The Clinical Challenge of Diagnosing and Treating Hyponatremia

January 25, 2011

Hyponatremia treatment should be based on the mechanism governing the impaired urine dilution and address the underlying cause of the condition.

Hyponatremia is the most common electrolyte disorder seen in clinical practice, affecting up to 30% of hospitalized patients. It has been estimated that up to 15% of patients in the US with hyponatremia also have cerebral symptoms (including nausea and vomiting, decreased consciousness, confusion, seizures, and coma), mostly caused by cerebral edema.

Because hyponatremia is associated with high mortality, prompt diagnosis and treatment is essential. However, according to the authors of “Initial Approach to the Hyponatremic Patient,” published in the February 2011 issue of Acta Anaesthesiologica Scandiavica, there is considerable controversy over which treatment approach is best. They identified a number of factors that make the diagnosis and treatment of hyponatremia problematic (under-diagnosis, complications from overcorrection and osmotic demyelination, challenges in the clinical application of traditional classifications, etc). Specific treatment challenges include:

  • Recognition of the condition
  • Controversy regarding the optimal correcting speed
  • Best approach to correcting plasma sodium concentration (plasma [Na ]) “in light of the numerous etiologies and different classifications available”
  • Oversimplified formulae that consider only the patient's input of water and electrolytes

In terms of identification and diagnosis, the authors wrote that hyponatremia is characterized by “an impaired ability to excrete properly diluted urine and downward resetting of the osmotic threshold for thirst” caused by insufficient suppression of antidiuretic hormone (ADH) secretion. The authors noted that this “defect in urine dilution” can be identified with an abnormal water load test and that clinicians can identify hyponatremia types by considering the mechanisms preventing urine dilution. They identified two groups: one that includes “syndromes in which ADH is inappropriately elevated [syndrome of inappropriate ADH secretion (SIADH)],” and a second group that includes “conditions wherein ADH is elevated as a homeostatic response to other diseases.” In this latter group, ADH secretion is stimulated by “a reduced effective arterial blood volume (EABV) sensed by the arterial baroreceptors.”

Accordingly, the authors of this study sought to present “a practical approach to this intriguing condition that rests on an understanding of the changes in plasma [Na ] and the effects of hyponatremia on the brain.” Data used in this study was collected during a literature search using MEDLINE, Embase, and The Cochrane Library.

The authors stated several pertinent observations, recommendations, and conclusions in this paper, including:

  • Studies have demonstrated that “even a moderate decrease in plasma [Na ] in pigs caused significant brain edema,” with the increase in brain water content corresponding to the change observed in the plasma [Na ] level. Based on these results, it may be reasonable “to believe that brain swelling plays a pivotal role in symptomatic hyponatremia.” However, the authors said that “a direct causal link between symptoms and brain edema may be missing” because the cerebral symptoms associated with edema may be cause by other factors (an “efflux of excitatory neurotransmitters,” altered membrane potentials caused by low plasma [Cl−], etc). Thus, starting treatment based on the symptoms of brain dysfunction alone (with treatment focusing on increasing the plasma [Na ] level) “would therefore seem to be a rational approach.”
  • Although “there there is a substantial risk of hypoxia in symptomatic hyponatremia,” hypoxia seems to worsen the primary damage, rather than be the primary cause of brain damage in hyponatremia. The authors recommend using an ABCDE approach to manage the proximate causes of hypoxia “without delay.” This “will also treat hypoperfusion and hyper-/hypocapnia, which would otherwise worsen the effect of the increased intracranial pressure.”
  • Patients at a risk of high intracranial pressure (tumor, bleeding, hydrocephalus, infection and children) “must be treated more aggressively, because they have less capability to compensate for the cell swelling than people at a lesser risk.”
  • Correcting acute hyponatremia bears a low risk of osmotic demyelination (OD), whereas “chronic hyponatremia must be corrected more cautiously. The distinction between acute and chronic is arbitrary and difficult to implement in practice.”
  • There have been no prospective studies that have sought to establish the definitive speed and extent of correction in hyponatremia.
  • Because OD is observed “when patients are corrected at a pace faster than corresponding to 12 mmol/l/day,” the authors wrote that “it seems reasonable, in light of the brain's adaption mechanisms, not to treat patients at a faster pace than that, even though there is no absolute safe rate.”
  • The conflict between previously opposing standpoints is “gradually giving way to an emerging consensus: Treatment of symptomatic hyponatremia should involve a prompt, but small increase in plasma [Na ] followed by slow correction.”
  • When plasma [Na ] is below 130 mmol/l or hyponatremia is suspected together with cerebral symptoms, it is recommended to “immediately administer one or more boluses of 2 ml/kg 3% NaCl (or corresponding amounts of more hypertonic NaCl) intravenously.”
  • When the cerebral function is improved, “the main danger is inadvertent overcorrection with the risk of OD.” To guard against unintended overcorrection by brisk dieresis, clinicians should monitor water balance by inserting a bladder catheter and recording diuresis “together with frequent plasma [Na ] measurement. Urine should be analyzed to determine Na and K output.”
  • Other studies have proposed conservative therapeutic goals for correction of 8 mmol/l in 24 h, 14 mmol/l in 48 h and 16 mmol/l in 72 h.
  • Hypervolemic hyponatremia in patients with conditions such as congestive heart failure, cirrhosis, nephrotic syndrome, etc should be diagnosed from the patient's history. The underlying conditions “can occasionally be improved to reduce the non-osmotic ADH stimulus (eg, by the use of ACE inhibitors in heart failure). Plasma [Na ] is corrected with water restriction and loop diuretics (prevents the maximal concentration of urine), and eventually, vasopressin antagonists may be used.”

The authors summarized the results of their study by noting that the” emerging consensus regarding the initial treatment of hyponatremia” supports the use of bolus therapy with 2 ml/kg 3% saline. They urged clinicians to avoid overcorrection and OD and focus treatment decisions on addressing the underlying cause of hyponatremia. They noted that this can be “a challenging task and traditional classifications based on hydration are difficult to use in the clinic. Therefore, an approach based on the mechanism governing the impaired urine dilution has been proposed.”