Population pharmacokinetics of daptomycin in critically ill patients.

Daptomycin has shown activity against a wide range of Gram-positive bacteria; however, the approved dosages usually seem insufficient for critically ill patients. The aim of this study was to develop a population pharmacokinetic model for daptomycin in critically ill patients and to estimate the success of the therapy by applying pharmacokinetic/pharmacodynamic (PK/PD) criteria. Sixteen intensive care unit patients were included, four of whom underwent continuous renal replacement therapies (CRRT). Blood and, when necessary, effluent samples were drawn after daptomycin administration at previously defined time points. A population approach using NONMEM 7.3 was performed to analyse data. Monte Carlo simulations were executed to evaluate the suitability of different dosage regimens. The probabilities of achieving the PK/PD target value associated with treatment success (ratio of the area under the plasma concentration-time curve over 24 h divided by the minimum inhibitory concentration (AUC24/MIC ≥ 666)) and to reach daptomycin concentrations linked to toxicity (minimum concentration at steady-state (Cminss) ≥ 24.3 mg/L) were calculated. The pharmacokinetics of daptomycin was best described by a one-compartment model. Elimination was conditioned by the creatinine clearance (Clcr) and also by the extra-corporeal clearance when patients were subjected to continuous renal replacement therapy (CRRT). The PK/PD analysis confirmed that 280- and 420-mg/d dosages would not be enough to achieve high probabilities of target attainment for MIC values ≥ 1 mg/L in patients with Clcr ≥ 60 mL/min or in subjects with lower Clcrs but receiving CRRT. In these patients, higher dosages (560-840 mg/d) should be needed. When treating infections due to MIC values ≥ 4 mg/L, even the highest dose would be insufficient.

[Hemodynamic monitoring in the critically patient. Recomendations of the Cardiological Intensive Care and CPR Working Group of the Spanish Society of Intensive Care and Coronary Units]. / Monitorización hemodinámica en el paciente crítico. Recomendaciones del Grupo de Trabajo de Cuidados Intensivos Cardiológicos y RCP de la Sociedad Española de Medicina Intensiva, Crítica y Unidades Coronarias.

Hemodynamic monitoring offers valuable information on cardiovascular performance in the critically ill, and has become a fundamental tool in the diagnostic approach and in the therapy guidance of those patients presenting with tissue hypoperfusion. From introduction of the pulmonary artery catheter to the latest less invasive technologies, hemodynamic monitoring has been surrounded by many questions regarding its usefulness and its ultimate impact on patient prognosis. The Cardiological Intensive Care and CPR Working Group (GTCIC-RCP) of the Spanish Society of Intensive Care and Coronary Units (SEMICYUC) has recently impulsed the development of an updating series in hemodynamic monitoring. Now, a final series of recommendations are presented in order to analyze essential issues in hemodynamics, with the purpose of becoming a useful tool for residents and critical care practitioners involved in the daily management of critically ill patients.

Effects of regular and abusive intake of alcohol at weekends on physiological parameters in Spanish young.

OBJECTIVES: The aim of this study was to evaluate the effects of excessive intake at weekends, on different parameters in young university students. STUDY DESIGN: Cross sectional, descriptive study. METHODS: A group of 180 subjects were selected (young males between 18 and 22 years old) and were classified into three groups by their alcohol consumption habits: The control group of non-drinkers (ND; n = 60), the group of one day/weekend drinkers (1D/W, n = 60) and the group of two day/weekend drinkers (2D/W, n = 60). An evaluation of the body composition, a spirometry test (FVC, PEF and MVV), a maximal cycle ergometer test (Heart rate, blood pressure, VO2 max, total watts and time test until exhaustion), a blood sample (GOT, Triglycerides, Total Cholesterol, HDL cholesterol, LDL cholesterol and Glucose) were performed. RESULTS: It was observed that 2D/W group presented significantly higher levels than ND in the following parameters: total cholesterol [185.66 (16.06) compared to 154.28 (25.53) mg/dl]; triglycerides [113.66 (22.47) compared to 45.75 (12.76) mg/dl]; systolic blood pressure [130 (9.50) compared to 115 (5.77) mmHg] and waist to hip ratio [0.92 (0.08) compared to 0.84 (0.05)], and 1D/W group also showed significantly higher levels of triglycerides [71.04 (24.31) compared to 45.75 (12.76) mg/dl] than ND. Moreover, it was confirmed that the accumulation of triglycerides in weekend drinkers is influenced by smoking and the lack of physical activity, and that the relationship between alcohol drinking and systolic blood pressure could be modified by smoking. CONCLUSIONS: Young people's abusive intake of alcohol at weekends can cause negative changes in various health parameters, similar to those observed in alcoholics that drink regularly during the week.

[Assessment of cardiovascular preload and response to volume expansion]. / Valoración de la precarga y la respuesta cardiovascular al aporte de volumen.

Volume expansion is used in patients with hemodynamic insufficiency in an attempt to improve cardiac output. Finding criteria to predict fluid responsiveness would be helpful to guide resuscitation and to avoid excessive volume effects. Static and dynamic indicators have been described to predict fluid responsiveness under certain conditions. In this review we define preload and preload-responsiveness concepts. A description is made of the characteristics of each indicator in patients subjected to mechanical ventilation or with spontaneous breathing.

Effects of aerobic exercise on urinary estrogens and progestagens in pre and postmenopausal women.

The purpose of this study was to elucidate the effect of 6 months of aerobic exercise on urinary excretion of female steroid hormones in pre and postmenopausal women and to check the basal values of urinary steroid. To this end, 20 premenopausal (age 45.56 ± 4.06 years) and 20 postmenopausal (age 52.27 ± 3.80 years) women, all sedentary, were studied before and after a supervised 6-month exercise training program (at 60-70% of maximal heart rate, 60 min/day, 3 days/week), based on aerobic dance. The exercise included standing on one leg, squatting, walking, and touching their heels. Before and after the program, anthropometric data and VO(2max) were measured and urine samples were collected and analyzed by gas chromatography/mass spectrometry (GC/Q-MS). Both, pre and postmenopausal women, improved their VO(2max) after the aerobic exercise program. Regarding the urinary steroids, on the one hand, important differences were observed between urinary estrogens and progestagens in pre and postmenopausal women in basal values. Estrone (P < 0.05), pregnanediol (P < 0.01), pregnanetriol (P < 0.05), and estriol (P < 0.01) levels were lower in postmenopausal women than in premenopausal women. On the other hand, the aerobic exercise program did not affect postmenopausal women in the same way as premenopausal women. After the exercise program, no changes in urinary steroid levels were observed in premenopausal women. However, the aerobic exercise program caused an increase in urinary excretion of pregnanediol (P < 0.05) and pregnanetriol (P < 0.05) in postmenopausal women.

[Estimating cardiac output. Utility in the clinical practice. Available invasive and non-invasive monitoring]. / Estimación del gasto cardíaco. Utilidad en la práctica clínica. Monitorización disponible invasiva y no invasiva.

This aim of this review is to provide a detailed review of the physiologic conditions and variables of the cardiac output, as well as review the different techniques available for its measurement. We also want to establish the clinical situations in which the measurement of cardiac output can add valuable information for the management of critically ill patients. The Fick technique, used in the beginning to calculate cardiac output, has been replaced today by thermodilution techniques (transcardiac or transpulmonary), lithium dilution, bioreactance, Doppler technique or echocardiography. Pulse wave analysis allows a continuous minimally invasive cardiac output measurement. Other methods, such bioreactance, Doppler technique or echocardiography currently provide a valid, fast and non-invasive measurement of cardiac output.

The effect of high level tennis matches on urine steroid profiles in professional tennis players.

AIM: Modern day, tennis matches are characterized by shorter and more intense efforts with players enduring great physical and psychological stress. The aim of this study was to evaluate acute changes in the urinary steroid profile of elite tennis players following professional tournament matches. METHODS: Eight professional male tennis players participated in this study. Urine samples were collected before and after tennis matches corresponding to the quarter finals of the Spanish Tennis Masters. RESULTS: After the match, there was a significant fall (P<0.05) in testosterone, androsterone, etiocholanolone, and dehydroepiandrosterone (DHEA). Cortisone increased whereas tetrahydrocortisone (THE) decreased. The anabolic/catabolic hormone ratio also decreased, although only the fall in total suprarenal androgen (TSA)/total corticosteroid (TC) and DHEA/(THE+THF) ratios had a significant decrease (P<0.05). CONCLUSION: These results indicate that a professional tennis match modifies the urine steroid profiles of players, increasing corticosteroid and decreasing androgen excretion in urine, suggesting an important adrenal activation.

Evaluation of urinary steroid profile in highly trained cyclists.

AIM: A regular and intense physical exercise significantly modifies hormonal metabolism and there are many reports of a change in urine steroid levels accompanying the practice of sport. The aim of this study was to compare the urinary steroid profile between highly trained cyclists and untrained subjects. METHODS: Urine levels of testosterone (T), epitestosterone (Epit), androstenedione, dehydroepiandrosterone (DHEA), androsterone (A), etiocholanolone (E), beta-estradiol (E2), estrone (E1) and the most abundant urine metabolites of cortisol and cortisone, tetrahydrocortisone (THE) and tetrahydrocortisol (THF) were determined by gas chromatography-mass spectrometry in urine samples from a group of professional cyclists (n=15) submitted to maximum level training for several years and compared with urine samples from sedentary subjects (n=15). The relationships between T/Epit, A+E/ THE, A+E/ THF, DHEA/THE and DHEA/THF were also studied. RESULTS: Cyclists showed lower urine levels of T, A, E and E2 and higher urine levels of androstenedione and E1 than sedentary individuals. A+E/THE and A+E/ THF ratios were higher in sedentary subjects than in cyclists. CONCLUSION: We conclude that cyclists showed a urinary steroid profile different from sedentary individuals, probably due to an adaptation to regular and intense physical training .

Elimination of piperacillin and tazobactam by renal replacement therapies with AN69 and polysulfone hemofilters: evaluation of the sieving coefficient.

BACKGROUND/AIM: Piperacillin-tazobactam is commonly used to treat infections in ICU patients. Controversial data have been published about the sieving/saturation coefficient (Sc/Sa) of piperacillin during continuous renal replacement therapies (CRRT). The objective was to evaluate the Sc/Sa of piperacillin-tazobactam during continuous venovenous hemofiltration (CVVH) and continuous venovenous hemodialysis (CVVHD) using AN69 and polysulfone. METHODS: Ringer lactate, BSA-containing Ringer lactate and plasma were circulated at 150 ml/min. The ultrafiltrate/dialysis flow was kept at 1,500 ml/min. A bolus was injected and samples were taken. Drugs were measured using HPLC. Sc/Sa was calculated according to standard formula. RESULTS: Free passage of drugs through the membranes was reported with protein free solutions. In the presence of proteins the Sc/Sa lowered and correlated to protein free fraction. Polysulfone had a significantly higher permeability than AN69 during CVVH. CONCLUSION: Drug binding to albumin contributes to the decrease of the Sc/Sa of piperacillin but it does not completely justify the in vivo value obtained by some authors.

Determination of ceftazidime and cefepime in plasma and dialysate-ultrafiltrate from patients undergoing continuous veno-venous hemodiafiltration by HPLC.

We have developed and validated a new, rapid and reproducible HPLC method for the determination of cefepime and ceftazidime in plasma and dialysate-ultrafiltrate samples obtained from intensive care unit (ICU) patients undergoing continuous veno-venous hemodiafiltration (CVVHDF). The method for plasma samples involved protein precipitation with acetonitrile, followed by washing with dichloromethane to remove apolar lipophilic compounds. Dialysate-ultrafiltrate samples did not require any preparation. Separation was performed on a muBondapak C18 (30 cm x 3.9 mm x 10 microm) with UV detection. The mobile phase contained acetate buffer: ACN and was delivered at 2 ml/min. The coefficients of determination of the calibration curves were always > or = 0.998 and R.S.D.% of the response factors <10%. The intra and inter-assay precision and accuracy of the quality controls (QC) and limit of quantification (LOQ) were satisfactory in all cases. Plasma and dialysate-ultrafiltrate samples were stable at -20 and -80 degrees C for 2 months and also after three freeze/thaw cycles. Dialysate-ultrafiltrate samples were stable in the chromatographic rack for 24h at room temperature, but we recommend storing processed plasma samples at 4 degrees C until the analysis. The described method has proved to be useful to give accurate measurements of ceftazidime and cefepime in samples obtained from patients undergoing CVVHDF.

Quantitation and stability of piperacillin and tazobactam in plasma and ultrafiltrate from patients undergoing continuous venovenous hemofiltration by HPLC.

Simple and reproducible HPLC methods for the determination of piperacillin and tazobactam have been developed and a complete stability study carried out. The method for piperacillin plasma samples consisted of protein precipitation with methanol using penicillin G as internal standard. No sample preparation was needed for ultrafiltrate samples. Tazobactam sample preparation involved protein precipitation with acetonitrile and the removal of lipids with dichloromethane. Piperacillin separation was performed on a microBondapack C(18) column (300 x 3.9, 10 microm) and tazobactam on a Novapack C(18) column (150 x 3.9, 4 microm) with UV detection set at 229 and 225 nm, respectively. The mobile phase consisted of phosphate buffer-acetonitrile, delivered at 1.5 mL[sol ]min. Calibration curves determination coefficients were >or=0.999 and response factors CV% < 5%. Intra- and inter-assay precision and accuracy of the quality control and limit of quantification were satisfactory. Plasma and ultrafiltrate samples were stable at -20 and -80 degrees C for 2 months and after three freeze-thaw cycles. In the chromatographic rack, tazobactam ultrafiltrate samples were stable for 24 h and plasma samples for 12 h, piperacillin ultrafiltrate samples for 8 h, but plasma samples for only 4 h. Storage of piperacillin samples at 4 degrees C until analysis is recommended. Piperacillin was stable in the presence of tazobactam.

Menopause-induced changes in lipid fractions and total fatty acids in plasma.

UNLABELLED: The purpose of the present work was to evaluate the changes induced by the menopause in plasma lipids and total fatty acids. METHODS: 35 post-menopausal and 25 non-postmenopausal women were included in the study. Plasma triglycerides (TG), total cholesterol (TC) and HDL-C concentrations were detemined enzymatically. Plasma fatty acids were determined by capillary gas chromatography. RESULTS: Total cholesterol was higher (p < 0.05) in the postmenopausal women (6.18 +/- 0.77 mmol/l vs. 5.21 +/- 0.85 mmol/l). No significant changes were observed, however, in TG, HDL-C or LDL-C. The study of plasma fatty acids showed the post-menopausal women to have raised levels (p < 0.05) of stearic acid (C18:0), oleic acid (C18:1), and decrease of arachidonic acid (C20:4). Also noteworthy was the significant decrease (p < 0.001) of the desaturation index D5 (3.82 +/- 1.75) in the post-menopausal women. The SHBG level was lower (p <0.001) in the post-menopausal women (55.98 +/- 20nmol/l) than in the non-menopausal women (68.36 +/- 30 nmol/l). Multivariate analysis revealed correlation between menopause and SHBG (r = -0.3904, p < 0.05), D5 (r = -0.500, p < 0.001), TC (r = 0.3137, p <0.05), stearic acid (r = 03564, p < 0.05) and oleic acid (r = 0.2954, p < 0.05). CONCLUSION: In post-menopausal women, as well as higher total cholesterol, the alterations in plasma fatty acids may constitute an important risk factor for cardiovascular diseases.

Urine excretion of androgen hormones in professional racing cyclists.

This study was performed on 16 professional racing cyclists to examine changes in urine concentrations of androgen hormones (testosterone, epitestosterone, androsterone, etiocholanolone, 11-hydroxy-androsterone and 11-hydroxy-etiocholanolone) and plasma sex hormone binding globulin (SHBG) after training and after competition. The urinary concentrations of androgen hormones decreased during the period of training and increased during competition, this being the reverse of what happened to SHBG plasma concentrations. These changes would suggest that physical activity may have an influence on the elimination of androgen hormones and on the synthesis of its transporting protein SHBG.

Effect of submaximal physical exercise performed by sedentary men and women on some parameters of the immune system.

Submaximal physical exercise by sedentary men and women on a bicycle ergometer for 60 min at 58% (men) and 55% (women) of VO2 max. was evaluated for its effect on the number of total leukocytes (WBC), lymphocytes, monocytes and neutrophils and the percentages of CD3+, CD4+, CD8+ and CD19+ lymphocyte subpopulations, as well as on IgA, IgG and IgM serum immunoglobulin levels as one measure of B-lymphocyte function. Blood samples were collected before, immediately after, and 15 minutes after physical exercise. Exercise did not significantly change the total number of WBC, lymphocytes, monocytes or neutrophils, or the percentages of CD3+, CD4+, CD8+ and CD19+ positive cells and the IgA and Ig M immunoglobulins. However the serum level of IgG immunoglobulins immediately after exercise was significantly lower than both before (p < 0.001) and 15 min later (p < 0.05). No differences in the results between men and women were detected.

Determination of ephedrines in urine by high-performance liquid chromatography.

An improved high-performance liquid chromatographic method with ultraviolet detection for the simultaneous determination of norephedrine, norpseudoephedrine, ephedrine, pseudoephedrine, methylephedrine and ethylephedrine in urine is described. The six substances were separated on a reversed-phase column with phosphate buffer-triethylamine (pH 5.5) as the mobile phase. The linearity and reproducibility were satisfactory for the levels usually found in urine (1-30 micrograms/ml).

Erythrocyte free radical scavenger enzymes in bicycle professional racers. Adaptation to training.

This study was designed to investigate the influence of endurance training on the activities of the scavenger enzymes superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) measured in erythrocytes from sedentary subjects, amateur bicycle racers and in professional bicycle racers who were cycling in two real cyclist contests including the top-class race Vuelta a España (VCE). Under resting conditions the SOD activity was higher (p less than 0.01) in cyclists than in controls. The activities of CAT and GSH-Px were higher (p less than 0.05 and p less than 0.01, respectively) under resting conditions in professional cyclists versus measured both in sedentary subjects and amateur cyclists. The enzyme activities were not modified significantly in professional cyclists after a bout of exercise of 22 km in 5 hrs, but the SOD activity was increased (p less than 0.05) and CAT activity reduced (p less than 0.05) after 2800 km in 20 days (VCE). The present results shown that aerobic endurance training, when at a professional level, produces an increase in the erythrocyte activities of the main free radicals scavenger enzymes.