| The rate of the patients got the sick of severe sepsis in the ICU ranged from 15% to 50%,and the mortality remains high, and severe sepsis can easily merge kidney damage so that the patients need renal replacement therapy. Studies have shown that early and plenty of application of antimicrobial agents can obviously increase the survival rate of severe sepsis patients.SSC recommend broad-spectrum antimicrobial agent used within 1 hour. Effective anti-infection treatment requires to achieve enough tissue concentrations in the infection of antibiotics, Roberts, Taccone shows that, due to factors such as acute liver failer and acute kidney injury, albumin level, application of antibiotic dose of sepsis patients are often inadequate or excessive. Drug concentration about anti-infection treatment is invalid or drug accumulation appear all sorts of side effects. For the severe patients that accept continuous renal replacement therapy, continuous renal replacement therapy to antibiotics in vitro to clear the change of concentration of antibiotic drugs is more complicated.Imipenem is a broad spectrum of β- lactam antibiotics, with strong antimicrobial activity, and have the stable influence on β- lactam. It is widely used in severe sepsis. Clinical curative effect is affirm. Right now, the application for continuous renal replacement therapy, though there are many doubts, sepsis of instruction based solely on creatinine clearance gives the recommended dose of chronic dialysis patients, for continuous renal replacement therapy patients how to apply is not mentioned. In the past, during the period of adjustment strategy research, they gave the recommended dose, but treatment factors such as dosage, mode was not unified, recommended dosage was different. In the present, the continuous renal replacement therapy technology application of high-throughput filter makesthe removal of the solute increase significantly, the research of therapeutic doses also make the continuous renal replacement therapy removal efficiency is more optimized, previous studies are not suitable for now maybe.Imipenem is a kind of antibiotics which is affected by time, which is higher than 40% can get reliable bactericidal effect. In concentrations reach 4MIC can get the highest bactericidal activity. Studies have shown that increasing drug dose, cutting down the dosing interval, to extend the time of dosing, continuous dosing can prolong T>MIC to achieve better anti-infective effectPurpose: Explores CVVH mode on removal efficiency in vitro Imipenem, as well as in different infusion time of Imipenem, medicine generation of dynamics and the effect on pharmacodynamics of continuous renal replacement therapy for clinical Imipenem adjustment strategy in order to provide the reference.Methods: This study is a prospective, randomized trial, 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 choose Imipenem Cilastatin anti-infection treatment in 2013-2014.This study selected 18 patients, 8 cases of men and 10 cases of women. Patients received Imipenem Cilastatin 1g(Imipenem 0.5g, Cilastatin 0.5g) each 8h, the patients were divided into 2 groups with infusion time is 2h and 0.5h, respectively. After the first agent dosage of 0h, 0.25 h, 0.5h, 0.75 h, 1h, 2h, 3h, 4h, 6h, 8h before sampling filter, filter blood specimens 2ml, ultrafiltrate samples 2ml. Specimen collection keep in 2min, to ensure the whole process of specimen collection continuous renal replacement therapy. Immediately following blood specimen collection is 4000r/min centrifuge for 10 min, the centrifugal supernatant after complete plasma 1-1 with a 0.5mol/L of 2-(N-morpholine) ethyl sulfonic acid buffer mixture, vortex blending 1min, after frozen at 80℃ refrigerator. Specimen after ultrafiltrate 1-1 with a 0.5mol/L 3-(N-morpholine) propionic acid mixture, vortex blending 1min, after frozen-80℃ refrigerator. All specimens thaw before measurement. Liquid chromatography-tandem mass spectrometry determination of plasma and ultrafiltrate specimens from south central Asia amine concentration, when plotted medicine- will the data curve, and use the DAS3.0 pharmacokinetic analysis.Results: Give Imipenem Cilastatin 1g for each 8h, the 30 min infusion time group, the plasma drug concentration peak of 15.77±4.89 mg/L, at peak time for 30 min, the MIC value is 1 or 2mg/L respectively, T>4MIC can reach the proportion of 46%±7%,20%±11%. Infusion time 2h group, the plasma drug concentration peak of 12.41±3.31mg/L, at peak time for 2h, the MIC value of 1 or 2mg/L respectively, T>4MIC can reach the proportion of 56%±8%,26%±9%.(P < 0.05).Under the mode of CVVH, the prescription dose is 35m/kg/h, during the life of a flitter, actual delivery dose was 30.57±1.38ml/kg/h, calculated CVVH to remove Imipenem CL=1.86±0.62L/h, accounting for 35%±8% of the total removal.Conclusion: In two groups of patients, the MIC is 1mg/L, this two kinds of dosage regimen can make T>4MIC achieve above 40%, 2h dosing time T>MIC obviously prolong; as MIC is 2mg/L, both dosage regimen both cannot make T>4MIC to achieve above 40%, all need to increase the dose, but 2h group still shows a higher T>4MIC. For patients with severe sepsis, extend the infusion time of Imipenem maybe also extend the time T>4MIC.This study shows that continuous renal replacement therapy clears Imipenem is significantly higher than 25% which need to adjust the Imipenem dosing strategy. In the study of the year of 2013, for the patients with severe sepsis who accepts continuous renal replacement therapy recommend 0.5g Imipenem for each 8h, the pathogenic bacteria of the MIC is 1mg/L, achieve the best anti-infection effect; when the MIC is 2mg/L, anti-infection, but cannot achieve the best anti-infection effect, increase the dose of Imipenem may be a better choice. |
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