<i>N</i>‐acetylcysteine for acetaminophen toxicity: The one‐bag regimen

We read with interest the recent commentary by Isbister and Chiew1 reviewing recent developments in the use of N-acetylcysteine (NAC) for the treatment of acetaminophen (APAP) toxicity. While we appreciate the authors' clear and succinct review of this exciting field, they omitted discussion of an important alternative NAC regimen that deserves readers' attention. We have used a one-bag NAC regimen for almost two decades. Unlike the standard FDA-approved three-bag regimen and some of the alternative regimens discussed in the editorial, our regimen uses a single standardized concentration of NAC for all patients (30 g of NAC in 1 L of 5% dextrose in water). We administer an initial bolus of 150 mg/kg NAC over 1 hour from this bag. After the bolus is complete, we make a single rate change to an infusion of 12.5 mg/kg/h (from the same bag), which continues until the patient meets clinical and laboratory criteria for cessation of antidotal therapy. This regimen has several advantages. First, the use of a single standardized concentration of NAC (as opposed to patient-specific concentrations in the three-bag and two-bag approaches) standardizes, simplifies and speeds antidote preparation. This reduces dosing and preparation errors, which are common under the three-bag approach.2, 3 Second, the use of a single bag eliminates the need to order and await delivery of additional bags of NAC, which can lead to significant interruptions in antidotal therapy.4, 5 Third, the elimination of multiple rate changes simplifies nursing workflow and decreases the risk of administration errors. Finally, we use programmable smart pumps (BD Alaris, Benton, Dickinson & Co., Franklin Lakes, NJ, USA) set with this standard concentration. These pumps automatically change the rate from the bolus to the infusion to eliminate another potential delay or error in administration. This regimen delivers slightly more NAC than the standard three-bag approach (assuming 21 hours of therapy, a total dose of 400 mg/kg as opposed to 300 mg/kg). Isbister and Chiew note in their commentary that doubling the dose of the second infusion bag in the two-bag regimen to produce a total dose of 400 mg/kg may be helpful in large APAP overdoses; our regimen essentially “builds in” this added safety factor. It also ensures that the infusion does not run out immediately after the completion of the standard 21-hour course, which is essential to prevent interruptions in therapy in cases requiring prolonged treatment with NAC. This regimen is effective and well tolerated with very infrequent interruptions in therapy and a lower error rate than the standard three-bag protocol.6 Repeated studies of this regimen have demonstrated safety, with a low rate of minor adverse events.7, 8 It is also in use at multiple other academic medical centres in the United States and three regional poison control centres in Canada.9, 10 We believe that the one-bag regimen deserves further rigorous study and widespread adoption in clinical practice. Discussion of this regimen would have enhanced Isbister and Chiew's already excellent commentary. The authors have no competing interests to declare. All authors discussed and planned the content of the letter. K.B. drafted the letter. A.F., D.L., J.D., E.S. and M.M. reviewed, commented on, and edited the letter.

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