Dilution Kinetics of Chemicals Used for Estimation of Water Content of Body Compartments in Perinatal Medicine

Abstract

PAH, p-aminohippurateNumerous studies of perinatal physiology, metabolism, nutrition, and pathologic conditions require estimation of the fluid content of various body compartments. As direct volumetric determinations are not possible in vivo, less direct methods must be relied upon to obtain an acceptable estimate. The most commonly used techniques involve a principle developed by Fick. Fick's principle states that the fluid content (V) of a given space may be calculated following the administration of a dye or chemical into that space if the exact amount (Q) of substance injected and its concentration (C) in the fluid of the space are Rece~ved August 15, 1988; accepted November 22, 1988 known, or V = Q/C. The dye or chemical must have five main properties: It must I ) be harmless to the organism; 2) be easily measurable; 3) diffuse evenly and within a predictable period of time throughout its vol of distribution; 4) have no effect on fluxes of fluids across membranes; and 5 ) neither be metabolized nor leave the space for which the vol is being measured for the duration of the study. This last requirement is seldom met. If, however, the decrease in dye concentration with time follows a straight line, extrapolation of that line to time 0 (y-intercept or Co) still allows a vol determination to be made, or V = Q/Co. In that case, the rate at which the substance escapes from its vol of distribution, be it by metabolism or excretion, may be also calculated (slope of the concentration versus time line).In cases where all four criteria are met, the marker diffuses as soon as it is administered to reach an even concentration throughout its vol of distribution. In cases where the fourth criterion is not met, two phenomena occur simultaneously as soon as the marker is administered. First, the marker diffuses to reach an even concentration throughout its vol of distribution; second it is being cleared from its assigned space. To interpret the data correctly, it is important to determine at what point in time equilibration is complete and the behavior of the marker concentration thereafter, i.e. the kinetics of the marker. Yet kinetic data have often been disregarded or remained buried in the investigators' laboratory data books and are scarce in the relevant literature. Also, in human perinatal medicine, there are ethical and practical limitations on the number and vol of body fluid samples that may be obtained. In this report, we have made use of the baboon (Papio cynocephalus), whose fetoplacentouterine unit and neonatal physiology and metabolism are very similar to those of Homo sapiens, to determine the kinetics of six markers: PAH (amniotic fluid vol), inulin (amniotic fluid vol), antipyrine (total body water), H2'" (total body water), bromide (extracellular water) and T-1824 (plasma vol). From these kinetics, precise recommendations may be made regarding optimal time and method of amniotic fluid or blood sampling. MATERIALS A N D METHODSPAIf and inulin dilution. The kinetics of PAH and inulin dilution in amniotic f...

Simultaneous Estimation of Neonatal Total Body Water by Antipyrine and H₂¹⁸O Dilution

“…Most literature suggests that the proportion of 180 in body fluids stabilizes within 1-4 h of ingestion or injection of water enriched in 180 and is maintained for at least 2 h [8,15], Our own data in neonates suggest that this is not accurate and that the l80 / l60 ratio in body fluids begins to return to normal within minutes of enrichment with 180 [7,16]. Plasma l80 / I60 decreases linearly with time.…”

“…In fact, the studies of Brodie and Axelrod [ 17] suggest that in adults metabolism is slow, on the average 6%/h (range: 1-12%/h) and that less than 5% is excreted in urine. Our data from baboons indicate that term neonates dispose of antipyrine at a similar rate of 6-9%/h [7], Low birthweight neonates, how ever, have considerably prolonged antipy rine half-lives and on the average dispose of only 1.2% during the first postnatal day and 3.1 %/h by the fourth day, and 21 %/h of anti pyrine losses result from urinary excretion of the unaltered drug [18], These data show that metabolism and/or excretion of antipy rine may be age-and maturity-dependent and unpredictable. At best, this objection only applies to studies that do not compen sate for metabolic losses.…”

“…At best, this objection only applies to studies that do not compen sate for metabolic losses. In fact compensa tion is easily achieved since, over a period of several hours following injection of the marker, anfipyrine losses are linearly related to time [7,19]. It suffices to obtain several blood samples at known time intervals, cal culate the regression line describing plasma antipyrine concentration vs. time, and use the y-intercept (zero-time) for determination of total body water by the Fick principle.…”

“…The intraassay coefficient of variation (standard deviation/mean X 100) was 1.8%. The preinjection 8 lsO was subtracted from each of the postinjection 8 I80 and the linear regression equation of 8 lsO vs. time was calculated by the least squares method [7], The 8l8OS was calculated from formulae 1 and 2 [8]: y-intercept plasma antipyrine concentration where P corrected for the proportion of water in plas ma, 0.977 for baboons [10] and 0.962 for lambs. The proportion of water in plasma of lambs was deter mined by desiccating at 100°C a known aliquot of plasma from 6 of the lambs used in this study (mean plasma water ± SD = 0.962 ± 0.013 g/ml).…”