Acetaminophen Poisoningin 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

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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

- Oliguriawww.sooothe.com

Stages of acetaminophen toxicity (cont.)

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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

Stages of acetaminophen toxicity (cont.)

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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

Rumack-Matthew nomogram for

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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Rumack-Matthew nomogram for

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 activatedcharcoal (within 1-2 hr ofingestion)

• The antidote for acetaminophenpoisoning is N- acetylcysteine(NAC) ( which works primarilyvia replenishing hepaticglutathione 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.)

1/22/2015

NAC is available in

oral and intravenous

forms, and both forms

are equally efficacious

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www.drugstore.com

www.indiamart.com

N- acetylcysteine (NAC) (cont.)

•

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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

N- acetylcysteine (NAC) (cont.)

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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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