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A 14-year-old boy with movement disorder and epilepsy developed status dystonicus leading to rhabdomyolysis and subsequent acute kidney injury requiring continuous renal replacement therapy (CRRT). He was given multiple intravenous sedatives and analgesics to control his dystonia and dyskinesia. 8 days after admission, his condition had improved and a trial termination of CRRT was carried out. The sedatives and analgesics were switched to oral diazepam, morphine, clonidine, and chloral hydrate. However, his renal function did not recover fully. There was rising trend of serum creatinine level with evolving hyperphosphatemia and metabolic acidosis. He also gradually developed hypoventilation, hypercapnia and pinpoint pupils after weaning CRRT. The clinical impression was over-sedation resulting in hypoventilation and respiratory failure, contributed by the deteriorating renal function. Non-invasive ventilatory support was then started and CRRT was resumed. His condition improved over the next 24 hours. Dexmedetomidine infusion was used during CRRT and he slowly required stepping up of sedatives again. A separate set of dosage for all his oral sedative agents was prepared for his subsequent CRRT weaning challenge and no more over-sedative episode was then encountered. Our case illustrated that patients at recovery phase of AKI are susceptible to medication overdose, especially during the period of CRRT weaning. Sedatives and analgesics including morphine and benzodiazepines should be used with caution during this period and alternatives may need to be considered. Advanced planning of medication dosage adjustment is advised to reduce the risk of medication overdose. [ABSTRACT FROM AUTHOR]

Background: Invasive fungal infections (IFIs) are important infectious complications amongst critically ill children. The most common fungal infections are due to Candida species. Aspergillus , Zygomycetes and Fusarium are also emerging because of the empirical use of antifungal drugs. This updated review discusses the epidemiology of IFIs as well as antifungal drugs, dosing and potential adverse effects in critically ill children., Methods: A PubMed search was conducted with Clinical Queries using the key terms "antifungal", "children", "critical care" AND "paediatric intensive care unit" OR "PICU". The search strategy included clinical trials, randomized controlled trials, meta-analyses, observational studies and reviews and was limited to the English literature in paediatrics., Results: Candida and Aspergillus spp. are the most prevalent fungi in paediatric IFIs, causing invasive candidiasis infections (ICIs) and invasive aspergillosis infections (IAIs), respectively. These IFIs are associated with high morbidity, mortality and healthcare costs. Candida albicans is the principal Candida spp. associated with paediatric ICIs. The risks and epidemiology for IFIs vary if considering previously healthy children treated in the paediatric intensive care unit or children with leukaemia, malignancy or a severe haematological disease. The mortality rate for IAIs in children is 2.5-3.5-fold higher than for ICIs. Four major classes of antifungals for critically ill children are azoles, polyenes, antifungal antimetabolites and echinocandins., Conclusions: Antifungal agents are highly efficacious. For successful treatment outcomes, it is crucial to determine the optimal dosage, monitor pharmacokinetics parameters and adverse effects, and individualized therapeutic monitoring. Despite potent antifungal medications, ICIs and IAIs continue to be serious infections with high mortality rates. Pre-emptive therapy has been used for IAIs. Most guidelines recommend voriconazole as initial therapy of invasive aspergillosis in most patients, with consideration of combination therapy with voriconazole plus an echinocandin in selected patients with severe disease. The challenge is to identify critically ill patients at high risks of ICIs for targeted prophylaxis. Intravenous/per os fluconazole is first-line pre-emptive treatment for Candida spp. whereas intravenous micafungin or intravenous liposomal amphotericin B is alternative pre-emptive treatment.This article is part of the Challenges and strategies in the management of invasive fungal infections Special Issue: https://www.drugsincontext.com/special_issues/challenges-and-strategies-in-the-management-of-invasive-fungal-infections., Competing Interests: Disclosure and potential conflicts of interest: Professor Kam Lun Hon and Professor Alexander KC Leung are associate editors of Drugs in Context. The authors declare that there is no conflict of interest otherwise. The International Committee of Medical Journal Editors (ICMJE) Potential Conflicts of Interests form for the authors is available for download at: https://www.drugsincontext.com/wp-content/uploads/2024/04/dic.2023-9-2-COI.pdf, (Copyright © 2024 Hon KLE, Chan VPY, Leung AKC, Leung KKY, Hui WF.)