AIMS: To investigate the relationship between decontamination procedures and seizure events caused by venlafaxine overdose and to estimate the time at which 90% of patients would have had their first seizure in the presence and absence of decontamination. METHODS: Data were collected from 319 patients who took an overdose of venlafaxine on 436 occasions. Seizures occurred on 24 of 436 occasions (5%). Patients received one of single dose activated charcoal (SDAC), whole bowel irrigation (WBI), a combination of either (SDAC/WBI) or no decontamination. Logistic regression and time to event analysis were used to investigate the influence of dose and decontamination on the probability of seizures and time to 90% (t(90) ) of seizure, respectively. RESULTS: A linear logistic regression model described the data. Simulation from the model showed that the probability of seizure was 0.05 (0.03-0.08), 0.19 (0.09-0.35) and 0.75 (0.30-0.96) at 1000, 5000 and 10 000 mg, respectively (median and 95% credible interval). At the mean dose of 2100 mg the odds ratios (OR) in the presence of SDAC, WBI and SDAC/WBI were 0.48 (0.25-0.89), 0.71 (0.35-1.22) and 0.25 (0.08-0.62), respectively. A modified Gompertz model described the time to seizure events. Simulations from the Gompertz model showed that the t(90) values for first seizure was 26 h and was not affected by dose or decontamination procedure. CONCLUSION: SDAC/WBI provided greater benefits than the sum of the independent effects of SDAC and WBI. Patients should be observed for at least 24 h for seizures based on the dose and risk of seizure occurring.
AIMS: To investigate the relationship between decontamination procedures and seizure events caused by venlafaxineoverdose and to estimate the time at which 90% of patients would have had their first seizure in the presence and absence of decontamination. METHODS: Data were collected from 319 patients who took an overdose of venlafaxine on 436 occasions. Seizures occurred on 24 of 436 occasions (5%). Patients received one of single dose activated charcoal (SDAC), whole bowel irrigation (WBI), a combination of either (SDAC/WBI) or no decontamination. Logistic regression and time to event analysis were used to investigate the influence of dose and decontamination on the probability of seizures and time to 90% (t(90) ) of seizure, respectively. RESULTS: A linear logistic regression model described the data. Simulation from the model showed that the probability of seizure was 0.05 (0.03-0.08), 0.19 (0.09-0.35) and 0.75 (0.30-0.96) at 1000, 5000 and 10 000 mg, respectively (median and 95% credible interval). At the mean dose of 2100 mg the odds ratios (OR) in the presence of SDAC, WBI and SDAC/WBI were 0.48 (0.25-0.89), 0.71 (0.35-1.22) and 0.25 (0.08-0.62), respectively. A modified Gompertz model described the time to seizure events. Simulations from the Gompertz model showed that the t(90) values for first seizure was 26 h and was not affected by dose or decontamination procedure. CONCLUSION:SDAC/WBI provided greater benefits than the sum of the independent effects of SDAC and WBI. Patients should be observed for at least 24 h for seizures based on the dose and risk of seizure occurring.
Authors: V V P Kumar; S Oscarsson; L E Friberg; G K Isbister; L P Hackett; S B Duffull Journal: Clin Pharmacol Ther Date: 2009-07-15 Impact factor: 6.875
Authors: Geoffrey K Isbister; Lena E Friberg; Barrie Stokes; Nicholas A Buckley; Christopher Lee; Naren Gunja; Simon G Brown; Ellen MacDonald; Andis Graudins; Anna Holdgate; Stephen B Duffull Journal: Ann Emerg Med Date: 2007-08-23 Impact factor: 5.721