(1007) Guideline Gaps: Current APAP Toxicity Treatment Protocols May Result in Premature NAC Termination

Introduction: Identification of patients requiring prolonged treatment with N-acetylcysteine (NAC) for acetaminophen (APAP) toxicity remains challenging with a limited evidence base to guide clinicians. Commonly accepted NAC cessation criteria include AST < 1000, absence of clinical symptoms, and undetectable APAP level after 20 hours of infusion. The NACSTOP trial suggested that earlier cessation at 12 hours is likely safe in low-risk patients. We report a higher-risk patient whose liver function worsened precipitously after per-protocol cessation of therapy.

Description: A 55-year-old male without chronic liver disease presented in acute hepatic dysfunction following ingestion approximately 16 hours prior to presentation of at least 5 grams of an unknown APAP formulation. A standard three-bag NAC infusion was initiated (T0) according to the Rumack-Matthew dosing nomogram. Adjunctive IV fomepizole was also administered because the INR (1.7) and lactate (6.2 mmol/L) suggested significant hepatic injury. AST peaked (786 U/L) 6 hours after T0 (T0+6h) and was 682 U/L with undetectable serum APAP at T0+21h. Lactate normalized and the patient remained asymptomatic and hemodynamically stable, yet the INR remained at 1.9. Per facility protocol and Poison Control recommendations, NAC was terminated at T0+25h and interval liver chemistry checks were continued at 4-hour intervals. By T0+28h, AST rebounded to 1130 U/L, and NAC was resumed. AST peaked again at T0+39h at 2911 U/L with simultaneous INR of 2.6. AST remained >1000 U/L until T0+76h. NAC was discontinued at T0+120h when INR was 1.0 and AST 117 U/L.

Discussion: Current NAC cessation criteria in acute APAP toxicity do not identify all patients that require prolonged therapy and can lead to premature cessation of therapy. Adjunctive medications, such as fomepizole, may also modify the use of the criteria. Alternative criteria should be explored.