Hanson Institute, Endocrine and Metabolic unit, Royal Adelaide Hospital, Adelaide, Australia.
Clin Endocrinol (Oxf). 2010 Sep;73(3):413-20. doi: 10.1111/j.1365-2265.2010.03817.x. Epub 2010 Apr 23.
Objectives Nitric oxide (NO) concentrations are elevated in sepsis and their vasodilatory action may contribute to the development of hyperdynamic circulatory failure. Hydrocortisone infusion has been reported to reduce nitric oxide metabolite (NOx) concentrations and facilitate vasopressor withdrawal in septic shock. Our aim was to determine whether NOx concentrations relate to (i) protocol-driven vasopressor initiation and withdrawal and (ii) plasma cortisol concentrations, from endogenous and exogenous sources. Demonstration of a relation between NOx, cortisol and vasopressor requirement may provide an impetus towards the study of hydrocortisone-mediated NOx suppression as a tool in sepsis management. Design A prospective study of 62 patients with severe sepsis admitted to the intensive care unit. Measurements Plasma NOx, total and free cortisol, and corticosteroid-binding globulin (CBG) concentrations were measured and related to protocol-driven vasopressor use for 7 days following admission. Results Patients who developed septic shock (n = 35) had higher plasma NOx, total and free cortisol, and lower CBG concentrations than the nonseptic shock group (n = 27). Cortisol, CBG and NOx concentrations correlated with illness severity. Free cortisol, and to a lesser extent total cortisol, but not NOx concentrations, predicted septic shock. NOx concentrations were higher in nonsurvivors, and the concentrations were characteristically stable within individuals but marked interindividual differences were only partly accounted for by illness severity or renal dysfunction. NOx concentrations did not correlate with cortisol, did not relate to vasopressor requirement and did not fall after standard dose hydrocortisone, given for clinical indications. Conclusions Nitric oxide production increased with sepsis severity but did not correlate with plasma cortisol or vasopressor requirement. NOx levels were not suppressed reproducibly by hydrocortisone. High interindividual variability of NOx levels suggests that absolute NOx levels may not be a suitable target for individualized hydrocortisone therapy.
目的 一氧化氮（NO）浓度在脓毒症中升高，其血管舒张作用可能导致高动力循环衰竭的发展。已经报道氢化可的松输注可降低一氧化氮代谢物（NOx）浓度并促进脓毒性休克中血管加压剂的撤药。我们的目的是确定 NOx 浓度是否与（i）方案驱动的血管加压剂启动和撤药以及（ii）内源性和外源性来源的血浆皮质醇浓度有关。NOx、皮质醇和血管加压剂需求之间关系的证明可能为研究氢化可的松介导的 NOx 抑制作为脓毒症管理工具提供动力。
设计 对入住重症监护病房的 62 例严重脓毒症患者进行前瞻性研究。
测量 入院后 7 天内，测量血浆 NOx、总皮质醇、游离皮质醇和皮质类固醇结合球蛋白（CBG）浓度，并与方案驱动的血管加压剂使用相关。
结果 发生脓毒性休克的患者（n=35）的血浆 NOx、总皮质醇、游离皮质醇和 CBG 浓度高于非脓毒性休克组（n=27）。皮质醇、CBG 和 NOx 浓度与疾病严重程度相关。游离皮质醇，以及在较小程度上总皮质醇，但不是 NOx 浓度，预测了脓毒性休克。非幸存者的 NOx 浓度较高，并且个体内浓度特征稳定，但个体间差异仅部分由疾病严重程度或肾功能障碍解释。NOx 浓度与皮质醇无关，与血管加压剂需求无关，并且在给予临床指征的标准剂量氢化可的松后也未下降。
结论 随着脓毒症严重程度的增加，一氧化氮的产生增加，但与血浆皮质醇或血管加压剂需求无关。NOx 水平不能被氢化可的松重复抑制。NOx 水平的个体间变异性很大，表明绝对 NOx 水平可能不是个体化氢化可的松治疗的合适目标。
