Using Pharmacokinetic Modeling and Electronic Health Record Data to Predict Clinical and Safety Outcomes after Methylprednisolone Exposure during Cardiopulmonary Bypass in Neonates.

IF 0.3 4区医学 Q4 CARDIAC & CARDIOVASCULAR SYSTEMS

Congenital Heart Disease Pub Date : 2023-01-01 DOI:10.32604/chd.2023.026262

Henry P Foote, Huali Wu, Stephen J Balevic, Elizabeth J Thompson, Kevin D Hill, Eric M Graham, Christoph P Hornik, Karan R Kumar

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引用次数: 0

Abstract

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.

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使用药代动力学模型和电子健康记录数据预测新生儿体外循环期间甲基强的松龙暴露后的临床和安全性结果。

背景:接受心脏手术合并体外循环(CPB)的婴儿经常在术中接受甲基强的松龙(MP)来抑制CPB相关炎症;然而，MP的最佳给药策略和疗效尚不清楚。方法:回顾性分析我院2014-2017年所有接受CPB心脏手术术中MP治疗的90天以下婴儿。我们结合来自电子健康记录(EHR)的真实剂量数据和两个先前开发的人群药代动力学/药理学模型，模拟MP和炎症细胞因子白介素-6 (IL-6)和白介素-10 (IL-10) 24小时的峰值浓度(Cmax)和浓度-时间曲线下面积(AUC24)。我们使用非参数测试评估了从电子病历中获得的术后、安全性和其他临床结果与每种预测暴露之间的关系。结果:142名中位出生年龄为8(四分位间距[IQR]: 5,37)天的婴儿接受了总剂量为30 (19,49)mg/kg的MP。12例(8%)死亡，37例(26%)达到术后综合结局，114例(80%)达到术后综合安全结局，23例(16%)出现主要并发症。在达到复合术后结局和有主要并发症的婴儿中，预测的中位Cmax和AUC24 IL-6暴露量显著更高。需要胰岛素的婴儿Cmax和AUC24 MP暴露的预测值中位数明显更高。没有暴露与死亡或其他安全结果相关。结论:促炎IL-6与术后器官功能障碍相关，而MP暴露与此无关，提示当前MP剂量可能不足以抑制IL-6或增加IL-10来影响临床结果。需要前瞻性研究来确定这些婴儿的最佳暴露-功效和暴露-安全概况。

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来源期刊

Congenital Heart Disease CARDIAC & CARDIOVASCULAR SYSTEMS-

CiteScore

0.40

自引率

33.30%

发文量

审稿时长

6-12 weeks

期刊介绍： Congenital Heart Disease is an open-access journal focusing on congenital heart disease in children and adults. Though the number of infants born with heart disease each year is relatively small (approximately 1% of the population), advances in treating such malformations have led to increased life spans for this population. Consequently, today most patients treated for congenital heart disease are over the age of 20. What are the special needs of adults with congenital heart disease? What are the latest developments in the care of the fetus, infants, and children? Who should treat these patients? How should they be treated? Congenital Heart Disease focuses on these questions and more. Conceived as a forum for the most up-to-date information on congenital heart disease, the journal is led by Editor-in-Chief Vladimiro L. Vida, MD, Ph.D., Professor in Cardiac Surgery, University of Padua in Italy, as well as an international editorial board. Congenital Heart Disease publishes articles on heart disease as it relates to the following areas: • Basic research of congenital heart disease • Clinical pediatric and adult cardiology • Cardiac imaging • Preventive cardiology • Diagnostic and interventional cardiac catheterization • Electrophysiology • Surgery • Long-term follow-up, particularly as it relates to older children and adult congenital heart disease • Exercise and exercise physiology in the congenital patient • Post-op and critical care • Common disorders such as syncope, chest pain, murmurs, as well as acquired disorders such as Kawasaki syndrome The journal includes clinical studies, invited editorials, state-of-the-art reviews, case reports, articles focusing on the history and development of congenital heart disease, and CME material. Occasional issues focus on special topics. Readership: Congenital Heart Disease was created for pediatric cardiologists; adult cardiologists who care for patients with congenital heart disease; pediatric and pediatric cardiology nurses; surgeons; radiologists; anesthesiologists; critical care physicians and nurses; and adult support staff involved in the care of patients with congenital heart disease.