Treatment Research On Capillary Leak Syndrome In Use Of Ulinastatin Combined With Small Doses Of Hormones

Background and objectivesRecent years, we often see some patients with refractory hypotension anddepressed central venous. Aggressive resuscitationa after shock is still difficult tocorrect, bulbar conjunctiva and systemic edema, hpyoxemia caused by increasedlung edema, severe cases will be secondary to the Multiple Organ Dysfunctionsyndrome (MODS), in ICU. These patients may have Capillary leak syndrome(CLS). According to the evolution process of the CLS and clinical manifestations,general it includes two periods: leakage periods and recovery period. Phase leakageeasily leads to MODS or MOF caused by tissuse hypoperfusion. Recovery may bedueto the improper theatment, acute pulmonary edema and acute acute left heartfailure. CLS is considered to be severe complications of systemic inflammatoryresponse (SIRS).The currently accepted pathogenesis of CLS is cytokine-mediatedvascular endothelial doctrine. In this doctrine, trauma, severe infection, ischemia,shock, poisoning will not only cause the immune system and complement systemdisorder, but also activate monocyte-macrophage system, release large amounts oftumor necrosis factor-a (TNF-a), interleukin-1(IL-1), IL-2and IL-6, plateletactivating factor, phospholipase A2and other pro-inflammatory cytokines, causingsystemic inflammatory response syndrome (SIRS). What’s more, it will damagecapillary endothelial, increase permeability, emerge hypoalbuminemia and lack ofeffective circulating blood volume because of vascular leakage of plasma proteinsand other macromolecules into the interstitial space. It can cause severehypoalbuminemia, pleural and peritoneal effusions, whole body edema, centralvenous pressure (CVP) and decreased blood pressure and other clinicalsyndrome.The bad thing can be severe multiple organ failure. Su Jun etc. Research shows that the aggravating SIRS，therombocytoperia,hypocacemia and aggravatedprimary disease is suscepitable factors of CLS. Once the secondary CLS, patientswill worsen sharmly, increase treatment difficulty and mortality. Now CLS iswithout special measures, the main treatment includs improving blood circulation,control inflammation and treating the primary disease. CLS leads to a sharpdeterioration in the patient’s condition, thus increasing the difficulty of treatment andmortality obviously.UTI is acid glycoprotein secreted by the liver, a broad-spectrum proteaseinhibitor and human endogenous anti-inflammatory substances, which can beisolated and purified by fresh urine of a healthy male.UTI can stabilize lysosomaland membrane, regulate inflammatory mediators, inhibit the release of free oxygenradicals and regulate immune system. Studies have shown that ulinastatin inhibit theextracellular neutrophil elastase activity dose-dependently and its activity in cellsand neutrophil-mediated endothelial cell injury, thereby reducing capillarypermeability.CLS can cause severe hypotension on the basis of multi-systemic inflammatoryresponse, patients should take low-dose hydrocortisone (200-300mg/day iv) within8hours in early stage to advoid shock timely.While low-dose glucocorticoids caninhibit synthesis and release of cytokines (IL-I, IL-6, TNF-α, etc.), chemokines (IL-8,etc.),adhesion molecules and other pro-inflammatory mediators; inhibit neutrophilmoving and adhering;inhibit lymphocyte proliferation and differentiation andpromote apoptosis;protect vascular endothelial cells, reduce the inflammatoryexudate to achieve a strong anti-inflammatory effect.Because glucocorticoid dose is smaller,CLS can avoid side effects caused byhyperglycemia and relevant immune suppression with the application of large dosesof hormones. Many studies suggest applying Ulinastatin alone, because low-dosehormone has a therapeutic effect on the CLS.However, it is not clear whetherUlinastatin combined with low dose hormone is better than CLS alone.This paperaims to explore therapeutic effect and safety of capillary leak(CLS) in use ofulinastatin combined with low doses of hormones. MethodsThe method is to continuously select secondary CLS of120patients during thetreatment in Comprehensive ICU of the first Affiliated Hospital of ZhengzhouUniversity from November,2012to December2013:84males,36Females at theaverage age of (88.7±8.5). According to the acute physiology and chronic healthevaluation П (APACHEП), the severity of the disease is evaluated. The120patientsof CLS clinical cases were randomly divided into four groups:the first group refersto the ulinastatin group (U,Tianpu Luoan, TECHPOOL Biochemical PharmaceuticalCo.,Ltd.) in use of ulinastatin needle based on hydroxyethyl starch, plasma andcrystal liquid treatment with500000U+250ml0.9%saline200ml ivgtt bid,5d fora course; the second refers to the hydrocortisone pine group(H) group in use ofhydrocortisone pine needle based on hydroxyethyl starch, plasma and crystal liquidtherapy with100mg hydrocortisone pine needles+0.9%saline100ml ivgtt bid,3-5dfor a course; the third group refers to the ulinastatin and hydrocortisone group (U+H) in use of hydrocortisone pine needle500000U+treatment250ml0.9%saline200ml ivgtt bid and hydrocortisone pine needles500,000U+250ml0.9%saline200ml ivgtt bid based on hydroxyethyl starch, plasma and crystal liquid therapy; thefourth group refers to the use of hydroxyethyl starch, plasma and crystal liquidtherapy CLS,5d as a course of treatment. Before treatment, each enrolled patientsare evaluted based on of APACHE Ⅱscore and Marshallorgan dysfunctionscore.The effective antibiotics are selected combined with susceptibility results ofindividual patients in order to avoid statistically significant between the groups.Before the five days of treatment and after treatment, we need monitor blood routine,liver function, kidney function, procalcitonin (PCT), the pH value,the red blood cellpressure product%(HCT)and lactic acid of blood gas analysis, white blood cellcount(WBC),neutrophil ratio(NE%) and platelet count(PLT) of blood routine,activaation of prothrombin time(APTT),prothrombin time(PT) of blood coagulationfunction, creatinne values of renal function, glutamic-pyruvic transaminase(ALT)andglutamic oxalacetic transaminase(AST) of liver function. At the same time,we needICU staylength,duration of mechanical ventilation,28d survival rate are added up.The monitoring indicators suggest that the application of Ulinastatin alone, low-dose hormone is more effective than Ulinastatin combined with small doses of hormonesby contrast of Ulinastatin group, hormones group, Ulinastatin+hormones groupand control group respectively. P <0.05indicates significant difference statisticallyResults1．Capareing the treatment numerical of ulinastain group and the contralgroup,we found the WBC，NE%, PCTvalue, APTT and PT value decrease.(P<0.05).PH value, lac, creatinine,ALT, AST and HCT%campared with controlgroup,there is no statistical significance.2．Capareing the treatment numerical of hormone group and the contralgroup,we found the WBC，NE%and PCT value is decreased (P<0.05).PH value, lac,creatinine,ALT, AST,HCT%,APTT and PT value campared with controlgroup,there is no statistical significance.3．Capareing the treatment numerical of ulinastatin+hormone group and thecontral group,we found the WBC，NE%and PCT value, lac,HCT%,APTT, PT valueand creatinine is decreased significantly(P<0.05).28d survival rate and PH value isimproved.The time of mechanical ventilation is shorten significantly(P<0.05).ALTand AST values, creatinine campared with control group,there is no statisticalsignificance.4．Capareing the treatment numerical of ulinastatin+hormone group and theulinastatin group,hormore group,we found the WBC，NE%and PCT value, lac,HCT%,APTT, PT value and creatinine is decreased obviously(P<0.05).28d survivalrate and PH value is improved.The time of mechanical ventilation is shortensignificantly(P<0.05).ALT,AST and creatinine valuesand have no obviousdifferences.5. There aren’t obvious adverse reactions,when patients use the Ulinastatin orhormone.Conclusion1． It is confirmed that UTI and low-dose hormone alone can reduce inflammation, blood capillary leak syndrome has a therapeutic effect.2．Ulinastain on capillary leakage coule improve the patients of coagulantfuncton.3．Jointing hydrocortisone and ulinastatin than single application of the twodrugs can reduce inflammaion,and can protect kidney function and blood coagulaionsystem,shorten the time of mechanical ventilation and improne28d survival rate.4．There is no obvious adverse reactions,when we use ulinastain and small doseof hormore.The effect of Ulinastatin joint hydrocortisone is more obvious than twodrugs alone to improve capillary leak.