Critical illness due to sepsis is a major global health concern associated with a high burden of mortality and cost. Glucocorticoid dysregulation in human sepsis is associated with poorer outcomes. This study examines glucocorticoid metabolism in septic canine patients to delineate elements of cellular dysregulation in common with critically ill humans and explore potential differences. This was a prospective case–control study conducted in the veterinary specialist critical care departments of two University teaching hospitals. Critically ill canine patients with naturally occurring sepsis or septic shock were compared with an in-hospital control population. Serum total, bound, and free cortisol concentrations were increased in septic shock (P < 0.001), and higher bound cortisol was associated with nonsurvival (P = 0.026). Urinary Gas Chromatography-Tandem Mass Spectrometry was performed to assess urinary glucocorticoid metabolites and estimate intracellular glucocorticoid metabolism. Decreased renal 11β-hydroxysteroid dehydrogenase 2 (11βHSD2) activity inferred from increased urinary cortisol-to-cortisone ratio was observed in critically ill dogs (P < 0.001). Decreased 11βHSD2 activity (P = 0.019) and increased A-ring reduction of cortisone (P = 0.001) were associated with nonsurvival within the critically ill dogs. Intriguingly, two dogs were identified with low circulating total cortisol (<2 mg/dL) associated with increased A-ring reduction of cortisol, not previously described. Investigation of spontaneous canine sepsis and septic shock reveals dysregulation of cortisol to cortisone conversion similar to that observed in human patients, but with differences in A-ring reduction compared with those reported in humans. In addition, two dogs with high levels of cortisol inactivation associated with low circulating cortisol concentrations were identified.

由败血症引起的危急疾病是与高死亡率和高成本相关的主要的全球健康问题。人败血症中糖皮质激素的失调与预后较差有关。这项研究检查了败血症犬类患者的糖皮质激素代谢，以描绘重症患者常见的细胞失调的要素，并探讨潜在的差异。这是在两家大学教学医院的兽医专业重症监护部门进行的前瞻性病例对照研究。将患有自然败血症或败血性休克的重症犬病患者与住院对照组进行比较。败血性休克时血清总的，结合的和游离的皮质醇浓度增加（P<0.001），且皮质醇含量较高与非生存相关（P  = 0.026）。进行尿气相色谱-串联质谱法评估尿糖皮质激素代谢产物并评估细胞内糖皮质激素代谢。在危重病犬中观察到由于尿皮质醇与可的松比的增加而推断肾11β-羟类固醇脱氢酶2（11βHSD2）活性降低（P  <0.001）。降低11βHSD2活性（P = 0.019）和增加可的松的A环减少（P= 0.001）与重症犬的非生存性有关。有趣的是，鉴定出两只狗的循环总皮质醇水平较低（<2 mg / dL），且皮质醇的A环减少增加，这在之前没有描述。对自发犬败血症和败血性休克的研究表明，皮质醇向可的松转化失调与人类患者相似，但与人类报告的相比，A环减少的差异。另外，鉴定出两只狗具有高水平的皮质醇失活和低水平的皮质醇浓度。