Paracetamol Overdose
Introduction
Paracetamol overdose, due to the availability of paracetamol, is one of the most common overdoses seen in Irish Emergency Departments. Paracetamol is metabolised in the liver and it is conjugated to sulphate and glucuronide. However if this mechanism is overwhelmed (like it is in overdose) a toxic metabolite, N-acetyl-p-benzoquinone imine (NAPQI) is created in large quantities via cytochrome P450 system, leading to acute liver injury. Acute liver injury and subsequent liver failure is the mechanism by which paracetamol overdose may be fatal or cause long term problems.
Risk Factors
Risk factors for significant liver injury include;
Ingestion > 150mg/kg
Signs of liver toxicity at initial presentation
late presentation > 12 hours post ingestion
history of high alcohol consumption or chronic liver failure
malnutrition, HIV, chronic diseases
Clinical Features
Symptoms
Nausea
Vomiting
RUQ pain (late >12 hours after ingestion)
Signs
24 - 72 hours
RUQ tenderness
Jaundice
Oliguria
<24 hours
vomiting
diaphoresis
Pallor
>72 hours
Hypoglycaemia
Confusion
Altered consciousness / Coma
Death
Differential Diagnosis
Frequently patients presenting after a toxic ingestion of paracetamol tell is that they have taken an overdose of paracetamol, however sometimes patients present with the symptoms described above but don’t disclose taking a toxic dose of paracetamol including on direct questioning about paracetamol. A high index of suspicion is required patients presenting with signs of acute liver injury with no obvious precipitant.
Patients also take accidental supra-therapeutic doses of paracetamol when self treating severe pain either by exceeding the recommended dose on the package or taking multiple paracetamol containing products ie: paracetamol and solpadiene and kapake etc. A careful analgesic history should be taken for all patients presenting with pain, particularly if they have symptoms or signs of liver injury
Other causes of the above clinical presentation include;
Alcoholic liver disease
Auto-immune hepatitis
Acute hepatic injury (other toxins)
Infective acute hepatitis
Clinical Investigations
Bedside
Glucose
bedside finger stick glucose in all patients with altered consciousness
Urine dip
may show bilirubin in late presentations
ECG
in case of polypharmacy overdose, patients may have co-ingested medications that affect the QT or QRSD
VBG
Check lactate and pH
Laboratory
FBC, U/E, LFT, Coag screen - all taken on arrival
Paracetamol level should only be taken 4 hours after ingestion, or on arrival in ED if >4 hours have elapsed since ingestion
Radiology
Radiology investigations are not usually required in paracetamol overdose however ultrasound gallbladder or liver may be useful in ruling out alternative diagnoses.
Management & Disposition
Initial Resuscitation
As with every ED patients check and manage A, B, Cs,
VBG & bloods
Check glucose, treat if needed
Reduced GCS is suggestive of severe ingestion or ingestion of other substances with paracetamol
Symptomatic Treatment
If signs of dehydration - fluid management
oral fluids if able to tolerate
iv fluids if unable to tolerate oral fluids
Treat nausea with anti-emetics
Specific Treatement
The approach to specific treatment is different depending on where the patient took a single acute overdose or a staggered overdose. A staggered overdose is excessive ingestion of paracetamol over greater than 1hour.
Always check Toxbase.org or your local toxicology resource for the most up to date information.
Single Acute Overdose
Check units carefully as different assays may use different units
Staggered Overdose
commence NAC without delay
>4hrs after last paracetamol ingested take bloods
FBC, U&E, LFT, Coag, Paracetamol Level
NAC may be discontinued if all of the following criteria are met;
paracetamol concentration <10mg/L
ALT within the normal range*
INR < 1.3*
Patient has no symptoms suggesting liver injury
*Patients with chronic liver disease may have an elevated ALT and INR at baseline, in these patients if their ALT and INR are at baseline NAC can be discontinued
Disposition
Disposition depends on a number of different factors
Is treatment with NAC required
Is there a clinical decision unit (CDU) who look after patients with toxicological presentations
Is there a liason psychiatry service on site 24 hours a day
Check local guidelines for exact management however general rules include;
All patients with intentional overdose should have a liason psychiatry referral
Patients requiring NAC will require admission either to a CDU or the acute floor under the medical team on call
References
This blog was written by Dr. Kasia Domanska and was last update in December 2020
Before you go have another look at the clinical case and see have your answers to any of the questions changed and if so how?