Yet another pitfall is differentiating patients with salt depletion from those with SIADH. In these situations, measurement of the change in PNa concentration after a test infusion of isotonic saline is helpful. In salt depletion, PNa usually increases ≥5 mmol/L after 2 L saline infusion, which is not the case with SIADH.13 Incorrectly diagnosing renal salt wasting (RSW) as SIADH results in fluid restriction and, consequently, ECV depletion and increased morbidity.14 The persistence of hypouricemia and elevated FEUrate after correction of the hyponatremia in RSW differentiates it from SIADH.13, 14
Given these challenges, recommendations to use an algorithmic approach for the evaluation and diagnosis of hyponatremia have surfaced. In a study of 121 patients admitted with hyponatremia, an algorithm-based approach to the diagnosis of hyponatremia yielded an overall diagnostic accuracy of 71%, compared with an accuracy of 32% by experienced clinicians.5 This study also highlighted SIADH as the most frequent false-positive diagnosis that was expected whenever the combination of euvolemia and a UNa >30 mmol/L was present.5 Cases of diuretic-induced hyponatremia often were misclassified due to errors in the accurate assessment of ECV status, as most of these patients appeared clinically euvolemic or hypervolemic.5 Therefore, it is important to use an algorithm in identifying SIADH and to use one that does not rely solely on clinical estimation of ECV status (see Figure 1, below).
Management of acute and symptomatic hyponatremia. When hyponatremia develops acutely, urgent treatment is required (see Figure 2, below).15 Hyponatremia is considered acute when the onset is within 48 hours.15 Acute hyponatremia is most easily identified in the hospital and is commonly iatrogenic. Small case reviews in the 1980s began to associate postoperative deaths with the administration of hypotonic fluids.16 Asymptomatic patients with hyponatremia presenting from home should be considered chronic hyponatremias as the duration often is unclear.
Acute hyponatremia or neurologically symptomatic hyponatremia regardless of duration requires the use of hypertonic saline.15 Traditional sodium correction algorithms are based on early case series, which were focused on limiting neurologic complications from sodium overcorrection.17 This resulted in protocols recommending a conservative rate of correction spread over a 24- to 48-hour period.17 Infusing 3% saline at a rate of 1 ml/kg/hr to 2 ml/kg/hr results in a 1 mmol/L/hr to 2 mmol/L/hr increase in PNa.15 This simplified formula results in similar correction rates as more complex calculations.15 Correction should not exceed 8 mmol/L to 10 mmol/L within the first 24 hours, and 18 mmol/L to 25 mmol/L by 48 hours to avoid CPM.15 PNa should be checked every two hours to ensure that the correction rate is not exceeding the predicted rate, as the formulas do not take into account oral intake and ongoing losses.15
Recent observations focused on the initial four hours from onset of hyponatremia suggest a higher rate of correction can be tolerated without complications.18 Rapid sodium correction of 4 mmol/L to 6 mmol/L often is enough to stop neurologic complications.18 This can be accomplished with a bolus infusion of 100 mL of 3% saline.19 This may be repeated twice at 10-minute intervals until there is neurologic improvement.19 This might sound aggressive, but this would correspond to a rise in PNa of 5 mmol/L to 6 mmol/L in a 50 kg woman. Subsequent treatment with hypertonic fluid might not be needed if symptoms resolve.
Management of chronic hyponatremia. Hyponatremia secondary to SIADH improves with the treatment of the underlying cause, thus an active search for a causative medication or condition should be sought (see Table 1, p. 17).20