Determinants of vancomycin clearance by continuous venovenous hemofiltration and continuous venovenous hemodialysis

The clearance of vancomycin is significantly reduced in patients with acute, as well as, chronic renal failure. Although multiple-dosage regimen adjustment techniques have been proposed for these patients, there is little quantitative data to guide the individualization of vancomycin therapy in acute renal failure patients who are receiving continuous renal replacement therapy (CRRT). To determine appropriate vancomycin dosing strategies for patients receiving continuous venovenous hemofiltration (CVVH) and continuous venovenous hemodialysis (CVVHD), we performed controlled clearance studies in five stable hemodialysis patients with three hemofilters: an acrylonitrile copolymer 0.6 m2 (AN69), polymethylmethacrylate 2.1 m2 (PMMA), and polysulfone 0.65 m2 (PS). Patients received 500 mg of vancomycin intravenously at least 12 hours before the start of the clearance study. The concentration of vancomycin in multiple plasma and dialysate/ultrafiltrate samples was determined by EMIT (Syva, Palo Alto, CA). The diffusional clearance and sieving coefficient (SC) of vancomycin were compared by a mixed-model repeated-measures analysis of variance (ANOVA) with filter and blood (Q(B)), dialysate inflow (Q(DI)), or ultrafiltration rate (Q(UF)) as the main effects and patient as a random effect. Vancomycin was moderately protein bound in these patients; free fraction ranged from 49% to 83%. The SCs of the three filters were similar and significantly correlated with the free fraction of vancomycin (P = 0.01; r2 = 0.465). Significant linear relationships were observed between the diffusional clearance of vancomycin and Q(DI) for all three filters: AN69 (slope = 0.482; r2 = 0.880); PMMA (slope = 0.853; r2 = 0.966); and PS (slope = 0.658; r2 = 0.887). The slope of this relationship for the PMMA filter was significantly greater than that of the AN69 and PS filters. The clearance of vancomycin, urea, and creatinine, however, was essentially constant at all Q(B)s for all three filters. Thus, the clearance of vancomycin was not membrane dependent during CVVH. However, during CVVHD, membrane dependence of vancomycin clearance was noted at a Q(DI) greater than 16.7 mL/min; vancomycin clearance with PMMA at a Q(DI) of 25 mL/min was 66% and 43% greater than that with the AN69 and PS filters, respectively. CVVH (62% to 262%) and CVVHD (90% to 540%) can significantly augment the clearance of vancomycin in acute renal failure patients. Dosing strategies for individualization of vancomycin therapy in patients receiving CVVH and CVVHD are proposed.     

The febrile stress of routine vaccination does not increase central apnoea in normal infants

Abstract We tested the hypothesis that the febrile stress of routine vaccination would increase central apnoea in normal infants. Twenty-one normal infants had continuous overnight breathing and temperature recorded at home, before and after 58 routine vaccination episodes. Central apnoea, of at least 5 sec duration, was detected by computer algorithm and confirmed by human inspection. The longest recorded apnoea was 16 sec ( n = 1) during 3629 h of sleep. Overnight rectal temperature increased after vaccination (median 0.52°C, 95% CI 0.40, 0.65). Apnoea density reduced on 46/53 vaccination nights (median -29%, 95% CI -20, -37) followed by an increase on subsequent nights (median +10%, 95% CI +1%, +21%). Overall, apnoea density was similar during the 3 nights preceding and 4 nights following vaccination (median +1%, 95% CI +9,-6). The febrile stress of routine vaccination did not increase central apnoea in normal infants.     

Dual energy X-ray absorptiometry of the hand and wrist–a possible technique to assess skeletal maturation: methodology and data in normal youths

Ninety five normal Caucasian subjects (51F, 44 M) aged from 2 to 25 y were measured at the hand and wrist level with a small DXA system (pDEXA™) in order to obtain the normal values of the bone mineral content (BMC), density (BMD) and projected area (A) of carpal (c) and metacarpal (m) bones. BMDc ranged from 0.065 ± 0.007 g/cm to 0.365 ± 0.035 g/cm in females and 0.425 ± 0.040 g/cm in males. It presented a sharp change of increase rate at 15.5 and 17 y of age in girls and boys, respectively. Ac presented the same kind of evolution as BMDc, but had a larger value dispersion. The second metacarpal bone had the highest BMCm value in 85% of females and 90% of males. The sum of BMCmi or Ami values (i = 1–5) and the projected mean density of the 5 metacarpal bones was well correlated with BMCc, Ac and BMDc, respectively ( r > 0.90). A volumetric mineral density, dmi, calculated for each of these bones, approximated to a cylinder, was correlated with age ( r > 0.85).     

Gastric emptying and intragastric distribution of oil in the presence of a liquid or a solid meal.

There is little information about gastric emptying of extracellular fat. A marker for liquid fat, 99mTc-(V)-thiocyanate, was used to compare gastric emptying and intragastric distribution of oil to that of aqueous liquid and solid meal components. Eight volunteers consumed 60 ml of 99mTc-labeled oil and 290 ml of 113m-In-labeled soup (total 505 kcal) on one day and 280 g 113mIn-minced beef (500 kcal), 60 ml 99mTc-labeled oil and 290 ml nonlabeled soup (505 kcal) on another day. In the oil/soup meal, gastric emptying of oil was slower than soup (50% emptying time 139.1 +/- 16.5 min versus 47.9 +/- 4.5 min, p less than 0.01). There was retention of oil in the proximal stomach (p less than 0.01) and retrograde movement of oil from distal into proximal stomach. In the oil/soup/beef meal, there was no difference in emptying of oil and beef from the total stomach (retention at 180 min 71.4% +/- 3.4% versus 58.3% +/- 7.6%, ns), but more oil was retained in the proximal stomach and more beef was retained in the distal stomach (p less than 0.01). The emptying rate of oil in the oil/soup meal was about twice that for oil consumed in the other meal. There was no difference between the two meals in the number of calories emptied in the first 180 min. These results demonstrate major differences in the intragastric distribution of oil compared to solid and aqueous liquid meals.