Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, UK.
Centre for Endocrinology, Diabetes and Metabolism, Birmingham Health Partners, Birmingham, UK.
J Clin Endocrinol Metab. 2020 Jul 1;105(7):2262-74. doi: 10.1210/clinem/dgaa133.
Patients with adrenal insufficiency require increased hydrocortisone cover during major stress to avoid a life-threatening adrenal crisis. However, current treatment recommendations are not evidence-based.
To identify the most appropriate mode of hydrocortisone delivery in patients with adrenal insufficiency who are exposed to major stress.
Cross-sectional study: 122 unstressed healthy subjects and 288 subjects exposed to different stressors (major trauma [N = 83], sepsis [N = 100], and combat stress [N = 105]). Longitudinal study: 22 patients with preserved adrenal function undergoing elective surgery. Pharmacokinetic study: 10 patients with primary adrenal insufficiency undergoing administration of 200 mg hydrocortisone over 24 hours in 4 different delivery modes (continuous intravenous infusion; 6-hourly oral, intramuscular or intravenous bolus administration).
We measured total serum cortisol and cortisone, free serum cortisol, and urinary glucocorticoid metabolite excretion by mass spectrometry. Linear pharmacokinetic modeling was used to determine the most appropriate mode and dose of hydrocortisone administration in patients with adrenal insufficiency exposed to major stress.
Serum cortisol was increased in all stress conditions, with the highest values observed in surgery and sepsis. Continuous intravenous hydrocortisone was the only administration mode persistently achieving median cortisol concentrations in the range observed during major stress. Linear pharmacokinetic modeling identified continuous intravenous infusion of 200 mg hydrocortisone over 24 hours, preceded by an initial bolus of 50-100 mg hydrocortisone, as best suited for maintaining cortisol concentrations in the required range.
Continuous intravenous hydrocortisone infusion should be favored over intermittent bolus administration in the prevention and treatment of adrenal crisis during major stress.
患有肾上腺功能不全的患者在面临重大压力时需要增加氢化可的松的剂量以避免危及生命的肾上腺危象。然而，目前的治疗建议并没有充分的证据支持。
确定在面临重大压力的肾上腺功能不全患者中，最合适的氢化可的松给药方式。
横断面研究：122 名未暴露于压力的健康受试者和 288 名暴露于不同压力源的受试者（重大创伤 [N=83]、脓毒症 [N=100] 和战斗应激 [N=105]）。纵向研究：22 名保留肾上腺功能的择期手术患者。药代动力学研究：10 名原发性肾上腺功能不全患者以 4 种不同的给药方式（持续静脉输注；每 6 小时口服、肌肉或静脉推注）接受 200mg 氢化可的松治疗 24 小时。
我们通过质谱法测量总血清皮质醇和皮质酮、游离血清皮质醇和尿糖皮质激素代谢产物的排泄量。线性药代动力学模型用于确定暴露于重大压力的肾上腺功能不全患者最合适的给药方式和剂量。
所有压力条件下血清皮质醇均升高，手术和脓毒症时最高。持续静脉内给予氢化可的松是唯一一种持续使皮质醇浓度保持在重大压力期间观察到的中位数范围内的给药方式。线性药代动力学模型确定，24 小时内持续静脉输注 200mg 氢化可的松，同时给予 50-100mg 氢化可的松的初始推注，是维持皮质醇浓度在所需范围内的最佳选择。
在预防和治疗重大压力期间的肾上腺危象时，应优先选择持续静脉内给予氢化可的松而非间歇性推注。
