We need a standardized North American acetylcysteine dosing regimen for the treatment of paracetamol (acetaminophen) poisoning.

INTRODUCTION: Acetylcysteine is the antidote for paracetamol (acetaminophen) poisoning. Prescott and colleagues introduced it in the 1970s as a three-infusion regimen. This regimen became standard care for several decades. Its efficacy is accepted, though its use is associated with low morbidity adverse effects that interrupt patient care. The complexity of the regimen is a source for dosing errors. These issues have spurred the development of multiple new regimens. Recently, an expert panel of the four North American clinical toxicology societies published a guideline for the treatment of paracetamol (acetaminophen) poisoning. They were unable to achieve consensus for a specific acetylcysteine regimen.

TWO-BAG VERSUS ONE-BAG TWO-STEP REGIMENS: Acetylcysteine intravenous regimens are classified as three-bag (the original regimen described by Prescott and colleagues), two-bag, and one-bag two-step. The latter two were developed to mitigate the shortcomings of the original regimen of Prescott and colleagues. The two-bag regimen requires the preparation of two unique patient weight-based solutions intended to be sequentially and completely infused. The one-bag two-step regimen consists of the preparation of a large volume of a standardized concentrated acetylcysteine solution. It serves as a reservoir intended to support both the initial and maintenance infusions. Shift to maintenance requires a ten-fold decrease in the infusion rate (the second step). The two-bag regimen employs unit-dose drug administration, a cardinal safety principle of drug therapy. It prevents overdose of the prescribed drug.

UNIQUE RISK OF THE ONE-BAG TWO-STEP REGIMEN: Failure to decrease the rate of infusion, the second step of the one-bag two-step regimen, risks overdose of acetylcysteine, which can produce encephalopathy. Features include coma, seizures, cerebral edema, and increased intracranial pressure. The prognosis is poor and often fatal. The three and two-bag regimens consist of unit-dose solutions intended to be completely infused. This prevents this specific error, which is the root cause of iatrogenic deaths due to the one-bag two-step regimen. Smart pumps programmed to trigger the second step address this issue. However, they are not universally available. This is particularly so in resource-challenged medical environments such as small rural hospitals and non-physician staffed facilities in remote, isolated communities.

DISCUSSION: There is a need for a North American acetylcysteine regimen as recommended by the Institute for Safe Medication Practices. This would support prompt and safe care by front-line providers by diminishing uncertainty, confusion, and the risk for medical error. Acetylcysteine overdose is uncommon but has clinically significant morbidity and mortality. Most deaths are due to unique dosing or administration errors. However, the one-bag two-step regimen has a shortcoming that has resulted in repeat deaths, thus making the two-bag regimen a safer choice.

THE WAY FORWARD: There is a need for a North American acetylcysteine regimen. The four North American clinical toxicology societies should commission an expert panel with the mandate to recommend a specific acetylcysteine dosing regimen for the treatment of paracetamol (acetaminophen) poisoning. The recent systematic review and meta-analysis, the lack of published data showing the advantage of the one-bag two-step regimen over the two-bag approach, and its unique hazard support a two-bag regimen.