Intravenous N-acetylcysteine is usually regarded as a safe antidote. However, during the infusion of the loading dose, different types of adverse drug reactions (ADR) may occur. The objective of this study was to investigate the relation between the incidence of different types of ADR and serum acetaminophen concentration in patients presenting to the hospital with acetaminophen overdose. This is a retrospective study of patients admitted to the hospital for acute acetaminophen overdose over a period of 5 years (1 January 2004 to 31 December 2008). Parametric and non-parametric tests were used to test differences between groups depending on the normality of the data. SPSS 15 was used for data analysis. Of 305 patients with acetaminophen overdose, 146 (47.9%) were treated with intravenous N-acetylcysteine and 139 (45.6%) were included in this study. Different types of ADR were observed in 94 (67.6%) patients. Low serum acetaminophen concentrations were significantly associated with cutaneous anaphylactoid reactions but not other types of ADR. Low serum acetaminophen concentration was significantly associated with flushing (p < 0.001), rash (p < 0.001) and pruritus (p < 0.001). However, there were no significant differences in serum acetaminophen concentrations between patients with and without the following ADR: gastrointestinal reactions (p = 0.77), respiratory reactions (p = 0.96), central nervous reactions (p = 0.82) and cardiovascular reactions (p = 0.37). In conclusion, low serum acetaminophen concentrations were associated with higher cutaneous anaphylactoid reactions. Such high serum acetaminophen concentrations may be protective against N-acetylcysteine-induced cutaneous ADR.
To investigate the relationship between different types of adverse drug reaction (ADR) and late time to N-acetylcysteine (NAC) infusion in patients presenting to the hospital with acetaminophen overdose.
Intravenous N-acetylcysteine (IV-NAC) is usually regarded as a safe antidote to acetaminophen overdose. However, during infusion of the loading dose, adverse drug reactions such as a headache may occur. The objectives of this study were to investigate the prevalence of headache in patients presenting to hospital after acetaminophen overdose and to determine which clinical findings are most predictive of headache among these patients. This is a retrospective cohort study of hospital admissions for acute acetaminophen overdose that was conducted over a period of 4 years from January 1, 2005 to December 31, 2008. Demographic data, clinical characteristics, and predictors of headache were analyzed. spss 15 was used for data analysis. Two-hundred and fifty-five patients were studied; their mean age was 23.1 ± 1.6; 83.9% of them were women and 14.9% had a headache during hospitalization. Headache among patients was significantly associated with IV-NAC administration (P = 0.001), intentional ingestion of drug (P = 0.04), acetaminophen concentration above 'possible toxicity' treatment line (P = 0.04), a high acetaminophen concentration (P = 0.04), and a long hospital stay (P = 0.03). Multiple logistic regression showed a significant risk factor for headache in patients administered IV-NAC (P = 0.04). We recorded a high frequency of headache in patients with acute acetaminophen overdose in our geographical area. This study suggests that among those patients, the use of IV-NAC is associated with an increased risk of headache.
Intravenous N-acetylcysteine (IV-NAC) is widely recognized as the antidote of choice for acetaminophen overdose. However, its use is not without adverse drug reactions (ADR) that might affect therapeutic outcome or lead to treatment delay.
Acetaminophen is one of the most commonly encountered medications in self-poisoning, with a high rate of morbidity. The prevalence and characteristics of acetaminophen intoxication associated with long hospital stay in patients are not well defined.
N-acetylcysteine (NAC) is an antidote to prevent acetaminophen (paracetamol-APAP)-induced acute liver injury (ALI). The 3-bag licensed 20.25 h standard regimen, and a 12 h modified regimen, are used to treat APAP overdose. This study evaluated the redox thiol response and APAP metabolites, in patients with a single APAP overdose treated with either the 20.25 h standard or 12 h modified regimen. We used liquid chromatography tandem mass spectrometry to quantify clinically important oxidative stress biomarkers and APAP metabolites in plasma samples from 45 patients who participated in a randomized controlled trial (SNAP trial). We investigated the time course response of plasma metabolites at predose, 12 h, and 20.25 h post-start of NAC infusion. The results showed that the 12 h modified regimen resulted in a significant elevation of plasma NAC and cysteine concentrations at 12 h post-infusion. We found no significant alteration in the metabolism of APAP, mitochondrial, amino acids, and other thiol biomarkers with the two regimens. We examined APAP and purine metabolism in overdose patients who developed ALI. We showed the major APAP-metabolites and xanthine were significantly higher in patients with ALI. These biomarkers correlated well with alanine aminotransferase activity at admission. Receiver operating characteristic analysis showed that at admission, plasma APAP-metabolites and xanthine concentrations were predictive for ALI. In conclusion, a significantly higher redox thiol response with the modified NAC regimen at 12 h postdose suggests this regimen may produce greater antioxidant efficacy. At baseline, plasma APAP and purine metabolites may be useful biomarkers for early prediction of APAP-induced ALI.