BackgroundCefepime can be removed by continuous renal replacement therapy (CRRT) due to its pharmacokinetics. The purpose of this study is to define the optimal cefepime dosing regimens for critically ill patients receiving CRRT using Monte Carlo simulations (MCS).MethodsThe CRRT models of cefepime disposition during 48 h with different effluent rates were developed using published pharmacokinetic parameters, patient demographic data, and CRRT settings. Pharmacodynamic target was the cumulative percentage of a 48-h period of at least 70% that free cefepime concentration exceeds the four times susceptible breakpoint of Pseudomonas aeruginosa (minimum inhibitory concentration, MIC of 8). All recommended dosing regimens from available clinical resources were evaluated for the probability of target attainment (PTA) using MCS to generate drug disposition in a group of 5000 virtual patients for each dose. The optimal doses were defined as achieving the PTA at least 90% of virtual patients with lowest daily doses and the acceptable risk of neurotoxicity.ResultsOptimal cefepime doses in critically ill patients receiving CRRT with Kidney Disease: Improving Global Outcomes (KDIGO) recommended effluent rates were a regimen of 2 g loading dose followed by 1.5–1.75 g every 8 h for Gram-negative infections with a neurotoxicity risk of < 17%. Cefepime dosing regimens from this study were considerably higher than the recommended doses from clinical resources.ConclusionAll recommended dosing regimens for patients receiving CRRT from available clinical resources failed to achieve the PTA target. The optimal dosing regimens were suggested based on CRRT modalities, MIC values, and different effluent rates. Clinical validation is warranted.

Previous literature regarding coronavirus disease 2019 outlined a presence of organ dysfunction including acute respiratory distress syndrome and acute kidney injury that are linked to mortality. Several patients require extracorporeal therapy. This review aims to gather available published resources including physicochemical and pharmacokinetic properties and suggests antiviral drug dosing adaptation for coronavirus disease 2019–infected critically ill patients receiving extracorporeal therapy. A literature search was performed using PubMed, clinical trial registries, and bibliographic review of textbooks and review articles. Unfortunately, no standard of pharmacologic management and recommendations of drug dosing for coronavirus disease 2019 infection for critically ill patients receiving extracorporeal therapy exist due to the limited data on pharmacokinetic and clinical studies. All available extracted data were analyzed to suggest the appropriate drug dosing adjustment. Antiviral drug dosing adjustments for critically ill patients receiving extracorporeal membrane oxygenation and continuous renal replacement therapy are presented in this review. Considering pathophysiologic changes, drug properties, and extracorporeal modalities, applying our suggestions is recommended.

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Background In this pilot study, we aimed to determine the efficacy and safety of enteral erythromycin estolate in combination with intravenous metoclopramide compared to intravenous metoclopramide monotherapy in mechanically ventilated patients with enteral feeding intolerance. Methods This randomized, double‐blind, controlled pilot study included 35 mechanically ventilated patients with feeding intolerance who were randomly assigned to receive 10‐mg metoclopramide intravenously every 6–8 hours in combination with 250‐mg enteral erythromycin estolate (study group) or placebo every 6 hours for 7 days. The primary outcome was an administered‐to‐target energy ratio of ≥80% at 48 hours, indicating a successful feeding. Secondary, prespecified outcomes were daily average gastric residual volume (GRV), total energy intake, administered‐to‐target energy ratio, hospital length of stay, in‐hospital mortality, and 28‐day mortality. Results The rate of successful feeding was not significantly different between the study and placebo groups (47.1% and 61.1%, respectively; P = .51). The average daily GRV was significantly lower in the study group than in the placebo group (β = 91.58 [95% Wald CI, −164.35 to −18.8]), determined by generalized estimating equation. Other secondary outcomes were comparable, and the incidence of adverse events was not significantly different between the 2 groups. One common complication was cardiac arrhythmia, which was mostly self‐terminated. Conclusion Although the combination therapy of enteral erythromycin estolate and intravenous metoclopramide reduced GRV, the successful feeding rate and other patient‐specific outcomes did not improve in mechanically ventilated patients with feeding intolerance.

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