Welcome to the 9th EAPS Congress Programme Scheduling

Abstract Body

Critically ill children and neonates are at risk for acute kidney injury (AKI), which leads to the sudden derangement of glomerular filtration rate (GFR). It is a frequent and serious condition that is an independent risk factor for prolonged mechanical ventilation, extended stay in the intensive care unit (ICU) and higher mortality . Also, AKI negatively affects a patient’s long-term prognosis. Furthermore, there is growing evidence that augmented renal clearance (ARC), which is enhanced kidney perfusion and glomerular hyperfiltration, is more prevalent in critically ill children than previously thought . As altered GFR affects fluid and electrolyte management, and requires dose adaptation for drugs cleared by the kidneys, accurate and timely diagnosis of both AKI and ARC is crucial.

First, the challenges of AKI and ARC diagnosis in critically ill children will be discussed, including pros and cons of different eGFR formulas to aid dosing in AKI and ARC patients. Next, the impact of AKI and ARC on drug disposition will be shown, and the results of the NeoDose project. In this project, the Dutch Pediatric Formulary developed dosing guidelines for children with renal insufficiency, which were implemented in the Netherlands, as well as through the Norwegian, Austrian and German affiliates of the Formulary. Finally, the concept of model-informed dosing and model-informed precision dosing will be presented, including state of art implementation in pediatric intensive care

Abstract Body

Extracorporeal devices modify PK of drugs, so prescription during this treatment remains a challenge. During ECMO treatment were reported: increased Volume of distribution, due to increased circulating blood volume and drug extraction by the circuit; decreased clearance, due to renal and/or hepatic insufficiency; increased T ½ due to renal and/or hepatic insufficiency. Fluid loss, PH, PCO2, Temperature, O2 may contribute to change PK. Lipophilicity, protein binding and Volume of distribution are drug characteristics mostly involved in these mechanisms. Moreover, drug absorption, distribution, excretion can be altered due to patients’ organ failure. As a result of all these mechanisms, a modification in drug concentration possibly results.

Drug dosing is particularly recommended for drugs with possible toxicity or for drugs with a narrow range of efficacy. Some molecules present both characteristics, for example antibiotics and antifungal. Meropenem shows a decrease in serum concentration whereas other antifungal drugs remain stable during ECMO treatment. Voriconazole, micafungine are highly absorbed in the circuit whereas fluconazole and caspofungine are not extracted. Anticonvulsants, anticoagulation and, particularly, immunosuppressant drugs should be kept within a strict range of serum concentration to obtain their effect. Anticoagulation is routinely monitored during ECMO treatment. Particularly for immunosuppressants serum level is unpredictable and accurate dosing is mandatory. Also, amiodarone, is highly extracted in the circuit so the dosing is recommended. Analgesic and sedatives are usually not monitored although highly absorbed in the circuit. According to literature, morphine is the most stable molecule and should be preferred during ECMO treatment.

Background and Aims

The need of renal replacement therapy (RRT) in septic children may occur and add variability leading to unpredictable anti-infective concentrations with risks of treatment failure, toxicity and emergence of multidrug resistant bacteria. We aim to better understand anti-infective prescription practices in children undergoing RRT.

Methods

An online survey was sent via email to physicians working in French-speaking pediatric intensive care units (PICU). The survey form assessed the characteristics of the PICU, practices of RRT, anti-infective prescription and therapeutic drug monitoring.

Results

From 04/2021 to 05/2021, 26 different centers including 21 French centers answered (88% of response rate for French PICU > 4 beds). Every PICU used continuous RRT with mainly Prismaflex® machine. Adaptation of anti-infective prescriptions to RRT were declared in 23 (89%) PICU according to the molecular weight in 6 (26%), to protein binding in 6 (26%), to lipo/hydrophilic nature in 4 (17%), to elimination routes in 15 (65%). The anti-infective were adapted to the residual diuresis in 9 (41%) PICU, to the RRT flow in 6 (26%) and to the type of RRT used in 15 (65%) with great variability (Fig. 1). Most of the centers (n=20, 77%) used therapeutic drug monitoring under RRT, systematically for betalactams in 18 (69%), for aminoglycosides in 22 (92%), for glycopeptides in 21 (84%). Obstacles for monitoring were mainly (n=11, 42%) the delay for the results and the absence of on-site laboratory (n=8, 31%).

Conclusions

Our survey reported great variability of anti-infective prescription practices in children undergoing RRT pointing out the need for specific guidelines.