ICF Compartment

The ICF is within the cell membranes. It is the largest fluid compartment, comprising approximately 33% of body weight by 1 year of age. Potassium and phosphate are the primary intracellular electrolytes.

ECF Compartment

The ECF is composed of intravascular fluid (plasma or serum), interstitial fluid (lymph), and transcellular water. The ECF comprises almost half of the body weight in the full-term infant; this percentage declines as the child grows.

Sodium and chloride are the primary electrolytes of the ECF. Although the largest volume within the ECF is interstitial fluid (20% of TBW), it is the plasma or intravascular volume that is essential to cardiac output and systemic perfusion. Transcellular water typically accounts for a small percentage of TBW and is found in the pleural, pericardial, peritoneal, and joint spaces. During some disease states, the volume of transcellular fluid increases.

Role of Osmolality

The term osmolality refers to the concentration of solute (electrolytes and proteins) per liter of fluid. Serum osmolality reflects ECF osmolality. It can be estimated with the following formula*:

Because sodium is the primary electrolyte that determines serum osmolality, a major increase or decrease in serum sodium concentration will increase or decrease the serum osmolality, respectively.

Changes in the osmolality of one body fluid compartment will affect all other compartments. Water shifts between the ICF and the ECF compartments in response to changes in the osmolality of either compartment, moving from the compartment of lower osmolality to the compartment of higher osmolality until osmolality equilibrates. When the osmolality of the extracellular compartment (including the vascular space) decreases, water will shift from the extracellular compartment into cells (Fig. 12-2). Conversely, when the osmolality of the extracellular compartment (including the vascular space) increases, water will shift from the intracellular to the extracellular compartment (including into the vascular space). The volume and acuity of the water shift, as well as likely clinical significance, is determined by the magnitude and acuity of the osmolality gradient between compartments. Significant water shifts can cause neurologic complications.

Renal Influences

The kidneys help maintain fluid balance through filtration and selective reabsorption. Changes in the glomerular filtration rate (GFR) alter the amount of water and sodium excreted or reabsorbed by the kidneys. Expansion of intravascular volume normally increases the GFR, increasing sodium and water excretion. When intravascular volume is depleted, the GFR falls and sodium and water excretion decrease (i.e., more sodium and water are reabsorbed into plasma from the renal filtrate). As noted previously, the kidney is less able to concentrate urine during the first months of life. (See Chapter 13 for more detailed information.)

Endocrine Influences

Several hormones contribute to regulation of fluid and electrolyte balance.

Etiology

Hyponatremia is a low serum sodium concentration, typically less than 130 to 135   mEq/L. It often develops as a complication of disease or therapy. The critically ill infant or child can develop hyponatremia from excessive water intake relative to sodium, excess water retention, increased sodium loss, or a combination of these factors.¹⁰

Hyponatremia can occur in conjunction with hypervolemia, euvolemia, or hypovolemia. Hypervolemic hyponatremia is associated with water intoxication, nephrotic syndrome, cardiac failure, renal failure, and the syndrome of inappropriate antidiuretic hormone (SIADH). Hypovolemic hyponatremia can occur with renal losses (e.g., osmotic diuresis, renal tubular acidosis) or extrarenal losses (e.g., diarrhea, vomiting, burns).¹⁰ Other potential causes include adrenal insufficiency, excessive use of diuretics, and cerebral salt-wasting syndrome.

A laboratory report of a low serum sodium concentration can be misleading. These pseudohyponatremic states are associated with hyperlipidemia, hyperproteinemia, or hyperglycemia. In hyperlipidemia or hyperproteinemia, the lipid or protein displaces fluid from serum, decreasing the relative volume of water and electrolytes. As a result, the reported serum sodium concentration will be low. The total body sodium actually may be normal, although its concentration (in milliequivalents per liter of plasma, or mEq/L) is reduced. Hyperlipidemia of this degree usually produces a milky white plasma.

Because the serum osmolality is determined by the combined effects of particles (solutes) in the serum—especially the sodium, glucose, and blood urea nitrogen—the serum osmolality can be normal if a fall in the concentration of one solute is accompanied by a commensurate (in osmotic effect) increase in the concentration of another solute. With significant hyperglycemia, the high glucose concentration increases serum osmolality, drawing fluid into the vascular space; this may artificially reduce the serum sodium concentration. The significance of this dilutional effect is debatable—the serum sodium concentration may still influence osmotic changes to which the cells are exposed. To estimate the potential effect of severe hyperglycemia on the serum sodium concentration, for every 100   mg/dL rise in serum glucose above normal, the serum sodium concentration is likely to be depressed approximately 1.6   mEq/L below 135   mEq/L.

Pathophysiology and Clinical Signs and Symptoms

An isolated decrease in serum sodium concentration (i.e., without a rise in glucose or blood urea nitrogen) reduces serum osmolality; an acute fall in serum osmolality produces a shift of water from the extracellular compartment (including vascular space) to the intracellular compartment. This fluid shift can cause swelling of cells (edema). Because there is limited capacity for volume expansion within the skull, swelling of brain cells (cerebral edema) can have catastrophic consequences, such as brain herniation and death.

The volume of water shift and the severity of clinical manifestations with hyponatremia are directly related to the acuity and the magnitude of the fall in serum sodium and osmolality. Infants and children who develop hyponatremia that gradually worsens over several days or weeks (e.g., with adrenocortical insufficiency) typically have milder clinical manifestations and may be asymptomatic until the serum sodium is very low.²⁶

Acute hyponatremia that develops within hours or days (i.e., <48   hours) is more likely to produce cerebral edema.²⁶ Seizures and coma are associated with a serum sodium concentration less than 120   mEq/L.

Management

If the child is at risk for hyponatremia, providers should closely monitor the child’s serum sodium concentration to detect and promptly treat hyponatremia before it becomes severe. Frequent neurologic assessments are indicated. Notify an on-call provider immediately if the child develops altered level of consciousness, seizures, or signs of increased intracranial pressure.

Hyponatremia associated with neurologic symptoms is a neurologic emergency. Urgent treatment includes administration of 2 to 4   mL/kg of 3% saline (513   mEq sodium/L, or 0.513   mEq/mL); this will typically raise the child’s serum sodium concentration approximately 1 to 2   mEq/L and raise serum osmolality sufficiently to slow the intracellular water shift. If the SIADH produces seizures or other severe symptoms, hyponatremia and water intoxication can be treated acutely by administration of hypertonic saline (2-4   mL/kg of 3% saline) and furosemide (1-2   mg/kg). These medications will increase the serum sodium concentration and eliminate excess free water (see section, Specific Diseases, Syndrome of Inappropriate Antidiuretic Hormone).

Management of hyponatremia includes restoration of appropriate intravascular volume, replacement of the sodium deficit, and identification and treatment of the underlying cause. Symptomatic hypovolemia is treated with boluses of normal saline or lactated Ringer’s solution. Management of hypervolemic hyponatremia may include fluid restriction and administration of loop diuretics.

Once the child’s neurologic status is stable and perfusion is adequate, plans are made to replace the sodium deficit. The following formula³⁶ is used to calculate the sodium deficit:

During treatment of hyponatremia, providers must closely monitor the serum sodium concentration and the rate of rise in the concentration. If the serum sodium and osmolality are raised too rapidly, the resulting water shifts from the cellular to the extracellular (including intravascular) compartments can produce neurologic complications including intracranial bleeding (Box 12-1). In general, the serum sodium should be raised no faster than approximately 0.5-1.0   mEq/L per hour.³⁵ Additional important assessments include strict monitoring of intake and output, urine specific gravity, serum electrolytes, serum osmolality, and daily weights.

Etiology

Hypernatremia (serum Na⁺ >145-150   mEq/L) occurs less frequently than hyponatremia. One of the body’s major defenses against hypernatremia is thirst. Infants, small children, and any children with significant developmental delay, decreased level of consciousness, or critical illness have an increased risk of hypernatremia during episodes of fluid loss, because they may not be able to signal caregivers of thirst or drink additional fluids.

Hypernatremia is most likely to result from a water deficit (e.g., dehydration, diuretic use, diabetes insipidus, DI). Less commonly, hypernatremia can result from excessive sodium intake, such as if powder for infant formula is incorrectly diluted. The child with hypernatremia may be hypovolemic, euvolemic, or hypervolemic; therefore, it is important to assess the child’s fluid volume status when determining the cause of the hypernatremia.

Pathophysiology and Clinical Signs and Symptoms

Hypernatremia typically increases the serum osmolality. The rise in osmolality stimulates the posterior pituitary to release ADH, which increases renal water reabsorption until the osmolality returns to normal. The increased osmolality associated with hypernatremia also leads to a shift in water from the intracellular to the extracellular compartment, including into the vascular space. This water movement from the cells can cause cellular dehydration and central nervous system dysfunction. Complications including subdural, subarachnoid, and intracerebral bleeding and sinus vein thrombosis can develop with acute and severe increases in serum sodium concentration and the resulting water shift (see Box 12-1). Permanent central nervous system dysfunction can result when the serum sodium concentration is extremely high (e.g., >165-170   mEq/L).¹² When serum osmolality is chronically elevated, brain cells will generate idiogenic osmoles to maintain cell volume (Box 12-2).

Patients who are unable to produce and/or respond to ADH (e.g., patients with DI) are at risk for development of significant hypernatremia and hypovolemia. These patients must be closely monitored to detect and treat these complications before they become severe.

Management

If the patient with hypernatremia has signs of inadequate tissue perfusion (i.e., shock), administer isotonic crystalloid by bolus (20   mL/kg) until perfusion is adequate. Avoid excessive bolus fluid administration (i.e., beyond that needed to treat shock), because it can contribute to a rapid fall in serum sodium and osmolality resulting in cerebral edema and other neurologic complications (see Box 12-2).

Once shock is corrected, estimate the fluid deficit and plan to replace the deficit over 48 to 72   hours, while providing for maintenance fluid requirements as well as for replacement of any ongoing additional fluid losses (e.g., persistent diarrhea). The type of IV fluids administered will vary depending on the rate at which the serum sodium is falling during therapy. Generally, the serum sodium should decrease at a rate no faster than 0.5 to 1.0   mEq/L per hour.

Monitor patients for the clinical manifestations of cerebral edema throughout the course of their treatment. Management of the child with hypervolemic hypernatremia will typically involve loop diuretics and decreased sodium administration.

Etiology

Causes of hypokalemia (serum K+ concentration <2.5 to 3.0   mEq/L) can be classified into three general categories: inadequate potassium intake (rare, but may be iatrogenic), shifts of potassium from the extracellular to the intracellular compartment (e.g., with alkalosis or a rise in serum pH), or excessive losses of potassium (see Evolve Fig. 12-3 in the Chapter 12 Supplement on the Evolve Website for more information). Critically ill patients often develop true potassium deficit following the use of diuretics, especially loop and thiazide diuretics. Some antimicrobial agents (e.g., amphotericin B or carbenicillin) can increase renal potassium losses. Hypokalemia also is associated with severe hypochloremia and the potassium-wasting Bartter’s syndrome.

Because gastrointestinal fluids all contain significant amounts of potassium in the form of potassium chloride salt, vomiting, diarrhea, intestinal fistulas of the small intestine or colon, ileostomy drainage, or gastric suctioning can all result in potassium losses as well as loss of hydrogen ions and chloride.

Pathophysiology and Clinical Signs and Symptoms

The large quantity of intracellular potassium serves as a reservoir to help maintain intravascular potassium concentration despite potassium loss. When the serum potassium concentration begins to decline, some intracellular potassium, known as the exchangeable potassium, moves from the intracellular space to the extracellular compartment (including the vascular space). Only when this amount of exchangeable potassium is depleted will further extracellular potassium loss produce a fall in serum potassium concentration. Thus, the serum potassium concentration may be normal or even elevated when a total body potassium deficit is present.

Evaluation of the patient’s potassium balance is further complicated by potassium shifts between the intracellular and extracellular compartments that result from administration of some medications and with changes in acid-base balance. β-Adrenergic agonists (e.g., inhaled albuterol) can cause a fall in serum potassium, whereas α-adrenergic agents can cause a rise in serum potassium. β-Adrenergic agonists increase intracellular sodium ion movement that stimulates the sodium-potassium pump to move sodium out of the cells. For every three sodium ions pumped out of cells, two potassium ions are allowed to enter cells. Thus, potassium shifts from the extracellular (including vascular) to the intracellular space.

Alpha-adrenergic agents can cause a rise in serum potassium, because potassium shifts from the intracellular to the extracellular (including vascular) space. Insulin administration can produce a fall in the serum potassium concentration, because insulin stimulates cellular uptake of potassium.

Acute alkalosis or a rise in serum pH (e.g., during treatment of acidosis) will cause a fall in serum potassium concentration, because hydrogen ion shifts out of the cell and is replaced by potassium (i.e., potassium moves into the cells). If the serum potassium concentration is within the normal range and the child’s serum pH then rises (e.g., as occurs with treatment of acidosis) hypokalemia may result.

Hypokalemia may also result from increased renal potassium excretion. This hypokalemia can be associated with metabolic alkalosis, renal tubular acidosis, and DKA. Hypokalemia can perpetuate metabolic alkalosis, particularly if either condition is chronic. When the serum potassium concentration is low, the kidney vigorously reabsorbs potassium and must excrete hydrogen ions. As a result, it may be necessary to treat the child’s hypokalemia to correct significant alkalosis.

Excessive renal potassium losses can also result from increased mineralocorticoid activity and increased delivery of sodium to the distal nephron. Excessive renal potassium losses have been associated with administration of antibiotics such as carbenicillin (and other penicillins), amphotericin B, gentamicin and aminoglycosides. A common cause of hypokalemia in the critically ill patient is the use of diuretics, especially loop and thiazide diuretics.

Chronic hypokalemia can change renal concentrating ability and cause polyuria. The kidney has little ability to conserve potassium when body potassium stores become low; as a result, urinary potassium excretion will remain greater than 20   mEq/L once hypokalemia persists for 10 to 20 days.

Although some potassium is lost with vomiting, diarrhea, and loss of other gastrointestinal fluids, potassium losses are exacerbated by intravascular volume contraction. Hypovolemia stimulates aldosterone secretion, which produces sodium and water retention, but it increases hydrogen ion and potassium excretion.

Hypokalemia can cause hyperpolarization of nerve and muscle cells, leading to muscle weakness, slowed nerve impulse conduction, and decreased muscle contraction. Hypokalemia can cause characteristic electrocardiogram (ECG) changes, including development of a U-wave (Fig. 12-3).

Management

Nurses should watch for ECG changes in patients with or at risk for development of hypokalemia. Patients with preexisting cardiac disease may be particularly likely to develop arrhythmias with even mild hypokalemia. Because hypokalemia will potentiate the effects and potential toxic effects of digitalis glycosides (as the result of depressive effects on the sodium-potassium adenosine triphosphatase pump), it is very important to monitor and maintain serum potassium concentration and promptly treat hypokalemia in patients receiving digitalis.

The appropriate speed and method of potassium replacement is based on the severity of the hypokalemia and the child’s clinical condition (including acid-base balance, renal function and urine output). Replacement is typically indicated if the serum potassium concentration is below 3 mEq/L or if the child becomes symptomatic. Enteral replacement in a dose of 0.5-1   mEq/kg will usually correct mild, asymptomatic hypokalemia.¹⁷ The dose may be repeated every 4 to 8   hours.

IV potassium administration is indicated when the serum potassium concentration is less than 2.5   mEq/L or when milder levels of hypokalemia are present in patients who cannot receive enteral replacement (Box 12-3). A typical IV supplement dose is 0.5 to 1.0   mEq/kg, infused over approximately 1 to 3   hours.^6,17 Dilute the potassium adequately and administer it over several hours to prevent bolus or rapid delivery that can produce lethal arrhythmias. Closely monitor the child’s serum potassium concentration and ECG.

The Institute for Safe Medication Practices lists IV potassium among drugs with heightened risk of causing patient harm when administered in error. Most institutions have developed policies regarding IV potassium supplement infusions that incorporate patient safety checks, frequent laboratory verification of serum potassium concentration, and pharmacy preparation of solutions.

If hypokalemia is induced by an acute respiratory or metabolic alkalosis, the treatment of choice is correction of the alkalosis. Potassium administration is rarely necessary.

Etiology

Hyperkalemia (serum potassium >5.0-5.5   mEq/L) can cause life-threatening arrhythmias; it can result from potassium administration, extracellular (including into the intravascular space) shift of potassium ions associated with a fall in serum pH, significant cell destruction (and release of intracellular potassium), or reduced renal excretion of potassium ions.

Pseudohyperkalemia is a high reported serum potassium concentration caused by release of intracellular potassium at the time of phlebotomy or in the specimen after collection.²⁸ Intracellular potassium is released during fingerstick or other traumatic blood sampling and can be released in a blood specimen after collection in patients with severe leukocytosis or thrombocytosis. Pseudohyperkalemia should be considered when an unexpected high serum potassium concentration is reported by the laboratory in patients who are asymptomatic and have an otherwise normal electrolyte and/or acid-base status. If there is a question about the accuracy of a high reported serum potassium concentration in an asymptomatic patient, the concentration should be rechecked before therapy is initiated to reduce the serum potassium.

Pathophysiology and Clinical Signs and Symptoms

A rise in serum potassium concentration in the healthy patient is usually transient because enhanced renal excretion can quickly return the serum potassium concentration to normal. However, if the rate of potassium accumulation exceeds the rate of renal potassium excretion, the serum potassium concentration will rise.

A rise in serum potassium is associated with a fall in serum pH, because potassium shifts from the intracellular to the extracellular compartment (including into the vascular space). Theoretically, for each 0.1 fall in the arterial pH, the serum potassium concentration can be expected to rise 0.6 to 0.8   mEq/L. When the acidosis is corrected (i.e., the serum pH rises), the serum potassium concentration should fall. In this situation, hypokalemia with acidosis is particularly dangerous, because correction of the acidosis can be associated with development of severe hypokalemia. Conversely, because alkalosis lowers the serum potassium concentration (see Hypokalemia, earlier), a high serum potassium concentration in an alkalotic patient is significant and will likely rise further when the alkalosis is corrected.

Additional causes of extracellular (including intravascular) shifts in potassium are: insulin deficiency, rapid cell breakdown, burns, trauma, hyperosmolality (e.g., hyperglycemia, mannitol administration), rhabdomyolysis, and the administration of succinylcholine.²³ Unless the amount of cellular potassium release is excessive, such as in crushing injuries, tumor necrosis syndrome, or administration of succinylcholine, such an extracellular potassium shift alone rarely causes clinically significant hyperkalemia.²³

Decreased potassium elimination can result from renal dysfunction or the administration of medications such as potassium-sparing diuretics. Although both acute and chronic renal failure can cause hyperkalemia, patients with acute renal failure are at higher risk for life-threatening hyperkalemia because the potassium concentration often rises quite rapidly, before the body is able to mount a compensatory response.²⁸ Acidosis or cell injury in these patients will likely worsen the severity of the hyperkalemia.

Hyperkalemia can produce characteristic changes in the ECG such as a tall, peaked T wave, followed by widening of the QRS complex, S-T segment depression, and decreased R-wave amplitude (see Fig. 12-3). If the serum potassium concentration continues to rise, the P-R interval is prolonged, the amplitude of the P wave decreases, and finally the P wave disappears. Ultimately the patient’s rhythm deteriorates into a classic sine wave. Ventricular arrhythmias or fibrillation can occur at any point during this progression.

Management

Critical care management of hyperkalemia includes recognition of at-risk patients, and rapid identification and correction of the hyperkalemia. Priorities of management are determined by the child’s clinical presentation (for more information regarding treatment of hyperkalemia in the patient with renal failure, see Chapter 13).

If the serum potassium concentration is less than 6.5   mEq/L and no ECG changes are present, it may be sufficient to discontinue potassium in IV fluids and medications and closely monitor the patient and the serum potassium concentration. Administration of polystyrene sulfonate (Kayexalate) may be warranted to increase intestinal potassium removal (it results in the exchange of sodium for potassium in the intestinal lumen). Polystyrene sulfonate may also bind calcium and magnesium; therefore, providers should monitor serum concentration of these electrolytes and assess patients for the clinical manifestations of hypocalcemia and hypomagnesemia.

Immediate intervention is required when the serum potassium concentration is greater than 6.5 to 7.0   mEq/L or is associated with ECG changes (see Fig. 12-3). Although the evidence supporting emergent therapies for hyperkalemia is largely anecdotal, widely accepted goals are to stabilize the myocardial cellular membrane, expand the ECF volume, shift potassium into the cells, and remove potassium from the body (Table 12-4).^16,19,20,24

Table 12-4 Emergent Management of Hyperkalemia

Management Goal	Intervention	Comments
Stabilize myocardium	Calcium salts • Calcium gluconate • Calcium chloride

Onset of action occurs within minutes and lasts for approximately 30   min* Expand ECF volume Intravenous fluids Decrease serum concentration of potassium Shift potassium into the ICF Sodium bicarbonate Results in an intracellular shift of potassium; it may take up to 60   min for this to occur,* and the effects can last several hours; acid-base status must be monitored closely.^†
Monitor children with respiratory failure carefully, because buffering of sodium bicarbonate increases CO₂ and may worsen respiratory acidosis if the lungs cannot clear CO₂.
Hypernatremia may develop as complication of this therapy. Insulin and glucose/dextrose Administration of insulin (0.1 unit regular insulin/kg) will activate the sodium-potassium pump, resulting in increased cellular uptake of potassium; insulin should be administered in conjunction with glucose/dextrose.^† The decrease in serum potassium occurs within 15   min and lasts approximately 60   min.* Albuterol Activates the sodium-potassium pump and stimulates the pancreas to release insulin, thereby causing an intracellular shift of potassium; administer albuterol in conjunction with insulin to produce cumulative effect in lowering serum potassium^‡ Remove potassium from the body Kayexalate Decreases potassium absorption in the intestine IV furosemide (thiazide diuretic) May not be a viable option in infants or children with hyperkalemia and impaired renal function Dialysis Indicated for hyperkalemia refractory to medical management

ECF, Extracellular fluid; ICF, intracellular fluid; IV, intravenous.

* Ahee P, Crowe AV: The management of hyperkalemia in the emergency department. J Accid Emerg Med 17:188-191, 2000.

† Jones RE, Brashers VL, Huether SE: Alterations of hormonal regulation. In: McCance KL, Huether SE, editors: Pathophysiology: the biologic basis for disease in adults and children, ed 6. Philadelphia, 2009, Mosby-Elsevier.

‡ Chmielewski CM: Hyperkalemic emergencies: mechanisms, manifestations and management. Crit Care Nursing Clin North Am 10:449-458, 1998.

Etiology

Hypocalcemia (total Ca²⁺ <8.0 to 8.5   mg/dL [<2.0 mmol/L]; ionized Ca²⁺ <4.0 mg/dL [<1.0 mmol/L]) is associated with significant morbidity and mortality in critically ill infants and children. Hypocalcemia can result from inadequate calcium intake, reduced calcium absorption, or excessive calcium excretion (Box 12-4).

The serum ionized calcium concentration will fall if the serum albumin concentration or serum pH rise (e.g., during correction of acidosis or with development of alkalosis). Hypocalcemia can develop after administration of stored whole blood or packed cells preserved with citrate, phosphate, and dextran, because serum ionized calcium can precipitate with the phosphate anticoagulant and can be bound by the citrate. Hyperphosphatemia will also produce hypocalcemia because the phosphate precipitates with calcium.

Pathophysiology and Clinical Signs and Symptoms

When the serum ionized calcium falls, PTH secretion and vitamin D act to increase the serum calcium and lower the serum phosphate. Both PTH and vitamin D increase intestinal calcium absorption and renal calcium reabsorption and decrease renal phosphate reabsorption. Both contribute to the liberation of calcium and phosphate from bone (osteoclastic activity).

Signs and symptoms of hypocalcemia result from increased neuromuscular excitability and can include tingling, muscle cramps, lethargy, carpal-pedal spasm, seizures, and prolonged QT interval on ECG. A classic sign of hypocalcemia is Chvostek’s sign, which is elicited by tapping on the facial nerve at the temple. A positive sign is a twitch of the lip or facial muscles near the nose. Trosseau’s sign is the development of carpal pedal spasm after an extremity artery is occluded for 3 minutes. Severe hypocalcemia can produce muscle tetany.

Management

Management of hypocalcemia includes correction of the cause, administration of calcium supplements as needed, and monitoring for cardiac, neuromuscular, and neurologic dysfunction. Any concurrent conditions (e.g., hyperphosphatemia, hypomagnesemia, respiratory alkalosis) must be identified and treated as indicated.

The healthcare team should immediately treat any acute episode of hypocalcemia in children at risk for impending cardiovascular or neurologic failure. Calcium chloride is the calcium supplement of choice for infants and children, because it provides greater bioavailability of calcium.^11,16a An IV dose of 20   mg/kg of 10% calcium chloride provides 5.4   mg/kg of elemental calcium. Calcium gluconate can be used in neonates (IV dose of 60-100   mg/kg of 10% calcium gluconate provides approximately 5.4-9   mg/kg). Administer IV calcium by slow push or infusion and monitor for arrhythmias. Rapid administration of calcium salts (faster than 100   mg/min) is not recommended because it may produce bradycardia and asystole.^24,32

Etiology

Hypercalcemia (total serum calcium >11-12   mg/dL [>2.75 mmol/L]) is an excess of calcium in the extracellular (including vascular) compartment. A serum calcium concentration greater than 15   mg/dL can be life threatening. Although hypercalcemia is not common, it may be seen in critically ill infants and children with hyponatremia, hyperkalemia, resolution of chronic renal failure, and prolonged immobility. Children with acute leukemias or a large tumor burden can also develop clinically significant hypercalcemia. Hemoconcentration can cause pseudohypercalcemia in hypovolemic patients. In addition, excessive calcium administration to treat hypocalcemia can cause iatrogenic hypercalcemia.

Pathophysiology and Clinical Signs and Symptoms

Hypercalcemia develops when an excessive amount of calcium moves from the bones and intestines into the ECF, overwhelming the regulatory hormones (vitamin D and PTH) and renal excretory systems, and if the function of either of these systems is compromised. Both serum albumin (protein) and pH can affect the serum ionized calcium concentration. An increase in serum protein concentration will increase total serum calcium concentration, but will reduce the ionized calcium concentration because more calcium is bound to protein. A fall in serum pH (acidosis) will decrease serum binding of calcium, so will increase ionized calcium.

Hypercalcemia produces a reciprocal fall in serum phosphate and can produce complications similar to hyperparathyroidism, including renal stones and osteoporosis. Severe hypercalcemia can produce a polyuria-polydipsia syndrome with dehydration. If the polyuria produces dehydration, renal excretion of calcium is reduced, exacerbating the hypercalcemia.

Hypercalcemia decreases excitability of nerve and muscle cells and can cause neuromuscular pain and tingling. Symptoms are often vague and may not be significant until the serum calcium concentration exceeds 12   mg/dL.

Management

Management of hypercalcemia includes identifying the underlying cause, reducing the concentration of calcium in the ECF, and managing clinical manifestations. In patients with known hypercalcemia or in those at risk for its development, it is essential to closely monitor neuromuscular and cardiac function.

A serum calcium concentration greater than 15   mg/dL can be life threatening and requires immediate treatment. Treatment is typically achieved through administration of IV fluids to expand the ECF and loop diuretics to enhance calcium excretion. Thiazide diuretics are contraindicated because they limit calcium excretion.

With life-threatening hypercalcemia, aggressive therapy is needed to reduce the serum calcium. Drugs are typically administered to reduce the serum calcium concentration over several days: biphosphonate inhibits bone reabsorption, calcitonin inhibits calcium reabsorption from bone, mithracin reduces osteoclast activity, and gallium nitrate interferes with osteoclast function (for more information, see Table 15-2).⁴ Administration of a biphosphate such as pamidronate (1   mg/kg) may be indicated in severe hypercalcemia. It can cause mild to moderate hypophosphatemia, hypomagnesemia, and transient hypocalcemia at 2 to 10 days after administration⁹; therefore, it will be important to monitor these electrolytes.

Etiology

Hypomagnesemia (serum magnesium <1.3   mg/dL [0.65 mmol/L]) is common in hospitalized patients, especially those with chronic illness. Hypomagnesemia results from decreased intestinal magnesium absorption or renal failure with increased renal magnesium losses. Diuretics and DKA with osmotic diuresis can produce hypomagnesemia.

Pathophysiology and Clinical Signs and Symptoms

Decreased intestinal absorption of magnesium may be intrinsic or induced by medications (e.g., laxatives) or disease.³⁰ Medical conditions associated with decreased absorption include pancreatitis, severe or chronic diarrhea, prolonged vomiting, malabsorption syndromes, and intestinal and biliary fistulas. Prolonged gastric suctioning can reduce serum magnesium.

Increased renal excretion of magnesium can also be caused by medications such as diuretics (especially loop diuretics), aminoglycosides, amphotericin B, cisplatin, and cyclosporine. Medical conditions that cause rapid diuresis (e.g., DKA; hyperosmolar, hyperglycemic, or nonketotic coma) can also cause an increase in magnesium excretion.

Hypomagnesemia can cause lethal ventricular arrhythmias, including torsades de points and ventricular fibrillation. Because magnesium is essential to ATP metabolism, hypomagnesemia can damage the sodium-potassium pump, which depends on ATP to function properly.

Hypomagnesemia can be associated with additional electrolyte imbalances and with complications of the primary disease (e.g., renal failure). Hypomagnesemia causes an extracellular potassium shift that may transiently increase serum potassium. However, hypomagnesemia also causes increased urinary losses of sodium, potassium, phosphate, and hydrogen; therefore, it typically causes deficiency of these electrolytes. Hypomagnesemia can also produce hypocalcemia and hyperphosphatemia through impairment of PTH synthesis or secretion. Signs of hypomagnesemia are similar to signs of hypocalcemia, including possible tingling, muscle cramps, Chvostek’s sign, tetany, and seizures (see under Hypocalcemia).

Management

If hypomagnesemia produces ventricular arrhythmias, cardiopulmonary resuscitation is needed (see Chapter 6) with bolus magnesium administration.²⁴ Acute hypomagnesemia in children at risk for impending cardiovascular or neurologic failure is treated immediately with IV administration of magnesium sulfate (25-50   mg/kg infusion over 10-20   minutes or longer).²⁴ Monitor for arrhythmias and hemodynamic instability during administration of magnesium supplements.³⁰

Additional critical care management of an acute episode of hypomagnesemia includes correction of the cause and administration of other electrolyte supplements as needed. Treatment of hyponatremia, hypokalemia, and hypocalcemia is often necessary (see sections on Hyponatremia, Hypokalemia, and Hypocalcemia in this chapter for more information).

Monitor cardiac, muscular, and neurologic function throughout therapy. Although altered neuromuscular excitability is the most common feature of hypomagnesemia, patients can develop respiratory muscle depression and hypoventilation, requiring mechanical ventilation.

Etiology

Hypermagnesemia (serum magnesium >2.5   mg/dL [1.25 mmol/L]) is far less common than hypomagnesemia. Hypermagnesemia can result from decreased renal excretion of potassium or, less commonly, an increase in magnesium intake through the intestine.

Pathophysiology, Clinical Signs, and Symptoms

Hypermagnesemia usually results from decreased renal excretion of magnesium, most commonly caused by chronic renal failure. Increased magnesium load and intestinal absorption may complicate the use of magnesium-containing laxatives or antacids.

Clinical signs and symptoms are associated with decreased neuromuscular and cardiovascular function. These signs and symptoms can include weakness, neurologic or respiratory depression, bradycardia, and hypotension.

Management

Patients at risk for hypermagnesemia should be monitored closely, because severe hypermagnesemia can lead to coma or cardiac arrest.²⁷ Management of the pediatric patient with hypermagnesemia includes identification and correction of the cause and administration of calcium salts and IV fluids. Calcium salts antagonize magnesium and can reverse cardiac complications.

If renal function is normal, administration of IV fluids will facilitate renal excretion of magnesium. Dialysis may be indicated, particularly for children with renal failure.

Pathophysiology

Dehydration is classified by severity and by its effect on serum sodium concentration. Hyponatremic dehydration (serum Na⁺ <130   mEq/L) occurs when there is a relatively greater loss of sodium than water, so the serum sodium concentration falls. This effect is often seen when gastrointestinal fluid losses are replaced with water or other hypotonic solution (e.g., 5% dextrose and water).²² The resulting hyponatremia creates an osmolality gradient between the extracellular (including vascular) and intracellular compartments, so that water shifts from the vascular and interstitial spaces to the intracellular compartment. This water shift increases the severity of the clinical signs of (intravascular) volume depletion at any given volume deficit.

Hypernatremic dehydration (serum Na⁺ >150   mEq/L) develops when there is a relatively greater loss of water than sodium (e.g., untreated DI). The resulting hypernatremia increases the extracellular osmolality, so that water shifts from the cellular to the extracellular compartment (i.e., intravascular and interstitial spaces). This free water shift decreases the severity of the clinical signs of volume depletion that will be present at any given volume deficit.

Clinical Signs and Symptoms

The clinical manifestations of dehydration will vary based on the severity of the fluid deficit and the serum sodium concentration. Table 12-5 shows a comparison of the clinical manifestations of mild, moderate and severe dehydration.

Management

The severity of a child’s fluid volume deficit is estimated on the basis of weight loss, clinical manifestations and diagnostic studies. If a weight before illness is available, 1   kg of weight loss is equivalent to 1000   mL (1   L) of fluid loss.

If signs of shock are present (i.e., signs of poor peripheral perfusion or hypotension), initial management focuses on restoring intravascular volume to treat shock. Typically, 20   mL/kg IV boluses of isotonic crystalloid are administered until signs of shock are corrected. Infants or children with a severe fluid volume deficit may require resuscitation with 60   mL/kg or more of isotonic crystalloid.¹¹

During volume resuscitation, providers should closely monitor signs of systemic perfusion (including mental status, skin perfusion and urine output), heart rate and blood pressure, to evaluate response to therapy. The fluid bolus administration is repeated, as needed. If volume resuscitation is adequate, the blood pressure and signs of systemic perfusion and blood pressure should improve and the heart rate should decrease toward normal; if the child fails to improve, additional boluses are needed or there may be other causes of the child’s shock. See Chapter 6 for further details of the management of hypovolemic shock.

Once initial fluid resuscitation is complete, ongoing management includes estimation and replacement of water and electrolyte deficits. In isotonatremic or hyponatremic dehydration, the fluid and electrolyte deficit is typically replaced over a period of 24 to 36   hours to restore intravascular volume within a short period of time while preventing overexpansion of the ECF.¹⁰ In the presence of hyponatremic dehydration, the need for sodium replacement should be carefully evaluated.

In hypernatremic dehydration, replacement of fluid and electrolyte deficit is typically accomplished more slowly, over a period of 48 to 72 hours. The goal is to prevent rapid decreases in the serum sodium and osmolality during rehydration because such decreases can produce an intracellular water shift and neurologic complications. Replacement fluids to treat the fluid deficit are administered in addition to routine maintenance fluids (see Table 12-2) and replacement of any ongoing fluid losses (e.g., emesis or diarrhea).

Etiology

SIADH is characterized by ADH secretion in the absence of a physiologic stimulus. Patients with SIADH demonstrate low serum osmolality, hyponatremia, and hypervolemia. Causes of SIADH include central nervous system injury (e.g., surgery, tumor, traumatic brain injury) or infection, disease or damage to the pituitary stalk or hypothalamus, holoprosencephaly, spinal cord injury or surgery, chemotherapy, pulmonary disease, and liver disease.³⁴ The critically ill patient with any of these conditions requires close monitoring for the development of SIADH.

Pathophysiology

ADH secretion results in increased permeability of the renal collecting ducts and distal tubules to water, resulting in increased water reabsorption, increased intravascular volume, and decreased urine volume. As a result, patients with SIADH develop a state of hypervolemia with dilutional hyponatremia (i.e., the dilutional effect of increased intravascular water).

Clinical Signs and Symptoms

Clinical manifestations of SIADH include adequate circulating volume, signs of hyponatremia, and decreased serum osmolality discussed in the second section of this chapter (see Hyponatremia). Urine volume is low (output typically <0.5   mL/kg per hour), with inappropriately high urine osmolality.

Laboratory studies consistent with SIADH include a low serum sodium (typically <130   mEq/L) and osmolality (<275   mOsm/L) with high urine sodium, specific gravity, and osmolality.

Management

Management of SIADH is targeted at the prevention of complications associated with hyponatremia. Early detection of neurologic deterioration is critical; therefore, frequent neurologic assessments are needed. If neurologic complications develop, including a change in mental status or seizure activity, immediate treatment includes administration of hypertonic saline (e.g., 2-4   mL/kg of 3% saline should raise serum sodium approximately 1 to 2   mEq/L) and loop diuretics (e.g., furosemide).³⁴ These therapies should raise the serum sodium sufficiently to slow the intracellular water shift.

Treatment of SIADH includes restriction of free water intake (to approximately half or two-thirds of estimated maintenance fluid requirements) and close monitoring of neurologic function, fluid intake and output, urine specific gravity, and serum sodium.

Etiology

Cerebral salt wasting (CSW) is caused by increased circulating levels of ANP with resulting natriuresis and contraction of intravascular volume, including potential hypovolemia. Causes of CSW are the same as those causing SIADH (see sections, Specific Diseases and Syndrome of Inappropriate Antidiuretic Hormone). When CSW is associated with a head injury, it typically develops 2 to 7 days after the injury. CSW can also complicate congestive heart failure, Cushing’s syndrome, DKA, and hyperaldosteronism.³³

Pathophysiology

Intracranial disease or injury and complications of other disease are thought to alter neurologic secretion of ANP and other natriuretic peptides.²⁵ Increased circulating levels of ANP lead to increased excretion of a large amount of sodium in a high volume of urine. Like SIADH, CSW produces hyponatremia with a low serum osmolality and a high urine sodium and urine osmolality. However, because ANP and other natriuretic peptides produce a high urine volume, the patient also develops mild to moderate dehydration.³⁴

Clinical Signs and Symptoms

Clinical manifestations of CSW include the signs and symptoms of hyponatremia (see “Hyponatremia” earlier in chapter) and those of mild to moderate dehydration (see Table 12-5). Laboratory studies confirm hyponatremia (serum Na⁺ <130   mEq/L) and increased urinary sodium (urine Na⁺ >80   mEq/L). Although not routinely monitored, serum levels of ANP are increased.³³

Management

Because the priorities of management differ, it is important to distinguish CSW from SIADH (Table 12-7).^14,33 Treatment of CSW includes sodium replacement with oral salts or hypertonic saline, volume replacement with isotonic crystalloids, and vigilant monitoring for and prompt treatment of adverse effects of hyponatremia and hypovolemia.²⁵ Mineralocorticoid therapy (fludrocortisone) can enhance sodium reabsorption and expand intravascular fluid volume in patients with CSW.²⁹

Etiology

DI is caused by a deficiency of ADH secretion (neurogenic or central DI) or an insensitivity of renal receptors to ADH (nephrogenic DI). Neurogenic DI is caused most commonly by lesions of the central nervous system (pituitary tumors, Langerhans cell histiocytosis, germinoma, craniopharyngioma, suprasellar tumors) or the resection of these lesions. DI also occurs as a complication of brain death from severe traumatic brain injury. Inherited mutations in the vasopressin gene are uncommon causes of central DI without associated central nervous system pathology.

Nephrogenic DI can be hereditary or acquired. The renal ADH receptor is carried on the X chromosome, resulting in a male predominance of inherited (X-linked) nephrogenic DI. DI can complicate drug administration or damage to the renal tubules. Amphotericin B, loop diuretics, and some anesthetics have been reported to cause reversible DI. Irreversible nephrogenic DI results from a loss of ADH sensitivity secondary to renal disease or an insult that interferes with the kidneys’ ability to concentrate water.

Pathophysiology

A deficit of ADH or lack of renal response to ADH results in decreased reabsorption of water by the renal distal tubules, so a significant volume of water is lost in the urine. As a result of this free water loss, unless fluid replacement is provided, patients can rapidly develop significant hypovolemia and hypernatremia (concentration effect).

Clinical Signs and Symptoms

The classic clinical manifestations of DI include polyuria, hypernatremia, and intense thirst. If not recognized early, the infant or child with DI can rapidly develop hypovolemic shock. In the chronic state, the excessive water intake associated with DI leads to anorexia, weight loss, and a catabolic state.

Patients at risk should be monitored closely for the clinical manifestations of hypovolemia and hypernatremia. Laboratory studies consistent with DI (see Table 12-7) include elevated serum sodium (Na⁺ >150   mEq/L) and osmolality (>295   mOsm/L) and low urine osmolality (<100-200   mOsm/L).³³

Management

Critical care management of DI includes administration of exogenous vasopressin (aqueous vasopressin [5-10 units subcutaneously] or lysine vasopressin [2-4 units IV]) or the vasopressin analog, 1-Deamino-8-d-Arginine Vasopressin (DDAVP[5-20 mcg intranasally every 12-24   hours]), careful fluid replacement, close monitoring of fluid intake and output, and close monitoring of serum sodium and other electrolytes.^33,34 While urine volume is high, it is also important to monitor for the signs and symptoms of hypovolemic shock and support electrolyte balance.

When urine output is high, urine output is totaled typically every 10 or 15   minutes. In the next equal time interval (i.e., the next 10 or 15   minutes), the volume lost in the urine is replaced milliliter for milliliter (typically alternating 5% dextrose and water with 5% dextrose and 0.2% sodium chloride). Replacement fluid is added to maintenance fluid requirements and must also include replacement of any additional sources of fluid loss (e.g., gastric drainage).

Etiology

DKA is a life-threatening complication of diabetes mellitus that includes the combination of severe hyperglycemia and ketoacidosis. Approximately 40% of children with diabetes mellitus present with DKA as their first clinical manifestation of diabetes mellitus.²⁵

Type I diabetes mellitus in children results from a loss of insulin-secreting pancreatic beta cells. The most common form of type I diabetes is triggered by a combination of genetic susceptibility and environmental factors, including some viruses, that produce autoimmune destruction of beta cells.¹⁵

Pathophysiology

DKA results from a severe deficiency of insulin that impairs glucose uptake into the cell. To correct the ensuing energy deficit, there is an increase in counter-regulatory hormones such as glucagon, catecholamines, cortisol, and growth hormone in an attempt to produce more glucose. As a result, the serum glucose concentration is extremely high, but glucose uptake by the cells continues to be impaired. A state of intracellular energy debt ensues, resulting in derangements in the metabolism of fat, protein, and carbohydrates. Gluconeogenesis occurs, with the breakdown of proteins and lipids to make amino acids and fatty acids available as energy substrates.

Ketoacids—acetoacetic acid and beta-hydroxybutyric acid—are released from adipocytes in instances of prolonged insulin deficiency. The presence of high levels of these circulating ketoacids results in ketoacidosis.³⁴ Children with DKA always experience acidosis and hyperosmolar dehydration with glucosuria and osmotic diuresis.

Deficits of sodium, potassium, and phosphate are always present. Although there are urinary losses of these electrolytes, the presence of severe dehydration and hemoconcentration with acidosis (producing an extracellular potassium shift) may initially mask these deficiencies. As a result, the child may have normal or even elevated serum sodium, potassium, and phosphate concentrations despite total body deficits of these electrolytes. After treatment and rehydration, the serum electrolyte concentrations fall, and hyponatremia and hypokalemia develop. Hypokalemia can contribute to cardiac arrhythmias and death on rare occasions if it is not corrected quickly (see section, Clinical Signs and Symptoms).

Finally, dehydration, acidosis, and osmotic water shifts into brain cells (see Box 12-1) can contribute to life-threatening cerebral edema or intracranial thrombotic events.¹⁸ A major difference between children and adults with DKA is the susceptibility of the young to potentially fatal episodes of cerebral edema. Proposed mechanisms of cerebral edema include: accumulation of intracellular idiogenic osmoles (see Box 12-2); vasopressin and atrial natriuretic factor producing water retention, natriuresis, and hyponatremia; disruption in cell membrane ion exchange processes, causing intracellular ion movement and cell swelling; hypoxia and ischemia; ketones and acidosis contributing to the inflammatory cascade; and abnormalities in water (aquaporin) channels in the glial cells of the brain.¹⁸

Symptomatic cerebral edema in children with DKA can cause death or neurologic devastation.²⁰ Additional intracranial pathologic conditions—including bleeding, thrombosis, infarction or emboli—can cause altered mental status in children with DKA.¹⁸

Clinical Signs and Symptoms

Children with DKA have severe hyperglycemia (serum glucose ≥180   mg/dL or >10   mmol/L) and ketoacidosis. Additional signs and symptoms are related to the severity of the resulting hyperosmolality, volume depletion, and acidosis. Children with DKA generally present with a 5% to 10% fluid deficit⁷ caused by the massive water losses secondary to glucosuria.

Acidosis results from the extremely large quantity of ketoacids in the blood. Acetoacetic acid may be reduced to beta-hydroxybutyric acid or decarboxylated to acetone. This ketonemia produces the classic “fruity breath” in children with DKA. The resulting urinary excretion of these ketone bodies, ketonuria, causes further osmotic loss of fluids and electrolytes. In the presence of acidosis, the body develops compensatory hyperpnea or Kussmaul breathing, a classic sign of DKA.

As noted previously, the serum sodium, potassium, and phosphate concentrations may be low, normal, or high but deficits of these electrolytes are present. The serum sodium should be interpreted in light of the serum glucose concentration (each 100   mg/dL rise in serum glucose above 180   mg/dL is likely to depress the serum sodium 1.6   mEq/L below 135   mEq/L). The serum potassium should be evaluated in the context of the serum pH: acidosis causes an extracellular shift in potassium, so the serum potassium rises. After treatment and rehydration, serum electrolyte concentrations fall; therefore, hyponatremia and hypokalemia can develop with attendant complications (see the Chapter 12 Supplement on the Evolve Website for a case study that demonstrates typical serum sodium and glucose values in a patient with DKA).

Dehydration, acidosis and osmotic fluid shifts in the brain can contribute to life-threatening cerebral edema or intracranial thrombotic events. These central nervous system complications can produce decreased responsiveness, posturing, abnormal respiratory patterns, and signs of increased intracranial pressure and cerebral herniation.¹⁸ Table 12-8 shows a summary of the clinical manifestations of DKA and their underlying mechanisms.

Table 12-8 Clinical Manifestations of Diabetic Ketoacidosis

Signs and Symptoms	Underlying Mechanisms
Hyperglycemia, dehydration, cardiovascular collapse	Osmotic diuresis secondary to hyperglycemia
Acidosis	Accumulation of ketoacids and lactic acid in serum from lipolysis, resulting in increased H+ concentration in serum
Electrolyte imbalance: sodium	Total body hyponatremia because of passive loss of electrolytes as a result of osmotic diuresis; however, serum sodium may be high as a result of hemoconcentration
Electrolyte imbalance: potassium	In acidosis, potassium shifts from ICF to ECF; therefore, initially serum potassium may be normal or even high, but will decrease as a result of osmotic diuresis and correction of acidosis
Cardiac arrhythmia	Hypokalemia or hyperkalemia
Ketonuria	Serum ketone levels rise above the renal threshold and are spilled in the urine
Hyperpnea	Compensatory mechanism; effort to blow off excess CO2 and thereby correct the degree of acidosis
Mental status changes, cerebral edema	Possibly related to rate of correction of hyperglycemia, level of acidosis, fluid shifts

ECF, Extracellular fluid; ICF, intracellular fluid.

From Trimarchi T: Endocrine critical care problems. In: Curley MAQ, Moloney-Harmon PA, editors: Critical care nursing of infants and children, ed 2, Philadelphia, 2001, WB Saunders, p. 817.

Management

Priorities of management of DKA in order of importance are: assessment and support of neurologic function (including support of patent airway and effective ventilation), assessment and support of circulation (including volume resuscitation), insulin therapy, and restoration and maintenance of electrolyte, glucose and acid-base balance (Box 12-5). Consideration is also given to confounding factors, such as infection, injury or other patient problems.

Although very few children present with neurologic compromise (primarily cerebral edema) this can be a very poor prognostic indicator. Most who present with this finding perish and those who survive are often severely neurologically compromised with little or no independent function.²⁰

If the child’s level of consciousness deteriorates, cerebral edema may be present, and urgent intervention is needed (see diagnostic criteria for cerebral edema^21a in Box 12-6). If clinical signs of cerebral edema develop, immediate treatment with IV mannitol (0.2-1.0   g/kg over 30-60   minutes) is indicated. Hypertonic saline (e.g., 3% sodium chloride, 10   mL/kg, administered IV over 30   minutes) may be used as an alternative to mannitol. If the child’s ability to protect the airway or spontaneous ventilation deteriorates, intubation and mechanical ventilation are indicated.

The child’s volume deficit is initially treated with the administration of normal saline or lactated Ringer’s. The quantity of fluid administered is determined by the patient’s clinical severity; if shock is present, bolus administration of isotonic crystalloids is needed. For less significant volume deficit, typically 10 to 20   mL/kg is administered over 1 to 2   hours and repeated as needed.¹⁸ Replacement of the total fluid deficit is planned over approximately 48   hours or longer. Isotonic crystalloids are used for initial fluid replacement; the sodium content may then be reduced to 0.45% sodium chloride with potassium added as the child’s condition stabilizes.

Replacement of insulin is generally accomplished by continuous IV infusion. An infusion of regular insulin (0.05 to 0.1 unit/kg per hour) is titrated to gradually reduce the serum glucose at the rate of approximately 50 to 100   mg/dL per hour. Simultaneous infusion of 10% glucose IV can be titrated to control the maximum rate of decline in the serum glucose to no more than 100   mg/dL per hour. Glucose infusion is preferable to slowing the insulin infusion, because reducing the insulin dose can worsen the patient’s acidosis.¹⁸

As noted previously, patients with DKA typically have deficits of water, sodium, potassium, and phosphate. Although serum electrolyte concentrations may be normal at the time of initial clinical presentation, with treatment hyponatremia, hypokalemia, and hypophosphatemia are likely to be present. Replacement fluids are selected to address these deficits. Some landmark studies suggest that phosphate replacement is of no clinical value.^8,38 There is no evidence that the addition of sodium bicarbonate to correct acidosis is of value, and it may contribute to hypokalemia and cerebral edema.¹⁸ To prevent a fall in serum osmolality when the serum glucose is reduced, the serum sodium concentration should rise approximately 1.6   mEq/L for every 100   mg/dL fall in serum glucose concentration.

Providers should look for evidence of confounding factors in a child with DKA. These factors include infection, illicit use of drugs or other medications, injury, or other intracranial pathologic finding. Most of these factors will aggravate acidosis and slow the recovery from DKA.

Box 12-7 contains a typical management plan for children with DKA. As a general rule, patients in DKA recover from acidosis within 24   hours after presentation.

Adrenal Insufficiency