Pharmacokinetic model of unfractionated heparin during and after cardiopulmonary bypass in cardiac surgery

Background: Unfractionated heparin (UFH) is widely used as a reversible anti-coagulant in cardiopulmonary bypass (CPB). However, the pharmacokinetic characteristics of UFH in CPB surgeries remain unknown because of the lack of means to directly determine plasma UFH concentrations. The aim of this study was to establish a pharmacokinetic model to predict plasma UFH concentrations at the end of CPB for optimal neutralization with protamine sulfate. Methods: Forty-one patients undergoing CPB during cardiac surgery were enrolled in this observational clinical study of UFH pharmacokinetics. Patients received intravenous injections of UFH, and plasma anti-F-IIa activity was measured with commercial anti-F-IIa assay kits. A population pharmacokinetic model was established by using nonlinear mixed-effects modeling (NONMEM) software and validated by visual predictive check and Bootstrap analyses. Estimated parameters in the final model were used to simulate additional protamine administration after cardiac surgery in order to eliminate heparin rebound. Plans for postoperative protamine intravenous injections and infusions were quantitatively compared and evaluated during the simulation. Results: A two-compartment pharmacokinetic model with first-order elimination provided the best fit. Subsequent simulation of postoperative protamine administration suggested that a lower-dose protamine infusion over 24 h may provide better elimination and prevent heparin rebound than bolus injection and other infusion regimens that have higher infusion rates and shorter duration. Conclusion: A two-compartment model accurately reflects the pharmacokinetics of UFH in Chinese patients during CPB and can be used to explain postoperative heparin rebound after protamine neutralization. Simulations suggest a 24-h protamine infusion is more effective for heparin rebound prevention than a 6-h protamine infusion.http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000350506400005&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=8e1609b174ce4e31116a60747a720701Medicine, Research & ExperimentalSCI(E)[email protected]

The effect of human immunodeficiency virus on functional recovery in hospitalized patients with stroke

Background and Objective: Given the known association between inflammatory conditions and stroke, this study was designed to assess whether the diagnosis of human immunodeficiency virus (HIV) – which is associated with chronic inflammation – would affect the functional trajectory of patients hospitalized for the treatment of stroke. Methods: This is a retrospective study comparing the functional outcomes of 688,066 stroke patients with a diagnosis of HIV to those without a diagnosis of HIV from 2002 to 2017. Results: HIV+ patients were found to have a much lower age at admission, with a difference of over 10 years when compared to HIV− patients. HIV+ patients were also less likely to discharge to home when compared to HIV− patients (P < 0.0001). Gains in functional independence measure (FIM) scores per day were found to be greater among those who were HIV− compared to those who were HIV+ (P = 0.086). Factors associated with a lower FIM efficiency included older age at admission, male gender, and having a hemorrhagic stroke (P < 0.0001). Conclusion: This study found that, among those hospitalized for the treatment of a stroke, the functional gain per day was inferior among those with HIV than among those without HIV at admission