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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Effect of acute versus chronic intoxication on clinical features of theophylline poisoning in children.

OBJECTIVES: To determine whether the method of intoxication influences the metabolic disturbances and pattern of life-threatening events that occur after theophylline intoxication in children. METHODS: Five-year prospective observational study of consecutive pediatric patients referred to a regional poison control center with a theophylline concentration (theo) greater than or equal to 30 micrograms/ml. At the time of referral, intoxication was categorized as acute (single toxic exposure), chronic (long-term toxic exposure), or acute-on-therapeutic (single toxic exposure superimposed on maintenance therapy). RESULTS: One-hundred twenty-five patients were monitored. Mean age was 12 years (range, 3 days to 20 y). Seventy-four patients (59%) had acute intoxication, 31 (25%) had chronic intoxication, and 20 (16%) had acute-on-therapeutic intoxication. Mean peak serum (theo) was 55 micrograms/ml. Life-threatening events occurred in 12 patients (10%). Patients with acute intoxication had a significantly lower serum potassium level (3.04 vs 3.80 mmol/L; p less than 0.001) and higher serum glucose level (10.8 vs 7.0 mmol/L (194 vs 127 mg/dl); p less than 0.001) than did children with chronic intoxication. Although life-threatening events (seizures or arrhythmias) occurred at a similar rate across categories, the (theo) at which these events occurred was significantly higher in patients with acute intoxication than in those with chronic intoxication (100 vs 42 micrograms/ml; p = 0.02). Among children with chronic intoxication, those who had life-threatening events had (theo) similar to those who remained well (42 vs 47 micrograms/ml) but were significantly younger (1.6 vs 8.0 years; p less than 0.001). CONCLUSIONS: These data indicate that method of intoxication has significant effects on the metabolic and clinical consequences of theophylline poisoning. Life-threatening events occur in those with acute theophylline intoxication at significantly higher (theo) than in those with chronic intoxication. After chronic intoxication, peak (theo) does not identify patients at risk for life-threatening events; young age appears to be the primary risk factor. These findings potentially complicate the management of theophylline poisoning, given the difficulty of extracorporeal drug removal in young infants.[1]


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