儿童脓毒性休克的临床特点及死亡危险因素分析
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摘要
目的：总结脓毒性休克的临床特征,探讨脓毒性休克死亡危险因素,以利于临床上对该病的早期认识、提高脓毒性休克抢救成功率。
方法：对2006年3月-2011年11月广西医科大学第一附属医院儿科重症监护病房(PICU)的83例确诊脓毒性休克住院患儿进行回顾性分析,研究因素包括年龄、性别、临床表现、血白细胞计数(WBC)、血红蛋白(HGB)浓度、血小板(PLT)计数、血清总蛋白浓度(TP)、血清白蛋白浓度(ALB)、动脉血气分析,C-反应蛋白(CRP)、血沉(ESR)、血糖、细菌内毒素、真菌葡聚糖、病原学检查、感染部位、原发病、功能障碍脏器数目、是否需机械通气、液体复苏时间等,统计学分析：1)总结脓毒性休克的临床特点2)探讨脓毒性休克死亡危险因素。
结果：1.本组资料中脓毒性休克总病死率32.5%,其中合并多脏器功能障碍(MODS)的发生率为74.5%,死亡率高达59.09%；脏器损害中肺是最常受累器官。2.本组脓毒性休克患儿死亡组的低血压发生率较非死亡组高,差别有统计学意义(P<0.05)。3.本组脓毒性休克多发生于原发病治疗中,原发病以血液系统疾病、肺炎及消化器官先天发育异常最多见,其中血液系统疾病占40.96%,居脓毒性休克死亡原发病首位。4.本研究中死亡组脓毒性休克患儿液体复苏时间较非死亡组长,休克持续时间长。5.死亡组脓毒性休克患儿较非死亡组病原菌培养阳性率高(P<0.05)。6.单因素分析结果表明,药物复苏时间长、动脉血气酸碱度(PH)<7.35、合并多器官功能受损、病原菌培养阳性4个影响因素是脓毒性休克的死亡危险因素。年龄、性别、住院时间、低血压、白细胞及中性粒细胞计数、HGB、血小板计数、C-反应蛋白、血浆白蛋白浓度、剩余碱(BE)、ESR、血糖、细菌内毒素、真菌葡聚糖、机械通气与脓毒性休克死亡关联无统计学意义。但多因素Logistic回归分析显示药物复苏时间长、动脉血气PH<7.35、合并多器官功能受损、病原体培养阳性4个影响因素与死亡的关联均无统计学意义(P>0.05)。
结论：1.儿童脓毒性休克死亡率高,早期识别和积极液体复苏有利于降低其死亡率。2.单因素分析复苏时间长、动脉血气PH<7.35、合并多器官功能障碍、病原菌培养阳性是脓毒性休克的死亡危险因素。3.加强预防院内感染也是降低脓毒性休克发生率及死亡风险的关键。4.早期识别的线索：原发病、微循环功能障碍指导意义更大。
Objective:To understand the clinical characteristics and to explore the death risks of septic shock in children for a better understanding of its early clinical stage so as to improve the success rate of septic shock.
Methods:Clinical data of83confirmed cases with septic shock who were hospitalized in the Pediatric Intensive Care Unit of the First Affiliated Hospital of Guangxi Medical University from March2006to December2011were collected. Data comprises of the ages, genders, clinical manifestations as well as laboratory informations of blood chemistries like white blood cell(WBC) count, hemoglobin(HGB) concentration,platelet (PLT)count, serum total protein (TP)concentration, serum albumin protein (ALB) concentration, arterial blood gas analysis, C-reactive protein(CRP), erythrocyte sedimentation rate(ESR), glucose. In addition, bacterial endotoxin, serum (1→3)βD glucan, microbiologic etiology, site of infection, underlying primary diseases, the number of dysfunctional organ, mechanical ventilation, time of fluid resuscitation and so on were also recorded. Based on the statistical analysis we could:1) find the clinical summary of pediatric septic shock characteristics, and2) investigate the death risk factors of pediatric septic shock.
Results:1. Of all the83cases, the total mortality rate was32.5%, the incidence of multiple organ dysfunction(MODS) was74.5%, whereas mortality rate in patients with MODS and septic shock was59.09%and in of all the dysfunctional organs, the lung was most often damaged.2. The incidence of hypotension for septic shock in the death group is higher than the non-death group, and the difference is statistically significant.3. Among primary diseases, hematological disease was accounted as the most common, with40.96%, during which septic shock occurs and consequently was also the main cause of death too; letting other disease like pneumonia, congenital abnormalities in digestive orgons to follows as second and third place respectively.4. Time taken of liquid resuscitation in the death group was longer than that in the non-fatal group(P<0.05) and the duration of shock in the death group was significantly higher than that in the non-fatal one.5. Positive rates of pathogen culture was significantly higher in the death group than that in non-death group (P<0.05).6. Univariate analysis revealed that the four factors, namely, long resuscitation times, arterial blood gas with PH<7.35, multiple organ dysfunction and positive pathogen culture were the main death risk factors of septic shock. Others like age, gender, duration of hospitalization, hypotension,WBC and neutrophil count, HGB, PLT, CRP,TP,ALB,BE, ESR, blood glucose, bacterial endotoxin, serum (1→3)β-D glucan, mechanical ventilation were not associated with death in pediatric septic shock. Multivariate logistic regression analysis showed no significant association between the four main death risk factors of septic shock (P>0.05).
Conclusion:1. Mortality in pediatric septic shock was high, and early identification and promptly resuscitation of septic shock can help to reduce mortality rates.2. Univariate analysis revealed that long time of drugs resuscitation, PH of arterial blood gas<7.35, complications like multiple organ dysfunction and positive pathogen culture were the most important death risk factors of septic shock.3. The key to reduce incidence and mortality of septic shock is to strengthen the prevention of nosocomial infection.4. Early identification clue such as underlying primary diseases and microcirculation dysfunction has more guidance significance.
方法：对2006年3月-2011年11月广西医科大学第一附属医院儿科重症监护病房(PICU)的83例确诊脓毒性休克住院患儿进行回顾性分析,研究因素包括年龄、性别、临床表现、血白细胞计数(WBC)、血红蛋白(HGB)浓度、血小板(PLT)计数、血清总蛋白浓度(TP)、血清白蛋白浓度(ALB)、动脉血气分析,C-反应蛋白(CRP)、血沉(ESR)、血糖、细菌内毒素、真菌葡聚糖、病原学检查、感染部位、原发病、功能障碍脏器数目、是否需机械通气、液体复苏时间等,统计学分析：1)总结脓毒性休克的临床特点2)探讨脓毒性休克死亡危险因素。
结果：1.本组资料中脓毒性休克总病死率32.5%,其中合并多脏器功能障碍(MODS)的发生率为74.5%,死亡率高达59.09%；脏器损害中肺是最常受累器官。2.本组脓毒性休克患儿死亡组的低血压发生率较非死亡组高,差别有统计学意义(P<0.05)。3.本组脓毒性休克多发生于原发病治疗中,原发病以血液系统疾病、肺炎及消化器官先天发育异常最多见,其中血液系统疾病占40.96%,居脓毒性休克死亡原发病首位。4.本研究中死亡组脓毒性休克患儿液体复苏时间较非死亡组长,休克持续时间长。5.死亡组脓毒性休克患儿较非死亡组病原菌培养阳性率高(P<0.05)。6.单因素分析结果表明,药物复苏时间长、动脉血气酸碱度(PH)<7.35、合并多器官功能受损、病原菌培养阳性4个影响因素是脓毒性休克的死亡危险因素。年龄、性别、住院时间、低血压、白细胞及中性粒细胞计数、HGB、血小板计数、C-反应蛋白、血浆白蛋白浓度、剩余碱(BE)、ESR、血糖、细菌内毒素、真菌葡聚糖、机械通气与脓毒性休克死亡关联无统计学意义。但多因素Logistic回归分析显示药物复苏时间长、动脉血气PH<7.35、合并多器官功能受损、病原体培养阳性4个影响因素与死亡的关联均无统计学意义(P>0.05)。
结论：1.儿童脓毒性休克死亡率高,早期识别和积极液体复苏有利于降低其死亡率。2.单因素分析复苏时间长、动脉血气PH<7.35、合并多器官功能障碍、病原菌培养阳性是脓毒性休克的死亡危险因素。3.加强预防院内感染也是降低脓毒性休克发生率及死亡风险的关键。4.早期识别的线索：原发病、微循环功能障碍指导意义更大。
Objective:To understand the clinical characteristics and to explore the death risks of septic shock in children for a better understanding of its early clinical stage so as to improve the success rate of septic shock.
Methods:Clinical data of83confirmed cases with septic shock who were hospitalized in the Pediatric Intensive Care Unit of the First Affiliated Hospital of Guangxi Medical University from March2006to December2011were collected. Data comprises of the ages, genders, clinical manifestations as well as laboratory informations of blood chemistries like white blood cell(WBC) count, hemoglobin(HGB) concentration,platelet (PLT)count, serum total protein (TP)concentration, serum albumin protein (ALB) concentration, arterial blood gas analysis, C-reactive protein(CRP), erythrocyte sedimentation rate(ESR), glucose. In addition, bacterial endotoxin, serum (1→3)βD glucan, microbiologic etiology, site of infection, underlying primary diseases, the number of dysfunctional organ, mechanical ventilation, time of fluid resuscitation and so on were also recorded. Based on the statistical analysis we could:1) find the clinical summary of pediatric septic shock characteristics, and2) investigate the death risk factors of pediatric septic shock.
Results:1. Of all the83cases, the total mortality rate was32.5%, the incidence of multiple organ dysfunction(MODS) was74.5%, whereas mortality rate in patients with MODS and septic shock was59.09%and in of all the dysfunctional organs, the lung was most often damaged.2. The incidence of hypotension for septic shock in the death group is higher than the non-death group, and the difference is statistically significant.3. Among primary diseases, hematological disease was accounted as the most common, with40.96%, during which septic shock occurs and consequently was also the main cause of death too; letting other disease like pneumonia, congenital abnormalities in digestive orgons to follows as second and third place respectively.4. Time taken of liquid resuscitation in the death group was longer than that in the non-fatal group(P<0.05) and the duration of shock in the death group was significantly higher than that in the non-fatal one.5. Positive rates of pathogen culture was significantly higher in the death group than that in non-death group (P<0.05).6. Univariate analysis revealed that the four factors, namely, long resuscitation times, arterial blood gas with PH<7.35, multiple organ dysfunction and positive pathogen culture were the main death risk factors of septic shock. Others like age, gender, duration of hospitalization, hypotension,WBC and neutrophil count, HGB, PLT, CRP,TP,ALB,BE, ESR, blood glucose, bacterial endotoxin, serum (1→3)β-D glucan, mechanical ventilation were not associated with death in pediatric septic shock. Multivariate logistic regression analysis showed no significant association between the four main death risk factors of septic shock (P>0.05).
Conclusion:1. Mortality in pediatric septic shock was high, and early identification and promptly resuscitation of septic shock can help to reduce mortality rates.2. Univariate analysis revealed that long time of drugs resuscitation, PH of arterial blood gas<7.35, complications like multiple organ dysfunction and positive pathogen culture were the most important death risk factors of septic shock.3. The key to reduce incidence and mortality of septic shock is to strengthen the prevention of nosocomial infection.4. Early identification clue such as underlying primary diseases and microcirculation dysfunction has more guidance significance.
引文
[1]Wikinson JD, Pollack MM, Ruttimann UE, et al. Outcome of pediatric patients with multiple organ system failure[J]. Crit Care Med,1986, 14(2):271-274.
[2]赵毅斌,唐国军,肖曙芳.脓毒性休克患儿液体复苏临床意义[J].中国医疗前沿,2009,4(21)：3-6.
[3]裘刚,张育才,徐梁,等小儿重症监护病房区脓毒性休克病因及病死危险因素分析[J].中国小儿急救医学,2008,(15)：161-163.
[4]Goldstein B, Giroir B, Randolph A, et al. International pediatric sepsis consensus conference:definitions for sepsis and organ dysfunction in pediatrics[J]. Pediatr Crit Care Med,2005,6(1):2-8.
[5]Jenett B, Bond M. Assessment of outcome after severe brain damage[J]. The Lancet,1975,305(7905):480-484.
[6]Smith L & Hernan L. Shock states[J]. Pediatric Critical Care,2006 3,(27):394-410.
[7]Hatherill M, Tibby SM, Turner C, et al. Procalcitonin and cytokine levels: Relationship to organ failure and mortality in pediatric septic shock[JJ. Crit Care Med,2000,28(7):2591-2594.
[8]王晓敏,赵津生.脓毒性休克死亡危险因素分析[J].中国小儿急救医学,2008,(15)：163-164.
[9]Lundberg JS, Perl TM, Wiblin T, et al. Septic shock:an analysis of outcomes for patients with onset on hospital wards versus intensive care units[J]. Crit Care Med,1998,26(6):1020-1024.
[10]Carcillo JA, Kuch BA, Han Y Y. Mortality and functional morbidity after use of PALS/APLS by community physicians [J]. Pediatrics,2009, 124(2):500-508.
[11]Han YY, Carcillo JA, Dragotta MA Early reversal of pediatric-neonatal septic shock by community physicians is associated with improved outcome[J]. Pediatrics,2003,112(4):793-799.
[12]Inwald DP, Tasker RC, Peters MJ. Emergency management of children with severe sepsis in the United Kingdom:the results of the Paediatric Intensive Care Society sepsis audit [J].Arch.Dis.Child,2009,94(5): 348-353.
[13]Rivers E, Nguyen B, Havstad S, et al. Early goal-directed therapy in the treatment of severe sepsis and septic shock[J]. N Engl J Med,2001, 345(19):1368-1377.
[14]De Swiet M, Fayers P, Shinebourne EA. Systolic BP in a population of infants in the first year of life:the brompton study[J]. Pediatrics,1980, 65(5):1028-1035.
[15]黄爱蓉,何时军等.脓毒性休克患儿死亡危险因素分析[J].中国当代儿科杂志,2009,11,(4)：280-282.
[16]陈研.急诊抢救中快速判读血气分析的临床意义[J].实用临床医学,2007,8(8)：28-31.
[17]Kutko MC,Calarvo MP,Flaherty MB,et al.Mortality rates in pediatric septic shock with and without multiple organ system failure [J]. Pediatr Crit Care Med,2003,4(3):333-337.
[18]M Militaru,D Martinovici.our experience in pediatric sepsis[J]. Juenalul Pediatrului,2005(29-30),8:26-31.
[19]张国英,魏艳等.成都市儿童医院重症监护病房2002～2006年病原菌流行分布与耐药趋势分析[J].中国小儿急救医学,2007,14(4)：313-316.
[20]Bochud PY, Glauser MP, Calandra T.Antibiotics in sepsis[J]. Intensive Care Medicine,2001,27:S33-S48.
[1]Bone BC. Sepsis, the sepsis symdrone, multi-organ failure:a plea for comparable definitions[J]. Ann Intern Med,1991,114(4):332-333.
[2]Von Rosenstiel N, Von Rosenstiel I,Adam D. Management of sepsis and septic shock in infants and children [J]. Paediatr Drugs,2001,3(1):9-27.
[3]American heart Association.2005 American heart association(AHA) guidelines for cardiopu lmonary resuscitation (CPR) and emergency cardiovascular care(ECC) of pediatrics,2006,117:1005-1028.
[4]Ni Choileain N, Redmond H P. The immunological consequences of injury[J]. Surg,2006,4(1):23-31.
[5]Niels C. Riedemann, Ren Feng goo, et al. Novel strategies for the treatment of sepsis[J]. NatMed,2003,9(6):517-524.
[6]Tetta C, Fonsato V, Ronco C, et al.Recent insights into the pathogenesis of severe sepsis[J]. Crit Care Resusc,2005,7(1):32-39.
[7]Goldstein B, Giroir B, Randolph A. International pediatric sepsis consensus conference:definitions for sepsis and organ dysfunction in pediatrics[J]. Pediatr Crit Care Med,2005,6(1):2-8.
[8]胡皓夫.与国际接轨,提高我国儿童脓毒症的诊治水平[J].中华急诊医学杂志,2006,15(6)：487-488.
[9]中华医学会儿科学分会急救学组,中华医学会急诊学分会儿科组,华儿科杂志.儿科感染性休克(脓毒性休克)诊疗推荐方案[J].中华儿科 杂志,2006,44(8)：596-598.
[10]Carcillo JA, Fields AI, de Forca-Tarefa C. Clinical practice parameters for hemodynamic support of pediatric and neonatal patients in septic shock[J]. J Pediatr(Rio J),2002,78(6):449-466.
[11]Dellinger RP, Levy MM, Carlet JM, et al. Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock:2008[J]. Intensive Care Med,2008,34(1):17-60.
[12]温文英.大剂量甲基强的松龙治疗小儿感染性休克的观察[J].实用诊断与治疗杂志,2004,18(5)：404-405.
[13]Kumar A, Roberts D, Wood KE, et al. Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock [J]. Crit Care Med,2006,34 (6): 1589-1596.
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[15]Gaieski DF, Mikkelsen ME, Band RA, et al. Impact of time to antibiotics on survival in patients with severe sepsis or septic shock in whom early goal-directed therapy was initiated in the emergency department [J]. Crit Care Med,2010,38(4):1045-1053.
[16]沈玉才,黄维本,张晓红.超小剂量肝素皮下注射治疗新生儿弥散性 血管内凝血的临床应用[J].中国小儿急救医学,2006,13(4)：316-318.
[17]Haque K N, Remo C, Bahakim H. Comparison of two types of intravenous immunoglobulins in the treatment of neonat al sepsis[J].Clin Exp Immunol,1995,101(2):328.
[2]赵毅斌,唐国军,肖曙芳.脓毒性休克患儿液体复苏临床意义[J].中国医疗前沿,2009,4(21)：3-6.
[3]裘刚,张育才,徐梁,等小儿重症监护病房区脓毒性休克病因及病死危险因素分析[J].中国小儿急救医学,2008,(15)：161-163.
[4]Goldstein B, Giroir B, Randolph A, et al. International pediatric sepsis consensus conference:definitions for sepsis and organ dysfunction in pediatrics[J]. Pediatr Crit Care Med,2005,6(1):2-8.
[5]Jenett B, Bond M. Assessment of outcome after severe brain damage[J]. The Lancet,1975,305(7905):480-484.
[6]Smith L & Hernan L. Shock states[J]. Pediatric Critical Care,2006 3,(27):394-410.
[7]Hatherill M, Tibby SM, Turner C, et al. Procalcitonin and cytokine levels: Relationship to organ failure and mortality in pediatric septic shock[JJ. Crit Care Med,2000,28(7):2591-2594.
[8]王晓敏,赵津生.脓毒性休克死亡危险因素分析[J].中国小儿急救医学,2008,(15)：163-164.
[9]Lundberg JS, Perl TM, Wiblin T, et al. Septic shock:an analysis of outcomes for patients with onset on hospital wards versus intensive care units[J]. Crit Care Med,1998,26(6):1020-1024.
[10]Carcillo JA, Kuch BA, Han Y Y. Mortality and functional morbidity after use of PALS/APLS by community physicians [J]. Pediatrics,2009, 124(2):500-508.
[11]Han YY, Carcillo JA, Dragotta MA Early reversal of pediatric-neonatal septic shock by community physicians is associated with improved outcome[J]. Pediatrics,2003,112(4):793-799.
[12]Inwald DP, Tasker RC, Peters MJ. Emergency management of children with severe sepsis in the United Kingdom:the results of the Paediatric Intensive Care Society sepsis audit [J].Arch.Dis.Child,2009,94(5): 348-353.
[13]Rivers E, Nguyen B, Havstad S, et al. Early goal-directed therapy in the treatment of severe sepsis and septic shock[J]. N Engl J Med,2001, 345(19):1368-1377.
[14]De Swiet M, Fayers P, Shinebourne EA. Systolic BP in a population of infants in the first year of life:the brompton study[J]. Pediatrics,1980, 65(5):1028-1035.
[15]黄爱蓉,何时军等.脓毒性休克患儿死亡危险因素分析[J].中国当代儿科杂志,2009,11,(4)：280-282.
[16]陈研.急诊抢救中快速判读血气分析的临床意义[J].实用临床医学,2007,8(8)：28-31.
[17]Kutko MC,Calarvo MP,Flaherty MB,et al.Mortality rates in pediatric septic shock with and without multiple organ system failure [J]. Pediatr Crit Care Med,2003,4(3):333-337.
[18]M Militaru,D Martinovici.our experience in pediatric sepsis[J]. Juenalul Pediatrului,2005(29-30),8:26-31.
[19]张国英,魏艳等.成都市儿童医院重症监护病房2002～2006年病原菌流行分布与耐药趋势分析[J].中国小儿急救医学,2007,14(4)：313-316.
[20]Bochud PY, Glauser MP, Calandra T.Antibiotics in sepsis[J]. Intensive Care Medicine,2001,27:S33-S48.
[1]Bone BC. Sepsis, the sepsis symdrone, multi-organ failure:a plea for comparable definitions[J]. Ann Intern Med,1991,114(4):332-333.
[2]Von Rosenstiel N, Von Rosenstiel I,Adam D. Management of sepsis and septic shock in infants and children [J]. Paediatr Drugs,2001,3(1):9-27.
[3]American heart Association.2005 American heart association(AHA) guidelines for cardiopu lmonary resuscitation (CPR) and emergency cardiovascular care(ECC) of pediatrics,2006,117:1005-1028.
[4]Ni Choileain N, Redmond H P. The immunological consequences of injury[J]. Surg,2006,4(1):23-31.
[5]Niels C. Riedemann, Ren Feng goo, et al. Novel strategies for the treatment of sepsis[J]. NatMed,2003,9(6):517-524.
[6]Tetta C, Fonsato V, Ronco C, et al.Recent insights into the pathogenesis of severe sepsis[J]. Crit Care Resusc,2005,7(1):32-39.
[7]Goldstein B, Giroir B, Randolph A. International pediatric sepsis consensus conference:definitions for sepsis and organ dysfunction in pediatrics[J]. Pediatr Crit Care Med,2005,6(1):2-8.
[8]胡皓夫.与国际接轨,提高我国儿童脓毒症的诊治水平[J].中华急诊医学杂志,2006,15(6)：487-488.
[9]中华医学会儿科学分会急救学组,中华医学会急诊学分会儿科组,华儿科杂志.儿科感染性休克(脓毒性休克)诊疗推荐方案[J].中华儿科 杂志,2006,44(8)：596-598.
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