Based on the Four Segments and Treatment by Syndrome
Based on the Four Segments and Treatment by Syndrome
Differentiation to Lower the Mortality of Sepsis
LIU Qing-quan
Lowering the mortality of sepsis has become an important issue in the international critical care medicine because of its unacceptably high incidence. In 2004 and 2008, there were no essential breakthroughs in international guidelines for the management of severe sepsis and shock. The treatments did not meet the objective of lowering the clinical mortality of severe sepsis, which still remains at 30%-50%(1,2). The most important reasons are the complicated and unknown pathological mechanisms of sepsis and difficulty in making clear diagnosis in the early stage. It is hard to achieve an early diagnosis, early intervention and early selection of targeted therapies and drugs.
Chinese medicine emphasizes the diagnosis and treatment based on an analysis of clinical characteristics. Syndrome differentiation is the basic method of clinical judgment. Our prior professors, WANG Jin-da and WANG Bao-en, have conducted large amounts of clinical studies on the recognition of sepsis in Chinese medicine. They have put forward an innovative theory of "treatment of bacterium and toxin coordinately", which has integrated the theory of traditional Chinese medicine
(TCM) with Western medicine. They also successfully developed Xuebijing Injection, Ergotrophic Composition and Shenqi Huoxue Granule to decrease the mortality of severe sepsis successively. We have been engaged in clinical and fundamental researches on sepsis for more than 10 years. By fully absorbing our predecessors' research results and combining the pathological features of sepsis and its clinical characteristics, under the guidance of the Chinese medicine theory of combination of disease and syndrome, we put forward the scheme "based on the four segments, following the concept of wholism and equilibrium, treatment by syndrome differentiation"(3).
Treating the Septic Fever according to the Location of the Pathogenic Factors Fever is the most common symptom of sepsis, with a clinical incidence rate of 100% and has been paid most attention to by clinicians. The curative effect can be improved by the rational use of antibiotics and combined with Chinese medicine on the basis of syndrome differentiation. TCM has abundant experience in treating febrile diseases. For examples, ZHANG Zhong-jing, a well-known doctor in the Han dynasty, used syndrome differentiation of the Six meridians in the treatment of febrile diseases. YE Tian-shi, a famous physician in the Qing dynasty used the differentiation of wei, qi, ying and blood to treat seasonal febrile diseases. Based on internal injury theory, LI Dong-yuan, a well-known doctor in the Jin-Yuan dynasty created the method of benefiting qi and invigorating yang to treat febrile diseases caused by internal injuries. Considering the incidence characteristics of sepsis, we believe the cause of the fever by sepsis should be exogenous pathogens, not be "internal injuries". Therefore, we should treat it according to the syndrome differentiations of the six meridians and wei, qi, ying and blood. Its location is in three yang channels, ying-blood, and the pathogenesis is the inner occlusion of pathogenic heat, depression and stagnation of qi. The basic treatment principles should highlight the mediating, relieving exterior syndrome, clearing and letting-out pathogenic factors in deeper layers(4). The basic prescriptions are Chaihu Prescription combined with Mahuang Prescription. For example, Xiao Chaihu Decoction combined with Mahuang Decoction added with southern wood should be used for the mild case. For severely stagnated interior heat accompanied with abdominal distention and constipation, Da Chaihu Decoction with Maxing Shigan Decoction and southern wood, should be used, and for the platelet progressively decreasing with early coagulation dysfunction, which indicates the heat has penetrated into ying-blood stage, Xijiao Emergency Department of Dongzhimen
Dihuang Decoction should be used together. CHEN Shi-duo, a doctor in the Qing dynasty considered Herba Artemisiae Annuae had the function of "purging pathogenic fire-heat without consuming qi and blood"(5). Professor ZHOU Hong, from The Fourth Military Medical University, has carried out plenty of studies on Herba Artemisiae Annuae and confirmed its good, anti-inflammatory effects. It is an effective drug for the fever induced by sepsis. Herba Artemisiae Annuae, with special characteristics such as "mediating, relieving exterior syndrome and clearing out pathogenic factors in deeper layers" and shows good curative effects on sepsis. It should be used in large doses, usually more than 30 g, in compound decoctions. As the pathogenic factors are located at the exterior layer, the treatment should be taken as early as possible. "If the pathogenic factor is at the exterior location, it should be dispersed by sweating". That is to say, the treatment should be taken according to the location of the pathogenic factors to achieve curative effect.
Regulating Qi and Blood Should Be Conducted in the Treatment of Coagulation Dysfunction of Sepsis Studies show that coagulation dysfunction is one of the important pathological mechanisms of sepsis, manifesting early as progressive platelet reduction and later appearance of disseminated intravascular coagulation (DlC). Even those with critically severe symptoms may be accompanied with shock. These are crucial points of severe sepsis. TCM considers that the pathogenesis belongs to the blood stasis syndrome. The major pathogenesis of sepsis is the accumulation of toxic heat and disturbance of qi flow, which further causes the mutual congealing of blood stasis and toxin in collaterals, consumes qi, impairs yin and yang. Therefore, it is a complex pathogenesis of "intermingling of asthenia and sthenia". But "dysfunction of qi and blood" induced by the "mutual congealing of blood stasis and toxin" is the main pathogenesis of sepsis at the stage of coagulation dysfunction.
Therefore, it's crucial to regulate qi and blood based on the principle of "qi acting as the commander of blood and blood being the mother of qi". Patients of mutual congealing blood stasis and toxin syndrome in a mild degree should be treated with the principle of regulating qi, activating blood and detoxication. The formula is Xuefu Zhuyu Decoction created by WANG Qing-ren, a famous doctor in the Qing dynasty, or Xue bijing Injection for intravenous transfusion. The curative effect could be achieved in three or five days. The "Depletion syndrome" may appear in more severe cases manifested as the symptoms of Shaoyin disease, such as "perspiration, cold extremities, unstable blood pressure with decreasing tendency, minor pulse almost disappearing", it is important to reinforce qi and retrieve depletion at this moment, combined with promoting blood flow and relieving toxin. Shengmai Powder and Shenfu Decoction may be used by adding Radix Notoginseng, Radix Angelicae
Sinensis, Flos Carthami, Radix et Rhizoma Rhei. Also, Shengmai Injection 100 mL and Shenfu Injection 100 mL can be used by continuous venous pumping, once a day, and Xuebiqing Injection 100 mL through venous pumping twice a day. That can be effective to prevent DIC from developing into the stage of fibrinolysis and hemorrhage(6). The key in this phase is early intervention, and regulating qi and blood according to the pathological mechanism of deficiency and excess syndromes at first.
Treatment of Septic Lung Injury Should Be Combined with the Treatment of Lung and Large Intestine Simultaneously The "Lung" is the primary organ first injured in severe sepsis, and manifests as acute lung injury in the early stage and as acute respiratory distress syndrome in the late stage. Mechanical ventilation is the key for the supportive treatment, but essentially, it only supports the function of the organ and provides opportunity for other therapies. After many years' clinical practice, we considered that TCM plays a crucial role in treating acute lung injury. The features of acute lung injury are breathlessness in the early stage and gastrointestinal dysfunction symptoms such as abdominal distension and constipation occurring subsequently or after mechanical ventilation in most patients. Therefore, the lung is further severely injured, developing to the acute respiratory distress syndrome or even leading to treatment failure.
The pathogenesis in TCM syndrome differentiation is that "stasis and poison damaging the lung collaterals, and then transmitting to the large intestine and resulting in transporting dysfunction, which leads to both disorders of the lung and large intestine simultaneously". As "the lung and large intestine are interior-exteriorly correlated through the meridians" in TCM, they should be treated at the same time and Xuanbai Chengqi Decoction, formulated by WU Ju-tong, a famous physician in the Qing dynasty, added herbs with the functions of promoting blood flow, detoxication and opening collaterals, such as Radix Salviae Miltiorrhizae, Radix Paeoniae Rubra, Radix Notoginseng and etc. In the decoction, Radix Et Rhizoma Rhei should be used in large doses to release the obstruction of wastes in the stomach and intestines. Practice has proven that Chinese medicinal therapy can not only treat lung injury, but also prevent the occurrence of acute respiratory distress syndrome.
Treatment of Multiple Organ Failure Syndrome Should Strengthen Genuine Qi and Rescue the Depletion. The final outcome of sepsis is multiple organ dysfunction syndrome and multiple organ failure, which is the main reason for sepsis death.
Therefore, prevention and treatment of multiple organ dysfunction syndrome is the key point to lower the mortality of sepsis. Organ support techniques in Western medicine can only support life, but cannot reduce the fatality rate. However, the applications of these techniques play a crucial supportive role in Chinese medicine to cure it. If sepsis develops to the stage of multiple organ dysfunction, its clinical features are similar to "the characteristics of deteriorated syndrome of Taiyang meridian disease and three yin disease", which belongs to the "prostration syndrome" with the depletion of vital qi.
At this point, emergent treatment for collapse should be carried out immediately. Symptoms of prostration syndrome are sudden dropping of high fever, cold extremities, profuse sweating, unstable blood pressure, or decreasing blood platelets. Single Ginseng Decoction can be used, with red Ginseng, in any dose but not less than 30 g. It may be thickly decocted and taken frequently. The author had successfully saved a septic patient with acute respiratory distress syndrome, acute renal dysfunction, DlC in fibrinolysis stage and shock, etc. Red Ginseng 250 g were thickly decocted and taken frequently through nasal feeding within 24 h, and the patient was in a stable condition five days later. Though the Single Ginseng Decoction is effective in clinic, the key is to grasp its amount and administration time. If the symptoms of yang deficiency with containment and disturbance of qi transformation, such as polyhidrosis, oliguria, cold four extremities and absent-mindedness appear, it is emergent to restore yang from collapse and Shenfu Decoction is mainly used. If patients have symptoms of oliguria and acute renal dysfunction, the following herbs must be given: prepared Radix Aconiti Lateralis Preparata, Radix Et Rhizoma Rhei, Calcing fossilia ossis mastoid and oyster, charred Radix Sanguisorbae, etc. are thickly decocted by rectal dripping, which may effectively prevent and treat acute renal dysfunction(7). Generally speaking, the objective of treatment at this stage should be to rescue the patient from the exhaustion of yang and yin as the core, protect the functions of organs and ultimately, reduce the mortality.
In the past two years under the guidance of the basic theory of Chinese medicine, we followed the concept of wholism andequilibrium, and used six-meridian and ying-blood as differentiation syndrome system. Based on the four segments, we havealready cured 96 severe sepsis patients and the death rate was 19.18%. It shows the advantages and potential capability of TCM in treating sepsis.
At present, we have formed a series of relatively complete integral protocol to treat sepsis. In the next step, the multi-center, randomized blind controlled clinical studies are being carried out in the following studies. Hopefully, the outcomesof those studies in the next three years may gradually lay the foundation to reduce sepsis fatality by means of traditionalChinese medicine.
Platform for TCM Education relies on Guilin Sino-western Medicine Joint Hospital and Guilin International Exchange Center for Traditional Chinese Medicine and bases on strong internet function of www.tcmdiscovery.com to set up a platform where people can learn and practice TCM so as to contribute to humankind health.
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