Luc P. Brion

The Use of Plasma Creatinine Concentration for Estimating Glomerular Filtration Rate in Infants, Children, and Adolescents

The formula GFR = kL/Pcr can be used to estimate GFR in infants, children, and adolescents who have grossly normal body habitus and are in steady-state condition. GFR is expressed in ml/min per 1.73 m2 BSA, L represents body length in cm, Pcr represents plasma creatinine concentration in mg per dl and k is a constant of proportionality that reflects the relationship between urinary creatinine excretion and units of body size. The value of k varies as a function of age and sex being 0.33 in preterm infants, 0.45 in full-term infants, 0.55 in children and adolescent girls, and 0.70 in adolescent boys. The advantages of rapid determination, reasonable accuracy, and the avoidance of urine collection justify the use of this formula in pediatric patients.

A simple estimate of glomerular filtration rate in low birth weight infants during the first year of life: Noninvasive assessment of body composition and growth

The management of the preterm infant often requires rapid assessment of glomerular filtration rate (GFR). We sought to develop a screening test using GFR = kL/Pcr, where GFR is expressed as ml/min/1.73 m2, L is body length in centimeters, Pcr is plasma creatinine concentration, and k is a constant that depends on muscle mass. The value for k in 118 appropriate for gestational age preterm infants (0.34 +/- 0.01 SE) was significantly less than that of full-term infants (0.43 +/- 0.02, P less than 0.001). There was no difference between 12- to 24-hour single-injection inulin clearance and either 0.33 L/Pcr or creatinine clearance in preterm infants. We compared the body habitus of preterm and full-term infants using the assessment of muscle mass from urinary creatinine excretion (UcrV) and from upper arm muscle area (AMA) and volume (AMV), and that of fatness from the sum of five skinfold thickness measurements. During the first year of life, premature infants were found to have a lower percentage of muscle mass than term infants did. On the other hand, they took on a relatively greater amount of subcutaneous fat. There was a very good correlation between AMA or AMV and urinary creatinine excretion (r = 0.91 and 0.94, respectively) in 68 infants with heterogeneous body composition during the first year, indicating the validity of the urinary creatinine measurement. Absolute GFR (ml/min) was also well estimated from AMA or AMV factored by Pcr. We conclude that GFR can be well estimated from 0.33 L/Pcr in preterm infants. The lower value for k reflects the smaller percentage of muscle mass in preterm versus term infants. As a screening test, 1.5 X k or 0.05 L/Pcr predicted low values of GFR with an efficiency of 73%, specificity of 67%, and sensitivity of 88%.

Targeted short-term fluconazole prophylaxis among very low birth weight and extremely low birth weight infants

OBJECTIVES. To assess whether targeted short-term fluconazole prophylaxis reduces late-onset (>3 days of age) invasive fungal infection (IFI) among very low birth weight infants and extremely low birth weight (ELBW) infants and to assess mortality rates, toxicity, and costs associated with this intervention. METHODS. An observational study of 2 subsequent epochs of inborn infants with birth weight of <1500 g or gestational age of <32 weeks, 1 before (control) and 1 after (fluconazole) initiation of routine targeted fluconazole prophylaxis in March 2003, was performed. Targeted fluconazole (3 mg/kg) prophylaxis was administered to infants for whom a decision was made to administer broad-spectrum antibiotics for >3 days. RESULTS. IFI was observed for 13 (6.3%) of 206 infants in the control epoch and 2 (1.1%) of 178 in the fluconazole epoch, with a common odds ratio of 0.166. Logistic regression analysis taking into account all published factors (except for fungal colonization) showed that the fluconazole epoch was associated significantly with lower IFI rates. We observed no change in late (>3 days) mortality rates (11 of 206 infants in the control epoch vs 8 of 178 infants in the prophylaxis epoch). The mortality rate for ELBW infants with IFI was low (15%) in our study. Fluconazole was administered to 81% of ELBW infants, who received a median of 8 doses, and 41% of larger infants, who received a median of 5 doses. The intervention was cost-effective, and the effective number needed to treat to prevent 1 IFI was 10. CONCLUSIONS. This study suggests that targeted short-course fluconazole prophylaxis in very low birth weight and ELBW infants may be efficacious and cost effective.

Amplitude-integrated EEG in preterm infants: Maturation of background pattern and amplitude voltage with postmenstrual age and gestational age

OBJECTIVE:Amplitude-integrated electroencephalogram (aEEG) is a single channel EEG recorded from two parietal electrodes. The objective of this study was to test the hypothesis that aEEG maturation follows postmenstrual age (PMA) irrespective of gestational age (GA).METHODS:We recruited inborn infants with a GA <33 weeks and without evidence of neurologic anomaly. Serial aEEG recordings were assessed for: presence of continuous activity and mature sleep-wake cycling (SWC); low base voltage (V), that is, the lowest amplitude margin; high base V, that is, the most common amplitude margin; upper high V, that is, upper margin during highest activity; and span, that is, the difference between upper high and simultaneous high base V. Statistical analysis included logistic regression and repeated measures analysis of variance.RESULTS:We obtained 119 aEEG recordings in 31 preterm infants (GA 25 to 32 weeks; birth weight 600 to 1704 g, PMA 25 to 35 weeks). The frequency of mature SWC increased with PMA independent of GA, while the frequency of continuity increased with PMA and was higher in extremely preterm infants after correcting for PMA. Low base and high base V increased with PMA, while span and upper high V significantly decreased with PMA. In addition, high base V was higher in extremely preterm infants after correcting for PMA.CONCLUSIONS:In preterm infants aEEG matures predominantly with PMA. Our data suggest that some aspects of aEEG maturation are enhanced, rather than inhibited by extremely preterm birth. These data suggest that aEEG in preterm infants may need to be analyzed by comparing results with standards of similar PMA and GA.

Micro-method for the measurement of carbonic anhydrase activity in cellular homogenates.

The kidney is responsible for the excretion of acid. Carbonic anhydrase (CA) activity facilitates H+ secretion by catalyzing the buffering by CO2 of cellular-generated base. We describe a simple and inexpensive micro-method for the determination of CA activity in monolayers of cultured renal cells using imidazole-Tris buffers. Our method is twice as sensitive as that originally described by Maren and the endpoint is much less affected by other cellular proteins. It can easily determine the CA activity of a monolayer of cells grown to confluence in a 75-cm2 flask. In some cases homogenates giving no detectable activity by Marens technique had assayable CA activity by the imidazole-Tris method. A smaller reaction system providing a 10-fold reduction in volume (or increase in sensitivity) permits the determination of CA activity in 25-cm2 monolayers and even in microdissected proximal tubular segments totaling less than 5 mm in length. We believe that the regulation of CA activity at the cellular level may be better understood using this more sensitive assay.

Splanchnic tissue oxygenation, but not brain tissue oxygenation, increases after feeds in stable preterm neonates tolerating full bolus orogastric feeding

Objective:The objective of this prospective, observational study was to test the hypothesis that tissue oxygenation in the splanchnic bed compared with tissue oxygenation in the cerebral circulation changes after feeding in preterm neonates who are tolerating full bolus orogastric feeds.Study Design:Clinically stable premature neonates with postmenstrual age between 32 and 356/7 weeks who were tolerating full bolus feedings were studied before feeding and 1 h after feeding using near-infrared spectroscopy. The ratio of oxygenated to reduced hemoglobin (tissue oxygenation index, TOI) in the splanchnic circulation bed was divided by the TOI in the cerebral circulation, thereby yielding the cerebro-splanchnic oxygenation ratio (CSOR). We compared TOI and CSOR before and after feeding. As the changes in TOI and CSOR had non-Gaussian distribution, nonparametric statistics were used.Result:Among 32 infants, CSOR increased significantly after feeding (median difference 0.08; range −0.48, +0.58; P=0.011), whereas pulse oximetry did not change significantly (P=0.600). The change in CSOR with feeding was associated with a significant increase in splanchnic TOI (preprandial median 43.8, range 25.2–68.4 vs postprandial 47.5, range 25.8–70.8; P=0.013), without any significant change in brain TOI (preprandial median 64.9, range 44.5–75.4 vs postprandial 58.9, range 42.2–72.3; P=0.153).Conclusion:This study indicates that CSOR and splanchnic TOI, but not brain TOI, increase significantly after feeding in stable preterm infants who are tolerating full orogastric feeds.

Is there an Advantage of Using Pressure Support Ventilation with Volume Guarantee in the Initial Management of Premature Infants with Respiratory Distress Syndrome? A pilot study

OBJECTIVE:To evaluate the feasibility of using the pressure support ventilation with volume guarantee (PSV-VG) as an initial ventilatory mode in preterm infants with respiratory distress syndrome (RDS) after surfactant treatment to achieve accelerated weaning of peak inspiratory pressure (PIP) and mean airway pressure (MAP).STUDY DESIGN:Initial 24-hour ventilatory parameters were compared in two groups of preterm infants managed by PSV-VG and the synchronized intermittent mandatory ventilation (SIMV) mode in a randomized controlled pilot study after surfactant treatment for RDS. A total of 16 babies were randomized to PSV-VG (1198±108 g [mean±SEM]; 27.9±0.6 weeks) and 18 babies to SIMV (birth weight 1055±77 g; gestational age 27.4±0.5 weeks). Repeated measures analysis of variance was used to compare serial values of PIP and MAP in the two groups.RESULTS:The PIP and MAP decreased over time (p<0.001) during the first 24 hours after surfactant administration in both groups but the decrease in MAP was faster in the SIMV group compared to PSV-VG group (p=0.035). The median numbers of blood gases during the first 24 hours were four and two in the SIMV and PSV-VG groups, respectively (p<0.001). The overall outcomes were not significantly different between the two groups.CONCLUSION:PSV-VG did not offer any ventilatory advantage over SIMV in the initial management of surfactant-treated premature newborns with RDS except for minimizing the number of blood gases.

Estimation of glomerular filtration rate in anorectic adolescents.

AbstractSevere malnutrition has been associated with a decrease in fat and lean body mass, as well as in renal function. This study was designed to evaluate the estimation of glomerular filtration rate (GFR, ml/min per 1.73 m2) in malnourished teenagers, by using the formula GFR=kL/Pcr (whereL is body height,Pcr is plasma creatinine concentration and k is a proportionality constant relating muscle mass to body size that has been found to equal 0.7 in adolescent boys and 0.55 in girls). Body composition was estimated using anthropometric measurements and urinary creatinine excretion (UcrV). Malnourished female patients showed depletion of fat and muscle, whereas males had primarily decreased muscle mass. There was a good correlation (r=0.74) between anthropometric [arm muscle volume (AMV)] and chemical UcrV estimates of muscle mass. However, our previously validated estimate of GFR did not give reliable results in this group of malnourished teenagers, probably because their muscle mass was so greatly altered by the severity of malnutrition. Therefore, we used anthropometric measurements and Pcr, to estimate GFR by multiple linear regression. The best prediction was obtained by using AMV/Pcr and the observed/expected (for age, height and sex) weight ratio (WR):

Up-Regulation of Carbonic Anhydrase Isozyme IV in CNS Myelin of Mice Genetically Deficient in Carbonic Anhydrase II

\begin{gathered} GFR (ml/min) = 0.06 AMV/P_{{\text{cr}}} + 131{\text{ WR - 79,}} \hfill \\ r = 0.82,n = 13. \hfill \\ \end{gathered}