Anaesthesia, critical care & pain medicine · 2020
Baclofen self-poisoning: Is renal replacement therapy efficient in patient with normal kidney function?
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Brunet Marion, Léger Maxime, Billat Pierre-André, Lelièvre Bénédicte, Lerolle Nicolas, Boels David, Le Roux Gaël
Аннотация
AIMS: We aimed at assessing the effectiveness of renal replacement therapy in patients severely self-poisoned with baclofen and with normal kidney function.
METHODS: A population pharmacokinetic model was built using analytical data extracted from 26 baclofen poisoning cases reported to a French Poison Centre: 8 patients underwent renal replacement therapy (RRT), 18 did not. In the RRT group, 2 patients suffered from kidney failure. Mechanical ventilation was required for 20 patients with normal kidney function; 15 were not treated by RRT and 5 were. Pharmacokinetic profiles of baclofen were measured in 28 patients and further modelled by a non-parametric approach (PMetrics®). The total data set was divided into a building data set (26 patients, 57 observations) and a validation set (2 external patients, 6 observations). Then, the estimated elimination half-life of baclofen and the duration of intubation were compared in patients with or without RRT using Wilcoxon-Mann-Whitney test.
RESULTS: A model using three parameters plus a lag time and bioavailability was necessary to determine the pharmacokinetics of baclofen. Estimated elimination half-life in the 'RRT' group and the 'no RRT' group were respectively 3.1 [2.2-4.8] h (n = 6 patients) and 3.4 [1.4-5.5] h (n = 19 patients, p = 0.53). The median duration of intubation was not significantly different between groups (72 [48-72] h and 72 [24-96] h, respectively; p = 0.38).
CONCLUSION: Renal replacement therapy did not appear to significantly increase baclofen clearance in patients without kidney failure.
METHODS: A population pharmacokinetic model was built using analytical data extracted from 26 baclofen poisoning cases reported to a French Poison Centre: 8 patients underwent renal replacement therapy (RRT), 18 did not. In the RRT group, 2 patients suffered from kidney failure. Mechanical ventilation was required for 20 patients with normal kidney function; 15 were not treated by RRT and 5 were. Pharmacokinetic profiles of baclofen were measured in 28 patients and further modelled by a non-parametric approach (PMetrics®). The total data set was divided into a building data set (26 patients, 57 observations) and a validation set (2 external patients, 6 observations). Then, the estimated elimination half-life of baclofen and the duration of intubation were compared in patients with or without RRT using Wilcoxon-Mann-Whitney test.
RESULTS: A model using three parameters plus a lag time and bioavailability was necessary to determine the pharmacokinetics of baclofen. Estimated elimination half-life in the 'RRT' group and the 'no RRT' group were respectively 3.1 [2.2-4.8] h (n = 6 patients) and 3.4 [1.4-5.5] h (n = 19 patients, p = 0.53). The median duration of intubation was not significantly different between groups (72 [48-72] h and 72 [24-96] h, respectively; p = 0.38).
CONCLUSION: Renal replacement therapy did not appear to significantly increase baclofen clearance in patients without kidney failure.