Hypotonic maintenance intravenous (IV) fluids are associated with mild to moderate hyponatremia in postoperative patients. Anesthesia, stress, and inflammatory mediators may contribute. Electrolyte monitoring in patients at risk is essential for detection and management of severe hyponatremia. This critical effect of the syndrome of inappropriate antidiuretic hormone may occur even in patients on isotonic IV fluids.
Growing evidence suggests that the choice of normal saline crystalloids, balanced solution crystalloids, or colloids for resuscitation and maintenance therapy should be influenced by the underlying pathology.
Albumin infusions have been generally safe but may introduce increased mortality risk in patients with traumatic brain injury. Those given albumin had increased intracranial pressure, which may contribute to the apparent risk.
Avoiding and correcting excessive fluid volume overload after initial resuscitation and hemodynamic stabilization will decrease morbidity and mortality among critically ill patients.
Traditional fluid and electrolyte management during critical illness is being refined by science, clinical experience, and expert opinion. Particular attention is drawn to intravenous fluid (IVF) composition, appropriate uses and choices of colloids, extracellular fluid (ECF) volume targets from resuscitation to maintenance, and approaches to removal of excessive ECF volume using diuresis, continuous renal replacement therapy (CRRT), and intermittent hemodialysis (IHD).
Fluid and electrolyte management often begins at resuscitation, but important choices are also made at anesthesia induction and at initial postoperative maintenance. Resuscitation with normal saline is physiologically effective and cost-effective in almost all circumstances. However, the chloride content imposes an acid load. Further, there are substantial data suggesting potential harm from fluids containing supraphysiological concentrations of chloride and improved outcomes for certain patients with balanced crystalloid solutions. , Increasing evidence highlights the importance of evaluating resuscitative fluid composition for specific patient populations. Similarly, intraoperative fluids influence acid-base and electrolyte status, particularly of vulnerable patients.
The Na + content of IVF for postoperative or critical care maintenance may be important for certain patients. Clearly, 0.180 and 0.225 mM saline are associated with a higher incidence of mild hyponatremia, , although controlled trials do not show this effect for 0.460 mM saline. , Severe hyponatremia has been infrequently associated with pulmonary or central nervous system (CNS) illness in pediatrics, with the exception of children with traumatic brain injury (TBI). Among patients with those and other illnesses, the evolving study of the influence of inflammatory mediators directly on the hypothalamus and indirectly on vasopressin secretion may further clarify which patients are at most risk of clinically significant hyponatremia. ,
Evidence for and against the use of colloids in specific groups of critically ill patients is accumulating. Intriguing but less than definitive studies suggest benefit in sepsis and septic shock and possible harm in patients with TBI, perhaps associated with increased intracranial pressure. Albumin does appear useful in stabilizing patients with severe hepatic failure and in prevention of hepatorenal syndrome. Evidence for albumin use with or without diuresis among those with acute respiratory distress syndrome (ARDS) suggests improved oxygenation but minimal effect on outcomes. In general, in patients with relatively intact vascular endothelium, 10 to 15 mL/kg of 4% or 5% albumin may be used for intravascular volume expansion with slower leakage into the ECF space compared with crystalloids. Albumin concentrate at 25% may be useful in temporarily redistributing ECF volume from the extravascular to the intravascular space to facilitate organ perfusion and spontaneous or drug-assisted diuresis with minimal additional infused fluid volume. In summary, consideration of albumin use in selected patients remains appropriate. , Currently, there are no formulations of hydroxyethyl starch that can be recommended for use in critically ill patients. ,
Adult and pediatric studies have generated strong evidence for deleterious effects of fluid volume overload, particularly in patients with sepsis or ARDS. , Patients with less fluid gain early in their illness have more ventilator-free days, shorter intensive care unit (ICU) stays, less acute kidney injury (AKI), and decreased in-hospital mortality compared with those with greater than 5% to 15% early positive fluid balance. The observed associations of increasing fluid balance on morbidity and mortality has led to proposals of a phased approach to fluid management, including aggressive resuscitation using appropriate fluids guided by careful clinical measurement and evaluation, prompt reduction of resuscitation fluid rates when hemodynamically tolerated, gradual correction of volume excesses using fluid restriction, colloid dosing to adjust fluid space distribution, continuous infusion diuresis, and, finally, CRRT or IHD when needed. Medications are a potentially overlooked and modifiable source of excess fluid volume in patients with fluid volume overload. ,
As ICU patients progress from stabilization to maintenance, ECF volume overload may spontaneously resolve, or it may warrant active intervention. Loop diuretics do not prevent or ameliorate AKI but may be useful in mobilizing excess ECF volume. Studies of this intervention are variable as to dosages, patient diagnoses, and renal conditions. Carefully titrated continuous infusion of loop diuretics may be superior to bolus dosing. In ARDS, continuous infusion plus albumin have enhanced fluid mobilization. Accompanying losses of K + , Ca ++ , and Mg ++ should be anticipated and replaced appropriately. For patients unresponsive to diuresis, either CRRT or IHD can provide electrolyte management, and gradual ECF correction though the optimal timing of CRRT among different patient groups is under evaluation.
Sodium distribution is 90% extracellular and, with its associated anions, largely determines the osmotic condition of the ECF. Disturbance of ECF osmolality affects cell volume, with critical clinical significance in the CNS. Therefore, neurologic symptoms dominate the clinical picture in both hyponatremia and hypernatremia. In pediatric patients in the ICU, young age, underlying neurologic conditions, developmental delay, cerebral hypoperfusion, and medication effects may obscure subtle neurologic findings; judicious laboratory monitoring along with careful clinical assessment is essential.
Emerging evidence in both adult and pediatric patients suggests an association between disturbances in sodium balance and adverse outcomes, including mortality, ICU length of stay (LOS), use of both noninvasive and invasive mechanical ventilation, and long-term neurologic sequelae. It is unclear at this time whether these adverse effects are a direct consequence of the sodium imbalance, a reflection of a greater severity of illness, or related to other underlying pathologic processes. Mild disturbances of sodium may serve as a warning of an ongoing process of greater significance. More severe hyponatremia or hypernatremia may be life threatening. These disturbances may result from the disproportionate gain or loss of either sodium or water. Pathologic sodium retention may occur in disorders such as congestive heart failure (CHF), cirrhosis, and nephrotic syndrome without causing a significant change in ECF concentration, but the concomitant expansion of the ECF volume may be damaging.
Sudden, severe hyponatremia is life threatening. Its management demands prompt, measured action with ongoing monitoring and therapeutic adjustment. The syndrome of inappropriate antidiuretic hormone secretion (SIADH) and cerebral salt wasting (CSW) are the most common causes of severe hyponatremia, although inappropriately dilute feeding or iatrogenic causes should also be considered. Severe hyponatremia, which is variably defined as a serum sodium concentration of either less than 125 mEq/L or less than 120 mEq/L, is uncommon and is usually associated with known risk factors such as pulmonary or CNS disease or the use of certain drugs. Mild hyponatremia is common among hospitalized pediatric patients and occurs predictably in postoperative patients. Patients with renal, hepatic, or cardiac disease and those exposed to prolonged general anesthesia are particularly at risk. Accurate identification of patients at risk will inform decisions on frequency of laboratory monitoring and will allow an early evaluation of and response to evolving hyponatremia.
Pathophysiology and etiology
Hyponatremia may occur in the presence of decreased, increased, or normal amounts of total body sodium ( eBox 71.1 ).
Decreased total body sodium
Sequestration: sepsis, peritonitis, pancreatitis, rhabdomyolysis, ileus
Cutaneous: burns, cystic fibrosis
Cerebral salt wasting
Thiazides, loop diuretics (listed in order of severity of salt wasting)
Osmotic diuretic agents: mannitol, glucose, urea
Medullary cystic disease, obstructive uropathy, tubulointerstitial nephritis, chronic pyelonephritis, renal tubular acidosis, Kearns-Sayre syndrome
Congenital adrenal hyperplasia, Addison disease
Increased total body sodium
Congestive heart failure
Advanced chronic kidney disease
Normal total body sodium
Syndrome of inappropriate antidiuretic hormone secretion
Infantile water intoxication
Abusive water intoxication
Decreased total body sodium
Loss of total body sodium results in hyponatremia if total body water is retained in relative excess of the sodium loss. Hypovolemic stimulation of antidiuretic hormone (ADH) release may overwhelm osmotic ADH control, maintaining water retention despite hyponatremia and hypoosmolality. A decrease of as little as 5% in circulating volume may be sufficient to trigger this response. Sodium deficit and volume loss may occur through extrarenal or renal losses. In children, extrarenal losses most often occur from vomiting and diarrhea. In critically ill patients, large extrarenal losses may result from fluid sequestration that occurs with sepsis, peritonitis, pancreatitis, ileus, rhabdomyolysis, ventriculostomy drains, and burns. Renal losses include diuretic use, osmotic diuresis, various salt-losing renal diseases, CSW, and adrenal insufficiency.
Renal sodium losses
Renal salt-wasting states are generally identified by a urinary sodium excretion in excess of 20 mEq/L and a fractional excretion (FE Na ) of more than 1%. The use of thiazide and loop diuretics can exacerbate hyponatremia and hypovolemia and lead to a characteristic hypokalemic metabolic alkalosis (i.e., contraction alkalosis). In normally functioning kidneys, concentrated urine is produced by the equilibration of fluid in the collecting tubules with the hyperosmotic medullary interstitium, which, in turn, is generated by sodium chloride (NaCl) reabsorption without water in the ascending limb of the loop of Henle. Thiazides act in the cortical distal tubule and do not impair the ability of ADH to increase water reabsorption in the collecting tubules and collecting duct, resulting in thiazide-associated hyponatremia. Osmotic sodium and water losses occur in a child with uncontrolled hyperglycemia with glucosuria, with mannitol use, and during urea diuresis following relief of urinary tract obstruction. Hyperglycemia and mannitol, in addition to inducing urinary sodium and water losses, produce osmotic water movement from the intracellular fluid (ICF) to the ECF, further lowering serum sodium. Sodium levels drop about 1.5 mEq/L for every 100 mg/dL rise in blood glucose level. Significant salt wasting may occur with several intrinsic renal diseases. Adrenal insufficiency is identified by hyponatremia in association with hyperkalemia and decreased urinary potassium excretion.
Cerebral salt wasting
Cerebral salt wasting (CSW) is a clinical entity that continues to generate controversy. First described by Peters and coworkers in 1950, it was superseded by the description of SIADH by Schwartz and coworkers in 1957 and then rediscovered in 1981 when Nelson and associates studied hyponatremia in a series of neurosurgical patients with isotopically measured low blood volumes. Despite lingering skepticism, its distinct clinical identity continues to be supported ( Table 71.1 ). Patients typically have an acute neurologic injury with hemorrhage, trauma, infection, or a mass and may have undergone neurosurgical procedures, although CSW is not exclusively associated with intracranial abnormalities. CSW differs from SIADH primarily related to intravascular volume depletion that may be difficult to clinically differentiate when hyponatremia is first detected. CSW, which may be more appropriately labeled renal salt-wasting syndrome , is caused by inappropriate natriuresis that results in volume depletion whereas SIADH is caused by inappropriate water retention that results in (often subclinical) volume expansion ( Table 71.2 ). , With the natriuresis in CSW, large urine volumes contain very high sodium concentrations, leading to rapid depletion of both sodium and ECF volume. An otherwise unexplained intravascular volume contraction is central to the diagnosis and may cause a secondary boost in ADH release. Left untreated, CSW results in intravascular volume depletion, hypotension, and hypoperfusion or hypovolemic shock as well as hyponatremia. Untreated SIADH, in contrast, leads to progressive hyponatremia and the clinical consequences thereof with maintenance or mild expansion of fluid balance. The pathophysiologic link between intracranial injury and renal salt wasting has yet to be elucidated, contributing in no small part to the controversy. Both brain natriuretic peptide (BNP) and atrial natriuretic peptide (ANP) are attractive as potential mediators, but neither has a proven etiologic role. , Decreased sympathetic input to the kidneys is another postulated mechanism. Distinguishing CSW from SIADH may be difficult in many complex clinical scenarios. Urate clearance as a means to differentiate the two has shown promise in early studies, though the pathophysiology is not completely understood. Hypouricemia and elevated urate clearance (FE Urate >12%) can be found in both SIADH and CSW, but only in CSW do these abnormalities persist following correction of hyponatremia. , In cases of severe or symptomatic hyponatremia, however, this may be temporarily unnecessary because the initial therapy is the same. Administration of enough concentrated sodium to result in a small increase in osmolality is appropriate, and support of intravascular volume is required. A reasonable approach might begin with the administration of 5 mL/kg of hypertonic (3%) NaCl followed by isotonic repletion of the remaining volume deficit. Once this is achieved, sufficient sodium and fluid administration to account for daily maintenance requirements as well as ongoing losses is necessary. Administration of fludrocortisone, a mineralocorticoid, has been reported to aid in CSW management in severe or prolonged cases that are refractory to initial therapy. In less severe cases, infusion of isotonic saline represents a reasonable first step in management; the observed response may help to differentiate between CSW and SIADH. In CSW, saline administration addresses volume depletion and hyponatremia. It is of limited or no benefit in patients with SIADH, who are more effectively managed with fluid restriction. The absolutely essential part of therapy is the frequent reassessment of sodium levels and volume status, with treatment adjustments as indicated.
|Trigger||Most commonly, acute intracranial injury or illness (subarachnoid hemorrhage, trauma, etc.) though can be seen with non-CNS disease|
|Onset||Typically, a few days after the injury occurs|
|Signs||Falling serum Na + , high urine output, high urine Na +|
|Course||Without treatment, proceeds to intravascular volume depletion, hypotension, and hypoperfusion|
|Treatment||Replace salt and water losses; may require 3% NaCl ± loop diuretics; fludrocortisone in refractory cases|
|Resolution||Days to weeks|
|Differential diagnosis||Syndrome of inappropriate antidiuretic hormone, adrenal insufficiency, osmotic diuresis|
|Urine Na +||Very high, often >100 mEq/LCan be lower if fluid and sodium are restricted||Variable, but usually >20 mEq/L|
|Urine output||Inappropriately high, leading to volume depletion||Variable; may be normal or decreased|
|Response to saline challenge||Improvement in volume deficit and serum Na +||No improvement in serum Na +|
|Response to fluid and salt restriction||No improvement; volume deficit and hyponatremia may worsen||Improvement in serum Na +|
Increased total body sodium
Hyponatremia with increased total body sodium occurs when the increase in total body water exceeds the sodium retention. Four clinical situations are commonly seen: CHF, cirrhosis, nephrotic syndrome, and advanced renal failure. In all four conditions, hyponatremia tends to be mild or moderate, asymptomatic, and nonprogressive or slowly progressive. These patients typically present to the ICU primarily for care related to these underlying conditions rather than for symptoms related to hyponatremia.
Congestive heart failure
Hyponatremia in heart failure is associated with a worse prognosis. , Low cardiac output states are characterized by a decrease in effective circulating volume that is detected by vasoreceptors in the carotid sinus, aortic arch, and renal juxtaglomerular apparatus. Activation of various neurohormonal modulators promotes vasoconstriction along with sodium and water retention. Increased sympathetic activity and stimulation of the renin-angiotensin-aldosterone system (RAAS) produce increased afferent and efferent arteriolar vascular resistance and decreased glomerular filtration rate (GFR) with a resultant decrease in urinary sodium excretion. Nonosmotic ADH release is stimulated, further impairing water excretion. In addition, decreased aldosterone degradation, along with altered levels of other vasoactive and nonvasoactive substances, leads to a primary increase in tubular sodium reabsorption. A deleterious positive feedback loop is created, in which the vasoconstrictive and fluid retentive effects of these neurohormonal systems promote further vasoconstriction and worsening renal perfusion. The complex interactions between renal and cardiovascular pathophysiology have been described as the cardiorenal syndromes, with five subtypes based on the primary organ affected and the acuity of the physiologic derangement.
Early in cirrhosis, increased intrahepatic pressure may initiate renal sodium retention even before ascites formation. The development of portal hypertension leads to nitric oxide–mediated peripheral vasodilation and to the formation of arteriovenous fistulae. The result is a decrease in effective circulating volume and activation of sodium-retaining mechanisms with higher levels of renin, aldosterone, ADH, and norepinephrine. Hyponatremia arises in the setting of persistent renal sodium and water retention, which also leads to ascites and further complicates the kidneys’ ability to excrete water. ,
Hyponatremia is an occasional finding in patients with nephrotic syndrome. However, it may be present in patients with apparently normal or decreased central volume. The humoral factors involved in patients with decreased central volume appear to be similar to those with decompensated cirrhosis.
As a diseased kidney loses nephrons, the remaining nephrons exhibit a dramatically elevated fractional sodium excretion in an effort to maintain sodium balance. Edema develops when larger quantities of sodium are ingested than cannot be excreted. The ability to excrete water is also impaired, primarily because of the progressive decrease in GFR. Hyponatremia occurs when water intake exceeds insensible losses plus the maximum volume that can be excreted.
Normal total body sodium
Hyponatremia without evidence of hypovolemia or edema in the pediatric population is usually associated with SIADH. Renal concentrating and diluting ability ultimately depends on the presence or absence of ADH to modulate water permeability in the collecting duct. Osmoreceptors for ADH reside in the anterior hypothalamus, responding to changes of as little as 1% in plasma osmolality. The nonosmotic stimuli that induce release of ADH are associated with changes in autonomic neural tone due to physical pain or trauma, emotional stress, hypoxia, cardiac failure, nausea and vomiting, adrenal insufficiency, volume depletion, and exposure to general anesthesia ( eBox 71.2 ). Nonosmotic stimuli, as the name implies, are active even in the face of normal plasma osmolality, and a decrease in plasma volume of as little as 5% is sufficient to trigger a strong ADH response. Vasopressin (ADH) synthesized in the hypothalamus is transported in neurosecretory granules to the axonal bulbs in the median eminence and posterior pituitary gland and is released by exocytosis in the presence of appropriate stimuli. Increasing evidence indicates that inflammatory mediators facilitate release and contribute to the high incidence of hyponatremia in Rocky Mountain spotted fever, Kawasaki, and other inflammatory illnesses. After release, ADH binds to V2 receptors in the basolateral membrane of the renal collecting duct, increasing cyclic adenosine 3′,5′-monophosphate formation and facilitating phosphorylation of aquaporin-2. Incorporation of aquaporin-2-containing vesicles in the apical (luminal) membrane increases cell permeability to water and provides a pathway for water reabsorption.
Encephalitis, including human immunodeficiency virus/acquired immunodeficiency syndrome encephalitis
Rocky Mountain spotted fever
Subarachnoid or subdural hemorrhage
Cerebral thrombosis or hemorrhage
Head trauma with cerebral edema
Cavernous sinus thrombosis
Hypoxic encephalopathy, including neonatal hypoxic-ischemic encephalopathy
Bacterial and viral pneumonias
Respiratory failure with positive pressure ventilation
Carcinomas of the lung, oropharynx, gastrointestinal tract (including the pancreas), and genitourinary tract
Ewing sarcoma, mesothelioma
Antidiuretic hormone analogs (vasopressin, desmopressin/1-deamino-8-D-arginine vasopressin, oxytocin)
Tricyclic antidepressants and selective serotonin reuptake inhibitors
Indomethacin and nonsteroidal antiinflammatory drugs
High levels of inflammatory mediators
Pain or emotional stress
Marathon running or endurance exercise
Hereditary (gain-of-function mutations in the vasopressin V2 receptor)
Clinically, SIADH is characterized by (1) hyponatremia, (2) euvolemia or mild hypervolemia, (3) hypoosmolality, (4) inappropriately elevated urine osmolality, and (5) elevated urine sodium concentration. It has been associated with several categories of clinical disease, including CNS and pulmonary disorders, malignancies, and as an adverse effect of numerous drugs (see eBox 71.2 ). Underlying renal function is normal. Under normal physiologic conditions, a decrease in serum sodium of 4 to 5 mEq/L below normal (with a serum osmolality of less than 270 mOsm) should maximally inhibit ADH secretion with a resultant urine osmolality of less than 100 mOsm. It is frequently difficult to determine, however, whether urine osmolality and urine sodium are inappropriately elevated, particularly in critically ill patients receiving IV fluids. Variable sodium and water administration rates, isotonic or hypertonic fluid boluses, fluctuations in hemodynamic status and urine output, and a history of diuretic use can all confound laboratory interpretation. The key consideration is the relative relationship between the degree of hyponatremia and hypoosmolality and the robustness of the dilutional response in the urine. Failure to maximally dilute urine in the face of hypoosmolality represents inappropriate ADH response so that a urine osmolality of 200 to 250 mOsm may reflect SIADH in hyponatremic patients. The urinary sodium level is generally more than 30 mEq/L but may be much less in patients who are provided a low sodium intake. When the urinary sodium concentration is very high, it is the net balance between intake and output that differentiates between SIADH and CSW syndrome. CSW is favored when the urinary sodium excretion grossly exceeds sodium intake.
Signs and symptoms
The severity of signs and symptoms depends on the rapidity of the development of hyponatremia. Neurologic symptoms predominate as plasma hypoosmolality causes a shift in fluid from the ECF to the ICF compartment, leading to generalized cellular swelling. The rigidity of the intracranial space leaves little room for cellular expansion, resulting in increasing intracranial pressure. Brain cells prevent massive swelling in the early phases of hyponatremia by extrusion of electrolytes and other cellular osmolytes. Acute decreases in sodium concentration are associated with lethargy, apathy, and disorientation, often accompanied by nausea, vomiting, and muscle cramps. No predictable correlation exists between the degree of hyponatremia and its resultant symptoms, as severe hyponatremia that develops gradually may present with minimal symptoms. Acute decreases in sodium to less than 120 mEq/L, however, generally produce severe symptoms, such as seizures or coma. Other findings may include decreased deep tendon reflexes, pathologic reflexes, pseudobulbar palsy, and a Cheyne-Stokes respiratory pattern. Cerebral edema and intracranial hypertension may be severe enough to result in herniation, permanent neurologic injury, and death.
Stimuli for ADH release are frequently present in both surgical and nonsurgical ICU patients, putting them at risk for hyponatremia. Use of hypotonic intravenous (IV) maintenance fluids increases the risk for development of hyponatremia. The appropriate administration of isotonic IV fluids in these patients will decrease the incidence of hyponatremia. , , For patients with severe SIADH or CSW, however, the use of isotonic fluids alone may not be adequate to prevent life-threatening disturbances in sodium and water balance. Thoughtful monitoring of sodium levels is mandatory, along with avoidance of large volumes of hypotonic fluids.
The time course over which hyponatremia develops is a key determinant of the therapeutic approach. Severe hyponatremia is associated with significant morbidity and mortality and requires urgent attention. Even with milder hyponatremia, critically ill patients who have serum sodium corrected have improved rates of mortality and longer survival. , As described previously, acute hyponatremia produces significant cerebral edema when initial compensation mechanisms are overwhelmed and more chronic adaptive mechanisms are not yet fully developed. Hyponatremia that has been present less than 4 hours can safely be corrected promptly. When the evolution of hyponatremia is gradual, however, brain cells respond adaptively to prevent cerebral edema.
Thus, there are two essential questions in constructing a therapeutic plan: (1) did hyponatremia evolve rapidly or slowly, and (2) does the patient have CNS symptoms or imaging suggestive of cerebral edema? CNS cellular swelling and its symptoms are more likely with acute hyponatremia or with severe chronic hyponatremia. , Symptomatic hyponatremia that develops suddenly—that is, in fewer than 4 hours—can be rapidly reversed without incurring risk. If asymptomatic hyponatremia has developed over many hours, days, or weeks (i.e., chronic hyponatremia), a gradual, conservative approach is likely to be uncomplicated. Symptomatic chronic hyponatremia, on the other hand, requires a small but rapid increase in serum sodium to stabilize or begin to reverse cerebral swelling and to avoid impending herniation, followed by a more gradual correction to normalize sodium balance. An increase of 5 mEq/L is usually sufficient to halt the progress of symptomatic cerebral edema and can be achieved with an initial bolus of 5 to 6 mL/kg of 3% saline. The subsequent correction rate for patients with either acute symptomatic hyponatremia or any chronic hyponatremia should not exceed 0.5 mEq/L per hour. In acute hyponatremia without CNS symptoms, rates of 0.7 to 1 mEq/L per hour have been reported without increased patient morbidity or mortality. A regimen of hypertonic 3% saline infused at 1 to 2 mL/kg per hour with intermittent administration of a loop diuretic results in an appropriate correction for those patients for whom “rapid” correction is safe. Further correction may require isotonic fluids or a mixture of isotonic and hypertonic fluids, particularly in patients with CSW with high renal sodium excretion. In resistant, severe CSW, mineralocorticoid (fludrocortisone) treatment has been helpful in several reports. , , Other protocol approaches are available.
Prolonged hyponatremia in animal studies is notable for a striking decrease in total brain amino acid content as well as lower brain water content. When this brain cell adaptation has occurred, a rapid rise in serum sodium concentration may induce a shift of water from the ICF to the ECF compartment, resulting in brain dehydration, brain injury, and the osmotic demyelination syndrome (ODS). Both central pontine and extrapontine myelinolysis have been reported in children. Extrapontine sites include the cerebellum, thalamus, basal nuclei, hippocampus, midbrain, and subcortical white matter. Traditional risk factors for ODS include chronic alcoholism, chronic liver disease, hypoxic/anoxic episodes, correction beyond serum sodium of 140 mEq/L, and rapid correction of hyponatremia (more than 25 mEq/L in 48 hours). , Osmotic demyelination can occur, however, without hyponatremia as a starting point. , , Large bolus doses of hypertonic saline may place the patient at risk regardless of starting sodium concentration. Electrolyte fluctuations around the time of liver transplantation may account for the risk of myelinolysis noted in these patients. Rarely, ODS has been reported in patients with diabetic ketoacidosis but without hyponatremia on admission, including one case in an 18-month-old child. , Even rapid correction of hypernatremia is a possible cause of myelinolysis and suggests that pressure effects may be capable of causing damage to myelinated structures. Symptoms of osmotic demyelination may include obtundation, quadriplegia, pseudobulbar palsy, tremor, amnesia, seizures, and coma. , Classically, the clinical presentation is that of a brief period of recovery from encephalopathy followed by emergence of a locked-in state or various movement disorders. When CNS symptoms concerning for ODS emerge during therapy, long-term neurologic sequelae may be avoided by decreasing serum sodium to its nadir followed by a slower rate of correction.
In cases of SIADH in which fluid restriction is a feasible option, a decrease in fluid intake, occasionally with the use of oral sodium supplements, may be all that is required to normalize serum sodium gradually and safely. In a patient with hypovolemia, volume status clearly must be corrected in addition to the hyponatremia. Patients with SIADH or fluid-retaining states may respond to treatment with an ADH receptor antagonist. This receptor blocker group increases urine volume and reduces urine osmolality, creating a water diuresis that leads to an increase in serum sodium concentration. , However, evidence for improvement in other clinical outcomes, such as mortality or ICU LOS, is currently lacking. Conivaptan is an IV ADH V 1 and V 2 receptor antagonist that is approved for the treatment of euvolemic and hypervolemic hyponatremia in adults. Tolvaptan, an oral ADH V 2 receptor antagonist, was approved in 2009 as therapy for euvolemic or hypervolemic hyponatremia in adult patients with heart failure, cirrhosis, or SIADH. Pediatric use of the ADH receptor blockers has been reported in the settings of SIADH and cardiac disease, but further study of kinetics, safety, and efficacy will be needed to clarify the clinical role in pediatrics.
As with hyponatremia, hypernatremia can develop with low, normal, or high levels of total body sodium ( eBox 71.3 ). History and weights are particularly important in evaluating the hydration state of patients with hypernatremia because a shift in the ICF to the ECF tends to obscure the physical findings of dehydration. Accurate assessment of total body sodium and water aids considerably in planning management, although the most important management principle is the frequent monitoring of the patient’s progress with treatment adjustments as needed.
Decreased total body sodium
Vomiting/diarrhea, excessive sweating
Administration of 70% sorbitol
Osmotic diuresis: mannitol, glucose, urea
Normal total body sodium
Respiratory insensible water losses
Cutaneous insensible water losses
Fever, burns, phototherapy
Radiant warmers, especially with premature infants
Diabetes insipidus (DI)
Hypodipsia (reset osmostat)
Increased total body sodium
Administration or ingestion of large sodium loads
Improperly diluted formula
Pathophysiology and etiology
Low total body sodium
Patients with a low total body sodium level and hypernatremia have a loss of water in relative excess of sodium losses. Because the ECF space is hyperosmolar, water movement from the ICF occurs, with resulting cellular dehydration. Therefore, the ECF space is somewhat preserved until an extreme degree of hypovolemia is present. Losses of sodium and water may be extrarenal or renal.
In the pediatric patient, extrarenal losses are commonly seen from vomiting and diarrhea, although hospital-acquired hypernatremia from insufficient free water administration is a major concern. , Renal causes include osmotic diuresis from mannitol, hyperglycemia, or increased urea excretion. Infants are particularly susceptible to hypernatremic dehydration due to their high surface area/weight ratio and their relative renal immaturity, which necessitates greater water losses for excretion of a solute load compared with older children and adults. Insufficient maternal lactation places young infants at risk of hypernatremic dehydration.
Normal total body sodium
Loss of water occurs without excessive sodium losses in some conditions. Extrarenal losses include (1) increased respiratory losses as may occur with tachypnea, hyperventilation, or mechanical ventilation with inadequate humidification and (2) transcutaneous losses associated with fever, burns, extreme prematurity, or use of phototherapy or radiant warmers in the neonate without adequate water replacement. Renal losses result from congenital or acquired diabetes insipidus (DI), either central or nephrogenic. Acquired forms of DI are more commonly seen in the ICU. Major insults resulting in central DI include head trauma, tumors, infections, hypoxic brain injury, neurosurgical procedures, and nontraumatic brain death. Classically, in experimental animals and in humans, three stages occur: (1) an initial polyuric phase (hours to several days), (2) a period of antidiuresis probably due to ADH release from injured axons (hours to days), and (3) a second period of polyuria that may or may not resolve. , Sudden onset of polyuria is characteristic, and the conscious patient will often experience a concomitant polydipsia. In the critically ill patient, the inability to access increased water intake—whether from altered mental status, impaired thirst regulation, or other causes—may result in life-threatening hypernatremia. Patients with the rare congenital forms of nephrogenic DI, resulting from X-linked alteration of the ADH V2 receptor or from autosomal recessive changes in the aquaporin II water channel itself, may have repeated bouts of hypernatremic dehydration. Causes of DI are shown in eBox 71.4 .
Arginine vasopressin, antidiuretic hormone, gene mutations, autosomal-dominant or (rarely) autosomal-recessive inheritance
Idiopathic (30%–50% of cases)
Head trauma, orbital trauma
Tumors, suprasellar and intrasellar
Hypoxic injury, including neonatal hypoxic-ischemic encephalopathy
Cerebral aneurysms, thrombosis, hemorrhage
Nontraumatic brain death
VR 2 mutation, X-linked
Chronic kidney disease
Renal tubulointerstitial diseases
K + depletion
Alcohol, lithium, diuretics, amphotericin B, methoxyflurane, demeclocycline
Sickle cell disease
Decreased sodium chloride intake
Severe protein restriction or depletion
Increased total body sodium
Hypernatremia with an increased total body sodium level is most often an iatrogenic problem. In the ICU, hypertonic solutions of sodium bicarbonate are administered during resuscitation efforts or as therapy for intractable metabolic acidosis. Additionally, excessive hypertonic saline administration, ingestion by infants of improperly diluted formula, and dialysis against a high sodium concentration can contribute to increased total body sodium. Normonatremic patients with massive edema who undergo a forced diuresis frequently become mildly hypernatremic because the induced urine may be hypotonic, with water loss exceeding sodium loss.
Hypernatremia is intentionally induced in patients with TBI as a form of osmotherapy for control of intracranial hypertension associated with cerebral edema. , Such patients have tolerated serum sodium as high as 175 mEq/L when carefully managed. When the ECF osmolality of these patients is manipulated, the risks involved with rapid changes in either direction must be kept in mind.
Signs and symptoms
Clinical manifestations of hypernatremia, as is the case with hyponatremia, relate predominantly to the CNS. Marked irritability, a high-pitched cry, altered sensorium varying from lethargy to coma, increased muscle tone, and overt seizure activity may occur in children with the development of severe hypernatremia over 48 hours or more. Hyperglycemia and hypocalcemia also may occur. In infants with acute hypernatremia, vomiting, fever, respiratory distress, spasticity, tonic-clonic seizures, and coma are common. Death from respiratory failure occurred in experimental animals when serum osmolality approached 430 mOsm/kg. Mortality in children with severe hypernatremia has ranged from 10% to 45% with chronic and acute hypernatremia, respectively.
Anatomic changes seen with the hyperosmolar state include loss of volume of brain cells with resultant tearing of cerebral vessels, capillary and venous congestion, subcortical or subarachnoid bleeding, and venous sinus thrombosis. During the first 4 hours of experimental acute hypernatremia, brain water significantly decreases, while the concentration of solutes (electrolytes and glucose) increases. This leads to a partial restitution of brain volume within a few hours’ time. Over several days, brain volume normalizes as a result of intracellular accumulation of organic osmolytes consisting of polyols, amino acids, and methylamines. ,
Whenever possible, therapy of hypernatremia should address correction of the underlying disease process as a primary goal. Correction of dehydration with slow hypernatremia correction is the target. When sodium exceeds 165 mEq/L, isotonic fluid or colloid may be used for correction of shock or circulatory collapse and initial reversal of hypernatremia. When hypernatremia has been present for more than a few hours, the presence of intracellular organic osmolytes dictates a slow rate of correction. Numerous fatal cases of cerebral edema and herniation have occurred with correction over a 24-hour period, leading to recommendations for correction over no less than 48 hours. , Newer studies suggest that rapid correction of hypernatremia is not associated with higher risk for mortality, seizure, or cerebral edema in critically ill adults , ; therefore, the ideal rate of correction remains unclear. General agreement is that plasma osmolality should not be decreased more rapidly than 2 mOsm/h, correlating with a rate of sodium decline that does not exceed 1 mEq/h. In cases of very severe or long-standing hypernatremia, a more conservative correction rate of 1 mOsm/h (0.5 mEq/h of sodium) may be appropriate. Thus, normalization from extreme hypernatremia may take several days. Estimated deficits, ongoing maintenance requirements, and additional excessive losses must be accounted for in calculations of the amount of fluid replacement required.
Central DI is a likely cause of hypernatremia in an ICU patient with high urine volume and low urine osmolality, particularly in patients who have head trauma or who have undergone a recent intracranial operation. In these patients, a trial of vasopressin is in order. Either aqueous vasopressin given subcutaneously or intravenously (0.5 to 10 mU/kg per hour) or 1-deamino-8-D-arginine vasopressin (DDAVP) given orally or intranasally may be used. Oral dosing is limited to tablet form at this time with a recommended dosing range of 0.05 to 0.40 mg administered twice daily. Intranasal DDAVP is generally begun in a dosage ranging from 0.05 to 0.10 mL once or twice daily. An increase in urine osmolality to values exceeding that of the serum after vasopressin administration supports the diagnosis of central DI. Hyponatremia has been reported after vasopressin administration in patients with central DI as well as in patients receiving vasopressin for hemodynamic support and for bleeding disorders in the perioperative period. , In the outpatient setting, symptomatic hyponatremia, including seizures and altered mental status, has been reported in patients receiving DDAVP for enuresis, particularly in periods of intercurrent illness or with excess fluid intake. Careful attention to the IV fluid prescription, serial monitoring of sodium levels, and timely adjustment in therapy are necessary to avoid severe complications in patients receiving any type of vasopressin therapy.
In patients with an increased total body sodium level and, often, hypervolemia, the goal is sodium removal. In patients with intact renal function, sodium removal may be accomplished with diuretics and a decrease in sodium administration, though in iatrogenic hypernatremia, a randomized controlled trial did not find any significant improvement in serum or urine sodium with use of enteral hydrochlorothiazide. If renal failure is present, dialysis may be required.
The total body K + of approximately 50 mEq/kg is stored primarily (98%) in the intracellular space. The transmembrane concentration gradient is large, with an intracellular concentration of 150 mEq/L that is maintained by sodium-potassium adenosine triphosphatase (Na + /K + -ATPase) pumps. The resultant transmembrane potential is tightly regulated and physiologically dynamic in contractile or conductive cells. Changes in extracellular or intracellular K + concentration may alter the critical transmembrane potential of cardiac, skeletal, or smooth muscle cells with serious results.
Hypokalemia is relatively common in pediatric intensive care unit (PICU) patients but generally is detectable and manageable. Severe hyperkalemia is much less frequent but more likely to be life threatening with minimal warning.
Potassium balance is primarily regulated through renal absorption and excretion and to a lesser extent by the gastrointestinal (GI) tract. Most of the filtered potassium is absorbed in the proximal tubule and loop of Henle in normal kidneys. The potassium excreted in the urine then is primarily due to secretion in the distal convoluted tubule and cortical collecting duct. As with sodium, the kidney’s capacity to vary potassium excretion is profound, ranging from a low of approximately 5 mEq/L to amounts exceeding 100 mEq/L of urine. Factors influencing renal potassium excretion include aldosterone and other mineralocorticoid and glucocorticoid hormones, acid-base balance, luminal charge potential, tubular fluid flow rate, sodium intake, potassium intake, ICF and plasma potassium concentrations, and diuretics. Aldosterone is a major kaliuretic hormone though activation of Na + /K + exchange pumps in the distal tubules and collecting ducts. Metabolic acidosis decreases and metabolic alkalosis increases intracellular potassium activity in cells of the distal tubule, causing enhanced potassium reabsorption during acidosis and enhanced secretion during alkalosis. Increased fluid delivery to the distal tubule enhances potassium secretion by two mechanisms: (1) increased distal delivery of Na + stimulates distal Na + absorption, which then creates a more negative luminal potential that increases K + secretion; and (2) as tubular fluid potassium concentration decreases as flow rate increases, a favorable concentration gradient for potassium secretion is promoted by higher flow rates.
Factors involved in total body distribution and fine-tuning of potassium homeostasis include acid-base status, insulin, catecholamines, and magnesium. Acidemia tends to increase the serum potassium, and alkalemia lowers it. The type of acid–base disturbance (metabolic or respiratory), the duration of the disturbance, and the nature of the anion accompanying the hydrogen ion in metabolic acidosis are important in determining what effect a particular acid-base disorder may have on potassium concentration. Diabetic ketoacidosis (DKA) may occasionally present with severe hypokalemia due to urinary and gastrointestinal losses; however, pretreatment serum levels can be normal or elevated due to acidemia, hyperosmolality, and decreased circulating insulin. , Epinephrine, albuterol, and other β-agonists decrease serum potassium by promoting intracellular uptake. β-Adrenergic blocking drugs abolish this effect. Changes in intracellular magnesium concentration may affect the Na + /K + -ATPase pump and alter the transcellular distribution.
Causes of hypokalemia
Hypokalemia without potassium deficit
The detection of a low serum potassium level may reflect a shift of K + from the ECF to the ICF pool and not a whole-body K + deficit. A shift to the ICF pool may occur in alkalemia, exogenous or endogenous release of a β-agonist, , increased insulin activity familial or thyrotoxic periodic paralysis, , and barium poisoning. In alkalemia, potassium moves intracellularly in exchange for H+ to maintain extracellular pH. The pediatric patient with alkalemia can have a true potassium deficit in addition due to decreased potassium intake or increased losses. β-Agonists and insulin promote intracellular potassium movement by increasing the activity of the Na + /K + -ATPase pump.
Periodic paralysis is a rare autosomal-dominant disorder presenting with intermittent episodes of profound muscle weakness associated with rapid falls in serum potassium concentration that may be precipitated by a high-carbohydrate diet, exercise, infection, stress, or alcohol ingestion. Barium poisoning can produce hypokalemic weakness and paralysis, probably by competitive blockade of inward rectifying K+ channels.
Hypokalemia with potassium deficit
A deficit in total body potassium may occur from decreased intake or increased renal and GI losses. Decreased intake is unlikely to cause significant hypokalemia in isolation, though prolonged deficits can exacerbate hypokalemia due to increased losses.
Major categories seen in the ICU include diuretics (loop, thiazide, osmotic), hyperaldosteronism, renal tubular acidosis (RTA), magnesium deficiency, renal tubular injury, and recovery from acute renal failure (ARF). Osmotic diuresis from glucosuria in prolonged DKA can cause severe renal potassium wasting DKA. The severity of K + loss in DKA may be masked by the shift of potassium from the ICF to the ECF space caused by insulin deficiency, metabolic acidosis, and hypertonicity.
Primary hyperaldosteronism, congenital adrenal hyperplasia, adrenal adenoma, and familial idiopathic hyperaldosteronism , are rare in children and even rarer in the PICU setting. Secondary hyperaldosteronism is common, however, typically from intravascular volume depletion but also caused by CHF, cirrhosis, or nephrotic syndrome. Patients with the latter conditions, however, rarely have severe hypokalemia unless they are additionally treated with diuretics. Infants with Bartter or Gitelman syndrome may initially present to the ICU with multiple metabolic derangements, including hypokalemia, metabolic alkalosis, hypomagnesemia, and hyperuricemia. Other findings include weakness, polyuria, and failure to thrive, with elevated renin and aldosterone levels in the absence of hypertension. Additional conditions associated with elevated renin secretion, secondary hyperaldosteronism, and hypokalemia include renal artery stenosis, malignant hypertension, renin-producing tumor, or Wilms tumor. Distal (type 1) RTA represents impaired distal urine acidification, which increases urinary potassium secretion, while proximal (type 2) RTA causes increased distal delivery of sodium bicarbonate secondary to reduced proximal absorption, which may increase urinary secretion of K + .
Other agents that induce excessive renal losses include amphotericin B (kaliuresis with reduced renal function and tubular injury); aminoglycosides, particularly gentamicin; and high-dose penicillin and carbenicillin, which produce an osmotic load in addition to acting as nonreabsorbable anions. Hypomagnesemia and caffeine toxicity may cause renal potassium wasting.
Gastrointestinal losses are a common cause of hypokalemia in children. Stool potassium content can be significant and diarrheal illness with hypokalemia has been associated with increased mortality among malnourished patients. Gastric potassium content ranges from 5 to 10 mEq/L. Hypokalemia from vomiting or from nasogastric (NG) suction is possible. However, hypokalemia from upper GI losses is more likely due to the secondary hyperaldosteronism induced by volume depletion and metabolic alkalosis from hydrogen ion losses, which also causes an increased filtered load of bicarbonate that promotes increased renal potassium secretion. Other GI causes are listed in eBox 71.5 .
Hypokalemia without potassium deficit
β-agonist, exogenous or endogenous
Familial periodic paralysis
Thyrotoxic periodic paralysis
Hypokalemia with potassium deficit
Primary or secondary
Barter, Liddle, Gitelman syndromes
Laxative or diuretic abuse
High-dose penicillin, carbenicillin
Renal tubular acidosis
Vomiting, nasogastric suction
Obstructed or long ileal loop
Signs and symptoms
For the intensivist, cardiovascular and neuromuscular effects of potassium deficiency are of particular concern, although metabolic, hormonal, and renal effects may also occur.
Electrocardiographic (ECG) changes include T-wave flattening or inversion, ST depression, and the appearance of a U wave. Resting membrane potential is increased, as are both the duration of the action potential and the refractory period. The decreased conductivity predisposes to arrhythmias, as do increased threshold potential and automaticity.
Hypokalemia diminishes skeletal muscular excitability. This can present as a dynamic ileus or a skeletal muscle weakness resembling Guillain-Barré syndrome. It can eventually affect the trunk and upper extremities, becoming severe enough to result in quadriplegia and respiratory failure. Hypokalemia can lead to severe rhabdomyolysis in a variety of underlying conditions and may progress to ARF and hyperkalemia. Autonomic insufficiency may also occur, generally manifested as orthostatic hypotension. In patients with severe liver disease, hypokalemia may precipitate or exacerbate encephalopathy. Glucose intolerance in the presence of primary hyperaldosteronism and in certain patients receiving thiazide diuretics has been corrected with potassium repletion. Renal effects of hypokalemia include polyuria and polydipsia, renal structural changes and functional deterioration with cellular vacuolization in the proximal tubule, and occasional interstitial fibrosis.
Because of the wide spectrum of abnormalities resulting from marked potassium depletion, judicious correction is generally in order. In most PICUs, patients with cardiovascular disease are given NG or IV supplements to maintain serum levels above 3.0 to 3.5 mEq/L. In the patient without life-threatening complications, the oral route is generally preferred for treatment because this route is rarely associated with “overshoot” hyperkalemia if normal renal function exists. Oral dosage is frequently 1 mEq/kg up to a maximum of 20 mEq per dose, repeated as necessary. If, however, depletion is associated with digoxin use or life-threatening complications—including cardiac arrhythmias, rhabdomyolysis, critical weakness with quadriplegia, or respiratory distress—then urgent IV therapy is generally needed. Recommendations for IV dosage in the pediatric patient have ranged from intermittent infusions of 0.25 mEq/kg to those as high as 1 mEq/kg in the face of severe hypokalemia associated with DKA, arrhythmias, or critical weakness. Ventricular tachycardia clearly associated with hypokalemia may initially require more rapid administration. Continuous ECG monitoring is essential, as well as frequent physical examination and determination of serum potassium levels to avoid hyperkalemic complications. Highly concentrated intravenous potassium solutions should only be administered centrally. Patients who receive albuterol continuously are frequently mildly hypokalemic, but they rarely warrant potassium chloride replacement.
The potential for catastrophic drug error in replacing potassium is real. In most PICUs, patients with cardiovascular disease frequently require NG or IV supplements. Steps to decrease the chance of error include satellite pharmacy dosing, use of a mandatory drug request form, NG replacement when possible, use of a single-solution concentration for all doses, and small aliquot solution containers. Continuing education for the PICU staff regarding this risk is essential.
Hyperkalemia may result from artifactual elevation; from redistribution of potassium from ICF to ECF space; or from increased load, impaired elimination, or both ( eBox 71.6 ).
Ischemic potassium loss from muscle due to tourniquet use
In vitro hemolysis, profound leukocytosis, thrombocytosis
β-blockers (β 2 -inhibitory activity)
Succinylcholine, arginine, or lysine hydrochloride
Epsilon-amino caproic acid
True potassium excess
IV infusion, PO supplements, potassium-containing salt substitutes, potassium penicillin, blood transfusion
Redistribution and tissue necrosis
In vivo red cell injury
Change in pH
Burns, trauma, rhabdomyolysis, intravascular coagulation
Tumor cell lysis
Reabsorption of hematoma
Diabetes mellitus, diabetic ketoacidosis
Acute kidney injury
Chronic kidney disease
Renal tubulointerstitial disease
Renal tubular secretory deficit
Sickle cell disease
Systemic lupus erythematosus
Renal allograft rejection
Urinary tract obstruction
Inhibition of tubular secretion
Spironolactone, triamterene, amiloride
Indomethacin, converting enzyme inhibitors, heparin, cyclosporine, tacrolimus
Trimethoprim, pentamidine, amphotericin B
Tight, prolonged tourniquet use produces spurious potassium elevation due to potassium release from ischemic muscle. Even more common is hemolysis of red cells with potassium release associated with capillary sampling, and aspiration or delivery under pressure through a small gauge needle. The lab may note hemolysis, but artifactual normality or actual elevation should always be considered. Less commonly, in vitro release of potassium occurs from white blood cells (WBCs; >100,000/uL) or platelets (>1,000,000/uL) and may result in increased levels.
In general, when extracellular pH acidemia develops, potassium exits from cells in exchange for hydrogen ions; this results in an increase in serum potassium. Metabolic acidosis from mineral acids has a more pronounced effect than that of organic acids. Respiratory acidosis does not usually cause a marked change in potassium concentration.
Hypertonicity produces a shift of potassium from ICF to ECF. Studies of anephric animals show potassium increasing by 0.1 to 0.6 mEq/L for each increment of 10 mOsm/kg H 2 O in tonicity. Hypertonicity causes cellular dehydration and therefore an increase in ICF potassium that favors increased passive diffusion out of cells. A very small percentage shift of intracellular potassium delivers a significant potassium load to the ECF. In the hyperkalemic patient in the ICU who has acute oliguria, mannitol should not be used for diuresis, as further K + elevation may result. In the patient with hyperglycemia, hypertonicity is likely only one of several mechanisms resulting in elevated serum potassium levels.
Several commonly used drugs result in net movement of potassium from ICF to ECF. Digoxin inhibits the net uptake of K by cells by inhibiting Na + /K + -ATPase activity, with hyperkalemia commonly occurring in severe digitalis poisoning. Other drugs include β-blockers with β 2 activity and the muscle relaxant succinylcholine. Succinylcholine induces a prolonged dose-related increase in the ionic permeability of muscle, with subsequent efflux of potassium from muscle cells. Normal serum potassium concentration rises about 0.5 mEq/L. Succinylcholine should be avoided in patients with burns, muscle trauma, spinal injuries, certain neuromuscular diseases, near drowning, and closed head trauma, as upregulated and new forms of acetylcholine receptors may respond with life-threatening hyperkalemia. , New examples of patients at risk will continue to be reported. , Hyperkalemia may result in nonsuspect patients via rhabdomyolysis or malignant hyperthermia following succinylcholine. Rhabdomyolysis has many causes, including influenza, severe exercise, drugs, ischemia, and many more. Familial hyperkalemic periodic paralysis appears to be related to potassium redistribution caused by changes in sodium channel function within skeletal muscle. Rebound hyperkalemia may be life threatening after coma-inducing barbiturate is stopped or surgical insulinoma removal.
Hyperkalemia due to an increased potassium load is unusual as long as renal function is normal. Serious elevations may be seen with inappropriate IV infusion, large-volume blood transfusions, bypass circuit initiation, oral potassium supplements, salt substitutes containing potassium, or large doses of potassium penicillin. Strict measures to guard against accidental potassium overdoses are mandatory. Large endogenous loads of potassium are more likely in the patient who is in the ICU. The release of cellular potassium associated with tissue necrosis from burns, trauma, rhabdomyolysis (including that from spider bites) or the propofol infusion syndrome, , massive intravascular coagulopathy, rapid hemolysis, or GI bleeding may lead to hyperkalemia. Massive cell lysis can overwhelm normal homeostasis, prompting aggressive management of the sudden shift of intracellular potassium into the ECF, particularly in the presence of compromised renal function.
Tumor lysis syndrome (TLS) is classically associated with drug or radiation treatment of sensitive lymphoid malignancies and results in hyperkalemia often accompanied by hypocalcemia, hyperphosphatemia, acidosis, and compromised renal function ( Table 71.3 ). Many fatalities have been reported. The list of TLS-producing events or therapies includes transcatheter chemical and embolic tumor necrosis, monoclonal antibody treatment with rituximab, and enzyme-inhibiting agents (bortezomib, imatinib, and sorafenib). Cases have occurred in tumor patients with surgical stress or dexamethasone given for potential airway edema (see also Chapter 92 ).