Identification of patients at risk of anaphylactoid reactions to N-acetylcysteine in the treatment of paracetamol overdose.

N-acetylcysteine (NAC) is acknowledged as an effective antidote for paracetamol overdose. However, adverse effects to NAC are common and may be a point of concern for the patient and the treating physician. The aim of the present study was to further analyse possible risk factors of anaphylactoid adverse effects to intravenous NAC in order to identify individual patients or groups of patients at particular risk. This study is an observational case series of adverse effects to NAC administered according to the standard guidelines in patients who presented with paracetamol overdose between March 1999 and September 2011. A total of 1218 admissions for paracetamol overdose receiving intravenous NAC were recorded in 950 patients. Anaphylactoid adverse effects occurred in 18.6%. The proportion of cases with adverse effects gradually declined from 25.9% in cases with undetectable p-paracetamol to 6.3% in cases with p-paracetamol above 1.5 mmol/L (226 μg/mL) (Spearman Rank R-test: p < 0.00001). The proportion of cases with adverse effects was significantly higher in cases of non-Danish origin than that of Danish origin (28.5% vs. 15.1%; Chi-square: p < 0.00001). In patients with repeated exposure to NAC, the rate of adverse effects on re-exposure was significantly higher in patients with a previous reaction to NAC compared to those without a previous reaction (Rate Ratio 6.2; 95% CI 2.9-17.1). The development of anaphylactoid adverse effects to intravenous NAC was strongly associated with a low p-paracetamol, non-Danish origin and a history of previous reaction to NAC. These adverse effects are common, but usually mild and easily manageable. The incidence of adverse effects may be reduced by pre-treating selected patients with antihistamines, in particular those with a previous reaction to NAC.