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CHAPTER 132:  Fluid and Electrolyte Ther apy in Infants and Childr en      851 protein–induced enterocolitis syndrome, and children regularly exposed to the allergenic food may develop chronic vomiting, diarrhea, anemia, or failure to thrive. Food protein–induced allergic proctocolitis most often presents in breastfed infants in the first 2 months of life. Infants generally appear healthy but have stools characterized by the presence of blood and mucus. Cow’s milk in the maternal diet is the most common trigger, and symptoms begin to improve within a few days of dietary modification. The condition generally resolves between the ages of 6 months and 2 years. Diagnostic tests used for IgE allergies such as skin prick testing are not useful in identifying the offending agents in non– IgE-mediated food allergies; therefore, the diagnosis is based on clinical suspicion. Dietary avoidance is the mainstay of management. Celiac disease is a T-cell–mediated inflammatory response triggered by the ingestion of gluten in genetically predisposed individuals. GI presentations are common in children and include chronic or intermittent diarrhea, abdominal pain, abdominal distention, and failure to thrive. Whereas young children most often have a “typical” presentation, extraintestinal symptoms such as fatigue, osteopenia, iron deficiency anemia, and short stature become more common as age increases. Treatment consists of lifelong adherence to a gluten-free diet. Antibiotic-Associated Diarrhea Antibiotic-associated diarrhea is otherwise unexplained diarrhea that occurs in association with the administration of antibiotics. The frequency of this complication varies, with diarrhea occurring in 5% to 10% of children treated with ampicillin, 10% to 25% treated with amoxicillin-clavulanate, and 15% to 20% treated with cefixime. The spectrum of findings in antibiotic-associated diarrhea ranges from mild diarrhea to severe colitis that may include abdominal cramping, fever, leukocytosis, fecal leukocytes, hypoalbuminemia, and colonic thickening with characteristic changes visible on endoscopy and biopsy. Although infection with Clostridium difficile accounts for only 10% to 20% of the cases of antibiotic-associated diarrhea, it accounts for most cases of colitis associated with antibiotic therapy. Nonclostridial antibiotic-associated diarrhea may be caused by other enteric pathogens, by the direct effects of antimicrobial agents on the intestinal mucosa, or by the metabolic consequences of reduced concentrations of fecal flora. Clindamycin, cephalosporins, and penicillins are the antibiotics most frequently implicated in C. difficile diarrhea. C. difficile disease can only be firmly diagnosed once its toxin is identified. However, because children can be asymptomatic hosts of toxin-producing strains, testing for C. difficile should only be performed when there is ample clinical suspicion and/or risk factors identified. When identified in the stool of children <2 years of age (even if diar rheal), it most commonly is not the cause of diarrhea and usually does not require treatment. The following two-step testing strategy has been proposed: screening should be performed through the conduct of an enzyme immunoassay for glutamate dehydrogenase, which is present in almost all strains of C. difficile, including those that do not produce toxin.

cause of diarrhea and usually does not require treatment. The following two-step testing strategy has been proposed: screening should be performed through the conduct of an enzyme immunoassay for glutamate dehydrogenase, which is present in almost all strains of C. difficile, including those that do not produce toxin. 65,66 If positive, this should be followed by a confirmatory enzyme immunoassay test for toxins A and B or, preferably, by a cell cytotoxin assay that demonstrates cytotoxicity of stool for human fibroblast cells. Polymerase chain reaction testing is a rapid, sensitive, and specific test that appears promising. However, significant variations exist in testing methodologies and kits, and thus further evaluation of its utility is war ranted before widespread adoption. 67,68 Indications for treatment include positive assays for C. difficile toxin, plus one of the following: evidence of colitis, moderate to severe diarrhea, persistent diarrhea despite the dis continuation of the implicated agent, or the need to continue treating the original infection. Oral metronidazole is the treatment of choice in most cases of pediatric C. difficile colitis. In the most severe cases, vancomycin (oral or rectal) may be used in conjunction with IV metronidazole. The anticipated response to treatment is resolution of fever within 1 day and resolution of diarrhea in 4 to 5 days. Treatment does not eradicate C. difficile, and asymptomatic patients should not be retested or treated based on a positive stool test. Metronidazole is preferred because it is less expensive than vancomycin and avoids the potential risk of promot ing vancomycin-resistant enterococci. Secondary Lactase Deficiency Secondary lactase deficiency implies that a pathophysiologic condition has resulted in an acquired lactase deficiency and lactose malabsorption. The most common etiology is acute GI infection resulting in small intestinal injury with loss of Fluid and Electrolyte Therapy in Infants and Children Melissa Chan Paul Enarson INTRODUCTION This chapter provides a basic guide to parenteral rehydration, mainte nance fluids, and management of common electrolyte abnormalities in children. The most common cause of fluid and electrolyte abnormalities in children is dehydration. Dehydration results from a negative fluid bal ance due to decreased intake, increased output (renal, GI, or insensible losses from the skin or respiratory tract), or disease states such as burns, sepsis, or diabetes. Negative fluid balance can occur in the intracellular fluid or extracellular fluid compartments and may be accompanied by derangements in electrolytes. Table 132-1 lists some of the common causes of dehydration. Common signs of dehydration are listed in Table 132-2, and a validated clinical scoring system predicting the need for parenteral rehydration is provided in Table 131-6. PATHOPHYSIOLOGY Infants and children are particularly susceptible to dehydration for a number of developmental and physiologic reasons. They are depen dent on caretakers to provide oral fluids and therefore cannot regulate CHAPTER lactase-containing epithelial cells at the tips of the villi. The immature epithelial cells that replace these are often lactase deficient, leading to secondary lactase deficiency and lactose malabsorption. Despite this, children with infectious diarrheal illnesses who have no or only mild dehydration can continue consuming human milk or standard formula without a significant effect on clinical course. Secondary lactase defi ciency with clinical signs of lactose intolerance can be seen in celiac disease, Crohn’s disease, and immune-related and other enteropathies, and should be considered as a possible etiology for diarrhea in children with these conditions.

rd formula without a significant effect on clinical course. Secondary lactase defi ciency with clinical signs of lactose intolerance can be seen in celiac disease, Crohn’s disease, and immune-related and other enteropathies, and should be considered as a possible etiology for diarrhea in children with these conditions. Diagnostic evaluation should be performed when secondary lactase deficiency is suspected and infection is not the cause. Parasitic Infection Parasites are uncommon causes of diarrhea but may be the source of waterborne outbreaks and are more severe in immunocompromised children. Cryptosporidium and Giardia are the parasites most likely to cause diarrhea. Nitazoxanide is the drug of choice for Cryptosporidium infections, and either metronidazole, tinidazole, or nitazoxanide may be used in the treatment of Giardia infections. For further discussion of parasitic diseases, see Chapter 160, “Food and Waterborne Illnesses, ” and Chapter 162, “Global Travelers. ”  TRAVELER’S DIARRHEA Limited data suggest that diarrhea is common in children traveling to high-risk regions. Although many cases of traveler’s diarrhea are selflimited, antibiotic therapy is appropriate for children with a history of travel to a high-risk region who have severe or prolonged symptoms (>5 days). Macrolides such as azithromycin are the first-line antibiotic therapy, and trimethoprim-sulfamethoxazole may also be considered. REFERENCES The complete reference list is available online at www.TintinalliEM.com. Tintinalli_Sec12_p0669-0996.indd 851 8/2/19 7:53 PM

region who have severe or prolonged symptoms (>5 days). Macrolides such as azithromycin are the first-line antibiotic therapy, and trimethoprim-sulfamethoxazole may also be considered. REFERENCES The complete reference list is available online at www.TintinalliEM.com. Tintinalli_Sec12_p0669-0996.indd 851 8/2/19 7:53 PM 852 SECTION 12: Pediatrics for water. Total body water as a percentage of body weight decreases from 70% in a term infant (75% to 80% in premature infants) to 60% at 1 year of age, remaining at this percentage until puberty. 1 The high percentage of total body water, coupled with a decreased ability to control water loss (e.g., insensible losses from larger surface area–to– body ratio and faster respiratory rate) and a decreased ability to con centrate the urine, predispose infants to dehydration. Furthermore, young children are more prone to hypermetabolic states, such as high fever, which also increases the need for free water. Fever increases the basal metabolic rate by 13% for each degree above 37.8 °C. Because sodium and water are tightly regulated together, dehydration is often described in relation to serum sodium concentrations. Children can develop isonatremic (isotonic) dehydration (sodium level of 135 to 145 mEq/L), hyponatremic (hypotonic) dehydration (sodium level of <135 mEq/L), or hypernatremic (hypertonic) dehydration (sodium level of >145 mEq/L). Isonatremic dehydration is the most common form of dehydration. Isonatremic (isotonic) dehydration occurs when the fluid sodium losses are proportionate in the intracellular fluid and extracellular fluid compartments. Hyponatremic (hypotonic) dehydration occurs when fluid that is lost contains proportionately more sodium than blood, which leads to osmotic shifts of free water from the intracellular fluid to the extracellular fluid compartments. Hypernatremic (hyper tonic) dehydration occurs when the fluid lost contains less sodium than the blood, which causes extracellular free water to move into the intracellular fluid space. CLINICAL FEATURES  HISTORY Suspicion of fluid or electrolyte disorders can often be raised through a properly taken history. Ask about symptoms (what they are, when they started, where they started; e.g., was the child in a hot environment), whether fever is present, whether the child is tachypneic, and prior treatment. For breastfeeding infants, inquire about frequency of feeds, whether the mother feels she has good milk production, and whether the infant is feeding or engaged in nonnutrient sucking for comfort. If not breastfeeding, ask what type of fluid has been given, because hypotonic fluids (e.g., water) are often used during illnesses and increase the risk of hyponatremia. If the infant is bottle-fed, ask whether the formula is premixed or made from powder; hypernatremia or hyponatremia can result from inappropriately prepared formula. Questions surrounding output aid in assessing whether replacement of losses has been adequate; excess output results from vomiting or diarrhea (quantify the frequency and volume if possible). Assess urine output by asking how often the child is urinating or the number of wet diapers if the child is not yet toilet trained. Inquire about volume status by asking about tear production, the presence or absence of sweat, and the child’s general appear ance and mental status: is the child increasingly irritable or lethargic? Has the parent noticed a change in the skin (cyanotic, pale, mottled)? Most important, if known, is a change in weight, because weight loss is the gold standard for assessment of volume status. 3 In addition to the specific questions, ask about signs or symptoms of infection, recent travel, sick contacts, and underlying chronic disease, which may point to a specific cause of dehydration.

Most important, if known, is a change in weight, because weight loss is the gold standard for assessment of volume status. 3 In addition to the specific questions, ask about signs or symptoms of infection, recent travel, sick contacts, and underlying chronic disease, which may point to a specific cause of dehydration. Children are at risk for accidental ingestion of toxins or plants, many of which can cause vomiting and lead to electrolyte disturbances.  PHYSICAL EXAMINATION Physical findings related to individual electrolyte disorders are discussed in relation to specific electrolyte disorders below. In general, children with dehydration demonstrate a spectrum of physical findings ranging from a normal exam if dehydration is mild, to hypovolemic shock if dehydration is severe. Table 131-6 presents a simplified and validated clinical scoring system for dehydration. Tachycardia is an early sign of dehydration as the body compensates for a decreased circulatory vol ume. Tachycardia can present with normal blood pressure with or without signs of shock (compensated shock) but may be accompanied by hypotension (uncompensated shock) in severe dehydration. Tachypnea TABLE 132-1 Causes of Dehydration in Children Decreased Intake: •  Voluntary  or involuntary •   Anatomic or pathologic diseases (pharyngitis, stomatitis, cleft lip/palate, facial dysmorphism, airway obstruction) •   Neurologic diseases (meningitis, encephalitis, brain tumor, seizures) •   Febrile illnesses Increased Output: •   Insensible losses (fever, heat, respiratory diseases, diaphoresis, thyroid disease, cystic fibrosis) •   GI losses (vomiting, diarrhea) •  Renal  losses: Osmotic (DKA, acute tubular necrosis) Nonosmotic (renal diseases, electrolyte disturbance, diabetes insipidus) •   Sodium losing (adrenal disease, diuretics, kidney disease, pseudohypoaldosteronism) Systemic Diseases: •   Moderate to severe burns •   Ascites •   Respiratory disease •   Peritonitis: medical or surgical with third spacing •   Anaphylaxis Abbreviation: DKA = diabetic ketoacidosis. TABLE 132-2 Clinical Guidelines for Assessing Dehydration in Children None to Minimal Dehydration (<3% loss of body weight) Some (mild to moderate) Dehydration (3% to 9% loss of body weight) Severe Dehydration (>9% loss of body weight) Mental status Well, alert Fatigued, restless, irritable Apathetic, lethargic, unconscious Thirst Normal, slight increase, or refusing fluids Increased, eager to drink Very thirsty or too lethargic to indicate Heart rate Normal Normal to increased Tachycardic with bradycardia in severe cases Blood pressure Normal Normal Normal to reduced Pulse quality Normal Normal to reduced Weak, thready Breathing Normal Normal to tachypneic Deep Eyes Normal Slightly sunken orbits Deeply sunken orbits Tears Present Decreased Absent Mucous membranes Moist Dry Parched Anterior fontanelle Normal Sunken Sunken Skin turgor Instant recoil Recoil in <2 s Recoil in >2 s Capillary refill Normal Prolonged 1–2 s Prolonged >2 s Extremities Warm Cool Cold, mottled, cyanotic Urine output Normal to decreased Decreased (<1 mL/kg/h) Minimal (<0.5 mL/kg/h) Courtesy of Stephen Freedman, MD, and Jennifer Thull-Freedman, MD. their intake. In addition, young children and infants have increased fluid requirements and are at risk of increased fluid losses compared to adults and older children. Basal metabolic rates are highest in young children, peaking at 12 months of age and gradually decreasing starting at 3 years of age. Infants also have a higher turnover rate Tintinalli_Sec12_p0669-0996.indd 852 8/2/19 7:53 PM

requirements and are at risk of increased fluid losses compared to adults and older children. Basal metabolic rates are highest in young children, peaking at 12 months of age and gradually decreasing starting at 3 years of age. Infants also have a higher turnover rate Tintinalli_Sec12_p0669-0996.indd 852 8/2/19 7:53 PM CHAPTER 132:  Fluid and Electrolyte Ther apy in Infants and Childr en      853 may also be noted as metabolic acidosis develops in moderate to severe dehydration. Note the mental status and the presence of lethargy or hypotonia, because these suggest severe dehydration or electrolyte abnormalities. In infants, the quality of the fontanelle (flat or sunken) may aid in assessment of hydration status, along with the presence or absence of tears when crying; assess the mucous membranes for cracked, dry lips or decreased saliva in mouth, and the temperature, color, and turgor of the skin (cool, mottled, cyanotic, decreased elasticity), as well as capillary refill time, which should be less then 2 seconds when nor mal. Finally, note the character of the pulses because diminished pulses may also reflect significant dehydration.  LABORATORY EVALUATION Laboratory testing for individual electrolyte disorders is discussed indi vidually below. Routine laboratory testing for assessing dehydration alone is generally not required, and several studies have found a lack of correlation between laboratory values and degree of dehydration based on percent weight lost. Measure serum electrolytes if IV insertion is required for rehydration and signs of electrolyte disturbance are present, 4,5 or if electrolyte abnormalities are expected due to certain underlying medical conditions (e.g., diabetic ketoacidosis or congenital adrenal hyperplasia). Perform a bedside glucose test in any child presenting with altered level of consciousness, and rapidly correct hypoglycemia (see Chapter 146, “Metabolic Emergencies in Infants and Children”). INITIAL TREATMENT OF DEHYDRATION Three main modalities exist for rehydration in children: oral, naso gastric, and parenteral. Treatment at each level of dehydration is discussed below and summarized in Table 132-3, and a detailed discussion of the treatment of mild to moderate dehydration is presented in Chapter 131, “Vomiting, Diarrhea, and Dehydration in Infants and Children. ” For children unable to tolerate oral rehydration, nasogastric hydra tion is effective, even in vomiting patients.3,6 In a large study comparing nasogastric hydration versus IV hydration over 3 hours, subjects in the nasogastric-treated group had fewer complications, achieved resolution of ketonuria more often, and had greater reduction in specific gravity than IV-treated subjects. Nasogastric treatment is more cost effective than IV treatment.  MODERATE AND SEVERE DEHYDRATION The child unable to tolerate oral/nasogastric rehydration therapy or with severe dehydration requires prompt fluid resuscitation with large volumes of fluid over a short period of time 7 (Table 132-4). Give 20 mL/kg boluses over 5 to 10 minutes repetitively until hemodynamics stabilize. Up to 60 mL/kg or more may be required in the first hour, unless contraindi cated based on underlying disease. 8 Use an isotonic solution such as 0.9% saline or a lactated Ringer’s solution during this resuscitation phase.9 For patients with moderate dehydration requiring parenteral fluids, there is no advantage of rapid or ultrarapid (50 to 60 mL/kg in 1 hour) hydration over standard hydration with 20 mL/kg over 1 hour, and a blinded randomized trial found increased hospitalization rates among those receiving ultrarapid hydration.

hase.9 For patients with moderate dehydration requiring parenteral fluids, there is no advantage of rapid or ultrarapid (50 to 60 mL/kg in 1 hour) hydration over standard hydration with 20 mL/kg over 1 hour, and a blinded randomized trial found increased hospitalization rates among those receiving ultrarapid hydration. 10 Further more, a study of fluid resuscitation among dehydrated children in Africa found that aggressive bolus fluid resuscitation was associated with increased mortality. After initial volume expansion, continue replacement with either normal saline or 5% dextrose in 0.9% normal saline. Use clinical judg ment, because there is no strong evidence to recommend one fluid over the other, although dextrose-containing fluids help clear ketones in the patient who has not been eating or drinking. 12,13 MAINTENANCE TREATMENT Caloric expenditure and therefore fluid requirements can be estimated from body surface area, which is relatively large in infants in comparison with older children and adults. However, in the ED, weight is a sufficiently accurate value for calculating fluid requirements. The primary formula for daily fluid requirements is calculated as follows: For the first 10 kg: 100 mL/kg/d (4 mL/kg/h) For the second 10 kg: 50 mL/kg/d (2 mL/kg/h) For each kg >20 kg: 20 mL/kg/d (1 mL/kg/h) For example: A 10-kg baby requires: 100 mL × 10 kg, or a total of 1000 mL/d. A 20-kg child requires: (100 mL × 10 kg) + (50 mL × 10 kg) = 1500 mL/d. A 40-kg child requires: (100 mL × 10 kg) + (50 mL × 10 kg) + (20 mL × 20 kg) = 1900 mL/d. Electrolyte requirements remain constant throughout childhood and can be estimated by body weight. All infant formulas contain sufficient electrolytes to satisfy these requirements, as do the commercially available oral rehydration solutions such as Pedialyte ® (see Table 131-9). The requirement is 2 to 3 mEq/kg/d for sodium and 2 mEq/kg/d for potassium. Because hyponatremia is the most common intragenic compli cation of IV fluid therapy, it is important that isotonic solutions TABLE 132-3 Treatment for Mild, Moderate, and Severe Dehydration Mild Moderate Severe Primary phase Secondary phase (if primary phase fails) PO* NG/IV PO* NG/IV‡ IV†, IO, NG Central line Tertiary phase (after rehydration to ensure ability to maintain oral intake—optional) * PO* ± PO* after initial IV/IO rehydration Laboratory studies None Optional# Electrolytes, BUN, creatinine, calcium, glucose levels; urinalysis Discharge criteria Appears clinically well, alert, and orientated Vital signs within normal limits for age Urine output during hydrating period Intake is equal or greater to ongoing losses Treatment failure Admit or place in observation unit *PO: Use dilute apple juice or patient-preferred fluid or a commercial rehydration solution such as Pedialyte® or Enfalyte® or WHO reduced-osmolality ORS. Rehydrate with 5 mL (1 tsp) every 2–3 min. Increase based on patient tolerance; aim for 50–100 mL/kg replacement plus 10 mL/kg per stool and 2 mL/kg per emesis episode. †IV (severe dehydration): 20 mL/kg over 5–30 min (NS or lactated Ringer’s solution). Aim for 60–100 mL/kg in the first hour. Contraindications include some forms of cardiac disease (e.g., cardiomyopathy). ‡IV NS 20 mL/kg over 20–30 min, repeat as needed; NG oral rehydration solution at a rate of 10–20 mL/kg/h. #Perform laboratory testing based on dietary history or disease state. Abbreviations: NG = nasogastric; NS = normal saline; ORS = oral rehydration salts; WHO = World Health Organization.

se (e.g., cardiomyopathy). ‡IV NS 20 mL/kg over 20–30 min, repeat as needed; NG oral rehydration solution at a rate of 10–20 mL/kg/h. #Perform laboratory testing based on dietary history or disease state. Abbreviations: NG = nasogastric; NS = normal saline; ORS = oral rehydration salts; WHO = World Health Organization. TABLE 132-4 IV Rehydration for Moderate to Severe Dehydration Degree of Dehydration IV Rehydration Replacement of Ongoing Losses After Initial Rehydration Severe with uncompensated shock 20 mL/kg 0.9% saline bolus over 5 min, repeated until hemodynamically stable 5–10 mL/kg 0.9% saline or 5% dextrose in 0.9% saline for each watery diarrheal stool and 2 mL/kg 0.9% saline or 5% dextrose in 0.9% saline for each emesis Moderate to severe without signs of shock 20 mL/kg 0.9% saline bolus over 1 h followed by 5% dextrose in 0.9% saline at 1–2× maintenance rate for 1 h Tintinalli_Sec12_p0669-0996.indd 853 8/2/19 7:53 PM

TABLE 132-4 IV Rehydration for Moderate to Severe Dehydration Degree of Dehydration IV Rehydration Replacement of Ongoing Losses After Initial Rehydration Severe with uncompensated shock 20 mL/kg 0.9% saline bolus over 5 min, repeated until hemodynamically stable 5–10 mL/kg 0.9% saline or 5% dextrose in 0.9% saline for each watery diarrheal stool and 2 mL/kg 0.9% saline or 5% dextrose in 0.9% saline for each emesis Moderate to severe without signs of shock 20 mL/kg 0.9% saline bolus over 1 h followed by 5% dextrose in 0.9% saline at 1–2× maintenance rate for 1 h Tintinalli_Sec12_p0669-0996.indd 853 8/2/19 7:53 PM 854 SECTION 12: Pediatrics be used as maintenance fluid, such as normal saline with 5% dextrose.14,15 An exception is during the neonatal period. Although there is little evidence as to which maintenance fluids should be used early in life, neonates have immature kidneys and higher glucose requirements compared to older infants and children. Controversy exists on the best maintenance fluids in the first few days of life. The National Institute for Health and Care Excellence guidelines recom mend using 5% or 10% dextrose in normal saline for all neonates from birth onward unless respiratory distress syndrome, meconium aspiration, or hypoxic ischemic encephalopathy is present. If any of these are present, give no sodium (e.g., 10% dextrose in water), until the postnatal diuresis with weight loss occurs, typically before day 5 of life. 16 Others recommend using salt-free fluids in all neonates until after the postnatal diuresis occurs. 17 DISORDERS OF SODIUM Table 132-5 outlines disease states associated with disruption in serum sodium levels and total body water (volume).  HYPONATREMIA Hyponatremia is a serum sodium level <135 mEq/L. First determine if a low sodium value is a true value by relating the sodium value to the osmolarity. If hyponatremia occurs in a hyperosmolar state (i.e., >290 mOsm/kg), this suggests an osmotically active solute in the plasma such as excess glucose or alcohol. If hyponatremia occurs in the presence of normal osmolarity (275 to 290 mOsm/kg), this is likely due to hyperlipidemia or hyperproteinemia. 18 In such cases, correct the underlying disorder rather than the serum sodium level. When hyponatremia occurs in a hypo-osmolar state (<275 mOsm/kg), this is likely due to an excess of free water or loss of sodium. The most com mon causes of hyponatremia seen in the ED are GI losses and water intoxication caused by ingestion of hypotonic replacement fluids, especially during infancy. Signs and symptoms of hyponatremia depend on the serum sodium level and the speed at which the sodium level falls. Symptoms primarily involve the CNS, as free water moves from the extracellular to intracellular space, and the musculoskeletal system. Neurologic symptoms include nausea, vomiting, headache, mental status changes, altered consciousness, diminished reflexes, hypothermia, pseudobulbar palsy, and seizures. Musculoskeletal symptoms include weakness, muscle cramps, and lethargy. Although patients may be only mildly symptomatic with sodium levels as low as 120 mEq/L if the low level is chronic (>48 hours), symptoms usually occur with an acute drop in serum sodium level below 120 mEq/L. Without appropriate treatment, complications include respiratory failure, seizures, and death. Treatment depends on the stability of the patient and associated symptoms. General guidelines are presented in Table 132-6. Take special care to avoid rapid shifts in sodium levels. Although hyponatremia itself can have dire consequences, rapid correction can cause severe demyelination of brainstem neurons. 19 Therefore, correct hyponatremia slowly and in a controlled manner (Table 132-6). The exception to this is in the setting of severe neurologic symptoms, such as confusion, altered level of consciousness, or seizures, typically with sodium level <120 mmol/L. When this occurs, a rapid, controlled increase in sodium level is required until neurologic symptoms resolve or a sodium level of 120 mmol/L is achieved.

tion to this is in the setting of severe neurologic symptoms, such as confusion, altered level of consciousness, or seizures, typically with sodium level <120 mmol/L. When this occurs, a rapid, controlled increase in sodium level is required until neurologic symptoms resolve or a sodium level of 120 mmol/L is achieved. For euvolemic hyponatremia, after correction of serum sodium level, begin water restriction and treat the underlying disorder. For hyper volemic hyponatremia (edema), start sodium and water restriction and administer diuretics if needed to treat the clinical condition (e.g., congestive heart failure).  HYPERNATREMIA Hypernatremia is a serum sodium level >145 mEq/L. Hypernatremia generally indicates a lack of total body water in relation to total body solute and often occurs as a result of dehydration (loss of water through the GI tract, kidney, or insensible losses), but may also occur secondary to excessive sodium intake (e.g., inadequate water intake or hypertonic solution intake) (Table 132-7). Diarrhea is the most common cause in children. Other diseases to consider include renal disease and diabetes insipidus. Children are at risk for hypernatremia if free water is limited or if formula is mixed improperly. Mild hypernatremia is commonly found in ill children, particularly infants with gastroenteritis. If mild, it is usually asymptomatic and corrects with treatment of the underlying TABLE 132-5 Conditions Altering Serum Sodium and Total Body Water Balance Total Body Water (volume) Hypernatremia Hyponatremia Increased Excessive saline infusion Congestive heart failure Cirrhosis Nephrotic syndrome Advanced renal failure Normal Hypertonic saline infusion Bicarbonate intoxication Salt poisoning Hyperaldosteronism SIADH Primary polydipsia Exercise-induced Low solute intake Renal osmostat Hypothyroidism Glucocorticoid deficiency Nephrogenic SIADH Decreased Cutaneous losses Sweating Radiant warmers Phototherapy Burns Inadequate intake Improperly prepared formula GI losses Vomiting Nasogastric suctioning Diarrhea Osmotic stool softeners Diuretics Renal losses Interstitial nephritis Mineralocorticoid deficiency Burns, heat illnesses (exhaustion/ stroke) Ascites Cystic fibrosis

Cutaneous losses Sweating Radiant warmers Phototherapy Burns Inadequate intake Improperly prepared formula GI losses Vomiting Nasogastric suctioning Diarrhea Osmotic stool softeners Diuretics Renal losses Interstitial nephritis Mineralocorticoid deficiency Burns, heat illnesses (exhaustion/ stroke) Ascites Cystic fibrosis Renal free water losses Diabetes insipidus Increased osmoles (diabetes mellitus, mannitol) Chronic kidney disease ATN (if polyuric) Postobstructive diuresis Abbreviations: ATN = acute tubular necrosis; SIADH = syndrome of inappropriate secretion of antidi uretic hormone. TABLE 132-6 Treatment of Hyponatremia Symptoms Treatment* If hypovolemic and hemodynamically unstable Correct instability with NS boluses (20 mL/kg over 5 min followed by reassessment after each bolus) Asymptomatic Correct deficit to normal over 48 h mEq Na required = [(Na + desired) – (measured Na +)] × (0.6 × weight in kg) Neurologic symptoms (altered mental status, seizures) 1–2 mL/kg/h of 3% sodium chloride until asymptomatic or Na level >120 mEq/mL, then increase Na level 0.5 mEq/mL/h (not to exceed increase of 12 mEq/mL in first 24 h or 18 mEq/mL in first 48 h) *Does not include maintenance requirements and ongoing losses. 0.9% NS = 0.15 mEq Na/L; 3% saline = 0.5 mEq Na/L Abbreviation: NS = normal saline. Tintinalli_Sec12_p0669-0996.indd 854 8/2/19 7:53 PM

Eq/mL, then increase Na level 0.5 mEq/mL/h (not to exceed increase of 12 mEq/mL in first 24 h or 18 mEq/mL in first 48 h) *Does not include maintenance requirements and ongoing losses. 0.9% NS = 0.15 mEq Na/L; 3% saline = 0.5 mEq Na/L Abbreviation: NS = normal saline. Tintinalli_Sec12_p0669-0996.indd 854 8/2/19 7:53 PM CHAPTER 132:  Fluid and Electrolyte Ther apy in Infants and Childr en      855 cause. Serum sodium levels of >160 mEq/L require immediate attention due to the potential for serious complications and permanent neuro logic sequelae, including intellectual deficits, seizure disorder, or other neurologic impairments. Conversely, patients who have a sodium level of <160 mEq/L and receive treatment typically have symptoms that are relatively mild and self-limited. Signs and symptoms of hypernatremia result from cellular dehydra tion as free water moves from the intracellular to extracellular space and include mental status changes, muscular weakness, ataxia, tremors, hyperreflexia, seizures, unresponsiveness, intracerebral hemorrhage, permanent neurologic dysfunction, and death. In addition, when extracellular fluid hypertonicity develops, brain intracellular osmolar contents increase to prevent or minimize cell shrinkage. In severe hypernatremic dehydration, neurologic findings may include any of the fol lowing: increased peripheral tone with brisk reflexes, muscle weakness, high-pitched cry, nuchal rigidity, myoclonus, asterixis, chorea, altered level of consciousness, or seizures. 3,21 Treatment consists of restoration of intravascular volume while decreasing the serum sodium level. Correct serum sodium gradually to avoid cerebral edema and associated central pontine myelinolysis (Table 132-7). Closely monitor serum sodium levels every hour initially to ensure that the level is reduced no faster than 1 mEq/L/h and no more than 15 mEq/L in the first 24 hours. This may require more than 48 hours for complete correction. Monitor urine output given the risk of acute tubular necrosis. 21 Correct underlying causes. Hyper volemic hypernatremia may require dialysis if sodium levels cannot be decreased without volume overload. Dialysis may also be required for hypernatremia of any type if the initial serum sodium is >180 mmol/L. DISORDERS OF POTASSIUM  HYPOKALEMIA Hypokalemia occurs when the serum potassium level falls to <3.4 mEq/L and most commonly occurs secondary to profuse vomiting and/or diarrhea. Other common causes include therapy with loop or thiazide diuretics, mineralocorticoids, or laxatives and diabetic ketoacidosis. In diabetic ketoacidosis, profound hypokalemia can result from osmotic diuresis, although in the face of the hydrogen–potassium shift that accompanies acidemia, serum levels may be normal or falsely elevated. Uncommon causes of hypokalemia include renal tubular acidosis, Bartter’s or Gitelman’s syndrome, Cushing’s syndrome, and familial hypokalemia-induced paralysis. In most cases, hypokalemia occurs slowly, and thus patients are asymptomatic. Clinical signs tend to reflect the rate of fall of serum potassium rather than the absolute level. However, severe potassium depletion can result in skeletal muscle weakness, ileus, and cardiac conduction disturbances. A prominent ECG manifestation is the U wave. Treatment is generally with oral replacement with potassium, 2 to 5 mEq/kg/d in two or three divided doses (maximum 40 mEq/dose). However, dehydration and magnesium abnormalities must also be cor rected to maintain normal potassium levels. If IV therapy is necessary, potassium 0.2 to 0.3 mEq/kg/h is generally adequate.

Treatment is generally with oral replacement with potassium, 2 to 5 mEq/kg/d in two or three divided doses (maximum 40 mEq/dose). However, dehydration and magnesium abnormalities must also be cor rected to maintain normal potassium levels. If IV therapy is necessary, potassium 0.2 to 0.3 mEq/kg/h is generally adequate. In extremely urgent situations, such as hypokalemia-induced respiratory insufficiency or cardiac manifestations, potassium 0.5 mEq/kg/h can be administered (maximum 20 mEq/dose), with continuous ECG monitoring. 22 If potassium chloride infusion concentration exceeds 60 mEq/L, the infusion will need to run through a central line, because potassium is a vein irritant. In diabetic ketoacidosis, potassium repletion should begin early in the course of therapy, because diuresis-induced depletion can result in profound hypokalemia as acidosis is corrected and serum potassium shifts into cells (see Chapter 147, “Diabetes in Children”).  HYPERKALEMIA Hyperkalemia is a serum potassium level of >5.5 mEq/L. In infants and children, a laboratory finding of hyperkalemia is most commonly due to hemolysis from phlebotomy and does not reflect serum levels. How ever, do not assume hyperkalemia is false; repeat the potassium level, reexamine the patient, obtain an ECG, and place the child on a cardiac monitor. Some common causes of true hyperkalemia include renal fail ure, rhabdomyolysis, burns, heatstroke, trauma, tumor lysis syndrome, hemolytic anemia, use of potassium-sparing diuretics, and adrenal corticoid insufficiency (e.g., Addison’s disease, salt-wasting congenital adrenal hyperplasia). Metabolic acidosis can result in hyperkalemia due to hydrogen–potassium shifts. Cardiac conduction delay is the most common manifestation of hyperkalemia and is potentially life threatening. Peaked T waves are the first manifestation, followed by prolonged PR interval and then widening of the QRS complex, an ominous finding that can precede the characteristic “sine wave” pattern, leading to ventricular dysrhythmias and asystole. Any patient with ECG changes requires emergent therapy to reverse cardiac conduction toxicity. Treatment is detailed in Table 132-8. Asymptomatic patients with normal ECG findings usually do well with therapy to enhance potassium TABLE 132-7 Treatment of Hypovolemic or Euvolemic Hypernatremia Condition Treatment* If hypovolemic and hemodynamically unstable Correct instability with NS boluses (20 mL/kg boluses followed by reassessment after each bolus) Once hemodynamically stable and hypovolemic or euvolemic hypernatremia Correct deficit to normal over 24 h Free water deficit (mL) = 4 mL × body weight (kg) × [desired change in serum sodium mEq/L (mmol/L)] Subtract bolus fluids given from deficit; correct remaining deficit giving half of deficit over first 8 h and remainder over the next 16 h (see text for monitoring criteria) † *Does not include maintenance requirements and ongoing losses. †Tonicity of fluid used for correction will depend on initial severity of hypernatremia. Abbreviation: NS = normal saline. TABLE 132-8 Treatment of Hyperkalemia Purpose Agent Dose Increase cardiac stability

the next 16 h (see text for monitoring criteria) † *Does not include maintenance requirements and ongoing losses. †Tonicity of fluid used for correction will depend on initial severity of hypernatremia. Abbreviation: NS = normal saline. TABLE 132-8 Treatment of Hyperkalemia Purpose Agent Dose Increase cardiac stability Calcium gluconate 10% (10% calcium gluconate contains 100 milligrams/mL) 100 milligrams/kg (1 mL/kg/dose) IV at rate not to exceed 100 milligrams/min; maximum 3 grams/dose. Can be administered peripherally or centrally. May be repeated in 5 min if necessary. Calcium chloride 10% (10% calcium chloride contains 100 milligrams/mL) 20 milligrams/kg (0.2 mL/kg/dose) IV at rate not to exceed 100 milligrams/min; maximum 1 gram/dose. Calcium chloride must be given via central line or IO due to vein sclerosis. May be repeated in 5 min if necessary. Decrease potassium Albuterol (Ventolin) 0.5% solution 2.5–5 milligrams via nebulization; every 20 min as needed. Sodium bicarbonate If acidotic (pH <7.3), 1–2 mEq/kg IV/IO; typical adult dose 50–100 mEq. Onset of action is in minutes. May be repeated every 5–10 min as needed. Regular insulin 0.1 unit/kg IV in 5 mL/kg 10% dextrose in water, 0.5 gram/kg IV over 30 min; check glucose level every 30 min; onset of action, 30 min. May be repeated every 30–60 min. Furosemide If renal function normal and patient is not hypovolemic, 0.5–1 milligram/kg/dose IV to a maximum of 40 milligrams/dose. Peak effect seen at 30 min. Sodium polystyrene sulfonate 1 gram/kg to a maximum of 60 grams orally, via nasogastric tube, or rectally. Onset of action, 1–2 h orally, <30 min rectally. Tintinalli_Sec12_p0669-0996.indd 855 8/2/19 7:53 PM

t is not hypovolemic, 0.5–1 milligram/kg/dose IV to a maximum of 40 milligrams/dose. Peak effect seen at 30 min. Sodium polystyrene sulfonate 1 gram/kg to a maximum of 60 grams orally, via nasogastric tube, or rectally. Onset of action, 1–2 h orally, <30 min rectally. Tintinalli_Sec12_p0669-0996.indd 855 8/2/19 7:53 PM 856 SECTION 12: Pediatrics excretion. In patients with renal failure with a gradual rise in serum potassium levels, sodium polystyrene sulfonate can be given. It is a resin that exchanges sodium for potassium at a 1:1 ratio and therefore enhances potassium excretion and can be administered orally or by enema. A dose of 1 gram/kg lowers the serum potassium level by up to 1.2 mEq/L. When administered orally, it is usually given with a cathartic to speed transit time through the GI tract. Hypernatremia and volume overload are potential complications. In patients with severe hyperkalemia from renal failure, dialysis is usually necessary, but emergency cor rection of potassium must be done first (Table 132-8). In patients with hyperkalemia secondary to metabolic acidosis, normalization of serum pH usually restores serum potassium to normal levels. DISORDERS OF CALCIUM  HYPOCALCEMIA Hypocalcemia is a serum calcium level <8 milligrams/dL (2 mmol/L) or ionized calcium level <4.4 milligrams/dL (1.1 mmol/L); however, levels must be adjusted for albumin levels and pH of the blood. Low calcium levels tend to result from hypoparathyroidism or end-organ resistance to parathyroid hormone. True hypoparathyroidism can be idiopathic, be associated with DiGeorge’s syndrome, occur after thyroid surgery, and/or be associated with magnesium deficiency. End-organ resistance to parathyroid hormone is most commonly associated with vitamin D deficiency. The most common causes are dietary deficiency and chronic renal failure. Y oung infants fed cow’s milk, which is high in phosphate, can develop severe hypocalcemia. Another common cause of hypocalcemia is hyperventilation: the decreased partial pressure of carbon dioxide results in an acute respiratory alkalosis that rapidly decreases levels of ionized calcium. Clinical manifestations of hypocalcemia include muscle weakness, vomiting, and irritability. Infants may simply appear “jittery. ” In severe cases, tetany, laryngospasm, carpopedal spasm, and seizures can occur. Carpopedal spasm is especially common in children with hyperventila tion syndrome. The most characteristic ECG abnormality is a prolonged QT interval. Investigation of hypocalcemia includes laboratory measurement of total serum and ionized calcium, phosphate, total protein and albumin, parathyroid hormone, BUN, and creatinine levels. Urine calcium level should also be collected. If a neonate is seen with hypocalcemia, a chest radiograph should be done to look for a thymic shadow in infants and young children. If the thymus is not present, consider DiGeorge’s syndrome. Treatment is the administration of IV calcium ( Table 132-9). Give calcium gluconate 10% in a dose of 100 milligrams/kg at a rate not to exceed 100 milligrams/min, with continuous ECG monitoring. Following initial correction, a calcium infusion may be required to maintain calcium levels. Further management depends on the cause.  HYPERCALCEMIA Hypercalcemia is a serum calcium level of >11 milligrams/dL and most often results from increased bone resorption. Probably the most common cause in children is malignancy involving the lymphoreticu lar system. Less common causes include vitamin A or D intoxication, hyperparathyroid syndromes, hyperthyroidism, adrenal insufficiency, and pheochromocytoma. Clinical manifestations include hypotonia, fatigue, irritability, anorexia, vomiting, and constipation.

cause in children is malignancy involving the lymphoreticu lar system. Less common causes include vitamin A or D intoxication, hyperparathyroid syndromes, hyperthyroidism, adrenal insufficiency, and pheochromocytoma. Clinical manifestations include hypotonia, fatigue, irritability, anorexia, vomiting, and constipation. Affected children may be clini cally dehydrated and complain of polyuria and/or polydipsia. An ECG may reveal bradycardia and a shortened QT interval. The laboratory evaluation of hypercalcemia includes measurement of total serum and ionized calcium levels, a CBC, and evaluation of total protein and albumin and alkaline phosphatase levels. An evaluation of the vitamin D level may also be indicated, depending on the patient’s medical history. Treatment (Table 132-9) depends on the cause. Acutely, patients with functioning kidneys can be treated with aggressive IV hydration (e.g., twice maintenance), 24 with or without furosemide, 1 to 2 milligrams/kg IV , to a maximum of 40 milligrams. Then, treat the underlying cause. DISORDERS OF MAGNESIUM  HYPOMAGNESEMIA Serum magnesium levels are age independent and range from 1.5 to 2.2 mEq/L. Dietary magnesium is absorbed in the intestine and reab sorbed in the urine, particularly in states of decreased intake. Serum levels of <1.5 mEq/L are considered low and usually result from GI or renal losses as well as some endocrine disturbances. Diarrhea, malabsorption, short gut, and fistulas are potential mechanisms of GI magnesium loss, but iatrogenic causes of renal loss (osmotic diuretics, parenteral fluids, antibiotics, and chemotherapeutics) predominate. Hypercalcemia may cause magnesium loss as well as hypophosphatemia. Hypomagnesemia may also occur in diabetes, disorders of the parathyroid glands, and primary hyperaldosteronism. Clinical manifestations are similar to those seen with hypocalcemia: muscle spasms, weakness, or even atrophy may occur; CNS symptoms include ataxia, abnormal movements, nystagmus, and seizures and occur with very low magnesium levels. Cardiac changes include pro longed PR and QT intervals and may predispose to arrhythmias such as torsades de pointes. Treatment (Table 132-9) depends on the underlying cause. Include magnesium in parenteral or enteral nutritional liquids in chronically ill children. In symptomatic patients (e.g., those with seizures, arrhyth mias), give IV magnesium sulfate, 25 to 50 milligrams/kg administered as a 10% solution over 30 minutes, and repeat every 4 to 6 hours as needed.  HYPERMAGNESEMIA Hypermagnesemia is rare. Serum levels of >2.2 mEq/L are considered elevated. The most common cause is ingestion of exogenous magnesium, typically found in antacids and laxatives. Patients with renal dysfunction are at increased risk. Clinical manifestations include hypotension, loss of deep tendon reflexes, and respiratory failure. Cardiac manifestations include widening of the QRS, PR, and QT intervals. Treatment (Table 132-9) is removal of exogenous sources and hydration accompanied by diuresis. Severe symptoms may be mitigated with IV calcium, 0.5 mL/kg delivered as calcium gluconate. Dialysis is effec tive in patients with renal failure. REFERENCES The complete reference list is available online at www.TintinalliEM.com. TABLE 132-9 Treatment of Disorders of Calcium and Magnesium Treatment Comments Calcium Hypocalcemia 10% calcium gluconate IV, 100 milligrams/kg, at a rate <100 milligrams/min Continuous ECG monitoring Hypercalcemia Hydrate with twice maintenance fluids, furosemide 1–2 milligrams/kg IV to a maximum of 40 milligrams Treat underlying cause Magnesium Hypomagnesemia 10% magnesium sulfate, 25–50 milligrams/kg over 30 min

a 10% calcium gluconate IV, 100 milligrams/kg, at a rate <100 milligrams/min Continuous ECG monitoring Hypercalcemia Hydrate with twice maintenance fluids, furosemide 1–2 milligrams/kg IV to a maximum of 40 milligrams Treat underlying cause Magnesium Hypomagnesemia 10% magnesium sulfate, 25–50 milligrams/kg over 30 min Hypermagnesemia Hydration, diuresis 1–2 milligrams/kg IV furosemide to a maximum of 40 milligrams; or 10% calcium gluconate IV, 0.5 mL/kg Tintinalli_Sec12_p0669-0996.indd 856 8/2/19 7:53 PM