Anaphylactoid reactions to intravenous N-acetylcysteine: a prospective case controlled study

Since its introduction in 1977, intravenous N-acetylcysteine has become the treatment of choice for paracetamol overdose. The aim of our study was to investigate the existence of predictive factors in the likelihood of developing anaphylactoid reactions to N-acetylcysteine.

Prospective case-controlled study of all patients who presented to our emergency department (ED) between January 1997 and June 1999, and who were treated with intravenous N-acetylcysteine on the short stay observation ward.

Sixty-four patients received N-acetylcysteine infusions; thirty-one (48.4%) developed an anaphylactoid reaction. Nineteen patients who reacted were commenced on N-acetylcysteine prior to receipt of paracetamol concentrations and fifteen (48.4%) were categorised as high-risk. Seventy-one percent of reactions occurred within the first 15 min. Thirteen patients who developed a reaction, had levels which fell below the treatment lines. The levels of a further nine reactors lay above the high-risk but below the normal-risk lines. Only five patients who reacted had levels above the normal-risk line. Two of the patients who reacted to intravenous N-acetylcysteine presented at a later date with a further paracetamol overdose. Both required treatment with intravenous N-acetylcysteine, the first bag being infused over one hour. Neither developed a reaction.

We report a substantially higher incidence of anaphylactoid reactions to intravenous N-acetylcysteine than has previously been documented. It appears that these reactions are more likely to occur in high-risk patients, when plasma paracetamol concentrations were found to be below the treatment lines and in late presenters. Perhaps, giving the loading dose of N-acetylcysteine over 60 min could reduce the incidence of adverse reactions.