POISON ALERT: Changes to acetaminophen overdose recommendations go live Tuesday, June 4 2019 at 0700! Learn more

Changes to Acetaminophen Overdose Treatment

The Ontario Poison Centre has recently contacted its health care partners across the province to advise them of upcoming changes to the treatment protocol for acetaminophen-poisoned patients. Notification of the changes have been sent to Chiefs of Emergency Medicine, Intensive Care, and Internal Medicine, as well as the Directors of Pharmacy for all hospitals in Ontario, Manitoba and Nunavut. The go-live date for the new recommendations will be April 2, 2019 – in order to give hospitals time to implement necessary changes to order sets and Smart Pump programming. 

Acetaminophen accounts for approximately 10% of all calls to the Ontario/Manitoba/Nunavut Poison Centres. Traditionally, it has been treated with the antidote n-Acetylcysteine (NAC), in varying concentrations, dosing regimens and protocols. Over the last 50 years, acetaminophen has become the most published toxin in the English language literature. In terms of managing these overdoses it has been noted that:

1. One dose does not fit all. There are some patients who may need more or less NAC depending on their time of presentation following an exposure, the dose of acetaminophen taken, underlying pre-morbid state and risk factors for hepatotoxicity.
2. Drug errors are common including excessive free fluid administration, excessive sodium administration, and delay in administration of each “bag” of the old protocol
3. Anaphylactoid reactions occur especially with the rapid rate of infusion of the one hour loading dose.

In order to better meet the needs of the acetaminophen-poisoned patient and prevent unnecessary harm, our Poison Centre has decided to make significant changes to our acetaminophen treatment protocol. Moving forward, when NAC administration is deemed to be necessary following an acetaminophen exposure, based on consultation with the Poison Centre, a 3% NAC solution will be recommended. All patients will receive a loading dose administered over 4 hours at one rate, and a subsequent maintenance dose administered at a different rate until it is recommended by the Poison Centre that NAC can be stopped. The prolonged loading dose hopes to reduce the histamine release reactions that have occurred from NAC in the past. Fluid requirements are adjusted for patient weight to reduce the risk of hyper or hyponatremia.

The following FAXABLE resources have been forwarded to each hospital along with the notification.
Please note the following correction:
On the Faxable Sheet titled: Intravenous n-Acetylcysteine (NAC) TYPICAL DOSING SCENARIO: the loading dose should correctly read: "2mL/kg/hr (maximum 200 mL/hr)" (not maximum 20 mL/hr as indicated on the original document)

Typical Dosing Scenario
High Risk Patients Dosing Scenario
Guidelines to prepare a 3% IV n-acetylcysteine bag
Recommended investigations for acetaminophen-overdose patients

Selected References:
1. Wong A, Graudins A. Simplification of the standard three-bag intravenous acetylcysteine regimen for paracetamol poisoning results in a lower incidence of adverse drug reactions. ClinTox, 2016: 54(2), 115–119. http://dx.doi.org/10.3109/15563650.2015.1115055
2. Bateman, DN, et al. Reduction of adverse effects from intravenous acetylcysteine treatment for paracetamol poisoning: a randomised controlled trial., Lancet 2014; 383: 697-704.
3. Bateman, DN, et al. New Regimens for intravenous acetylcysteine, where are we now? ClinTox, 2016; 54(2): 75-78.