The Therputeeutic Effects Of Shenfu Injection On The Multiple Organ Dysfunction Syndrome In Elderly

BackgroudThe formulation of Shenfu decoction is recorded in the volume59of Shenji Zonglu and was widely applicated in Traditional Chinese Medicine in urgent clinic. Based on the clinical needs, it has been developed as Shenfu injection and successfully used in the clinic for collapse such as infectiousness, blooding, etc.It has been reported by a lot of literature that Shenfu injection can be applied to various urgent and serious syndromes, such as shock induced by cardio disorder, infection, or blood losing. It can also be used to treat with multi-cardio disease. Combined with the experimental study on Shenfu injection, Shenfu Injection has a therapeutic effect on lung, heart, intestine, blood system, immune system and central nervous system.The modern medicine has had well research for the mechanism of MODSE and has been provided noval theory or hypothesis. However, the pharmacokinetics (PK) of main components has not been systematically investigated. Furthermore, there has been no report on the prevention and treatment effect on the syndrome of rats caused by multi-organ dysfunction.ObjectiveTo investigate the PK of7main components in Shenfu injection following administration to rats and the ameliorated effect on multi-organ dysfunctional syndrome of rats, provide the experimental basic for clinical application.Methods(1) PK investigationA high performance liquid chromatography coupled to time-of-flight mass spectrometry (HPLC-TOF MS) was first successfully developed and validated for the identification and determination of7ginsenosides, Re, Rf, Rb1, Rc, Rb2, Ro and Rd, in a Chinese herbal preparation Shenfu injection and rat plasma. Based on the method, the pharmacokinetic profiles of the7ginsenosides were investigated following intravenous administration of single dose of Shenfu injection to6rats.(2) Prevention and treatment effect on the syndrome of rats caused by multi-organfunctional disorder Forty five SD rats were randomly divided into3groupsas following:blank group physiological saline group and Shenfru injection (1ml/kg/d). Blood samples were taken via artery vein and the biochemical indicators including ALT, TB, BUN, Cr, CPK, and NO, were determined. In addition, the content of TNF-a in lung, heart, liver and kidney were assayed.Result(1)For PK research, the established method had high linearity, selectivity, sensitivity, accuracy and precise. Rb1, Re and Rb2had similar PK profiles and relatively long half-life (t1/2) values (19.29±6.36h,29.54±22.91h,35.60±30.66h). The t1/2valudes of Rf and Rd were4.21±3.68h and8.49±5.20h, respectively, indicating that they could be metabolized more rapidly than Rb1, Rc and Rb2·(2)The ALT,TB,CPK,BUN,and Cr were significantly increased after exposure with OA and LPS, compared to control group. Treated with Shenfu injection ameliorated the relevant biochemical indexes, which indicated the Shenfu injection alleviated the MODS of rats induced by OA and LPS.ConclusionThe7main components of Shenfu injection, Re, Rf, Rb1, Rc, Rb2, Ro and Rd, have different PK features. The relating parameters can provide helpful information and guidance for the clinic application, such as the dosage adjustment and administration interval. Shenfu injection has some efficacy on the syndrome of the elders caused by multi-organ dysfunction. BackgroundRecencely, the geriatric morbility is increase year by year companying with the lifetime of human being extented becuase of the social development, and scientific ang technologic advancement. Multiple organ dysfunction syndrome is common geriatric diseases as well as in emergency department that resulted in75-100%mortality, which is the main cause of old people death. Although the mechanism and/or hypothesis of MODSE had been provided, the clincial therapeutic were not improved. At present, the MODSE was treated with multiple organ surport therapy, anti-infection, etc., however, the mortality had not been decrease. It is important for concentrating on therapeutic and preventment of MODSE.Shenfu decotion, first recorded in Sheng Ji Zong lu, has rescuing from collapse by restoring yang and tonifying qi and preventing exhaustion, which is the key formula for emergency in clinical application of Chinese medicine. According to the clinical requirements, the shenfu decotion was prepared shenfu injection for clinical requirements of Chinese medicine with modern pharmaceutic technologic.Accumulating evidences confrimed that shenfu injection had been widely applied in clinic for therapying cardio-cerebral vascular diseases, diabetes and complication, and cancer, etc. Further researches of clinical application and pharmacological properties indicated that shenfu injection could prolong the tolerance of anti-hypoxia, protect against cardiac ischemia, antiarrhythmic, increase the blood flow volume of coronary, anti-shock, antilipid peroxidation, regulate immunological function, ameiorate hemorheology, excite hypophysis-adrenal cortex function, enhance non-specific resistance, and attenuate the diaphragmatic fatigue, etc.We hypothesized that shenfu injection can protected against the MODSE in accordance with the references, and then design the experiment for further explore the clinical volume of shenfu injection for MODSE.AimTo explore the therapeutic value of shenfu injection treated with MODSE by systematic clinical comparition and observation.Methods1.The106cases diagnosed MODSE were selected from august2010to april2012in our hospital adapted with MODSE criterion. All of the cases was randomly alloted into2groups as following:therapeutic and experimental groups, respectively. Excluding criterion:①With Montgomery diagnosed criterion producingg irreversible organ failure:ヽirculation function failure (infectious shock):the seriouse infection did not control with antibiotics and operation, finally formed refractoriness shock.②Heart failure:cardiogenic shock, ventricular fibrillation or sudden cardiac arrest.③Respiratory function failure:PaO2<5.3-6.7Kpa with mechanical ventilation.④central nervous system failure:non-cerebral blood flow or brain death.⑤Blood system failure: widely hemorrhage induced by DIC which can not rectify or vascular hemorrhage which can not rectify with operation.⑥Hepatic failure:hepatic encephalopathy or hepatorenal failure syndrome did not thrapy.⑦Renal failure:serious acidosis induced by renal failure or sudden cardiac arrest induced by hyperkalemia or hypercalcemia.(2) Differentiation of symptoms and signs with Chinese medicine:interior heat induced by noxious heat.2. Observation indexes:(1) Comparision of therapeutic effects:The therapeutic effects were designed in accordance with the indexes of diagnostic criteria. Excellent therapeutic effect:Most symptoms were rectified, and the organic dysfunction get back to normal; Efficacious therapeutic effect: Symptoms were significantly ameliorated, and the organic function had been arrived50%normal volume; Invalid:did not arrive the criterion or exacerbation, even death.(2) APACHEⅢ_evaluation:Before and after2weeks treatment, the indexes of acute and chronic physical function.(3) The death and survival ratio difference was assayed by statistical methods.(4) The TNF-α was assayed with commercial biochemical kits.3. The selective cases were divided into two grousp as following:shenfu injection (treated with shenfu injection and morden medial method) and modern medical treatment (treated with modern medical method) groups with single blind methods. Therapeutic mthods:morden medical methods:(1) positive control primary diseases,(2) rational applied antibiotics, prevented and contraol pulmonary infecton, and control secondary infection.(3)The organic sustaining therapeutic was used, especially provided respiration and renal function, such as:increasing mechanical ventilation_with and without operation, continuous renal replacement therapy.(4) Nutrition supplement and recuperation.(5)The two groups were basic treated with symptomatic therapy in accordance with modern medicine, such as:anti-infection, increase blood volume, maintaining acid-base equilibrium and electrolyte balance.(6) Control blood glucose. The shenfu injection was used for the patient in experimental groups with100ml and55GS250ml (when the random blood glucose over8.3mmol/L, the GS was replaced by NS), one time one day.4. Statistical analysis:all of data were expressed as means±SEM, and statistical comparisons between groups were analysed uing SPSS v11.0. Measurement data was analyzed using unpaired t test. Enumeratoin data was analyzed using X2. A value of p b0.05was considered to be statistically significant between groups.Results:Compared with the control group, the efficacy and total efficacy were significantly ameliorated in experimental groups. There was significant difference in volume of APACHE between experimental and control group. The pathophysiological conditions in experimental group had better than control. ConclusionShenfu injection can ameliorated the symptoms of MODSE, which can be considered as a general therapeutic agent in clinic.