearful

12. Case
• Speech rate was normal rate, rhythm, volume
and tone
• EP denied thought insertion, withdrawal,
broadcasting or flight of ideas
• She denied having suicidal or homicidal
thoughts in the department and her risk for
suicide score assessed her as medium risk of
suicide

13. Case
• having positive points for depression, previous
attempt, ethanol use, rational thinking loss
and organized plan using the SADPERSONS
score

14. • Patient was given 50g of activated charcoal
orally
7,700mg of N-Acetylcystine based on her
measured weight of 55.5kg (140mg/kg) in 500
mls of carbonated drink over one hour.

15. • Patient was subsequently referred to both the
internal medicine service and psychiatry.
• Admitted to under the internal medicine
service
• continued her N- Acetylcystine at 4.5g every
4hrly with a total of 17 doses and to get serial
liver function test done while on the ward

16. Labs
Full blood count value Normal range
Hemoglobin(hbc)
White blood count(wbc)
Mean corpuscular volume(mcv)
Platelets(plt)
Hematocrit(hct)
12.6
6.1
87.7
413
38
13-18g/dL
4-11 K/uL
76-96 fL
150-400 K/uL
40-54 %

17. Urea and electrolyte value Normal range
Sodium(Na)
Potassium (K)
Chloride (Cl)
Bicarbonate (CO²)
Urea
Creatinine (creat)
Bilirubin total(bili-t)
Alkaline phosphatase(Alp)
Alanine transaminase(Alt)
Aspartate Aminotransferase (AST)
139
3.9
101
17.3
1.4
53
5
52
15.4
26.8
138-144 mmol/L
3.1-4.1 mmol/L
101-107mmol/L
22-29 mmol/L
2.6-6.5mmol/L
68-126 umol/L
6-22 umol/L
39-106 IU/L
3-35 IU/L

18. Day 1
• Patient however developed abdominal pain
which she described as cramping in nature
associated with vomiting of ingested meal
• loose stools which were dark yellow
• she continued her N Acetylcystine but only
had 12 of the 17 recommended doses

19. Case
• she self-discharged after 3 days of admission
to return to the united kingdom to continue
her management
• She did have normal liver function test in
those 3 days of admission.

20. Paracetamol overdose
• Paracetamol or N-acetyl-p-aminophenol is a
common antipyretic and analgesic that has
been used since the 17th century
• it is especially effective for the management
of mild to moderate myalgia especially in
patients who cannot take aspirin because of
underlying bleeding or coagulation disorder

21. • It is also the most widely available over the
counter analgesic/antipyretic in the world
• single most commonly taken drug in
overdoses that lead to hospital presentation
and admission worldwide.

22. • Absorption of paracetamol is largely at the
small intestine where more than 80 percent of
the drug after undergoing first pass
metabolism in the liver
• Three mechanisms have been identified

23. • 40percent to 60 percent of the ingested
paracetamol undergo glucuronidation
• 20 percent undergo sulphonation
• 15 percent undergo N-hydroxylation and
rearrangement with cytochrome P450
enzymes

24. • All three processes result in the production of
toxic and non toxic products
• The non-toxic products eventually excreted by
the kidneys
• toxic product N-acetyl-P-benzoquinoneimine
(NAPQI) undergo detoxification by
glutathione and is eliminated in urine or bile

25. • In cases overdose sulphate and glucuronide
conjugation can be saturated
• accumulation of NAPQI and subsequent
saturation and eventual depletion of
glutathione

26. • NAPQI that is not detoxified then reacts with
sulphydryl groups on hepatocytes leading to
hepatocellular necrosis
• A minimum single dose of 150 mg/kg may be
associated with Hepatocellular damage
• EP took 100 tablets of 500 mg each which
would amount to 27,750 mg. At a dose of
150mg/kg which would amount to 8,325 mg

27. • Children however are less likely to have
paracetamol toxicity even if amount
consumed exceeds 150mg/kg because they
have more active oxidative pathway, resulting
in an increased rate of glutathione production,
thereby conferring a protective effect from
hepatotoxicity in young children

28. • Paracetamol toxicity occurs in 4 different
phase of presentation
• Summarised in the next slide

29. Phase Expected day Symptoms/signs Expected
laboratory
changes
I first 24 hours Asymptomatic,anorexia
Nausea, vomiting, malaise,
pallor and diaphoresis
Maybe normal
II 24-48 hours
after ingestion)
Phase I plus right upper
quadrant pain,hepatomegaly,
oliguria
Liver enzymes
and bilirubin
may be elevated
III 72-120 hrs after
ingestion
Phase I,II plus
hypoglycemia,signs of
hepatic
failure,jaundice,coagulopathy
Low blood
glucose,
deranged liver
function, urea
and electrolytes
IV six days to two
weeks
central nervous system
depression,shock,
hypothermia, metabolic
acidosis, hypoglycaemia,
convulsions and pulmonary
edema
Same as phase
III

30. • EP came to the accident and emergency on
day one of her ingestion, actually within the
hour after ingestion and she was
asymptomatic
• however on day 1 of admission she developed
abdominal pain and vomiting

31. case
• In centers where available, Serum
paracetamol concentrations should be
measured in any patient who admits to taking
excess paracetamol
• Prothrombin ratio (PTR) is the most sensitive
marker of ensuing liver dysfunction in
paracetamol poisoning; it becomes elevated
at 18 – 24 hours after significant ingestion.

32. • In certain centers a Nomogram to determine
the likelihood of developing hepatotoxicity
based upon plasma paracetamol levels can be
obtained. Nomogram cannot be applied if the
exact time of ingestion is unknown

33. Nomogram
plasma or serum acetimophen concentration
versus time post ingestion

34. • Management of paracetamol toxicity involve
the basics of life support which is to protect
airway, breathing and circulation
• . This might be necessary especially in patients
with multiple drug ingestion
• Paracetamol ingested as single drug rarely
causes airway compromise

35. Case
• However this also is dependent on the phase
of presentation, most patients would usually
present in phase I
• Activated charcoal can be given at a dose of
1g/kg but its efficacy in paracetamol toxicity is
yet to be established

36. Case
• Administer activated charcoal (AC) if the
patient is alert and presents
• Ideally, within 1 hour post ingestion
• Can be extended if the patient ingested an
acetaminophen-based sustained-release
medication or if the ingestion includes agents
that are known to slow gastric emptying

37. Case
• More important than gastrointestinal
decontamination after paracetamol ingestion
is the early administration of N-Acetylcysteine
• It is 100% hepatoprotective when it is given
within 8 hours after acute acetaminophen
ingestion

38. Case
• N-Acetylcysteine is composed of amino acid L-
cysteine with an acetyl molecule attached.
The former is responsible for the production
of glutathione in cells and also controls
production

39. • Acetylcysteine should be administered by
intravenous infusion preferably using Glucose
5% as the infusion fluid. Sodium Chloride 0.9%
solution may be used if Glucose 5% is not
suitable

40. • .The full course of treatment with
acetylcysteine comprises of 3 consecutive
intravenous infusions. Doses should be
administered sequentially with no break
between the infusions. The patient should
receive a total dose of 300 mg/kg body weight
over a 21 hour period

41. Case

42. • N-Acetyl cysteine carries the risk of
anaphylactoid reaction like flushing, pruritus,
rash bronchospasm and hypotension (< 2% of
patients)
• Stopping the infusion, administering an
antihistamine, and restarting N-Acetyl
cysteine at a slower infusion rate is
recommended.

43. • Oral formulation of N-Acetyl cysteine
(Mucomyst) can also be used for the
treatment of acetaminophen overdose
the route of choice and gastric decontamination
with activated charcoal prior to starting N-Acetyl
cysteine therapy does not change the
therapeutic schedule for treatment

44. • The approved dosage regimen for oral form
starts with a loading dose of 140 mg/kg,
followed by 17 doses, each at 70 mg/kg, given
every 4 hours. The total duration of the
treatment course is 72 hours

45. • In centers were N-acetylcysteine is not
available, methionine can be used (12 g orally
4-hourly, to a total of four doses) it is an
essential amino acid and an intermediate in
the biosynthesis of cysteine

46. • It is useful in paracetamol overdose because
it stimulates the production of gluthatoine
and prevents hepatic dysfunction
• Some argument in favour of methionine that
it carries less adverse effects when compared
with N-Acetylcysteine

47. • Some countries are advocating preparing
paracetamol with methionine which is then
converted into glutathione in the liver
• In chronic ingestion of paracetamol, N-Acetyl
cysteine can be commenced if the liver
function tests are deranged or persistently
elevated serum or plasma paracetamol
concentration when available.

48. Conclusion
• Paracetamol toxicity is a common
presentation in the accident and emergency
and accurate history is essential in particular
to the amount and time of ingestion.

49. • The availability of N- Acetylcysteine in the
intravenous form would be a added
advantage, the patient in this case sighted the
not so pleasant taste of the oral form of the
medication despite taking it with carbonated
soft drink as one of the reasons for
discharging against medical advice

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