严重烧伤早期“容量补充+动力扶持”复苏方案的临床研究
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摘要
研究背景
严重烧伤早期缺血缺氧是导致内脏继发性损伤和死亡的关键因素，休克是烧伤早期缺血缺氧最重要的原因。一般认为，休克的发生与血容量、心脏泵功能和血管张力(反应性)等三个主要因素密切相关，但对烧伤休克发生的认识并非如此。既往认为，烧伤休克血容量降低主要因毛细血管通透性增加，使血管内血浆样体液渗出，导致有效循环血容量减少所致，但目前还没有找到降低毛细血管通透性的有效措施，在治疗上主要采取补液替代治疗(容量补充)；在严重休克情况下或休克的后期，可出现血管反应性低下，使血管床扩张，导致有效循环血容量进一步减少。治疗上采用血管活性药物；而对于休克发生的另一重要因素——心脏泵功能，传统观点认为，心脏不出现结构损伤及器质性功能障碍，不参与早期休克的发生。但大量临床现象提示，在许多严重烧伤，即使伤后及时给予补液治疗，休克也很难纠正，且心肌损害指标早期迅速显著升高，心功能指标降低。表明严重烧伤后在有效循环血容量显著下降之前，心肌即发生了缺血缺氧损害和功能减退。由于心脏是循环的动力器官，严重烧伤后即早(在因毛细血管通透性增加导致有效循环血容量显著减少之前)出现的心肌损害及心泵功能减弱，可诱发或加重休克，成为烧伤早期缺血缺氧的重要启动因素之一，由此提出了烧伤早期组织器官缺血缺氧损害的“休克心”假说。因此，烧伤休克的发生除与血容量减少有关外，还与早期心肌损害引起的循环泵功能减弱有关。有效防治烧伤早期心肌损害和功能减退，是防治烧伤休克的重要环节。基于这些研究发现，提出了“容量补充+动力扶持”的烧伤休克复苏新方案。
近年来研究表明，严重烧伤早期应用小剂量依那普利拉注射液可改善烧伤早期心肌局部血流量，减轻心肌损害，又不会对循环血压造成明显影响；果糖二磷酸钠注射液可以调节心肌细胞的钙代谢紊乱,下调Fas基因的蛋白表达，从而抑制心肌细胞凋亡减轻心肌损害；前列地尔注射液可增强心肌SOD活性减少MDA生成，也可改善冠脉循环，减轻心肌损害。因此我们采用上述药物进行“动力扶持”。
本课题采取临床前瞻性随机对照研究(RCT)方法，针对立即复苏和延迟复苏两种情形，通过设计不同“容量补充+动力扶持”复苏方案，检测相关指标，在总结分析复苏效果及安全性的基础上，进而提出“容量补充+动力扶持”的烧伤休克复苏新方案，为烧伤临床休克治疗和提高严重大面积烧伤治愈率奠定基础。
试验方法
一、试验材料及主要仪器设备
1．主要药品及试剂：果糖二磷酸钠注射液(山东鲁抗辰欣药业有限公司提供)，批准文号：国药准字H20056909，规格100ml:10g。前列地尔注射液(西安力邦制药有限公司提供)，批准文号：国药准字H20103100，规格2ml:10ug。依那普利拉注射液(常州制药厂有限公司提供)，批准文号：国药准字H20010498，规格1ml:1.25mg (以C18H24N205计)。谷草转氨酶(AST)、谷丙转氨酶(ALT)检测试剂盒(日本Olympus公司提供)，肌酸激酶(CK)检测试剂盒(北京莱帮生物技术有限公司提供)，血尿素(BUN)检测试剂盒(德国罗氏诊断试剂有限公司提供)，血肌酐(Cr)检测试剂盒(北京利德曼生化技术有限公司提供),CK-MB检测试剂盒(北京莱帮生物技术有限公司提供),CK检测试剂盒(北京莱帮生物技术有限公司提供)，谷氨酰转肽酶(GGT)检测试剂盒(Beckman公司提供)，β2微球蛋白(β2-MG)检测试剂盒(原子高科股份有限公司提供)。cTnI检测试剂盒(Beckman公司提供)，乳酸(LA)检测试剂盒(南京建成生物研究所提供)。
2．主要仪器：Olympus AU5400全自动生化分析仪：日本产；ACCESS微粒子化学发光分析仪：美国产。BC-5800自动血细胞分析仪：中国产，DU640紫外分光光度计：美国产。自动放免仪：中国科大中佳公司。
二、病例资料
1．病例资料来源
第三军医大学西南医院烧伤科2009年12月至2012年03月住院烧伤患者。烧伤深度和面积分别按照三度四分法和中国九分法断定，选取符合纳入标准的住院病例。
2．纳入标准：必须满足所有以下标准才能进入试验组
①年龄18～65岁，性别不限；
②烧伤：选择热液及火焰烧伤患者，不选化学原因烧伤患者；
③TBSA：>30%，深二度、三度≥20%；
④烧伤后5小时内入院，或入院前已进行系统液体复苏治疗(立即复苏组)。烧伤后6小时入院，或入院前未进行液体复苏治疗(延迟复苏组)
⑤烧伤后心肌酶学检查提示cTnI>0.15ug/L(阳性)或CK-MB>25IU/L。
3．排除标准:存在以下任何一项均需排除
①既往有心血管病史的患者(如重度充血性心衰，病窦综合征，II或III度房室传导阻滞，房扑或房颤合并有房室旁路通道，已用β受体阻滞剂或洋地黄中毒的病人，QRS增宽(≥0.12秒)的室性心动过速病人)；
②既往患有高血压或低血压的患者，以及血压波动较大的患者；
③年龄＜18岁或＞65岁的患者；
④烧伤后心肌酶学检查提示cTnI<0.15ug/L(阴性)或CK-MB<25IU/L等患者；
⑤有严重心、肝、肾、肺等身体重要脏器器质性病变或者近期新发心肌梗塞、心肌损害等患者；
⑥有明显的精神障碍、癫痫等症状的患者；
⑦哺乳期或孕期妇女患者；
⑧对试验用药过敏或有相应禁忌症的患者；
⑨试验依从性较差或试验过程中失访的患者；
⑩其他判断不适宜入选的病例。
4．终止标准
①患者死亡；
②患者不配合(违背协议或失访)或出于安全考虑需要终止试验。
三、试验分组及过程
1．试验分组
符合纳入标准的住院病例，按患者入院先后顺序进行随机化分组(随机数字表)，分为单纯容量补充立即复苏对照组、立即容量补充＋动力扶持组(依那普利拉注射液、果糖二磷酸钠注射液、前列地尔注射液三种药物分别单独随机入组观察)、延迟复苏单纯容量补充对照组、延迟容量补充＋动力扶持组(依那普利拉注射液、果糖二磷酸钠注射液、前列地尔注射液三种药物分别单独随机入组观察)。各组病人在性别、年龄、致伤因素、致伤面积等方面进行均衡性控制，以保持各组之间的可比性。
2．试验过程
(1)容量补充对照组：病例入组后，按照补液复苏方案制定补液计划，进行“容量补充”，液体成分以晶体液、胶体液、糖分为主。根据受试者临床表现，需要应用西地兰注射液等治疗者，则按照临床常规临时使用，余处理因素在符合伦理原则条件下按照目前临床常规方法进行系统治疗。
(2)容量补充+动力扶持治疗组：病例入组后，按照补液复苏方案制定补液计划，进行“容量补充”，液体成分以晶体液、胶体液、糖分为主。同时分别应用5%葡萄糖注射液100ml+依那普利拉注射液1.25mg静脉输入1次/日，5%葡萄糖注射液100ml+果糖二磷酸钠注射液10g静脉输入2次/日，5%葡萄糖注射液100ml+前列地尔注射液10ug静脉输入2次/日，连用3天以行“动力扶持”治疗，余处理因素在符合伦理原则条件下按照目前临床常规方法进行系统治疗。
分别于入院时、伤后1天、2天、3天、1周、2周、3周观察指标及收集标本，其中生命体征以晨起6：00-8：00之间为准，血液指标按照临床常规，取晨起后6：00-8：00空腹血液，检测有关指标，并对复苏方案疗效及安全性等进行分析。
四、检测指标及方法
1．检测指标
(1)休克相关指标：休克期情况(补液量、尿量等)，生命体征、血乳酸等
(2)脏器损害指标：心脏－(cTnI、CK、CK-MB、aHBDH、LDH)、肝脏－(ALT、AST、GGT)、肾脏－(Cr、BUN、β2-MG、AG)；
(3)血液常规指标：血细胞比容(HCT)、白细胞数(WBC)、中性细胞分类(NEUT%)、红细胞数(RBC)、淋巴细胞分类(LYMPH%)、血小板(PLT)。
2．检测方法
(1)按照受试者伤后第一个24小时及第二个24小时实际补液量及尿量进行统计分析。同时按照受试者护理记录单生命体征为依据，收集生命体征、血常规等数据进行统计分析。
(2)血液指标：血清乳酸(LA)、谷草转氨酶(AST)、谷丙转氨酶(ALT)、谷氨酰转肽酶(GGT)活、血尿素(BUN)、血肌酐(Cr)、β2微球蛋白(β2-MG)、血清心肌肌钙蛋白I(cTnI)、血清激酸激酶(CK)、血清心肌型肌酸激酶同工酶(CK-MB)等按试剂盒检测说明书在西南医院检验科完成检测。
五、统计分析
所有计量数据均以(x±s)表示，采用SPSS13.0统计软件进行单因素方差分析及均数间多重比较，以P<0.05为相差显著，P<0.01为相差非常显著；所有计数资料采用SPSS13.0统计软件进行卡方检验，以P<0.05为相差显著，P<0.01为相差非常显著。
试验结果
总入选145例，脱落10例(立即果糖组2例，立即前列地尔组2例，立即依那普利拉组1例；延迟对照组1例，延迟果糖组1例，延迟前列地尔组2例，延迟依那普利拉组1例)，不合格3例(分别为立即前列地尔组1例患有癫痫、两例入院诊断为30%，校正面积分别为立即果糖组1例28%和立即前列地尔组1例29%)，有效病例为132例，其中失访8例(立即复苏和延迟复苏各失访4例)，总体失访率(8/132)为6.06%。
一、立即复苏
1．病例资料：立即容量补充对照组有效病例15例，致伤面积(45.07±4.58)%TBSA,其中51%TBSA以上者仅占总例数的20%，三度面积(11.00±4.34)%TBSA，合并吸入性损伤4例，气管切开4例，3周内死亡2例。立即容量补充+动力扶持治疗组(包括三种不同动力扶持药物治疗病例,其中果糖二磷酸钠注射液组20例，前列地尔注射液组21例和依那普利拉注射液组14例)有效病例共计55例，致伤总面积(47.78±2.51)%TBSA，其中51%TBSA以上者占总例数的30.9%，三度面积(14.67±2.42)%TBSA，合并吸入性损伤23例，气管切开18例，3周内无死亡病例。从绝对数来看，立即容量补充+动力扶持治疗组伤情重于立即容量补充对照组，但各组年龄、性别、致伤因素、吸入性损伤发生率无显著差异(卡方检验，P>0.05)，提示各组均衡性较好。立即复苏失访4病例为对照组2例(未完成试验，患者死亡失访)，果糖组1例(未完成试验，出院后失去联系)，前列地尔组1例(未完成试验，出院后失去联系)。
2．死亡率：“容量补充”对照组死亡率为13.30%(2/15)，容量补充+果糖二磷酸钠注射液(20例)、前列地尔注射液(21例)和依那普利拉注射液(14例)三个治疗组3周内均无死亡病例。表明即使在伤情重于容量补充对照组的情况下，“容量补充+动力扶持”复苏方案能显著降低立即复苏烧伤患者的死亡率。
3．抗休克相关试验结果：在维持满意尿量的前提下，尽管动力扶持组(果糖二磷酸钠注射液、前列地尔注射液及依那普利拉注射液)烧伤面积和三度烧伤面积均大于容量补充对照组，但动力扶持组补液量稍少于对照组，而尿量稍多于对照组。容量补充+果糖二磷酸钠注射液、前列地尔注射液和依那普利拉注射液三种药物治疗组血压、血清乳酸(LA)含量未见明显差异，但血清乳酸(LA)含量均显著低于容量补充对照组(P<0.05)；各组RBC、HCT、HGB、WBC、体温、脉搏、呼吸、血压等在观测期内均未见显著差异(P>0.05)。
4．脏器功能损害指标：容量补充+果糖二磷酸钠注射液、容量补充+前列地尔注射液和容量补充+依那普利拉注射液三组脏器功能损害指标差异不明显，但三组cTnI、CK-MB、CK、a-HBDH、LDH、β2-MG均优于容量补充对照组。入院后1天、2天、3天容量补充+动力扶持组cTnI、CK-MB、CK、a-HBDH、LDH、血清β2-MG均低于容量补充对照组(P<0.05)。
二、延迟复苏
1．病例资料：延迟容量补充对照组14例，致伤总面积(48.00±3.90)%TBSA，其中51%TBSA以上者仅占总例数的35.70%，三度面积(16.00±4.98)%TBSA，合并吸入性损伤3例，3周内死亡2例；延迟容量补充+动力扶持组(包括三种不同动力扶持药物治疗病例，其中果糖二磷酸钠注射液组17例，前列地尔注射液组15例和依那普利拉注射液组16例)共计48例，致伤总面积(59.13±3.08)%TBSA，其中51%TBSA以上者占总例数的62.50%，三度面积(23.06±3.19)%TBSA，合并吸入性损伤25例，3周内死亡2例(果糖二磷酸钠及依那普利拉治疗组各1例)。延迟容量补充对照组、延迟容量补充+果糖二磷酸钠注射液、前列地尔注射液或依那普利拉注射液以及延迟容量补充+动力扶持组(三个药物治疗组汇总)年龄、性别、致伤因素等无显著差异(P>0.05)。从绝对数来看，延迟容量补充+动力扶持治疗组伤情重于延迟容量补充对照组。延迟复苏失访4例：对照组死亡2例失访，果糖组死亡1例失访，依那普利拉组死亡1例失访。
2．死亡率：延迟“容量补充”对照组死亡率为14.30%(2/14)，延迟容量补充+果糖二磷酸钠注射液及延迟容量补充+依那普利拉注射液分别为5.90%(1/17)和6.30%(1/16)，延迟容量补充+前列地尔注射液组无死亡病例。表明即使在伤情重于容量补充对照组的情况下，“容量补充+动力扶持”复苏方案能显著降低延迟复苏烧伤患者的死亡率。
3．抗休克有关试验结果：从第1个和第2个24小时补液量及尿量可分析发现，在维持满意尿量的前提下，尽管动力扶持组烧伤面积和三度烧伤面积均大于对照组，但动力扶持组补液量、尿量、血压未见明显差异。容量补充+果糖二磷酸钠注射液、容量补充+前列地尔注射液和容量补充+依那普利拉注射液三组血压、血清乳酸(LA)含量未见明显差异，但血清乳酸(LA)含量均低于容量补充对照组(P<0.05)；各组RBC、HCT、HGB、WBC、体温、脉搏、呼吸、血压等在观测期内均未见显著差异(P>0.05)。
4．脏器功能损害指标：容量补充+果糖二磷酸钠注射液、容量补充+前列地尔注射液和容量补充+依那普利拉注射液三组脏器功能损害指标差异不明显，但三组cTnI、CK-MB、CK、a-HBDH、LDH、β2-MG均低于容量补充对照组。容量补充+动力扶持治疗组cTnI、CK-MB、CK、LDH、a-HBDH、β2-MG等显著低于容量补充对照组(P<0.05)。
讨论与结论
1．对严重烧伤后早期入院或延迟复苏患者，应用第三军医大学补液公式立即复苏进行“容量补充”，或应用第三军医大学延迟复苏补液公式进行“容量补充”。分别应用依那普利拉、果糖二磷酸钠及前列地尔注射液行“动力扶持”治疗，三种药物治疗，均可有效地改善组织器官缺血缺氧、改善组织氧合和有氧代谢，从而减少内脏并发症，提高治愈率，但三种药物的效果无显著差异。
2．本试验提出的“容量补充+动力扶持”复苏方案为：
立即复苏方案：第1个24小时补液总量(ml)=TBSA(1%)×体重(kg)×1.5ml+生理需要量(2000ml)+动力扶持药物(依那普利拉或果糖二磷酸钠或前列地尔)；第2个24小时补液总量(ml)=TBSA(1%)×体重(kg)×1.0ml+生理需要量(2000ml)+动力扶持药物(依那普利拉或果糖二磷酸钠或前列地尔)。
延迟复苏方案：第1个24小时补液总量(ml)=TBSA(1%)×体重(kg)×2.6ml+生理需要量(2000ml)+动力扶持药物(依那普利拉或果糖二磷酸钠或前列地尔)；第2个24小时补液总量(ml)=TBSA(1%)×体重(kg)×1.0ml+生理需要量(2000ml)+动力扶持药物(依那普利拉或果糖二磷酸钠或前列地尔)。
3．“容量补充+动力扶持”复苏方案安全、有效，不仅有助于烧伤休克复苏治疗，减少并发症，提高严重烧伤救治水平，通过该临床试验，进一步验证了严重烧伤早期缺血缺氧损害的“休克心”假说，对于进一步认识烧伤休克/缺血缺氧的发生机制和严重烧伤休克的治疗均有重要意义。
Objective and background
The key factors of visceral secondary injury and death after severe burns are ischemiaand hypoxia，and shock is the most important reason for ischemia and hypoxia during theearly stage.It is well known that the occurrence of shock are closely related to the bloodvolume, cardiac pump function and vascular tone (reactivity), but the understanding of burnshock is not the case. Previously thought that, blood volume decrease of the burn shock wasprimarily due to the increased capillary permeability, plasma-like fluid in the intravascularleakage, resulting in a decrease in effective circulating blood volume. As there are noeffective measures to reduce capillary permeability so far, now fluid replacement therapy(Volume replacement) is the main treatment. In the circumstances of a serious shock or thelate stage of shock, the low vascular reactivity makes the expansion of the vascular bed,resulting in effective circulating blood volume to further reduce, and vasoactive drug can beused in this case. Another important factor for the shock is the heart pump function. Thetraditional view is that the heart does not appear to structural damage and organic dysfunction,does not participate in the occurrence of early shock. But a large number of clinical findingssuggest that, in many severe burn patients, even if given prompt fluid infusion after injury,shock is difficult to correct. Meanwhile the early myocardial damage indicators significantlyincreased and heart function reduced, suggesting that before the effective circulating bloodvolume decreased significantly, myocardial ischemia and hypoxia damage and dysfunctionhave occurred following severe burns. Because the heart is the power organ of the circulation,the early and prompt myocardial damage and heart dysfunction(before a significant reductionin effective circulating blood volume due to increased capillary permeability), not only causedcardiac dysfunction, but also induced or exacerbated the shock. It becomes one of theimportant factors to start early ischemia and hypoxia. Therefore, a "shock heart" hypothesis for ischemic and hypoxic damage of visceral organs and tissues during early stage followingsevere burns has been proposed. Thus, effective control of early postburn myocardial damageand dysfunction is an important part of prevention and treatment of burn shock. Based on theabove findings, the new protocol for burn shock resuscitation including "volume replacementplus cardiodynamic support" has been presented.
Recent studies have shown that early application of small doses of enalaprilat injectionafter severe burns can improve the regional myocardial blood flow, reduce myocardialdamage and does not affect systemic blood pressure significantly. FDP injection can regulatecalcium dismetabolism of the myocardial cells, and inhibit cardiomyocyte apoptosis to reducemyocardial damage. Alprostadil injection can enhance the SOD activity of myocardial toreduce the MDA formation, improve the coronary circulation, and reduce myocardial damage.Therefore, we use these drugs for "cardiodynamic support".
This subject is a clinical prospective randomized controlled trial (RCT), for immediateresuscitation and delayed resuscitation, analyze the efficacy and safety of the resuscitationprotocol, and then propose a new program of "volume replacement plus cardiodynamicsupport" for the burn shock resuscitation, and lay the foundation for the burn clinical therapyand improve the cure rate of severe burns.
Materials and methods
Hospitalized patients during December,2009to March,2012in burn unit of SouthwestHospital, Third Military Medical University were enrolled. Burn depth and surface area weredetermined according to clinic diagnostic criteria for burn patients. The selected hospitalizedpatients met the inclusion criteria as follows:①patients with age above18and under65years old, male or female;②patients with flame or hot liquid injury;③TBSA>30%withdeep second degree and third degree burn area≥20%);④At admission within6hourspostburn, or regular fluid resuscitation received prior to admission (immediate resuscitationgroup). At admission after6hours postburn, or irregular fluid resuscitation received whenadmitted (delayed resuscitation group);⑤Serum cTnI>0.15ug/L (positive) orCK-MB>25IU/L when admitted. The exclusion criteria are as follows:①patients withhistory of cardiovascular disease;②Patients suffering from hypertension, hypotension, orblood pressure fluctuations previously;③patients with age <18or>65;④Serum cTnI <0.15ug/L (negative) or CK-MB<25IU/L when admitted;⑤serious organic disease such as liver, kidney, lungs and other vital organs of the body;⑥patients with significant mentaldisorders, epilepsy and other symptoms;⑦lactating or pregnant female patients;⑧patientswho are allergic to experimental drugs or patients with corresponding contraindications;⑨patients dropped during the period of research;⑩other cases that are considered to be notsuitable for research. Termination criteria:①patients died;②patients do not fit (contrary tothe agreement or lost to follow) or for security reasons.
Patients who met the inclusion criteria were divided into four groups randomly:immediate volume replacement (V group), immediate volume replacement pluscardiodynamic support (V+D group， including three subgroups enalapril, fructosediphosphate sodium, and alprostadil), delayed volume replacement (DV group), delayedvolume replacement plus cardiodynamic support (DV+D group). Cardiodynamic supportwere performed by application of1.25mg of enalaprilat(E) once a day，10g of FDP(F) twicea day or10ug of alprostadil(A) twice a day, lasting for3days. Indicators were observed andrecorded at admission, day1,2,3,7,14and21postburn respectively, including vital signs (T,P, R, BP recorded at6:00-8:00in the morning), LA, cTnI, CK, CK-MB, aHBDH, LDH, ALT,AST, GGT, Cr, BUN, β2-MG, AG, HCT, WBC, NEUT%, RBC, LYMPH%, and PLT.
Statistical analysis
All data are expressed as (x±s) and analyzed using statistical software SPSS13.0.Probability values less than0.05were considered to be significant, and P <0.01were verysignificant.
Results
1. Immediate resuscitation
1) Cases description: There were15effective cases in V group, the mean burn area was(45.07±4.58)%TBSA,20%of cases suffered more than51%TBSA burns, the mean Ⅲ°burn area was (11.00±4.34)%TBSA,4cases combined with inhalation injury, and2casesdied in3weeks after burn injury. There were55effective cases in V+D group (includingsubgroup enalapril14cases, fructose diphosphate sodium20cases, and alprostadi21cases),the mean burn area was (47.78±2.51)%TBSA,30.9%of cases suffered more than51%TBSAburns, the mean Ⅲ°burn area was (14.67±2.42)%TBSA,23cases combined with inhalationinjury, and no case died in3weeks after burn injury. Considering of the absolute value, theseverity of burn patients in V+D group was more severe than that in V group. However, there was no significant difference (p>0.05) in age, gender, injury factors, and inhalation injuryincidence, suggesting a good balance between immediate V group and immediate V+D group.
2) Mortality: There was a13.30%(2/15) mortality in V group, however, in enalapril,fructose diphosphate sodium, and alprostadil treated groups, no patients died, suggesting thatthe resuscitation scheme of “volume replacement plus cardiodynamic support” significantlydecreased the mortality of burn patients in V+D group, even in the case of burn injury issevere than that in V group.
3) Results of anti-shock indicators: Based on maintaining a satisfactory urine output,although there was a larger area and more severe burn injury, less fluid infusion volume in thethree treated subgroups and V+D group than those in V group was used, the urine output wasslightly more than that in V group, and there was no significant difference in blood pressureamong the three treated subgroups and the control, as well as V and V+D groups. Comparedwith V group, the serum level of lactate (LA) was significantly decreased in the three treatedsubgroups and V+D group (P <0.05) after admission; There were no significant difference (P>0.05) in RBC、HCT、HGB、WBC、body temperature, pulse, respiration rate and blood pressureamong the three treated subgroups and the control, as well as V and V+D groups.
4) Laboratory results of organ functions: There were no differences among three kinds ofdrugs (enalapril,fructose diphosphate sodium, alprostadil)in laboratory results of organsfunctions. Compared with V group, the serum levels of cTnI, CK-MB, CK, a-HBDH andLDH were significantly decreased in in the three treated subgroups and V+D group (P <0.05);The serum level of β2-MG was significantly decreased in in the three treated subgroups andV+D group (P <0.05).
2. Delayed resuscitation
1) Cases description: There were also14effective cases in DV group (including threesubgroups enalapril, fructose diphosphate sodium, and alprostadil), the mean burn area was(48.00±3.90)%TBSA,35.70%of cases suffered more than51%TBSA burn, the mean Ⅲ°burn area was (16.00±4.98)%TBSA,3cases combined with inhalation injury, and2cases diedin3weeks after burn injury. There were effective48cases in DV+D group (includingsubgroup enalapril16cases, fructose diphosphate sodium17cases, and alprostadi15cases),the mean burn area was (59.13±3.08)%TBSA,62.50%of cases suffered more than51%TBSA burns, the mean Ⅲ°burn area was (23.06±3.19)%TBSA,25cases combined with inhalation injury, and2cases died in3weeks after burn injury. It is obvious that the severityof burn injury in DV+D group was more severe than that in DV group. However, there was nosignificant difference (p>0.05) in age, gender, injury factors, suggesting a good balancebetween DV group and DV+D group. However, there was a higher inhalation injury incidencein DV+D group than that in DV group (chi-square test, p>0.05).
2) Mortality: The mortality in the control group was14.30%(2/14),5.90%(1/17) infructose diphosphate sodium treated subgroup,6.30%(1/16) in subgroup enalapril, and4.20%(2/48) in DV+D group, a10.10%decrease of mortality in DV+D group compared withthat in DV group, suggesting that the resuscitation scheme of “volume replacement pluscardiodynamic support” significantly decreased the mortality of burn patients suffering fromdelayed resuscitation, even in the case of burn injury is more severe than DV group.
3) Results of anti-shock: after analyzing the fluid volume and urine output in the first andsecond24-hour of burn injury, based on maintaining a satisfactory urine output, althoughthere was a bigger area of burn injury in the three treated subgroups and DV+D group thanthose in DV group, the fluid infusion volume was slightly less in all the treated groups, but nosignificant differences were found among the treated groups. There was also no significantdifference in blood pressure in the three treated subgroups and DV+D group than those in DVgroup. Compared with DV group, the serum level of LA was significantly decreased in thethree treated subgroups and DV+D group (P <0.05), no significant differences were foundamong the three treated subgroups and the control, as well as V+D and V group. There wereno significant difference (P>0.05) in RBC、HCT、HGB、WBC、body temperature, pulse,respiration rate and blood pressure between groups in the observation period.
4) Laboratory results of organs functions: There were no differences of parametersreflecting organs dysfunctions among the treated groups. Compared with DV group, theserum levels of cTnI, CK-MB, CK, a-HBDH and LDH were significantly decreased in thethree treated subgroups and DV+D group (P <0.05). The serum level of β2-MG was alsosignificantly decreased in the three treated subgroups and DV+D group (P <0.05).
Discussion and conclusion
1. Cardiodynamic supports plus fluid resuscitation attenuated ischemic and hypoxicdamage, promoted oxygenation or oxygen metabolism, reduced organ complications andimproved survival rate in severe burn patients. There were no differences among three kinds of drugs (enalapril, fructose diphosphate sodium, and alprostadil)in clinical efficacy.
2. The recommended new resuscitation strategy to severe burn patients according to ourcurrent research is as following:
1) for immediate resuscitation patients, the fluid volume of the first24h postburn (ml)=TBSA×boby weight(kg)×1.5+2000+cardiodynamic support drugs (enalapril or fructosediphosphate sodium or alprostadil)；the fluid volume of the second24h postburn (ml)=TBSA×boby weight(kg)×1.0+2000+cardiodynamic support drugs;
2) for delayed resuscitation patients, the fluid volume of the first24h postburn (ml)=TBSA×boby weight (kg)×2.6+2000+cardiodynamic support drugs (enalapril or fructosediphosphate sodium or alprostadil)；the fluid volume of the second24h postburn (ml)=TBSA×boby weight(kg)×1.0+2000+cardiodynamic support drugs.
3. Our prospective clinic research provided further evidence for the "shock heart"hypothesis for ischemic and hypoxic damage of visceral organs and tissues during early stagefollowing severe burns, and thus shed a new light for us to understand the underlyingmechanisms of burn shock. The recommended new strategy improved fluid resusciation andreduced organ complications, which may be therefore great significant for the treatment ofsevere burn patients.
严重烧伤早期缺血缺氧是导致内脏继发性损伤和死亡的关键因素，休克是烧伤早期缺血缺氧最重要的原因。一般认为，休克的发生与血容量、心脏泵功能和血管张力(反应性)等三个主要因素密切相关，但对烧伤休克发生的认识并非如此。既往认为，烧伤休克血容量降低主要因毛细血管通透性增加，使血管内血浆样体液渗出，导致有效循环血容量减少所致，但目前还没有找到降低毛细血管通透性的有效措施，在治疗上主要采取补液替代治疗(容量补充)；在严重休克情况下或休克的后期，可出现血管反应性低下，使血管床扩张，导致有效循环血容量进一步减少。治疗上采用血管活性药物；而对于休克发生的另一重要因素——心脏泵功能，传统观点认为，心脏不出现结构损伤及器质性功能障碍，不参与早期休克的发生。但大量临床现象提示，在许多严重烧伤，即使伤后及时给予补液治疗，休克也很难纠正，且心肌损害指标早期迅速显著升高，心功能指标降低。表明严重烧伤后在有效循环血容量显著下降之前，心肌即发生了缺血缺氧损害和功能减退。由于心脏是循环的动力器官，严重烧伤后即早(在因毛细血管通透性增加导致有效循环血容量显著减少之前)出现的心肌损害及心泵功能减弱，可诱发或加重休克，成为烧伤早期缺血缺氧的重要启动因素之一，由此提出了烧伤早期组织器官缺血缺氧损害的“休克心”假说。因此，烧伤休克的发生除与血容量减少有关外，还与早期心肌损害引起的循环泵功能减弱有关。有效防治烧伤早期心肌损害和功能减退，是防治烧伤休克的重要环节。基于这些研究发现，提出了“容量补充+动力扶持”的烧伤休克复苏新方案。
近年来研究表明，严重烧伤早期应用小剂量依那普利拉注射液可改善烧伤早期心肌局部血流量，减轻心肌损害，又不会对循环血压造成明显影响；果糖二磷酸钠注射液可以调节心肌细胞的钙代谢紊乱,下调Fas基因的蛋白表达，从而抑制心肌细胞凋亡减轻心肌损害；前列地尔注射液可增强心肌SOD活性减少MDA生成，也可改善冠脉循环，减轻心肌损害。因此我们采用上述药物进行“动力扶持”。
本课题采取临床前瞻性随机对照研究(RCT)方法，针对立即复苏和延迟复苏两种情形，通过设计不同“容量补充+动力扶持”复苏方案，检测相关指标，在总结分析复苏效果及安全性的基础上，进而提出“容量补充+动力扶持”的烧伤休克复苏新方案，为烧伤临床休克治疗和提高严重大面积烧伤治愈率奠定基础。
试验方法
一、试验材料及主要仪器设备
1．主要药品及试剂：果糖二磷酸钠注射液(山东鲁抗辰欣药业有限公司提供)，批准文号：国药准字H20056909，规格100ml:10g。前列地尔注射液(西安力邦制药有限公司提供)，批准文号：国药准字H20103100，规格2ml:10ug。依那普利拉注射液(常州制药厂有限公司提供)，批准文号：国药准字H20010498，规格1ml:1.25mg (以C18H24N205计)。谷草转氨酶(AST)、谷丙转氨酶(ALT)检测试剂盒(日本Olympus公司提供)，肌酸激酶(CK)检测试剂盒(北京莱帮生物技术有限公司提供)，血尿素(BUN)检测试剂盒(德国罗氏诊断试剂有限公司提供)，血肌酐(Cr)检测试剂盒(北京利德曼生化技术有限公司提供),CK-MB检测试剂盒(北京莱帮生物技术有限公司提供),CK检测试剂盒(北京莱帮生物技术有限公司提供)，谷氨酰转肽酶(GGT)检测试剂盒(Beckman公司提供)，β2微球蛋白(β2-MG)检测试剂盒(原子高科股份有限公司提供)。cTnI检测试剂盒(Beckman公司提供)，乳酸(LA)检测试剂盒(南京建成生物研究所提供)。
2．主要仪器：Olympus AU5400全自动生化分析仪：日本产；ACCESS微粒子化学发光分析仪：美国产。BC-5800自动血细胞分析仪：中国产，DU640紫外分光光度计：美国产。自动放免仪：中国科大中佳公司。
二、病例资料
1．病例资料来源
第三军医大学西南医院烧伤科2009年12月至2012年03月住院烧伤患者。烧伤深度和面积分别按照三度四分法和中国九分法断定，选取符合纳入标准的住院病例。
2．纳入标准：必须满足所有以下标准才能进入试验组
①年龄18～65岁，性别不限；
②烧伤：选择热液及火焰烧伤患者，不选化学原因烧伤患者；
③TBSA：>30%，深二度、三度≥20%；
④烧伤后5小时内入院，或入院前已进行系统液体复苏治疗(立即复苏组)。烧伤后6小时入院，或入院前未进行液体复苏治疗(延迟复苏组)
⑤烧伤后心肌酶学检查提示cTnI>0.15ug/L(阳性)或CK-MB>25IU/L。
3．排除标准:存在以下任何一项均需排除
①既往有心血管病史的患者(如重度充血性心衰，病窦综合征，II或III度房室传导阻滞，房扑或房颤合并有房室旁路通道，已用β受体阻滞剂或洋地黄中毒的病人，QRS增宽(≥0.12秒)的室性心动过速病人)；
②既往患有高血压或低血压的患者，以及血压波动较大的患者；
③年龄＜18岁或＞65岁的患者；
④烧伤后心肌酶学检查提示cTnI<0.15ug/L(阴性)或CK-MB<25IU/L等患者；
⑤有严重心、肝、肾、肺等身体重要脏器器质性病变或者近期新发心肌梗塞、心肌损害等患者；
⑥有明显的精神障碍、癫痫等症状的患者；
⑦哺乳期或孕期妇女患者；
⑧对试验用药过敏或有相应禁忌症的患者；
⑨试验依从性较差或试验过程中失访的患者；
⑩其他判断不适宜入选的病例。
4．终止标准
①患者死亡；
②患者不配合(违背协议或失访)或出于安全考虑需要终止试验。
三、试验分组及过程
1．试验分组
符合纳入标准的住院病例，按患者入院先后顺序进行随机化分组(随机数字表)，分为单纯容量补充立即复苏对照组、立即容量补充＋动力扶持组(依那普利拉注射液、果糖二磷酸钠注射液、前列地尔注射液三种药物分别单独随机入组观察)、延迟复苏单纯容量补充对照组、延迟容量补充＋动力扶持组(依那普利拉注射液、果糖二磷酸钠注射液、前列地尔注射液三种药物分别单独随机入组观察)。各组病人在性别、年龄、致伤因素、致伤面积等方面进行均衡性控制，以保持各组之间的可比性。
2．试验过程
(1)容量补充对照组：病例入组后，按照补液复苏方案制定补液计划，进行“容量补充”，液体成分以晶体液、胶体液、糖分为主。根据受试者临床表现，需要应用西地兰注射液等治疗者，则按照临床常规临时使用，余处理因素在符合伦理原则条件下按照目前临床常规方法进行系统治疗。
(2)容量补充+动力扶持治疗组：病例入组后，按照补液复苏方案制定补液计划，进行“容量补充”，液体成分以晶体液、胶体液、糖分为主。同时分别应用5%葡萄糖注射液100ml+依那普利拉注射液1.25mg静脉输入1次/日，5%葡萄糖注射液100ml+果糖二磷酸钠注射液10g静脉输入2次/日，5%葡萄糖注射液100ml+前列地尔注射液10ug静脉输入2次/日，连用3天以行“动力扶持”治疗，余处理因素在符合伦理原则条件下按照目前临床常规方法进行系统治疗。
分别于入院时、伤后1天、2天、3天、1周、2周、3周观察指标及收集标本，其中生命体征以晨起6：00-8：00之间为准，血液指标按照临床常规，取晨起后6：00-8：00空腹血液，检测有关指标，并对复苏方案疗效及安全性等进行分析。
四、检测指标及方法
1．检测指标
(1)休克相关指标：休克期情况(补液量、尿量等)，生命体征、血乳酸等
(2)脏器损害指标：心脏－(cTnI、CK、CK-MB、aHBDH、LDH)、肝脏－(ALT、AST、GGT)、肾脏－(Cr、BUN、β2-MG、AG)；
(3)血液常规指标：血细胞比容(HCT)、白细胞数(WBC)、中性细胞分类(NEUT%)、红细胞数(RBC)、淋巴细胞分类(LYMPH%)、血小板(PLT)。
2．检测方法
(1)按照受试者伤后第一个24小时及第二个24小时实际补液量及尿量进行统计分析。同时按照受试者护理记录单生命体征为依据，收集生命体征、血常规等数据进行统计分析。
(2)血液指标：血清乳酸(LA)、谷草转氨酶(AST)、谷丙转氨酶(ALT)、谷氨酰转肽酶(GGT)活、血尿素(BUN)、血肌酐(Cr)、β2微球蛋白(β2-MG)、血清心肌肌钙蛋白I(cTnI)、血清激酸激酶(CK)、血清心肌型肌酸激酶同工酶(CK-MB)等按试剂盒检测说明书在西南医院检验科完成检测。
五、统计分析
所有计量数据均以(x±s)表示，采用SPSS13.0统计软件进行单因素方差分析及均数间多重比较，以P<0.05为相差显著，P<0.01为相差非常显著；所有计数资料采用SPSS13.0统计软件进行卡方检验，以P<0.05为相差显著，P<0.01为相差非常显著。
试验结果
总入选145例，脱落10例(立即果糖组2例，立即前列地尔组2例，立即依那普利拉组1例；延迟对照组1例，延迟果糖组1例，延迟前列地尔组2例，延迟依那普利拉组1例)，不合格3例(分别为立即前列地尔组1例患有癫痫、两例入院诊断为30%，校正面积分别为立即果糖组1例28%和立即前列地尔组1例29%)，有效病例为132例，其中失访8例(立即复苏和延迟复苏各失访4例)，总体失访率(8/132)为6.06%。
一、立即复苏
1．病例资料：立即容量补充对照组有效病例15例，致伤面积(45.07±4.58)%TBSA,其中51%TBSA以上者仅占总例数的20%，三度面积(11.00±4.34)%TBSA，合并吸入性损伤4例，气管切开4例，3周内死亡2例。立即容量补充+动力扶持治疗组(包括三种不同动力扶持药物治疗病例,其中果糖二磷酸钠注射液组20例，前列地尔注射液组21例和依那普利拉注射液组14例)有效病例共计55例，致伤总面积(47.78±2.51)%TBSA，其中51%TBSA以上者占总例数的30.9%，三度面积(14.67±2.42)%TBSA，合并吸入性损伤23例，气管切开18例，3周内无死亡病例。从绝对数来看，立即容量补充+动力扶持治疗组伤情重于立即容量补充对照组，但各组年龄、性别、致伤因素、吸入性损伤发生率无显著差异(卡方检验，P>0.05)，提示各组均衡性较好。立即复苏失访4病例为对照组2例(未完成试验，患者死亡失访)，果糖组1例(未完成试验，出院后失去联系)，前列地尔组1例(未完成试验，出院后失去联系)。
2．死亡率：“容量补充”对照组死亡率为13.30%(2/15)，容量补充+果糖二磷酸钠注射液(20例)、前列地尔注射液(21例)和依那普利拉注射液(14例)三个治疗组3周内均无死亡病例。表明即使在伤情重于容量补充对照组的情况下，“容量补充+动力扶持”复苏方案能显著降低立即复苏烧伤患者的死亡率。
3．抗休克相关试验结果：在维持满意尿量的前提下，尽管动力扶持组(果糖二磷酸钠注射液、前列地尔注射液及依那普利拉注射液)烧伤面积和三度烧伤面积均大于容量补充对照组，但动力扶持组补液量稍少于对照组，而尿量稍多于对照组。容量补充+果糖二磷酸钠注射液、前列地尔注射液和依那普利拉注射液三种药物治疗组血压、血清乳酸(LA)含量未见明显差异，但血清乳酸(LA)含量均显著低于容量补充对照组(P<0.05)；各组RBC、HCT、HGB、WBC、体温、脉搏、呼吸、血压等在观测期内均未见显著差异(P>0.05)。
4．脏器功能损害指标：容量补充+果糖二磷酸钠注射液、容量补充+前列地尔注射液和容量补充+依那普利拉注射液三组脏器功能损害指标差异不明显，但三组cTnI、CK-MB、CK、a-HBDH、LDH、β2-MG均优于容量补充对照组。入院后1天、2天、3天容量补充+动力扶持组cTnI、CK-MB、CK、a-HBDH、LDH、血清β2-MG均低于容量补充对照组(P<0.05)。
二、延迟复苏
1．病例资料：延迟容量补充对照组14例，致伤总面积(48.00±3.90)%TBSA，其中51%TBSA以上者仅占总例数的35.70%，三度面积(16.00±4.98)%TBSA，合并吸入性损伤3例，3周内死亡2例；延迟容量补充+动力扶持组(包括三种不同动力扶持药物治疗病例，其中果糖二磷酸钠注射液组17例，前列地尔注射液组15例和依那普利拉注射液组16例)共计48例，致伤总面积(59.13±3.08)%TBSA，其中51%TBSA以上者占总例数的62.50%，三度面积(23.06±3.19)%TBSA，合并吸入性损伤25例，3周内死亡2例(果糖二磷酸钠及依那普利拉治疗组各1例)。延迟容量补充对照组、延迟容量补充+果糖二磷酸钠注射液、前列地尔注射液或依那普利拉注射液以及延迟容量补充+动力扶持组(三个药物治疗组汇总)年龄、性别、致伤因素等无显著差异(P>0.05)。从绝对数来看，延迟容量补充+动力扶持治疗组伤情重于延迟容量补充对照组。延迟复苏失访4例：对照组死亡2例失访，果糖组死亡1例失访，依那普利拉组死亡1例失访。
2．死亡率：延迟“容量补充”对照组死亡率为14.30%(2/14)，延迟容量补充+果糖二磷酸钠注射液及延迟容量补充+依那普利拉注射液分别为5.90%(1/17)和6.30%(1/16)，延迟容量补充+前列地尔注射液组无死亡病例。表明即使在伤情重于容量补充对照组的情况下，“容量补充+动力扶持”复苏方案能显著降低延迟复苏烧伤患者的死亡率。
3．抗休克有关试验结果：从第1个和第2个24小时补液量及尿量可分析发现，在维持满意尿量的前提下，尽管动力扶持组烧伤面积和三度烧伤面积均大于对照组，但动力扶持组补液量、尿量、血压未见明显差异。容量补充+果糖二磷酸钠注射液、容量补充+前列地尔注射液和容量补充+依那普利拉注射液三组血压、血清乳酸(LA)含量未见明显差异，但血清乳酸(LA)含量均低于容量补充对照组(P<0.05)；各组RBC、HCT、HGB、WBC、体温、脉搏、呼吸、血压等在观测期内均未见显著差异(P>0.05)。
4．脏器功能损害指标：容量补充+果糖二磷酸钠注射液、容量补充+前列地尔注射液和容量补充+依那普利拉注射液三组脏器功能损害指标差异不明显，但三组cTnI、CK-MB、CK、a-HBDH、LDH、β2-MG均低于容量补充对照组。容量补充+动力扶持治疗组cTnI、CK-MB、CK、LDH、a-HBDH、β2-MG等显著低于容量补充对照组(P<0.05)。
讨论与结论
1．对严重烧伤后早期入院或延迟复苏患者，应用第三军医大学补液公式立即复苏进行“容量补充”，或应用第三军医大学延迟复苏补液公式进行“容量补充”。分别应用依那普利拉、果糖二磷酸钠及前列地尔注射液行“动力扶持”治疗，三种药物治疗，均可有效地改善组织器官缺血缺氧、改善组织氧合和有氧代谢，从而减少内脏并发症，提高治愈率，但三种药物的效果无显著差异。
2．本试验提出的“容量补充+动力扶持”复苏方案为：
立即复苏方案：第1个24小时补液总量(ml)=TBSA(1%)×体重(kg)×1.5ml+生理需要量(2000ml)+动力扶持药物(依那普利拉或果糖二磷酸钠或前列地尔)；第2个24小时补液总量(ml)=TBSA(1%)×体重(kg)×1.0ml+生理需要量(2000ml)+动力扶持药物(依那普利拉或果糖二磷酸钠或前列地尔)。
延迟复苏方案：第1个24小时补液总量(ml)=TBSA(1%)×体重(kg)×2.6ml+生理需要量(2000ml)+动力扶持药物(依那普利拉或果糖二磷酸钠或前列地尔)；第2个24小时补液总量(ml)=TBSA(1%)×体重(kg)×1.0ml+生理需要量(2000ml)+动力扶持药物(依那普利拉或果糖二磷酸钠或前列地尔)。
3．“容量补充+动力扶持”复苏方案安全、有效，不仅有助于烧伤休克复苏治疗，减少并发症，提高严重烧伤救治水平，通过该临床试验，进一步验证了严重烧伤早期缺血缺氧损害的“休克心”假说，对于进一步认识烧伤休克/缺血缺氧的发生机制和严重烧伤休克的治疗均有重要意义。
Objective and background
The key factors of visceral secondary injury and death after severe burns are ischemiaand hypoxia，and shock is the most important reason for ischemia and hypoxia during theearly stage.It is well known that the occurrence of shock are closely related to the bloodvolume, cardiac pump function and vascular tone (reactivity), but the understanding of burnshock is not the case. Previously thought that, blood volume decrease of the burn shock wasprimarily due to the increased capillary permeability, plasma-like fluid in the intravascularleakage, resulting in a decrease in effective circulating blood volume. As there are noeffective measures to reduce capillary permeability so far, now fluid replacement therapy(Volume replacement) is the main treatment. In the circumstances of a serious shock or thelate stage of shock, the low vascular reactivity makes the expansion of the vascular bed,resulting in effective circulating blood volume to further reduce, and vasoactive drug can beused in this case. Another important factor for the shock is the heart pump function. Thetraditional view is that the heart does not appear to structural damage and organic dysfunction,does not participate in the occurrence of early shock. But a large number of clinical findingssuggest that, in many severe burn patients, even if given prompt fluid infusion after injury,shock is difficult to correct. Meanwhile the early myocardial damage indicators significantlyincreased and heart function reduced, suggesting that before the effective circulating bloodvolume decreased significantly, myocardial ischemia and hypoxia damage and dysfunctionhave occurred following severe burns. Because the heart is the power organ of the circulation,the early and prompt myocardial damage and heart dysfunction(before a significant reductionin effective circulating blood volume due to increased capillary permeability), not only causedcardiac dysfunction, but also induced or exacerbated the shock. It becomes one of theimportant factors to start early ischemia and hypoxia. Therefore, a "shock heart" hypothesis for ischemic and hypoxic damage of visceral organs and tissues during early stage followingsevere burns has been proposed. Thus, effective control of early postburn myocardial damageand dysfunction is an important part of prevention and treatment of burn shock. Based on theabove findings, the new protocol for burn shock resuscitation including "volume replacementplus cardiodynamic support" has been presented.
Recent studies have shown that early application of small doses of enalaprilat injectionafter severe burns can improve the regional myocardial blood flow, reduce myocardialdamage and does not affect systemic blood pressure significantly. FDP injection can regulatecalcium dismetabolism of the myocardial cells, and inhibit cardiomyocyte apoptosis to reducemyocardial damage. Alprostadil injection can enhance the SOD activity of myocardial toreduce the MDA formation, improve the coronary circulation, and reduce myocardial damage.Therefore, we use these drugs for "cardiodynamic support".
This subject is a clinical prospective randomized controlled trial (RCT), for immediateresuscitation and delayed resuscitation, analyze the efficacy and safety of the resuscitationprotocol, and then propose a new program of "volume replacement plus cardiodynamicsupport" for the burn shock resuscitation, and lay the foundation for the burn clinical therapyand improve the cure rate of severe burns.
Materials and methods
Hospitalized patients during December,2009to March,2012in burn unit of SouthwestHospital, Third Military Medical University were enrolled. Burn depth and surface area weredetermined according to clinic diagnostic criteria for burn patients. The selected hospitalizedpatients met the inclusion criteria as follows:①patients with age above18and under65years old, male or female;②patients with flame or hot liquid injury;③TBSA>30%withdeep second degree and third degree burn area≥20%);④At admission within6hourspostburn, or regular fluid resuscitation received prior to admission (immediate resuscitationgroup). At admission after6hours postburn, or irregular fluid resuscitation received whenadmitted (delayed resuscitation group);⑤Serum cTnI>0.15ug/L (positive) orCK-MB>25IU/L when admitted. The exclusion criteria are as follows:①patients withhistory of cardiovascular disease;②Patients suffering from hypertension, hypotension, orblood pressure fluctuations previously;③patients with age <18or>65;④Serum cTnI <0.15ug/L (negative) or CK-MB<25IU/L when admitted;⑤serious organic disease such as liver, kidney, lungs and other vital organs of the body;⑥patients with significant mentaldisorders, epilepsy and other symptoms;⑦lactating or pregnant female patients;⑧patientswho are allergic to experimental drugs or patients with corresponding contraindications;⑨patients dropped during the period of research;⑩other cases that are considered to be notsuitable for research. Termination criteria:①patients died;②patients do not fit (contrary tothe agreement or lost to follow) or for security reasons.
Patients who met the inclusion criteria were divided into four groups randomly:immediate volume replacement (V group), immediate volume replacement pluscardiodynamic support (V+D group， including three subgroups enalapril, fructosediphosphate sodium, and alprostadil), delayed volume replacement (DV group), delayedvolume replacement plus cardiodynamic support (DV+D group). Cardiodynamic supportwere performed by application of1.25mg of enalaprilat(E) once a day，10g of FDP(F) twicea day or10ug of alprostadil(A) twice a day, lasting for3days. Indicators were observed andrecorded at admission, day1,2,3,7,14and21postburn respectively, including vital signs (T,P, R, BP recorded at6:00-8:00in the morning), LA, cTnI, CK, CK-MB, aHBDH, LDH, ALT,AST, GGT, Cr, BUN, β2-MG, AG, HCT, WBC, NEUT%, RBC, LYMPH%, and PLT.
Statistical analysis
All data are expressed as (x±s) and analyzed using statistical software SPSS13.0.Probability values less than0.05were considered to be significant, and P <0.01were verysignificant.
Results
1. Immediate resuscitation
1) Cases description: There were15effective cases in V group, the mean burn area was(45.07±4.58)%TBSA,20%of cases suffered more than51%TBSA burns, the mean Ⅲ°burn area was (11.00±4.34)%TBSA,4cases combined with inhalation injury, and2casesdied in3weeks after burn injury. There were55effective cases in V+D group (includingsubgroup enalapril14cases, fructose diphosphate sodium20cases, and alprostadi21cases),the mean burn area was (47.78±2.51)%TBSA,30.9%of cases suffered more than51%TBSAburns, the mean Ⅲ°burn area was (14.67±2.42)%TBSA,23cases combined with inhalationinjury, and no case died in3weeks after burn injury. Considering of the absolute value, theseverity of burn patients in V+D group was more severe than that in V group. However, there was no significant difference (p>0.05) in age, gender, injury factors, and inhalation injuryincidence, suggesting a good balance between immediate V group and immediate V+D group.
2) Mortality: There was a13.30%(2/15) mortality in V group, however, in enalapril,fructose diphosphate sodium, and alprostadil treated groups, no patients died, suggesting thatthe resuscitation scheme of “volume replacement plus cardiodynamic support” significantlydecreased the mortality of burn patients in V+D group, even in the case of burn injury issevere than that in V group.
3) Results of anti-shock indicators: Based on maintaining a satisfactory urine output,although there was a larger area and more severe burn injury, less fluid infusion volume in thethree treated subgroups and V+D group than those in V group was used, the urine output wasslightly more than that in V group, and there was no significant difference in blood pressureamong the three treated subgroups and the control, as well as V and V+D groups. Comparedwith V group, the serum level of lactate (LA) was significantly decreased in the three treatedsubgroups and V+D group (P <0.05) after admission; There were no significant difference (P>0.05) in RBC、HCT、HGB、WBC、body temperature, pulse, respiration rate and blood pressureamong the three treated subgroups and the control, as well as V and V+D groups.
4) Laboratory results of organ functions: There were no differences among three kinds ofdrugs (enalapril,fructose diphosphate sodium, alprostadil)in laboratory results of organsfunctions. Compared with V group, the serum levels of cTnI, CK-MB, CK, a-HBDH andLDH were significantly decreased in in the three treated subgroups and V+D group (P <0.05);The serum level of β2-MG was significantly decreased in in the three treated subgroups andV+D group (P <0.05).
2. Delayed resuscitation
1) Cases description: There were also14effective cases in DV group (including threesubgroups enalapril, fructose diphosphate sodium, and alprostadil), the mean burn area was(48.00±3.90)%TBSA,35.70%of cases suffered more than51%TBSA burn, the mean Ⅲ°burn area was (16.00±4.98)%TBSA,3cases combined with inhalation injury, and2cases diedin3weeks after burn injury. There were effective48cases in DV+D group (includingsubgroup enalapril16cases, fructose diphosphate sodium17cases, and alprostadi15cases),the mean burn area was (59.13±3.08)%TBSA,62.50%of cases suffered more than51%TBSA burns, the mean Ⅲ°burn area was (23.06±3.19)%TBSA,25cases combined with inhalation injury, and2cases died in3weeks after burn injury. It is obvious that the severityof burn injury in DV+D group was more severe than that in DV group. However, there was nosignificant difference (p>0.05) in age, gender, injury factors, suggesting a good balancebetween DV group and DV+D group. However, there was a higher inhalation injury incidencein DV+D group than that in DV group (chi-square test, p>0.05).
2) Mortality: The mortality in the control group was14.30%(2/14),5.90%(1/17) infructose diphosphate sodium treated subgroup,6.30%(1/16) in subgroup enalapril, and4.20%(2/48) in DV+D group, a10.10%decrease of mortality in DV+D group compared withthat in DV group, suggesting that the resuscitation scheme of “volume replacement pluscardiodynamic support” significantly decreased the mortality of burn patients suffering fromdelayed resuscitation, even in the case of burn injury is more severe than DV group.
3) Results of anti-shock: after analyzing the fluid volume and urine output in the first andsecond24-hour of burn injury, based on maintaining a satisfactory urine output, althoughthere was a bigger area of burn injury in the three treated subgroups and DV+D group thanthose in DV group, the fluid infusion volume was slightly less in all the treated groups, but nosignificant differences were found among the treated groups. There was also no significantdifference in blood pressure in the three treated subgroups and DV+D group than those in DVgroup. Compared with DV group, the serum level of LA was significantly decreased in thethree treated subgroups and DV+D group (P <0.05), no significant differences were foundamong the three treated subgroups and the control, as well as V+D and V group. There wereno significant difference (P>0.05) in RBC、HCT、HGB、WBC、body temperature, pulse,respiration rate and blood pressure between groups in the observation period.
4) Laboratory results of organs functions: There were no differences of parametersreflecting organs dysfunctions among the treated groups. Compared with DV group, theserum levels of cTnI, CK-MB, CK, a-HBDH and LDH were significantly decreased in thethree treated subgroups and DV+D group (P <0.05). The serum level of β2-MG was alsosignificantly decreased in the three treated subgroups and DV+D group (P <0.05).
Discussion and conclusion
1. Cardiodynamic supports plus fluid resuscitation attenuated ischemic and hypoxicdamage, promoted oxygenation or oxygen metabolism, reduced organ complications andimproved survival rate in severe burn patients. There were no differences among three kinds of drugs (enalapril, fructose diphosphate sodium, and alprostadil)in clinical efficacy.
2. The recommended new resuscitation strategy to severe burn patients according to ourcurrent research is as following:
1) for immediate resuscitation patients, the fluid volume of the first24h postburn (ml)=TBSA×boby weight(kg)×1.5+2000+cardiodynamic support drugs (enalapril or fructosediphosphate sodium or alprostadil)；the fluid volume of the second24h postburn (ml)=TBSA×boby weight(kg)×1.0+2000+cardiodynamic support drugs;
2) for delayed resuscitation patients, the fluid volume of the first24h postburn (ml)=TBSA×boby weight (kg)×2.6+2000+cardiodynamic support drugs (enalapril or fructosediphosphate sodium or alprostadil)；the fluid volume of the second24h postburn (ml)=TBSA×boby weight(kg)×1.0+2000+cardiodynamic support drugs.
3. Our prospective clinic research provided further evidence for the "shock heart"hypothesis for ischemic and hypoxic damage of visceral organs and tissues during early stagefollowing severe burns, and thus shed a new light for us to understand the underlyingmechanisms of burn shock. The recommended new strategy improved fluid resusciation andreduced organ complications, which may be therefore great significant for the treatment ofsevere burn patients.
引文
1. Wolf SE, Rose JK, Desai MH, et al. Mortality determinants in massive pediatric burns:ananalysis of103children with≥80%TBSA burns(≥70%full-thickness).Ann Surg，1997,225:554.
2.黎鳌．黎鳌烧伤学．上海：上海科学技术出版社，2001：38-66．
3. Yuesheng Huang, Baigang Yan, Zongcheng Yang. Clinical study of a formula for delayedrapid fluid resuscitation for patients with burn shock.2005; Burns31(5):617–622
4.杨宗城等.烧伤治疗学.北京：人民卫生出版社，2006,167.
5. Yuesheng Huang, Jiaping Zhang, Xiaohui Li. A serial studies on postburn shock heart.Burns2007;33(1, suppl): s14-15
6. Yuesheng Huang, Zhiqing Li, Zongcheng Yang. Roles of ischemia and hypoxia and themolecular pathogenesis of post-burn cardiac shock. Burns.2003;29:828-833
7. Liang Wanyi, Yang Zongcheng, Huang Yuesheng. Calcium induced the damage ofmyocardial mitochondrial respiratory function in the early stage after severe burns. Burns.2002;28:134-136
8. Yuesheng Huang, Jun Zheng, Pengju Fan, et al. Transfection of antisense p38alpha geneameliorates myocardial cell injury mediated by hypoxia and burn serum. Burns.2007;33:599-605.
9. Jia-Ping Zhang; Wan-Yi Liang, Zhong-Hua Luo, et al. Involvement of P38MAP kinase inburn-induced degradation of membrane phospholipids and upregulation of cPLA2incardiac myoctes. Shock.2007;28:86-93
10. Yuesheng Huang. Molecular mechanism of c-jun antisense gene transfection inalleviating injury of cardiomyocytes treated with burn serum and hypoxia. World J Surg.2004;28:951-957
11. Yuesheng Huang, Zongcheng Yang, Baigang Yan. Pathogenesis of early cardiac myocytedamage after severe burns. J Trauma1999;46(3):428-432
12. Yuesheng Huang, Zongcheng Yang, Bogang Yan. Improvement of early postburn cardiacfunction by use of Panax notoginseng and immediate total eschar excision in oneoperation. Burns1999;25(1):35-41
13.黄跃生.“容量补充+动力扶持”——烧伤休克有效复苏新方案的思考.中华烧伤杂志，2008，24(3)：161-163.
14.张兵钱,黄跃生,张东霞,等.依那普利拉对严重烫伤大鼠早期心肌损害的防治作用.中华烧伤杂志2007；23(5)：335-338.
15.张兵钱,黄跃生.依那普利对心肌损害的保护作用.重庆医科大学学报2007,32(10):1111-1113.
16.张兵钱,王广,胡炯宇,等.依那普利拉减轻大鼠烧伤早期脏器损害的研究.中华外科杂志，2008,46(13)：1014-1017.
17.张兵钱,王广,张东霞,等.依那普利拉对严重烫伤大鼠早期心肌力学的影响.中华烧伤杂志，2008,24(3)：183-186.
18.查新建.果糖二磷酸钠及手术对烧伤患者心肌的影响.医药论坛杂志，2007,28(16):61-62.
19.张成志,周远大.果糖二磷酸钠镁对大鼠离体心脏缺血再灌注心肌损伤的保护作用及对能量代谢的影响.重庆医学,2003,32(6)：718-719，721.
20.李旭初,於建鹏,黄国喜.果糖二磷酸钠对心肌缺血病人围术期心肌钙蛋白及C-反应蛋白的影响.时珍国医国药,2006,17(6):985-986.
21.朱深银,周远大,何海霞.果糖二磷酸钠镁对大鼠心肌梗死的保护作用.中国药学杂志,2002,37(3):181-183.
22.陆龙,崔振田.果糖二磷酸钠对室间隔缺损修补术后心肌保护作用的研究.临床军医杂志,2010,38(4):492-494.
23.邢颖,龙村,谷春久等.前列地尔乳剂对缺血再灌注心肌的保护作用.中华实验外科杂志,2004,21(11):1317-1319.
24.王翠,刘学辉.前列地尔对急性心肌梗死患者血管活性物质影响的观察.现代医药卫生,2008,24(6):822-823.
25.冯国清,王振基,宋丽杰等.前列地尔对培养乳鼠心肌细胞缺氧复氧损伤的保护作用.中国新药与临床杂志,,2004,23(7):415-418.
26.魏宏，何并文，黄冰等.前列地尔后处理对大鼠缺血再灌注心肌Bcl-2、Bax表达的影响.广西医学,2009,31(6):786-788.
27.朱稚丹,周建华.前列地尔注射液对急性心肌梗死患者梗死面积及心功能的影响.现代中西医结合杂志,2005,14(8):995-996.
28.刘畅，梅晰凡，陶贵周等.前列地尔预处理对大鼠心肌缺血再灌注损伤的保护性作用.解剖科学进展,2009,15(3):286-289.
29.高航,杨美婷.前列地尔后处理对兔再灌注心肌离子通道的影响.中国老年学杂志,2010,30(5):660-662.
30.倪国华,张向阳.前列地尔对异丙肾上腺素致急性心肌缺血损伤大鼠心电图和血清心肌酶的影响.新疆医科大学学报,2008,31(2):171-173.
31.杨建民,杨宗城,陈发明,等.大鼠烧伤后心肌局部肾素—血管紧张素系统的改变.中华整形烧伤外科杂志,1999,15(2)：102-104.
32.雷泽源;黄跃生;肖蓉;张兵钱;张琼.大鼠严重烧伤早期RAS的变化对心功能及心肌损害的影响.第三军医大学学报,2008,30(19):1779-1782.
33.雷泽源,黄跃生,肖蓉,等. Ang(1-7)和依那普利拉对大鼠严重烧伤早期心脏保护作用的研究.现代生物医学进展，2008，8(7)，1242-1244.
34.尹泽钢,黄跃生,李百姓.大鼠严重烧伤后早期心功能和脏器血流量的变化及关系.中华烧伤杂志,2010,26(1):10-13.
35. Chrysopoulo MT, Jeschke MG, Dziewulski P. Acute renal dysfunction in severely burnedadults. J Trauma,1999,46(1):141–41.
36. Ramzy PI, Barret JP, Herndon DN, et al. Thermal injury. Crit Care Clin,1999,15(2):333-521.
37.路卫,陈玉林,陈士明,等烧伤休克延迟补液对肝肾的影响.中华外科杂志,1995,33(12):34–61.
38. Deitch EA. Multiple organ failure: Pathophysiology and potential future therapy. AnnSurg,1992,216(2):117-134.
39.方林森.烧伤休克延迟复苏与感染对多脏器功能不全综合征的影响.安徽医科大学学报,1999,34(3):203-204.
40. Xia ZF, He F, Barrow R. Reperfusion injury in burned rats after delayed fluidresuscitation. J Burn Care Rehabil,1991,12:430-436.
1. Kelley D M．Hypovolemic shook：an overview．Crit Care Nurs Q，2005，28(1)：2－19．
2.柴家科，盛志勇．有关烧伤休克复苏问题的探讨．解放军医学杂，2005，30(11)：943－946．
3.刘良明.战伤休克的液体复苏进展.解放军医学杂志,2005,7(30):561.
4.孙永华，孙迎放．现代烧伤治疗与手术图谱．北京：人民军医出版社，2003．
5.孙永华,陈炯.严重烧伤休克期液体复苏.实用医学杂志.2010,26(11):1872-1873.
6. Wolf SE, Rose JK, Desai MH, et al. Mortality determinants in massive pediatric burns:ananalysis of103children with≥80%TBSA burns(≥70%full-thickness). Ann Surg，1997,225:554.
7.黎鳌．黎鳌烧伤学．上海：上海科学技术出版社，2001：38－66．
8.贾赤宇．从循证医学的角度看烧伤休克复苏的现状．中华损伤与修复杂志：电子版，2007，2(4)：249－250．
9.肖贵喜，于冶，贾立平，等．大面积烧伤休克复苏42例体会．实用医学杂志，2010，26(11)：1882－1884．
10.黄跃生.“容量补充+动力扶持”——烧伤休克有效复苏新方案的思考.中华烧伤杂志，2008，24(3)：161-163.
11.杨宗城．改善早期补液减轻烧伤早期内脏损害∥孙永华．现代临床医学外科进展：烧伤分册．北京：科学技术文献出版社，2006．
12.葛绳德．烧伤临床治疗∥方之杨．烧伤理论与实践．沈阳：辽宁科学技术出版社，1989：286.
13. Luo G， Peng Y， Yuan Z， et al．Fluid resuscitation for major burn patients with theTMMU protocol．Burns，2009，35(8)：1118－1123．
14. Ahrns KS, Harkins DR. Initial resuscitation after burn injury: therapies strategies, andcontroversies. AACN Clinical Issues,1999,10:46-60.
15. Nolan J. Fluid resuscitation for the trauma patient.Resuscitation,2001,48:57-69.
16. Jeng JC. Controversies in resuscitation p roblems in genernal surgery.Surgery,2003,20:37-46.
17. Whartin SM, Khanna A. Current attitudes to burn resuscitations in the UK. Burns,2001,27:183-184.
18.韩春茂．为什么烧伤休克液体复苏的争论这么大——证据的来源分析．实用医学杂志，2010，26(11)：1874-1876．
19. Boldt J. New light on intravascular volume rep lacement regimens, what did we learnfrom the past three years? Anesth Analg,2003,97:1595-1604.
20. Helm C. Resuscitation in shock, associated with bases, tradition or evidenced-basedmedicine. Resuscitation,2000,44:157-164.
21. Shoemaker WC, Appil PL, Kram HB, et al. Prospective trial of supernormal values ofsurvivors as the therapeutic goals in high risk surgical patients. Chest,1988,94:1176-1186.
22. SchillerWR, Bay KC, Garrey KL, et al. Hyperdynamic resuscitation improves survival inpatientswith life threatening burns. J Burn Care Rehil,1997,18:10-16.
23. Balogh Z, Mckinley BA, Cocanour CS, et al. Supernormal trauma resuscitation causesmore cases of abdominal compartment syndrome. Arch Surg,2003,138:637–642.
24. Venkatech B, Meacher R, MullerMJ, et al. Monitoring tissue oxygenation duringresuscitation of major burns. J Trauma,2001,50:485-494.
25. Pruitt BJ. Protection from excessive resuscitation “push the pendulum back”. J Trauma,2000,49:567-568.
26. Cartotto R, Choi J, Gomez M, et al. Prospective study on the implications of a basedeficit during fluid resuscitation. J Burn Care Rehil,2003,24:75-84.
27. Bikoveski RN, Rivers EP, Horst HM. Targeted resuscitation strategies after injury. CurrOp in Crit Care,2004,10:520-525.
28. Andrew R, David BE. Early goal-directed therapy: An evidenced-based review. Crit CareMed,2004,32(supp l):450-498.
29.郭振荣．烧伤休克期补液治疗∥杨宗城．中华烧伤医学．北京：人民卫生出版社，2008：21－34．
30. Chen J，Han C M，Su G L，et al．Randomized controlled trial of the absorbency of fourdressings and their effects on the evaporation of burn wounds． Chin Med J (Engl)，2007，120(22)：1788-1791．
31.陈炯，唐志坚，夏照帆，等．聚酰胺薄纱对烧伤切痂后微型皮片移植创面蒸发量和愈合的影响．中华医学杂志，2009，89(2)：105-108．
32.陈炯，苏国良，李强，等．不同敷料组合对患者供皮区创面微环境的影响．中华烧伤杂志，2009，25(3)：26-29．
33. Lin Y S，Chen J，Li Q，et al．Moisture vapor transmission rates of various transparentdressings at different temperatures and humidities．Chin Med J(Engl)，2009，122(8)：927-930．
34.郭振荣，刁力，盛志勇，等．烧伤创面水蒸发量影响因素的实验研究．中华医学杂志，1994，74(4)：221-223．
35. Fodor L，Fodor A，Ramon Y，et al．Controversies in fluid resuscitation for burnmanagement：Literature review and our experience．Injury，2006，37(5)：374-379．
36. Blumetti J，Hunt J L，Arnoldo B D，et al．The Parkland formula under fire：is the criticismjustified？ J Burn Care Res，2008，29(1)：180-186．
37.陈炯，郑一双，韩春茂，等．烧伤休克期患者液体复苏中羟乙基淀粉的应用．中华医学杂志，2009，89(38)：2726-2731．
38.陈炯，韩春茂，夏时春，等．新型羟乙基淀粉应用于烧伤休克期液体复苏的疗效及安全性评价．中华烧伤杂志，2006，22(5)：333-336．
39.夏时春，陈炯，唐志坚，等．羟乙基淀粉应用于烧伤休克期液体复苏的临床观察．中国基层医药，2008，15(3)：482-483．
40. Elkinton J R，Wolff W A，Lee W E．Plasma transfusion in the treatment of the fluid shiftin severe burns．Ann Surg，1940，112(1)：150-157．
41. Pruitt B A Jr， Mason A D Jr， Moncrief J A． Hemodynamic changes in the earlypostburn patient： the influence of fluid administration and of a vasodilator(hydralazine)．J Trauma，1971，11(1)：36-46．
42.吴志勇．输血∥陈孝平．7年制规划教材外科学．北京：人民卫生出版社，2002：64．
43. Human albumin administration in critically ill patients：systematic review of randomisedcontrolled trials． Cochrane Injuries Group Albumin Reviewers． BMJ，1998，317(7153)：235-240．
44. Regtien J G，Stienstra Y，Ligtenberg J J，et al．Morbidity in hospitalized patientsreceiving human albumin：a metaanalysis of randomized，controlled trials．Crit CareMed，2005，33(4)：915-917．
45. Cochran A，Morris S E，Edelman L S，et al．Burn patient characteristics and outcomesfollowing resuscitation with albumin．Burns，2007，33(1)：25-30．
46. Goodwin C W，Dorethy J，Lam V，et al．Randomized trial of efficacy of crystalloid andcolloid resuscitation on hemodynamic response and lung water following thermalinjury．Ann Surg，1983，197(5)：520-531．
47. Dawidson I，Eriksson B，Gelin L E，et al．Oxygen consumption and recovery fromsurgical shock in rats：a comparison of the efficacy of different plasma substitutes．CritCare Med，1979,7(10)：460-465．
48.李钢，李小兵，张鹏，等．中重度烧伤与其呼吸系统合并症的复苏液体治疗．天津医科大学学报，2005，11(1)：102-104．
49. Kramer G，Hoskins S，Copper N，et al．Emerging advances in burn resuscitation．JTrauma，2007，62(6Suppl)：S71-S72．
50.孙永华，盛志勇．临床诊疗指南：烧伤外科学分册．北京：人民卫生出版社，2007：24－38．
51. Ivy M E，Atweh N A，Palmer J，et al．Intra-abdominal hypertension and abdominalcompartment syndrome in burn patients．J Trauma，2000，49(3)：387-391．
52. Cancio L C，Cha′vez S，Alvarado-Ortega M，et al．Predicting increased fluid requirementsduring the resuscitation of thermally injured patients．J Trauma，2004，56(2)：404-413．
53.胡泉，郝岱峰，柴家科．战时烧伤休克早期液体复苏研究进展．军医进修学院学报，2008，29(2)：151-152．
54.卢才教，郭海雷，刘政军，等．羟乙基淀粉溶液用于烧伤休克期液体复苏的疗效．实用医学杂志，2010，26(11)：1880-1882．
55.陈炯，郑一双，韩春茂，等．特重度烧伤患者液体复苏应用羟乙基淀粉策略的探讨．实用医学杂志，2010，26(11)：1877-1879．
56. Cartotto R, InnesM, Musgrave MA, etal. How well does the Parkland formulae estimateactual fluid resuscitation volumes? J Burn Care Rehil,2002,25:258-265.
57. Perless J. Fluid management of trauma patient. Cur Op in Anesth,2001,14:221-225.
58. Lucans CC, JedgerAM. Physiology of colloid supplemented resuscitation from shock. JTrauma,2003,54:575.
59. Hernden D N．Total burn care．SAUNDERS，2002：1-10．
60. Deilth EA, Han PS, Fekeleova E, et al. Hypertonic saline resuscitation limits neutrophileactivation after trauma-hemorrhagic shock. Shock,2003,19:328-335.
61. Milner SM, Kinsdy MP, Guha SC, et al. A comparison of the two different2400mOsmsolutions for resuscitation of major burns. J Burn Care Rehabil,1997,18:109.
62. Elgjo GI, Figueiredo LF, Schenarts PJ, et al. Effect of two doses of hypertonic salinedextran on fluid balance during burn resuscitation: a blinded, randomized trial in sheep.Am Burn Assoc,1997,19:S88.
63. Elgjo GI, Traber DL, Hawkins HK, et al. Burn resuscitation with two doses of4ml/kghypertonic saline dextran provides sustained fluid sparing: a48hour porspective study inconscious sheep. J Trauma,2000,49:251.
64.方之扬.烧伤理论与实践.沈阳:辽宁科技出版社.1998,36～103.
65.黄跃生等.烧伤休克延迟快速复苏补液公式的临床研究.中国医师杂志，2003,5(12)：1586-1588.
66.杨宗城等.烧伤治疗学.北京：人民卫生出版社，2006,167.
67. Chrysopoulo MT, Jeschke MG, Dziewulski P. Acute renal dysfunction in severely burnedadults. J Trauma,1999,46(1):141–41.
68. Ramzy PI, Barret JP, Herndon DN, et al. Thermal injury. Crit Care Clin,1999,15(2):333-521.
69. Xia ZF, He F, Barrow R. Reperfusion injury in burned rats after delayed fluidresuscitation. J Burn Care Rehabil,1991,12:430-436.
70.路卫,陈玉林,陈士明,等烧伤休克延迟补液对肝肾的影响.中华外科杂志,1995,33(12):34–61.
71. Deitch EA. Multiple organ failure: Pathophysiology and potential future therapy. AnnSurg,1992,216(2):117-134.
72.方林森.烧伤休克延迟复苏与感染对多脏器功能不全综合征的影响.安徽医科大学学报,1999,34(3):203-204.
73. Pruitt Basil A. Jr. Fluid resuscitation: What, when, and how much? Burns2007;33(1suppl): S161–S162.
74.胡安根,黄跃生. c-fos反义基因重组体转染对缺氧复合烧伤血清心肌细胞防护作用的研究.第三军医大学学报,2003,25:1599-1601.
75.胡安根,黄跃生. c-jun反义基因重组体转染对缺氧复合烧伤血清处理心肌细胞防护作用的研究.中华烧伤杂志,2003,19:267-270.
76.梁晚益,黄跃生,杨宗城.二氮嗪对严重烧伤大鼠心肌损伤的防护作用及其机制.第三军医大学学报,2003,25:1731-1733.
77.张兵钱,黄跃生,张家平,等.依那普利拉对严重烫伤大鼠早期心肌损害的保护作用研究.中华烧伤杂志,2007,23(5):335-338.
78.张兵钱,王广,胡炯宇,张家平,黄跃生.依那普利拉减轻大鼠烧伤早期脏器损害的研究.中华外科杂志，2008,46(13)：1014-1017
79.张兵钱,王广,张东霞等.依那普利拉对严重烫伤大鼠早期心肌力学的影响.中华烧伤杂志，2008,24(3)：183-186
80.周军利,黄跃生,党永明,等.甘氨酸对SD乳鼠心肌细胞缺氧损伤的防护作用.第三军医大学学报,2004,26(23):2105-2107.
81. Zhong Z, Wheeler MD, Li X, etal. L-Glycine: anovel anti-inflammatory,immunomodulatory, and cytoprotective agent. Curr Opin Clin Nutr Metab Care,2003,6(2):229-240.
82. Hu Jiong-yu, Han Jian, Chu Zhi-gang, Song Hua-pei, Zhang Dong-xia, Zhang Qiong,Huang Yue-sheng. Astragaloside Ⅳattenuates hypoxic rat cardiomyocyte damage byupregulating superoxide dismutase-1levels.Clinical and Experimental Pharmacology andPhysiology.2009;36:351-357.
83.吴祖煌等.严重延迟复苏烧伤患者心肌损害防治的临床研究.中国急救医学,2004,24(3):157-159.
84. Yuesheng Huang, Jiaping Zhang, Xiaohui Li. A serial studies on postburn shock heart.Burns2007;33(1, suppl): s14-15.
85. Yuesheng Huang, Zhiqing Li, Zongcheng Yang. Roles of ischemia and hypoxia and themolecular pathogenesis of post-burn cardiac shock. Burns.2003;29:828-833.
86. Liang Wanyi, Yang Zongcheng, Huang Yuesheng. Calcium induced the damage ofmyocardial mitochondrial respiratory function in the early stage after severe burns. Burns.2002;28:134-136.
87. Yuesheng Huang, Jun Zheng, Pengju Fan, Xiaorong Zhang. Transfection of antisense p38alpha gene ameliorates myocardial cell injury mediated by hypoxia and burn serum.Burns.2007;33:599-605.
88. Jia-Ping Zhang; Wan-Yi Liang, Zhong-Hua Luo, Zong-Cheng Yang, Hsiao-Chang Chan,Yue-Sheng Huang. Involvement of P38MAP kinase in burn-induced degradation ofmembrane phospholipids and upregulation of cPLA2in cardiac myoctes. Shock.2007;28:86-93.
89. Yuesheng Huang. Molecular mechanism of c-jun antisense gene transfection inalleviating injury of cardiomyocytes treated with burn serum and hypoxia. World J Surg.2004;28:951-957.
90. Yuesheng Huang, Zongcheng Yang, Bogang Yan. Pathogenesis of early cardiac myocytedamage after severe burns. J Trauma1999;46(3):428-432.
91. Yuesheng Huang, Zongcheng Yang, Bogang Yan. Improvement of early postburn cardiacfunction by use of Panax notoginseng and immediate total eschar excision in oneoperation. Burns1999;25(1):35-41.
92.黄跃生,杨宗城,肖光夏,等.烧伤早期损害的防治措施对提高烧伤存活率的作用.第三军医大学学报,2001,23(2):217-2201.
93.杨建民,杨宗城,陈发明,等.心肌局部肾素血管紧张素系统在烧伤早期心肌损害中的作用.中国危重病急救医学,1998,10(1):23-25.
94. Fiddian-Green RG, Hugland U, Gutierrez G, et al. Goal for the resuscitation of shock. CritCare Med,1993,21: S25-30.
95. Carlos M. Ferrario, Jewell Jessup, Mark C. Chappell, et al. Effect ofangiotensin-converting enzyme inhibition and angiotensin II receptor blockers on cardiacangiotensin-converting enzyme. Circulation,2005,111:2605-2610.
96. Whinney RR, Cohn SM, Zacar SJ. Fluid resuscitation from trauma patient in21century.Curr Op in Crit Care,2000,6:395-400.
2.黎鳌．黎鳌烧伤学．上海：上海科学技术出版社，2001：38-66．
3. Yuesheng Huang, Baigang Yan, Zongcheng Yang. Clinical study of a formula for delayedrapid fluid resuscitation for patients with burn shock.2005; Burns31(5):617–622
4.杨宗城等.烧伤治疗学.北京：人民卫生出版社，2006,167.
5. Yuesheng Huang, Jiaping Zhang, Xiaohui Li. A serial studies on postburn shock heart.Burns2007;33(1, suppl): s14-15
6. Yuesheng Huang, Zhiqing Li, Zongcheng Yang. Roles of ischemia and hypoxia and themolecular pathogenesis of post-burn cardiac shock. Burns.2003;29:828-833
7. Liang Wanyi, Yang Zongcheng, Huang Yuesheng. Calcium induced the damage ofmyocardial mitochondrial respiratory function in the early stage after severe burns. Burns.2002;28:134-136
8. Yuesheng Huang, Jun Zheng, Pengju Fan, et al. Transfection of antisense p38alpha geneameliorates myocardial cell injury mediated by hypoxia and burn serum. Burns.2007;33:599-605.
9. Jia-Ping Zhang; Wan-Yi Liang, Zhong-Hua Luo, et al. Involvement of P38MAP kinase inburn-induced degradation of membrane phospholipids and upregulation of cPLA2incardiac myoctes. Shock.2007;28:86-93
10. Yuesheng Huang. Molecular mechanism of c-jun antisense gene transfection inalleviating injury of cardiomyocytes treated with burn serum and hypoxia. World J Surg.2004;28:951-957
11. Yuesheng Huang, Zongcheng Yang, Baigang Yan. Pathogenesis of early cardiac myocytedamage after severe burns. J Trauma1999;46(3):428-432
12. Yuesheng Huang, Zongcheng Yang, Bogang Yan. Improvement of early postburn cardiacfunction by use of Panax notoginseng and immediate total eschar excision in oneoperation. Burns1999;25(1):35-41
13.黄跃生.“容量补充+动力扶持”——烧伤休克有效复苏新方案的思考.中华烧伤杂志，2008，24(3)：161-163.
14.张兵钱,黄跃生,张东霞,等.依那普利拉对严重烫伤大鼠早期心肌损害的防治作用.中华烧伤杂志2007；23(5)：335-338.
15.张兵钱,黄跃生.依那普利对心肌损害的保护作用.重庆医科大学学报2007,32(10):1111-1113.
16.张兵钱,王广,胡炯宇,等.依那普利拉减轻大鼠烧伤早期脏器损害的研究.中华外科杂志，2008,46(13)：1014-1017.
17.张兵钱,王广,张东霞,等.依那普利拉对严重烫伤大鼠早期心肌力学的影响.中华烧伤杂志，2008,24(3)：183-186.
18.查新建.果糖二磷酸钠及手术对烧伤患者心肌的影响.医药论坛杂志，2007,28(16):61-62.
19.张成志,周远大.果糖二磷酸钠镁对大鼠离体心脏缺血再灌注心肌损伤的保护作用及对能量代谢的影响.重庆医学,2003,32(6)：718-719，721.
20.李旭初,於建鹏,黄国喜.果糖二磷酸钠对心肌缺血病人围术期心肌钙蛋白及C-反应蛋白的影响.时珍国医国药,2006,17(6):985-986.
21.朱深银,周远大,何海霞.果糖二磷酸钠镁对大鼠心肌梗死的保护作用.中国药学杂志,2002,37(3):181-183.
22.陆龙,崔振田.果糖二磷酸钠对室间隔缺损修补术后心肌保护作用的研究.临床军医杂志,2010,38(4):492-494.
23.邢颖,龙村,谷春久等.前列地尔乳剂对缺血再灌注心肌的保护作用.中华实验外科杂志,2004,21(11):1317-1319.
24.王翠,刘学辉.前列地尔对急性心肌梗死患者血管活性物质影响的观察.现代医药卫生,2008,24(6):822-823.
25.冯国清,王振基,宋丽杰等.前列地尔对培养乳鼠心肌细胞缺氧复氧损伤的保护作用.中国新药与临床杂志,,2004,23(7):415-418.
26.魏宏，何并文，黄冰等.前列地尔后处理对大鼠缺血再灌注心肌Bcl-2、Bax表达的影响.广西医学,2009,31(6):786-788.
27.朱稚丹,周建华.前列地尔注射液对急性心肌梗死患者梗死面积及心功能的影响.现代中西医结合杂志,2005,14(8):995-996.
28.刘畅，梅晰凡，陶贵周等.前列地尔预处理对大鼠心肌缺血再灌注损伤的保护性作用.解剖科学进展,2009,15(3):286-289.
29.高航,杨美婷.前列地尔后处理对兔再灌注心肌离子通道的影响.中国老年学杂志,2010,30(5):660-662.
30.倪国华,张向阳.前列地尔对异丙肾上腺素致急性心肌缺血损伤大鼠心电图和血清心肌酶的影响.新疆医科大学学报,2008,31(2):171-173.
31.杨建民,杨宗城,陈发明,等.大鼠烧伤后心肌局部肾素—血管紧张素系统的改变.中华整形烧伤外科杂志,1999,15(2)：102-104.
32.雷泽源;黄跃生;肖蓉;张兵钱;张琼.大鼠严重烧伤早期RAS的变化对心功能及心肌损害的影响.第三军医大学学报,2008,30(19):1779-1782.
33.雷泽源,黄跃生,肖蓉,等. Ang(1-7)和依那普利拉对大鼠严重烧伤早期心脏保护作用的研究.现代生物医学进展，2008，8(7)，1242-1244.
34.尹泽钢,黄跃生,李百姓.大鼠严重烧伤后早期心功能和脏器血流量的变化及关系.中华烧伤杂志,2010,26(1):10-13.
35. Chrysopoulo MT, Jeschke MG, Dziewulski P. Acute renal dysfunction in severely burnedadults. J Trauma,1999,46(1):141–41.
36. Ramzy PI, Barret JP, Herndon DN, et al. Thermal injury. Crit Care Clin,1999,15(2):333-521.
37.路卫,陈玉林,陈士明,等烧伤休克延迟补液对肝肾的影响.中华外科杂志,1995,33(12):34–61.
38. Deitch EA. Multiple organ failure: Pathophysiology and potential future therapy. AnnSurg,1992,216(2):117-134.
39.方林森.烧伤休克延迟复苏与感染对多脏器功能不全综合征的影响.安徽医科大学学报,1999,34(3):203-204.
40. Xia ZF, He F, Barrow R. Reperfusion injury in burned rats after delayed fluidresuscitation. J Burn Care Rehabil,1991,12:430-436.
1. Kelley D M．Hypovolemic shook：an overview．Crit Care Nurs Q，2005，28(1)：2－19．
2.柴家科，盛志勇．有关烧伤休克复苏问题的探讨．解放军医学杂，2005，30(11)：943－946．
3.刘良明.战伤休克的液体复苏进展.解放军医学杂志,2005,7(30):561.
4.孙永华，孙迎放．现代烧伤治疗与手术图谱．北京：人民军医出版社，2003．
5.孙永华,陈炯.严重烧伤休克期液体复苏.实用医学杂志.2010,26(11):1872-1873.
6. Wolf SE, Rose JK, Desai MH, et al. Mortality determinants in massive pediatric burns:ananalysis of103children with≥80%TBSA burns(≥70%full-thickness). Ann Surg，1997,225:554.
7.黎鳌．黎鳌烧伤学．上海：上海科学技术出版社，2001：38－66．
8.贾赤宇．从循证医学的角度看烧伤休克复苏的现状．中华损伤与修复杂志：电子版，2007，2(4)：249－250．
9.肖贵喜，于冶，贾立平，等．大面积烧伤休克复苏42例体会．实用医学杂志，2010，26(11)：1882－1884．
10.黄跃生.“容量补充+动力扶持”——烧伤休克有效复苏新方案的思考.中华烧伤杂志，2008，24(3)：161-163.
11.杨宗城．改善早期补液减轻烧伤早期内脏损害∥孙永华．现代临床医学外科进展：烧伤分册．北京：科学技术文献出版社，2006．
12.葛绳德．烧伤临床治疗∥方之杨．烧伤理论与实践．沈阳：辽宁科学技术出版社，1989：286.
13. Luo G， Peng Y， Yuan Z， et al．Fluid resuscitation for major burn patients with theTMMU protocol．Burns，2009，35(8)：1118－1123．
14. Ahrns KS, Harkins DR. Initial resuscitation after burn injury: therapies strategies, andcontroversies. AACN Clinical Issues,1999,10:46-60.
15. Nolan J. Fluid resuscitation for the trauma patient.Resuscitation,2001,48:57-69.
16. Jeng JC. Controversies in resuscitation p roblems in genernal surgery.Surgery,2003,20:37-46.
17. Whartin SM, Khanna A. Current attitudes to burn resuscitations in the UK. Burns,2001,27:183-184.
18.韩春茂．为什么烧伤休克液体复苏的争论这么大——证据的来源分析．实用医学杂志，2010，26(11)：1874-1876．
19. Boldt J. New light on intravascular volume rep lacement regimens, what did we learnfrom the past three years? Anesth Analg,2003,97:1595-1604.
20. Helm C. Resuscitation in shock, associated with bases, tradition or evidenced-basedmedicine. Resuscitation,2000,44:157-164.
21. Shoemaker WC, Appil PL, Kram HB, et al. Prospective trial of supernormal values ofsurvivors as the therapeutic goals in high risk surgical patients. Chest,1988,94:1176-1186.
22. SchillerWR, Bay KC, Garrey KL, et al. Hyperdynamic resuscitation improves survival inpatientswith life threatening burns. J Burn Care Rehil,1997,18:10-16.
23. Balogh Z, Mckinley BA, Cocanour CS, et al. Supernormal trauma resuscitation causesmore cases of abdominal compartment syndrome. Arch Surg,2003,138:637–642.
24. Venkatech B, Meacher R, MullerMJ, et al. Monitoring tissue oxygenation duringresuscitation of major burns. J Trauma,2001,50:485-494.
25. Pruitt BJ. Protection from excessive resuscitation “push the pendulum back”. J Trauma,2000,49:567-568.
26. Cartotto R, Choi J, Gomez M, et al. Prospective study on the implications of a basedeficit during fluid resuscitation. J Burn Care Rehil,2003,24:75-84.
27. Bikoveski RN, Rivers EP, Horst HM. Targeted resuscitation strategies after injury. CurrOp in Crit Care,2004,10:520-525.
28. Andrew R, David BE. Early goal-directed therapy: An evidenced-based review. Crit CareMed,2004,32(supp l):450-498.
29.郭振荣．烧伤休克期补液治疗∥杨宗城．中华烧伤医学．北京：人民卫生出版社，2008：21－34．
30. Chen J，Han C M，Su G L，et al．Randomized controlled trial of the absorbency of fourdressings and their effects on the evaporation of burn wounds． Chin Med J (Engl)，2007，120(22)：1788-1791．
31.陈炯，唐志坚，夏照帆，等．聚酰胺薄纱对烧伤切痂后微型皮片移植创面蒸发量和愈合的影响．中华医学杂志，2009，89(2)：105-108．
32.陈炯，苏国良，李强，等．不同敷料组合对患者供皮区创面微环境的影响．中华烧伤杂志，2009，25(3)：26-29．
33. Lin Y S，Chen J，Li Q，et al．Moisture vapor transmission rates of various transparentdressings at different temperatures and humidities．Chin Med J(Engl)，2009，122(8)：927-930．
34.郭振荣，刁力，盛志勇，等．烧伤创面水蒸发量影响因素的实验研究．中华医学杂志，1994，74(4)：221-223．
35. Fodor L，Fodor A，Ramon Y，et al．Controversies in fluid resuscitation for burnmanagement：Literature review and our experience．Injury，2006，37(5)：374-379．
36. Blumetti J，Hunt J L，Arnoldo B D，et al．The Parkland formula under fire：is the criticismjustified？ J Burn Care Res，2008，29(1)：180-186．
37.陈炯，郑一双，韩春茂，等．烧伤休克期患者液体复苏中羟乙基淀粉的应用．中华医学杂志，2009，89(38)：2726-2731．
38.陈炯，韩春茂，夏时春，等．新型羟乙基淀粉应用于烧伤休克期液体复苏的疗效及安全性评价．中华烧伤杂志，2006，22(5)：333-336．
39.夏时春，陈炯，唐志坚，等．羟乙基淀粉应用于烧伤休克期液体复苏的临床观察．中国基层医药，2008，15(3)：482-483．
40. Elkinton J R，Wolff W A，Lee W E．Plasma transfusion in the treatment of the fluid shiftin severe burns．Ann Surg，1940，112(1)：150-157．
41. Pruitt B A Jr， Mason A D Jr， Moncrief J A． Hemodynamic changes in the earlypostburn patient： the influence of fluid administration and of a vasodilator(hydralazine)．J Trauma，1971，11(1)：36-46．
42.吴志勇．输血∥陈孝平．7年制规划教材外科学．北京：人民卫生出版社，2002：64．
43. Human albumin administration in critically ill patients：systematic review of randomisedcontrolled trials． Cochrane Injuries Group Albumin Reviewers． BMJ，1998，317(7153)：235-240．
44. Regtien J G，Stienstra Y，Ligtenberg J J，et al．Morbidity in hospitalized patientsreceiving human albumin：a metaanalysis of randomized，controlled trials．Crit CareMed，2005，33(4)：915-917．
45. Cochran A，Morris S E，Edelman L S，et al．Burn patient characteristics and outcomesfollowing resuscitation with albumin．Burns，2007，33(1)：25-30．
46. Goodwin C W，Dorethy J，Lam V，et al．Randomized trial of efficacy of crystalloid andcolloid resuscitation on hemodynamic response and lung water following thermalinjury．Ann Surg，1983，197(5)：520-531．
47. Dawidson I，Eriksson B，Gelin L E，et al．Oxygen consumption and recovery fromsurgical shock in rats：a comparison of the efficacy of different plasma substitutes．CritCare Med，1979,7(10)：460-465．
48.李钢，李小兵，张鹏，等．中重度烧伤与其呼吸系统合并症的复苏液体治疗．天津医科大学学报，2005，11(1)：102-104．
49. Kramer G，Hoskins S，Copper N，et al．Emerging advances in burn resuscitation．JTrauma，2007，62(6Suppl)：S71-S72．
50.孙永华，盛志勇．临床诊疗指南：烧伤外科学分册．北京：人民卫生出版社，2007：24－38．
51. Ivy M E，Atweh N A，Palmer J，et al．Intra-abdominal hypertension and abdominalcompartment syndrome in burn patients．J Trauma，2000，49(3)：387-391．
52. Cancio L C，Cha′vez S，Alvarado-Ortega M，et al．Predicting increased fluid requirementsduring the resuscitation of thermally injured patients．J Trauma，2004，56(2)：404-413．
53.胡泉，郝岱峰，柴家科．战时烧伤休克早期液体复苏研究进展．军医进修学院学报，2008，29(2)：151-152．
54.卢才教，郭海雷，刘政军，等．羟乙基淀粉溶液用于烧伤休克期液体复苏的疗效．实用医学杂志，2010，26(11)：1880-1882．
55.陈炯，郑一双，韩春茂，等．特重度烧伤患者液体复苏应用羟乙基淀粉策略的探讨．实用医学杂志，2010，26(11)：1877-1879．
56. Cartotto R, InnesM, Musgrave MA, etal. How well does the Parkland formulae estimateactual fluid resuscitation volumes? J Burn Care Rehil,2002,25:258-265.
57. Perless J. Fluid management of trauma patient. Cur Op in Anesth,2001,14:221-225.
58. Lucans CC, JedgerAM. Physiology of colloid supplemented resuscitation from shock. JTrauma,2003,54:575.
59. Hernden D N．Total burn care．SAUNDERS，2002：1-10．
60. Deilth EA, Han PS, Fekeleova E, et al. Hypertonic saline resuscitation limits neutrophileactivation after trauma-hemorrhagic shock. Shock,2003,19:328-335.
61. Milner SM, Kinsdy MP, Guha SC, et al. A comparison of the two different2400mOsmsolutions for resuscitation of major burns. J Burn Care Rehabil,1997,18:109.
62. Elgjo GI, Figueiredo LF, Schenarts PJ, et al. Effect of two doses of hypertonic salinedextran on fluid balance during burn resuscitation: a blinded, randomized trial in sheep.Am Burn Assoc,1997,19:S88.
63. Elgjo GI, Traber DL, Hawkins HK, et al. Burn resuscitation with two doses of4ml/kghypertonic saline dextran provides sustained fluid sparing: a48hour porspective study inconscious sheep. J Trauma,2000,49:251.
64.方之扬.烧伤理论与实践.沈阳:辽宁科技出版社.1998,36～103.
65.黄跃生等.烧伤休克延迟快速复苏补液公式的临床研究.中国医师杂志，2003,5(12)：1586-1588.
66.杨宗城等.烧伤治疗学.北京：人民卫生出版社，2006,167.
67. Chrysopoulo MT, Jeschke MG, Dziewulski P. Acute renal dysfunction in severely burnedadults. J Trauma,1999,46(1):141–41.
68. Ramzy PI, Barret JP, Herndon DN, et al. Thermal injury. Crit Care Clin,1999,15(2):333-521.
69. Xia ZF, He F, Barrow R. Reperfusion injury in burned rats after delayed fluidresuscitation. J Burn Care Rehabil,1991,12:430-436.
70.路卫,陈玉林,陈士明,等烧伤休克延迟补液对肝肾的影响.中华外科杂志,1995,33(12):34–61.
71. Deitch EA. Multiple organ failure: Pathophysiology and potential future therapy. AnnSurg,1992,216(2):117-134.
72.方林森.烧伤休克延迟复苏与感染对多脏器功能不全综合征的影响.安徽医科大学学报,1999,34(3):203-204.
73. Pruitt Basil A. Jr. Fluid resuscitation: What, when, and how much? Burns2007;33(1suppl): S161–S162.
74.胡安根,黄跃生. c-fos反义基因重组体转染对缺氧复合烧伤血清心肌细胞防护作用的研究.第三军医大学学报,2003,25:1599-1601.
75.胡安根,黄跃生. c-jun反义基因重组体转染对缺氧复合烧伤血清处理心肌细胞防护作用的研究.中华烧伤杂志,2003,19:267-270.
76.梁晚益,黄跃生,杨宗城.二氮嗪对严重烧伤大鼠心肌损伤的防护作用及其机制.第三军医大学学报,2003,25:1731-1733.
77.张兵钱,黄跃生,张家平,等.依那普利拉对严重烫伤大鼠早期心肌损害的保护作用研究.中华烧伤杂志,2007,23(5):335-338.
78.张兵钱,王广,胡炯宇,张家平,黄跃生.依那普利拉减轻大鼠烧伤早期脏器损害的研究.中华外科杂志，2008,46(13)：1014-1017
79.张兵钱,王广,张东霞等.依那普利拉对严重烫伤大鼠早期心肌力学的影响.中华烧伤杂志，2008,24(3)：183-186
80.周军利,黄跃生,党永明,等.甘氨酸对SD乳鼠心肌细胞缺氧损伤的防护作用.第三军医大学学报,2004,26(23):2105-2107.
81. Zhong Z, Wheeler MD, Li X, etal. L-Glycine: anovel anti-inflammatory,immunomodulatory, and cytoprotective agent. Curr Opin Clin Nutr Metab Care,2003,6(2):229-240.
82. Hu Jiong-yu, Han Jian, Chu Zhi-gang, Song Hua-pei, Zhang Dong-xia, Zhang Qiong,Huang Yue-sheng. Astragaloside Ⅳattenuates hypoxic rat cardiomyocyte damage byupregulating superoxide dismutase-1levels.Clinical and Experimental Pharmacology andPhysiology.2009;36:351-357.
83.吴祖煌等.严重延迟复苏烧伤患者心肌损害防治的临床研究.中国急救医学,2004,24(3):157-159.
84. Yuesheng Huang, Jiaping Zhang, Xiaohui Li. A serial studies on postburn shock heart.Burns2007;33(1, suppl): s14-15.
85. Yuesheng Huang, Zhiqing Li, Zongcheng Yang. Roles of ischemia and hypoxia and themolecular pathogenesis of post-burn cardiac shock. Burns.2003;29:828-833.
86. Liang Wanyi, Yang Zongcheng, Huang Yuesheng. Calcium induced the damage ofmyocardial mitochondrial respiratory function in the early stage after severe burns. Burns.2002;28:134-136.
87. Yuesheng Huang, Jun Zheng, Pengju Fan, Xiaorong Zhang. Transfection of antisense p38alpha gene ameliorates myocardial cell injury mediated by hypoxia and burn serum.Burns.2007;33:599-605.
88. Jia-Ping Zhang; Wan-Yi Liang, Zhong-Hua Luo, Zong-Cheng Yang, Hsiao-Chang Chan,Yue-Sheng Huang. Involvement of P38MAP kinase in burn-induced degradation ofmembrane phospholipids and upregulation of cPLA2in cardiac myoctes. Shock.2007;28:86-93.
89. Yuesheng Huang. Molecular mechanism of c-jun antisense gene transfection inalleviating injury of cardiomyocytes treated with burn serum and hypoxia. World J Surg.2004;28:951-957.
90. Yuesheng Huang, Zongcheng Yang, Bogang Yan. Pathogenesis of early cardiac myocytedamage after severe burns. J Trauma1999;46(3):428-432.
91. Yuesheng Huang, Zongcheng Yang, Bogang Yan. Improvement of early postburn cardiacfunction by use of Panax notoginseng and immediate total eschar excision in oneoperation. Burns1999;25(1):35-41.
92.黄跃生,杨宗城,肖光夏,等.烧伤早期损害的防治措施对提高烧伤存活率的作用.第三军医大学学报,2001,23(2):217-2201.
93.杨建民,杨宗城,陈发明,等.心肌局部肾素血管紧张素系统在烧伤早期心肌损害中的作用.中国危重病急救医学,1998,10(1):23-25.
94. Fiddian-Green RG, Hugland U, Gutierrez G, et al. Goal for the resuscitation of shock. CritCare Med,1993,21: S25-30.
95. Carlos M. Ferrario, Jewell Jessup, Mark C. Chappell, et al. Effect ofangiotensin-converting enzyme inhibition and angiotensin II receptor blockers on cardiacangiotensin-converting enzyme. Circulation,2005,111:2605-2610.
96. Whinney RR, Cohn SM, Zacar SJ. Fluid resuscitation from trauma patient in21century.Curr Op in Crit Care,2000,6:395-400.