Abstract
In this chapter, we will discuss three problem areas for achieving fluid and electrolyte balance in the extremely low birth weight (ELBW) infant less than 1000 g at birth, and for his/her historical predecessor, the very low birth weight (VLBW) infant less than 1500 g at birth. The most recent clinical research on fluid and electrolyte therapy addresses these groups as separate; however, the principles for achieving fluid balance in each group represent the same physiology at different phases of fetal development. The first of these problems is poor epidermal barrier function. Especially in ELBW babies, thin, gelatinous skin promotes rapid transcutaneous evaporation, producing severe electrolyte disturbances in the first few days of life as well as presenting a poor barrier to the invasion of infections, and is also subject to trauma from tape/adhesive injury and from routine contact with bedclothes and handling. A second area of major concern is pulmonary edema formation. Increased lung water (pulmonary edema) has been suggested in the pathogenesis of several conditions (including patent ductus arteriosus [PDA], with congestive heart failure, and bronchopulmonary dysplasia [BPD]), leading to the controversy of fluid restriction versus fluid replenishment in preventing chronic lung disease in both VLBW and ELBW babies. Also controversial is the routine use of diuretics and steroids for the treatment of pulmonary edema with acute respiratory distress syndrome (RDS) and with BPD and chronic lung disease. Finally, a relatively new area of concern is the neurodevelopmental outcome of those infants manifesting severe electrolyte imbalances early in life, particularly in those who develop hyponatremia or hypernatremia/hyperosmolality in the first few weeks.
Keywords
fluid and electrolyte physiology, fluid and electrolyte balance, extremely low birth weight (ELBW), very low birth weight (VLBW), premature neonate, insensible water loss, transcutaneous water loss, lung water, patent ductus arteriosus (PDA), ductal ligation, hyponatremia, hypernatremia, renal development, skin development, prenatal steroid therapy, postnatal steroid therapy, indomethacin therapy, neurodevelopmental outcomes
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Immature Epidermal Barrier Function and the Extremely Low Birth Weight Habitus
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Transcutaneous (Insensible) Water Loss
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Water Loss and Pathogenesis of Transcutaneous Dehydration
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Salt Restriction Prophylaxis
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Nonoliguric Hyperkalemia in Extremely Low Birth Weight Babies
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The Epidermal Barrier: Reducing Transcutaneous Evaporation
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Pulmonary Edema Formation
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Electrolyte Imbalances and Neurodevelopment
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Areas for Further Investigation
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Between a Rock and a Hard Place: Suggestions for Vigilant Fluid Balance Therapy in Extremely Low Birth Weight Babies
Introduction
In this chapter, we will discuss three problem areas for achieving fluid and electrolyte balance in the extremely low birth weight (ELBW) infant (<1000 g at birth), and for his/her historical predecessor, the very low birth weight (VLBW) infant (<1500 g at birth). The most recent clinical research on fluid and electrolyte therapy addresses these groups as separate; however, the principles for achieving fluid balance in each group represent the same physiology at different phases of fetal development.
The first of these problems is poor epidermal barrier function. Especially in ELBW infants, thin, gelatinous skin promotes rapid transcutaneous evaporation, producing severe electrolyte disturbances in the first few days of life as well as presenting a poor barrier to infectious agents, and is also subject to trauma from tape/adhesive injury and from routine contact with bedclothes and handling.
A second area of major concern is pulmonary edema formation. Increased lung water (pulmonary edema) has been suggested in the pathogenesis of several conditions (including patent ductus arteriosus [PDA], with congestive heart failure, and bronchopulmonary dysplasia [BPD]), leading to the controversy of fluid restriction versus fluid replenishment in preventing chronic lung disease in both VLBW and ELBW infants. Equally controversial is the routine use of diuretics and steroids for the treatment of infants with pulmonary edema with acute respiratory distress syndrome (RDS) and chronic lung disease.
Finally, a relatively new area of concern is the neurodevelopmental outcome of those infants manifesting severe electrolyte imbalances early in life, particularly in those who develop hyponatremia or hypernatremia/hyperosmolality in the first few weeks.
Immature Epidermal Barrier Function and the Extremely Low Birth Weight Habitus
The tiny baby (ELBW) experiences large transepidermal water losses immediately upon birth. The ELBW baby has little in the way of skin keratin content, and the skin appears translucent, gelatinous, and shiny ( Fig. 13.1 ). In addition, these infants have a proportionally larger extracellular pool (with a nearly normal saline content in equilibrium with the plasma compartment) from which the evaporation of body water leaves the sodium behind ( Fig. 13.2 ). During early fetal life, more than 85% of body mass may be composed of water, two-thirds of which resides in the extracellular space; and only one-third of this water resides in the intracellular space. In contrast, by term gestation, the infant is comprised of about 75% water, with approximately one-half in the extracellular and intracellular spaces, respectively. By 3 months postnatal age, only 60% of body mass is water, with two-thirds residing in the intracellular compartment and only one-third in the extracellular space. Finally, the ELBW neonate has a geometrically larger skin surface area than in more mature infants and adults ( Fig. 13.3 ).
The ELBW baby proportionally has over 6 times the skin surface area exposed per kilogram of body weight, with at least 3 times the mass of water content vulnerable to evaporation. A 500-g infant has as much as 1400 cm 2 skin exposed per kilogram compared with about 750 cm 2 /kg in a term infant and 240 cm 2 /kg in the adult. It is important to remember this exposed body mass is largely comprised of extracellular, sodium-rich water available for evaporation.
Transcutaneous (Insensible) Water Loss
In 1981, we proposed a geometric model ( Fig. 13.4 ) for estimating insensible water loss (IWL) in extremely low birth weight infants, using a metabolic balance (Potter Baby Scale, Hartford, Connecticut) for the continuous measurement of body weight loss (insensible weight loss [IL]) over a 1- to 3-hour period. Although not widely accepted at the time (IWL estimates in ELBW infants ≤700 g were as high as 7.0 mL/kg per hour approaching 170 mL/kg per day), these findings were exactly reproduced by Hammarlund and Sedin in 1983, using an entirely different method to measure water evaporation directly from the skin (transcutaneous water loss [TEWL]) by measuring vapor gradients (Transcutaneous Evaporimeter, Servomed, Stockholm) measured over the immature skin surface of ELBW and VLBW premature neonates during the first weeks of life. These investigators reported similar estimations of transcutaneous evaporation, yielding rates of 50 to 60 g/m 2 per hour, or approximately 170 to 200 mL/kg per day in the first 1 to 3 days of life ( Fig. 13.5 ).
Water Loss and Pathogenesis of Transcutaneous Dehydration
In 1982, we reported a small series of extremely low birth weight infants, who, despite fluid replenishment to as much as 250 mL/kg per day, nevertheless developed hypernatremic serum sodium concentrations by day 3 of life, with values averaging 155 mEq/L ( Fig. 13.6 ) and peaking in the smallest infants at a serum sodium of nearly 180 mEq/L. These observations led to our first description of the pathogenesis of water depletion, with the “iatrogenic” development of hypernatremia, hyperglycemia, hyperosmolarity, and a hyperkalemic state peculiar to the extremely low birth weight baby, and developing in the first 72 hours of life ( Fig. 13.7 ). In the figure, large free-water losses through transcutaneous evaporation were balanced by clinicians increasing the rates of fluid replacement, usually adding sodium in the second day of life to match anticipated urinary sodium losses. These influxes contributed to an immense sodium load presented to an immature kidney. Added to this exogenous sodium load, the large fluid reservoir in the extracellular space was subjected to transcutaneous evaporation of sodium-free water; the low glomerular filtration rate (GFR) of the fetal kidney compensated by retaining sodium. Furthermore, immature renal tubular function with poor concentrating ability tended to waste additional free water. An osmolar diuresis commonly resulted from dextrose overload and hyperglycemia. These physiologic disturbances ultimately led to a hyperosmolar, hypernatremic state. This state contributed to the development of life-threatening hyperkalemia.
Salt Restriction Prophylaxis
To prevent this syndrome, Costarino et al. conducted a randomized and blinded control trial of sodium restriction versus maintenance sodium administration during the first 5 days of life in infants born less than 1000 g and less than 28 weeks’ gestation. Infants were randomly assigned to either a low-sodium group who received no maintenance sodium additive with their parenteral nutrition or to a high-sodium replenishment group who received 3 to 4 mEq/kg per day added to their daily maintenance fluids and administered beginning on day 2 of life.
A safety committee analyzed data at half-enrollment and stopped the study. Two out of the nine infants in the sodium-restricted group became hyponatremic with serum sodium concentrations of 130 mEq/L or less by day 5 of life and were taken out of the study. Conversely, two of the eight infants in the sodium replenishment group became hypernatremic with a serum sodium of 150 mEq/L or more by day 4 and were also removed from the study. Daily assessments of serum sodium concentrations were significantly and consistently higher in the sodium-supplemented infants after day 1 of life ( Fig. 13.8 ).
By study design, sodium intake (seen in the top graph, Fig. 13.9 ) ranged between 4 and 6 mEq/kg per day in the sodium-supplemented maintenance group (shaded bars). Infants in the restricted group received between 1 and 
mEq/kg per day of sodium as additives (shown as lightly shaded bars vs. dark shaded bars in the graph) with medications containing sodium (sodium heparin, sodium ampicillin, and sodium citrated transfusions, etc.). It was impossible to eliminate sodium intake entirely due to these unrecognized sources of exogenously applied salt. Sodium excretion (shown in the middle graph of Fig. 13.9 ) remained the same for the first 3 days of the study, but began to increase after day 4 in infants in the sodium-supplemented group. And shown in the bottom graph (see Fig. 13.9 ), calculated sodium balance was nearly zero in the sodium-supplemented group (shaded bars) where intake matched urinary sodium excretion, but remained markedly negative in the sodium-restricted group by as much as 6 mEq/kg per day net sodium loss (light shaded bars).
mEq/kg per day of sodium as additives (shown as lightly shaded bars in the graph) with medications containing sodium (see text). It was impossible to eliminate sodium intake entirely due to these often unrecognized sources of exogenously applied salt. In the bottom graph, calculated sodium balance was nearly zero in the sodium-supplemented group (shaded bars) where intake matched urinary sodium excretion, but remained markedly negative in the sodium-restricted group by as much as 6 mEq/kg per day net sodium loss (2 standard deviations, lightly shaded bars ). Fluid intakes prescribed independent of the study by the physicians (who did not know the group assignment) were similar in both groups of infants, ranging between 90 and 130 mL/kg per day throughout the first 3 days of life ( Fig. 13.10 , top graph ). However, after 3 days, fluid volume exceeded 130 mL/kg per day in the sodium-supplemented infants (indicated by dark shaded circles ) and was significantly higher than in the salt-restricted infants who only received approximately 90 mL/kg per day (shown by light shaded circles ). These results suggest that infants in the sodium-supplemented group were prescribed increasing amounts of fluid to compensate for their rising serum sodium. Conversely, infants in the sodium-restricted group required relative fluid restrictions, probably in response to falling serum sodium concentrations. Failure to restrict fluid intake volume after 5 days of age may result in clinically significant hyponatremia.
Of interest (as seen in the bottom graph, Fig. 13.10 ), urine output was fixed throughout the study in both groups, at between 2 and 4 mL/kg per hour (or about 50–100 mL/kg per day), and was not dependent on either the volume of fluid administered or the amount of sodium intake.
Survival was similar in both groups, and the comorbidities of intraventricular hemorrhage (IVH) and patent ductus arteriosum were also similar. There was a trend, however, towards infants developing BPD in the high sodium/high fluid intake group: 7 of 7 infants versus 4 of 8 infants in the low sodium/low fluid intake group ( P = .08). However, this safety analysis was underpowered to detect the impact of fluid volume administration on these secondary outcomes.
Nonoliguric Hyperkalemia in Extremely Low Birth Weight Infants
During these studies, we encountered an additional electrolyte disturbance, hyperkalemia, in the absence of renal failure (“nonoliguric hyperkalemia”) that we further investigated. Gruskay et al. identified eight ELBW infants with serum potassium levels 6.8 mEq or more and compared them to 10 comparable ELBW infants who remained normokalemic. Peak serum potassium values averaged 8.0 ± 0.3 mEq/L in the hyperkalemic infants, and all of these infants developed electrocardiographic abnormalities requiring treatment.
Renal testing in these two groups of infants demonstrated similar serum creatinine values and GFRs ( Fig. 13.11 ). In contrast, urine sodium excretion was markedly increased in the hyperkalemic infants, with urine concentrations of sodium exceeding 140 mEq/L ( Fig. 13.12 ); the fractional excretion of sodium was nearly 15% in the hyperkalemic group, compared to only 5% in the normokalemic infants. Both of these observations suggest a profoundly immature tubular conservation of filtered sodium. The hyperkalemic infants revealed significantly less potassium excretion than the normokalemic infants ( Fig. 13.13 ). These authors suggested an immaturity in renal tubular response to aldosterone resulting in these electrolyte disturbances.
