Paracetamol-associated acute liver failure in Australian and New Zealand children: high rate of medication errors.

BACKGROUND: In children, paracetamol overdose due to deliberate self-poisoning, accidental exposure or medication errors can lead to paediatric acute liver failure and death. In Australia and New Zealand, the nature of ingestion and outcomes of paracetamol-associated paediatric acute liver failure have not been described. OBJECTIVE: To describe the nature and outcomes of paracetamol-associated paediatric acute liver failure. DESIGN: Retrospective analysis of paracetamol-associated paediatric acute liver failure cases presenting 2002-2012. SETTING: New Zealand and Queensland Paediatric Liver Transplant Services. RESULTS: 14 of 54 cases of paediatric acute liver failure were attributed to paracetamol, the majority were secondary to medication errors. 12 of the 14 children were under the age of 5 years. Seven children received doses in excess of 120 mg/kg/day. Many of the other children received either a double dose, too frequent administration, coadministration of other medicines containing paracetamol or regular paracetamol for up to 24 days. Three children underwent transplant. One of these and one other child died. CONCLUSIONS: In Australia and New Zealand, paracetamol overdose secondary to medication errors is the leading cause of paediatric acute liver failure. A review of regional safety practices surrounding paracetamol use in children is indicated.

Artificial neural network is highly predictive of outcome in paediatric acute liver failure.

Current prognostic models in PALF are unreliable, failing to account for complex, non-linear relationships existing between multiple prognostic factors. A computational approach using ANN should provide superior modelling to PELD-MELD scores. We assessed the prognostic accuracy of PELD-MELD scores and ANN in PALF in children presenting to the QLTS, Australia. A comprehensive registry-based data set was evaluated in 54 children (32M, 22F, median age 17 month) with PALF. PELD-MELD scores calculated at (i) meeting PALF criteria and (ii) peak. ANN was evaluated using stratified 10-fold cross-validation. Outcomes were classified as good (transplant-free survival) or poor (death or LT) and predictive accuracy compared using AUROC curves. Mean PELD-MELD scores were significantly higher in non-transplanted non-survivors (i) 37 and (ii) 46 and transplant recipients (i) 32 and (ii) 43 compared to transplant-free survivors (i) 26 and (ii) 30. Threshold PELD-MELD scores ≥27 and ≥42, at meeting PALF criteria and peak, gave AUROC 0.71 and 0.86, respectively, for poor outcome. ANN showed superior prediction for poor outcome with AUROC 0.96, sensitivity 82.6%, specificity 96%, PPV 96.2% and NPV 85.7% (cut-off 0.5). ANN is superior to PELD-MELD for predicting poor outcome in PALF.