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Acute aminoglycoside overdose : management and risks

Book Contribution - Book Abstract Conference Contribution

Aims/Purpose: Aminoglycosides have a narrow therapeutic range and therapeutic drug monitoring (TDM) is widely used to prevent nephroand ototoxicity during prolonged therapy. However, the management and risks of an acute overdose of aminoglycosides are less well-known. We describe the case of a young child who received an amikacin overdose together with an overview of management strategies and toxicity risks, based on a literature review. Methods: A systematic literature search for cases of acute aminoglycoside overdoses was performed in PubMed and Embase. Results: Case. An amikacin dose of 125 mg/kg (recommended dose: 15 mg/kg q24h) was accidentally administered to a girl of fve months old with pyelonephritis and normal renal function. On the advice of the Belgian Poison Center and the pediatric nephrologists, she was started on intermittent hemodialysis. Hemodialysis was initiated seven hours after administration and continued for four hours until subtherapeutic trough plasma levels were reached. Amikacin levels showed a rapid decline before the start of (half life: 1.6 h) and during (half life: 1 h) hemodialysis. No toxic efects were observed during follow-up. Literature review. 22 cases on acute aminoglycoside overdoses have been published. Most cases involve children (15), the majority being neonates (10). Various treatment strategies have been applied: supportive therapy (intravenous hydration, monitoring of the vital signs and renal function, and aminoglycoside TDM), hemodialysis, peritoneal dialysis, and exchange transfusion. From these interventions, intermittent hemodialysis is most efective at removing aminoglycosides from the body. Nine out of the 22 patients (40%) experienced nephro-, oto- and/ or neurotoxic efects. These patients included three adults with severe renal or hepatic impairment and four neonates. The incidence of toxicity did not differ between patients on supportive therapy and those treated with hemodialysis. Conclusion: Because of their low molecular mass, small volume of distribution, and low protein binding, aminoglycosides are efficiently removed from the body by extracorporeal treatments. However, scientifc evidence on the added value of hemodialysis above supportive therapy for acute aminoglycoside overdoses is scarce and mainly based on expert opinion, except in patients with pre-existing renal impairment. When hemodialysis is preferred, it is advisable to start as fast as possible with high-fux intermittent hemodialysis. The risk of toxicity from an acute overdose appears to be low in patients without comorbidities and a normal renal clearance.
Volume: 38
Pages: S66 - S67
Publication year:2023