Acetaminophen poisoning

Acetaminophen
Poisoning
in children
Prof. Dr. Saad S Al Ani
Senior Pediatric Consultant
Head of Pediatric Consultant
Khorfakkan Hospital , Sharjah, UAE
saadsalani@aol.com

Acetaminophen
Is a nonsteroidal anti-inflammatory drug with
potent antipyretic and analgesic actions but with
very weak anti-inflammatory activity
1/22/2015
Acetaminophen poisoning
Prof.Dr.Saad S Al Ani Khorfakkan Hospital
2
http://cid.oxfordjournals.org/content/31/Supplement_5/S202.full
dailymed.nlm.nih.gov

Acetaminophen can be:
- Unintentionally ingested by young children
-Taken in an intentional overdose by adolescents
and adults
- Inappropriately dosed in all ages
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Acetaminophen
www.turbosquid.com

Acetaminophen toxicity
Results from the formation of a highly
reactive intermediate metabolite, N-acetyl-
p-benzoquinone imine (NAPQI)
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www.prevention.com

Acetaminophen Metabolism
42% - 67%
26% - 36%
5% - 8%
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1
2
3
acetadote.com

NAPQI
In therapeutic use:
Only a small percentage of a dose (approximately
5%) is metabolized by the hepatic cytochrome P450
enzyme CYP2E1 to NAPQI, which is then
immediately conjugated with glutathione to form a
nontoxic mercapturic acid conjugate.
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drugstudy.weebly.com

In overdose:
Glutathione stores are overwhelmed, and free
NAPQI is able to combine with hepatic
macromolecules to produce hepatocellular
damage
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NAPQI (Cont.)
www.walmart.com

Acute toxic dose of acetaminophen
The single acute toxic dose of acetaminophen is
generally considered to be >200 mg/kg in
children
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www.13wmaz.com

Acute toxic dose of acetaminophen
(Cont.)
Supratherapeutic doses ( >75 mg/kg/day for
consecutive days) can lead to hepatic injury or
failure in some children, especially in the setting
of :
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Fever
Dehydration
Poor
nutrition
Other conditions
↓
↓glutathione stores

Clinical & Laboratory manifestations
Classically, four stages of acetaminophen
toxicity have been described
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fox8.com

Stages of acetaminophen toxicity
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Stage 1
• Within first 0.5 -24 hr
• Clinically:
Anorexia ,Nausea ,Vomiting ,Malaise,
Pallor ,Diaphoresis
• Lab findings :
Normal except acetaminophen level
www.boiseweekly.com

Stages of acetaminophen toxicity (cont.)
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Stage 2
• Within 24-48 hr
• Clinically:
-Resolution of earlier symptoms
-Right upper quadrant abdominal pain and
tenderness
• Lab findings :
-↑Bilirubin , Prothrombin time ,Hepatic
enzymes
- Oliguria
www.sooothe.com

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Stage 3
• Within 72-96 hr
• Clinically& Lab findings:
- Peak liver function abnormalities
- Fulminant hepatic failure
- Multisystem organ failure
- Potential death
http://www.3dchem.com/molecules

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Stage 4
• Within 4 days – 2 weeks
• Clinically& Lab findings:
- Resolution of liver abnormalities
- Clinical recovery precedes histologic recovery
www.lef.org

Laboratory investigations
If a toxic ingestion is suspected, a serum
acetaminophen level should be measured 4 hr
after the reported time of ingestion.
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For patients who present to medical care >4
hr after ingestion, a stat acetaminophen level
should be obtained.
curriculum.toxicology.wikispaces.net

Laboratory investigations (cont.)
Acetaminophen levels obtained <4 hr after
ingestion are difficult to interpret and cannot be
used to estimate the potential for toxicity.
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Other important baseline labs include :
- Hepatic transaminases
- Renal function tests
- Coagulation parameters www.ganfyd.org

Rumack-Matthew nomogram for
acetaminophen poisoning
This nomogram is only
intended for use in
patients who present
within 24 hr of a single
acute acetaminophen
ingestion with a known
time of ingestion
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www.rxlist.com

acetaminophen poisoning(CONT.)
Any patient with a
serum acetaminophen
level in the possible or
probable hepatotoxicity
range per the Rumack-
Matthew nomogram
should be treated with
N-acetylcysteine (NAC)
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acetaminophen poisoning(CONT.)
Patients who have an
initially nontoxic level and
have ingested combination
products or co-ingestants
that can slow GI motility
(e.g., diphenhydramine,
opioids) should have a
second acetaminophen
level drawn 6-8 hr after
ingestion
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Unknown time of ingestion or a history of chronic
supratherapeutic ingestion?
For assessment of such patient,
check :
- Acetaminophen level
- Hepatic transaminases
- Coagulation parameters.
If the acetaminophen level is
>10 μg /mL, even with normal
liver function tests, this patient
is a candidate to be treated
with NAC
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Why?
To catch patients in the
asymptomatic phase of
toxicity,before hepatotoxicity
develops, because a level of
10 g/ mL is potentially toxic
at 20 hr after ingestion
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Remember
Patients who have any signs
of hepatotoxicity (elevated
transaminases and international
normalized ratio [INR]), even
with a low or nondetectable
acetaminophen level, are
also candidates for antidotal
therapy
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Remember (cont.)
Patients who have an
acetaminophen level <10
μg/mL and normal
transaminases are unlikely to
develop significant toxicity.
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Treatment
•Initial treatment :
• Basic life support (ABCs)
• Decontamination with activated
charcoal (within 1-2 hr of
ingestion)
• The antidote for acetaminophen
poisoning is N- acetylcysteine
(NAC) ( which works primarily
via replenishing hepatic
glutathione stores )
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http://www.drclarkstore.eu/images/P/45171-Activated-Charcoal.jpg
www.iherb.com

N- acetylcysteine (NAC)
• Most effective when initiated
within 8 hr of ingestion
• There is no demonstrated benefit
to giving NAC before the 4 hr
post-ingestion mark.
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www.sedico.net
www.shinsheng.com.tw

N- acetylcysteine (NAC) (cont.)
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NAC is available in
oral and intravenous
forms, and both forms
are equally efficacious
26
www.drugstore.com
www.indiamart.com

•
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N- Acetylcysteine (Mucomyst)
Dosage: 140 mg /kg loading ,followed by 70 mg / Kg
every 4 hrs. for 17 doses
Route of administration : Oral
Side effects: Nausea ,vomiting
N.B. Most effective if given within 8 hr of ingestion
eshop.chothuoc24h.com

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N- Acetylcysteine (Acetadote)
Dosage: 150 mg /kg over 1 hr ,followed by 50 mg /
Kg over 4 hrs. followed by 100 mg /Kg over 16 hrs.
Route of administration : IV
Side effects: Anaphylactoid reactions
(most commonly with loading dose)
thehealthscience.com www.webmd.com

What is next
A patient who is being on NAC ,the following
lab tests : Transaminases, synthetic function, and
renal function should be followed daily
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Patients who develop hepatic failure in spite of
NAC therapy may be candidates for liver
transplantation

King’s College criteria
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• Are used to determine which patients should
be referred for consideration of liver
transplant.
• These criteria include :
1. Acidosis (pH <7.3) after adequate fluid
resuscitation,
2. Coagulopathy (prothrombin time [PT] >100
sec),
3. Renal dysfunction (creatinine >3.4 mg/dL),
4. Hepatic encephalopathy grade III or IV

References
• Dart RC, Rumack BH: Patient-tailored acetylcysteine administration, Ann Emerg Med
50:280–281, 2007
• Centers for Disease Control and Prevention: Fatal poisoning among young children from
diethylene glycol–contaminated acetaminophen—Nigeria, 2008–2009, MMWR Morb Mortal
Wkly Rep 58:1345–1346, 2009.
• http://www.healthdietmedicine.com/side-effects-of-acetaminophen-paracetamol/
• http://cid.oxfordjournals.org/content/31/Supplement_5/S202.full
• "Paracetamol". University of Oxford Centre for Suicide Research. 25 March 2013.
• "Paracetamol overdose: new guidance on treatment with intravenous acetylcysteine". Drug
Safety Update 6 (2): A1. September 2012.
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Acetaminophen poisoning

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