N-acetylcysteine as a treatment for amatoxin poisoning: a systematic review

Introduction: Amatoxin leads to the majority of deaths by mushroom poisoning around the world. Amatoxin causes gastrointestinal disturbances and multiple organ dysfunction, including liver and renal failure. As a potential treatment for amatoxin poisoning, N-acetylcysteine (NAC) has been used for decades but its benefit is still unproven.Objectives: We undertook a systematic review to evaluate the performance and safety of N-acetylcysteine on patients suffering amatoxin intoxication.Methods: We searched Pubmed, EMBASE, CENTRAL and SinoMed databases, from inception to August 31, 2019. Articles were eligible if there were five or more patients with amatoxin poisoning and N-acetylcysteine was included in the therapeutic regimen. Mortality rate including liver transplant cases (MRLTi) was the primary outcome. Mortality rate not including liver transplant cases, liver and renal function, clinical complications, as well as any adverse reactions to intravenous NAC were secondary outcomes.Results: Thirteen studies with a total of 506 patients were included. The MRLTi of amatoxin-poisoning patients with NAC treatment was 11% (57/506), and a MRLTe of 7.9% (40/506) and a liver transplantation rate of 4.3% (22/506). Transaminase concentrations generally peaked around 3 days after ingestion, prothrombin time/International Normalized Ratio (PT/INR) generally worsened during the first 3-4 days after ingestion before returning to normal four to 7 days after ingestion, and Factor V levels normalized in about 4-5 days after ingestion in patients treated with NAC. Renal failure was reported in 3% (3/101) and acute kidney injury was reported in 19% (5/27). Gastrointestinal bleeding occurred in 21% (15/71). Anaphylactoid reactions were the principle adverse reaction to NAC treatment in amatoxin-poisoning patients with an incidence of 5% (4/73).Conclusions: NAC treatment combined with other therapies appears to be beneficial and safe in patients with amatoxin poisoning. Until further data emerge, it is reasonable to use NAC in addition to other treatments for amatoxin poisoning.