Severe hyponatremia (sodium [Na] ≤ 120 mmol) can result in hyponatremic encephalopathy requiring emergent treatment with hypertonic saline to prevent death or permanent neurologic impairment (1). The relationship between the rapidity of correction and the development of osmotic demyelination syndrome (ODS) can be difficult to ascertain, as ODS is a rare, multifactorial condition associated with risk factors, including alcohol use disorder, hypokalemia, severe liver disease, malnutrition, hyperemesis, hypophosphatemia, and central nervous system hypoxia, with many reported cases occurring in the absence of hyponatremia or with slow correction (2–4). The optimal rate and limits for the correction of hyponatremia are uncertain. US and European clinical practice guidelines in 2013 and 2014, respectively, recommend limits of correction of between 8 and 10 mmol/L/24 hours, with re-lowering of the serum Na with free water or desmopressin if these limits are exceeded, for the prevention of ODS (5, 6). A recent NEJM Evidence report found ODS to be rare and unrelated to rapid correction (7), prompting us to suggest in an accompanying editorial that more liberal treatment guidelines are warranted (8). Since then, a report in the Journal of Critical Care found more rapid correction to be associated with improved patient outcomes, without increased development of ODS, in patients with severe hyponatremia in the intensive care unit (ICU) (9).
Evidence published after the treatment guidelines supports more liberal rates of correction. Eleven studies involving 7695 patients with severe hyponatremia (120 mmol/L or lower) reported 26 cases (0.34%) of ODS, and approximately 80% of these had alcohol use (Table 1) (7, 9–18). Rapid correction of hyponatremia (>8 mmol/L/24 hours) was common, occurring in approximately 40% of patients, and was not associated with ODS in the absence of alcohol use. The NEJM Evidence study found 12 suspected cases of ODS (0.05%) in 23,445 patients presenting to the emergency department with hyponatremia (Na < 130 mmol/L) (7). ODS was unrelated to rate of correction, with rates of correction at 24 and 48 hours being ≤4 and 8 mmol/L in three patients (25%) and ≤9 and 14 mmol/L in nine patients (75%). Two recent case series involving 60 patients with ODS found two-thirds with alcohol use disorder or liver disease, only 20% with severe hyponatremia, and 25% with rapid correction (>8 mmol/L/day) (2, 3). These studies suggest that ODS is related to underlying risk factors rather than rapid correction of hyponatremia.
Rates of correction and outcomes in patients with severe hyponatremia
NA, not available; PNa, plasma sodium.
aRapid correction.
bIntermediate correction.
cSlow correction.
The report in the Journal of Critical Care was a large, retrospective, multi-center study across 208 US hospitals that included 1024 patients with severe hyponatremia (≤120 mmol/L) in the ICU (9). Rapid correction (>8 mmol/L/day) occurred in 44% of patients and was associated with decreases in adjusted mortality (4.37%) and length of hospital (1.8 days) and ICU (1.16 days) stays. A subanalysis found rates of correction of 8-12 and >12 mmol/L/day to be associated with a decreased length of stay when compared with <8 mmol/L/day and rates between 10 and 20 mmol/L/day to be associated with the shortest length of stay. A further analysis of 376 patients with high-risk factors for ODS (Na ≤ 105 mmol/L, potassium ≤ 3.5, or a history of liver failure) found no cases of ODS, despite 52% receiving rapid correction.
One of the premises of the hyponatremia treatment guidelines was lack of evidence that rapid treatment of hyponatremia improves outcomes (5). Evidence now demonstrates that rapid correction is associated with improved patient outcomes and that ODS is rare and related to risk factors—in particular, alcohol use—and not to rapid correction. The current treatment guidelines are overly restrictive and could be contributing to worse patient outcomes with increased mortality and length of stay. Hyponatremia treatment guidelines should be revised in favor of a single, 48-hour limit of 15–20 mmol/L (19, 20), which would simplify treatment, allow for more active treatment with rapid intermittent bolus with hypertonic saline, and decrease the use of desmopressin to control correction, all without producing ODS.
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