RESUMO
Drug treatments for coronavirus disease 2019 (COVID-19) dramatically improve patient outcomes, and although extracorporeal membrane oxygenation (ECMO) has significant use in these patients, it is unknown whether ECMO affects drug dosing. We used an ex vivo adult ECMO model to measure ECMO circuit effects on concentrations of specific COVID-19 drug treatments. Three identical ECMO circuits used in adult patients were set up. Circuits were primed with fresh human blood (temperature and pH maintained within normal limits). Three polystyrene jars with 75 ml fresh human blood were used as controls. Remdesivir, GS-441524, nafamostat, and tocilizumab were injected in the circuit and control jars at therapeutic concentrations. Samples were taken from circuit and control jars at predefined time points over 6 h and drug concentrations were measured using validated assays. Relative to baseline, mean (± standard deviation [SD]) study drug recoveries in both controls and circuits at 6 h were significantly lower for remdesivir (32.2% [±2.7] and 12.4% [±2.1], p < 0.001), nafamostat (21.4% [±5.0] and 0.0% [±0.0], p = 0.018). Reduced concentrations of COVID-19 drug treatments in ECMO circuits is a clinical concern. Remdesivir and nafamostat may need dose adjustments. Clinical pharmacokinetic studies are suggested to guide optimized COVID-19 drug treatment dosing during ECMO.
Assuntos
Monofosfato de Adenosina , Alanina , Tratamento Farmacológico da COVID-19 , Oxigenação por Membrana Extracorpórea , Oxigenação por Membrana Extracorpórea/métodos , Humanos , Monofosfato de Adenosina/análogos & derivados , Monofosfato de Adenosina/uso terapêutico , Monofosfato de Adenosina/farmacocinética , Alanina/análogos & derivados , Alanina/farmacocinética , Alanina/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/farmacocinética , Antivirais/farmacocinética , Antivirais/uso terapêutico , Guanidinas/farmacocinética , Guanidinas/uso terapêutico , Benzamidinas , COVID-19/terapia , SARS-CoV-2 , Adenosina/análogos & derivadosRESUMO
BACKGROUND: Venous thromboembolism (VTE), including Portomesenteric vein thrombosis (PMVT), is a major complication of sleeve gastrectomy (SG). We changed our practice in July 2021 to routinely discharge all SG patients postoperatively with extended chemoprophylaxis for 30 days. OBJECTIVES: Evaluate the efficacy and safety of routine extended chemoprophylaxis compared to 2 prior timeframes using selective extended chemoprophylaxis. SETTING: University Hospital. METHODS: Between 2012-2018, SG patients were discharged on extended chemoprophylaxis for patients deemed "high-risk" for VTE, including patients with body mass index (BMI) >50, and previous VTE. Between 2018-2021, extended chemoprophylaxis was broadened to include patients with positive preoperative thrombophilia panels (including Factor VIII). After 2021, all SG were routinely discharged on extended chemoprophylaxis. The typical regimen was 30 days Lovenox BID (40-mg twice daily for BMI> 40, 60-mg twice daily for BMI >60). Outcomes evaluated were rate of VTE/PMVT and postoperative bleed, including delayed bleed. RESULTS: A total of 8864 patients underwent SG. Average age and BMI were 37.5 years and 43.0 kg/m2, respectively. The overall incidence of PMVT was 33/8864 (.37%). Converting from selective extended chemoprophylaxis (Group 1) to routine extended chemoprophylaxis (Group 3) decreased the rate of PMVT from .55% to .21% (P = .13). There was a significantly higher overall bleeding rate (.85%), including delayed bleeds (.34%) in the routine extended chemoprophylaxis patients (P < .05). These bleeds were mainly managed nonoperatively. CONCLUSIONS: Routine extended (30 day) chemoprophylaxis for all SG may reduce PMVT rate but lead to a higher bleeding rate post-operatively. The vast majority of the increased bleeds are delayed and can be managed non-operatively.