急性颅脑创伤后低糖皮质醇血症的观察及临床意义
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摘要
目的研究颅脑创伤(traumatic brain injury, TBI)患者伤后14天内血清总皮质醇(total cortisol, TC)、类固醇结合球蛋白(Corticosteroid—Binding Globulin, CBG)以及游离皮质醇(free cortisol, FC)、游离皮质醇指数(free cortisol index, FCI)的变化,了解TBI后肾上腺皮质功能状态,为临床应用糖皮质激素(glucosteroids, GCs)提供理论指导。
方法：以2007年1月至2008年2月受伤24h内入住天津医科大学总医院神经外科及天津市静海县医院脑外科的38名TBI患者为研究对象,并以30例无应激健康体检者为对照组进行分析对比,采用放射免疫分析法测定血清TC. CBG水平,应用Cool ens公式计算FC及FCI。实验数据采用SPSS16.0统计软件进行分析处理,以p<0.05作为有统计学差异,观察不同程度急性TBI后相应激素水平的动态变化,评价TBI后的肾上腺皮质功能。
结果：急性TBI后,与对照组比较,患者伤后1天TC、FC及FCI均出现显著升高(p<0.05),之后逐渐下降,伤后14天左右接近正常水平；有9例患者出现肾上腺皮质功能低下(adrenal insufficiency, AI),其中7例(77.8%)预后不良；余29例患者在观察期内未出现AI,其中1例(3.4%)预后不良。两者预后不良的发生率差别有统计学意义(p<0.05),可见AI的发生是导致不良预后的关键因素之一。
结论：在急性TBI后,不同伤情患者与对照组比较,TC、FC及FCI在轻、中、重型TBI组均高于对照组并且达到最高峰,TC水平在重型TBI组、中型TBI组及轻型TBI组均升高,以重型TBI组升高最为显著；FC水平在重型TBI组、中型TBI组及轻型TBI均升高；FCI水平在重型TBI组、中型TBI组显著升高。TC、FC及FCI迅速升高后均逐渐下降,于伤后第14天左右才逐渐下降至正常水平；在急性TBI后,创伤后预后良好组的TC恢复较快,于伤后第2日即降至正常范围,预后不良组TC恢复较慢；急性TBI后,各伤情组第1天、第3天均未出现AI,而第7天AI的发生率达到高峰(77.7%),随后逐渐减少,AI的发生与不良预后密切相关,而TBI后第7天AI最易发生；在TBI早期,不同伤情患者TC、FC均显著升高,在此显著高水平的状态下,采用GCs大剂量冲击疗法进一步提高体内的GCs水平,并不一定能加强GCs的神经保护作用,相反有可能增加其导致细胞调亡等副作用。故在伤后早期,患者无低糖皮质激素的情况下,应用GCs大剂量冲击疗法应慎重考虑；血清TC尤其FC的动态测定,可以更客观地反映脑创伤患者伤后机体应激状态、肾上腺皮质功能状况及体内活性皮质醇的真实水平,从而避免不必要的GCs应用。如发现患者存在着低糖皮质醇血症或有明确的其他GCs应用指征,不应限制GCs的应用,此时对AI的合理治疗,可能是改善TBI患者预后的关键因素之一。
Objective To investigate the serum status of total cortisol(TC), corticoster-oid-binding-globulin (CBG), free cortisol (FC) and free cortisol index (FCI) within14days after acute traumatic brain injury(TBI), and to find out the functional status of adrenal cortex, then help to guide clinical administration of glucocorticoids(GCs).
Methods The research was carried out in neurosurgical department of General Hospital, Tianjin Medical University and neurosurgical department of Jinghai Hospi-tal in Tianjin. From January2007to February2008,38TBI patients with an admit-ting post-trauma period within24h were included in this study,30non-stress indi-viduals were studied as contrast. Serum status of TC and CBG was measured by ra-dioimmunoassay, FC and FCI was calculated by Coolens equation. Data were ana-lyzed with SPSS16.0,p<0.05was considered statistical significance. So the dynamic changes of the related hormones after different degrees of acute TBI was elucidated, meanwhile, adrenal cortex function was evaluated in these patients.
Results In most patients of this group, within24h following acute TBI, TC, FC and FCI were higher than non-stress contrast(P<0.05), then dropped gradually, and returned to normal level about14days later. Adrenal insufficiency(AI) was observed in9patients,7patients (77.8%) of them showed poor outcome; there was no adrenal insufficiency in the other29patients during the research period, but1patients(3.4%) of them showed poor outcome. The incidence of the poor prognosis between the two group had statistical significance (P<0.05), so the occurrence of the AI was one of the key factors leading to poor prognosis.
Conclusions Compared with control groups, TC, FC and FCI were higher and reached a peak in mild, moderate, and severe group after acute traumatic brain in-jury(TBI). TC were higher in mild, moderate, and severe injured group, especially in severe group. FC were higher in severe, moderate, and mild injured group. FCI were higher in severe and moderate injured group. TC, FC and FCI elevated rapidly, then decreased gradually, returned to normal level on day14after acute traumatic brain injury(TBI). The level of TC in favorable outcome group returned to normal range quicker than poor outcome group, nearly2days later. All patients didn't appear AI on the1st and3rd day, but the AI incidence rate attained the peak(77.7%) on the7th day, and reduce gradually later on.
Al occurrence closely related to bad outcomes. The AI most occur on the7th day after acute traumatic brain injury(TBI); In TBI earlier period,TC、FC were significant higher in different damaged groups, during this high-level condition, high dose GCs chemotherapy, further raising the GCs level in the body, can not necessarily strengthen the GCs nerve protection function, and instead, probably cause apoptosis side effects. Therefor, in earlier period, no hypocortisolism, the high dose GCs che-motherapy should be carefully considered. Blood TC, especially FC dynamic meas-uring can better objectively reflect patient physical stress condition, adrenocortical function and active cortisol, avoiding unnecessary GCs application. If patients have hypocortisolism or other definite application indication, do not inhibit GCs applica-tion. at this time, rational therapy to the AI, may act as a key role to improve a TBI patient outcome.
方法：以2007年1月至2008年2月受伤24h内入住天津医科大学总医院神经外科及天津市静海县医院脑外科的38名TBI患者为研究对象,并以30例无应激健康体检者为对照组进行分析对比,采用放射免疫分析法测定血清TC. CBG水平,应用Cool ens公式计算FC及FCI。实验数据采用SPSS16.0统计软件进行分析处理,以p<0.05作为有统计学差异,观察不同程度急性TBI后相应激素水平的动态变化,评价TBI后的肾上腺皮质功能。
结果：急性TBI后,与对照组比较,患者伤后1天TC、FC及FCI均出现显著升高(p<0.05),之后逐渐下降,伤后14天左右接近正常水平；有9例患者出现肾上腺皮质功能低下(adrenal insufficiency, AI),其中7例(77.8%)预后不良；余29例患者在观察期内未出现AI,其中1例(3.4%)预后不良。两者预后不良的发生率差别有统计学意义(p<0.05),可见AI的发生是导致不良预后的关键因素之一。
结论：在急性TBI后,不同伤情患者与对照组比较,TC、FC及FCI在轻、中、重型TBI组均高于对照组并且达到最高峰,TC水平在重型TBI组、中型TBI组及轻型TBI组均升高,以重型TBI组升高最为显著；FC水平在重型TBI组、中型TBI组及轻型TBI均升高；FCI水平在重型TBI组、中型TBI组显著升高。TC、FC及FCI迅速升高后均逐渐下降,于伤后第14天左右才逐渐下降至正常水平；在急性TBI后,创伤后预后良好组的TC恢复较快,于伤后第2日即降至正常范围,预后不良组TC恢复较慢；急性TBI后,各伤情组第1天、第3天均未出现AI,而第7天AI的发生率达到高峰(77.7%),随后逐渐减少,AI的发生与不良预后密切相关,而TBI后第7天AI最易发生；在TBI早期,不同伤情患者TC、FC均显著升高,在此显著高水平的状态下,采用GCs大剂量冲击疗法进一步提高体内的GCs水平,并不一定能加强GCs的神经保护作用,相反有可能增加其导致细胞调亡等副作用。故在伤后早期,患者无低糖皮质激素的情况下,应用GCs大剂量冲击疗法应慎重考虑；血清TC尤其FC的动态测定,可以更客观地反映脑创伤患者伤后机体应激状态、肾上腺皮质功能状况及体内活性皮质醇的真实水平,从而避免不必要的GCs应用。如发现患者存在着低糖皮质醇血症或有明确的其他GCs应用指征,不应限制GCs的应用,此时对AI的合理治疗,可能是改善TBI患者预后的关键因素之一。
Objective To investigate the serum status of total cortisol(TC), corticoster-oid-binding-globulin (CBG), free cortisol (FC) and free cortisol index (FCI) within14days after acute traumatic brain injury(TBI), and to find out the functional status of adrenal cortex, then help to guide clinical administration of glucocorticoids(GCs).
Methods The research was carried out in neurosurgical department of General Hospital, Tianjin Medical University and neurosurgical department of Jinghai Hospi-tal in Tianjin. From January2007to February2008,38TBI patients with an admit-ting post-trauma period within24h were included in this study,30non-stress indi-viduals were studied as contrast. Serum status of TC and CBG was measured by ra-dioimmunoassay, FC and FCI was calculated by Coolens equation. Data were ana-lyzed with SPSS16.0,p<0.05was considered statistical significance. So the dynamic changes of the related hormones after different degrees of acute TBI was elucidated, meanwhile, adrenal cortex function was evaluated in these patients.
Results In most patients of this group, within24h following acute TBI, TC, FC and FCI were higher than non-stress contrast(P<0.05), then dropped gradually, and returned to normal level about14days later. Adrenal insufficiency(AI) was observed in9patients,7patients (77.8%) of them showed poor outcome; there was no adrenal insufficiency in the other29patients during the research period, but1patients(3.4%) of them showed poor outcome. The incidence of the poor prognosis between the two group had statistical significance (P<0.05), so the occurrence of the AI was one of the key factors leading to poor prognosis.
Conclusions Compared with control groups, TC, FC and FCI were higher and reached a peak in mild, moderate, and severe group after acute traumatic brain in-jury(TBI). TC were higher in mild, moderate, and severe injured group, especially in severe group. FC were higher in severe, moderate, and mild injured group. FCI were higher in severe and moderate injured group. TC, FC and FCI elevated rapidly, then decreased gradually, returned to normal level on day14after acute traumatic brain injury(TBI). The level of TC in favorable outcome group returned to normal range quicker than poor outcome group, nearly2days later. All patients didn't appear AI on the1st and3rd day, but the AI incidence rate attained the peak(77.7%) on the7th day, and reduce gradually later on.
Al occurrence closely related to bad outcomes. The AI most occur on the7th day after acute traumatic brain injury(TBI); In TBI earlier period,TC、FC were significant higher in different damaged groups, during this high-level condition, high dose GCs chemotherapy, further raising the GCs level in the body, can not necessarily strengthen the GCs nerve protection function, and instead, probably cause apoptosis side effects. Therefor, in earlier period, no hypocortisolism, the high dose GCs che-motherapy should be carefully considered. Blood TC, especially FC dynamic meas-uring can better objectively reflect patient physical stress condition, adrenocortical function and active cortisol, avoiding unnecessary GCs application. If patients have hypocortisolism or other definite application indication, do not inhibit GCs applica-tion. at this time, rational therapy to the AI, may act as a key role to improve a TBI patient outcome.
引文
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