Dysnatremia a predictor for morbidity and mortality in hospitalised patients with COVID-19

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Abnormal sodium levels during hospitalisation was a risk factor for poor prognosis, with hypernatremia and hyponatremia being associated with a greater risk of death and respiratory failure, respectively, in patients with coronavirus disease 2019 (COVID-19), according to a study published in The Journal of Clinical Endocrinology & Metabolism.

“Hypernatremia at any timepoint during hospital stay is related to excess in-hospital mortality, while hyponatremia at presentation is associated with a higher likelihood to require advanced ventilatory support. Hyponatremia was not a risk factor for inhospital mortality, except for the subgroup of hypovolemic hyponatremia,” reported Ploutarchos Tzoulis, MD, University College London, London, United Kingdom, and colleagues. “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.”

This retrospective longitudinal cohort study, which included 488 patients (median age 68 years) with COVID-19 admitted to two hospitals in London between February and May 2020, evaluated the association of hyponatremia (serum sodium < 135 mmol/L) and hypernatremia (serum sodium > 145 mmol/L) at several time points with inpatient mortality, need for advanced ventilatory support and acute kidney injury (AKI). More than half of the patients (56.8%) were male. At presentation, 24.6% of patients were hyponatremic, mainly due to hypovolemia, and 5.3% were hypernatremic.

Multivariable analysis identified three independent risk factors for higher in-hospital mortality: older age (adjusted hazard ratio [aHR], 1.04; 95% confidence interval [CI], 1.01-1.07; P = 0.007), higher C-reactive protein concentrations (aHR, 1.10 per 20 mg/l; 95% CI, 1.04-1.17; P <0.001), and hypernatremia at any time point during the first five days of hospitalisation (aHR, 2.74; 95% CI, 1.16 – 6.40); P = 0.02). Meanwhile, hypernatremia on day 3 and on day 6 predicted mortality with an estimated hazard ratio of 2.34 (95% CI 1.08 – 5.05, P = 0.0014) and 2.40 (95% CI 1.18 – 4.85, P = 0.0011), respectively, whereas hyponatremia was not associated with death.

A longitudinal analysis of sodium data during hospital stay demonstrated that 37.9% of patients remained normonatremic throughout hospitalisation, 36.9% had exposure to hyponatremia, 10.9% were exposed to hypernatremia, and 14.3% experienced both hypernatremia and hyponatremia.

Researchers found that exposure to hypernatremia (odds ratio [OR], 3.05; 95% CI 1.69-5.49; P <0.0001,) or both hypernatremia and hyponatremia (OR, 2.25; 95% CI 1.33-3.82; P = 0.0038) was associated with significantly increased mortality rate compared to normonatremia. Meanwhile, patients exposed to hyponatremia had a mortality rate which was not significantly different compared to that of normonatremic individuals. However, the subgroup of patients who developed hypovolemic hyponatremia at any time point had a higher mortality rate than normonatremic individuals (OR, 2.59; 95% CI, 1.44–4.81, P = 0.0017).

On the other hand, hyponatremia at admission was linked to a 2-fold increase in the likelihood of needing ventilatory support (OR, 2.18; 95% CI, 1.34-3.46; P = 0.0011). Meanwhile, hypernatremia was not associated with an increased likelihood to need respiratory support since the percentage of patients exposed to hypernatremia at any time point during hospitalisation who required advanced ventilatory support was not significantly different from that of normonatremic patients (P = 0.39).

In addition, sodium values were found to be not associated with the risk for AKI and length of hospital stay.

“The key novel finding of our study was that hospital-acquired hypernatremia, rather than hypernatremia 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 hospitalisation,” the authors noted.

“The high frequency of volume depletion in COVID-19 illness might be explained by low oral intake due to anorexia or nausea, or significant increases in insensible fluid losses, or, less commonly, fluid losses due to diarrhea,” the authors remarked. “Until more data are available and in line with the standard clinical approach in patients with other pathologies, an approach to fluid resuscitation which recognises the frequency and severity of volume depletion, whilst taking appropriate care to prevent fluid overload or pulmonary oedema, should be strongly considered.”

“Studies are promptly warranted in order to explore further the pathophysiological basis of dysnatremia in COVID-19 patients, its subtypes and its link with lung inflammation, severity of infection, and cytokine release, the authors added. “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.”