9: Fluid and Electrolytes

An assessment of body water metabolism and electrolyte balance plays an important role in the early medical management of preterm infants and sick term infants coming to neonatal intensive care. Intravenous or intra-arterial fluids given during the first several days of life are a major factor in the development, or prevention, of morbidities such as intraventricular hemorrhage (IVH), necrotizing enterocolitis (NEC), patent ductus arteriosus (PDA), and bronchopulmonary dysplasia. Clinicians must pay close attention to the details of maintaining and monitoring body water and serum electrolytes, and the management of fluid infusion therapies.

Bodily fluid balance is a function of the distribution of water in the body, water intake, and water losses. Body water distribution gradually changes with increasing gestational age of the fetus. At birth these gestational changes in body water are reflected in the developing maturity of renal function, trans-epidermal insensible water losses, and neuroendocrine adaptations. One must account for these variables when deciding the amount of infusion fluids to administer to an infant.

1. Total body water (TBW). Water accounts for nearly 75% of the body weight in term infants and as much as 85–90% of body weight of preterm infants. TBW is divided into 2 basic body water compartments: intracellular water (ICW) and extracellular water (ECW). ECW is composed of intravascular and interstitial water. For the fetus there is a gradual decrease in ECW to 53% at 32 weeks' gestation and a gradual increase in ICW. Thereafter the proportions remain fairly constant until 38 weeks of gestation when increasing body mass of protein and fat stores reduce ECW further by ~5%.

   At birth there begins a further contraction of the ECW as a function of the normal transition from intrauterine to extra-uterine life. A diuresis occurs that reduces body weight proportionally to gestational age. For the very low birthweight preterm infant body, weight losses of 10–15% can be expected, whereas full-term infants usually lose 5% of body weight. These losses are largely accounted for as water and, to a lesser extent, body fat stores.

2. TBW balance in the newborn

   1. Renal. Fetal urine flow steadily increases from 2–5 mL/h to 10–20 mL/h at 30 weeks' gestation. At term, fetal urine flow reaches 25–50 mL/h and then drops to 8–16 mL/h (1–3 mL/kg/h). These volume changes illustrate the large exchange of body water during fetal life and the abrupt changes forcing physiologic adaptation at birth. Despite marked fetal urine flow in utero, glomerular filtration rates (GFRs) are low. At birth, GFR remains low but steadily increases in the newborn period under the influence of increasing systolic blood pressure, increasing renal blood flow, and increasing glomerular permeability. Infant kidneys are able to produce dilute urine within limits dependent on GFR. The low GFR of preterm infants is the result of low renal blood flow but increases considerably after 34 weeks' postconceptional age. Term infants can concentrate urine up to 800 mOsm/L compared to the 1500 mOsm/L of older children and adults. The preterm infant kidney is less able to concentrate urine secondary to a relatively low interstitial urea concentration, an anatomically shorter loop of Henle, and a distal tubular and collecting system that is less responsive to antidiuretic hormone (ADH). In extreme prematurity, urine osmolarity can be as low as 70 mOsm/L. Although limitations exist, healthy preterm infants with constant sodium intake but variable fluid infusion between 90 and 200 mL/kg/d are able to concentrate or dilute urine to maintain a balance of body water.

      Against the backdrop of changing GFR and variable urine concentrating ability, all infants undergo a diuresis and a natriuresis in the days immediately following birth. Newborn diuresis is a contraction of the ECW and the initiation of body water conservation as the adaptation from an aquatic intrauterine existence to the less humidity and free water-dependent newborn state. The diuresis is facilitated by limited ADH responsiveness but is diminished by increasing serum osmolality (>285 mOsm/kg) and decreasing intravascular volume. Natriuresis is the result of increasing levels of atrial natriuretic peptide and decreased renal sodium absorption; infant kidneys also have decreased secretion of bicarbonate, potassium, and hydrogen ion.

   2. Insensible water loss (IWL). Evaporation of body water occurs largely through the skin and mucous membranes (two-thirds) and the respiratory tract (one-third). A most important variable influencing IWL is the maturity of the infants' skin. The greater IWL in preterm infants results from body water evaporation through an immature epithelial layer. The stratum corneum is not well developed until 34 weeks' gestation. Throughout the third trimester the stratum corneum and epidermis thicken. Keratinization of the stratum corneum forms the principal barrier to water loss. Keratinization begins early in the second trimester and continues throughout the third trimester. Additionally, IWL is related to a larger skin surface area–to–body weight ratio in preterm infants and relatively greater skin vascularity.

      IWL through the respiratory tract is related to the respiratory rate and the water content of the inspired air or air-oxygen mix (humidification). Table 9–1 lists other factors for IWL in newborn infants.

      In general, for healthy premature infants weighing 800–2000 g cared for in double-walled incubators, IWL increases linearly as body weight decreases (Table 9–2).

      However, for sick infants of similar weight cared for under a radiant warmer and undergoing ventilator respiratory support, IWL increases exponentially as body weight decreases.

      Phototherapy may increase IWL by way of increasing body temperature and increasing peripheral blood flow. Generally, recommended fluid increases for preterm infants have been 10–20 mL/kg/d. This may not be necessary with newer phototherapy lights using light emitting diodes (LEDs) because they generate very little heat. Moreover, term infants receiving adequate fluid intake and with no other increased body water loss may not need added fluid intake. Occasionally, phototherapy induces loose stools and IWL would need to be reconsidered.

   3. Neuroendocrine. TBW balance is also influenced by hypothalamic osmo-receptors and carotid baroreceptors. Serum osmolarity >285 mOsm/kg stimulates the hypothalamus and ADH is released to affect free water retention. Additionally, volume diminution affects carotid bodies and baroreceptors to further stimulate ADH secretion to retain free water at the level of the collecting ducts of the distal nephrons. Collectively the osmo-receptors and the baroreceptors seek to maintain TBW with adequate intravascular volume at normal serum osmolarity. In the neonate, hypoxia with acidemia and hypercarbia are potent stimulators of ADH. An excessive secretion of ADH can follow one or more insults such as intracranial hemorrhage, sepsis, and/or hypotension. Conversely, excessive ADH secretion can occur in the absence of hyperosmolarity or volume depletion. Thus a phenomenon known as the syndrome of inappropriate ADH secretion (SIADH) can occur. It is manifested as hyponatremia, hypo-osmolar serum, dilute urine, and low blood urea nitrogen. Because ADH secretion begins early in fetal development, SIADH can occur as readily in preterm infants as in term infants.

3. Monitoring TBW balance

   1. Body weight. Using in-bed scales, body weight should be recorded daily for all infants undergoing intensive care, and twice daily for very low birthweight and extremely low birthweight infants. Expected weight loss during the first 3–5 days of life is 5–10% of birthweight for term infants and 10–15% of birthweight for preterm infants. A loss of >15% of birthweight during the first week of life should be considered excessive and body water balance carefully reevaluated. If weight loss is <2% in the first week of life, maintenance infusion fluid administration may be excessive.

   2. Physical examination. Edema or loss of skin turgor, moist or dry mucous membranes, sunken or puffy periorbital tissues, and full or sunken anterior fontanel have been time-honored sites to examine for dehydration or overhydration. They may be helpful when observing newborn infants but are unreliable in low birthweight infants. They must be observed within the context of all other TBW points of monitoring.

   3. Vital signs

      1. Blood pressure can be an indicator of altered intravascular volume, but usually is later rather than earlier. Pressure changes and trends are needed in the overall assessment of TBW balance.

      2. Pulse volumes, decreased in dehydration with tachycardia, are somewhat sensitive indicators of early intravascular volume loss.

      3. Tachypnea can be an early sign of metabolic acidosis accompanying inadequate intravascular volume.

      4. Capillary refill time (CRT) has been a reliable and time-honored observation. CRT of >3 seconds in term infants is suspect for decreased intravascular volume, whereas a CRT of barely 3 seconds in a preterm infant should be equally suspected.

   4. Hematocrit (Hct). Increases or decreases of central Hct (venous or arterial) from accepted normal values suggest changes in intravascular volume as it relates to TBW. Apart from obvious hemorrhage, changes in Hct may reflect overhydration or dehydration and must be considered in the assessment of TBW for fluid therapy in the first week of life.

   5. Serum chemistries

      1. Sodium values of 135–140 mEq/L are indicative of TBW and sodium balance. Values above or below are suggestive of hyper- or hypo-osmolarity. A sodium value of ≤130 mEq/L strongly suggests that SIADH may be a factor.

      2. Serum osmolarity of 285 mOsm/L (±3 mOsm) is the standard for TBW balance; values above or below must be considered indicative of over- or underhydration. If serum osmolarity is <280 mOsm/L, SIADH must also be considered in any preterm or sick full-term infant.

   6. Acid-base status

      1. Hydrogen ion (pH). A less than normal pH (7.28–7.35) is indicative of metabolic acidosis and will be accompanied by other factors, suggesting a contracted intravascular volume and hyperosmolarity.

      2. Base deficit. An increasing base deficit (ie, metabolic acidosis with deficit >5.0) with decreased urine output, decreased blood pressure, and a prolonged CRT strongly suggests hypovolemia.

      3. Chloride ion, carbon dioxide (CO₂) content, and bicarbonate (HCO₃). These determinations are important for calculating anion gap and overall acid-base status.

      4. Anion gap. The anion gap is a unifying determination for identifying metabolic acidosis in the face of dehydration. It is the sum of the serum sodium and potassium ions minus the sum of the serum chloride and bicarbonate ions. The normal range for anion gap is 8–16. Values for an anion gap >16 are indicative of an organic acidemia. In the face of dehydration with decreased intravascular volume, lactic acidemia follows poor tissue perfusion and is reflected as a widening anion gap. See Chapter 46.

   7. Urine

      1. Urine output should be 1–3 mL/kg/h by the third day of life in all newborn infants with normal kidneys. Preterm infants have limited urine formation on day 1 of life, but should begin to increase urine production throughout day 2.

      2. Urine specific gravity of 1.005–1.012 is consistent with TBW balance.

      3. Urine electrolytes and urine osmolarity offer additional information as to renal concentrating ability. Term infants can concentrate urine to 800 mOsm/kg, whereas preterm infants are limited to 600 mOsm/kg.

4. Maintenance of TBW. Infusion fluid therapy for newborn infants (term and preterm) must be calculated to allow for normal ECW losses and body weight losses while avoiding dehydration from excessive IWL. The consequences of dehydration are hypotension, hypernatremia, and acidosis. Conversely, excessive infusion fluid therapy is associated with clinically significant patent ductus arteriosus and may aggravate respiratory distress. Given careful monitoring for TBW as detailed earlier, the following infusion fluid therapy guidelines are offered for maintenance of TBW balance in term and preterm infants (with the exception of infusion fluid therapy for extremely low birthweight infants; see Chapter 12).

   1. Term infants in need of infusion fluid therapy

      1. Day 1. Give dextrose 10% in water (D10W) at a rate of 60–80 mL/kg/d. This provides 6–7 mg/kg/min of glucose in support of energy needs while providing limited hydration during the immediate postnatal adaptation period. Neither sodium nor potassium supplementation are needed unless unusual body fluid losses are known.

      2. Days 2–7. Once tolerance of infusion fluid therapy has been established and confirmed by TBW monitoring (eg, urine output of 1–2 mL/kg/h), the rate and composition of fluid therapy can be modified. The goals of infusion fluid therapy include expected weight loss of 5% body weight, confirmed normal serum electrolyte values, and continued urine output of 2–3 mL/kg/h. Specifics of fluid therapy are as follows:

         1. Infusion fluid volume 80–120 mL/kg/d. May increase to 120–160 mL/kg/d by week's end as tolerated, or to meet needs per monitoring.

         2. Glucose to be provided to maintain serum glucose values >60 mg/dL; may increase to 8–9 mg/kg/min infusion as D10W or D12.5W.

         3. Sodium requirement daily is 2–4 mEq/kg/d per monitoring of serum (target values, 135–140 mEq/L).

         4. Potassium daily requirements are 1–2 mEq/kg/d per monitoring of serum (target values, 4.0–5.0 mEq/L). Potassium supplementation is not begun until the second or third day, and only when normal renal function is confirmed by adequate urine output and normal serum electrolyte values have been established.

         5. Nutrition. Infusion fluid glucose does not meet all energy needs for basal metabolism, growth, and activity. Enteral feeds must be started as soon as possible; however, if the patient is unable to take formula by mouth or only in limited amount then total parenteral nutrition (TPN) becomes necessary. As enteral feeds increase, infusion fluids or TPN can be progressively decreased, but keeping total volume intake at 120–160 mL/kg/d.

   2. Preterm infants

      1. Day 1. During the immediate postnatal period, critically ill premature infants may require volume resuscitation for shock or acidosis. Fluids administered during stabilization should be considered when planning subsequent fluid management.

      2. Days 1–3. Infusion fluid therapy is aimed at allowing a 10–15% body weight loss through the first week while maintaining TBW balance and electrolyte balance.

         1. Infusion fluid volumes. Preterm low birthweight infants (>1500 g) require 60–80 mL/kg/d. Preterm very low birthweight infants (1000–1500 g) require 80–100 mL/kg/d. Preterm extremely low birthweight infants (<1000 g) require a range of fluid volumes from 50–80 mL/kg/d if cared for in double-walled humidified (80%) incubators. If cared for under a radiant warmer or in incubators without humidity, fluid requirements may be 100–200 mL/kg/d (see Table 12–1 for breakdown into 100-g birthweight increments).

         2. Glucose supplementation. Best achieved by using D5W or D7.5W infusion fluids to avoid hyperglycemia. Because of the high fluid requirements in the smallest infants, glucose utilization may not be sufficient to prevent buildup of serum glucose and a hyperosmolar state secondary to hyperglycemia. If allowable, reduced glucose maintenance is preferred, but extremes of hyperglycemia (>150 mg/dL) may require insulin therapy.

         3. Sodium. During the first week of life, fluid therapy should be managed by increments or decrements of 20–40/mL/kg/d depending on weight changes and serum sodium values, while attempting to keep serum sodium at 135–140 mEq/L. Sodium supplementation is not usually required in the first 2–3 days of life. Sodium supplementation is begun on the basis of body weight losses (postnatal isotonic contraction of ECW compartment, a physiologic diuresis). Usually by day 3–5, weight loss and a slight serum sodium decrease from baseline dictate the need to start sodium supplementation by way of the infusion fluids. Judicious restriction of sodium intake during the first 3–5 days of life facilitates a trend for normal serum osmolarity throughout the first week of life for preterm infants.

         4. Potassium. Supplementation follows that of term infants, meaning that well-established renal function with good urine output is required before supplementation at 1–2 mEq/kg/d.

         5. Nutrition. Caloric needs to provide for the relative hypermetabolic state of low birthweight infants can be met through TPN fluid therapy. Initiation of TPN after the first 24 hours of life is desirable (see Chapters 10 and 12).

      3. Days 3–7. Infusion fluid and electrolyte management is dictated by the monitoring parameters as already given. Infusion fluids should be advanced or decreased as the transition period progresses. Excessive weight loss suggests increased IWL losses and the threat of dehydration. Likewise, edema and minimal or no weight loss suggests excessive fluid administration or decreasing renal function and decreased urine output. All preterm infants should be cared for whenever possible in double-walled incubators for a more stable humidity control and less IWL.

   3. Other infusion fluid calculations and considerations

      1. Environmental

         1. Radiant warmers. Infusion fluid volume recommendations as outlined earlier are for assumed double-walled incubator care. If radiant warmer exposure is to be maintained, fluid therapy must be increased by 50–100%. Plastic sheeting limits increased needs to 30–50%.

         2. Phototherapy. If infant is full term, increased fluid therapy may not be needed. If infant is low birthweight, most likely 10–20 mL/kg/d will be needed to minimize IWL while phototherapy lights are in use.

      2. Glucose. The normal glucose requirement is 6–8 mg/kg/min, and intake can be slowly increased to 10–12 mg/kg/min as needed, but with careful monitoring for hyperglycemia and glucosuria to avoid an osmotic diuresis. Calculations for glucose supplementation are

         

         An alternate method is

         

      3. Sodium. The normal sodium requirement for infants is 2–3 mEq/kg/d. The following calculations can be used to determine the amount of sodium (Na⁺) per day that an infant will receive from a given saline infusion fluid:

         

      4. Potassium. The normal potassium requirement for infants is 1–2 mEq/kg/d. Potassium supplementation should not begin until adequate urine output is established.

1. Sodium. Serum values of 135–145 mEq/L represent homeostatic sodium balance. The wide range of 131–149 mEq/L is the lower and upper limit for sodium (Na⁺) balance. Values above or below are clinical indicators of either hyper- or hyponatremia.

   1. Hypernatremia

      1. Decreased ECW with Na⁺ of ≥150 mEq/L

         1. Causes. Include increased renal free water losses and/or increased IWL, primarily through skin, especially very low birthweight and extremely low birthweight infants.

         2. Clinical findings. Weight loss, low blood pressure, tachycardia, decreased or absent urine output, and increased urine specific gravity.

         3. Treatment. Requires careful infusion fluid management. Replacing free water is the first goal, and maintaining Na⁺ balance is the second goal. Both goals need to be accomplished without precipitating rapid ICW and ECW shifts of water or sodium, especially within the central nervous system (CNS). Excessively rapid correction of hypernatremia can result in seizures. Hypernatremic dehydration does not represent a deficit of body sodium. Infusion therapy should be guided to reduce serum Na⁺ by not more than 0.5 mEq/L/kg/h, or less, with a target of total correction time of 24–48 hours. Consider using D5W 0.25 normal saline (NS) as an initial infusion fluid for correction.

      2. Increased ECW and hypernatremia

         1. Causes. Include excessive administration of normal saline or sodium bicarbonate as in resuscitation efforts or postresuscitation treatment for perinatal asphyxia with metabolic acidosis and hypotension.

         2. Clinical findings. Increased weight gain and edema. If cardiac output has been compromised, findings of edema and weight gain increase. Depending on cardiac status, heart rate, blood pressure, and urine output will be within normal limits or decreased.

         3. Treatment. Involves identification of cardiac status. Identify infusion fluid excesses and establish maintenance infusion fluid limits; thereafter, restrict sodium until serum Na⁺ values return to normal range.

   2. Hyponatremia. See also Chapter 64.

      1. Increased ECW as increased intravascular water and increased third space interstitial water

         1. Causes. Increased ECW with serum Na⁺ <130 mEq/L, which most likely represents excessive infusion fluid administration, and increased third space (interstitial) water secondary to sepsis, shock, and capillary leakage. It may also be secondary to cardiac failure or pharmacologic neuromuscular paralysis during mechanical ventilation. More frequently it occurs in newborn infants as SIADH following CNS trauma, intracranial hemorrhage, meningitis, perinatal asphyxia, or pneumothorax.

         2. Clinical findings. Result from inadvertent excessive infusion fluid administration: body weight is increased with edema, serum Na⁺ is decreased, and urine output is increased with decreased urine osmolarity and specific gravity. Conversely, if SIADH is the root cause of increased ECW and hyponatremia, the clinical findings reveal increased body weight, variable presence of edema, decreased serum Na⁺, decreased urine output, and increased urine specific gravity. Some cases of SIADH do not reflect increased ECW but rather manifest simply as hyponatremia with decreased urine output and urine specific gravity.

         3. Treatment. In both situations is free water restriction allowing serum Na⁺ to concentrate to normal levels. If serum Na⁺ is <120 mEq/L and neurologic symptoms are present, consider titrating with infusion of 3% saline solution boluses. Consultation by a nephrologist is recommended.

      2. Decreased ECW with hyponatremia

         1. Causes. Include excessive diuretic therapy, glycosuria with an osmotic diuresis, vomiting, diarrhea, and third space fluid with necrotizing enterocolitis.

         2. Clinical findings. Include decreased body weight, signs of dehydration with sunken fontanel, loss of skin turgor, dry mucous membranes, increased blood urea nitrogen (BUN), metabolic acidosis, decreased urine output, and increased urine specific gravity.

         3. Treatment. Involves replacing sodium and water while minimizing any ongoing sodium losses.

      3. Isotonic losses may occur and present as hyponatremia. Such losses may be cerebrospinal fluid from drainage procedures, thoracic as in chylothorax, nasogastric drainage, or peritoneal fluid (ascites).

         Normal saline for fluid replacement usually suffices, or normal saline plus colloid as fresh-frozen plasma or human albumin may facilitate intravascular volume and restore serum saline.

2. Potassium

   1. Hyperkalemia. Represented by serum K⁺ values >5.5 mEq/L. Some infants do not manifest symptoms until serum levels reach 7–8 mEq/L. Hyperkalemia can be caused by or related to renal failure, hemolysis, blood transfusions, exchange transfusions, or inadvertent excessive administration of a potassium solution (eg, KCl). Cardiac conduction is the most immediate concern, and electrocardiographic monitoring is essential until treatment corrects serum K⁺ levels. For a detailed discussion of hyperkalemia and treatment, see Chapter 60.

   2. Hypokalemia. Potassium levels <4.0 mEq/L suggest impending hypokalemia, and values <3.5 mEq/L require treatment to correct. Meanwhile, cardiac conduction abnormalities may occur, and monitoring electrocardiographically, as in hyperkalemia, is essential until hypokalemia is corrected. For a detailed discussion of hypokalemia and treatment, see Chapter 63.

3. Chloride. See also Chapter 46, section on metabolic alkalosis.

   1. Hypochloremia. Serum values of 97–110 mEq/L are taken as normal in most newborn infants. Serum values <97 mEq/L are indicative of low chloride and suggest either inadequate supplementation during infusion fluid therapy or, more commonly, chloride ion losses. Typically, chloride ion accompanies Na⁺ and K⁺ as NaCl or KCl solutions in maintenance infusion solutions. Chloride losses independent of Na⁺ or K⁺ occur usually from excessive gastrointestinal fluid losses, particularly gastric hydrochloric acid losses. Chloride losses lead to increased bicarbonate reabsorption and metabolic alkalosis.

   2. Hyperchloremia. Uncommon in the newborn period but may be found when inadvertent concentrations of Cl⁻ ion are given in parenteral nutrition solutions. Occasionally increased Cl⁻ ion is reflective of excessive renal conservation of Cl⁻ during correction of alkalosis when forming alkaline urine.