Aminoglycoside Administration in Septic Patients
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 50
- 试验地点
- 2
- 主要终点
- Cpeak aminoglycoside achievement
研究概览
简要总结
Sepsis is one of the main causes of mortality and morbidity in an ICU setting, while the responsible microorganisms most frequently isolated are multidrug-resistant gram-negative bacteria. Aminoglycoseides (AG) seem to be particularly effective in dealing with these microbes, however their potential toxicity, especially nephrotoxicity, often makes them an unsuitable treatment option. This becomes particularly evident in patients with already impaired renal function, a common occurrence in septic patients requiring ICU treatment. AG are bacteriocidal antibiotics the efficiency of which depends on the maximum concentration in patients' serum (Cpeak).
Pathophysiological changes in critically ill patients, result in significant distribution of the drug extravascullary resulting in a decreased concentration of the biologically active component. On the other hand, impaired renal clearance results in high serum drug levels (C trough) making the desired once-daily administration not always achieved.
The purpose of this study is to test the hypothesis of successful clearance of AG after achieving satisfactory serum levels and therefore their maximum effect minimizing potential toxicity, by using continuous veno-venous haemodiafiltration in patients with sepsis or septic shock and impaired renal function. This way, the aforementioned antibiotics could become a more frequent and potentially earlier choice for physicians in the treatment of sepsis and septic shock patients from multidrug-resistant microbes.
详细描述
Sepsis is one of the leading causes of ICU mortality and morbidity. Globally, the first place in the list of responsible microorganisms appears to be occupied by multidrug-resistant gram-negative microorganisms (Escherichia Coli, Klebsiella pneumoniae, Pseudomonas aeruginosa και Acinetobacter baumannii). In the quiver of antibiotics we have against them, aminoglycosides (amikacin, gentamicin, tobramycin) have been particularly effective, either as monotherapy or in combination with other antibiotics, e.g. β-lactams. These are bactericidal antibiotics whose action depends on the concentration they achieve in the patients' plasma. As a measure based on which their effectiveness is predicted, the ratio of their maximum plasma concentration (Cpeak) against their minimum inhibitory concentration (MIC) is used, i.e. Cpeak/MIC and when this ratio is >8.
Pathophysiological changes that occur in the critically ill patient with sepsis involve the change in the volume of distribution (Vd) of the antibiotics, either due to increased renal clearance (increased GFR) or reduced renal clearance. In addition, studies have demonstrated a significant transcapillary escape of albumin extravascularly which increases the free fraction of the circulating antibiotic leading, especially in the case of hydrophilic drugs, to a greater and faster distribution extravascularly and thus to a lower concentration of the biologically active drug intravascularly (subtherapeutic concentrations).
Regarding aminoglycoside nephrotoxicity, this appears to occur in 10-20% of patients. Aminoglycosides are drugs that are not metabolized and are removed mainly by glomerular filtration.
Risk factors that have been associated with the occurrence of nephrotoxicity are increased serum trough levels, duration and frequency of administration, pre-existing kidney damage, hypoalbuminemia, liver dysfunction and the co-administration of nephrotoxic drugs, especially vancomycin.
Aminoglycosides are antibiotics with bactericidal activity based on reaching the maximum concentration of the antibiotic. Based on the above, it is understood that the prescription of aminoglycosides is a particular challenge, in terms of administering the effective dose. In practice this means that when the recommended daily dose of aminoglycoside is given, in patients with reduced renal clearance the minimum concentration (Ctrough measured 1 hour before the next administration) is at toxic levels (>5mg/dL for amikacin and >2mg/dL for tobramycin-gentamicin). Thus, administration of the planned next dose becomes impossible, resulting in possibly reduced clinical efficacy - response to treatment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •age >18 years
- •diagnosis of sepsis or septic shock based on established criteria (Sepsis-3) 29
- •patients with GFR <40 ml/min
- •microbiemia from a Gram-negative microorganism and for which the attending physician decides to receive an aminoglycoside or sepsis/septic shock for which it is decided to administer it
- •signed consent of the patients' next of kin
排除标准
- •absence of consent
- •known allergic reaction to aminoglycosides
- •infection from strains resistant to aminoglycosides. As long as the patient has received an aminoglycoside (empirical regimen) and the antibiogram follows it, the treatment can be modified based on the judgment of the attending physician, but the patient's data for the time he received the treatment under consideration are recorded and evaluated
- •unattainable placement of a central venous line for renal replacement therapy
结局指标
主要结局
Cpeak aminoglycoside achievement
时间窗: 8 days
Evaluation of aminoglycoside Cpeaks in the serum of patients following such a protocol
Number of total aminoglycoside doses during 8 days.
时间窗: 8 days
Number of total aminoglycoside doses during the study period of 8 days
Clinical effectiveness through SOFA score evaluation.
时间窗: 11 days
Evaluate clinical effectiveness of the protocol based on the Sequential Organ Failure Assessment (SOFA) score during days 1, 4, 8, 11 of their monitoring. Score range 0-24, with higher values denoting worse clinical condition.
次要结局
- ICU length of stay(from day of enrollment up to 6 months)
- 28day mortality(28 days from day of enrollment)
- CVVHDF free days(28 days from day of enrollment)
- Renal function(28 days ffrom day of enrollment)
- inflammatory marker evaluation(8 days from day of enrollment)
- ICU mortality(from day of enrollment up to 6 months)
- Renal Function(28 days ffrom day of enrollment)
- Inflammatory Marker Evaluation(8 days from day of enrollment)
研究者
Vasiliki Tsolaki
Academic scholar
University of Thessaly