OVERVIEW: What every practitioner needs to know
Are you sure your patient has a disorder of sodium? What are the typical findings for this disease?
Sodium is the major cation of the extracellular space. It is a primary determinant of serum osmolarity, though not the only one. The normal range of serum sodium in children is 135 – 145 mEq/L as it is in adults. A serum sodium concentration of > 145 mEq/L is considered hypernatremia vs hyponatremia is regarded as a serum sodium < 135 mEq/L.
Both disorders of sodium are most often discovered in hospitalized children on routine evaluations of serum chemistry. Mild abnormalities, or severe derangements which develop slowly, can go without overt clinical manifestations. Clinical signs and symptoms are often “soft” and non-specific, requiring clinical suspicion.
(Abbreviations used: SNa = serum sodium concentration, UNa = urine sodium concentration, SOsm = serum osmolarity, UOsm = urine osmolarity, CNS = central nervous system, DI = diabetes insipidus, ADH = antidiuretic hormone, SIADH = syndrome of inappropriate ADH secretion, IVF = intravenous fluids)
Hypernatremia vs Hyponatremia
Though hypernatremia often occurs in the context of dehydration, the latter implies hypovolemia, and hypovolemia need not be present for hypernatremia to be a significant clinical concern. Symptoms may include muscle weakness, irritability and agitation, high-pitched cry, insomnia, and lethargy.
A rise in SNa draws water out of cells. Thus, despite dehydration, tachycardia and other clinical symptoms of hypovolemia may be minimal and develop ominously late because intravascular volume is “protected.” Subcutaneous tissue is classically described as “doughy” and skin is “like velvet.” Serious CNS manifestations can be observed, especially when the patient is hypovolemic. Neural cell dehydration and subsequent brain shrinkage can lead to tearing of bridging veins with subdural or subarachnoid hemorrhages. Increased blood viscosity can cause capillary and venous congestion and possibly sinus venous thrombosis. Encephalopathy and seizures have been reported.
Hyponatremia may occur in the context of hypovolemia, euvolemia, or hypervolemia. SNa < 120 mEq/L may manifest acutely as seizures, or with altered mental status ranging from disorientation to lethargy to coma. At < 115 mEq/L, hyperreflexia, pseudobulbar palsy, and Cheyne-Stokes respiration may be observed.
Hypernatremia vs Hyponatremia: What caused these diseases to develop at this time?
Hypernatremia is most often due to free water loss in excess of sodium and potassium. People normally compensate by drinking more water, but impaired thirst and inability to access water are not uncommon in hospitalized children. Less frequently, intake of excess sodium – or this combined with free water loss – is to blame. Common etiologies in hospitalized children are accompanied by brief explanations below.
Gastrointestinal (GI) losses: Both gastric and intestinal fluid losses can result in hypernatremia because in each instance, the fluid lost has sodium + potassium concentrations far lower than serum (Secretory diarrheas are notable exceptions, in which fluid losses are usually equivalent to serum in sodium + potassium concentrations). Examples include acquired viral enteritides, iatrogenic diarrhea (lactulose, charcoal, antibiotic-induced), and chronic nasogastric suctioning. Isotonic fluid replacement does not provide sufficient solute-free water, potentiating the issue.
Renal losses: Loop diuretics such as furosemide impair tubular concentrating ability by disrupting the countercurrent gradient, resulting in water loss in excess of electrolytes. This is also true in osmotic diuresis resulting from mannitol, hyperglycemia which exceeds the kidneys’ reabsorptive capacity (usually 240 mg/dL), or urea from high-protein tube feedings.
Central diabetes insipidus (DI) may develop in brain injury or be pre-existing in midline disorders of the neuroaxis (e.g., holoprosencephaly, septo-optic dysplasia, acquired panhypopituitarism); in this disorder, inadequate antidiuretic hormone (ADH, or vasopressin) production severely limits the renal tubular capacity for water resorption, resulting in excess solute-free water loss. The same is true in nephrogenic DI, though the pathogenesis involves renal insensitivity to ADH rather than inadequate ADH production. The polyuric phase of acute tubular necrosis is also marked with impaired concentrating ability and excessive free water loss.
Skin loss: Sweat represents a route for excess free water loss. For instance, pre-term or term infants who breastfeed inadequately, and/or who are kept under radiant warmers or “bili-lights,” may be prone to developing hypernatremic dehydration due to unreplaced, insensible loss.
Other losses: Other sources of chronic fluid loss which should be considered in hospitalized pediatric patients include externalized ventricular drains, thoracostomy tubes, peritoneal drains, ostomy output, wound VACs, and externalized oral secretions (“drool”).
Inadequate free water provision: Replacement of GI output with isotonic fluid does not provide sufficient solute-free water, which potentiates hypernatremia. Tube feeds may require the addition of scheduled water administration to prevent development of a free water deficit during periods of increased free-water loss. Urea-induced (osmotic) diuresis from protein-rich feeds has also been described.
Excess sodium provision: Hypertonic saline (typically 3%) is given intermittently or as an infusion to induce hypernatremia and control intracranial hypertension in the setting of brain injury. Frequent sodium bicarbonate administration to treat ongoing metabolic acidosis can present a significant sodium load. Use of normal saline for volume resuscitation followed by excess free-water loss induced by loop diuretics is another example of hypernatremia caused by sodium loading.
Normally, a reduction in serum sodium is paralleled by a reduction in serum osmolarity (SOsm), which suppresses ADH secretion. Hyponatremia develops most often as a result of an impaired ability to suppress ADH despite a SOsm fall. Rarely, the cause is water intake which is so massive that it exceeds the kidneys’ ability to excrete it. A convenient way to classify hyponatremia is by volume status.
Hypovolemic hyponatremia can result from GI or renal losses of fluid. It was previously noted that vomiting and diarrhea typically involves fluid loss which has sodium + potassium concentration less than that of plasma and may result in hypernatremia. However, in the setting of severe intravascular depletion, baroreceptors respond by overcoming ADH suppression and instead causing its release in an attempt to recover intravascular volume. The contribution of renal fluid loss can be magnified by thiazide diuretics, which allow sodium and chloride to be secreted, but in contrast to loop diuretics, do not disrupt the countercurrent gradient; thus, ADH is still able to mediate urine concentration.
Euvolemic hyponatremia is exemplified by the syndrome of inappropriate ADH secretion (SIADH), which can also be hypervolemic in the extreme. Commonly encountered causes unrelated to osmotic and hemodynamic stimuli (which would be “appropriate”) include bronchiolitis, asthma, pneumonia, positive-pressure ventilation, CNS insults and trauma. Hospitalized pediatric patients also have several reasons for physiologically elevated ADH levels such as nausea, vomiting, pain, stress, and hypoxia. Given that iatrogenic hyponatremia has been associated with the routine administration of hypotonic fluids to hospitalized pediatric patients, some authors advocate for the predominant use of isotonic fluids in this setting.
Hypervolemic hyponatremia is seen with heart failure, cirrhosis, advanced renal failure, and water intoxication. Diminished cardiac output in heart failure and arteriolar dilation in cirrhosis can inappropriately signal ‘volume depletion’ to baroreceptors despite volume retention, once again triggering ADH release. Meanwhile, atrial stretch-induced natriuretic peptide release causes sodium secretion. Severe renal failure results in impaired renal free water excretion. Hyponatremia is often a late finding in these conditions and reflects severity of disease. In pediatrics, water intoxication is encountered most frequently in infants who are given large amounts of water, overwhelming the kidney’s ability to excrete free water.
Hyperosmolar states can fall in any volemic category. Profound hyperglycemia, or alternate osmole accumulation such as mannitol in the setting if renal failure, will draw water out of cells and cause a dilutional hyponatremia (If the osmotic diuresis is profound, however, electrolyte-free water loss will cause SNa to rise as noted previously). Significant hyperlipidemia or hyperproteinemia reduces the proportion of plasma that is free water; while sodium concentration in the free water fraction remains the same, it is reduced relative to total plasma volume because the free water fraction is reduced; this has earned it the name ‘factitious.’
Other causes of hyponatremia such as adrenal insufficiency and hypothyroidism are described in other sections.
What laboratory studies should you request to help confirm the diagnosis? How should you interpret the results?
A careful review of the history, underlying problems, clinical course, and inpatient management strategy is often sufficient to identify causes of serum sodium derangement when comparing hypernatremia vs hyponatremia. For instance, excessive GI fluid losses, hyperglycemia, reasons for osmotic diuresis, and heart failure are readily identifiable. Adjunctive laboratory studies can be helpful.
Serum and urine sodium concentrations (SNa, UNa) and osmolarity (SOsm and UOsm) can help distinguish DI, SIADH, and cerebral salt wasting. With DI, SNa and SOsm are high (latter usually > 300) while UOsm is low (usually 50-200). Polyuria is typically present; with profound volume depletion, however, urine output may appear “normal” or olguric, and polyuria may only be unmasked when glomerular filtration is restored with volume resuscitation.
The fractional excretion of sodium (FENa) can be very helpful but loses meaning in the context of diuretic therapy. A FENa of < 0.2% suggests early volume depletion; however, because FENa is dependent upon filtered sodium, i.e. GFR, FENa can rise to 1% with progressive renal impairment. With normal renal function, a FENa > 1% is suggestive of excess sodium provision.
SIADH should be suspected with any hyponatremic patient who is eu- or hypervolemic. UOSm is 300 – 600 mOsm/L, and exceeds SOsm. UNa is typically > 20 mmol/L (and FENa is > 1%) in SIADH due to natriuretic peptide-induced sodium secretion. Strict definitions of oliguria need not be met in SIADH, only relative oliguria given what a patient’s urine output is expected to be given their volemic state. Large studies suggest “cerebral” salt wasting is a rare cause of hyponatremia at best. A patient must be hypovolemic, and salt wasting due to renal injury must be excluded. UNa is > 20 mmol/L and FENa is > 1%.
Confirming the diagnosis of Hypernatremia vs Hyponatremia
Due to the diverse nature of the disorders present, overarching clinical decision algorithms are not applicable.
Hypernatremia vs Hyponatremia: If you are able to confirm that the patient has a disorder of sodium, what treatment should be initiated?
Treatments should be selected based upon suspected etiology, and coupled with a lab surveillance strategy for monitoring correction.
Priority is given to restoring circulatory volume if the patient is in shock. With serum sodium < 175 mEq/L, normal saline (NS) may be used for boluses. However, if serum sodium is > 175 mEq/L then NS is excessively hypotonic and may reduce SNa too rapidly. Instead, IVF should be constituted to be 15 mEq/L less than the SNa.
Next, consideration is given to whether the hypernatremia is acute (< 48 hrs) or chronic (> 48 hrs). If chronic, the free water deficit (FWD) is calculated to reduce the serum concentration to 145 mEq/L – or to reduce it by no more than 15 mEq/L – over 24 hours. FWD = 0.7 x weight[kg] x (1 – current sodium / desired sodium). The hourly “restoration water” rate is added to “maintenance” IVF (chosen as usual) running at a rate that takes into account ongoing loss. Sodium is monitored every 2-4 hours. If SNa decline is faster than 0.6 mEq/h (or 1-2 mOsm/hr), the “restoration water” rate can be decreased or the sodium concentration in the maintenance fluid can be increased.
In central DI, hypotonic IVF should be run at a rate to keep up with losses until the DI is controlled with exogenous vasopressin.
If hypernatremia is the result of 3% saline or sodium bicarbonate administration, endogenous natriuresis and usual hypotonic maintenance IVF (e.g., 1/2NS) will offer correction. Normal saline should be used in the setting of brain injury where mild, ongoing hypernatremia may be desired.
Severe sodium toxicity coupled with renal insufficiency should be addressed with dialysis.
Again, priority should be given to restoring circulatory volume if the patient is in shock. Ringer’s lactate (130 mEq/L sodium) should be used to avoid excessively rapid correction. Serum sodium < 120 mEq/L – or any extent of hyponatremia at which seizures are occurring – also demands immediate correction. 5-6 mL/kg of 3% saline is infused over 1 hour, which is expected to raise the serum sodium by 5 mEq/L.
The remaining hyponatremia should be corrected at a rate up to 1 mEq/L/hr if it developed acutely, but no faster than 0.5 mEq/L/hr if it is chronic. SIADH requires immediate volume restriction, which can be tightened in a step-wise fashion starting at 75% of maintenance, 50% of maintenance, and so on. Otherwise, maintenance fluids can be changed to D5
NS and infused at a rate which offers correction over 24 (mild) – 48 (severe) hours. If the rate of correction is too fast the infusion rate can be slowed. If it is too slow, 3% saline can be infused at 1-2 mL/kg/hr, though this is infrequently required. SIADH and physiological ADH elevations are usually transient and self-limited.
Unless symptomatic, hyponatremia should not be corrected with IVF in the setting of heart failure and cirrhosis. Hyponatremia associated with severe hyperglycemia, hyperlipidemia, or hyperproteinemia should be addressed by managing the underlying derangement.
What are the adverse effects associated with each treatment option?
Osmotic demyelination syndrome (formerly known as central pontine myelinolysis when it was thought to be limited to the pons) has been reported with rapid correction of both hyper- and hyponatremia, though the risk is thought to be greatest with chronic hyponatremia that has had time to elicit neural cellular adaptation. CNS symptoms can include dysarthria, dysphagia, obtundation, quadriplegia, pseudobulbar palsy, and coma. Their appearance can be delayed by a few days, but also be seen during correction. If suggestive symptoms are encountered, the sodium correction should be reversed and then re-instituted more slowly.
What causes this disease and how frequent is it?
While the exact overall incidence of hypernatremia in hospitalized children has not been rigorously studied, it has been estimated that hyponatremia may affect up to 25% of children who receive intravenous fluids in an acute care setting.
What complications might you expect from the disease or treatment of the disease?
Please see, “What are the typical findings for the disease,” and “What are the adverse effects associated with each treatment option” above.
How can disorders of sodium be prevented?
Often, disorders of sodium are encountered at the time the patient presents and is admitted. However, they frequently develop during hospitalization as well. For hypernatremia vs hyponatremia, preventions can be achieved by thinking through which pathophysiological processes of the underlying disease, and what aspects of management, might result in sodium derangements. For instance, the clinician can anticipate GI and renal losses, or detect when they become abnormal. Similarly, brain injury or the post-operative state can heighten one’s suspicion of and surveillance for DI and SIADH, respectively.
What is the evidence?
Wood, EG, Lynch, RE, Fuhrman, Zimmerman. “Electrolyte management in pediatric critical illness”.
Aune, GJ, Cust, Rau. “Fluids and electrolytes”.
Rivkees, SA. “Differentiating appropriate antidiuretic hormone secretion, inappropriate antidiuretic hormone secretion and cerebral salt wasting: the common, uncommon, and misnamed”. Curr Opin Pediatr. vol. 20. pp. 448-452.
Schwaderer, AL, Schwartz, GJ. “Treating hypernatremic dehydration”. Pediatrics in Review. vol. 26. pp. 148-150.
Waseem, M, Hussain, A. “Index of suspicion”. Pediatrics in Review. vol. 25. pp. 397-403.
Moritz, ML, Ays, JC. “Intravenous fluid management for the acutely ill child”. Curr Opin Pediatr. vol. 23. pp. 186-19.
Ongoing controversies regarding etiology, diagnosis, treatment
Iatrogenic hyponatremia has been associated with the routine administration of hypotonic fluids to hospitalized pediatric patients in multiple studies. This is suspected to be due to the high prevalence of risk factors for ADH elevation in this population. Some authors advocate for the predominant use of 0.9% saline (NS) as maintenance IVF in the inpatient setting, with exceptions classified broadly into edema-forming and oliguric states.
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- OVERVIEW: What every practitioner needs to know
- Are you sure your patient has a disorder of sodium? What are the typical findings for this disease?
- What caused this disease to develop at this time?
- What laboratory studies should you request to help confirm the diagnosis? How should you interpret the results?
- Confirming the diagnosis
- If you are able to confirm that the patient has a disorder of sodium, what treatment should be initiated?
- What are the adverse effects associated with each treatment option?
- What causes this disease and how frequent is it?
- What complications might you expect from the disease or treatment of the disease?
- How can disorders of sodium be prevented?
- What is the evidence?
- Ongoing controversies regarding etiology, diagnosis, treatment