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In the name of God Pediatrics hypernatremia Hypernatremia is defined as a serum sodium concentration of more than 145 mEq/L. It is characterized by a deficit of total body water (TBW) relative to total body sodium levels due to either loss of free water, or infrequently, the administration of hypertonic sodium solutions.[1] In healthy subjects, the body's 2 main defense mechanisms against hypernatremia are thirst and the stimulation of vasopressin release. Figure A: Normal cell. Figure B: Cell initially responds to extracellular hypertonicity through passive osmosis of water extracellularly, resulting in cell shrinkage. Figure C: Cell actively responds to extracellular hypertonicity and cell shrinkage in order to limit water loss through transport of organic osmolytes across the cell membrane, as well as through intracellular production of these osmolytes. Figure D: Rapid correction of extracellular hypertonicity results in passive movement of water molecules into the relatively hypertonic intracellular space, causing cellular swelling, damage, and ultimately death. Pathophysiology Hypernatremia represents a deficit of water in relation to the body's sodium stores, which can result from a net water loss or a hypertonic sodium gain. Net water loss accounts for most cases of hypernatremia. Hypertonic sodium gain usually results from clinical interventions or accidental sodium loading. As a result of increased extracellular sodium concentration, plasma tonicity increases. This increase in tonicity induces the movement of water across cell membranes, causing cellular dehydration. The following 3 mechanisms may lead to hypernatremia, alone or in concert: Pure water depletion (eg, diabetes insipidus) Water depletion exceeding sodium depletion (eg, diarrhea) Sodium excess (eg, salt poisoning) Sustained hypernatremia can occur only when thirst or access to water is impaired. Therefore, the groups at highest risk are infants and intubated patients. Because of certain physiologic characteristics, infants are predisposed to dehydration. They have a large surface area in relation to their height or weight compared with adults and have relatively large evaporative water losses. In infants, hypernatremia usually results from diarrhea and sometimes from improperly prepared infant formula or inadequate mother-infant interaction during breastfeeding. Hypernatremia causes decreased cellular volume as a result of water efflux from the cells to maintain equal osmolality inside and outside the cell. Brain cells are especially vulnerable to complications resulting from cell contraction. Severe hypernatremic dehydration induces brain shrinkage, which can tear cerebral blood vessels, leading to cerebral hemorrhage, seizures, paralysis, and encephalopathy. In patients with prolonged hypernatremia, rapid rehydration with hypotonic fluids may cause cerebral edema, which can lead to coma, convulsions, and death. Epidemiology Frequency United States Hypernatremia is primarily a hospital-acquired condition occurring in children of all ages who have restricted access to fluids, mostly due to significant underlying medical problems such as a chronic disease, neurologic impairment, a critical illness, or prematurity. The incidence is estimated to be greater than 1% in hospitalized patients. Hospital-acquired hypernatremia accounts for 60% of hypernatremia cases in children. Gastroenteritis contributes to the hypernatremia in only 20% of cases. The group most affected is intubated, critically ill patients. Most cases result from a failure to freely administer water to patients. The incidence of breastfeeding-related hypernatremia is 1-2%. International In developing nations, the reported incidence is 1.5-20%. Mortality/Morbidity In children with acute hypernatremia, mortality rates are as high as 20%. Neurologic complications related to hypernatremia occur in 15% of patients. The neurologic sequelae consist of intellectual deficits, seizure disorders, and spastic plegias. In cases of chronic hypernatremia in children, the mortality rate is 10%. Race No predilection is documented. Sex No sex difference is known. Age In the pediatric population, hypernatremia usually affects newborns and toddlers who depend on caretakers for water, as well patients of any age who have significant underlying medical problems such as a chronic disease, neurologic impairment, a critical illness, or prematurity. History Patients in certain situations or with certain conditions are at risk for hypernatremia, as follows: o Hospitalized patients who receive exclusive intravenous fluids o Patients with coma o Newborns o Toddlers o Patients with diabetes insipidus o Patients receiving alkali therapy o Patients with diarrhea o Patients with fever o Patients with renal disorders (eg, dysplasia, medullary cystic disease, polycystic kidney disease, tubulointerstitial disease) o Patients with obstructive uropathy o Patients with electrolyte disturbances (eg, hypokalemia, hypercalcemia) o Patients with heat stroke or excessive hypotonic fluid loss Signs and symptoms of hypernatremia include the following: o Irritability o High-pitched cry or wail o Periods of lethargy interspersed with periods of irritability o Altered sensorium o Seizures o Increased muscle tone o Fever o Rhabdomyolysis[2, 3] o Oligoanuria o Excessive diuresis Physical Skin turgor is a physical finding in patients with hypernatremia. Extracellular and plasma volumes tend to be maintained in hypernatremic dehydration until dehydration is severe (ie, when the patient loses >10% of body weight). When dehydration is severe, skin turgor is reduced, and the skin develops a characteristic doughy appearance. Causes Hypovolemic hypernatremia o Diarrhea o Excessive perspiration o Renal dysplasia o Obstructive uropathy o Osmotic diuresis Euvolemic hypernatremia o Central diabetes insipidus causes o Idiopathic causes o Head trauma o Suprasellar or infrasellar tumors (eg, craniopharyngioma, pinealoma) o Granulomatous disease (sarcoidosis, tuberculosis, Wegener granulomatosis) o Histiocytosis o Sickle cell disease o Cerebral hemorrhage o Infection (meningitis, encephalitis) o Associated cleft lip and palate o Nephrogenic diabetes insipidus causes o Congenital (familial) conditions o Renal disease (obstructive uropathy, renal dysplasia, medullary cystic disease, reflux nephropathy, polycystic disease) o Systemic disease with renal involvement (sickle cell disease, sarcoidosis, amyloidosis) o Drugs (amphotericin, phenytoin, lithium, aminoglycosides, methoxyflurane) Hypervolemic hypernatremia o Improperly mixed formula o NaHCO3 administration o NaCl administration o Primary hyperaldosteronism Differential Diagnoses Diabetes Insipidus Nephrogenic Diabetes Insipidus Laboratory Studies The following studies are indicated in patients with suspected hypernatremia: Serum tests of sodium, osmolality, BUN, and creatinine levels Urine tests of sodium concentration and osmolality o In cases of hypovolemic hypernatremia, extrarenal losses show urine sodium levels of less than 20 mEq/L, and in cases of renal losses, urine sodium values are more than 20 mEq/L. o In euvolemic hypernatremia, urine sodium data vary. o In hypervolemic hypernatremia, the urine sodium level is more than 20 mEq/L. Imaging Studies Imaging studies of the head should be considered in alert patients with severe hypernatremia to rule out a hypothalamic lesion affecting the thirst center. CT scans may help in diagnosing intracranial tumors, granulomatous diseases (eg, sarcoid, tuberculosis, histiocytosis), and other intracranial pathologies. MRI further delineates the pathology. Other Tests Aldosterone test Cortisol test Antidiuretic hormone (ADH) test Corticotropin (ACTH) test Medical Care Medical care involves the correction of hypernatremia. In correcting hypernatremia, do not rapidly decrease the sodium level because a rapid decline in the serum sodium concentration can cause cerebral edema. The recommended rate of sodium correction is 0.5 mEq/h or as much as 10-12 mEq/L in 24 hours. Dehydration should be corrected over 48-72 hours. Guidelines for hydration management have been established.[4] If the serum sodium concentration is more than 200 mEq/L, peritoneal dialysis should be performed using a high-glucose, low-sodium dialysate. One of the following equations may be used to calculate body water deficit: o The equations are based on a goal of plasma sodium concentration of 145 mEq/L. In children, total body water (TBW) is 60% of their lean body weight. Therefore, TBW = 0.6 X weight. Babies are an exception to these equations and may have a TBW as much as 80% of their body weight. Water deficit (in L) = [(current Na level in mEq/L ÷ 145 mEq/L) - 1] X 0.6 X weight (in kg) Water deficit (in L) = [(current Na level in mEq/L - 145 mEq/L)/145 mEq/L)] X 0.6 X weight (in kg) Water deficit (in L) = [1- (145 mEq/L ÷ current Na level in mEq/L)] X 0.6 X weight (in kg) o Example calculation: A child weighs 10 kg and has a plasma sodium concentration of 160 mEq/L. By using the first equation, water deficit (in L) = [(160 mEq/L ÷ 145 mEq/L) - 1] X 0.6 X 10 = 0.62 L. The volume of replacement fluid needed to correct the water deficit is determined by using the concentration of sodium in the replacement fluid. The replacement volume can be determined as follows: o Replacement volume (in L) = TBW deficit X [1 ÷ 1 - (Na concentration in replacement fluid in mEq/L ÷ 154 mEq/L)] o Example calculation: If the patient from the example calculation above has a TBW of 0.62, and if the replacement fluid contains 0.2% NaCl (Na concentration of 34 mEq/L), the replacement volume (in L) = 0.62 L X [1 ÷ 1 - (34 mEq/L ÷ 154 mEq/L)] = 0.79 L. This volume has to be replaced slowly over 48-72 hours. The election of intravenous fluid is based on the following: o If the patient is hypotensive, normal saline (lactated Ringer solution, or 5% albumin solution) should be used regardless of a high serum sodium concentration. o In hypernatremic dehydration, 0.45% or 0.2% NaCl should be used as a replacement fluid to prevent excessive delivery of free water and a too-rapid decrease in the serum sodium concentration. o In cases of hypernatremia caused by sodium overload, sodium-free intravenous fluid (eg, 5% dextrose in water) may be used, and a loop diuretic may be added. o The serum sodium concentration should be monitored frequently to avoid toorapid correction of hypernatremia. o In cases of associated hyperglycemia, 2.5% dextrose solution may be given. Insulin treatment is not recommended because the acute decrease in glucose, which lowers plasma osmolality, may precipitate cerebral edema. o Once the child is urinating, add 40 mEq/L KCl to fluids to aid water absorption into cells. o Calcium may be added if the patient has an associated low serum calcium level. Serum sodium levels should be monitored every 4 hours. Consultations Consultation is also recommended for patients with renal dysplasia, medullary cystic disease, reflux nephropathy, or polycystic disease. Diet Critical care specialist: Patients with symptomatic hypernatremia may need to be transferred to a pediatric ICU for appropriate treatment and monitoring. Endocrinologist: Consult an endocrinologist for patients with primary hyperaldosteronism. Nephrologist: Consult a nephrologist in cases of renal failure, obstructive uropathy, and serum sodium levels of more than 180 mEq/L for possible peritoneal dialysis. In diabetes insipidus, a sodium-restricted and protein-restricted diet should be prescribed. Medication Summary Vasopressin and vasopressin analogs Class Summary Desmopressin is a synthetic ADH with actions mimicking vasopressin. These agents are used to treat diabetes insipidus, which deprives the kidney of its capacity to produce concentrated urine. This effect results in large volumes of dilute urine (polyuria) and excessive thirst (polydipsia). Serum sodium concentrations may be elevated, but hypernatremia is most likely to be severe when fluid is restricted. View full drug information Desmopressin acetate (DDAVP) Structural analog of vasopressin (ADH), the endogenous posterior pituitary hormone that maintains serum osmolality in a physiologically acceptable range. Works in neurohypophysial (eg, central) diabetes insipidus. Exerts similar antidiuretic effects. Vasopressin increases resorption of water at level of renal collecting duct, reducing urinary flow and increasing urine osmolality. View full drug information Vasopressin (Pitressin) Exogenous, parenteral form of ADH. Antidiuretic and increases resorption of water at renal collecting ducts. Diuretics Class Summary These drugs promote the excretion of water and electrolytes by the kidneys. They are used in patients with nephrogenic diabetes insipidus. View full drug information Hydrochlorothiazide (Esidrix, HydroDIURIL) Works by increasing excretion of sodium, chloride, and water by inhibiting sodium ion transport across renal tubular epithelium. Resulting sodium depletion reduces glomerular filtration rate, enhancing reabsorption of fluid in proximal portion of nephron, decreasing The medications described below are used in patients with diabetes insipidus who have hypernatremia. delivery of sodium to ascending limb of loop of Henle and consequently reducing capacity to dilute urine. Further Inpatient Care Record daily body weights in patients with hypernatremia. Frequently monitor electrolyte concentrations. Restrict sodium and protein intake. Treat the underlying disease. Further Outpatient Care Treat the underlying disease. Restrict sodium and protein intake. Transfer Patients with symptomatic hypernatremia should be transferred to a pediatric intensive care unit for appropriate treatment and close monitoring. Patients should be transferred to a facility that has dialysis in case of renal failure or in case the serum sodium concentration is more than 180 mEq/L. Deterrence/Prevention Parents and caregivers should avoid making oral rehydration solutions at home or adding salt to any commercial infant formula. Treat the underlying cause. Complications Seizures can occur because of hypernatremia per se, which is rare. They usually occur during the treatment of hypernatremia because of a rapid decline in serum sodium levels. Therefore, slowly correcting hypernatremia is important. Other complications include the following: o Mental retardation o Intracranial hemorrhage o Intracerebral calcification o Cerebral infarction o Cerebral edema, especially during treatment o Hypocalcemia o Hyperglycemia Prognosis Patients usually recover from hypernatremia. Patients with recurrent hypernatremic dehydration develop neurologic sequelae, especially infants with diabetes insipidus. Patient Education Parents and caregivers should avoid making oral rehydration solutions at home or adding salt to any commercial infant formula. Parents, especially breastfeeding mothers, should watch for neonatal dehydration and perinatal care. The breastfed infant should be routinely monitored during the first weeks of life.[5] In patients with diabetes insipidus, the following is indicated: o Monitor weight and urine output because clinically significant changes in sodium values are associated with changes in weight. o Restrict sodium and protein intake. o The patient should drink liberal amounts of water. o The patient and parents should ensure thirst develops before taking or giving medications. Pediatric Hyponatremia Practice Essentials Hyponatremia, defined as a serum sodium (Na) concentration of less than 135 mEq/L, can lead to hyponatremic encephalopathy, particularly in prepubescent pediatric patients. Signs and symptoms CNS findings Early signs of hyponatremia include the following: Anorexia Headache Nausea Emesis Advanced signs include the following: Impaired response to verbal stimuli Impaired response to painful stimuli Bizarre behavior Hallucinations Obtundation Incontinence Respiratory insufficiency Seizure activity Far-advanced signs include the following: Decorticate or decerebrate posturing Bradycardia Hypertension or hypotension Altered temperature regulation Dilated pupils Seizure activity Respiratory arrest Coma Cardiovascular and musculoskeletal findings Cardiovascular: Hypotension and tachycardia Musculoskeletal: Weakness and muscular cramps See Clinical Presentation for more detail. Diagnosis Routine laboratory studies used in the diagnosis and evaluation of hyponatremia include the following: Serum Na level Serum osmolality Blood urea nitrogen (BUN) and creatinine levels Urine osmolality Urine Na level Urine Na concentrations The urine Na level differs according to the type of hyponatremia present. In hypovolemic hyponatremia, Na concentrations are as follows: Renal losses caused by diuretic excess, osmotic diuresis, salt-wasting nephropathy, adrenal insufficiency, proximal renal tubular acidosis, metabolic alkalosis, or pseudohypoaldosteronism result in a urine Na concentration of more than 20 mEq/L Extrarenal losses caused by vomiting, diarrhea, sweat, or third spacing result in a urine Na concentration of less than 20 mEq/L secondary to increased tubular reabsorption of Na In normovolemichyponatremia caused by syndrome of inappropriate antidiuretic hormone (SIADH) secretion, reset osmostat, glucocorticoid deficiency, hypothyroidism, or water intoxication, the urine Na concentration is more than 20 mEq/L Hypervolemichyponatremia results in the following urine Na concentrations: If hyponatremia is caused by an edema-forming state (eg, congestive heart failure, hepatic failure), the urine Na concentration is less than 20 mEq/L If hyponatremia is caused by acute or chronic renal failure, the urine Na concentration is more than 20 mEq/L In SIADH with normal dietary salt intake, urine sodium concentration is more than 40 mEq/L, while in cerebral salt-wasting syndrome (CSWS), the concentration frequently exceeds 80mEq/L. Other studies Special laboratory studies include the following: Aldosterone level Cortisol level Free T4 and thyroid-stimulating hormone (TSH) levels Adrenocorticotropic hormone (ACTH) level Antidiuretic hormone (ADH) level See Workup for more detail. Management Hypovolemic hyponatremia The immediate goal is to correct volume depletion with normal saline. As soon as the patient is hemodynamically stable, hyponatremia should be corrected. Physiologic considerations indicate that a relatively small increase in the serum Na concentration, on the order of 5%, should substantially reduce cerebral edema. Normovolemichyponatremia Treatment of normovolemichyponatremia due to SIADH can include fluid restriction and the administration of normal saline. The use of 3% NaCl and the intravenous (IV) administration of furosemide may also be needed. Hypervolemichyponatremia Treatment includes the following: Fluid restriction Administration of 3% NaCl to stop the symptoms Treatment of the underlying cause Asymptomatic hyponatremia Hypovolemic hyponatremia: The main principle is to avoid hypotonic fluids and to slowly correct Na levels Normovolemichyponatremia: Restriction of fluids to two thirds (or less) of the volume needed for maintenance is the mainstay of treatment Recalcitrant euvolemichyponatremia: Demeclocycline can be used to induce therapeutic nephrogenic diabetes insipidus, which may help to eliminate excessive water See Treatment and Medication for more detail. Image library Drugs that impair water excretion. Background Hyponatremia is defined as serum sodium (Na) concentration of less than 135 mEq/L. Plasma Na plays a significant role in plasma osmolality and tonicity (serum osmolarity = 2Na + Glu/18 + BUN/2.8). Changes in plasma osmolality are responsible for the signs and symptoms of hyponatremia and also the complications that happen during treatment in the presence of highrisk factors. Whereas hypernatremia always denotes hypertonicity, hyponatremia can be associated with low, normal, or high tonicity. Hyponatremia is the most common electrolyte disorder encountered in hospitalized patients. Clinical presentation of hyponatremia happens as a result of a rapid of fall in serum Na and also the absolute level of serum Na. Fifty percent of presenting children develop symptoms when serum Na levels fall below 125 mEq/L, a relatively high level when compared with adults. Although morbidity widely varies, serious complications can arise from hyponatremia and can also happen during treatment. Understanding the pathophysiology and treatment options for hyponatremia is important because significant morbidity and mortality are possible. Pathophysiology Hyponatremia can develop because of (1) excessive free water, a common cause in hospitalized patients receiving hypotonic solutions; (2) excessive renal or extrarenal losses of Na or renal retention of free water; (3) rarely, deficient intake of Na. Under normal circumstances, the human body is able to maintain serum Na in the normal range (135-145 mEq/L) despite wide fluctuations in fluid intake. The body's defense against developing hyponatremia is the kidney's ability to generate dilute urine and excrete free water in response to changes in serum osmolarity and intravascular volume status. Hospital-acquired hyponatremia is the most common cause of hyponatremia in children. Some studies have outlined the association of hyponatremia and the hypotonic fluid typically used in the pediatric population. Excessive antidiuretic hormone (ADH) is present in most hospitalized patients, either as an appropriate response to hemodynamic and/or osmotic stimuli or as an inappropriate secretion of ADH. ADH is also secreted in response to pain, nausea, and vomiting and during the use of certain medications such as morphine during the postoperative period. Use of hypotonic fluids in presence of circulating ADH can causes free water retention resulting in hyponatremia. In certain clinical conditions, ADH secretion occurs even when serum osmolarity is low or normal, hence the term syndrome of inappropriate ADH secretion (SIADH). Other conditions that can lead to hyponatremia include states with increased total body water such as with cirrhosis, cardiac failure, or nephrotic syndrome. Diuretic use and decreased intake of Na can also lead to hyponatremia. Loss of Na via the GI tract and or urinary tract in excess of free water can result in hyponatremia. GI losses can occur in different disease states with excessive fluid loss, namely gastroenteritis, fistulas, or serous fluid drainage after surgery. Na can be lost via the kidney; use of diuretics is the most common culprit, followed by other causes, such as salt-losing nephritis, mineralocorticoid deficiency, and cerebral salt-wasting syndrome (CSWS). Hyponatremia is rarely caused by deficient Na intake. Clinical manifestations vary from an asymptomatic state to severe neurologic dysfunction. CNS symptoms predominate in hyponatremia, although cardiovascular and musculoskeletal findings may be present. Factors that contribute to CNS symptoms are (1) the rate at which serum Na levels change, (2) the absolute serum Na level, (3) the duration of the abnormal serum Na level, (4) the presence of other CNS pathology risk factors, and (5) the presence of excessive ADH levels. CNS effects Hyponatremia exerts most of its clinical effects on the brain. Brain volume is regulated by equal osmolality of extracellular and intracellular fluid. When extracellular osmolality decreases, water influx occurs in the brain resulting in cerebral edema. Cerebral edema is responsible for symptoms such as headache, nausea, vomiting, irritability, and seizures. If hyponatremia is acute (ie, within hours), the change in osmolality causes influx of water resulting in cerebral edema. If hyponatremia occurs slowly (ie, over days), the brain has adaptive response to protect itself from edema formation. The brain’s adaptive response is mediated through different mechanisms and also modified by different factors as discussed below. Mechanisms implied in cerebral edema formation include the following: Na-K ATPase system Aquaporin channels Organic osmolytes Hyponatremia and resulting reduced osmolarity leads to an influx of water into the brain, primarily through glial cells and largely via the water channel aquaporin (AQP). Water is then shunted to astrocytes, which swell, largely preserving the neurons. Na is extruded at the same time using Na-K ATPase system. Potassium ions extrusion follows Na but is slower. In addition, inorganic osmolytes and organic osmolytes (eg, glycine, taurine, creatine, and myoinositol) have been shown to efflux from cells during hypo-osmolar states in animal studies. The brain’s adaptive response to protect itself from edema occurs over several days. Once the brain has adapted to the hypo-osmolar conditions, a correction of the hypo-osmolar extracellular space to aneuvolemic or hyper-osmolar state that is too rapid leads to a rapid efflux of water from brain tissue, resulting in dehydration of brain cells. The resultant condition is called osmotic demyelination syndrome (ODS). Previously, this pathological injury was described only in the pons, hence the term central pontinemyelinolysis (CPM). Although it predominantly affects the pons, this condition is now known to occur in other parts of brain as well (see Complications). Hyponatremic encephalopathy Risk factors for hyponatremic encephalopathy include age, sex, hypoxia and vasopressin levels. Sex o o Epidemiologic data have shown that the risk for developing permanent neurologic sequelae or death from hyponatremic encephalopathy is substantially higher in menstruating women than in men or postmenopausal women.[1] The relative risk of death or permanent neurologic damage due to hyponatremic encephalopathy is about 30 times greater for women than for men and about 25 times greater for menstruating women than for postmenopausal women. Although estrogen hormones have been implicated as the cause of this high incidence of hyponatremic encephalopathy, cellular level mechanisms have now been elucidated. Estrogen has a core steroidal structure similar to cardiac glycosides known to inhibit the Na-K ATPase system, impairing adaptive responses. In addition, estrogen also appears to regulate water movement and neurotransmission by affecting AQP4 expression. Age o o Prepubescent children are at increased risk to develop complications because of hyponatremia. Although many other factors may contribute to this increased risk, brain–to–cranial vault ratio plays an important role. The brain reaches adult size by age 6 years, whereas the skull does not reach adult size until age 16 years. As a consequence, children can develop symptomatic hyponatremia with relatively higher Na concentrations than those observed in adults. o Good outcomes are reported in young babies with open fontanelles; increased vault compliance supports this hypothesis. Hypoxia o Hypoxia is a major risk factor for hyponatremic encephalopathy. Patients with symptomatic hyponatremia can develop hypoxia by 2 different mechanisms: noncardiogenic pulmonary edema and hypercapnic respiratory failure. Hypercapnic respiratory failure is due to central respiratory depression and is often the first sign of impending herniation. Noncardiogenic pulmonary edema, on the other hand, is a complex disorder during with increased vascular permeability and increased catecholamine release that often occurs secondary to elevated intracranial pressure. o Hypoxia worsens clinical outcomes in hyponatremic encephalopathy by impairing the brain’s adaptive response through the active transport of Na, which is an energy-dependent process that requires oxygen. It also affects astrocyte volume regulation, which is also energy dependent. Under ordinary circumstances, hypoxia results in an increase in cerebral blood flow to increase the delivery of oxygen;[2] the increase in cerebral blood flow can lead to an increase in cerebral blood volume, which also contributes to an increase in intracranial pressure. Vasopressin o Hyponatremia, except in cases of pure water intoxication, virtually always occurs in the presence of increased plasma levels of vasopressin.[3] o Vasopressin leads to decreased cerebral oxygen use in female rat brain but not in male rats. Vasopressin decreases cerebral blood flow by vasoconstriction, resulting in decreased oxygen delivery that, in turn, impairs brain adaptation. Vasopressin also facilitates direct movement of water into brain cells independent of hyponatremia. In addition, it also decreases synthesis of ATP and phosphocreatine, lowers intracellular pH and intracellular buffering, and decreases Ca2+, which affects energy-dependent processes involved in brain adaptation. Cardiovascular response to hyponatremia Hyponatremia is also often classified by body water volume status: hyponatremia in conjunction with hypervolemia, euvolemia, or hypovolemia. The distribution of water and solute in the intracellular and extracellular spaces determine the intravascular volume. Fluid shifts from the extracellular space to the intracellular space with a subsequent decrease in arterial blood volume. The reduction in intravascular volume may result in hypotension. Because of this fluid shift, hyponatremia causes hemodynamic disturbance more pronounced than that expected for the degree of dehydration. Frequency United States Reported frequency varies from 1-30% among hospitalized pediatric patients. International In India, the frequency of hyponatremia is 29.8%.[4] It is more frequent in summer (36%) than in winter (24%). Mortality/Morbidity Overall morbidity and mortality is 42%. Sex The incidence of hyponatremia is equal in both sexes. However, CNS complications are most likely to occur among premenopausal women. Age Hyponatremic encephalopathy is most common in prepubescent children. History Physical Causes Show All Multimedia Library References History The history of patients with hyponatremia may include the following: Hypotonic fluid use for maintenance hydration in hospitalized children (potential risk factor) Feeding with hypotonic formula or excessive free water during infancy Conditions that cause GI, Na-rich fluid loss, including the following: o Diarrhea o Vomiting o Fistulas Renal disorders, including the following: o Salt-losing nephropathy o Acute renal failure o Chronic renal failure Postoperative states[5] Psychiatric conditions Coma Drug use CNS and pulmonary diseases Hypothyroidism Adrenal insufficiency Cirrhosis Congestive heart failure Acquired immunodeficiency syndrome (AIDS) Cystic fibrosis Physical CNS findings Early signs include the following: o Anorexia o Headache o Nausea o Emesis Advanced signs include the following: o Impaired response to verbal stimuli o Impaired response to painful stimuli o Bizarre behavior o Hallucinations o Obtundation o Incontinence o Respiratory insufficiency o Seizure activity Far-advanced signs include the following: o Decorticate or decerebrate posturing o Bradycardia o Hypertension or hypotension o Altered temperature regulation o Dilated pupils o Seizure activity o Respiratory arrest o Coma Cardiovascular findings Hypotension Tachycardia Musculoskeletal findings Weakness Muscular cramps Causes Hypervolemichyponatremia (excess free-water retention) Congestive heart failure Cirrhosis Nephrotic syndrome Acute or chronic renal failure Hypovolemic hyponatremia due to renal loss of sodium in excess of free-water Diuretic excess Osmotic diuresis Salt-wasting diuresis Adrenal insufficiency Metabolic alkalosis Pseudohypoaldosteronism Hypovolemic hyponatremia due to extrarenal loss of sodium in excess of freewater GI conditions, such as the following: o Vomiting o Diarrhea o Drains o Fistula Sweat Cystic fibrosis Cerebral salt-wasting syndrome (CSWS) Third-spacing conditions, such as the following: o Pancreatitis o Burns o Muscle trauma o Peritonitis o Effusions o Ascites Normovolemichyponatremia Syndrome of inappropriate antidiuretic hormone secretion (SIADH) o Tumors - Adenocarcinoma of the duodenum, adenocarcinoma of the pancreas, carcinoma of the ureter, carcinoma of the prostate, Hodgkin disease, thymoma, acute leukemia, lymphosarcoma, or histiocytic lymphoma o Chest disorders - Infection (eg, tuberculosis or bacterial, mycoplasmal, viral, or fungal infection), positive-pressure ventilation, decreased left atrial pressure (eg, o due to pneumothorax, atelectasis, asthma, cystic fibrosis, mitral valve commissurotomy, ligation of the patent ductusarteriosus ligation), or malignancy CNS disorders - Infection (eg, tuberculous meningitis, bacterial meningitis, encephalitis), trauma, hypoxia-ischemia, psychosis, brain tumor, or miscellaneous CNS disorders (eg, Guillain-Barré syndrome, ventriculoatrial shunt obstruction, acute intermittent porphyria, cavernous sinus thrombosis, multiple sclerosis, anatomic abnormalities, vasculitis, stress, idiopathic causes) o Drugs (see image below) Drugs that impair water excretion. Reset osmostat Glucocorticoid deficiency Hypothyroidism Water intoxication due to intravenous (IV) therapy, tap-water enema, or psychogenic water drinking Differential Diagnoses Adrenal Insufficiency Cerebral Salt-Wasting Syndrome Diarrhea Hypothyroidism Syndrome of Inappropriate Antidiuretic Hormone Secretion Laboratory Studies Verify the accuracy of laboratory results in patients with hyponatremia. Exclude pseudohyponatremia. o Findings on flame emission spectrophotometry If Na measurement is performed by using flame emission spectrophotometry, hyponatremia is falsely low in patients with hyperproteinemia and hypertriglyceridemia. Raised proteins and lipid levels increase the nonaqueous portion of plasma, which normally forms 7% of the plasma. However, new ion-specific Na electrodes measure Na from only the aqueous phase, enabling accurate estimation of serum Na concentrations. o Correction factors for raised proteins and lipids Triglycerides (in milligrams per deciliter) X 0.002 = decrease in plasma Na level (in milliequivalents per liter) (Plasma protein level [in grams per deciliter] - 8) X 0.25 = decrease in plasma Na (in milliequivalents per liter) Exclude distributive hyponatremia. o Distributive hyponatremia occurs when the plasma glucose concentration exceeds 100 mg/dL. o Each 100-mg/dL increase in the glucose level above 100 mg/dL leads to a 1.6mEq/L decrease in the Na concentration. Obtain routine laboratory studies to assess the following: o Serum Na level o Serum osmolality o BUN and creatinine levels o Urine osmolality o Urine Na level Urine Na level changes according to the type of hyponatremia. o Hypovolemic hyponatremia Renal losses caused by diuretic excess, osmotic diuresis, salt-wasting nephropathy, adrenal insufficiency, proximal renal tubular acidosis, metabolic alkalosis, or pseudohypoaldosteronism result in a urine Na concentration of more than 20 mEq/L. Extrarenal losses caused by vomiting, diarrhea, sweat, or third spacing result in a urine Na concentration of less than 20 mEq/L secondary to increased tubular reabsorption of Na. o Normovolemichyponatremia: When hyponatremia is caused by syndrome of inappropriate antidiuretic hormone secretion (SIADH), reset osmostat, glucocorticoid deficiency, hypothyroidism, or water intoxication, the urine Na concentration is more than 20 mEq/L. o Hypervolemichyponatremia If hyponatremia is caused by an edema-forming state (eg, congestive heart failure, hepatic failure), the urine Na concentration is less than 20 mEq/L because effective arterial perfusion is low despite an increase in total body water. Use of diuretics affects urine Na concentration. If hyponatremia is caused by acute or chronic renal failure, the urine Na concentration is more than 20 mEq/L. o SIADH: Urine sodium concentration is more than 40mEq/L with normal dietary salt intake. o Cerebral salt-wasting syndrome (CSWS): Urine loss is significantly higher and frequently exceeds 80 mEq/L. Special laboratory studies include tests of the following: o Aldosterone level o Cortisol level o Free T4 and thyroid-stimulating hormone (TSH) levels o Adrenocorticotropic hormone (ACTH) level o Antidiuretic hormone (ADH) level Imaging Studies Neuroimaging (only if clinically indicated, not routinely performed) o CT scanning is useful for evaluating causative intracranial pathologies, such as tumors, hydrocephalus, and hemorrhage. It is also useful for detecting cerebral edema and demyelinating lesions that occur during treatment. CT scanning is superior to MRI in delineating hemorrhage and calcifications. o MRI is sensitive for detecting tumors and demyelination. Abdominal imaging (only if clinically indicated, not routinely performed) o Ultrasonography may be performed to detect abdominal masses, such as those due to bilateral adrenal hyperplasia, and adrenal tumors. Medical Care Principles of treatment in hyponatremia o The most common and devastating effects of hyponatremia are of CNS origin. Therefore, identifying the risk factors that lead to hyponatremia and instituting prompt treatment while avoiding complications is crucial. o Although cerebral adaptation to low serum Na occurs slowly, it protects the brain from deleterious effects of hypo-osmolality. However, this protective mechanism leaves the brain susceptible to osmotic demyelination syndrome (ODS) during treatment, especially in persons with chronic hyponatremia, if the correction is rapid. Equations used in managing hyponatremia o To estimate the effect of 1 L of any infusate on serum Na concentration: Change in Na concentration = (infusate Na level - serum Na level)/(total body water + 1) o To estimate the effect of 1 L of any infusate containing Na and potassium (K) on serum Na concentration: Change in serum Na level = [(infusate Na level + infusate K level) - serum Na level]/(total body water + 1) Na concentrations of various fluids used in pediatric practice o 5% NaCl in water - 855 mEq/L o 3% NaCl in water - 513 mEq/L o 0.9% NaCl in water - 154 mEq/L o Ringer lactate solution - 130 mEq/L o 0.45% NaCl in water - 77 mEq/L o 0.2% NaCl in water - 34 mEq/L o 5% dextrose in water - 0 mEq/L Management of hypovolemic hyponatremia o The immediate goal is to correct volume depletion with normal saline. As soon as the patient is hemodynamically stable, hyponatremia should be corrected as per the treatment principles described below. In patients with seizure, 3% NaCl should be given while volume depletion is being corrected. o No consensus has been reached about the optimal treatment of symptomatic hyponatremia. However, guidelines for hydration management have been established.[6] Physiologic considerations indicate that a relatively small increase in the serum Na concentration, on the order of 5%, should substantially reduce cerebral edema. Available evidence indicates that even a 9 mEq/L increase in serum Na concentration over 24 hours can result in demyelinating lesions. Given the risk of demyelinating lesions, the recommended rate of correction should not exceed 8 mEq/L/d. Even hyponatremia-induced seizures can be stopped with changes in serum Na concentration of only 3-7 mEq/L. o Treatment of normovolemichyponatremia due to syndrome of inappropriate antidiuretic hormone secretion (SIADH) can include fluid restriction, along with the administration of normal saline; the use of 3% NaCl, and intravenous (IV) administration of furosemide may also be needed. Furosemide is given to offset the volume expansion created by the 3% Na infusion. As previously discussed, when confronted with neurologic symptoms the plan is to raise the serum Na concentration until symptoms resolve, this can be done by giving doses of 1-2 mL/Kg of 3% saline, symptoms typically resolve with a rise in sodium of 3-7 mEq/L; subsequently, closely monitor electrolyte levels so that the correction does not exceed 8 mEq/L/d. This appears to leave little room for elevation of serum sodium after immediately addressing symptoms; however, it appears that maintaining control of the absolute rise over 24 hours remains beneficial, even after the immediate emergent increase in serum sodium. Management of hypervolemichyponatremia: In patients with hypervolemichyponatremia, restrict fluids, administer 3% NaCl to stop the symptoms, and treat the underlying cause. Management of asymptomatic hyponatremia o In asymptomatic individuals with hypovolemic hyponatremia, one should not rush to correct hyponatremia. The main principle is to avoid hypotonic fluids and to slowly correct Na levels, especially when hyponatremia has been present for 48 hours or longer. When the duration of hyponatremia is unknown, as is encountered in outpatient settings, assume hyponatremia is chronic and treat accordingly. Closely monitor electrolyte values, and the rate of correction should not exceed 8 mEq/L/d. o In patients with normovolemichyponatremia, restriction of fluids to two-thirds (or less) of the volume needed for maintenance is the mainstay of treatment. Diuretics can be administered with fluid restriction to remove excessive free water. Once again, the change in Na levels should not exceed 8 mEq/L/d. o In recalcitrant euvolemichyponatremia, one can use demeclocycline to induce therapeutic nephrogenic diabetes insipidus, which might help eliminate excessive water. However, one must remember that total correction should not exceed the established goal. Consultations Transfer patients with symptomatic hyponatremia to a pediatric ICU for appropriate treatment and close monitoring. Consult an endocrinologist when patients have hypothyroidism or adrenal insufficiency. Consult a nephrologist when patients have salt-losing nephropathy, renal failure, or recalcitrant hyponatremia. Appropriate neurosurgical care is required when CNS conditions are the cause of SIADH. Diet Patients with salt-wasting disorders (eg, salt-losing nephropathies) need Na supplementation throughout the period of continued loss of excessive Na. Patients with SIADH and renal failure require fluid restriction. o CT and MRI may help in further delineating the tumor. Medication Summary Diuretics Class Summary These agents promote renal excretion of water and electrolytes. They are used to treat heart failure or hepatic, renal, or pulmonary disease when Na and water retention results in edema or ascites. View full drug information Furosemide (Lasix) Potent loop diuretic. Inhibits reabsorption of sodium and chloride in proximal and distal tubules and loop of Henle. High efficacy largely due to unique site of action. Action on distal tubule independent of any possible inhibitory effect on carbonic anhydrase or aldosterone. ADH inhibitors Class Summary These agents produce diuresis by inhibiting antidiuretic hormone (ADH)-induced water reabsorption. Rarely used to treat pediatric hyponatremia in the pediatric ICU setting. View full drug information Lithium (Eskalith, Lithobid) Inhibits renal response to ADH. View full drug information Medical therapy in hyponatremia includes the administration of 3% Na chloride (Na, 513 mEq/L), normal Na chloride solution (Na, 154 mEq/L), diuretics, and other drugs used to treat syndrome of inappropriate antidiuretic hormone secretion (SIADH), such as lithium carbonate, demeclocycline, ethanol, phenytoin, and vasopressin analogs.[7] Demeclocycline (Declomycin) Only tetracycline used to treat SIADH. Produces diuresis by inhibiting ADH-induced water reabsorption in distal portion of convoluted tubules and collecting ducts of kidneys. Effects observed within 5 d and are reversed 2-6 d after cessation of therapy. Administer 1 h before or 2-3 h after ingestion of milk or food. View full drug information Phenytoin (Dilantin) Inhibits secretion of ADH. Deterrence/Prevention Carefully monitor patients receiving drugs that can cause hyponatremia. Give careful consideration to the type of intravenous (IV) hydrating solution used in pediatric patients. The findings of one study conclude that the use of hypotonic maintenance fluids increases the incidence of hyponatremia because they decrease blood sodium levels in normonatremic patients. Isotonic maintenance fluids did not increase the incidence of dysnatremia and showed a reduced incidence of hyponatremia in the patients studied. The findings suggest that the administration of isotonic fluids should be considered the standard of care in critically ill children.[8] Prudently monitor serum electrolytes in postoperative patients, patients on IV fluids, and in those with brain tumors, intracranial infections, pulmonary infections, or head trauma. Complications Osmotic demyelination syndrome (ODS) Brain damage and cerebral demyelination can develop if the serum Na level raises rapidly in chronic hyponatremia. Epidemiology: The exact incidence of ODS is unknown, and data are derived primarily from autopsy series. In 3548 consecutive autopsies in adults with ODS, the typical lesions were found in 9 (0.25%).[9] In another study, Sterns et al observed myelinolysis in as many as 25% of patients with hyponatremia who were treated with aggressive protocols.[10] The incidence is highest among high-risk groups. Risk factors o Alcoholism (common) o Malnutrition (common) o After prolonged diuretic use (frequent) o Psychogenic polydipsia (rare if acute) o Burns (infrequent, and often in context of hypernatremia) o o o o o Liver transplantation (well recognized)[11] Pituitary surgery (rare) Urologic or gynecologic surgery, especially if it involved glycine infusions (rare) Correcting serum Na into hypernatremic levels Hypoxia Subtypes o Central pontinemyelinolysis (CPM): Lesions are confined to the pons. o Extrapontinemyelinolysis (EPM): Lesions are confined to the basal ganglia, cerebrum, and cerebellum. o ODS: CPM and EPM lesion sites are both present. Pathogenesis: The pathogenesis of ODS is unknown. Cells conditioned to hypo-osmotic hyponatremia may have a decreased adaptive capacity to osmotic stress. The predilection for myelinolysis in the pons is thought to be a result of the grid arrangement of the oligodendrocytes in the base of pons, which limits their mechanical flexibility and, therefore, their capacity to swell. During hyponatremia, these cells can adapt only by losing ions instead of swelling. This limitation makes them prone to damage when Na is replaced. The risk factors mentioned above make normal adaptation difficult. Clinical manifestations of CPM Ataxia Coma Depressed or absent reflexes Dysarthria Dysphasia Lethargy Ophthalmoplegia Quadriparesis Clinical manifestations of EPM Akinesis Ataxia Catatonia Choreoathetosis Cogwheel rigidity Disorientation Dysarthria Dystonia Emotional lability Extra pyramidal symptoms Gait disturbance Movement disorders Mutism Myoclonus Myokymia Parkinsonism Rigidity Tremor Diagnosis of CPM The diagnosis of CPM is based on clinical suspicion and confirmed with imaging studies. MRI is the primary method for diagnosis and is superior to CT. During the acute phase, symmetrical and hypointense lesions can be identified on a T1-weighted MRI. During the subacute phase, symmetrical and hypointense lesions are seen on T2-weighted images. Lesions on MRI may appear days to weeks after the onset of symptoms; in some cases, these may resolve, over months. Management At present, supportive treatment is all that can be recommended with certainty. Therefore, prevention becomes important because hyponatremia is preventable and causes neurologically significant morbidity and mortality. To the authors' knowledge, no trials for the treatment of ODS have been conducted. Small case series or single case reports of treatments, including steroids, IV immunoglobulin, and thyrotrophin-releasing hormone, have all shown good outcomes. However, the results are difficult to interpret because of the lack of clinical trials. Prognosis Older reports of ODS indicated almost a 100% mortality rate within 3 months after hospital admission. More recent studies of ODS reveal a relatively mild clinical course without substantial neurologic deficits in survivors. Patient Education Advise parents not to replace diarrheal fluid loss with hypotonic fluids such as tea or soda. Pediatrics Hyperkalemia Background Hyperkalemia is defined as a serum potassium concentration greater than the upper limit of the normal range; the range in children and infants is age-dependent, whereas the range for adults is approximately 3.5-5.5 mEq/L. The upper limit may be considerably high in young or premature infants, as high as 6.5 mEq/L[1] . Because hyperkalemia can cause lethal cardiac arrhythmia, it is one of the most serious electrolyte disturbances. Pathophysiology Potassium is the primary intracellular cation; more than 95-98% of the total body potassium is found in the intracellular space, primarily in muscle. Normal homeostatic mechanisms serve to precisely maintain the serum potassium level within a narrow range. The primary mechanisms for maintaining this balance are the buffering of extracellular potassium against a large intracellular potassium pool (via the sodium-potassium pump) and urinary excretion of potassium. Under normal, nonpathologic conditions, approximately 90% of potassium excretion occurs in the urine, with less than 10% of potassium excreted through sweat or stool. Within the kidneys, potassium excretion occurs mostly in the principal cells of the cortical collecting duct (CCD). Urinary potassium excretion depends on adequate luminal sodium delivery to the distal convoluted tubule (DCT) and CCD, as well as the effect of aldosterone and other adrenal corticosteroids with mineralocorticoid activity. Laboratory hyperkalemia (fictitious or pseudohyperkalemia) can easily occur because of hemolysis, tissue lysis, and "milking" of extremities (which can introduce a significant amount of interstitial fluid into the blood sample) during phlebotomy, especially with heel-poke and finger-stick phlebotomy, which are commonly performed in infants and small children. Hemolysis can also be caused by fist clenching during phlebotomy or during prolonged tourniquet application, which can also lead to an acidotic sample with resultant hyperkalemia). Blood sampled "upstream" of an intravenous line with potassium-containing fluid (or from a multiple lumen central venous catheter where the sampling lumen is near the lumen containing potassium-rich infusate) can have falsely elevated levels of potassium that do not reflect circulating levels. Similarly, serum potassium levels may be falsely lowered by sampling upstream of a catheter delivering fluid deficient in potassium or when a small blood sample is obtained and placed in testing media low in potassium, which may be the case with specific point-of-care analyzers.[2] When in doubt, blood samples should be obtained and tested using standard methods. Thrombocytosis can also lead to false elevations of serum potassium levels. The normal serum potassium level is 0.4 mEq/L higher than the plasma level because of potassium release during clot formation. For every 100,000/mL elevation in the platelet count, the serum potassium increases by approximately 0.15 mEq/L. This can easily be corrected based on a measurement of whole blood potassium level. A similar effect on serum but not plasma potassium can also be seen with leukocytosis. True hyperkalemia is caused by one of 3 basic mechanisms, although the root cause for any individual patient is often multifactorial. Increased K+ intake: Increased K+ intake is most commonly caused by intravenous or oral potassium supplementation. Packed RBCs (PRBCs) also carry potentially high concentrations of potassium that can lead to hyperkalemia during PRBC transfusion[3] . Since serum potassium levels represent only a small percentage (usually < 2-5%) of total body potassium stores, long-term increases in potassium intake are only rarely associated with significant serum hyperkalemia, unless excretion is inadequate. Decreased potassium excretion: The most common cause of decreased potassium excretion leading to hyperkalemia is oliguric renal failure. Other causes include primary adrenal disease (eg, Addison disease, salt-wasting forms of congenital adrenal hyperplasia), hyporeninemichypoaldosteronism, renal tubular disease (pseudohypoaldosteronismI[4] or II), or medications (eg, ACE inhibitors, angiotensin II blockers, spironolactone or other potassium-sparing diuretics). Transcellular potassium shifts: In a transcellular potassium shift, a hydrogen ion enters a cell and leads to decreased K+ uptake by the cell in order to maintain electrical neutrality. Acidosis is the most common cause of hyperkalemia due to transcellular potassium shift, but any process that leads to cellular injury or death (eg, tumor lysis syndrome, rhabdomyolysis, crush injury, massive hemolysis) can cause hyperkalemia, as intracellular potassium is released by disruption of the cell membrane. Other causes of hyperkalemia due to transcellular shift of potassium include propofol ("propofol infusion syndrome"),[5] toxins (digitalis intoxication or fluoride intoxication), succinylcholine, beta-adrenergic blockade, strenuous or prolonged exercise, insulin deficiency, malignant hyperthermia, and hyperkalemic periodic paralysis. Plasma potassium levels are generally maintained at 3.5-5 mEq/L in adults, with higher levels in neonates and small infants. levels greater than 7 mEq/L can lead to significant hemodynamic and neurologic consequences, while levels exceeding 8.5 mEq/L can cause respiratory paralysis or cardiac arrest and can quickly be fatal. High levels of potassium cause abnormal heart and skeletal muscle function by lowering cell-resting action potential and preventing repolarization, leading to muscle paralysis. Classic ECG findings begin with tenting of the T wave (as is shown in the image below), followed by lengthening and eventual disappearance of the P wave and widening of the QRS complex.[6] Peaked T waves. Prior to asystole, the QRS and T wave may merge to form a sinusoidal wave (as is shown in the image below). Sinusoidal wave. Table. Select Factors Affecting Plasma Potassium (Open Table in a new window) Factor Aldosterone Insulin Effect on Plasma K+ Decrease Decrease Mechanism Increases sodium resorption, and increases K+ excretion Stimulates K+ entry into cells by increasing sodium efflux (energy-dependent process) Beta-adrenergic agents Alpha-adrenergic agents Acidosis (decreased pH) Alkalosis (increased pH) Cell damage Succinylcholine Decrease Increases skeletal muscle uptake of K+ Increase Impairs cellular K+ uptake Increase Impairs cellular K+ uptake Decrease Enhances cellular K+ uptake Increase Increase Intracellular K+ release Cell membrane depolarization Epidemiology Frequency United States Hyperkalemia is a manifestation of a disease and is not a disease by itself. The incidence of hyperkalemia in the pediatric population is unknown, although the prevalence of hyperkalemia in extremely low birth weight premature infants can exceed 50%.[7] Hyperkalemia in pediatric patients is most commonly associated with renal insufficiency, acidosis, and with diseases that involve defects in mineralocorticoid, aldosterone, and insulin function.[8] Mortality/Morbidity Sudden and rapid onset of hyperkalemia can be fatal. With slow or chronic increase in potassium levels, adaptation occurs via renal excretion, with fractional potassium excretion increasing by as much as 5-10 times the reference range. Race No racial predilection is observed. Sex No sex-related predilection is observed. However, neuromuscular disorders including myotonic and muscular dystrophies and related disorders that can predispose patients to hyperkalemia with succinylcholine administration are more prevalent in males.[9] Age Extremely low birth weight premature infants are particularly prone to hyperkalemia primarily due to immature renal function. Even otherwise full-term infants may have transient hyperkalemia and hyponatremia due to decreased responsiveness to aldosterone (pseudohypoaldosteronism I). History History for a previously well child with acute hyperkalemia should focus on how the blood sample was obtained, potassium intake or recent blood product transfusion, risk factors for transcellular shift of potassium (acidosis) or tissue death/necrosis, medication use (by the child, other family members, pets, etc) associated with hyperkalemia, and presence or signs of renal insufficiency. Specific questions may be focused on the following: Urine output (last void or number of wet diapers) and fluid intake Cola-colored urine (which may indicate acute glomerulonephritis) Bloody stool (which may indicate hemolytic-uremic syndrome [HUS]) Presence of drugs in the household (or used by recent visitors), such as potassium preparations, digoxin, and diuretics Any history of trauma (crush injuries) or thermal injury (burns) Medical history, family history, and review of systems should be explored for any of the following: Acute or chronic renal failure Hypertension Diabetes Adrenogenital syndromes Malignancy (tumor lysis syndrome) Family history (hyperkalemic periodic paralysis, miscarriages, deaths of very young siblings) Neuromuscular disorders Malignant hyperthermia Physical High potassium levels interfere with repolarization of the cellular membrane following completion of the action potential. Findings depend on the degree of hyperkalemia and primarily relate to the deleterious effects of elevated plasma potassium levels on cardiac conduction. Children with hyperkalemia can present with cardiac arrest due to wide-complex tachycardia or ventricular fibrillation. Symptoms short of circulatory collapse/cardiac arrest include respiratory failure and weakness that progresses to paralysis. Patients may report nausea, vomiting, and paresthesias (eg, tingling). Most often, patients with hyperkalemia are asymptomatic, with the first clinical manifestation of the condition either ECG changes (peaked T waves) or sudden cardiac arrest. Nonspecific findings can include muscle weakness (skeletal, respiratory), fatigue, ileus with hypoactive or absent bowel sounds, and depression. Causes Although the etiology of hyperkalemia can be multifactorial, differential diagnoses include fictitious hyperkalemia and hyperkalemia due to increased potassium intake, transcellular potassium shift, or decreased potassium excretion. Fictitious hyperkalemia o Hemolysis, tissue lysis, or tissue ischemia during phlebotomy o Contamination of blood sample with potassium-containing fluids o Thrombocytosis or leukocytosis (affects serum K+ but not plasma K+) Hyperkalemia due to increased K+ intake o Blood transfusion (increasing risk with increased duration of cell storage) o Intravenous (IV) or oral potassium o Maintenance K+ in IV or oral solutions combined with decreased renal function Hyperkalemia due to transcellular K+ shift o Metabolic acidosis o Beta-adrenergic blockade[10, 11] o Acute tubular necrosis o Electrical burns o Thermal burns o Cell depolarization o Head trauma o Rhabdomyolysis o Digitalis toxicity o Fluoride toxicity[12] o Cyclosporin A[13] o Methotrexate[14] o Propofol infusion syndrome o Tumor lysis syndrome o Succinylcholine use in a child with neuromuscular disease, prolonged bed rest (including patients in ICUs), or more than 24 hours after crush or burn injury[15] Hyperkalemia due to decreased K+ excretion o Acute renal failure o Primary adrenal disease (Addison disease, salt-wasting congenital adrenal hyperplasia) o Hyporeninemichypoaldosteronism o Renal tubular disease Medications (eg, potassium sparing diuretics, ACE inhibitors, angiotensin II blockers, trimethoprim, nonsteroidal anti-inflammatory agents [NSAIDs]) Differential Diagnoses Acidosis, Metabolic Acute Tubular Necrosis Burns, Electrical Burns, Thermal Congenital Adrenal Hyperplasia Head Trauma Rhabdomyolysis Toxicity, Digitalis Tumor Lysis Syndrome Laboratory Studies Laboratory studies depend on the etiology of hyperkalemia but may include the following: Serum electrolyte tests Serum BUN and creatinine tests Urinalysis (UA) Depending on the etiology or on clinical suspicion, other studies to consider include the following: Arterial or free-flowing venous blood gas sampling (for acid-base disorders): Capillary blood gas sampling should not routinely be used to evaluate for hyperkalemia due to significant risks of factitious hyperkalemia. Serum uric acid and phosphorous tests (for tumor lysis syndrome) Serum creatinine phosphokinase (CPK) and calcium measurements (for rhabdomyolysis) Urine myoglobin test (for crush injury or rhabdomyolysis; suspect if UA reveals blood in the urine but no RBCs are seen on urine microscopy) Specific drug level tests for suspected toxicity (digoxin) CBC count (for thrombocytosis, leukocytosis, or malignancy) Urine electrolyte tests, including potassium and osmolality (osm) tests Plasma osm test When the etiology of hyperkalemia remains unclear, calculation of the transtubular potassium gradient (TTKG) using the following formula may be useful: TTKG = (K+ urine X Osm plasma)/(K+ plasma X Osm urine) The normal TTKG varies from 5-15. In the setting of hyperkalemia with normal renal excretion of potassium, the TTKG should be greater than 10. A TTKG of less than 8 in the setting of hyperkalemia implies inadequate potassium excretion, which is usually secondary to aldosterone deficiency or unresponsiveness. Checking a serum aldosterone level may be helpful. Imaging Studies Imaging studies are not generally indicated, except to assess the primary disease state (eg, excluding obstructive uropathy as a cause for acute renal failure). Other Tests An ECG is essential in all children in whom hyperkalemia is suspected. ECG reveals the sequence of changes as follows: Serum K+ 5.5-6.5 mEq/L - Tall, peaked T waves with narrow base, best seen in precordial leads (as is shown in the image below) Peaked T waves. Serum K+ 6.5-8.0 mEq/L - Peaked T waves, prolonged PR interval, decreased or disappearing P wave, widening of QRS, amplified R wave Serum K+ greater than 8.0 mEq/L - Absence of P wave; progressive QRS widening, intraventricular/fascicular/bundle branch blocks; progressive widening of QRS, eventually merging with the T wave just before cardiac arrest, forming the sine wave pattern (as is shown in the image below) Sinusoidal wave. dical Care Hyperkalemia is a true medical emergency, with 3 primary goals of immediate management (in addition to prompt discontinuation of potassium-containing fluids and medications that lead to hyperkalemia):[16] Stabilize the myocardial cell membrane to prevent lethal cardiac arrhythmia (and to gain time to shift potassium intracellularly and enhance potassium elimination - Intravenous (IV) calcium chloride or gluconate Enhance cellular uptake of potassium o Sodium bicarbonate IV o Regular insulin and glucose IV o Beta-adrenergic agents, such as albuterol (used to manage hyperkalemia with variable results), terbutaline, dobutamine Enhancing total body potassium elimination o Sodium polystyrene sulfonate (Kayexalate) orally (PO)/rectally (PR) o Furosemide (only if renal function is maintained) o Emergent hemodialysis Arrhythmias due to hyperkalemia are very difficult to treat with defibrillation, epinephrine, or antiarrhythmic drugs without emergently lowering the serum potassium level. After initial stabilization, further workup should be performed to diagnose the etiology of the hyperkalemia. Children with acquired Addison disease or other primary adrenal disease require stress-dose steroid supplementation and children with hypoaldosteronism require mineralocorticoid supplementation. Emergent hemodialysis is sometimes necessary to treat severe symptomatic hyperkalemia that is resistant to drug therapy, particularly in patients without adequate renal function. Even in patients with severe hyperkalemia and a high gradient, peritoneal dialysis (PD) is not as efficient as hemodialysis in the removal of potassium. Rates of removal with PD are almost equal to the removal rate using sodium polystyrene sulfonate (Kayexalate). Continuous arteriovenous hemofiltration with dialysis (CAVHD) or continuous venovenous hemofiltration with dialysis (CVVHD) have also been used to remove potassium. However, potassium removal with these methods is similar to that of PD and sodium polystyrene sulfonate (Kayexalate). CVVHD or CAVHD may be used for long-term removal of potassium, but in acute, severe, life-threatening hyperkalemia unresponsive to medical therapy, hemodialysis remains the procedure of choice. Surgical Care Tumor debulking may be considered to decrease the risk of hyperkalemia from tumor lysis syndrome for solid tumors.[17] Consultations Consultations with the following specialists may be necessary in cases of hyperkalemia that result from certain conditions or disease states: Pediatric intensivist or neonatologist - Management of life-threatening hyperkalemia (hyperkalemia with ECG changes) Nephrologist - Hyperkalemia associated with renal failure Hematologist/oncologist - Hyperkalemia resulting from tumor lysis syndrome Social services specialist - Children who develop hyperkalemia following unintentional ingestions or poisonings Nutritional support specialist - Particularly for patients whose hyperkalemia is caused by renal failure, which requires close regulation of potassium and sodium intake Endocrinologist - Patients with suspected mineralocorticoid abnormalities such as congenital adrenal hyperplasia Diet Potassium intake must be closely monitored (and possibly restricted) in patients with renal failure. Medication Summary Myocardium stabilizers Intracellular transporters Alkalinizing agents Exchange resins Multimedia Library Tables References Medication Summary Treatment for severe hyperkalemia consists of 3 steps: (1) immediate stabilization of the myocardial cell membrane, (2) rapidly shifting potassium intracellularly, and (3) enhancing total body potassium elimination (see Medical Care). In addition, all sources of exogenous potassium should be immediately discontinued; including intravenous (IV) and oral (PO) potassium supplementation, total parenteral nutrition, and any blood product transfusion. Drugs associated with hyperkalemia should also be discontinued. Albuterol and other beta-adrenergic agents induce the intracellular movement of potassium via the stimulation of the sodium/potassium–adenosine triphosphate (Na+/K+ -ATP) pump. Studies have shown that IV salbutamol (not available in the United States) is highly effective in lowering serum potassium levels. Some studies in adults and children using nebulized albuterol indicate that this method of therapy is effective in lowering serum potassium levels. However, peak response is unclear; therefore, it has not been established as the first line of therapy in severe hyperkalemia. Myocardium stabilizers Class Summary Calcium does not lower serum potassium levels. It is primarily used to protect the myocardium from the deleterious effects of hyperkalemia (ie, arrhythmias) by antagonizing the membrane actions of potassium. View full drug information Calcium chloride IV calcium is indicated in all cases of severe hyperkalemia (ie, >7 mEq/L), especially when accompanied by ECG changes. Calcium chloride contains about 3 times more elemental calcium than an equal volume of calcium gluconate. Therefore, when hyperkalemia is accompanied by hemodynamic compromise, calcium chloride is preferred over calcium gluconate. Administration of calcium should be accompanied by the use of other therapies that actually help lower the K+ serum levels. Other calcium salts (eg, glubionate, gluceptate) have even less elemental calcium than calcium gluconate and are generally not recommended for therapy of hyperkalemia. Calcium chloride 1 g = 270 mg (13.5 mEq) of elemental calcium. Calcium gluconate 1 g = 90 mg (4.5 mEq) of elemental calcium. Intracellular transporters Class Summary Regular insulin and glucose cause a transcellular shift of potassium into muscle cells, thereby temporarily lowering K+ serum levels. Insulin and dextrose, IV Regular insulin presence results in intracellular movement of glucose, followed by K+ entry into muscle cells. Although effect is almost immediate, it is temporary, and, therefore, should be followed by therapy that actually enhances potassium clearance (eg, sodium polystyrene sulfonate). Alkalinizing agents Class Summary Sodium bicarbonate IV is used as a buffer that breaks down to water and carbon dioxide after binding free hydrogen ions. View full drug information Sodium bicarbonate IV infusion helps shift K+ into cells, further lowering serum K+ levels. Can be considered in treatment of hyperkalemia even in absence of metabolic acidosis. Also increases sodium delivery to the kidney, which assists in potassium excretion. Exchange resins Class Summary Sodium polystyrene sulfonate is an exchange resin that can be used to treat mild-to-moderate hyperkalemia. Each mEq of potassium is exchanged for 1 mEq of sodium. View full drug information Sodium polystyrene sulfonate (Kayexalate) Exchanges sodium for potassium and binds it in the gut, primarily in large intestine, and decreases total body potassium. Onset of action after PO administration ranges from 2-12 hours and is longer when administered PR. Do not use as a first-line therapy for severe life-threatening hyperkalemia. Use in second stage of therapy to reduce total body potassium Pediatrics Hypokalemia Background Potassium is the most abundant intracellular cation and is necessary for maintaining a normal charge difference between intracellular and extracellular environments. Potassium homeostasis is integral to normal cellular function and is tightly regulated by specific ion-exchange pumps, primarily by cellular, membrane-bound, sodium-potassium adenosine triphosphatase (ATPase) pumps. Derangements of potassium regulation may lead to neuromuscular, GI, and cardiac conduction abnormalities. Hypokalemia is generally defined as a serum potassium level of less than 3.5 mEq/L in children, although exact values for reference ranges of serum potassium are age-dependent, and vary among laboratories. It is frequently present in pediatric patients who are critically ill and reflects a total body deficiency of potassium or, more commonly, reflects conditions that promote the shift of extracellular potassium into the intracellular space. Pathophysiology Hypokalemia may be due to a total body deficiency of potassium, which may result from prolonged inadequate intake or excessive losses (including but not limited to, long-term diureticor laxative use, and chronic diarrhea, hypomagnesemia, or hyperhidrosis). Acute causes of potassium depletion include diabetic ketoacidosis,[1] severe GI losses due to vomiting and diarrhea, dialysis, and diuretic therapy. Hypokalemia may also be the manifestation of large potassium shifts from the extracellular to intracellular space, as seen with alkalosis, insulin, catecholamines (including albuterol and other commonly-used beta2-adrenergic agonists),sympathomimetics, and hypothermia. Other recognizable causes include renal tubular disorders, such as distal renal tubular acidosis, Bartter syndrome,[2] and Gitelman syndrome, periodic hypokalemic paralysis, hyperthyroidism, andhyperaldosteronism. Other mineralocorticoid excess states that may cause hypokalemia include cystic fibrosis (with hyperaldosteronism from severe chloride and volume depletion), Cushing syndrome, and exogenous steroid administration. Excessive natural licorice consumption can also cause or exacerbate potassium loss due to inhibition of 11-betahydoxysteroid dehydrogenase, which leads to elevated endogenous mineralocorticoid activity.[3] Epidemiology Mortality/Morbidity Mortality is rare, except when hypokalemia is severe or occurs following cardiac surgery, when accompanied by arrhythmia, or in patients who have underlying heart disease and require digoxin therapy. Short-term morbidity is common and may include GI hypomotility or ileus; cardiac dysrhythmia; QT prolongation; appearance of U waves that may mimic atrial flutter, T-wave flattening, or STsegment depression; and muscle weakness or cramping. Mortality and morbidity can also be related to treatment for hypokalemia with potassium supplementation, particularly if potassium is given in large doses or rapidly. Because of the risk associated with potassium replacement, alleviation of the cause of hypokalemia may be preferable to treatment, especially if hypokalemia is mild, asymptomatic, or transient and is likely to resolve without treatment. Race Racial differences may be present in predisposing conditions such as Bartter syndrome, Gitelman syndrome, Conn syndrome (ie, hyperaldosteronism), Cushing syndrome, and familial hypokalemic paralysis. In addition, significant hypokalemia and hypokalemic paralysis develop in 2-8% of Asians with hyperthyroidism. Sex No known sex predilection has been noted. Age Viral GI infections tend to be more common in infants and younger children. Younger children with emesis or diarrhea are at an increased risk of hypokalemia because the depletion of fluid volume and electrolytes from GI loss is relatively higher than that found in older children and adults. Insulin-dependent diabetes mellitus that results in diabetic ketoacidosis (with its inherent fluid and potassium loss) is more common in children. Excessive corticosteroid and mineralocorticoid secretion, as in Cushing syndrome and Conn syndrome, is a less common cause of hypokalemia in the pediatric patient. Periodic hypokalemic paralysis may appear in childhood or young adulthood, precipitated by rest after strenuous exercise, physical or metabolic stress (eg, exposure to cold, alcohol ingestion), a high-carbohydrate meal, or exposure to exogenous insulin or catecholamines (eg, epinephrine and albuterol). Hypokalemia due to hyperthyroidism is generally observed in adults. History Hypokalemia due to excessive loss is usually accompanied by a history of GI loss (emesis or diarrhea), urinary output, or sweating. This may be exacerbated by inadequate oral intake. Query about current or recent treatment with medications and herbal products (especially natural licorice), including insulin, albuterol or other beta2-sympathomimetics, corticosteroids, diuretics, laxatives,enemas, or bowel-prep solutions. A complete and upto-date medication and supplement list is essential, especially if the patient is taking new medications or may have had medication substitutions. The patient may have had similar episodes in the past. Familial historical data may include surgery for pituitary or adrenal tumors or acute intermittent episodes of paralysis, with or without association with hyperthyroidism. Periodic familial hypokalemia Physical Physical examination findings may frequently be within the reference range. Occasionally, muscle weakness is evident. Cardiac arrhythmias and acute respiratory failure from muscle paralysis are lifethreatening complications that require immediate diagnosis. Cardiovascular examination findings may also be within normal limits. Occasionally, tachycardia with irregular beats may be heard. Severe hypokalemia may manifest as bradycardia with cardiovascular collapse. Hypoactive bowel sounds may suggest hypokalemic gastric hypomotility or ileus. Causes Hypokalemia may be due to a total body deficit of potassium, which may occur chronically with the following: o Prolonged diuretic use o Inadequate potassium intake o Laxative use o Diarrhea (including congenital chloride diarrhea)[4] o Hyperhidrosis o Hypomagnesemia o Renal tubular losses (including Fanconi syndrome,[5] Bartter syndrome, Gitelman syndrome, and others) o Dengue syndrome[6] Acute causes of potassium depletion include the following: o Diabetic ketoacidosis o Severe GI losses from vomiting and diarrhea o Dialysis and diuretic therapy o Alcohol intoxication/overdose[7] Hypokalemia may also be due to excessive potassium shifts from the extracellular to the intracellular space, as seen with the following: o Alkalosis o Insulin use o Catecholamine use o Sympathomimetic use o Use of sodium bicarbonate, especially during therapeutic alkalinization (commonly used to treat salicylate and cyclic antidepressant overdoses, tumor lysis syndrome, rhabdomyolysis, etc) o Use of sodium polystyrene sulfonate to treat transient hyperkalemia o Hypothermia Other recognizable causes of hypokalemia include the following: o Renal tubular disorders, such as Bartter syndrome and Gitelman syndrome o Type I or classic distal tubular acidosis o Periodic hypokalemic paralysis o Hyperaldosteronism o Celiac disease[8] Other states of mineralocorticoid excess that may cause hypokalemia include the following: o Cystic fibrosis with hyperaldosteronism from severe chloride and volume depletion o Cushing syndrome o Exogenous steroid administration, including fludrocortisone and other mineralocorticoids o Excessive licorice consumption[3] Other conditions that may cause hypokalemia include acute myelogenous, monomyeloblastic, or lymphoblastic leukemia. Drugs that may commonly cause hypokalemia include the following: o Furosemide, bumetanide, and other loop diuretics o Methylxanthines (theophylline, aminophylline, caffeine) o Verapamil (with overdose) o Amphotericin B, micafungin[9] o Quetiapine (particularly in overdose) o Ampicillin, carbenicillin, high-dose penicillins[10] o Sirolimus[11] o Drugs associated with magnesium depletion, such as aminoglycosides, amphotericin B, and cisplatin Differential Diagnoses Bartter Syndrome Hyperthyroidism Hypochloremic Alkalosis Hypomagnesemia Metabolic Alkalosis Laboratory Studies The following studies are indicated in patients with hypokalemia: Serum electrolyte tests: Screen for concurrent electrolyte abnormalities, which may affect treatment. Blood gas analysis o Assess acid-base status. o Alkalosis may induce hypokalemia, and treatment of acidosis may worsen existing hypokalemia. Drug screen (serum or urine) o Amphetamines and other sympathomimetic stimulants can cause hypokalemia. o Other drugs that can cause hypokalemia include verapamil (with overdose), theophylline, amphotericin B, aminoglycosides, and cisplatin. Serum adrenocorticotropic hormone (ACTH), cortisol, renin activity, and aldosterone tests: Evaluate for suspected Cushing, Conn, or adrenal hyperplasia syndromes, including 11-beta-hydroxylase deficiency. Simultaneous serum insulin and C-peptide tests: Because hyperinsulinism can cause transient hypokalemia, elevated serum insulin without appropriately elevated C-peptide suggests exogenous insulin administration, which may represent Münchhausen-by-proxy syndrome. Imaging Studies MRI: Perform brain MRI if a brain or pituitary tumor is suspected as a cause of hypercortisolism. Ultrasonography and CT scanning: Perform abdominal ultrasonography or CT scanning if an adrenal tumor or hyperplasia is suspected. Other Tests Although ECG changes may be helpful if present, their absence should not be taken as reassurance of normal cardiac conduction.[12] The ECG in hypokalemia may appear normal or may have only subtle findings immediately before clinically significant dysrhythmias. ECG findings may include the following (see the image below): o o o o Ventricular dysrhythmia Prolongation of QT interval ST-segment depression T-wave flattening o Appearance of U waves Prominent U waves after T waves in hypokalemia. During therapy, monitor for changes associated with overcorrection and hyperkalemia, including a prolonged QRS, peaked T waves, bradyarrhythmia, sinus node dysfunction, and asystole. Medical Care The treatment of hypokalemia depends on severity and etiology. Unlike hyponatremia, in which the total body sodium deficit can be readily estimated, serum potassium may not accurately reflect total body stores. Indeed, during diabetic ketoacidosis, serum potassium levels are usually initially elevated, even in the face of severe depletion of total body potassium. Correction of acidosis in diabetic ketoacidosis may cause a precipitous drop in serum potassium levels. Treatment of hypokalemia should be directed at the etiology of hypokalemia as well as its correction, as treatment of hypokalemia carries with it a significant risk of iatrogenic hyperkalemia. Transient, asymptomatic, or mild hypokalemia may spontaneously resolve or may be treated with enteral potassium supplements. Symptomatic or severe hypokalemia should be corrected with a solution of intravenous potassium. Whenever practical, treatment of hypokalemia should be performed in a monitored setting with medications and personnel available to intervene in the event that treatment results in symptomatic hyperkalemia. Surgical Care Except for excision of tumors leading to hypokalemia, management is nonsurgical. Consultations After resolution, consultation with subspecialists (including, but not limited to, endocrinologist, nephrologist, pulmonologist, gastroenterologist, geneticist, or specialist in metabolic disease) may be necessary to diagnose and manage predisposing conditions. Consultation with a dietitian may be helpful in cases of hypokalemia due to inadequate dietary intake. Consultation with mental health professionals may be necessary for ongoing treatment of hypokalemia secondary to anorexia and/or bulimia. Diet Dietary modification may be necessary for patients with excessive potassium losses (eg, diuretic or laxative use) or patients with hypokalemia who are at increased risk, such as those receiving digoxin. Avoidance of specific foods (eg, licorice) may also be necessary for high-risk individuals. Activity Patients with hypokalemic periodic paralysis may need to modify exercise regimens to avoid periods of strenuous exercise. Patients at risk of hypokalemia from sweat losses should have adequate potassium and fluid available during activities likely to result in significant sweating and should be given anticipatory guidance regarding symptoms of hypokalemia. Medication Summary Potassium supplements Class Summary These agents are used to restore body potassium storage. Electrolytes are used to correct disturbances in fluid and electrolyte homoeostasis or acid-base balance and to reestablish osmotic equilibrium of specific ions. View full drug information Potassium chloride (also citrate, acetate, bicarbonate, gluconate) Potassium chloride is the preferred salt for patients with preexisting alkalosis. First choice for IV therapy. Essential for transmission of nerve impulses; contraction of cardiac muscle; and maintenance of intracellular tonicity, skeletal and smooth muscles, and normal renal function. Gradual potassium depletion occurs via renal excretion, through GI loss, or because of low intake. Depletion may result from diuretic therapy, primary or secondary hyperaldosteronism, diabetic ketoacidosis, severe diarrhea, vomiting, or inadequate replacement during prolonged parenteral nutrition. Medical therapy is aimed at potassium supplementation by the enteral (ie, oral or through feeding tubes) or parenteral route. Transient, asymptomatic, or mild hypokalemia may resolve spontaneously, or it may be treated using enteral potassium supplements. Symptomatic or severe hypokalemia should be corrected with intravenous potassium preparations. Further Inpatient Care After the initial phase of hypokalemia therapy is completed, focus further inpatient care on matching potassium intake to losses, periodic testing of serum potassium levels, and electrocardiographic monitoring for hypokalemia or hyperkalemia due to therapy. Alleviation of aggravating conditions, simplification of medication administration, and patient education form the basis of ongoing patient health and safety. Further Outpatient Care If the condition is expected to persist beyond inpatient care, patients should receive follow-up medical care for home treatment. Additional medical follow-up must be obtained for associated medical conditions. Inpatient & Outpatient Medications Other than potassium supplementation as described above, no additional medications are required. If current medications are responsible for hypokalemia, substitution of potassium-sparing alternatives may help reduce degree of hypokalemia and may help minimize requirements for potassium supplementation. Transfer Patients with severe or symptomatic hypokalemia require transfer to an ICU for intravenous potassium supplementation and continuous electrocardiographic monitoring. Deterrence/Prevention Because many medications (particularly loop diuretics, mineralocorticoids, catecholamines, methylxanthines, alkalinizing agents) may be responsible for hypokalemia, eliminating or reducing the doses of these medications may be helpful in preventing or minimizing hypokalemia. Complications Hyperkalemia due to excessive/rapid potassium replacement Cardiac dysrhythmia Gastric erosions Strictures Prognosis With adequate control of potassium levels and resolution of any predisposing condition, prognosis is excellent. Patient Education Patients should be educated in terms of predisposing conditions. The importance and risks involved with potassium supplementation and the warning signs of hypokalemia or overtreatment must be emphasized upon discharge from the hospital. Knowledge of cardiopulmonary resuscitation and education on timely access to emergency medical services may prevent morbidity or mortality. Ongoing communication is essential for reducing the risks and in therapy, especially in patients with chronic conditions associated with hypokalemia. For excellent patient education resources, see the Endocrine System Center, as well as Low Potassium.