RESUMO
Extracorporeal life support (ECLS) devices are lifesaving for critically ill patients with multi-organ dysfunction. Despite this, patients supported with ECLS are at high risk for ECLS-related complications, including nosocomial infections, and mortality rates are high in this patient population. The high mortality rates are suspected to be, in part, a result of significantly altered drug disposition by the ECLS circuit, resulting in suboptimal antimicrobial dosing. Cefepime is commonly used in critically ill patients with serious infections. Cefepime dosing is not routinely guided by therapeutic drug monitoring and treatment success is dependent upon the percentage of time of the dosing interval that the drug concentration remains above the minimum inhibitory concentration of the organism. This ex vivo study measured the extraction of cefepime by continuous renal replacement therapy (CRRT) and extracorporeal membrane oxygenation (ECMO) circuits. Cefepime was studied in four closed-loop CRRT circuit configurations and a single closed-loop ECMO circuit configuration. Circuits were primed with a physiologic human blood-plasma mixture and the drug was dosed to achieve therapeutic concentrations. Serial blood samples were collected over time and concentrations were quantified using validated assays. In ex vivo CRRT experiments, cefepime was rapidly cleared by dialysis, hemofiltration, and hemodiafiltration, with greater than 96% cefepime eliminated from the circuit by 2 hours. In the ECMO circuits, the mean recovery of cefepime was similar in both circuit and standard control. Mean (standard deviation) recovery of cefepime in the ECMO circuits (n = 6) was 39.2% (8.0) at 24 hours. Mean recovery in the standard control (n = 3) at 24 hours was 52.2% (1.5). Cefepime is rapidly cleared by dialysis, hemofiltration, and hemodiafiltration in the CRRT circuit but minimally adsorbed by either the CRRT or ECMO circuits. Dosing adjustments are needed for patients supported with CRRT.
Assuntos
Oxigenação por Membrana Extracorpórea , Hemofiltração , Humanos , Cefepima , Oxigenação por Membrana Extracorpórea/métodos , Estado Terminal/terapia , Diálise RenalRESUMO
The pathogenesis of steroid-resistant nephrotic syndrome (SRNS) is not completely known. Recent advances in genomics have elucidated some of the molecular mechanisms and pathophysiology of the disease. More than 50 monogenic causes of SRNS have been identified; however, these genes are responsible for only a small fraction of SRNS in outbred populations. There are currently no guidelines for genetic testing in SRNS, but evidence from the literature suggests that testing should be guided by the genetic architecture of the disease in the population. Notably, most genetic forms of SRNS do not respond to current immunosuppressive therapies; however, a small subset of patients with monogenic SRNS will achieve partial or complete remission with specific immunomodulatory agents, presumably due to non-immunosuppressive effects of these agents. We suggest a pragmatic approach to the therapy of genetic SRNS, as there is no evidence-based algorithm for the management of the disease.