Biomedical subjects

Javier Maynar

Publications and source records attributed to Javier Maynar.

5 recordsLinked to original sources

PubMed2005

Study protocol: the DOse REsponse Multicentre International collaborative initiative (DO-RE-MI).

INTRODUCTION: Current practices for renal replacement therapy in intensive care units (ICUs) remain poorly defined. The DOse REsponse Multicentre International collaborative initiative (DO-RE-MI) will address the issue of how the different modes of renal replacement therapy are currently chosen and performed. Here, we describe the study protocol, which was approved by the Scientific and Steering Committees. METHODS: DO-RE-MI is an observational, multicentre study conducted in ICUs. The primary end-point will be the delivered dose of dialysis, which will be compared with ICU mortality, 28-day mortality, hospital mortality, ICU length of stay and number of days of mechanical ventilation. The secondary end-point will be the haemodynamic response to renal replacement therapy, expressed as percentage reduction in noradrenaline (norepinephrine) requirement. Based on the the sample analysis calculation, at least 162 patients must be recruited. Anonymized patient data will be entered online in electronic case report forms and uploaded to an internet website. Each participating centre will have 2 months to become acquainted with the electronic case report forms. After this period official recruitment will begin. Patient data belong to the respective centre, which may use the database for its own needs. However, all centres have agreed to participate in a joint effort to achieve the sample size needed for statistical analysis. CONCLUSION: The study will hopefully help to collect useful information on the current practice of renal replacement therapy in ICUs. It will also provide a centre-based collection of data that will be useful for monitoring all aspects of extracorporeal support, such as incidence, frequency, and duration.

Blood Pressure↗

PubMed2005

Cefepime and continuous renal replacement therapy (CRRT): in vitro permeability of two CRRT membranes and pharmacokinetics in four critically ill patients.

BACKGROUND: Cefepime is a fourth-generation cephalosporin with a broad spectrum of antimicrobial activity against gram-positive and gram-negative micro-organisms. It is a useful option for treating infections in critically ill patients in intensive care due to its high degree of activity and its tolerability. OBJECTIVE: The aim of this study was to characterize in vitro the permeability to cefepime of 2 membranes frequently used in continuous renal replacement therapies (CRRTs). An in vivo study was also carried out to determine the pharmacokinetics of cefepime in critically ill patients undergoing CRRT. METHODS: In vitro procedures were conducted in 3 different fluids using polyacrylonitrile (AN69) or polysulfone (PS) membranes. Continuous venovenous hemofiltration (CVVH) and continuous venovenous hemodialysis (CVVHD) were simulated. Four male patients undergoing CVVH or continuous venovenous hemodiafiltration, who received 2000 mg of cefepime intravenously every 8 hours, entered the in vivo study. Prefilter and ultrafiltrate samples were collected, and concentrations of cefepime were measured using high-performance liquid chromatography. The sieving coefficient (Sc), defined as the fraction of drug eliminated across the membrane, and the saturation coefficient (Sa), defined as the fraction of drug diffused through the membrane to the dialysate fluid, were analyzed. Pharmacokinetic parameters were determined according to a noncompartmental analysis. RESULTS: The patients ranged in age from 18 to 75 years and weighed from 65 to 80 kg. By analyzing Sc and Sa values in the in vitro procedures, no differences were detected in the permeability of AN69 or PS membranes to cefepime in CVVH or CVVHD. Sc/Sa values were between 0.93 and 1.03 in Ringer's lactate and in bovine albumin-containing Ringer's lactate samples, but Sc/Sa values were lower in plasma samples (0.82-0.95). In the in vivo portion of the study, the patients' mean (SD) Sc/Sa value was 0.76 (0.21) and correlated well with the fraction unbound to proteins (0.79 [0.09]). Clearance by CRRT (mean [SD]) was 29.0 (16.8)% of the total clearance. Serum elimination t(1/2) was 4.6 (0.9) hours, and the volume of distribution at steady state was 0.6 (0.3) L/kg (mean [SD] values). CONCLUSIONS: Cefepime was significantly removed by CRRT. No significant differences were found in the Sc or Sa of cefepime between AN69 and PS membranes used in the CVVH or CVVHD procedures. The clearance of cefepime by CRRT must be considered when dosing critically ill patients.

Acrylic Resins↗

PubMed2005

In vitro and in vivo evaluation of enoxaparin removal by continuous renal replacement therapies with acrylonitrile and polysulfone membranes.

BACKGROUND: Enoxaparin is a low-molecular-weight heparin for which the degree of elimination through hemofilters during continuous renal replacement therapy (CRRT) is not well established. OBJECTIVE: The elimination of enoxaparin by CRRT, using acrylonitrile (AN69) or polysulfone (PS) membranes, was studied in vitro and among critically ill patients. METHODS: In vitro procedures were carried out using Ringer's lactate, bovine albumin-containing Ringer's lactate, or fresh human plasma as enoxaparin vehicle, using AN69 or PS membranes, and following continuous veno-venous hemofiltration (CVVH) or continuous veno-venous hemodialysis (CVVHD). Prefilter and ultrafiltrate samples were collected over 60 minutes. All procedures were carried out in triplicate. Patients undergoing CRRT entered the in vivo study. Enoxaparin was administered subcutaneously once daily. The sieving coefficient (Sc) and saturation coefficient (Sa) were calculated as the relation between anti-factor Xa activity in simultaneously collected dialysate/ultrafiltrate samples and plasma samples. RESULTS: Mean Sc (for CVVH) or Sa (for CVVHD) values in the in vitro procedures ranged from 0.16 to 0.57. Sc values during CVVH were significantly higher than Sa values during CVVHD in the Ringer's lactate procedures for both membranes (AN69 membrane, P = 0.014; PS membrane, P < 0.001) and in the plasma procedures with the PS membrane (P < 0.001). Six male and 2 female patients (all white) participated in the in vivo study. Their mean body weight ranged from 55 to 80 kg, and their age ranged from 71 to 82 years. In patients, Sc or Sa achieved values between 0.26 and 0.67. No significant differences were found in vivo in the permeability of the 2 membranes to enoxaparin. CONCLUSIONS: In these studies, the Sc and Sa values suggested that enoxaparin passed through AN69 and PS membranes during CRRT. Further pharmacokinetic and clinical studies are needed to determine whether a dose adjustment for enoxaparin is needed for patients undergoing CRRT.

Acrylonitrile↗

PubMed2005

Influence of renal function on the pharmacokinetics of piperacillin/tazobactam in intensive care unit patients during continuous venovenous hemofiltration.

The pharmacokinetics of piperacillin/tazobactam (4 g/0.5 g every 6 or 8 hours, by 20-minute intravenous infusion) were studied in 14 patients with acute renal failure who underwent continuous venovenous hemofiltration with AN69 membranes. Patients were grouped according to severity (CL(CR) < or =10 mL/min, 10 < CL(CR) < or =50 mL/min, and CL(CR) > 50 mL/min). A noncompartmental analysis was performed. The sieving coefficient (0.78 +/- 0.28) was similar to the unbound fraction (0.65 +/- 0.24) for tazobactam, but it was significantly different (0.34 +/- 0.25) from the unbound fraction (0.78 +/- 0.14) for piperacillin. Extracorporeal clearance was 37.0% +/- 28.8%, 12.7% +/- 12.6%, and 2.8% +/- 3.2% for piperacillin in each group and 62.5% +/- 44.9%, 35.4% +/- 17.0%, and 13.1% +/- 8.0% for tazobactam. No patients presented tazobactam accumulation. In patients with CL(CR) < 50 mL/min, t(%)ss >MIC90 values were 100% for a panel of 19 pathogens, but in those with CL(CR) > 50 mL/min, t(%)ss >MIC90 indexes were 55.5% and 16.6% for pathogens with MIC90 values of 32 and 64. The extracorporeal clearance of piperacillin/tazobactam is clinically significant in patients with CL(CR) > 50 mL/min, in which the risk of underdosing and clinical failure is important and extra doses are required.

Aged↗

PubMed2005

Meropenem and continuous renal replacement therapy: in vitro permeability of 2 continuous renal replacement therapy membranes and influence of patient renal function on the pharmacokinetics in critically ill patients.

The pharmacokinetics of meropenem were characterized in 20 patients with different degrees of renal function who underwent continuous renal replacement therapy. Previously, no differences were detected in vitro in the removal of meropenem by continuous venovenous hemofiltration or continuous venovenous hemodialysis or when AN69 or polysulfone membranes were compared. In patients, no significant differences in the sieving coefficient or the saturation coefficient with the renal function were found, and the mean sieving coefficient/saturation coefficient value (0.80 +/- 0.12) was similar to the unbound fraction (0.79 +/- 0.08). An increase in total clearance and a decrease in elimination half-life were observed to the extent that the patient's creatinine clearance was higher. Likewise, the contribution of continuous renal replacement therapy to total clearance diminished in patients with less renal impairment. The results suggest that the renal function of the patient may influence meropenem pharmacokinetics during continuous renal replacement therapy. The lower trough plasma levels observed in nonrenal patients would not lead to adequate time during which serum drug concentrations are above the minimum inhibitory concentration values in many infections.

Acrylic Resins↗