脉冲式高容量血液滤过治疗脓毒症合并急性肾损伤患者的疗效及预后分析

目的:评价脉冲式高容量血液滤过(PHVHF)治疗脓毒症合并急性肾损伤患者的疗效,并分析影响预后的因素。方法:回顾性分析接受PHVHF治疗的56例患者的临床资料,对治疗前后生命体征、生化指标、炎症指标、急性生理与慢性健康状况(APACHEⅡ)评分、序贯器官衰竭(SOFA)评分进行比较。根据28 d存活情况,将患者分为存活组和死亡组,组间比较PHVHF治疗前临床资料的差异,多元回归分析影响预后的因素。运用受试者工作特征曲线(ROC)评价APACHEⅡ评分及SOFA评分对预后的判断价值。结果:56例患者死亡19例,病死率34%,明显低于APACHEⅡ评分预测的病死率(52.83%)。与治疗前相比,治疗72 h后体温、心率、呼吸明显下降(P0.01),白细胞、C反应蛋白、降钙素原(PCT)、乳酸、肌酐、APACHEⅡ评分及SOFA评分明显降低(P0.01)。死亡组的年龄、血源性感染比例、呼吸频率、乳酸浓度、低血压发生率、机械通气比例、脏器衰竭个数、APACHEⅡ评分及SOFA评分均高于存活组(P0.05),多因素Logistic回归分析提示:呼吸衰竭使用机械通气(OR=29.841,95%CI:2.22～401.12,P=0.01)、脏器衰竭个数(OR=10.080,95%CI:1.277～79.581,P=0.028)、SOFA评分(OR=1.922,95%CI:1.013～3.646,P=0.028)是预后的独立影响因素。APACHEⅡ评分、SOFA评分的ROC曲线下面积(AUC)分别为0.885和0.910。结论:PHVHF治疗脓毒症合并AKI患者安全有效,可降低死亡率。呼吸衰竭使用机械通气、脏器衰竭个数、SOFA评分是死亡的独立危险因素。     

急性重度有机磷农药中毒患者死亡危险因素分析

目的：探讨急性重度有机磷农药中毒死亡的危险因素。方法回顾性分析急性重度有机磷农药中毒44例患者的临床资料,对各项危险因素进行统计分析,比较患者的病死率。结果44例急性重度有机磷农药中毒患者住院期间病死率22.7%(10/44),其中急性生理学及慢性健康状况评分(APACHE)≥20分和<20分、年龄≥60岁和<60岁、合并低血压和未合并低血压、合并低氧血症和未合并低氧血症、合并代谢性酸中毒和未合并代谢性酸中毒的患者病死率比较,差异均有统计学意义(P <0.05或<0.01)。结论 APACHEⅡ分值、高龄、低血压、低氧血症、代谢性酸中毒可能是急性重度有机磷农药中毒患者死亡的危险因素,在临床中可以用于评估患者病情严重程度与死亡风险。     

外周血血小板计数在ICU脓毒血症患者30d死亡率预测中的价值

目的 分析血小板计数和重症监护病房(ICU)脓毒血症患者死亡的关系,评价血小板计数在ICU脓毒血症患者入院30 d预后评估的应用价值。方法 采用回顾性病例对照研究分析2022年1-12月该院收治的117例ICU脓毒血症患者临床资料,分析血小板计数与急性生理学与慢性健康状况评分Ⅱ(APACHEⅡ)评分、死亡风险系数及序贯器官衰竭(SOFA)评分的关系,及其对ICU脓毒血症患者入院后30 d内预后的评估价值。绘制Kaplan-Meier生存曲线,分析ICU脓毒血症患者血小板计数和患者总生存率的关系。结果 根据入院后30 d内的存活情况,117例脓毒血症患者被分为存活组(80例)和死亡组(37例),两组年龄、性别比较,差异无统计学意义(P>0.05);与存活组比较,死亡组血小板计数降低,APACHEⅡ评分、死亡风险系数、SOFA评分升高(P<0.05);血小板计数与APACHEⅡ评分、死亡风险系数无关(P>0.05),而与SOFA评分呈负相关(r=-0.324,P<0.05);受试者工作特征(ROC)曲线分析结果表明,ICU脓毒血症患者血小板计数、APACHEⅡ评分、...     

降钙素原和N末端前体脑钠肽对脓毒血症预后评估意义的研究

目的探讨血清降钙素原(PCT)和N末端前体脑钠肽(NT-proBNP)对脓毒血症预后评估的临床意义。方法 72例脓毒血症患者按预后分为存活组和死亡组,比较发病早期PCT、NT-proBNP及急性生理与慢性健康状况(APACHEⅡ)评分,并建立ROC曲线观察两种标记物对预后评估的临床价值。结果 PCT、NT-proBNP和APACHEⅡ评分两组患者中均有统计学差异(P<0.05),两种标记物水平与APACHEⅡ评分存在明显相关;PCT和NT-proBNP预测死亡的受试者工作特征曲线(ROC)下面积分别为0.822和0.843,PCT的敏感性和特异性分别为78.3%和71.4%,NT-proBNP敏感性和特异性分别为82.6%和85.7%,NT-proBNP对脓毒血症预后的评估优于PCT,两种标记物联合应用特异性更高(90.0%)。结论 PCT和NT-proBNP对脓毒血症患者预后具有较好的预测作用,联合检测可提高特异性。     

脓毒血症患者病情严重程度与血小板活化因子水平相关性分析

目的探讨脓毒血症患者病情严重程度与血浆血小板活化因子(PAF)水平的相关性。方法选择脓毒血症患者68例,根据病情分为脓毒症29例、严重脓毒症20例、脓毒性休克19例,根据预后情况分为存活组(40例)与死亡组(28例),选择同期正常志愿者20名作为正常对照组。根据临床症状及实验室指标进行急性生理与慢性健康(APACHE)Ⅱ评分和序贯器官功能衰竭(SOFA)评分,同期检测血浆PAF水平。比较各组APACHE Ⅱ评分、SOFA评分及PAF水平,并分析APACHE Ⅱ评分、SOFA评分与PAF水平的相关性。结果脓毒症、严重脓毒症、脓毒性休克患者PAF水平及APACHE Ⅱ评分、SOFA评分依次增高,组间比较差异均有统计学意义(P0.05),脓毒血症各组PAF水平均明显高于正常对照组(P0.05)。脓毒血症死亡组APACHE Ⅱ评分、SOFA评分明显高于存活组(P0.05)。正常对照组、存活组、死亡组血浆PAF水平依次增高,组间比较差异均有统计学意义(P0.05)。脓毒血症患者血浆PAF水平与APACHE Ⅱ评分、SOFA评分呈明显正相关(r值分别为0.658、0.519,P均0.05)。结论血浆PAF水平与脓毒血症患者病情严重程度有关。     

急诊脓毒症死亡风险评分、降钙素原对脓毒血症预后评估的价值

目的:探讨急诊脓毒症死亡风险(MEDS)评分、血清降钙素原(PCT)对脓毒血症预后评估的临床意义。方法:102例脓毒血症患者按预后分为存活组和死亡组,比较治疗早期MEDS评分、PCT及急性生理与慢性健康状况(APACHEⅡ)评分,并建立ROC曲线观察三者对预后评估的临床价值。结果:两组MEDS评分、PCT和APACHEⅡ评分均有明显差异,且MEDS评分、PCT与APACHEⅡ评分存在明显相关;MEDS评分和PCT预测死亡的ROC曲线下面积分别为0.85和0.78,MEDS的敏感性和特异性分别为80.6%和86.7%,PCT的敏感性和特异性分别为82.3%和78.4%,MEDS评分对脓毒血症预后的评估特异性优于PCT、敏感性逊于PCT;两种联合应用敏感性及特异性更高(86.3%、89.9%)。结论:MEDS评分和PCT对脓毒血症患者预后有较好的预测作用,联合使用可提高敏感性及特异性。     

老年脓毒血症患者胆碱酯酶水平与病情及预后的关系

目的探讨脓毒血症患者胆碱酯酶水平与患者病情及预后的关系。方法 2007年6月-2009年6月,将89例脓毒血症患者设定为脓毒血症组,进行血清胆碱酯酶测定及APACHEⅡ评分;另择82例健康人为正常组,测定血清胆碱酯酶值,比较两者之间差异;89例脓毒症患者按病况再分为存活组及死亡组,比较两者之间血清胆碱酯酶及APACHEⅡ评分差异。结果治疗前脓毒血症组胆碱酯酶水平明显低于正常组,有统计学意义（P〈0.01）;脓毒血症组APACHEⅡ评分与血清胆碱酯酶呈负相关;死亡组APACHEⅡ评分明显高于存活组,而血清胆碱酶低于存活组（P〈0.01）。结论胆碱酯酶同APACHEⅡ评分呈负相关,能明显反映脓毒症患者病情严重程度及预后。     

脓毒症心肌损伤患者的预后影响因素分析

目的探讨影响脓毒症心肌损伤患者预后的相关危险因素。方法回顾性分析2013年1月至2018年12月首都医科大学附属北京友谊医院收治的147例脓毒症心肌损伤患者的病例资料,研究终点为患者28 d死亡,按照预后将患者分为生存组和死亡组,采用多元Logistic回归分析法分析两组患者的临床资料,分析影响患者死亡预后的危险因素。结果147例患者中,其中66例死亡,死亡率为44.89%,单因素分析显示,与生存组相比,死亡组(n=66,44.89%)患者高血压比率高,以肺部感染为感染源比率高,血糖、血肌酐、血清钾离子水平高,7 d累积液体正平衡多,急性生理与慢性健康评分II(APACHEⅡ评分)、全身感染相关性序贯器官衰竭评分(SOFA评分)高,使用机械通气、血管活性药物、合并急性肾损伤比率大;而生存组24 h乳酸清除率高于死亡组。根据单因素分析筛选指标,进行多元logistic回归分析显示,24 h乳酸清除率(OR=0.348,95%CI:0.155~0.786,P=0.011)、APACHE II评分(OR=2.037,95%CI:1.970~2.109,P=0.028)、肺部感染(OR=4.556,95%CI:1.527~13.593,P=0.007)、合并急性肾损伤(OR=21.443,95%CI:4.119~43.879,P<0.01)是影响脓毒症心肌损伤患者预后的独立危险因素。结论脓毒症心肌损伤患者病死率高,24 h乳酸清除率、APACHEⅡ评分、肺部感染和合并急性肾损伤是影响其预后的危险因素。     

采用持续血液滤过治疗脓毒血症导致急性肾衰的疗效观察

目的观察持续血液滤过对脓毒血症导致急性肾衰患者的治疗效果,探究该方式的临床有效性。方法选取医院收入科室治疗的106例脓毒血症后急性肾衰患者为受试对象,根据不同治疗方式分为治疗组50例,对照组56例。两组均接受常规治疗,治疗组在其基础上应用持续血液滤过法。结果两组治疗后生化指标比较P0.05,APACHEⅡ评分比较P0.001,住院时间、机械通气时间以及总的治疗时间相比较P0.001,差异均存在统计学意义。结论持续血液滤过治疗更能改善患者生化指标,治疗效果更好,有利于抑制患者病情进展,帮助肾功能恢复。     

N末端B型利钠肽原和降钙素原在老年脓毒血症患者预后评估中作用

目的探讨N末端B型利钠肽原(N-terminal pro-brain natriuretic peptide,NT-proBNP)、降钙素原(procalcitonin,PCT)在老年脓毒血症患者病情及预后评估中的作用。方法老年脓毒血症患者36例,依据病情分为脓毒血症组15例,严重脓毒血症组13例,脓毒性休克组8例。比较3组入院后NT-proBNP、PCT水平及急性生理学与慢性健康状况评分系统Ⅱ(Acute Physiology and Chronic Health EvaluationⅡ,APACHEⅡ)评分,并应用Pearson相关分析NT-proBNP、PCT与APACHEⅡ评分的相关性;记录患者28d生存情况。结果严重脓毒血症组NT-proBNP、PCT水平及APACHEⅡ评分分别为(1 898.32±479.17)ng/L、(13.67±3.14))μg/L、24.66±3.54,脓毒性休克组分别为(4 733.58±1 022.35)ng/L、(18.55±6.35)μg/L、28.15±3.22,均高于脓毒血症组[(1 071.84±101.69)ng/L、(7.17±1.92)μg/L、20.10±2.82](P0.05),脓毒性休克组高于严重脓毒血症组(P0.01);死亡患者NT-proBNP[(4 978.22±1 012.35)ng/L]、PCT[(19.16±7.14)μg/L]及APACHEⅡ评分(28.21±3.08)高于存活者[(2 144.25±967.65)ng/L、(14.95±3.07)μg/L、25.20±2.63],差异有统计学意义(P0.05或P0.01);NT-proBNP(r=0.465,P=0.029)、PCT(r=0.641,P=0.002)与APACHEⅡ评分均呈正相关。结论 NT-proBNP和PCT可作为老年脓毒血症患者病情评估及预后判断的生物学指标,其值越高,预后越差。     

Pharmacokinetics of moxifloxacin in patients undergoing continuous venovenous haemodiafiltration

OBJECTIVE: Moxifloxacin is an 8-methoxy quinolone with a broad range of activity against clinically important pathogens. Therefore it is frequently administered in severe respiratory tract infections. Continuous venovenous haemodiafiltration (CVVHDF) is an important extracorporeal renal replacement therapy for intensive care patients suffering from sepsis and multiple organ failure. The aim of this study was to investigate the pharmacokinetics of intravenous moxifloxacin in anuric critically ill patients undergoing CVVHDF. PATIENTS AND METHODS: Pharmacokinetic analysis was performed in nine intensive care patients with acute renal failure and suspected or proven infection sensitive to moxifloxacin, who received moxifloxacin 400 mg intravenously once daily. The concentration of moxifloxacin in serum and ultradiafiltrate was determined by HPLC. RESULTS: Peak and trough serum concentrations were 3.76 +/- 2.02 mg/L and 0.24 +/- 0.14 mg/L, respectively, at the arterial port after the first dose. The mean elimination half-life was 9.87 +/- 3.26 h, the volume of distribution 270 +/- 133 L and the calculated AUC0-24 18.41 +/- 8.46 mg.h/L. Total clearance was 19.09 +/- 8.22 L/h and the clearance of haemodiafiltration 1.63 +/- 0.33 L/h. CONCLUSIONS: The pharmacokinetics of moxifloxacin in critically ill patients with acute renal failure undergoing CVVHDF was comparable to healthy subjects and patients without renal impairment. We recommend 400 mg of intravenous moxifloxacin once per day in anuric patients during CVVHDF.     

Pharmacokinetics of voriconazole during continuous venovenous haemodiafiltration

OBJECTIVES: Voriconazole is a new triazole antifungal agent that is frequently used in intensive care patients with severe fungal infections. Continuous venovenous haemodiafiltration (CVVHDF) is an important extracorporal renal replacement therapy in critically ill patients suffering from severe infections and multiple organ failure. This study investigates the pharmacokinetics of voriconazole in anuric patients undergoing CVVHDF. PATIENTS AND METHODS: Pharmacokinetic analysis was performed in nine intensive care patients-one of them with liver cirrhosis-with suspected or proven fungal infection and acute renal failure undergoing CVVHDF who received voriconazole intravenously. The concentration of voriconazole in serum and ultradiafiltrate was determined by HPLC. RESULTS: Mean peak pre-filter voriconazole concentration in eight patients without cirrhosis was 5.9 +/- 2.9 mg/L and mean pre-filter trough level was 1.1 +/- 0.3 mg/L. Mean elimination half-life, mean volume of distribution, mean AUC(0-12) and mean sieving coefficient were 14.7 +/- 6.5 h, 228 +/- 42 L, 22.4 +/- 3.7 mg.h/L and 0.56 +/- 0.16, respectively. The total clearance was 12.9 +/- 6.7 L/h and the clearance via CVVHDF was 1.1 +/- 0.3 L/h. In the patient with liver cirrhosis, elimination half-life, volume of distribution, AUC(0-12) and sieving coefficient were 52 h, 301 L, 19.8 mg.h/L and 0.31, respectively. CONCLUSIONS: Voriconazole should be given without a dosage adaptation in critically ill patients without liver cirrhosis undergoing CVVHDF. However, according to results in one patient, reduction of the maintenance dosing regimen of voriconazole seems to be meaningful in patients with liver cirrhosis.     

Pharmacokinetics of ciprofloxacin in ICU patients on continuous veno-venous haemodiafiltration

OBJECTIVES: To investigate the pharmacokinetics of intravenous ciprofloxacin 200 mg every 8 h in critically ill patients on continuous veno-venous haemodiafiltration (CVVHDF), one form of continuous renal replacement therapy (CRRT). DESIGN AND SETTING: Open, prospective clinical study in a multidisciplinary, intensive care unit in a university-affiliated tertiary referral hospital. PATIENTS: Six critically ill patients with acute renal failure on CVVHDF. INTERVENTIONS: Timed blood and ultrafiltrate samples were collected to allow pharmacokinetics and clearances to be calculated of initial and subsequent doses of 200 mg intravenous ciprofloxacin. CVVHD was performed with 1 l/h of dialysate and 2 l/h of predilution filtration solution, producing 3 l/h of dialysis effluent. The blood was pumped at 200 ml/min using a Gambro BMM-10 blood pump through a Hospal AN69HF haemofilter. MEASUREMENTS AND RESULTS: Ten pharmacokinetic profiles were measured. The CVVHDF displayed a urea clearance of 42 +/- 3 ml/min, and removed ciprofloxacin with a clearance of 37 +/- 7 ml/min. This rate was 2-2.5 greater than previously published for ciprofloxacin in other forms of CRRT. On average the CVVHDF was responsible for clearing a fifth of all ciprofloxacin eliminated (21 +/- 10%). The total body clearance of ciprofloxacin was 12.2 +/- 4.3 l/h. The trough concentration following the initial dose was 0.7 +/- 0.3 mg/l. The area under the plasma concentration time curves over a 24-h period ranged from 21 to 55 mg.h l-1. CONCLUSIONS: Intravenous ciprofloxacin 600 mg/day in critically ill patients using this form of CRRT produced adequate plasma levels for many resistant microbes found in intensive care units.     

Epidemiology and prognostic factors of critically ill patients treated with hemodiafiltration

PURPOSE: The objective of this study is to study the epidemiology, outcome, and prognostic factors of critically ill patients treated with continuous venovenous hemodiafiltration (CVVHDF). MATERIALS AND METHODS: Observational cohort was done in a French 16-bed intensive care unit (ICU) from a university-affiliated urban hospital. All patients requiring, in the opinion of the treating physician, the initiation of CVVHDF were included in the study. RESULTS: One hundred ninety-seven patients with acute renal failure (ARF) treated with CVVHDF were studied. The incidence of ARF treated with CVVHDF was 5.9% in the ICU with a mortality rate of 71.6%. A multivariate analysis identified 3 independent factors associated with fatal outcome: mechanical ventilation, sepsis, and septic shock requiring vasoactive drug. In contrast, 2 independent factors predicted a favorable outcome: nonoliguric ARF and serum creatinine concentration higher than 34 mg/L at CVVHDF initiation. A flowchart determined by the chi2 Automatic Interaction and Detection statistical method allowed for the identification of patients' subgroups with different mortality rates ranging from 25% to 100%. CONCLUSIONS: In our series, ARF treated with CVVHDF was associated with a high overall ICU mortality rate (71.6%). However, our prognostic flowchart identified patients with low mortality rates for which renal replacement therapy must be initiated with no discussion as soon as required.     

连续血液净化治疗脓毒症合并急性肾损伤的进展

脓毒症（sepsis）是导致重症监护患者死亡的常见原因。脓毒症患者如合并急性肾损伤（AKI），其病死率明显增加。但目前对脓毒症的发生机制尚不明确。近年国内外关于脓毒症治疗的研究证实，连续性肾脏替代治疗（CRRT），又称连续性血液净化（CBP），在脓毒症的治疗中可发挥显著作用，使患者内环境和免疫内稳态机制得到明显改善，遏制了一系列严重病理生理紊乱，提高了危重病患者救治的成功率。本文将对CRRT/CBP在脓毒症合并AKI中的临床疗效和研究进展作一综述。     

Pharmacokinetics of Ganciclovir during Continuous Venovenous Hemodiafiltration in Critically Ill Patients

Ganciclovir is an antiviral agent that is frequently used in critically ill patients with cytomegalovirus (CMV) infections. Continuous venovenous hemodiafiltration (CVVHDF) is a common extracorporeal renal replacement therapy in intensive care unit patients. The aim of this study was to investigate the pharmacokinetics of ganciclovir in anuric patients undergoing CVVHDF. Population pharmacokinetic analysis was performed for nine critically ill patients with proven or suspected CMV infection who were undergoing CVVHDF. All patients received a single dose of ganciclovir at 5 mg/kg of body weight intravenously. Serum and ultradiafiltrate concentrations were assessed by high-performance liquid chromatography, and these data were used for pharmacokinetic analysis. Mean peak and trough prefilter ganciclovir concentrations were 11.8 ± 3.5 mg/liter and 2.4 ± 0.7 mg/liter, respectively. The pharmacokinetic parameters elimination half-life (24.2 ± 7.6 h), volume of distribution (81.2 ± 38.3 liters), sieving coefficient (0.76 ± 0.1), total clearance (2.7 ± 1.2 liters/h), and clearance of CVVHDF (1.5 ± 0.2 liters/h) were determined. Based on population pharmacokinetic simulations with respect to a target area under the curve (AUC) of 50 mg · h/liter and a trough level of 2 mg/liter, a ganciclovir dose of 2.5 mg/kg once daily seems to be adequate for anuric critically ill patients during CVVHDF.     

Effects of coagulation factor XIII on intestinal functional capillary density, leukocyte adherence and mesenteric plasma extravasation in experimental endotoxemia

Introduction

In seriously infected patients with acute renal failure and who require continuous renal replacement therapy, data on continuous infusion of ceftazidime are lacking. Here we analyzed the pharmacokinetics of ceftazidime administered by continuous infusion in critically ill patients during continuous venovenous haemodiafiltration (CVVHDF) in order to identify the optimal dosage in this setting.

Method

Seven critically ill patients were prospectively enrolled in the study. CVVHDF was performed using a 0.6 m² AN69 high-flux membrane and with blood, dialysate and ultrafiltration flow rates of 150 ml/min, 1 l/hour and 1.5 l/hour, respectively. Based on a predicted haemodiafiltration clearance of 32.5 ml/min, all patients received a 2 g loading dose of ceftazidime, followed by a 3 g/day continuous infusion for 72 hours. Serum samples were collected at 0, 3, 15 and 30 minutes and at 1, 2, 4, 6, 8, 12, 24, 36, 48 and 72 hours; dialysate/ultrafiltrate samples were taken at 2, 8, 12, 24, 36 and 48 hours. Ceftazidime concentrations in serum and dialysate/ultrafiltrate were measured using high-performance liquid chromatography.

Results

The mean (± standard deviation) elimination half-life, volume of distribution, area under the concentration-time curve from time 0 to 72 hours, and total clearance of ceftazidime were 4 ± 1 hours, 19 ± 6 l, 2514 ± 212 mg/h per l, and 62 ± 5 ml/min, respectively. The mean serum ceftazidime steady-state concentration was 33.5 mg/l (range 28.8–36.3 mg/l). CVVHDF effectively removed continuously infused ceftazidime, with a sieving coefficient and haemodiafiltration clearance of 0.81 ± 0.11 and 33.6 ± 4 mg/l, respectively.

Conclusion

We conclude that a dosing regimen of 3 g/day ceftazidime, by continuous infusion, following a 2 g loading dose, results in serum concentrations more than four times the minimum inhibitory concentration for all susceptible pathogens, and we recommend this regimen in critically ill patients undergoing CVVHDF.     

Procalcitonin: a marker to clearly differentiate systemic inflammatory response syndrome and sepsis in the critically ill patient?

OBJECTIVES: To define the role of procalcitonin in the differential diagnosis, prognosis and follow-up of critically ill patients. DESIGN: Prospective study during the 2-year period from January 1998-2000. PATIENTS: One hundred nineteen critically ill patients: 29 with systemic inflammatory response syndrome (SIRS) without any signs of infection, 11 with sepsis, 17 with severe sepsis, 10 with septic shock and 52 controls. Daily measurements of procalcitonin were performed by an immunocheminoluminometric assay, and values were correlated to the clinical characteristics of the patients. RESULTS: Mean concentrations of procalcitonin were 5.45 (95% CI: 2.11, 8.81), 7.29 (95% CI: -1.92,14.59), 6.26 (95% CI: -1.32, 13.85) and 38.76 ng/ml (95% CI: 0.15, 77.38) on the 1st day in patients with SIRS, sepsis, severe sepsis and septic shock, respectively, and were statistically superior to those of control patients. Procalcitonin was gradually diminished over time with the resolution of the syndrome, while it was sustained in the same or more augmented levels upon worsening. Mean concentrations of procalcitonin on the 1st day for patients finally progressing to ARDS, to ARDS and acute renal failure, to ARDS, acute renal failure and DIC and to ARDS, acute renal failure, DIC and hepatic failure were 10.48, 8.08, 32.72 and 43.35 ng/ml, respectively. ROC curves of the sensitivity and specificity of procalcitonin for the evaluation of SIRS and sepsis were similar. CONCLUSIONS: The definite differential diagnosis between SIRS and sepsis may not rely on a single application of procalcitonin but on the complete clinical and laboratory evaluation of the patient with procalcitonin playing a considerable role. Procalcitonin is an early prognostic marker of the advent of MODS; therefore, daily determinations might help in the follow-up of the critically ill patient.     

Cardiac troponin elevations among critically ill patients

PURPOSE OF THE REVIEW: Elevated levels of cardiac troponins, indicative of the presence of cardiac injury, have been reported in critically ill patients. In this review, the incidence, significance, and clinical relevance of elevated troponin levels among this group of patients will be discussed. RECENT FINDINGS: It has been shown that elevated cardiac troponin levels can be present among critically ill septic patients without evidence of myocardial ischemia. Recent studies show that elevated troponin levels are also present in a diverse group of critically ill patients without sepsis or septic shock. In addition, several but not all studies show that the mortality rate of troponin-positive patients is significantly higher compared with troponin-negative patients. SUMMARY: Elevated troponin levels are not only present in patients suffering from acute coronary syndromes but can also be present in critically ill patients. Even minor elevations are specific for myocardial injury. However, every elevated troponin level in the critically ill patient should not be rigorously diagnosed or treated as a myocardial infarction.     

Population pharmacokinetics of fluconazole in critically ill patients receiving continuous venovenous hemodiafiltration: using Monte Carlo simulations to predict doses for specified pharmacodynamic targets

Fluconazole is a widely used antifungal agent that is extensively reabsorbed in patients with normal renal function. However, its reabsorption can be compromised in patients with acute kidney injury, thereby leading to altered fluconazole clearance and total systemic exposure. Here, we explore the pharmacokinetics of fluconazole in 10 critically ill anuric patients receiving continuous venovenous hemodiafiltration (CVVHDF). We performed Monte Carlo simulations to optimize dosing to appropriate pharmacodynamic endpoints for this population. Pharmacokinetic profiles of initial and steady-state doses of 200 mg intravenous fluconazole twice daily were obtained from plasma and CVVHDF effluent. Nonlinear mixed-effects modeling (NONMEM) was used for data analysis and to perform Monte Carlo simulations. For each dosing regimen, the free drug area under the concentration-time curve (fAUC)/MIC ratio was calculated. The percentage of patients achieving an AUC/MIC ratio greater than 25 was then compared for a range of MIC values. A two-compartment model adequately described the disposition of fluconazole in plasma. The estimate for total fluconazole clearance was 2.67 liters/h and was notably 2.3 times faster than previously reported in healthy volunteers. Of this, fluconazole clearance by the CVVHDF route (CL(CVVHDF)) represented 62% of its total systemic clearance. Furthermore, the predicted efficiency of CL(CVVHDF) decreased to 36.8% when filters were in use >48 h. Monte Carlo simulations demonstrated that a dose of 400 mg twice daily maximizes empirical treatment against fungal organisms with MIC up to 16 mg/liter. This is the first study we are aware of that uses Monte Carlo simulations to inform dosing requirements in patients where tubular reabsorption of fluconazole is probably nonexistent.