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Interdisciplinary management of acute acetaminophen poisoning guided by therapeutic drug monitoring

European Statement

Patient Safety and Quality Assurance

Author(s)

Irene Centeno López, Eva M Legido Perdices, Maria José Cano Cano, Salvador Benlloch Pérez, Federico Peydró Tomás, José Manuel Ventura Cerdá

Why was it done?

Acetaminophen is the most used antipyretic and analgesic drug around the world. Intentional and non-intentional acetaminophen overdose is related to acute liver failure and it is important to start the treatment during the first hours after the intake to reduce liver injury. The main treatment to prevent liver failure is n-acetilcysteine (NAC) and it is administered depending on acetaminophen plasmatic concentrations using Rumack-Matthew nomogram during the first 24 hours. Variability in sampling time and duration of NAC administration was detected when acetaminophen intake was unknown or above the first 24h. Moreover, different NAC administration protocols were used in our institution.

What was done?

An interdisciplinary team involving Hospital Pharmacy, Emergency, Gastroenterology Department and Critical Care Unit was created to establish an agreed protocol for the management of acute acetaminophen poisoning.

How was it done?

The interdisciplinary team agreed the following procedures:
– To change the traditional NAC protocol of three intravenous infusions (150 mg/kg over 1 h, 50 mg/kg over 4h and 100 mg/kg over 16h) to the SNAP protocol of two bags (100 mg/kg over 2h and 200 mg/kg over 10h) reducing duration of administrations from 21 to 12 h.
– To establish the sampling times for the determination of acetaminophen serum concentrations: the extraction will be 4h after the ingestion during the first 24h of the intake. When time is unknown or greater than 24h, two samples separated by at least 2h will be extracted to calculate acetaminophen half-life to assess the probability of liver damage (high probability when half-life (t1/2)>4h).
– Define NAC discontinuation when INR<1.3, transaminases are in normal range and acetaminophen concentration<10 mcg/ml. If one of these parameters remains altered, the last NAC perfusion must be repeated.

What has been achieved?

– Reduce the duration of NAC treatment in the Emergency and hospitalization rooms if all analytical parameters are normalised.
– Reduce the variability in the management of acetaminophen poisoning and sampling time.
– To perform a closer clinical follow up of intoxicated/over-medicated patients.

What next?

Measure the reduction of hospital admissions and safety improvement by modifying NAC administration protocol and therapeutic drug monitoring of acetaminophen.

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