Physiological management of fluid and electrolyte therapy in newborns

Introduction

Water is critical to the support of all life, and ensuring appropriate balance of fluid and electrolytes is a central aspect of the clinical management of patients. It has been extremely difficult to study and define optimal fluid and electrolyte management in premature infants, despite the fact that this is a population that is essentially completely dependent on what is administered. Study in this area is difficult because each individual patient is different, the impact of maturation changes with each day of gestational age (GA) or postnatal age, and environmental factors and clinical conditions are quite variable.

Management should be based on understanding the basic physiological processes and particular environmental factors in each case and then making judgments about the impact of these factors on an individual patient. It is equally important to then monitor each patient, to assess the infant’s individual fluid and electrolyte status, and then to empirically adjust therapy and reassess at a later time point. This pattern of repeated refinements as needed is continued until clinical stability is assured, and the frequency of these assessments is determined by individual factors including GA birth weight and environment. These and other variables make it almost impossible to make perfect calculations of fluid and electrolyte needs at one point in time. At the same time, it is encouraging to understand that the system is dynamic, and most often even the most immature kidneys will function well enough to aid in achieving homeostasis.

Water and electrolyte homeostasis in newborn infants is variable because each patient’s status is affected by numerous factors, including GA, postnatal physiological changes in renal function, altered response to hormones, redistribution of total body water (TBW), and water loss secondary to environmental factors including the use of radiant warmers or humidified environments. The water content of the newborn is higher than that of the adult, ranging from 73% to 80% in term and premature infant, to as high as 90% in infants of 23 weeks’ gestation. As a result, management of neonatal fluid and electrolyte therapy is challenging, as these factors and the clinical setting need to be accounted for while caring for neonates, especially preterm infants.

Examples that demonstrate how the understanding of physiology can be translated into clinical practice are interspersed within the following discussion. A few caveats and principles are worth noting:

1.
Not every situation can be illustrated.
2.
The best fluid management depends on calculations based on physiology and to some extent, reasonable approximations. It is essential to follow up any therapy or changes with repeat laboratory determinations and to then adjust that therapy based on the individual patient.
3.
It is unnecessary to attempt to put too fine a point on calculations. The system is dynamic and even the immature kidney has mechanisms that are aimed at achieving homeostasis (see following discussion). Maturation is ongoing as each day passes and, in most instances, renal function changes progressively.

Neonatal management is uniquely difficult

Water and electrolyte physiology are primarily dependent on renal function and the balance between fluid intake and fluid losses. In the newborn period, there is an increased risk of derangements in water and electrolyte homeostasis, in large part because the intake and environment are completely controlled by caregivers, and there are progressive changes in body water components, functional immaturity of the neonatal kidney, and skin that are rapidly evolving. Newborns have increased insensible water losses and a greater dependence on environment compared with older patients, and they lack the ability to independently access water. The magnitude of postnatal diuresis, immaturity of renal function, and insensible fluid loss all increase as GA decreases. Water and electrolyte balance are of course integrally linked, but to better understand the basic physiologic mechanisms that regulate them, it is worth considering them separately at first.

Progressive changes in total body water

TBW is composed of extracellular fluid (ECF), which includes intravascular and interstitial fluid and intracellular fluid. The amount of TBW as a percentage of body weight and its distribution in various fluid compartments vary with GA. In a newborn term infant, the TBW is 75% of the body weight as compared with 80% in an infant born at 27 weeks’ gestation and may be as high as 90% in the most immature infants at 22–23 weeks’ gestation. ECF volumes are 45% and 70%, respectively.

Water in the newborn is the balance between intake (which also includes the tiny amount of water derived from metabolism) and losses including insensible water loss and urine losses (including the tiny amounts for stool and negligible water for growth in the days immediately following birth). Functionally this means that the fluid balance can be considered as the difference between intake and the sum of insensible and urine losses. This difference is reflected in weight loss or gain.

After birth, there is a physiologic, isotonic diuresis of ECF resulting in an expected weight loss during the first week of life, ^, and this weight loss is essentially the difference in water balance. The mechanism for this necessary diuresis and the relative loss of weight is as yet not identified, but the percent of weight loss decreases with increasing GA. Preterm infants normally lose 10% to 15% of birth weight, and term breastfed infants average about a 5% loss of birth weight in the first day. The postnatal diuresis is approximately 1 to 3 mL/kg per hour in term infants and is greater in preterm infants. Since fluid administration in these infants is entirely regulated by caregivers, recognition of this normal physiologic fluid loss is a major determinant for fluid management. In addition, other concomitant fluid losses vary depending on the clinical setting. As a result, monitoring of intake and output is important to ensure adequate fluid intake. For the term infant, prior to discharge, parents are counseled on assessing intake and urinary output, and a follow-up appointment is scheduled within 48 to 72 hours after discharge to monitor weight loss and fluid intake.

Fluid and electrolytes in the premature infant

Prospective studies involving very low birth weight infants (birth weight ≤ 1500 g) and extremely low birth weight infants (birth weight ≤ 1000 g) have demonstrated a consistent pattern of fluid and sodium homeostasis despite varying intakes of sodium and water over the first 5 to 7 days of life. In this study infants were randomized to different fluid regimens intended to produce different degrees of negative water balance. When infants with birth weights of 750–1000 g were allowed a weight loss of 1%–2% per day (up to 10% during the first 5 days of life), their mean weight loss was only marginally smaller than that in the group allowed a 3%–5% weight loss per day (up to 15% during the first 5 days of life), despite a much higher fluid intake. This demonstrates that negative water balance in the first few days of life is physiologic and that even immature kidneys that are capable of compensating for varying fluid intakes at least to some degree. There was no difference in rates of major morbidities including patent ductus arteriosus, bronchopulmonary dysplasia, intraventricular hemorrhage, and necrotizing enterocolitis, and the mortality rates were similar.

In another study, premature infants (23–33 weeks) were randomized to receive either 60–70 mL/kg per day on day 1, increasing to 150 mL/kg per day by day 7, or to an intake restricted to 80% of these volumes. Weight loss and both short- and long-term morbidities were similar between the groups. These results demonstrate that as long as regimens allow for contraction of the ECF and a goal weight loss of 6%–12% without hypernatremia, it is not possible to define a single optimal approach. When the postnatal weight loss is prevented ^, by high rates of fluid administration, the risks of bronchopulmonary dysplasia or death may be increased.

Shaffer and Meade randomized infants to 1 or 3 mEq/kg per day of sodium intake over the first 10 days of life and found no difference between the groups in weight loss, decrease in extracellular volume, or sodium balance. This demonstrates that, as with water intake, negative sodium balance is physiologic in the first week of life and that even immature kidneys are capable of compensating for varying sodium intakes at least to some degree.

The underlying physiology of the early water, sodium, and weight loss in premature infants occurs in three sequential phases of water and sodium changes :

Prediuretic phase—The first day after birth is characterized by oliguria (<1 mL/kg per hour) with low glomerular filtration rate (GFR) and low fractional excretion of sodium (FENa). There is a normal rise in sympathetic nervous system activity that results from the processes of birth, including the changes in temperature and cardiac output. This leads to increased renal vascular resistance and the suppression of renal blood flow and decreased GFR. Fluid requirements are much lower on this day, and there is little need for supplemental sodium administration.
Diuretic and natriuretic phase—On days 2 to 3 after birth, urine output and sodium losses normally increase abruptly along with sodium losses. The reabsorption of lung fluid leads to an increase in the ECF volume, which results in an inhibition of renal sympathetic activity. Renal vascular resistance decreases, causing an increase in GFR, FENa, and urine output and resulting in negative water and sodium balance. Weight loss during this phase is both normal and expected, and urine output may exceed the level of 2 mL/kg per hour (45 mL/kg per day) that is expected with later equilibration. Caregivers should be vigilant to neither interfere with this nor to ignore possible causes should it fail to occur.
Postdiuretic phase—On days 4 to 5 urine output is more directly dependent on fluid intake, and the ongoing equilibration of the ECF volume results in a reduction of GFR and FENa compared with the prior phase. Weight loss due to fluid shifts becomes smaller during this phase.
These phases unfold in the patient with otherwise normal renal function and blood pressure.
Illnesses, including but not limited to hypoxic ischemic injury, hypotension, and infection, may significantly disrupt these stages. Fluid management must be appropriately adjusted as necessary.

Water losses

As noted previously, water loss occurs primarily through insensible losses (via the skin and respiratory tract) and renal output. Sensible water loss from the skin (sweating) is negligible in newborn infants. The absolute and relative amounts of water loss through these routes change with GA and postnatal age. Other sources of fluid losses may include stool (usually negligible in the first several days) and those losses that are unique to individual patients, such as gastric or ileostomy drainage or thoracostomy output.

Skin

Evaporation through the skin is a major component of insensible water losses in newborns. Rates of loss are highest in extremely low birth weight (<1000 g) infants with very thin skin (increased skin permeability). In addition, the surface area–to–body volume (related to body weight) ratio increases with decreasing GA and size, resulting in increased rates of fluid loss per kilogram body weight.

As the skin matures with increasing GA and postnatal age, these evaporative losses diminish, and with growth the surface area–to–volume ratio ultimately decreases as well. The impact of skin maturity is less significant for infants born after 28 weeks’ GA and even less for more mature infants. Progressive changes in the skin contribute to a marked diminution in these losses by about 1 week after birth. As an example, insensible water loss in an infant born at 24 weeks’ gestation may be as high as 200 mL/kg per day in the first 24–48 hours compared with a loss of 20 mL/kg per day for a term infant, but will be only a fraction of that amount by 7–10 days. There are less common conditions in which skin integrity is compromised (e.g., epidermolysis bullosa, abdominal wall defect) and insensible skin losses will be very high.

Environmental factors can contribute to increased insensible losses, although many are less commonly used than previously. Radiant warmers for care may increase evaporative water loss by approximately 50%, although this can be mitigated by introducing humidification and covering the bed with plastic wrap. With the introduction of hybrid incubators, these warmers are rarely used in care. These modern incubators include systems for humidification, which reduces the water losses significantly, but not entirely.

Older heat-emitting phototherapy devices also increase transepidermal water loss, ^, but these too are much less commonly employed in care today. The newer devices employ high-intensity gallium nitride light-emitting diode phototherapy, which have no effect on transepidermal water loss.

Most neonatal units aim to provide higher levels of ambient humidity, which reduces the insensible losses from the respiratory system. In ambient humidity, about half of insensible losses are from the respiratory system in spontaneously breathing term infants. ^, Respiratory insensible water loss is independent of GA, although the portion of insensible water loss that is respiratory is less because transepidermal water loss is less. Insensible water loss via the respiratory tract increases as respiratory rate rises. Respiratory losses are decreased for infants who are cared for in humidified air and are especially low in those who are intubated and mechanically ventilated using humidified gases. This is also true for continuous positive airway pressure and high-flow systems that include humidification, but in all cases the amount of respiratory water loss increases at lower gestational age. In comparison, however, the major losses in these immature infants are transepidermal.

Changes in care practices themselves may also impact water losses. The antenatal administration of glucocorticoids to women with threatened premature deliveries affects organ maturation that extends to the skin and kidneys. In one report, infants who were exposed to antenatal glucocorticoids had lower insensible water loss, less hypernatremia, and an earlier diuresis and natriuresis over the first several days after birth than a similar group of infants who were unexposed, presumably due to accelerated maturation of the skin. In vitro studies have demonstrated that glucocorticoid exposure results in maturation of ion channels in the proximal renal tubular epithelium, ^, and other reports have noted that accelerated renal maturation and upregulation of sodium-potassium ATPase (Na-K-ATPase) activity may be the mechanism by which glucocorticoid exposure prevents nonoliguric hyperkalemia.

Renal function

Neonatal renal function varies between patients and changes over time for each individual patient. Especially in the premature infant, the kidneys are developmentally immature and function improves with increasing GA. In addition, the postnatal hemodynamic changes that follow birth affect function, and these are impacted by GA and illness severity.

Developmental immaturity has greater impact in the more immature preterm infant, and it can result in water and electrolyte imbalance by impacting the GFR and the ability to concentrate urine. The balance between the reabsorption of sodium and bicarbonate and the secretion of potassium and hydrogen is also affected by the shorter length of renal tubules, and thus there is a greater risk of derangement in the levels of these critical electrolytes.

The newborn kidney is limited in the ability to create a medullary osmotic gradient needed for the concentration of urine, in part because of the anatomically shortened loop of Henle. This limits the countercurrent multiplication needed to form the osmotic gradient from the corticomedullary junction to the inner medulla. As a result, the maximum level of urine concentration is only 400 mOsmol/kg in the first few days after birth (and only about 300 mOsmol/kg in the premature infant), with maturation to 1200 mOsmol/kg at 1 year of age. The relatively low levels of sodium and protein in human milk and premature formula and the typically anabolic metabolic state result in lower concentration of osmolar molecules (e.g., urea) to be excreted, and the obligate urine volume is at least 50 mL/kg per day per risk for hypovolemia and hypernatremia. Fluid intake must be adequate to account for these renal losses as well as insensible losses noted previously.

The immature kidney also has a diminished response to antidiuretic hormone (ADH) because of immaturity and reduced surface area in the tubules and a lack of activation of ADH receptors. Water permeability in the collecting tubules is diminished, and as a result urine concentration is limited. Maturation of ADH response is, like most aspects, inversely related to GA.

In all infants the maturation of concentrating ability increases after birth, but the pace of this maturation is lower in infants of lower GA. Understanding these processes allows caregivers to assess the status of each individual patient and adjust the intake of water and electrolytes as needed.

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