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Objectives The most optimal method of attaining therapeutic vancomycin concentrations during continuous venovenous haemofiltration (CVVH) remains unclear. Studies have shown continuous infusion vancomycin (CIV) achieves target concentrations more rapidly and consistently when compared with intermittent infusion. Positive correlations between CVVH intensity and vancomycin clearance (CLvanc) have been noted. This study is the first to evaluate a CIV regimen in patients undergoing CVVH that incorporates weight-based CVVH intensity (mL/kg/h) into the dosing nomogram. Methods This was a prospective, observational study of patients undergoing CVVH and receiving CIV based on the nomogram. The primary outcome was achievement of a therapeutic vancomycin concentration (15-25 mg/L) at 24 h. Secondary outcomes included the achievement of therapeutic concentrations at 48 and 72 h. Results The nomogram was analysed in 52 critically ill adults. Vancomycin concentrations were therapeutic in 43/52 patients (82.7%) at 24 h. Of the nine patients who were not therapeutic at 24 h, seven were supratherapeutic and two were subtherapeutic. The mean (SD) concentration was 20.1 (4.2) mg/L at 24 h, 20.7 (3.7) mg/L at 48 h and 21.9 (3.5) mg/L at 72 h. Patients with CVVH intensity >20 mL/kg/h experienced higher CLvanc at 24 h compared with patients with CVVH intensity

International audience; OBJECTIVES:Whilst commonly performed in ICUs, renal replacement therapies (RRTs) differ in their solute clearances. There is a paucity of data on ciprofloxacin clearances in different RRT techniques. The aim of this study was to compare the population pharmacokinetics of ciprofloxacin during equal doses of continuous venovenous haemofiltration (CVVHF) and continuous venovenous haemodiafiltration (CVVHDF) in septic patients.METHODS:Patients receiving 400 mg of ciprofloxacin intravenously 8 or 12 hourly and undergoing either CVVHF or CVVHDF were eligible. Up to 10 blood samples were collected over one dosing interval and analysed by a validated chromatographic method. Population pharmacokinetic analysis and Monte Carlo simulation was undertaken using Pmetrics.RESULTS:Eighteen sampling intervals were included (8 CVVHDF and 10 CVVHF) from 11 patients (6 patients having sampling during both RRT modes). A two-compartment linear model best described the data. Increasing patient weight was the only covariate associated with increasing drug clearance. The mean (SD) parameter estimates were: clearance, 10.7 (5.3) L/h; volume of distribution of the central compartment, 21.3 (11.3) L; rate constant for drug distribution from the central compartment to the peripheral compartment, 10.9 (4.3) L/h; and rate constant for drug distribution from the peripheral compartment to the central compartment, 2.3 (1.8) L/h. After accounting for patient weight, the mean ciprofloxacin clearance was not statistically different between CVVHF and CVVHDF [11.8 (9.9) and 10.3 (7.4) L/h, respectively, P = 0.43].CONCLUSIONS:The present study indicates a high pharmacokinetic variability of ciprofloxacin during CVVHF and CVVHDF with no significant differences in clearance apparent. Based on patient weight, higher ciprofloxacin dosing regimens should be used in critically ill patients when difficult-to-treat pathogens are suspected.

International audience; OBJECTIVES:Few data are available to guide linezolid dosing during renal replacement therapy. The objective of this study was to compare the population pharmacokinetics of linezolid during continuous venovenous haemofiltration (CVVHF, 30 mL/kg/h) and continuous venovenous haemodiafiltration (CVVHDF, 15 mL/kg/h + 15 mL/kg/h).METHODS:Patients requiring linezolid 600 mg iv every 12 h and CVVHF or CVVHDF were eligible for this prospective study. Seven blood samples were collected over one dosing interval and analysed by a validated chromatographic method. Population pharmacokinetic analysis was undertaken using Pmetrics. Monte Carlo simulations evaluated achievement of a pharmacodynamics target of an AUC from 0-24 h to MIC (AUC0-24/MIC) of 80.RESULTS:Nine CVVHDF and eight CVVHF treatments were performed in 13 patients. Regimens of CVVHDF and CVVHF were similar. A two-compartment linear model best described the data. CVVHDF was associated with a 20.5% higher mean linezolid clearance than CVVHF, without statistical significance (P = 0.39). Increasing patient weight and decreasing SOFA score were associated with increasing linezolid clearance. The mean (SD) parameter estimates were: clearance (CL), 3.8 (2.2) L/h; volume of the central compartment, 26.5 (10.3) L; intercompartmental clearance constants from central to peripheral, 8.1 (12.1) L/h; and peripheral to central compartments, 3.6 (4.0) L/h. Achievement of pharmacodynamic targets was poor for an MIC of 2 mg/L with the studied dose.CONCLUSIONS:During CVVHF and CVVHDF, there is profound pharmacokinetic variability of linezolid. Suboptimal achievement of therapeutic targets occurs at the EUCAST breakpoint MIC of 2 mg/L using 600 mg iv every 12 h.

Background In continuous venovenous haemofiltration (CVVH), high ultrafiltration rates provide survival benefits in acute renal failure. This study measured clearances obtained at ultrafiltration rates of up to 4.5 l/h. Methods Clearances of small solutes (urea, creatinine, phosphate and urate) and of beta(2)-microglobulin (beta(2)-M) were measured during CVVH. Five preset Multiflow-100 (M-100) and five HF1000 hollow-fibre filters were compared. For the M-100, clearances obtained by haemofiltration were compared with those obtained by haemodiafiltration at similar total effluent rates from a previous study. Results For small solutes, the effluent to plasma ratio (E/P) remained close to 1.0 at all ultrafiltration rates; filter clearances were thus equal to Quf for both filters. Increasing Quf from 1.0 to 4.5 l/h did not significantly modify E/P. Convective clearances of beta(2)-M were lower than those obtained for small solutes. For the M-100, average beta(2)-M E/P was 0.62+/-0.10 and did not significantly change while increasing Quf. For the HF1000, average beta(2)-M E/P were significantly lower compared with the M-100 (0.42+/-0.09 at 1.0 l/h) and decreased progressively to 0.26+/-0.06 while increasing Quf to 4.5 l/h. With pre-dilution, progressive decreases in clearances delivered to patients were observed reaching 40% at a Quf rate of 4.5 l/h. There was no clinically significant adsorption of beta(2)-M. For the M-100, at similar total effluent flow rates, clearances delivered to patients using haemodiafiltration were significantly higher for small solutes but lower for beta(2)-M in comparison to haemofiltration only. Conclusions Filter clearance for small solutes equalled Quf at evaluated rates. At high ultrafiltration rates there was significant loss of clearances with pre-dilution. At similar total effluent rates with the use of pre-dilution, haemodiafiltration is superior to haemofiltration for small solute clearance but inferior for beta(2)-M.

To explore the pharmacokinetics (PK) and pharmacodynamics (PD) of micafungin in patients undergoing continuous venovenous haemofiltration (CVVH).Ten patients receiving CVVH treated with 100 mg/day micafungin were included (April-December 2012). CVVH was performed using polyethersulphone or polysulphone haemofilters. Dialysis membranes were not changed on sampling days. On Days 1 and 2, blood samples from arterial pre-filter and venous post-filter ports and ultrafiltrate samples were collected at the start and end of the infusion and at 3, 5, 8, 18 and 24 h. Concentrations were determined using HPLC. Values for the area under the concentration-time curve (AUC0-24) were calculated. Monte Carlo simulations were performed using pre-filter and post-filter AUC0-24/MIC ratios on Days 1 and 2. The probability of target attainment (PTA) was calculated using AUC0-24/MIC cut-offs: 285 (C. parapsilosis), 3000 (all Candida spp.) and 5000 (non-parapsilosis Candida spp.). Cumulative fraction responses (CFRs) were calculated using EUCAST MIC distributions.Mean post-filter AUC0-24 (mg·h/L) values were higher than pre-filter values on Day 1 (83.31 ± 15.87 versus 71.31 ± 14.24; P = 0.008) and Day 2 (119.01 ± 27.20 versus 104.54 ± 21.23; P = 0.005). PTAs were ≥90% for MICs of 0.125 mg/L (cut-off = 285), 0.016 mg/L (cut-off = 3000) and 0.008 mg/L (cut-off = 5000) on Day 1, and for MICs of 0.25 mg/L (cut-off = 285) and 0.016 mg/L (cut-off = 3000 and 5000) on Day 2, without differences between pre- and post-filter values. On Day 2, CFRs90% were obtained for C. albicans (cut-off = 3000 and 5000) and C. glabrata (cut-off = 3000), but not for C. parapsilosis.There was no removal of micafungin by CVVH or need for dose adjustment, and there was optimal PK/PD coverage for non-parapsilosis Candida and equivalence of pre- and post-filter PD.

Background Little is known about the effects of renal replacement therapy (RRT) with fluid removal on intra-abdominal pressure (IAP). The global end-diastolic volume index (GEDVI) and extravascular lung water index (EVLWI) can easily be measured bedside by transpulmonary thermodilution (TPTD). The aim of this study is to evaluate the changes in IAP, GEDVI and EVLWI in critically ill patients receiving slow extended daily dialysis (SLEDD) or continuous venovenous haemofiltration (CVVH) with the intention of net fluid removal. Methods We performed a retrospective cohort study in ICU patients who were treated with SLEDD or CVVH and in whom IAP was also measured, and RRT sessions were excluded when the dose of vasoactive medication needed to be changed between the pre- and post-dialysis TPTD measurements and when net fluid loss did not exceed 500 ml. The TPTD measurements were performed within 2 h before and after SLEDD; in case of CVVH, before and after an interval of 12 h. Results We studied 25 consecutive dialysis sessions in nine patients with acute renal failure and cardiogenic or non-cardiogenic pulmonary oedema. The GEDVI and EVLWI values before dialysis were 877 ml/m² and 14 ml/kg, respectively. Average net ultrafiltration per session was 3.6 l, with a net fluid loss 1.9 l. The GEDVI decreased significantly during dialysis, but not more than 47.8 ml/m² (p = 0.008), as also did the EVLWI with 1 ml/kg (p = 0.03). The IAP decreased significantly from 12 to 10.5 mmHg (p < 0.0001). Conclusions Net fluid removal by SLEDD or CVVH in the range observed in this study decreased IAP, GEDVI and EVLWI in critically ill patients although EVLWI reduction was modest.

It has been reported that linezolid (LZD) is highly removed in patients undergoing high-flow continuous venovenous haemofiltration (CVVH: blood flow and filtration rates were 186 ± 15 and 40 ± 8 ml/minute) compared with patients with normal renal function (NRF). It is generally considered that no adjustment of LZD dosage is needed in subjects undergoing CVVH. In Japan, continuous venovenous haemodiafiltration (CVVHDF) has preferentially been administered under low flow rate. Investigating the effects of flow rate on LZD removal during continuous renal replacement therapy is essential to regulate therapeutic dosages. We aimed to investigate the pharmacokinetics of LZD in CVVHDF patients in this setting.

Background For patients hospitalised in our intensive care unit (ICU), continuous venovenous haemofiltration (CVVH) with citrate has been implemented since 2013. This study was conducted to assess the change in practices and restitution fluids (RF), analysing the impact on consumption and costs. Reflection on this was conducted between physicians, nurses and pharmacists. Purpose The aim of the study was to assess the cost implications of citrate anticoagulation. Material and methods We performed a retrospective study in the ICU in patients requiring CVVH in 2014. Data collected were: patient characteristics (age, sex ratio, BMI, IGS2) and CVVH data (indications, effective duration, filters, RF, calcium and phosphorus consumption). Prescription data allowed estimation of the total cost with RF, filters and ion consumption. Costs of other RF with integrated ions were used to simulate the cost impact. Results were expressed for 24 h of effective CVVH. The citrate and non-citrate groups were compared with the Student’s test (significant if p Results We included 64 patients. They had a mean age of 68.1 ± 16.6 years, a mean SAPS II of 58.2 ± 20.5, a mean stay in the ICU of 9.0 ± 9.6 days and a mortality rate of 28.1%. Volume overload was an indication for CVVH in 46.8% of patients, hyperkaliaema in 31.2% and acidosis in 14.2%. Duration was Conclusion This study highlighted an interesting assessment of CVVH practices. Simulations showed that 5726.3€ could be saved with integrated ion RF, especially as it did not take into account human costs. Most CVVH were shorter than 24 h and reflection about intermittent haemofiltration is needed. Evaluation of the cost impact of fluid and material consumption in the ICU could help physicians and pharmacists to identify where some interesting savings could be made. No conflict of interest.

We present a rare case of para-influenza type 1 virus-induced rhabdomyolysis, complicated by acute renal failure (ARF). The child underwent continuous venovenous haemofiltration and has shown full clinical and biochemical recovery. ARF due to rhabdomyolysis in para-influenza type 1 infection in a child has, to the best of our knowledge, not been previously reported.

In vitro studies suggest that there is significant adsorption of amikacin, netilmicin, gentamicin and tobramycin to polyacrylonitrile haemofilters. This occurs rapidly and has the potential to substantially reduce the peak aminoglycoside concentration, which will reduce efficacy [1]. However, whether significant adsorption occurs in vivo is unknown. We therefore carried out a controlled in vivo study of the effect of amikacin adsorption by polyacrylonitrile filters during haemofiltration, using a porcine model of acute renal failure.

In patients with severe theophylline toxicity charcoal haemoperfusion is the recommended method for rapid reduction of serum theophylline levels. However, access to this technique is limited in most hospitals. This case report shows that continuous venovenous haemofiltration, a technique available in most hospitals, is an effective alternative to charcoal haemoperfusion.

Metformin-associated lactic acidosis (MALA) is a life-threatening condition (up to 50% mortality is described [1]) and its developing rate increases with the number of contraindications to the treatment.

One of the greatest problems with continuous renal replacement therapy (CRRT) is early coagulation of the filters. Few studies have monitored circuit function prospectively. The purpose of this study was to determine the variables associated with circuit life in critically ill children with CRRT.A prospective observational study was performed in 122 children treated with CRRT in a pediatric intensive care unit from 1996 to 2006. Patient and filter characteristics were analyzed to determine their influence on circuit life. Data were collected on 540 filters in 122 patients and an analysis was performed of the 365 filters (67.6%) that were changed due to circuit coagulation.The median circuit life was 31 hours (range 1 to 293 hours). A univariate and multivariate logistic regression study was performed to assess the influence of each one of the factors on circuit life span. No significant differences in filter life were found according to age, weight, diagnoses, pump, site of venous access, blood flow rate, ultrafiltration rate, inotropic drug support, or patient outcome. The mean circuit life span was longer when the heparin dose was greater than 20 U/kg per hour (39 versus 29.1 hours; P = 0.008), with hemodiafiltration compared with hemofiltration (34 versus 22.7 hours; P = 0.001), with filters with surface areas of 0.4 to 0.9 m2 (38.2 versus 26.1 hours; P = 0.01), and with a catheter size of 6.5 French or greater (33.0 versus 25.0 hours; P = 0.04). In the multivariate analysis, hemodiafiltration, heparin dose of greater than 20 U/kg per hour, filter surface area of 0.4 m2 or greater, and initial creatinine of less than 2 mg/dL were associated with a filter life of more than 24 and 48 hours. Total effluent rate of greater than 35 mL/kg per hour was associated only with a filter life of more than 24 hours.Circuit life span in CRRT in children is short but may be increased by the use of hemodiafiltration, higher heparin doses, and filters with a high surface area.

Many studies have demonstrated that prompt appropriate treatment for the critically ill patient improves outcome. Moving patients to the best place for instituting care, however, is not always associated with improved outcome. Recent studies on delivering patients to the best place for treatment as well as further work on the effects of volume are discussed. Finally, a large retrospective cohort study comparing outcomes of patients treated with continuous venovenous haemofiltration or intermittent haemodialysis is outlined.

Further work on the use of albumin in the intensive care unit is discussed. The interesting pilot study by Dubois and colleagues examines the potential benefits for albumin supplementation in the hypoalbuminaemic critically ill patient. Maintaining the fluid theme, we discuss recent work on factors influencing post-intensive care unit blood transfusion as well as another study on erythropoietin. Finally, a large multicentred trial comparing continuous venovenous haemofiltration with intermittent haemodialysis is outlined, the results of which pose more questions than answers.

Sotalol is a non-selective beta blocker with class III antiarrhythmic properties. It is not protein bound and is mostly excreted unchanged in the urine. Both peritoneal dialysis [1] and haemodialysis [2] have been successful in treating Sotalol-induced arrhythmias in the prescence of renal failure. Clearance of Sotalol by continuous venovenous haemofiltration (CVVH) is not described. We report a case of massive Sotalol overdose in which CVVH was successfully used.

Septic shock in spite of the new therapeutic strategies. still has a high mortality. There are multiple factors. and we may consider that the main objectives are the recovery of cardiovascular function and haemodynamic stability. Venovenous haemofiltration (CVVH), a technique used in septic patients with renal failure is now proposed in septic shock without renal failure. We studied the haemodynamic effects of the CVVH in septic shock patients that had not responded to high doses of catecholamines.