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Study on the relationship between endocrine hormone and prognosis in critically ill patients Objective: To investigate the profile of changes in blood glucose、thyroid function and cortisol which occurring under critical illness and to explore the interrelation of these endocrine factors in order to direct clinical therapy. Method: A total of 51 patients with critical illness were studied in this prospective clinical study, either with multiple organ dysfunction syndrome(MODS, n=17) or without MODS(n=28) except 6 dead patients. Serum thyroid hormone、TSH and cortisol concentrations were measured in 51 patients of intensive care unit(ICU) in the first day by Chemiluminescent Microparticle Immunoassay(CMIA),except six patients of death in two days after hospitalization in ICU, continuing to measure the blood sample of other 45 patients in the third day. Patients’ age, blood glucose and APACHE-II score were recorded at first ICU day. Results: In the alive 45 patients, serum FT3 decreased in 41 patients(91%)、cortisol increased in 33 patients(73%), especially in the first 24 hours. Compared with non-MODS patients, the level of serum FT3 were much lower in MODS group(1.81±0.30&2.19±0.64,P=0.012), cortisol were much higher in MODS group(1164.53±219.91&798.34±317.83,P=0.002), and serum glucose increased markedly(12.1±3.6&8.9±2.5,P=0.027). Serum FT4 reduced apparently in six dead patients, with remarkable difference comparing with other 45 patients(5.59±0.87& 11.91±3.02,P=0.000). Serum FT3 was negatively related with APACHE-II score(r=-0.460,P=0.01), and serum cortisol was positively related with APACHE-II score(r=0.575,P=0.000). Conclusions: This clinical study revealed that: I. Blood glucose was increased in critically ill patients and correlated with the severity of illness; II. Thyroid hormone and cortisol were apparently abnormal and correlated with APACHE-II score, especially in MODS patients; III. Serum FT4 might serve as an index to judge the prognosis. 机体在大手术、创伤、重症感染等所致的严重应激状态下,不仅会发生肺脏、心血管、肾脏或胃肠道等脏器功能障碍,也会发生内分泌代谢紊乱,并引起一系列代谢、营养、免疫等方面变化,从而影响病人的临床过程和预后。本文通过动态监测51例不同病因的危重症病人血糖、血清甲状腺激素(thyroid hormone, TH),皮质醇(cortisol, COR)等改变,以了解应激状态下内分泌激素的变化规律以及相互间关系,并了解各项指标与疾病预后的相关性,为是否需要干预治疗提供依据。 1甲状腺激素及皮质醇异常发生率 存活的45例病人,41例(91%)发生血清FT3水平下降,27例(60%)发生血清TSH水平下降,仅有9例(20%)血清FT4水平下降,33例(73%)发生血清COR水平增高;6例死亡病人血清FT3均明显降低,4例病人FT4下降异常明显,同时TSH也有所下降,有1例病人早期发生DIC,COR未升高,考虑与DIC导致肾上腺皮质出血或微血栓形成引起急性肾上腺皮质功能不全有关,其余5例COR均明显增高。 2存活病人循环中激素水平变化 2.1血糖水平变化 51例病人入室血糖均升高,其中存活的45例病人中,MODS组明显高于非MODS组,P<0.05(见表2)。 2.2血清甲状腺激素与TSH变化 45例病人的血清FT3在疾病最初24小时内明显低于正常,P<0.01;血清TSH水平也有显著降低,P<0.05(见表1)。在疾病发展的不同时相中,MODS组血清FT3明显低于非MODS组,两组间比较有显著性差异(P<0.05),TSH也低于非MODS组,但两组没有差异(见表2)。在第三天各检测值均略呈递升趋势,但血清FT3仍明显低于正常(P<0.01)(见表1)。 2.3血清皮质醇变化 45例病人中33例发生血清COR水平增高,在疾病24小时内更加明显,第三天水平略有下降,但仍明显高于正常值,P<0.01(见表1)。MODS组血清COR在整个病程中均高于非MODS组,且有高度显著性差异(P<0.01)(见表2)。 3存活组与死亡组血清各激素水平比较 共有6例病人于入室两天内死亡,除1例发生急性肾上腺皮质功能不全外,其余5例血清COR及血糖均明显升高。血清FT4下降非常明显,与45例存活者比较存在高度显著性差异(P<0.01);血清FT3和TSH也明显下降(P<0.05)。 4甲状腺激素、皮质醇与疾病严重程度的相关性 循环中甲状腺激素改变与疾病严重程度密切相关,血清FT3与APACHE-II改变呈负相关(r=-0.460,P=0.01);血清COR浓度与APACHE-II呈正相关(r=0.575,P=0.000)(见图1)。 三、讨论 在成年病人应激可导致明显的神经内分泌和代谢改变[1]。由于人体对各种严重损伤的反应是极其复杂的相互作用的过程,人体内分泌系统对应激的反应、产生这些反应的循环介质、这些反应与器官功能及预后的关系等尚有许多不明之处,需加以探讨。 1应激高血糖 近年来人们逐渐认识到危重症病人血糖升高是机体对应激的一种适应性反应。然而,实验室研究已经证实细胞外血糖增高会影响机体许多方面的生理功能:减弱宿主对感染的应答[2];减慢伤口愈合[3];使交感系统活性增加[4];促进高凝状态[5];增加心律失常的发生率[6];诱发炎症反应[7]。其中最主要的危害就是增加了感染发生的风险及其严重性。有研究表明应激状态下血糖升高的水平与疾病的严重程度密切相关,本研究中,MODS组病人血糖明显高于非MODS组,两组之间比较具有显著性差异,尤其在存活组与死亡组间比较,死亡的病人应激高血糖更加明显,也表明血糖与病情严重程度之间的相关性。 2下丘脑-垂体-肾上腺轴 严重的疾病、创伤和手术等应激情况时会激活下丘脑-垂体-肾上腺(HPA)轴,使肾上腺合成和分泌皮质醇增加,同时伴有血浆皮质醇清除率的下降,导致血皮质醇浓度升高,从而对抗过度的应激反应。Weissman[8]等指出皮质醇是应激激素活性最重要的指示物,其血中浓度和机体的损伤程度有相关性。本文测定结果表明,51例危重症病人大多存在血清皮质醇浓度明显增高,且随APACHE-II评分增加而升高,与APACHE-II评分呈正相关。死亡组病人血清皮质醇明显高于生存组,说明过高的皮质醇提示预后不良。在疾病不同时期,血清皮质醇水平也不同,病情越严重,血清皮质醇水平也越高,随着病情好转,其水平也逐渐降低。 3非甲状腺疾病综合症(Euthyroid sick syndrome,ESS) 在应激状态下,下丘脑-垂体-甲状腺轴也会受到影响并导致暂时性的甲状腺功能检查异常[9]。ESS是指危重症病人常见的一种甲状腺功能检查的异常,表现为循环中总T3、游离T3水平下降,反T3增加,总T4、游离T4正常或下降,垂体促甲状腺激素(TSH)释放减少或正常,临床可无“甲低”表现。已有研究证实,甲状腺激素水平低下是危重症病人高死亡率的可靠指标,同时FT4水平与死亡率高度相关[10]。本研究中FT3水平下降明显,TSH也有所降低,与文献报道的ESS一致。入室后第三天甲状腺激素和TSH逐渐恢复,表明ESS确实是危重症病人在应激状态下表现出的一种甲状腺功能检查的异常,随着病情的好转可以逐渐恢复正常。血中T4全部来自甲状腺,受TSH调节,病危时肿瘤坏死因子增多,阻断了TSH对甲状腺的作用,使T4分泌减少。6例死亡病人FT4明显降低,提示伴随FT4下降的ESS预后凶险,与文献报道一致[11]。 总之, 机体在应激状态下内分泌代谢指标会发生明显变化,检测血糖、甲状腺激素及皮质醇等对监测病情变化,指导临床治疗及判断病人预后有积极意义。 参考文献: 1.Voerman HJ, Strack van, Schjndel RJ, et al. 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Lancet 1994;343:155-8. 7.Yu WK,Li WQ,Li N,et al.Influence of acute hyperglycemia in human sepsis on inflammatory cytokine and counterregulatory hormone concentrations. World J Gastroenterol 2003;9:1824-7. 8.Weissman C. The metabolic response to stress: an overview and uptake.Anesthesiology.1990, 73:308-327 9.Chopra IJ. Euthyroid sick syndrome: is it a misnoer?J Clin Endocrinol Metab 1997;82:329-34. 10.Slag MF, Morley JE, Elson MK,et al. Hypothyroxenemia in critically ill patients as predictor of high mortality. JAMA 1981;245:43-5. 11.姜志荣,陈志周,尹占莉等。充血性心力衰竭患者甲状腺激素的变化。临床荟萃,1992,7(10):441-442 |
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