Fluid and Electrolyte Management Elizabeth G. Doherty Charles F. Simmons Jr.

Careful fluid and electrolyte management in term and preterm infants is an essential component of neonatal care. Developmental changes in body composition in conjunction with functional changes in skin, renal, and neuroendocrine systems account for the fluid balance challenges faced by neonatologists on a daily basis. Fluid management requires the understanding of several physiologic principles. I. DISTRIBUTION OF BODY WATER A. General principles. Transition from fetal to newborn life is associated with major changes in water and electrolyte homeostatic control. Before birth, the fetus has constant supply of water and electrolytes from the mother across the placenta. After birth, the newborn assumes responsibility for its own fluid and electrolyte homeostasis. The body composition of the fetus changes during gestation with a smaller proportion of body weight being composed of water as gestation progresses. B. Definitions Total body water (TBW) = intracellular fluid (ICF) + extracellular fluid (ECF) (see Fig. 9.1). ECF is composed of intravascular and interstitial fluid. Insensible water loss (IWL) = fluid intake urine output + weight change. C. Perinatal changes in TBW. A proportion of diuresis in both term and preterm infants during the first days of life should be regarded as physiologic. This diuresis results in a weight loss of 5% to 10% in term infants and up to 15% in preterm infants. At lower gestational ages, ECF accounts for a greater proportion of birth weight (Fig. 9.1). Therefore, very low birth weight (VLBW) infants must lose a greater percentage of birth weight to maintain ECF proportions equivalent to those of term infants. Larger weight loss is possibly beneficial to the preterm infant, as administration of excessive fluid and Na may increase risk of chronic lung disease (CLD) and patent ductus arteriosus (PDA). D. Sources of water loss 1. Renal losses. Renal function matures with increasing gestational age (GA). Immature Na and water homeostasis is common in the preterm infant. Contributing factors leading to varying urinary water and electrolyte losses include the following: a. Decreased glomerular filtration rate (GFR).

b. Reduced proximal and distal tubule Na reabsorption. c. Decreased capacity to concentrate or dilute urine. d. Decreased bicarbonate and potassium (K) and hydrogen ion secretion. 2. Extra renal losses. In VLBW infants IWL can exceed 150 mL/kg/day owing to increased environmental and body temperatures, skin breakdown, radiant warmers, phototherapy, and extreme prematurity (see Table 9.1). Respiratory water loss increases with decreasing GA and with increasing respiratory rate; in intubated infants, inadequate humidification of the inspired gas may lead to increased IWL. Other fluid losses that should be replaced if amount is deemed significant include stool (diarrhea or ostomy drainage), cerebrospinal fluid (from ventriculotomy or serial lumbar punctures), and nasogastric tube or thoracostomy tube drainage.

Figure 9.1. Body composition in relation to fetal weight and gestational age. (From Dweck HS. Feeding the prematurely born infant. Fluids, calories, and methods of feeding during the period of extrauterine growth retardation. Clin Perinatol 1975;2:183. Data from Widdowson EM. Growth and composition of the fetus and newborn. In: Assali NS, ed. Biology of gestation, Vol. 2. New York: Academic Press, 1968). Incubators for newborn infants are being designed to improve maintenance of warmth and humidity and may lead to decreased IWL (e.g., the Giraffe Isolette). II. ASSESSMENT OF FLUID AND ELECTROLYTE STATUS A. History 1. Maternal. The newborn's fluid and electrolyte status partially reflects maternal hydration status and drug administration. Excessive use of oxytocin, diuretics, or hyponatremic intravenous (IV)

fluid can lead to maternal and fetal hyponatremia. Antenatal steroids may increase skin maturation, subsequently decreasing IWL and the risk of hyperkalemia. 2. Fetal/perinatal. The presence of oligohydramnios may be associated with congenital renal dysfunction, including renal agenesis, polycystic kidney disease, or posterior urethral valves. Severe in utero hypoxemia or birth asphyxia may lead to acute tubular necrosis.

* Values represent mean IWL for infants in incubators during the first week of life. IWL is increased by phototherapy (up to 40%), radiant warmers (up to 50%), and fever. IWL is decreased by the use of humidified gas with respirators and heat shields in incubators Bell et al. 1980, Bell et al. 1980, Fanaroff et al. 1972 and Okken et al. 1979. B. Physical examination 1. Change in body weight. Acute changes in an infant's weight generally reflect a change in TBW. The compartment affected will depend on the gestational age and clinical course of the infant. For example, long-term use of paralytic agents and peritonitis may lead to increased interstitial fluid volume and increased body weight but decreased intravascular volume. Therefore, weight should be measured at least daily. 2. Skin and mucosal manifestations. Altered skin turgor, sunken anterior fontanelle, and dry mucous membranes are not sensitive indicators of fluid or electrolyte balance. 3. Cardiovascular. Tachycardia can result from ECF excess (e.g., heart failure) or hypovolemia. Capillary refill time can be delayed with reduced cardiac output or peripheral vasoconstriction and hepatomegaly can occur with increased ECF volume. Blood pressure changes occur late in the sequence of responses to reduced cardiac output.

C. Laboratory studies 1. Serum electrolytes and plasma osmolarity reflect the composition and tonicity of the ECF. Frequent monitoring, every 4 to 6 hours, should be done in the extremely low birth weight (ELBW) infants during the first few days of life owing to high IWL. 2. Fluid balance with input and output measurements should be monitored. Normal urine output is 1 to 3 mL/kg/hour. With ECF depletion (dehydration), urine output may fall to <1 mL/kg/hour. However, in neonates with immature renal function, urine output may not decrease despite ECF volume depletion. 3. Urine electrolytes and specific gravity (SG) can reflect renal capacity to concentrate or dilute urine and reabsorb or excrete Na. Increases in SG can occur when the infant is receiving decreased fluids, has decreased urine output, or is spilling glucose. Neither urine electrolytes nor SG is very helpful when infant is on diuretics. 4. Fractional excretion of Na (FE-Na) reflects the balance between glomerular filtration and tubular reabsorption of Na. FE-Na = (urine Na plasma creatinine)/(plasma Na urine creatinine) 100 Level of <1% indicates prerenal factors reducing renal blood flow. Level of 2.5% occurs with acute renal failure (ARF). Level of >2.5% is frequently seen in infants of <32 weeks' gestation. 5. Blood urea nitrogen (BUN) and serum Cr values provide indirect information about ECF volume and GFR. Values in the early postnatal period reflect placental clearance. 6. Arterial pH, carbon dioxide tension (Pco2), and Na bicarbonatedeterminations can provide indirect evidence of intravascular volume depletion because poor tissue perfusion leads to highanion-gap metabolic acidosis (lactic acidosis). III. MANAGEMENT OF FLUIDS AND ELECTROLYTES. The goal of early management is to allow initial ECF loss over the first 5 to 6 days as reflected by weight loss, while maintaining normal tonicity and intravascular volume as reflected by blood pressure, heart rate, urine output, serum electrolyte levels, and pH. Subsequent fluid management should maintain water and electrolyte balance, including requirements for body growth. A. The term infant. Body weight decreases by 3% to 5% over the first 5 to 6 days. Subsequently, fluids should be adjusted so that changes in body weight are consistent with caloric intake. Clinical status should be monitored for maldistribution of water (e.g., edema). Na supplementation is not usually

required in the first 24 hours unless ECF expansion is necessary. Small-for-gestational-age term infants may require early Na supplementation to maintain adequate ECF volume.

*Infants in humidified incubators. Infants under radiant warmers usually require higher initial fluid rates. Very low birth weight (VLBW) infants frequently require even higher initial rates of fluid administration, and frequent reassessment of serum electrolytes, urine output, and body weight. B. The premature infant. Allow a 5% to 15% weight loss over the first 5 to 6 days. Table 9.2 summarizes initial fluid therapy. Then, adjust fluids to maintain stable weight until an anabolic state is achieved and growth occurs. Frequently assess response to fluid and electrolyte therapy during the first 2 days of life. Physical examination and urine output and SG and serum electrolyte determinations may be required initially as frequently as every 6 to 8 hours in infants <1,000 g (see VIII.A). Water loss through skin and urine may exceed 200 mL/kg/day, which can represent up to onethird of TBW. IV Na supplementation is not required for the first 24 hours unless ECF volume loss exceeds 5% of body weight/day (see Chap. 6). If ECF volume expansion is necessary, normal saline (NS) is preferred over 5% albumin solutions in order to reduce risk of CLD. IV. APPROACH TO DISORDERS OF NA AND WATER BALANCE. Abnormalities can be grouped into disorders of tonicity or ECF volume. The conceptual approach to disorders of tonicity (e.g., hyponatremia) depends on whether the newborn exhibits normal ECF (euvolemia), ECF depletion (dehydration), or ECF excess (edema).

A. Isonatremic disorders 1. Dehydration a. Predisposing factors frequently involve equivalent losses of Na and water (through thoracostomy, nasogastric, or ventriculostomy drainage) or third-space losses that accompany peritonitis, gastroschisis, or omphalocele. Renal Na and water losses in the VLBW infant can lead to hypovolemia despite normal body tonicity. b. Diagnosis. Dehydration is usually manifested by weight loss, decreased urine output, and increased urine SG. However, infants of <32 weeks' gestation may not demonstrate oliguria in response to hypovolemia. Poor skin turgor, tachycardia, hypotension, metabolic acidosis, and increasing BUN may coexist. A low FE-Na (<1%) is usually only seen in infants of >32 weeks' gestational age (see II.C.4). c. Therapy. Administer Na and water to first correct deficits and then adjust to equal maintenance needs plus ongoing losses. Acute isonatremic dehydration may require IV infusion of 10 mL/kg of NS if acute weight loss is >10% of body weight with signs of poor cardiac output. 2. Edema a. Predisposing factors include excessive isotonic fluid administration, heart failure, sepsis, and neuromuscular paralysis. b. Diagnosis. Clinical signs include periorbital and extremity edema, increased weight, and hepatomegaly. c. Therapy includes Na restriction (to decrease total-body Na) and water restriction (depending on electrolyte response). B. Hyponatremic disorders (see Table 9.3). Consider factitious hyponatremia due to hyperlipidemia or hypoosmolar hyponatremia due to osmotic agents. True hyposmolar hyponatremia can then be evaluated. 1. Hyponatremia due to ECF volume depletion a. Predisposing factors include diuretic use, osmotic diuresis (glycosuria), VLBW with renal water and Na wasting, adrenal or renal tubular salt-losing disorders, gastrointestinal losses (vomiting, diarrhea), and third-space losses of ECF (skin sloughing, early necrotizing enterocolitis [NEC]). b. Diagnosis. Decreased weight, poor skin turgor, tachycardia, rising BUN, and metabolic acidosis are frequently observed. If renal function is mature, the newborn may develop decreased urine output, increased urine SG, and a low FE-Na. c. Therapy. If possible, reduce ongoing Na loss. Administer Na and water to replace deficits and then adjust to match maintenance needs plus ongoing losses.

2. Hyponatremia with normal ECF volume a. Predisposing factors include excess fluid administration and the syndrome of inappropriate antidiuretic hormone (SIADH) secretion. Factors that cause SIADH include pain, opiate administration, intraventricular hemorrhage (IVH), asphyxia, meningitis, pneumothorax, and positive-pressure ventilation. Diagnosis of SIADH. Weight gain usually occurs without edema. Excessive fluid administration without SIADH results in low urine SG and high urine output. In contrast, SIADH leads to decreased urine output and increased urine osmolarity. Urinary Na excretion in infants with SIADH varies widely and reflects Na intake. The diagnosis of SIADH presumes no volume-related stimulus to antidiuretic hormone (ADH) release, such as reduced cardiac output or abnormal renal, adrenal, or thyroid function. c. Therapy. Water restriction is therapeutic unless (i) serum Na concentration is less than approximately 120 mEq/L or (ii) neurologic signs such as obtundation or seizure activity develop. In these instances, furosemide 1 mg/kg IV q6h can be initiated while replacing urinary Na excretion with hypertonic NaCI (3%) (1-3 mL/kg initial dose). This strategy leads to loss of free water with no net change in total-body Na. Fluid restriction alone can be utilized once serum Na concentration is >120 mEq/L and neurologic signs abate. 3. Hyponatremia due to ECF volume excess a. Predisposing factors include sepsis with decreased cardiac output, late NEC, heart failure, abnormal lymphatic drainage, and neuromuscular paralysis. b. Diagnosis. Weight increase with edema is observed. Decreasing urine output, increasing BUN and urine SG, and a low FE-Na are often present in infants with mature renal function. c. Therapy. Treat the underlying disorder and restrict water to alleviate hypotonicity. Na restriction and improving cardiac output may be beneficial. C. Hypernatremic disorders 1. Hypernatremia with normal or deficient ECF volume a. Predisposing factors include increased renal and IWL in VLBW infants. Skin sloughing can accelerate water loss. ADH deficiency secondary to IVH can occasionally exacerbate renal water loss. b. Diagnosis. Weight loss, tachycardia and hypotension, metabolic acidosis, decreasing urine output, and increasing urine SG may occur. Urine may be dilute if the newborn exhibits central or nephrogenic diabetes insipidus. c. Therapy. Increase free water administration to reduce serum Na no faster than 1 mEq/kg/hour. If signs of ECF depletion or excess develop, adjust Na intake. Hypernatremia does not necessarily imply excess total-body Na. For example, in the VLBW infant, hypernatremia in the first 24 hours of life is almost always due to free water deficits (see VIII.A.1).

2. Hypernatremia with ECF volume excess a. Predisposing factors include excessive isotonic or hypertonic fluid administration, especially in the face of reduced cardiac output. b. Diagnosis Weight gain associated with edema is observed. The infant may exhibit normal heart rate, blood pressure, and urine output and SG, but an elevated FE-Na. c. Therapy. Restrict Na administration. V. OLIGURIA exists if urine flow is <1 mL/kg/hour. Although delayed micturition in a healthy infant is not of concern until 24 hours after birth, urine output in a critically ill infant should be assessed by 8 to 12 hours of life, using urethral catheterization if indicated. Diminished urine output may reflect abnormal prerenal, renal parenchymal, or postrenal factors (see Table 9.4). The most common causes of neonatal ARF are asphyxia, sepsis, and severe respiratory illness. It is important to exclude other potentially treatable etiologies (see Chap. 31). In VLBW infants oliguria may be normal in the first 24 hours of life (see VIII.A.1). A. History and physical examination. Screen the maternal and infant history for maternal diabetes (renal vein thrombosis), birth asphyxia (acute tubular necrosis), and oligohydramnios (Potter syndrome). Force of the infant's urinary stream (posterior urethral valves), rate and nature of fluid administration and urine output, and nephrotoxic drug use (aminoglycosides, indomethacin, furosemide) should be evaluated. Physical examination should determine blood pressure and ECF volume status; evidence of cardiac disease, abdominal masses, or ascites; and the presence of any congenital anomalies associated with renal abnormalities (e.g., Potter syndrome, epispadias).

B. Diagnosis 1. Initial laboratory examination should include urinalysis, BUN, Cr, and FE-Na determinations. These aid in diagnosis and provide baseline values for further management. 2. Fluid challenge consisting of a total of 20 mL/kg of NS, is administered as two infusions at 10 mL/kg/hour if no suspicion of structural heart disease or heart failure exists. Decreased cardiac output not responsive to ECF expansion may require the institution of inotropic/chronotropic pressor agents. Dopamine at a dose of 1 to 5 g/kg/minute may increase renal blood flow and a dose of 2 to 15 g/kg/minute may increase total cardiac output. These effects may augment GFR and urine output (see Chap. 17). 3. If no response to fluid challenge occurs one may induce diuresis with furosemide 2 mg/kg IV. 4. Patients who are unresponsive to increased cardiac output and diuresis should be evaluated with an abdominal ultrasonography to define renal, urethral, and bladder anatomy. IV pyelography, renal scanning, angiography, or cystourethrography may be required (see Chap. 31). C. Management. Prerenal oliguria should respond to increased cardiac output. Postrenal obstruction requires urologic consultation, with possible urinary diversion and surgical correction.

If parenchymal ARF is suspected, minimize excessive ECF expansion and electrolyte abnormalities. If possible, eliminate reversible causes of declining GFR, such as nephrotoxic drug use. 1. Monitor daily weight, input and output, and BUN, Cr, and serum electrolytes. 2. Fluid restriction. Replace insensible fluid loss plus urine output. Withhold K supplementation unless hypokalemia develops. Replace urinary Na losses unless edema develops. 3. Adjust dosage and frequency of drugs eliminated by renal excretion. Monitor serum drug concentrations to guide drug-dosing intervals. 4. Peritoneal or hemodialysis may be indicated in patients whose GFR progressively declines causing complications related to ECF volume or electrolyte abnormalities (see Chap. 31). P.107VI. METABOLIC ACID-BASE DISORDERS A. Normal acid-base physiology. Metabolic acidosis results from excessive loss of buffer or from an increase of volatile or nonvolatile acid in the extracellular space. Normal sources of acid production include the metabolism of amino acids containing sulfur and phosphate, as well as hydrogen ion released from bone mineralization. Intravascular buffers include bicarbonate, phosphate, and intracellular hemoglobin. Maintenance of normal pH depends on excretion of volatile acid (e.g., carbonic acid) from the lungs, skeletal exchange of cations for hydrogen, and renal regeneration and reclamation of bicarbonate. Kidneys contribute to maintenance of acid-base balance by reabsorbing the filtered load of bicarbonate, secreting hydrogen ions as titratable acidity (e.g., H2PO4), and excreting ammonium ions. B. Metabolic acidosis (see Chap. 29D) 1. Anion gap. Metabolic acidosis can result from accumulation of acid or loss of buffering equivalents. Anion gap determination will suggest mechanism. Na, Cl, and bicarbonate are the primary ions of the extracellular space and exist in approximately electroneutral balance. The anion gap, calculated as the difference between the Na concentration and sum of the Cl and bicarbonate concentrations, reflects the unaccounted-for anion composition of the ECF. An increased anion gap indicates an accumulation of organic acid whereas a normal anion gap indicates a loss of buffer equivalents. Normal values for the neonatal anion gap are 5 to 15 mEq/L and vary directly with serum albumin concentration. 2. Metabolic acidosis associated with an increased anion gap (>15 mEq/L). Disorders (see Table 9.5) include renal failure, inborn errors of metabolism, lactic acidosis, late metabolic acidosis, and toxin exposure. Lactic acidosis results from diminished tissue perfusion and resultant anaerobic metabolism in infants with asphyxia or severe cardiorespiratory disease. Late metabolic acidosis typically occurs during the second or third week of life in premature infants who ingest high

casein-containing formulas. Metabolism of sulfurcontaining amino acids in casein and increased hydrogen ion release due to the rapid mineralization of bone cause an increased acid load. Subsequently, inadequate hydrogen ion excretion by the premature kidney results in acidosis. 3. Metabolic acidosis associated with a normal anion gap (<15 mEq/L) results from buffer loss through the renal or gastrointestinal systems (Table 9.5). Premature infants <32 weeks' gestation frequently manifest a proximal or distal renal tubular acidosis (RTA). Urine pH persistently >7 in an infant with metabolic acidosis suggests a distal RTA. Urinary pH <5 documents normal distal tubule hydrogen ion secretion but proximal tubular bicarbonate resorption could still be inadequate (proximal RTA). IV Na bicarbonate infusion in infants with proximal RTA will result in a urinary pH >7 before attaining a normal serum bicarbonate concentration (22-24 mEq/L). 4. Therapy. Whenever possible, treat the underlying cause. Lactic acidosis due to low cardiac output or due to decreased peripheral oxygen delivery should be treated with specific measures. The use of a low-casein formula may alleviate late metabolic acidosis. Treat normal anion gap metabolic acidosis by decreasing the rate of bicarbonate loss (e.g., decreased small-bowel drainage) or providing buffer equivalents. IV Na bicarbonate or Na acetate (which is compatible with Ca salts) is most commonly used to treat arterial pH <7.25. Oral buffer supplements can include citric acid (Bicitra) or Na citrate (1-3 mE/kg/day). Estimate bicarbonate deficit from the following formula: Deficit = 0.4 body weight (desired bicarbonateactual bicarbonate) The premature infant's acid-base status can change rapidly, and frequent monitoring is warranted. The infant's ability to tolerate an increased Na load and to metabolize acetate is an important variable that influences acid-base status during treatment. C. Metabolic alkalosis. The etiology of metabolic alkalosis can be clarified by determining urinary Cl concentration. Alkalosis accompanied by ECF depletion is associated with decreased urinary Cl, whereas states of mineralocorticoid excess are usually associated with increased urinary Cl (see Table 9.6). Treat the underlying disorder. VII. DISORDERS OF K BALANCE. K is the fundamental intracellular cation. Serum K concentrations do not necessarily reflect totalbody K because extracellular and intracellular K distribution also depends on the pH of body compartments. An increase of 0.1 pH unit in serum results in approximately a 0.6 mEq/L fall in serum K concentration due to an intracellular shift of K ions. Total-body K is regulated by balancing K intake (normally 1-2 mEq/kg/day) and excretion through urine and the gastrointestinal tract. A. Hypokalemia can lead to arrhythmias, ileus, renal concentrating defects, and obtundation in the newborn.

1. Predisposing factors include nasogastric or ileostomy drainage, chronic diuretic use, and renal tubular defects. 2. Diagnosis. Obtain serum and urine electrolytes, pH, and an electrocardiogram (ECG) to detect possible conduction defects (prolonged QT interval and U waves). 3. Therapy Reduce renal or gastrointestinal losses of K. Gradually increase intake of K as needed. P.109B. Hyperkalemia. The normal serum K level in a nonhemolyzed blood specimen at normal pH is 3.5 to 5.5 mEq/L; symptomatic hyperkalemia may begin at a serum K level >6 mEq/L. 1. Predisposing factors. Hyperkalemia can occur unexpectedly in any patient but should be anticipated and screened for in the following scenarios: a. Increased K release secondary to tissue destruction, trauma, cephalhe-matoma, hypothermia, bleeding, intravascular or extravascular hemolysis, asphyxia/ischemia, and IVH. b. Decreased K clearance due to renal failure, oliguria, hyponatremia, and congenital adrenal hyperplasia. c. Miscellaneous associations including dehydration, birth weight <1,500 g (see VIII.A.2), blood transfusion, inadvertent excess (KCl) administration, CLD with KCl supplementation, and exchange transfusion. d. Up to 50% of VLBW infants born before 25 weeks' gestation manifest serum K levels >6 mEq/L in the first 48 hours of life (see VIII.A.2). The most common cause of sudden unexpected hyperkalemia in the neonatal intensive care unit (NICU) is medication error. 2. Diagnosis. Obtain serum and urine electrolytes, serum pH, and Ca concentrations. The hyperkalemic infant may be asymptomatic or may present with a spectrum of signs including bradyarrhythmias or tachyarrhythmias, cardiovascular instability or collapse. The ECG findings progress with increasing serum K from peaked T waves (increased rate of repolarization), flattened P waves and increasing PR interval (suppression of atrial conductivity), to QRS widening and slurring (conduction delay in ventricular conduction tissue as well as in the myocardium itself), and finally supraventricular/ventricular tachycardia, bradycardia, or ventricular fibrillation. The ECG findings may be the first indication of hyperkalemia (see Chap. 25). Once hyperkalemia is diagnosed, remove all sources of exogenous K (change all IV solutions and analyze for K content, check all feedings for K content), rehydrate the patient if necessary, and eliminate arrhythmiapromoting factors. The pharmacologic therapy of neonatal hyperkalemia consists of three components: a. Goal 1: stabilization of conducting tissues. This can be accomplished by Na or Ca ion administration. Ca gluconate (10%) given carefully at 1 to 2 mL/kg IV (over 0.5-1 hour) may be the

most useful in the NICU. Treatment with hypertonic NaCl solution is not done routinely. However, if the patient is both hyperkalemic and hyponatremic, NS infusion may be beneficial. Use of antiarrhythmic agents such as lidocaine and bretylium should be considered for refractory ventricular tachycardia (see Chap. 25). b. Goal 2: dilution and intracellular shifting of K. Increased serum K in the setting of dehydration should respond to fluid resuscitation. Alkalemia will promote intracellular K-for-hydrogen-ion exchange. Na bicarbonate 1 to 2 mEq/kg/hour IV may be used, although the resultant pH change may not be sufficient to markedly shift K ions. Na treatment as described in goal 1 may be effective. In order to reduce risk of IVH, avoid rapid Na bicarbonate administration, especially in infants born before 34 weeks' gestation and younger than 3 days. Respiratory alkalosis may be produced in an intubated infant by hyperventilation, although the risk of hypocarbia-diminishing cerebral perfusion may make this option more suited to emergency situations. Theoretically, every 0.1 pH unit increase leads to a decrease of 0.6 mEq/L in serum K. Insulin enhances intracellular K uptake by direct stimulation of the membrane-bound Na-K ATPase. Insulin infusion with concomitant glucose administration to maintain normal blood glucose concentration is relatively safe as long as serum or blood glucose levels are frequently monitored. This therapy may begin with a bolus of insulin and glucose (0.05 unit/kg of human regular insulin with 2 mL/kg of dextrose 10% in water [D10W]) followed by continuous infusion of D10W at 2 to 4 mL/kg/hour and human regular insulin (10 units/100 mL) at 1 mL/kg/hour. To minimize the effect of binding to IV tubing, insulin diluted in D10W may be flushed through the tubing. Adjustments in infusion rate of either glucose or insulin in response to hyperglycemia or hypoglycemia may be simplified if the two solutions are prepared individually (see Chap. 29A). -2-Adrenergic stimulation enhances K uptake, probably through stimulation of the Na-K ATPase. The immaturity of the -receptor response in preterm infants may contribute to nonoliguric hyperkalemia in these patients (see VIII.A.2). To date, stimulation is not primary therapy for hyperkalemia in the pediatric population. However, if cardiac dysfunction and hypotension are present, use of dopamine or other adrenergic agents could, through -2 stimulation, lower serum K. c. Goal 3: enhanced K excretion. Diuretic therapy (e.g., furosemide 1 mg/kg IV) may increase K excretion by increasing flow and Na delivery to the distal tubules. In the clinical setting of inadequate urine output and reversible renal disease (e.g., indomethacin-induced oliguria), peritoneal dialysis and double volume exchange transfusion are potentially life-saving options. Peritoneal dialysis can be successful in infants weighing <1,000 g and should be considered if the patient's clinical status and etiology of hyperkalemia suggest a reasonable chance for good longterm outcome. Use fresh whole blood (<24 hours old) or deglycerolized red blood cells reconstituted with fresh-frozen plasma for double volume exchange transfusion. Aged, banked blood may have K levels as high as 10 to 12 mEq/L; aged, washed packed red blood cells will have low K levels (see Chap. 26E).

Enhanced K excretion using cation exchange resins such as Na or Ca polystyrene sulfonate has been studied primarily in adults. The resins can be administered orally per gavage (PG) or rectally. A study involving uremic and control rats demonstrated that Na polystyrene sulfonate (Kayexalate) administered by rectum with sorbitol was toxic to the colon, but rectal administration after suspension in distilled water produced only mild mucosal erythema in 10% of animals. Another possible complication of resins is bowel obstruction secondary to bezoar or plug formation. The reported experience with resin use in neonates covers those born at 25 to 40 weeks' gestation. PG administration of Kayexalate is not recommended in preterm infants because they are prone to hypomotility and are at risk for NEC. Rectal administration of Kayexalate (1 g/kg at 0.5 g/mL of NS) with a minimum retention time of 30 minutes should be effective in lowering serum K levels by approximately 1 mEq/L. The enema should be inserted 1 to 3 cm using a thin silastic feeding tube. Published evidence supports the efficacy of this treatment in infants. Kayexalate prepared in water or NS (eliminating sorbitol as a solubilizing agent) and delivered rectally should be a therapeutic agent with an acceptable risk-benefit ratio. The clinical condition, ECG, and actual serum K level all affect the choice of therapy for hyperkalemia. Figure 9.2 contains guidelines for treatment of hyperkalemia. VIII. COMMON CLINICAL SITUATIONS A. VLBW infant 1. VLBW infants undergo three phases of fluid and electrolyte homeostasis prediuretic (first day of life), diuretic (second to third day of life), and postdiuretic (fourth to fifth day of life). Marked diuresis and natriuresis can occur during the diuretic phase leading to hypernatremia and the need for frequent serum electrolyte determinations (q6-8h) and increased rates of parenteral fluid administration. Increased free water loss through skin and dopamine-associated natriuresis (due to increased GFR) can further complicate management. Hypernatremia often occurs despite a total-body Na deficit. Lack of a brisk diuretic phase has been associated with increased CLD incidence. In addition, impaired glucose tolerance can lead to hyperglycemia, requiring reduced rates of parenteral glucose infusion (see Chap. 29A). This combination frequently leads to administration of reduced dextrose concentrations (<5%) in parenteral solutions. Avoid the infusion of parenteral solutions containing <200 mOsmol/L (i.e., D3W), to minimize local osmotic hemolysis and thereby reduce renal K load. 2. VLBW infants often develop a nonoliguric hyperkalemia in the first few days of life. This is caused by a relatively low GFR combined with an intracellular to extracellular K shift due to decreased Na, K ATPase activity. Postnatal glucocorticoid use may further inhibit Na, K ATPase activity. Insulin infusion to treat hyperkalemia may be necessary but elevates the risk of iatrogenic hypoglycemia. Treatment with Kayexalate (see VII.B.2.c) can occasionally be beneficial in infants

born before 32 weeks' gestation despite the obligate Na load and potential irritation of bowel mucosa by rectal administration. Na restriction can reduce the risk of CLD. 3. Late-onset hyponatremia of prematurity often occurs 6 to 8 weeks postnatally in the growing premature infant. Failure of the immature renal tubules to reabsorb filtered Na in a rapidly growing infant often causes this condition. Other contributing factors include the low Na content in breast milk and diuretic therapy for CLD. Infants at risk should be monitored with periodic electrolytes measurements and if affected, treated with simple Na supplementation (start with 2 mEq/kg/day). B. Severe chronic lung disease (CLD) (see Chap. 24J). CLD requiring diuretic therapy often leads to hypokalemic, hypochloremic metabolic alkalosis. Affected infants frequently have a chronic respiratory acidosis with partial metabolic compensation. Subsequently, vigorous diuresis can lead to total-body K and ECF volume depletion, causing a superimposed metabolic alkalosis. If the alkalosis is severe, alkalemia (pH >7.45) can supervene and result in central hypoventilation. If possible, gradually reduce urinary Na and K loss by reducing the diuretic dose, and/or increase K intake by administration of KCl (starting at 1 mEq/kg/day). Rarely, administration of ammonium chloride (0.5 mEq/kg) is required to treat the metabolic alkalosis. Long-term use of loop diuretics such as furosemide promotes excessive urinary Ca losses and nephrocalcinosis. Urinary Ca losses may be reduced through concomitant thiazide diuretic therapy (see Chap. 24J).