摘要
目的：结合APACHEⅡ评分及SOFA评分,评价血清降钙素原(procalcitonin, PCT)评估急性胰腺炎严重程度和判断预后的价值,探讨血清降钙素原浓度与急性胰腺炎患者发生重症急性胰腺炎及死亡之间的关系。
方法：选取2009年5月-2010年3月在湘雅医院住院的急性胰腺炎患者41例,根据2008年美国急性胰腺炎临床指南将其分为轻症急性胰腺炎组(17例),重症急性胰腺炎组(24例),并随机选取正常健康志愿者15例作为对照组。同时将41例急性胰腺炎患者按照PCT浓度正常为<0.5ng/ml;轻度升高为0.5ng/ml≤PCT浓度<2.0ng/ml；明显升高为2.0ng/ml;为标准分为正常组,轻度升高组和明显升高组。对急性胰腺炎患者在入院后24小时内进行SOFA(Sepsis-related organ failure assessmen, SOFA)评分及APACHEⅡ(Acute physiology and chronic health evaluation, APACHEⅡ)评分,并抽取急性胰腺炎患者及健康志愿者外周静脉血用于PCT检测。密切追踪观察患者直至其出院,并记录住院期间的死亡病例数。将PCT浓度、APACHEⅡ评分、SOFA评分、病死率之间的关系进行分析。
结果：1.血清PCT浓度重症急性胰腺炎组显著高于轻症急性胰腺炎组(p<0.001)和正常对照组(p<0.001)；轻症急性胰腺炎组显著高于正常对照组(p<0.001)
2.将PCT浓度与APACHEⅡ评分及SOFA评分进行非参数等级相关分析,结果显示PCT浓度与APACHEⅡ评分(r=0.668,P<0.001)及SOFA评分(r=0.722,P<0.001)呈明显正相关。
3.PCT浓度明显升高组的病死率大于PCT浓度轻度升高组的病死率(P=0.022)和PCT浓度正常组的病死率(P=0.006); PCT浓度轻度升高组的病死率与PCT浓度正常组的病死率差异无统计学意义(P=0.528)。
4.采用logistic回归分析结果显示PCT是急性胰腺炎患者发生重症急性胰腺炎的危险因素。
5.进一步采用logistic回归分析结果显示SOFA评分是急性胰腺炎患者死亡的危险因素。
结论：1.检测血清PCT浓度可以客观判断急性胰腺炎患者病情的严重程度。
2.PCT浓度越高,急性胰腺炎患者为重症急性胰腺炎的风险越大。
3.PCT在低浓度时对急性胰腺炎患者的病死率没有影响；高浓度时,急性胰腺炎患者的病死率可能增大,但PCT不是急性胰腺炎患者死亡的危险因素。
Objective:To assess the diagnostic and prognostic value of procalcitonin(PCT) and discuss the relations among PCT concentrations, severe acute pancreatitis and death in patients with acute pancreatitis by combining with APACHEⅡscore and SOFA score.
Methods:The method adopted was to select a sample of 41 patients with acute pancreatitis from May 2009 to March 2010 in Xiangya Hospital.These patients were classified into mild acute pancreatitis group(17 cases), severe acute pancreatitis group (24 cases) according to the definition of Diagnosis and treatment guidelines for acute pancreatitis of USA in 2008. And 15 healthy volunteers were also chosen as a control group. Meanwhile,41 patients were divided into PCT concentrations normal groups,mild rise group and obvious rise group according to the normal PCT concentrations<0.5ng/ml,mild rise of 0.5ng/ml≤PCT concentrations<2.0ng/ml and obvious rise of PCT concentrations≥2.0ng/ml.SOFA score, APACHEⅡscore and blood samples were obtained with in 24 hours after admission. Blood samples were used to detect the concentrations of PCT.Through follow-up visit to the patients with acute pancreatitis,and record of the number of deaths, their relations were analyzed.
Results:1. Procalcitonin concentrations was significantly higher in patients with severe acute pancreatitis than in patients with mild acute pancreatitis (▲p<0.001) and the control group(p<0.001).It was also found that the procalcitonin concentrations was much higher in patients with mild acute pancreatitis than that of the control group(p<0.001).
2.PCT concentrations were positively correlated with the severity of acute pancreatitis. Spearman's correlation coefficient between PCT concentrations and APACHEⅡscore was 0.668(p<0.001);and the Spearman's correlation coefficient between PCT concentrations and SOFA score was 0.722(p<0.001).
3.It was concluded that the case-fatality rate of the PCT concentrations obvious rise group was significantly higher than the group of PCT concentrations mild rise group (p=0.022) and that of PCT concentrations normal group(p=0.006). However,there was no statistic difference between PCT concentrations mild rise group and PCT concentrations normal group(p=0.528)
4.Binary Logistic regression analysis confirmed that PCT concentrations was obviously correlated with severe acute pancreatitis when eliminating confusion factors including age,sex and SOFA score.
5. SOFA score was found highly correlated with death in patients with acute pancreatitis by using binary Logistic regression analysis without considering confusion factors including age,sex,PCT and APACHEⅡscore.
Conclusion:1. PCT concentrations detecting could be used to juge the severity of acute pancreatitis.
2.Higher concentrations of PCT increases the risk of developing severe acute pancreatitis in patients with acute pancreatitis.
3. When the PCT concentrations was at a lower level,it had no influence on the Fatality rate.If it was at a higher level, the Fatality rate might be rise up. But it was not the risk factor that leading to death in patients with acute pancreatitis.
引文
[1]Zilvinas Dambrauskasl, Juozas Pundzius GiedriusBarauskas.Predicting development of infected necrosis in acute necrotizing pancreatitis[J]. Medicina (Kaunas) 2006; 42(6):441-450.
[2]Hartwig W,Maksan S,Thomas F,et al.Reduction in mortality with delayed surgical therapy of severe pancreatitis[J]. Gastrointest Surg,2002,6(3):481-487.
[3]Claeys R,Vinken S, Spapen H, et al. Plasma procalcitonin and C-reactive protein in acute septic shock:clinical and biological corerlates[J]. Crit Care Med,2002, 30(4):757-762.
[4]Assicot M.Gendrel D.Carsin H.High serum procalcitonin concentrations in patients with sepsis and infection [J].Infection,1993,16(5):384-389.
[5]Kretzschmar M, Kruger A, Schirrmeister W. Procalcitonin following elective partial liver resection-origin from the liver?[J]. Acta Anaesthesiol Scand. 2001;45(9):1162-1167.
[6]Pezzilli R, Morselli-Labate AM, Romboli E, et al. Pancreatic involvement during the early phase of shock[J]. JOP.2002;3(5):139-143.
[7]Maruna P, Nedelnikova K, Gurlich R. Physiology and genetics of procalcitonin. Physiol Res[J].2000;49(Suppl 1):S57-S61.
[8]Meisner M, Tschaikowsky K, Hutzler A, et al. Postoperative plasma concentrations of procalcitonin after different types of surgery[J]. Intensive Care Med.1998; 24(7):680-684.
[9]Meisner M, Muller V, Khakpour Z, et al. Induction of procalcitonin and pro inflammatory cytokines in an anhepatic baboon endotoxin shock model [J]. Shock.2003; 19(2):187-90.
[10]Kiriyama Y, Nomura Y, Tokumitsu Y. Calcitonin gene expression induced by lipopolysaccharide in the rat pituitary [J]. Am J Physiol Endocrinol Metab.2002; 282(6):E1380-1384.
[11]Oberhoffer M, Stonans I, Russwurm S, et al. Procalcitonin expression in human peripheral blood mononuclear cells and its modulation by lipopolysaccharides and sepsis-related cytokines in vitro[J]. J Lab Clin Med.1999; 134(1):49-55.
[12]Pugin J, Widmer MC, Kossodo S, et al. Human neutrophils secrete gelatinase B in vitro and in vivo in response to endotoxin and proinflammatory mediators[J]. Am J Respir Cell Mol Biol.1999;20(3):458-464.
[13]Hatherill M, Tibby SM, Turner C, rt al. Procalcitonin and cytokine levels: relationship to organ failure and mortality in pediatric septic shock[J]. Crit Care Med.2000;28(7):2591-2594.
[14]Reinhart K, Karzai W, Hartog-Schier C. Procalcitonin(PCT)and its Role in the Diagnosis of Sepsis[J]. Lancet,2003,23(2):157-161.
[15]Luzzani A, Polati E, Dorizzi Ret al. Comparison of procalcitonin and C-reactive portein as markers ofsepsis[J]. Crit Care Med,2003,31(6):1737-1741.
[16]Sato N, Endo S, Kasai T, Inoue Y, Fujino Y, Onodera M, Imai S, Takahashi G, Miyata M, Kitamura M, Wakabayashi G. Relationship of the serum procalcitonin level with the severity of acute pancreatitis[J]. Res Commun Mol Pathol Pharmacol. 2004; 115-116:243-249.
[17]Mofidi R, Suttie SA, Patil PV, Ogston S, Parks RW. The value of procalcitonin at predicting the severity of acute pancreatitis and development of infected pancreatic necrosis:systematic review[J].Surgery.2009 Jul; 146(1):72-81.
[18]Olah A, Belagyi T, Issekutz A, Makay R, Zaborszky A. Value of procalcitonin quick test in the differentiation between sterile and infected forms of acute pancreatitis[J]. Hepatogastroenterology.2005,Jan-Feb;52(61):243-245.
[19]Makay R, Issekutz A, Banga P,et al. Role of procalcitonin rapid test in the differential diagnosis of uninfected and infected forms of acute pancreatitis[J]. Magy Seb,2003,56(1):31-34.
[20]邢豫宾,戴路明,赵芝焕,李志伟,李超.血清降钙素原和血清常用炎症指标结合SOFA评分对脓毒症早期诊断和预后价值的评价[J].中国危重病急救医学2008,20(1)：23-28.
[21]Gurlich R,Marun P,spicak J,et,al.Prediction and monitoring of severe acute pancreatitis[J].Cas Leck Cesk,2006,14(5):437-441
[22]Kylanpaa-Back ML, Takala A, Kemppainen EA, et al. Procalcitonin, soluble interleukin-2 receptor, and soluble E-selectin in predicting the severity of acute pancreatitis[J]. Crit Care Med,2001,29(6):63-69
[23]Ammori BJ.Becker KL.Kite P,et al. Calcitonin precursors in the prediction of severity of acutepancreatitis on the day of admission [J].Br J Surg,2003,90(12): 197-204
[24]Nurullah B.Osman D.Refik A,et al. Procalcitonin is a predictive marker for severe acute pancreatitis[J].Ulus Travma Derg,2006,12(6):115-120
[25]Modrau IS.Floyd AK.Thorlacius-Ussing O.The clinical value of procalcitonin in early assessment of acute panereatitis[J].Am J Gastroenterol,2005,100(13): 1593-1597.
[26]Nusrat S.Samir M.Deepak KB Estimating the diagnostic accuracy of procaleitonin as a marker of the severity of acute pancreatitis:A meta-analytic approach[J]. JOP Pancreas,2005,6(3):231-237.
[27]Neoptolemos JP, Kemppainen EA, Mayer JM, et al. Early prediction of severty in acute pancreatitis by urinary trypsinogen activation peptide:a multicentre study [J]. lancet,2000,355:1955-1960.
[28]Ala Kokko, Tieranta N, Ⅰ aurila J, et al. Determinants of ICU mortality in necrotizing pancreatitis:the influence of StaphylOcOccus epidermidis[J]. Acta Anaesthesiol Scand,2001,23(2):1123-1127.
[29]Ture M, Memis D, Kurt Ⅰ, Pamukcu Z. Predictive value of thyroid hormones on the first day in adult respiratory distress syndrome patients admitted to ICU: comparison with SOFA and APACHE Ⅱ scores[J]. Ann Saudi Med.2005 Nov-Dec;25(6):466-472.
[30]Oberhoffer M, Stonans I, Russwurm S, et al. Procalcitonin expression inhuman peripheral blood mononuclear cells and its modulation by lipopolysaccharides and sepsis related cytokines in vitro[J]. Lab Clin Med,1999,134:49-54.
[31]Maruna P,Nedelnikova K, Gurlich R. Physiology and genetics of procalcitonin[J]. Physiol Res,2000,49(11):57-59.
[32]贲其稳 袁耀宗.降钙素原与急性胰腺炎[J].国际消化病志,2008,28(1)：69-73
[33]Nylen ES, Whang KT, Snider RH, et al. Mortality is increased by procalcitonin and decreased by an antiserum reactive to procalcitonin in experimental sepsis. Crit Care Med 1998;26(6):1001-1006.
[34]Martinez JM, Wagner KE, Snider RH, et al. Late immunoneutralization of procalcitonin arrests the progression of lethal porcine sepsis. Surg Infect (Larchmt). 2001;2(3):193-202; discussion 202-203.
[35]Luzzani A,Polati E,Dorizzi R,et al.Comparison of procalcitonin and C-reactive protein as markers of sepsis[J]. Crit Care Med,2003,31(6):1737-1741.
[36]Meisner M,Tschaikowsky K,Palmaers T,et al.Compa-risonof procalcitonin (PCT)and C-reactive protein (CRP) plasma concentrations at different SOFA scores during the course of sepsis and MODS[J]. Crit Care,1999,3(1):45-50.
[37]Wagner KE,Martinez JM, Vath SD, et al. Early immunoneutralization of calcitonin precursors attenuates the adverse physiologic response to sepsis in pigs.Crit Care Med.2002;30(10):2313-2321.
[1]李兆坤.急性胰腺炎治疗研究进展——从外科手术到介入治疗[J].中国现代普通外科进展,2008,12(12)：1013-1017.
[2]Hartwig W,Maksan S,Thomas F,et al.Reduction in mortality with delayed surgical therapy of severepancreatitis[J]. Gastrointest Surg,2002,6(3):481-487.
[3]黄晓丽,刘顺英,王国.降钙素原—重症急性胰腺炎早期评估的一项新指标[J].胰腺病学,2005,5(4)：246-248.
[4]Karzai W,Oberhoffer M,Meier-H ellmann A,et,al.Procalcitonin-a new indicator of the systemic response to severe infections[J]. Infection,1997,25: 329-334
[5]Karzai W,Oberhoffer M,Meier-H ellmann A,et,al.Procalcitonin-a new indicator of the systemic response to severe infections [J]. Infection,1997,25: 329-334
[6]Broad PM, Symes AJ, Thakker RV, et al. Structure and methylation of the human calcitonin/alpha-CGRP gene[J]. Nucleic Acids Res 1989; 17: 6999-7011.
[7]Poschl E, Lindley I, Hofer E, et al. The structure of procalcitonin of the salmon as deduced from its cDNA sequence. FEBS Lett.1987; 226(1):96-100.
[8]Collyear K, Girgis SI, Saunders G, et al. Predicted structure of the bovine calcitonin gene-related peptide and the carboxy-terminal flanking peptide of bovine calcitonin precursor[J]. J Mol Endocrinol.1991;6(2):147-152.
[9]Rosenblatt MI, Dickerson IM. Endoproteolysis at tetrabasic amino acid sites in procalcitonin gene-related peptide by pituitary cell lines[J]. Peptides.1997; 18(4):567-576.
[10]Amara SG, Jonas V, Rosenfeld MG, et al. Alternative RNA processing in calcitonin gene expression generates mRNAs encoding different polypeptide products[J]. Nature 1982; 298:240-2444.
[11]Thiagalingam A, De Bustros A, Borges M, et al. RREB-1, a novel zinc finger protein, is involved in the differentiation response to Ras in human medullary thyroid carcinomas[J]. Mol Cell Biol 1996; 16:5335-5345.
[12]Rehli M, Luger K, Beier W, et al Molecular cloning and expression procalcitonin[J]. Biochem Biophys Res Commun 1996; 226:420-5.
[13]Oberhoffer M,Vogelsang H,Jager L,et al.Katacalcin and calcltonin immunoreactivity in different types of leukocytes inDicate intracellular procalcitonin cotent [J]. Crit Care,1999,14:29-33
[14]Meisner M, Schmidt J, Huettner H, et al. The natural elimination rate of procalcitonin in patients with normal and impaired renal function[J]. Intensive Care Med 1999; 26(Suppl):212-216.
[15]Steinwald PM, Whang KT, Becker KL, et al. Elevated calcitonin precursor levels are related to mortality in an animal model of sepsis[J]. Crit Care. 1999；3(1):11-16.
[16]Maruna P, Nedelnikova K, Gurlich R. Physiology and genetics of procalcitonin[J]. Physiol Res.2000;49(Suppl 1):S57-61.
[17]Oberhoffer M, Stonans Ⅰ, Russwurm S, et al. Procalcitonin expression inhuman peripheral blood mononuclear cells and its modulation by lipopolysaccharides and sepsis related cytokines in vitro [J]. Lab Clin Med, 1999,134:49-54.
[18]Maruna P,Nedelnikova K, Gurlich R. Physiology and genetics of procalcitonin[J]. Physiol Res,2000,49[Suppl 1]:57-59.
[19]Morgenthaler NG,Struck J,Chancerelle Y, et al. Production of procalcitonin (PCT) in nonthyroidal tissue after LPS injection [J]. HormMetab Res,2003,35 (5):290-296.
[20]白晓川,白志勇,武淑兰.8种肿瘤细胞系降钙素基因甲基化模式及其与甲基转移酶活性的关系[J].癌症,2001,20(2)：156-159.
[21]汪明明,孙玉秋,张绢,等.血清降钙素原玉感染性疾病并全身炎性反应综合征的相关性研究[J].中华内科杂志,2002,41(10)：69-71.
[22]张崴,陈礼明,张世兰等.肝硬化伴自发性细菌性腹膜炎患者血浆降钙素原的检测及临床意义[J].中华医学杂志,2003,83(7)：605-607.
[23]Berger C,Schwarz S,Schaebitz WR. Serum procalcitonin in cerebral ventriculitis[J]. Crit Care Med,2002,30 (8):1778-1782.
[24]GiamarellosBourboulis EJ,Grecka P,Poulakou G,et al. Assessment of procalcitonin as a diagnostic marker of underlying infection in patients with febrile neutropenia[J]. Clin Infect Dis,2001,32 (12):1718-1723.
[25]Hatherill M,Tibby SM,Turner C,et al. Procalcitonin and cytokine levels: relationship to organ failure and mortality in pediatric septic shock [J].Crit Care Med,2000,28 (7):2591-2594.
[26]Luzzani A,Polati E,Dorizzi R,et al. Comparison of procalcitonin and Creactive protein as markers of sepsis[J]. Crit Care Med,2003,31 (6) 1737-1741.
[27]王赤,任天成等.血清降钙素原对多器官功能障碍综合征早期诊断的价值[J].山东医药,2009,49(37)：56-57
[28]费军,余洪俊,周健,等.多发伤患者血清降钙素原的变化[J].中华创伤杂志,2005,21(10)：75-77.
[29]王赤,任天成等.降钙素原变化在严重创伤致MODS早期诊断中的临床意义[J].山东医药,2010,50(5)：61-63
[30]Gurlich R,Marun P,spicak J,et,al.Prediction and monitoring of severe acute pancreatitis[J].Cas Leck Cesk,2006,14(5):437-441
[31]Kylanpaa-Back ML, Takala A, Kemppainen EA, et al. Procalcitonin, soluble interleukin-2 receptor, and soluble E-selectin in predicting the severity of acute pancreatitis[J]. Crit Care Med,2001,29(6):63-69
[32]Ammori BJ.Becker KL.Kite P,et al. Calcitonin precursors in the prediction of severity of acutepancreatitis on the day of admission [J].Br J Surg,2003, 90(12):197-204
[33]Nurullah B.Osman D.Refik A,et al. Procalcitonin is a predictive marker for severe acute pancreatitis[J].Ulus Travma Derg,2006,12(6):115-120
[34]Modrau IS.Floyd AK.Thorlacius-Ussing O.The clinical value of procalcitonin in early assessment of acute panereatitis[J].Am J Gastroenterol,2005, 100(13):1593-1597.
[35]Nusrat S.Samir M.Deepak KB Estimating the diagnostic accuracy of procaleitonin as a marker of the severity of acute pancreatitis:A meta-analytic approach[J]. JOP Pancreas,2005,6(3):231-237.
[36]Dellinger RP.Carlet JM.Masur H Surviving sepsis campaign guidelines for management of severe sepsis and septic shock [J]. Crit Care Med,2004, 32(5):868-873.
[37]Makay R.Issekutz A.Banga P Role of procalcitonin rapid test in the differential diagnosis of uninfected and infected forms of acute pancreatitis[J]. Magy Seb,2003,56(7):31-33.
[38]Yonetci N.Sunqurtekin U.Oruc N Is procalcitonin a reliable marker in the diagonosis of infectedpancreatic necrosis?[J].ANZ J Surg,2004,74 (34): 591-595.
[39]Florence CR,Bernard PC,Marie-Josephe. Inflammatory cytokines,C reactive protein,and procalcitonin as early predictors of necrosis infection in acute necrotizing pancreatitis [J].Surgery,2003,27(5):257-262.
[40]Ammori BJ,Becker KL,Kite P. Caleitonin precursors:Early markers of gut Barrier dysfunction in patients with acute pancreatitis[J]. Pancreas,2003, 27(4):239-243.
[41]Becker KL,Nylen ES,Snider RH.Immunoneutralization of procalcitonin as therapy of sepsis[J].Endotoxin Re,2003,19(11):367-374.