Patient-Tailored Acetylcysteine Administration

Abstract

Acetylcysteine is a familiar friend of emergency physicians, intensivists, and medical toxicologists. There are 2 broad categories of acetaminophen toxicity that receive acetylcysteine therapy: acute single overdose ingestion and repeated supratherapeutic (“chronic”) ingestion. Since the 1970s, we have used acetylcysteine to reduce liver injury and death in patients with an acute overdose ingestion of acetaminophen. The introduction of an intravenous formulation of acetylcysteine in the United States has fostered the adaptation of a shorter period of acetylcysteine administration, 20 hours instead of 72 hours. Both of these time-based protocols imply that all cases of acetaminophen toxicity receive the same duration of therapy. However, clinical experience indicates that a patient who presents late ( 8 hours after ingestion) or who already has manifested liver injury after a single acute overdose needs a longer duration of acetylcysteine therapy than a patient who presents soon (within 8 hours) after acute overdose ingestion. Further, in many patients who receive acetylcysteine, the exact time of acute ingestion is unknown, or the ingestion has occurred during an unknown period. Although a variety of dosage regimens has been proposed for the various patterns of acetaminophen overdosage, the optimal duration of acetylcysteine therapy is unknown. Currently, the administration of acetylcysteine is determined by the individual physician, with very little information to guide the decision. In this issue of Annals, Betten et al report a poison center study of truncated acetylcysteine therapy for acute overdose ingestion of acetaminophen. Their results indicate that treatment with oral acetylcysteine for 20 to 48 hours was associated with excellent outcomes. The study has weaknesses, but the authors addressed major concerns, particularly the concern that poor outcomes may have been missed in patients lost to follow-up. We believe the implications by Betten et al go farther, exposing a more fundamental issue of medical importance. The concepts of patient-tailored therapy and goal-directed therapy have enjoyed growing acceptance in recent years. The concept involves treating the patient’s condition only as long as necessary, as determined by their clinical condition. Betten et al used a compound clinical endpoint to recommend termination of acetylcysteine therapy. Defining treatment as a period (eg, 20 hours) is much different from treatment to a clinical endpoint. For example, the 20-hour