Söderberg E, Eriksson M, Larsson A, Lipcsey M
Anaesthesiology and Intensive Care, Department of Surgical Sciences, Uppsala University, 751 85, Uppsala, Sweden.
Section of Clinical Chemistry, Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
Intensive Care Med Exp. 2017 Dec;5(1):4. doi: 10.1186/s40635-017-0117-6. Epub 2017 Jan 19.
A key feature of sepsis is systemic inflammatory activation that could be counteracted by steroids. In this experimental model of systemic inflammation, we sought to investigate whether septic neutrophil activation, evaluated by the plasma levels of neutrophil gelatinase-associated protein (NGAL), is modulated by the timing of hydrocortisone treatment.
Sixteen anesthetized pigs were allocated to one of four equally sized groups. Three of these groups received endotoxin at 2 μg × kg × h for 6 h so as to induce endotoxemic shock. Hydrocortisone (5 mg × kg) was administered intravenously before endotoxemic challenge, or at the onset of endotoxemic shock. Endotoxemic pigs not receiving hydrocortisone and non-endotoxemic pigs served as control groups. Physiologic variables, hematology, and biochemistry, including plasma NGAL, were measured repeatedly.
Hydrocortisone treatment prior to endotoxemia attenuated some inflammatory, hematological, circulatory, and metabolic manifestations of shock (i.e., higher white blood cell count, higher mean arterial pressure, lower heart rate and mean pulmonary arterial pressure, higher left ventricular stroke work index, higher base excess). Endotoxemic shock increased plasma NGAL (p < 0.001). In pigs given hydrocortisone before the endotoxin infusion, plasma NGAL was lower as compared to those given hydrocortisone at endotoxemic shock (p < 0.05). Plasma NGAL levels correlated inversely to neutrophil granulocyte counts (rho = -0.65) but not to urine output (rho = -0.10) at the end of the experiment.
The increase in plasma NGAL is counteracted by hydrocortisone administration prior to endotoxemia; concomitantly, this treatment was associated with less expressed circulatory derangement. Urine NGAL did not differ between the groups, suggesting that the NGAL response was not primarily related to kidney injury.
脓毒症的一个关键特征是全身炎症激活，而类固醇可以对抗这种炎症。在这个全身炎症的实验模型中，我们试图研究通过中性粒细胞明胶酶相关蛋白（NGAL）血浆水平评估的脓毒症中性粒细胞激活是否受氢化可的松治疗时机的调节。
将16只麻醉猪分为四个等规模的组。其中三组接受2μg×kg×h的内毒素注射6小时，以诱导内毒素血症休克。在进行内毒素血症攻击前或内毒素血症休克发作时静脉注射氢化可的松（5mg×kg）。未接受氢化可的松的内毒素血症猪和非内毒素血症猪作为对照组。反复测量生理变量、血液学和生物化学指标，包括血浆NGAL。
内毒素血症前给予氢化可的松治疗可减轻休克的一些炎症、血液学、循环和代谢表现（即白细胞计数升高、平均动脉压升高、心率和平均肺动脉压降低、左心室每搏功指数升高、碱剩余升高）。内毒素血症休克会增加血浆NGAL（p<0.001）。与在内毒素血症休克时给予氢化可的松的猪相比，在内毒素注射前给予氢化可的松的猪血浆NGAL较低（p<0.05）。在实验结束时，血浆NGAL水平与中性粒细胞计数呈负相关（rho=-0.65），但与尿量无关（rho=-0.10）。
内毒素血症前给予氢化可的松可抵消血浆NGAL的升高；同时，这种治疗与较轻的循环紊乱相关。各组间尿NGAL无差异，提示NGAL反应并非主要与肾损伤有关。
