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您的检索式：作者名="Eric M.Graham"
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| 1 | Using Pharmacokinetic Modeling and Electronic Health Record Data to Predict Clinical and Safety Outcomes after Methylprednisolone Exposure during Cardiopulmonary Bypass in Neonates显示文摘Background:Infants undergoing cardiac surgery with cardiopulmonary bypass(CPB)frequently receive intraoperative methylprednisolone(MP)to suppress CPB-related inflammation;however,the optimal dosing strategy and efficacy of MP remain unclear.Methods:We retrospectively analyzed all infants under 90 days-old who received intra-operative MP for cardiac surgery with CPB from 2014–2017 at our institution.We combined real-world dosing data from the electronic health record(EHR)and two previously developed population pharmacokinetic/pharmacodynamic models to simulate peak concentration(Cmax)and area under the concentration-time curve for 24 h(AUC24)for MP and the inflammatory cytokines interleukin-6(IL-6)and interleukin-10(IL-10).We evaluated the relationships between post-operative,safety,and other clinical outcomes obtained from the EHR with each predicted exposure using non-parametric tests.Results:A total of 142 infants with median post-natal age 8(interquartile range[IQR]:5,37)days received a total dose of 30(19,49)mg/kg of MP.Twelve(8%)died,37(26%)met the composite post-operative outcome,114(80%)met the composite safety outcome,and 23(16%)had a major complication.Predicted median Cmax and AUC24 IL-6 exposure was significantly higher for infants meeting the composite post-operative outcome and those with major complications.Predicted median Cmax and AUC24 MP exposure was significantly higher for infants requiring insulin.No exposure was associated with death or other safety outcomes.Conclusions:Pro-inflammatory IL-6,but not MP exposure,was associated with post-operative organ dysfunction,suggesting current MP dosing may not adequately suppress IL-6 or increase IL-10 to impact clinical outcomes.Prospective study will be required to define the optimal exposure-efficacy and exposure-safety profiles in these infants. | Henry P.Foote Huali Wu Stephen J.Balevic Elizabeth J.Thompson Kevin D.Hill Eric M.Graham Christoph P.Hornik Karan R.Kumar | 2023 | Congenital Heart Disease2023，18，3： | 0 |
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