Abnormal sodium levels predict morbidity, death in hospitalized COVID-19 patients

Sodium levels during hospitalization are predictive of clinical outcomes in patients with COVID-19, with hypernatraemia and hyponatraemia correlating with a greater risk of death and respiratory failure, respectively, a study has found. Of note, hyponatraemia does not predict in-hospital mortality, except for the subgroup of hypovolaemic hyponatraemia.

“Therefore, serum sodium values could be used in clinical practice to identify patients with COVID-19 at high risk of poor outcomes who would benefit from more intensive monitoring and judicious rehydration,” the researchers said.

All adult patients who presented with COVID-19 to two hospitals in London over an 8-week period were included in this retrospective longitudinal cohort study, which examined the association of dysnatraemia (serum sodium <135 mmol/L for hyponatraemia or >145 mmol/L for hypernatraemia) at several time points with inpatient mortality, need for advanced ventilatory support, and acute kidney injury (AKI).

Of the 488 patients (median age 68 years) included in this study, 24.6 percent were hyponatraemic, primarily due to hypovolaemia, and 5.3 percent were hypernatraemic at presentation. [J Clin Endocrinol Metab 2021;106:1637-1648]

Hypernatraemia 2 days after admission and exposure to hypernatraemia at any time point during hospitalization resulted in a 2.34-fold (95 percent confidence interval [CI], 1.08–5.05; p=0.0014) and 3.05-fold (95 percent CI, 1.69–5.49; p<0.0001) higher risk of death, respectively, relative to normonatraemia.

On the other end, hyponatraemia at admission correlated with a 2.18-fold (95 percent CI, 1.34–3.45; p=0.0011) greater odds of requiring ventilation support. Hyponatraemia was not associated with a higher risk of in-hospital mortality, except for those with hypovolaemic hyponatraemia. Notably, sodium values showed no association with the risk for AKI and length of hospital stay.

“The key novel finding of our study was that hospital-acquired hypernatraemia, rather than … at admission, was a predictor for in-hospital mortality, with the worst prognosis being reported in patients with the largest increase in serum sodium in the first 5 days of hospitalization,” the researchers said.

“Hypernatremia reflects a deficit of total body water relative to total body sodium and is often accompanied by reduced extracellular fluid volume, highlighting hypovolaemia as driver of mortality in COVID-19,” they added. [Best Pract Res Clin Endocrinol Metab 2003;17:471-503]

The finding on the association between hyponatraemia at hospital admission and an increased likelihood of needing advanced ventilatory support was consistent with that in other COVID-19 studies and those in patients with community-acquired pneumonia (CAP). [Crit Care Med 2020;48:e1211-e1217; New Microbes New Infect 2020;37:100753; Clin Infect Dis 2008;47:1571-1574]

“Contrary to the independent association of hyponatremia with mortality in CAP, our study did not identify hyponatraemia as a predictor of mortality in patients with COVID-19,” the researchers said, noting that their data on the link of hypovolaemic hyponatraemia with excess mortality supported those from recent studies in general hospital populations. [Respir Med 2014;108:1696-1705; Eur J Intern Med 2018;54:46-52; BMC Pulm Med 2008;8:16; J Clin Endocrinol Metab 2020;105:3428-3436]

Further research is warranted to explore the pathophysiological basis of dysnatraemia in COVID-19 patients, its subtypes, and its association with lung inflammation, infection severity, and cytokine release, according to the researchers.

“In addition, prospective intervention studies are required to determine whether correction of sodium abnormalities could improve clinical outcomes and establish the most effective fluid-resuscitation strategy,” they said.