The Effects Of Different Dose Of CRRT On The Concentration Of Meropenem In Patients With Sepsis

The current epidemiology of sepsis show us that the incidences of sepsis increased,the mortality related to sepsis has been declined,but the absolute number of sepsis-related mortality cases is considerably high.Severe sepsis is the trigger of MODS,sepsis-induced AKI is associated with the increased mortality rates.In many cases,the patients need the therapy of CRRT.Among all the factors,sepsis is the trigger for the development of approximately 50%of cases of AKI.Broad-spectrum antibiotic agent used within 1 hour is very important.Studies have shown that early and plenty of application of antimicrobial agents can obviously increase the survival rate of severe sepsis.Effective anti-infection treatment requires achieving enough tissue concentrations.To the patients who receive the therapy of CRRT,lots of factors can influence the concentration of the drug: Vd,albumin level,the dose of CRRT and so on.If we ignore those factors,the effects of anti-infection would be failed.Meropene is a broad-spectrum carbapenem and is one of the most prescribed antibiotics for the empirical treatment of severe infections.It exhibits optimal killing activity when the concentrations of the unbound fraction of drug in plasma are maintained above the MIC of the bacteria for a certain percentage of dosing interval,which in studies has been defined to be about 40%.a higher percentage of the T > MIC,even 100%,can get better effects.Meropene is a hydrophilic,small molecule and a very low level of protein binding.These characteristics make meropene a drug mainly eliminated by the kidneys and the CRRT.However,insufficient drug concentration may lead to drug resistance.So it's a big challenge to the empirical use of antimicrobial agents in patients with CRRT.In all the factors influenced drug concentration,the dose of CRRT hasbeen long debated.The research results of Ronco suggest that higher dose of CRRT can improve survival rates of patients;unfortunately some studies get the opposite results.In the different studies of CRRT dose,not only were they comparing high and low CRRT dose,but also comparing lower antibiotic serum concentrations VS higher antibiotic serum concentrations,this phenomenon usually been ignored by some researchers.So if appropriate antibiotic dosing and get the appropriate drug concentration,it is quite interesting that patient outcomes with high intensity CRRT were not inferior to low dose CRRT.There are lots of studies on the influence of CRRT dose on drug concentration,but the results of meropene don't reach a consensus.More studies need to be done to explore the phenomenon.Purpose : Explores the effects of different dose of CRRT on the concentration of meropen in patients with sepsis who receive the CVVH mode therapy,and whether the recommended dose of meropen can reach the appropriate concentration in blood.Provide references for the choice of CRRT dose and the dosing of antibiotic.Method: The object of study for patients with severe sepsis require continuous renal replacement therapy and according to the experience of results or the clinical experience to choose meropen.This study selected 16 patients,10 cases of men and 6 cases of women.The patients were divided into 2 groups: the lower dose of 25ml/kg/h,and the higher dose of 35ml/kg/h.all the Patients received meropen 1g each 12 hours;the drug should be infused in 30 minutes.24 hours After the first agent dosage,blood collection at 0h,0.5h,1h,1.5h,2h,4h,6h,8h,10 h,12h before sampling filter blood,filter blood specimens 2ml,ultrafiltrate samples 2ml,and then frozen at-80? refrigerator.All specimens thaw before measurement.The method of HPLC-MS/MS was used to measure the concentration of meropen.According to the plasma concentration,plotted medicine-will the data curve,and use the DAS3.0 pharmacokinetic analysis.Results:1 In the lower dose group,the plasma drug concentration peak of 53.4±2.78mg/L,the MIC value is 4 or 8 mg/L respectively,T > MIC is94.86%±0.05%,77.4%±3.55%.the higher dose group,the plasma drug concentration peak of 57.03±4.12%,the MIC value is 4 or 8 mg/L respectively,T>MIC is 93.33%±0.07%,68.67%±7.86%;2 Under the CRRT mode of CVVH,the lower dose group with the prescription dose of 25ml/kg/h,the actual deliver dose was 20.8±1.20ml/kg/h,CRRT to remove meropen CL=1.84±0.56L/h,accounting for 42.7%±15.6% of the total clearance.the higher dose group with the prescription dose of35ml/kg/h,the actual deliver dose was29.88±0.90ml/kg/h,CRRT to remove meropen CL=2.30±0.43L/h,accounting for 48.56%±12.77% of the total clearance.3 The prescription dose of 25ml/kg/h group,the actual deliver dose was20.8±1.20ml/kg/h;the prescription dose of 35ml/kg/h,the actual deliver dose was29.88±0.90ml/kg/h,there is a significant statistic difference between two groups.Conclusions: Despite the dose of CRRT,the two groups can both achieve the high plasma medicine concentration.When the MIC is 4mg/L,In the two groups,the T > MIC both can achieve above 40%,so the level of effective anti-infection can be reached.There is no statistic difference.When the MIC is 8mg/L,In the two groups,the T>MIC both can achieve above40% too.But the lower dose group can get better effect,and there is a significant statistic difference.The deliver dose of lower dose group is far lower than higher dose group,and there is a significant statistic difference.When come to the clearance of meropen,there is no statistic difference between two groups.So the 44 th Sanford guidelines recommend 1g meropen for each 12 hours can achieve the effective anti-infection,regardless the dose of CRRT.Besides the dose of CRRT has little influence on the clearance of meropen.