益气健脾法治疗腹部手术后全身炎症综合征的临床研究
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摘要
研究背景
半个世纪以来,人们逐步认识到外科手术(尤其是大手术)是一种应激性损伤,组织的切除和/或破坏,导致失血、组织低灌注、大量细胞损坏和器官功能紊乱,使其正常的生理功能及代谢状态发生突然迅速和强烈的变化,在腹部外科受到的打击尤为突出,因此手术与重症创伤、烧伤、脓毒症(sepsis)一样,均可导致机体早期出现发热、心率快、呼吸急促、以及白细胞计数升高等类似于全身炎症反应综合征(systemic inflammatory response syndmne,SIRS)样表现,而SIRS是多器官功能障碍综合征(multiple organ dysfuction syndrome,MODS)发生的基础,是危重病患者的主要死因。因此积极治疗SIRS,阻断SIRS向MODS的转化显得尤为重要。
在开展中西医结合研究的过程中,许多专家运用中医理论探讨SIRS发生发展过程的辨证论治规律,并取得一些的认识,但大多认为SIRS是实证、热证,并使用通腑、泻热及活血祛瘀的方法治疗。吴咸中院士提出SIRS/MODS是当前外科治疗与研究的热点,早期用中医通里攻下法及清热解毒法进行防治已取得肯定的疗效。而实际上缺血/再灌注损伤、免疫抑制是SIRS中后期的共同病理损害,此期应用补气益气、培正扶本及行气活血药物是否有助于改善组织血供及减少再灌注损害,增强机体免疫力这是一个很有发展潜力的研究课题。我院外科专家针对术后SIRS病人早期有发热、心率快、呼吸急促、以及白细胞计数升高等表现,提出热、毒、瘀的病机本质:而到后期因患者表现面色苍白,气短懒言,声低息微,食欲减退,神疲肢倦,潮热盗汗,提出是由于手术创伤,正邪相争,正不胜邪,耗伤气血,致气血阴阳不足,其本质是手术攻伐,损伤脾胃,脾失健运,气血生化乏源,致机体术后出现快速疲劳所致,其主要病理因素是脾气虚。从中医学理论提出SIRS是一动态的临床症侯群,在其早期阶段,机体动员正气,与病邪相争,邪实正不衰,此时表现为实证、热证的病理阶段,但由于正气消耗,正不胜邪,机体不可避免地出现虚证的病理机制,这一过程发展相当迅速。
为此广东省中医院大外科曾对此进行了专题研究,通过对106例腹部手术后SIRS后期(术后三天以上)患者进行中医证型的辩证分析,发现以虚证(占比68%)为主要证型,且以脾气虚(占比62%)为主,并发现SIRS后期临床证候主要分为脾气虚、肝郁脾虚、只有小部分患者表现为气滞及中焦湿热、但均与脾的生理功能损伤密切相关。参考近年来的文献报道,提示黄芪及四君子汤对机体炎症反应具有多方面调节作用,且能明显改善免疫系统功能,纠正脾虚导致的运化功能失调;黄芪具有益气固表、利水退肿、脱毒生肌等功效,是一种作用广泛的免疫调节剂,从中药性味归经分析是补益类中草药;现代医学证实黄芪多糖可明显促进烧伤小鼠T淋巴细胞转化,促进巨噬细胞产生白介素-1以增强机体免疫功能,对感染性休克大鼠能通过抑制促炎性细胞因子TNF和IL-6的产生,从而拮抗过度的全身性炎症反应,提高存活率。
因此,可以认为腹部外科手术后并发SIRS患者后期存在脾气虚的病机本质,而且实验室研究亦证实益气健脾类中药在改善免疫系统功能,拮抗SIRS过程中过度炎症释放,下调炎症反应有积极意义,有必要进一步探索健脾益气类中药对腹部手术后SIRS患者的影响。
目的
通过证候研究及实验室微观辨证指标,归纳出手术后SIRS患者中医病机规律,并在此基础上选用益气健脾类中药(黄芪注射液)进行治疗手术后脾虚证SIRS患者,并就其疗效与传统西药(乌司他丁)作对照研究,探讨益气健脾类中药对腹部大中手术后SIRS患者,其临床指标(体温、心率、白细胞计数)及炎症细胞因子IL-6、IL-8、IL-10、TNF-a的影响。
方法
本研究采用前瞻性队列研究,病例来源:2006年10月至2009年1月广东省中医院外科住院病人106例,其中男58例,女48例;年龄范围14～75岁,平均年龄为50.3±8.46岁,全部患者均接受腹部外科择期手术治疗。施术者为高年资主治以上职称的专科医师。入选病人中,其中肝胆胰手术者40例,胃小肠手术者25例,结肠手术者31例,腹膜后肿瘤者10例。入选病例符合SIRS诊断标准中两项以上,排除以下病例:(1)患者术前已表现SIRS者;(2)术中输浓缩红细胞≧400ml者;(3)术后出现伤口感染,消化道瘘及其他手术相关的并发症;(4)术前心肺功能检查不正常者;(4)术前贫血Hb＜100克/升者。研究病例于手术后第3天上午查房时,按照中医望、闻、问、切四诊收集病人的临床资料,填写证侯调查表录入数据库,将全部58项临床中医证侯作为变量,按患者病症出现的频次逐步聚类,最后根据聚类结果,总结出这群研究对象的病机规律。同时对上述病例术后第三天清晨空腹抽血,采用放射免疫法检测血肾上腺素(E)、去甲肾上腺素浓度(NE),并与同期腹部手术后未发生SIRS患者对比;此外,比较腹部手术后不同证型的SIRS患者E、NE的血清学浓度,探讨各组间是否存在显著性差异;此外入选患者根据当日专家辨证结果及病情轻重,分为脾虚组和非脾虚组及对照组,分别使用健脾益气中药黄芪注射液、乌司他丁及常规综合治疗。乌司他丁治疗组给予常规抗感染、补液治疗同时加用乌司他丁20万U,1次/12h静滴,连用5 d;中药治疗组在常规抗感染、补液治疗基础上给予黄芪注射液20毫升,1次/12h静滴,连用5 d;对照组常规补液、抗感染等综合治疗,与治疗组差别仅是不用乌司他丁或黄芪注射液。常规监测各组间患者心率、呼吸频率、体温、尿量、WBC、SIRS症状改善时间和病死率;治疗前后抽取静脉血检测血清肿瘤坏死因子α((TNF-α)、IL-6、IL-8、IL一10浓度。成组均数若符合正态分布时比较用成组t检验,配对均数符合正态分布时用配对t检验,P≤0.05表示差别有显著性。
结果
1.通过对106例腹部大中手术后SIRS患者中后期中医证型的分析,发现术后SIRS患者以虚证(占比68%)为主要证型,且以脾气虚(占比62%)为主要病机
2.腹部手术后并发SIRS患者,其血清学NE和E水平明显低于非SIRS患者,但属于脾虚证的SIRS患者,其NE、E的血清学浓度与其他证型的SIRS患者,统计学分析无显著性差异。
3.益气健脾类中药黄芪注射液对腹部外科大中手术后SIRS患者体温、心率、白细胞计数及液体负平衡的影响,与传统SIRS治疗药物—乌司他丁无显著性差异,但与对照组有显著性差异(P≤0.05)。
4.益气健脾类中药黄芪注射液对腹部外科大中手术后SIRS患者TNF-a、IL一6、IL-8、IL一10等炎症介质血清浓度的影响,与传统SIRS治疗药物—乌司他丁组无显著性差异,但与对照组有显著性差异(P≤0.05)。
结论
1.腹部大中手术后发生SIRS的患者其中后期主要表现为脾气虚的中医病机。
2.益气健脾类中药(黄芪注射液)对手术后脾虚型SIRS患者,能改善其临床症状,对体温、心率、白细胞计数及液体负平衡的影响有积极意义。
3.益气健脾类中药(黄芪注射液)对手术后脾虚型SIRS患者TNF-a、IL一6、IL-8、IL一10等炎症介质有拮抗作用,能下调炎症介质,避免机体过度的炎症反应,从而达到保护机体、避免多脏器功能不全综合征的发生、降低重症患者的病死率的作用。
4.益气健脾类中药(黄芪注射液)对手术后SIRS患者,能加快患者术后的快速康复,为围手术期中医药治疗提供了新思路
Background
Through the past 50 years,people had gradually realized that surgical intervention is a type of damage caused by stress.The removal and destruction of tissues lead to blood loss,hypoperfusion of tissue,damage of bulk cells and functional disorder of organs,which destroy the normal physiologic function and metabolism in an unexpectedly quick and violent way.Such destruction is especially obvious in abdominal surgery.Surgery,as the same as grave trauma,empyrosis and sepsis,can also result in fever,fast heart rate,shortness of breath,higher white blood count and other resembling systemic inflammatory response syndrome(SIRS).SIRS is the basic cause of multiple organ dysfunction syndrome(MODS),and also the main death cause of severe case.Therefore,it is quite important to give active treatment on SIRS and prevent it from developing into MODS.
Through the study of combination of TCM with Western Medicine,many experts approach the differentiation and treatment system on the occurrence and development of SIRS in use of TCM theory.And they make certain progress.But most experts regard SIRS as excess syndrome and heat syndrome.Meanwhile,they treat SIRS with methods like purging fu-organs,expelling the heat-evil, activating the blood and dissolving stasis.Academician Wu xianzhong has said that SIRS and MODS are two hot spots of study and surgery treatment at the moment.At its earlier stage,it can be effectively treated by internal cleaning,offensive purgative method and heat-cleaning and detoxicating method,however,blood deficiency,reperfusion injury and immune suppression are the shared pathological lesions in the middle and later stages of SIRS. During the two stages,those drugs with effect of invigorating and benefiting qi,reinforcing healthy qi and strengthening nature,activating blood and moving qi may improve tissue blood supply,reduce reperfusion lesion and reinforce body immunity,or may not,which is a study and research topic of great potential.In clinical practice,to aim directly at syndromes such as fever,rapid heart rate,breathlessness and higher white cell count at earlier period,the expert of surgery subject in our hospital raises the essential mechanism of heat,toxin and stasis.However,at later period,the syndromes develop into lusterless complexion,lassitude of spirit,no desire to speak, fatigue,shortness of qi,swelling limbs,fatigue of limbs,low voice,weak breathing,loss of appetite,night sweating,pale tongue,white tongue fur, vacuous and weak pulse,so the expert holds that surgery trauma,struggle between healthy qi and pathogenic qi,pathogenic qi conquering healthy qi and wasting qi-blood lead to insufficiency of qi-blood and yin-yang.Actually its essential causes are surgery attack,damage of the spleen and stomach,spleen failing in transportation and lack of source for the production and transformation of qi and blood.And its main pathology is deficiency of spleen qi.It is clear that SIRS is a dynamic group of syndrome from the point of TCM theory.At its earlier period,healthy qi struggle with pathogenic qi. At tbe time,pathogenic qi is excess while healthy qi is not deficient,so the syndromes manifest excess syndrome and heat syndrome.However,healthy qi is declining and finally be defeated by pathogenic qi,therefore the body carries deficient syndrome,which develops rapidly.
Therefore,the surgical department in the Guangdong Provincial Hospital of Traditional Chinese Medicine has made specific study of this topic and discovered that patients with SIRS at the later period mainly shows deficient syndrome(68%proportion) and the main pathological mechanism is deficiency of spleen qi under the clinic TCM syndrome research of 106 cases of patients with operation on abdominal region.And the clinic syndrome of SIRS at later period is divided into liver depression and spleen deficiency,and also deficiency of spleen qi.A small number of patients show qi stagnation and damp-heat in middle jiao,both of which are closely related to the physiologic function of spleen.In the recent years,a great number of documents have reported that Huangqi Si junzi Tang(HQSJZT) has multiple regulation functions. Also,they show that HQSJZT can improve immune function system,retrieve functional disorder of transportation and transmission caused by deficiency of spleen.Moreover,Huangqi has functions such as replenish qi and consolidate the superficial resistance,water-draining and swelling-dispersing, detoxification and promoting granulation.Huangqi is immunomodulator with wide applications,but it is a tonic type of Chinese herbal medicine according to its property and meridian.Modern medicine proves that astragalus polysaccharides can accelerate the change of T lymphocyte in burned mice and promote macrophage to produce interleukin -1 as to strengthen the immune function of the body.Besides,to the infective shock mice,astragalus polysaccharides can suppress the production of proinflammatory cytokine TNF and IL-6 to against excessive systemic inflammatory response and increase survival rate.
In short,SIRS patients with abdominal surgery share the essential pathogenesis of deficiency of spleen qi,and experimental studies have proved that traditional Chinese medicine which can fortify the spleen and replenish qi plays positive role in improving immune functional system,preventing the excessive release of inflammatory mediators and declining inflammatory response.Therefore,it is necessary to further study the influence of traditional Chinese medicine which can fortify the spleen and replenish qi on SIRS patients after abdominal operation.
Objective
On the basis of researching the syndrome rules and the advancement of treatment by TCM among patients who had undergone abdominal surgeries and then got SIRS,Hierarchical Cluster Method combining with experts' differentiation of symptoms and signs is adopted and the TCM pathological essence of the SIRS patients is concluded.Radio-immunity method is employed to test the levels of adrenaline and noradrenaline which are microcosmic syndrome differentiation indexes that reflect splenasthenic syndrome so as to prove that the main pathological factor of the SIRS patients after surgeries is splenasthenic syndrome;and on the basis of this conclusion,Chinese crude drug(astragalus mongholicus injectio) that can invigorate the spleen and benefit qi is adopted to treat these patients.Then a control study on the curative effects between astragalus mongholicus injectio and a traditional western medicine(Ulinastain for Injection) is conducted to inquire into the influences of Chinese crude drug that can invigorate the spleen and benefit qi on clinical indexes(body temperature,heart rate and leukocyte count), IL-6,IL-8,IL-10,and TNF- a of SIRS patients who have undergone major or medium abdominal surgeries.
Methods
Prospective random test design is used in this research.The 106 cases are those patients in Surgical Department of Guangdong Hospital of TCM who were respectively in hospital between October 2006 and January 2009,including 58 males and 48 females who aged 14～75 with a mean age of 50.3±8.46.All these patients have received selective operation treatment of abdominal surgery by the experienced specialists whose professional titles are above physician-in-charge.Among these 106 patients,40 of them received operation on liver,gall and pancreas,25 of them on stomach and small intestine,31 of them on coion and 10 of them on retroperitoneal tumor.The selected cases correspond with over two diagnostic criteria of SIRS while the following cases are ruled out:(1) those whose manifestation of signs was SIRS before operations;(2) those who received concentrated red blood cells≧400ml during operations;(3) those who got wound injection or alimentary fistula or other concurrent diseases after operations;(4) those whose cardio respiratory function was proved to be abnormal before operations;(5) those who got anemia (Hb(100g/L) before operations.Three days after operations,four methods of examination for TCM-inspection,listening,smelling and questioning are conducted on these patients to collect their clinical data that are typed into the database and to fill in the syndrome survey form.All the 58 clinical syndromes of TCM are regarded as variables and on the basis of the frequency of occurrences of the patients' syndromes,cluster method is employed and the pathological features of this group of patients are concluded.In the third morning after operation,blood is drawn from these patients on an empty stomach. And radio-immunity method is applied to examine adrenaline(E) and noradrenaline(NE) in the blood.Then the result is compared with that of the patients who had also received operations on abdominal region but did not get SIRS.In addition,the serological levels of adrenaline and noradrenaline of patients with different types of syndrome after operations on abdominal region are compared to see whether there is any significant difference.Finally,these 106 patients are classified into group with spleen deficiency and group without spleen deficiency according to their types of syndrome.The first group is treated with a Chinese crude drug that can invigorate the spleen and benefit qi-astragalus mongholicus injection 10ml/time and twice a day in 5 successive days,while the other group with Ulinastain for Injection 200,000U/time and twice a day in 5 successive days.Both groups are also provided with treatments of conventional anti-infection and fluid replacement,A control group is established for routinely monitoring the heart rates,breathing frequencies, body temperatures,urinary productions,WBC,the time of SIRS' s improving and the case fatality rate of patients in each group.Before and after the treatment,venous blood is collected to test the levels of tumor necrosis factorα((TNF-α) of the serum,IL-6、IL-8、and IL-10.If the group mean and pairing mean meet normal distribution,T-test is used when comparing,and when P≤0.05,it indicates that there is a significant difference.
Effects
1.After analyzing the types of syndrome on TCM of these 106 patients who got SIRS after receiving major or medium operations on abdominal region,we discovered that their main types of syndrome is deficiency syndrome(which takes 68%) and the main pathomechanism of which is deficiency of spleen-Qi, which is closely related with the spleen' s physiological function.
2.For those whose type of syndrome is spleen deficiency,their serological levels of adrenaline and noradrenaline are significantly lower when compared with those of the control group and the other groups with different syndromes. According to the statistical analysis,there is a significant difference.
3.There is no significant difference between the influence of astragalus mongholicus injection(a Chinese crude drug that can invigorate the spleen and benefit qi) on the body temperatures,heart rates,leukocyte counts of these patients as well as the early occurrence of negative fluid balance in them and that of the traditional drug(Ulinastain for Injection) for treating SIRS,but the difference is significant when the influence of astragalus mongholicus injection on the aforementioned factors of these patients is compared with those of the control group(P≤0.05).
4.There is no significant difference between the influence of astragalus mongholicus injection(a Chinese crude drug that can invigorate the spleen and benefit qi) on the serological levels of inflammatory mediators(TNF-a, IL-6,IL-8,IL-10) in these patients and that of the traditional drug(Ulinastain for Injection) for treating SIRS,but the difference is significant when the influence of astragalus mongholicus injection on the aforementioned factors of these patients is compared with those of the control group(P≤0.05).
Conclusions
1.The main latter manifestation of patients who got SIRS after receiving major or medium operations on abdominal region is the pathomechanism of TCM-deficiency of spleen-Qi.
2.Astragalus mongholicus injection(a Chinese crude drug that can invigorate the spleen and benefit qi) can improve the clinical symptom of the SIRS patients whose type of syndrome is deficiency of spleen-QI after operations.It' s of positive significance on these patients' body temperatures,heart rates,leukocyte counts as well as the early occurrence of negative fluid balance in them.
3.Astragalus mongholicus injection(a Chinese crude drug that can invigorate the spleen and benefit qi) shows antagonistic action towards inflammatory mediators(TNF-a,IL-6,IL-8,IL-10,ect) in patients who got SIRS and whose type of syndrome is spleen deficiency after operations. It can reduce the inflammatory mediators to avoid the organism' s excessive inflammatory reaction,so that the organism is under protection,the occurrence of multi-organ dysfunction syndrome is avoided and the case fatality rate of the seriously ill patients is lowered.
4.Astragalus mongholicus injection(a Chinese crude drug that can invigorate the spleen and benefit qi) can speed up the postoperative rehabilitation of the SIRS patients,which provides a new train of thought for the treatment on TCM during the perioperative period.
半个世纪以来,人们逐步认识到外科手术(尤其是大手术)是一种应激性损伤,组织的切除和/或破坏,导致失血、组织低灌注、大量细胞损坏和器官功能紊乱,使其正常的生理功能及代谢状态发生突然迅速和强烈的变化,在腹部外科受到的打击尤为突出,因此手术与重症创伤、烧伤、脓毒症(sepsis)一样,均可导致机体早期出现发热、心率快、呼吸急促、以及白细胞计数升高等类似于全身炎症反应综合征(systemic inflammatory response syndmne,SIRS)样表现,而SIRS是多器官功能障碍综合征(multiple organ dysfuction syndrome,MODS)发生的基础,是危重病患者的主要死因。因此积极治疗SIRS,阻断SIRS向MODS的转化显得尤为重要。
在开展中西医结合研究的过程中,许多专家运用中医理论探讨SIRS发生发展过程的辨证论治规律,并取得一些的认识,但大多认为SIRS是实证、热证,并使用通腑、泻热及活血祛瘀的方法治疗。吴咸中院士提出SIRS/MODS是当前外科治疗与研究的热点,早期用中医通里攻下法及清热解毒法进行防治已取得肯定的疗效。而实际上缺血/再灌注损伤、免疫抑制是SIRS中后期的共同病理损害,此期应用补气益气、培正扶本及行气活血药物是否有助于改善组织血供及减少再灌注损害,增强机体免疫力这是一个很有发展潜力的研究课题。我院外科专家针对术后SIRS病人早期有发热、心率快、呼吸急促、以及白细胞计数升高等表现,提出热、毒、瘀的病机本质:而到后期因患者表现面色苍白,气短懒言,声低息微,食欲减退,神疲肢倦,潮热盗汗,提出是由于手术创伤,正邪相争,正不胜邪,耗伤气血,致气血阴阳不足,其本质是手术攻伐,损伤脾胃,脾失健运,气血生化乏源,致机体术后出现快速疲劳所致,其主要病理因素是脾气虚。从中医学理论提出SIRS是一动态的临床症侯群,在其早期阶段,机体动员正气,与病邪相争,邪实正不衰,此时表现为实证、热证的病理阶段,但由于正气消耗,正不胜邪,机体不可避免地出现虚证的病理机制,这一过程发展相当迅速。
为此广东省中医院大外科曾对此进行了专题研究,通过对106例腹部手术后SIRS后期(术后三天以上)患者进行中医证型的辩证分析,发现以虚证(占比68%)为主要证型,且以脾气虚(占比62%)为主,并发现SIRS后期临床证候主要分为脾气虚、肝郁脾虚、只有小部分患者表现为气滞及中焦湿热、但均与脾的生理功能损伤密切相关。参考近年来的文献报道,提示黄芪及四君子汤对机体炎症反应具有多方面调节作用,且能明显改善免疫系统功能,纠正脾虚导致的运化功能失调;黄芪具有益气固表、利水退肿、脱毒生肌等功效,是一种作用广泛的免疫调节剂,从中药性味归经分析是补益类中草药;现代医学证实黄芪多糖可明显促进烧伤小鼠T淋巴细胞转化,促进巨噬细胞产生白介素-1以增强机体免疫功能,对感染性休克大鼠能通过抑制促炎性细胞因子TNF和IL-6的产生,从而拮抗过度的全身性炎症反应,提高存活率。
因此,可以认为腹部外科手术后并发SIRS患者后期存在脾气虚的病机本质,而且实验室研究亦证实益气健脾类中药在改善免疫系统功能,拮抗SIRS过程中过度炎症释放,下调炎症反应有积极意义,有必要进一步探索健脾益气类中药对腹部手术后SIRS患者的影响。
目的
通过证候研究及实验室微观辨证指标,归纳出手术后SIRS患者中医病机规律,并在此基础上选用益气健脾类中药(黄芪注射液)进行治疗手术后脾虚证SIRS患者,并就其疗效与传统西药(乌司他丁)作对照研究,探讨益气健脾类中药对腹部大中手术后SIRS患者,其临床指标(体温、心率、白细胞计数)及炎症细胞因子IL-6、IL-8、IL-10、TNF-a的影响。
方法
本研究采用前瞻性队列研究,病例来源:2006年10月至2009年1月广东省中医院外科住院病人106例,其中男58例,女48例;年龄范围14～75岁,平均年龄为50.3±8.46岁,全部患者均接受腹部外科择期手术治疗。施术者为高年资主治以上职称的专科医师。入选病人中,其中肝胆胰手术者40例,胃小肠手术者25例,结肠手术者31例,腹膜后肿瘤者10例。入选病例符合SIRS诊断标准中两项以上,排除以下病例:(1)患者术前已表现SIRS者;(2)术中输浓缩红细胞≧400ml者;(3)术后出现伤口感染,消化道瘘及其他手术相关的并发症;(4)术前心肺功能检查不正常者;(4)术前贫血Hb＜100克/升者。研究病例于手术后第3天上午查房时,按照中医望、闻、问、切四诊收集病人的临床资料,填写证侯调查表录入数据库,将全部58项临床中医证侯作为变量,按患者病症出现的频次逐步聚类,最后根据聚类结果,总结出这群研究对象的病机规律。同时对上述病例术后第三天清晨空腹抽血,采用放射免疫法检测血肾上腺素(E)、去甲肾上腺素浓度(NE),并与同期腹部手术后未发生SIRS患者对比;此外,比较腹部手术后不同证型的SIRS患者E、NE的血清学浓度,探讨各组间是否存在显著性差异;此外入选患者根据当日专家辨证结果及病情轻重,分为脾虚组和非脾虚组及对照组,分别使用健脾益气中药黄芪注射液、乌司他丁及常规综合治疗。乌司他丁治疗组给予常规抗感染、补液治疗同时加用乌司他丁20万U,1次/12h静滴,连用5 d;中药治疗组在常规抗感染、补液治疗基础上给予黄芪注射液20毫升,1次/12h静滴,连用5 d;对照组常规补液、抗感染等综合治疗,与治疗组差别仅是不用乌司他丁或黄芪注射液。常规监测各组间患者心率、呼吸频率、体温、尿量、WBC、SIRS症状改善时间和病死率;治疗前后抽取静脉血检测血清肿瘤坏死因子α((TNF-α)、IL-6、IL-8、IL一10浓度。成组均数若符合正态分布时比较用成组t检验,配对均数符合正态分布时用配对t检验,P≤0.05表示差别有显著性。
结果
1.通过对106例腹部大中手术后SIRS患者中后期中医证型的分析,发现术后SIRS患者以虚证(占比68%)为主要证型,且以脾气虚(占比62%)为主要病机
2.腹部手术后并发SIRS患者,其血清学NE和E水平明显低于非SIRS患者,但属于脾虚证的SIRS患者,其NE、E的血清学浓度与其他证型的SIRS患者,统计学分析无显著性差异。
3.益气健脾类中药黄芪注射液对腹部外科大中手术后SIRS患者体温、心率、白细胞计数及液体负平衡的影响,与传统SIRS治疗药物—乌司他丁无显著性差异,但与对照组有显著性差异(P≤0.05)。
4.益气健脾类中药黄芪注射液对腹部外科大中手术后SIRS患者TNF-a、IL一6、IL-8、IL一10等炎症介质血清浓度的影响,与传统SIRS治疗药物—乌司他丁组无显著性差异,但与对照组有显著性差异(P≤0.05)。
结论
1.腹部大中手术后发生SIRS的患者其中后期主要表现为脾气虚的中医病机。
2.益气健脾类中药(黄芪注射液)对手术后脾虚型SIRS患者,能改善其临床症状,对体温、心率、白细胞计数及液体负平衡的影响有积极意义。
3.益气健脾类中药(黄芪注射液)对手术后脾虚型SIRS患者TNF-a、IL一6、IL-8、IL一10等炎症介质有拮抗作用,能下调炎症介质,避免机体过度的炎症反应,从而达到保护机体、避免多脏器功能不全综合征的发生、降低重症患者的病死率的作用。
4.益气健脾类中药(黄芪注射液)对手术后SIRS患者,能加快患者术后的快速康复,为围手术期中医药治疗提供了新思路
Background
Through the past 50 years,people had gradually realized that surgical intervention is a type of damage caused by stress.The removal and destruction of tissues lead to blood loss,hypoperfusion of tissue,damage of bulk cells and functional disorder of organs,which destroy the normal physiologic function and metabolism in an unexpectedly quick and violent way.Such destruction is especially obvious in abdominal surgery.Surgery,as the same as grave trauma,empyrosis and sepsis,can also result in fever,fast heart rate,shortness of breath,higher white blood count and other resembling systemic inflammatory response syndrome(SIRS).SIRS is the basic cause of multiple organ dysfunction syndrome(MODS),and also the main death cause of severe case.Therefore,it is quite important to give active treatment on SIRS and prevent it from developing into MODS.
Through the study of combination of TCM with Western Medicine,many experts approach the differentiation and treatment system on the occurrence and development of SIRS in use of TCM theory.And they make certain progress.But most experts regard SIRS as excess syndrome and heat syndrome.Meanwhile,they treat SIRS with methods like purging fu-organs,expelling the heat-evil, activating the blood and dissolving stasis.Academician Wu xianzhong has said that SIRS and MODS are two hot spots of study and surgery treatment at the moment.At its earlier stage,it can be effectively treated by internal cleaning,offensive purgative method and heat-cleaning and detoxicating method,however,blood deficiency,reperfusion injury and immune suppression are the shared pathological lesions in the middle and later stages of SIRS. During the two stages,those drugs with effect of invigorating and benefiting qi,reinforcing healthy qi and strengthening nature,activating blood and moving qi may improve tissue blood supply,reduce reperfusion lesion and reinforce body immunity,or may not,which is a study and research topic of great potential.In clinical practice,to aim directly at syndromes such as fever,rapid heart rate,breathlessness and higher white cell count at earlier period,the expert of surgery subject in our hospital raises the essential mechanism of heat,toxin and stasis.However,at later period,the syndromes develop into lusterless complexion,lassitude of spirit,no desire to speak, fatigue,shortness of qi,swelling limbs,fatigue of limbs,low voice,weak breathing,loss of appetite,night sweating,pale tongue,white tongue fur, vacuous and weak pulse,so the expert holds that surgery trauma,struggle between healthy qi and pathogenic qi,pathogenic qi conquering healthy qi and wasting qi-blood lead to insufficiency of qi-blood and yin-yang.Actually its essential causes are surgery attack,damage of the spleen and stomach,spleen failing in transportation and lack of source for the production and transformation of qi and blood.And its main pathology is deficiency of spleen qi.It is clear that SIRS is a dynamic group of syndrome from the point of TCM theory.At its earlier period,healthy qi struggle with pathogenic qi. At tbe time,pathogenic qi is excess while healthy qi is not deficient,so the syndromes manifest excess syndrome and heat syndrome.However,healthy qi is declining and finally be defeated by pathogenic qi,therefore the body carries deficient syndrome,which develops rapidly.
Therefore,the surgical department in the Guangdong Provincial Hospital of Traditional Chinese Medicine has made specific study of this topic and discovered that patients with SIRS at the later period mainly shows deficient syndrome(68%proportion) and the main pathological mechanism is deficiency of spleen qi under the clinic TCM syndrome research of 106 cases of patients with operation on abdominal region.And the clinic syndrome of SIRS at later period is divided into liver depression and spleen deficiency,and also deficiency of spleen qi.A small number of patients show qi stagnation and damp-heat in middle jiao,both of which are closely related to the physiologic function of spleen.In the recent years,a great number of documents have reported that Huangqi Si junzi Tang(HQSJZT) has multiple regulation functions. Also,they show that HQSJZT can improve immune function system,retrieve functional disorder of transportation and transmission caused by deficiency of spleen.Moreover,Huangqi has functions such as replenish qi and consolidate the superficial resistance,water-draining and swelling-dispersing, detoxification and promoting granulation.Huangqi is immunomodulator with wide applications,but it is a tonic type of Chinese herbal medicine according to its property and meridian.Modern medicine proves that astragalus polysaccharides can accelerate the change of T lymphocyte in burned mice and promote macrophage to produce interleukin -1 as to strengthen the immune function of the body.Besides,to the infective shock mice,astragalus polysaccharides can suppress the production of proinflammatory cytokine TNF and IL-6 to against excessive systemic inflammatory response and increase survival rate.
In short,SIRS patients with abdominal surgery share the essential pathogenesis of deficiency of spleen qi,and experimental studies have proved that traditional Chinese medicine which can fortify the spleen and replenish qi plays positive role in improving immune functional system,preventing the excessive release of inflammatory mediators and declining inflammatory response.Therefore,it is necessary to further study the influence of traditional Chinese medicine which can fortify the spleen and replenish qi on SIRS patients after abdominal operation.
Objective
On the basis of researching the syndrome rules and the advancement of treatment by TCM among patients who had undergone abdominal surgeries and then got SIRS,Hierarchical Cluster Method combining with experts' differentiation of symptoms and signs is adopted and the TCM pathological essence of the SIRS patients is concluded.Radio-immunity method is employed to test the levels of adrenaline and noradrenaline which are microcosmic syndrome differentiation indexes that reflect splenasthenic syndrome so as to prove that the main pathological factor of the SIRS patients after surgeries is splenasthenic syndrome;and on the basis of this conclusion,Chinese crude drug(astragalus mongholicus injectio) that can invigorate the spleen and benefit qi is adopted to treat these patients.Then a control study on the curative effects between astragalus mongholicus injectio and a traditional western medicine(Ulinastain for Injection) is conducted to inquire into the influences of Chinese crude drug that can invigorate the spleen and benefit qi on clinical indexes(body temperature,heart rate and leukocyte count), IL-6,IL-8,IL-10,and TNF- a of SIRS patients who have undergone major or medium abdominal surgeries.
Methods
Prospective random test design is used in this research.The 106 cases are those patients in Surgical Department of Guangdong Hospital of TCM who were respectively in hospital between October 2006 and January 2009,including 58 males and 48 females who aged 14～75 with a mean age of 50.3±8.46.All these patients have received selective operation treatment of abdominal surgery by the experienced specialists whose professional titles are above physician-in-charge.Among these 106 patients,40 of them received operation on liver,gall and pancreas,25 of them on stomach and small intestine,31 of them on coion and 10 of them on retroperitoneal tumor.The selected cases correspond with over two diagnostic criteria of SIRS while the following cases are ruled out:(1) those whose manifestation of signs was SIRS before operations;(2) those who received concentrated red blood cells≧400ml during operations;(3) those who got wound injection or alimentary fistula or other concurrent diseases after operations;(4) those whose cardio respiratory function was proved to be abnormal before operations;(5) those who got anemia (Hb(100g/L) before operations.Three days after operations,four methods of examination for TCM-inspection,listening,smelling and questioning are conducted on these patients to collect their clinical data that are typed into the database and to fill in the syndrome survey form.All the 58 clinical syndromes of TCM are regarded as variables and on the basis of the frequency of occurrences of the patients' syndromes,cluster method is employed and the pathological features of this group of patients are concluded.In the third morning after operation,blood is drawn from these patients on an empty stomach. And radio-immunity method is applied to examine adrenaline(E) and noradrenaline(NE) in the blood.Then the result is compared with that of the patients who had also received operations on abdominal region but did not get SIRS.In addition,the serological levels of adrenaline and noradrenaline of patients with different types of syndrome after operations on abdominal region are compared to see whether there is any significant difference.Finally,these 106 patients are classified into group with spleen deficiency and group without spleen deficiency according to their types of syndrome.The first group is treated with a Chinese crude drug that can invigorate the spleen and benefit qi-astragalus mongholicus injection 10ml/time and twice a day in 5 successive days,while the other group with Ulinastain for Injection 200,000U/time and twice a day in 5 successive days.Both groups are also provided with treatments of conventional anti-infection and fluid replacement,A control group is established for routinely monitoring the heart rates,breathing frequencies, body temperatures,urinary productions,WBC,the time of SIRS' s improving and the case fatality rate of patients in each group.Before and after the treatment,venous blood is collected to test the levels of tumor necrosis factorα((TNF-α) of the serum,IL-6、IL-8、and IL-10.If the group mean and pairing mean meet normal distribution,T-test is used when comparing,and when P≤0.05,it indicates that there is a significant difference.
Effects
1.After analyzing the types of syndrome on TCM of these 106 patients who got SIRS after receiving major or medium operations on abdominal region,we discovered that their main types of syndrome is deficiency syndrome(which takes 68%) and the main pathomechanism of which is deficiency of spleen-Qi, which is closely related with the spleen' s physiological function.
2.For those whose type of syndrome is spleen deficiency,their serological levels of adrenaline and noradrenaline are significantly lower when compared with those of the control group and the other groups with different syndromes. According to the statistical analysis,there is a significant difference.
3.There is no significant difference between the influence of astragalus mongholicus injection(a Chinese crude drug that can invigorate the spleen and benefit qi) on the body temperatures,heart rates,leukocyte counts of these patients as well as the early occurrence of negative fluid balance in them and that of the traditional drug(Ulinastain for Injection) for treating SIRS,but the difference is significant when the influence of astragalus mongholicus injection on the aforementioned factors of these patients is compared with those of the control group(P≤0.05).
4.There is no significant difference between the influence of astragalus mongholicus injection(a Chinese crude drug that can invigorate the spleen and benefit qi) on the serological levels of inflammatory mediators(TNF-a, IL-6,IL-8,IL-10) in these patients and that of the traditional drug(Ulinastain for Injection) for treating SIRS,but the difference is significant when the influence of astragalus mongholicus injection on the aforementioned factors of these patients is compared with those of the control group(P≤0.05).
Conclusions
1.The main latter manifestation of patients who got SIRS after receiving major or medium operations on abdominal region is the pathomechanism of TCM-deficiency of spleen-Qi.
2.Astragalus mongholicus injection(a Chinese crude drug that can invigorate the spleen and benefit qi) can improve the clinical symptom of the SIRS patients whose type of syndrome is deficiency of spleen-QI after operations.It' s of positive significance on these patients' body temperatures,heart rates,leukocyte counts as well as the early occurrence of negative fluid balance in them.
3.Astragalus mongholicus injection(a Chinese crude drug that can invigorate the spleen and benefit qi) shows antagonistic action towards inflammatory mediators(TNF-a,IL-6,IL-8,IL-10,ect) in patients who got SIRS and whose type of syndrome is spleen deficiency after operations. It can reduce the inflammatory mediators to avoid the organism' s excessive inflammatory reaction,so that the organism is under protection,the occurrence of multi-organ dysfunction syndrome is avoided and the case fatality rate of the seriously ill patients is lowered.
4.Astragalus mongholicus injection(a Chinese crude drug that can invigorate the spleen and benefit qi) can speed up the postoperative rehabilitation of the SIRS patients,which provides a new train of thought for the treatment on TCM during the perioperative period.
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