The Prognostic Value of Hyponatremia for Predicting Poor Outcome in Patients With COVID-19: A Systematic Review and Meta-Analysis

Akbar, Mohammad Rizki; Pranata, Raymond; Wibowo, Arief; Irvan, Irvan; Sihite, Teddy Arnold; Martha, Januar Wibawa

doi:10.3389/fmed.2021.666949

Cited by 30 publications

(41 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…At admission, 26.5% patients had hyponatremia: this finding is consistent with data from a meta-analysis on 11,493 COVID-19 patients showing a 24% pooled incidence for this disorder ( 27 ).…”

Section: Discussionsupporting

confidence: 87%

“…The first, retrospective Chinese data on hyponatremia in COVID-19 pneumonia reported a 10–27% prevalence, which is far lower than the 60% previously demonstrated for SARS-CoV-1 ( 24 , 25 , 26 ). Data from a recent meta-analysis on the same topic showed a pooled incidence of 16–31% for hyponatremia ( 27 ), which has been directly correlated with PaO 2 /FiO 2 ratio, inversely with IL-6 and associated with worse COVID-19 outcomes (non-invasive ventilation, ICU transfer, death) ( 24 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 ). Despite its prognostic value in critical illnesses, data concerning COVID-19-related hypernatremia are scarce ( 24 , 33 , 34 , 35 ); specifically, only one study looked for the development of hypernatremia in COVID-19 inpatients, showing this was associated with in-hospital mortality ( 35 ).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Sodium alterations impair the prognosis of hospitalized patients with COVID-19 pneumonia

Martino¹,

Falcioni²,

Giancola³

et al. 2021

Endocrine Connections

View full text Add to dashboard Cite

Objective: Dysnatremia is common in hospitalized patients, often worsening the prognosis in pneumopathies and critical illnesses. Information on COVID-19-related hyponatremia is partially conflicting, whereas data on hypernatremia in this context are scarce. We assessed, in a cohort of COVID-19 inpatients: the prevalence of sodium alterations at admission and throughout their hospitalization; their association with inflammation/organ damage indexes; their short-term prognostic impact. Study design and methods: 117 patients (81 males, 64±13 years) hospitalized for COVID-19 between 1st March and 30th April 2020 were retrospectively followed-up for their first 21 days of stay by collecting all serum sodium measurements, basal CRP and serum lactate levels, maximum IL-6 and information on care setting, required ventilation, length of hospitalization, in-hospital death. Results: At admission, 26.5% patients had hyponatremia, 6.8% had hypernatremia. During their hospitalization, 13.7% patients experienced both disorders (“mixed dysnatremia”). Lower sodium levels at admission were correlated with higher CRP (p=0.039) and serum lactate levels (p= 0.019), but not IL-6. Hypernatremia and a wider sodium variability were associated to maximum required ventilation, need of ICU assistance and duration of the hospitalization. Mean estimated time to ICU admission was 20 days shorter in patients exposed to sodium alterations at any time of their hospital course (Log-Rank test p=0.032). Conclusions: Sodium alterations frequently affect hospitalized COVID-19 patients. Hyponatremia could indicate pulmonary involvement, whereas hypernatremia is associated to prolonged hospitalization and need for intensive care/mechanical ventilation, particularly when resulting from prior hyponatremia. Optimizing in-hospital sodium balance is crucial to improve patients’ prognosis.

show abstract

Section: Discussionsupporting

confidence: 87%

Section: Introductionmentioning

confidence: 99%

Sodium alterations impair the prognosis of hospitalized patients with COVID-19 pneumonia

Martino¹,

Falcioni²,

Giancola³

et al. 2021

Endocrine Connections

View full text Add to dashboard Cite

show abstract

“…Hypovolemic hyponatremia is common in COVID 19 infected patients after admission because of the presence of increased insensible loses (taquipnea, fever), vomiting, diarrhea, and anorexia that accompany severe respiratory symptoms and the use of hypotonic fluids ( 11 ). However, in our population hyponatremia was present at admission before any therapeutic intervention took place.…”

Section: Discussionmentioning

confidence: 99%

“…Hyponatremia can result from inflammation due to non-osmotic stimuli for vasopressin production (9) and is a risk factor for death in general hospitalized patients (10). Thus, hyponatremia linked to severe inflammation could be another prognostic factor for poor outcomes in COVID 19 infected patients as has been recently shown in a recent meta-analysis (11). However, all the previous studies have been retrospective or cross-sectional in nature.…”

Section: Introductionmentioning

confidence: 99%

Hyponatremia, Inflammation at Admission, and Mortality in Hospitalized COVID-19 Patients: A Prospective Cohort Study

et al. 2021

View full text Add to dashboard Cite

Background: Systemic inflammation has been associated with severe coronavirus disease 2019 (COVID-19) disease and mortality. Hyponatremia can result from inflammation due to non-osmotic stimuli for vasopressin production.Methods: We prospectively studied 799 patients hospitalized with COVID-19 between March 7 and November 7, 2020, at Hospital Posadas in Buenos Aires, Argentina in order to evaluate the association between hyponatremia, inflammation, and its impact on clinical outcomes. Admission biochemistries, high-sensitivity C-reactive protein (hsCRP), ferritin, patient demographics, and outcome data were recorded. Outcomes (within 30 days after symptoms) evaluated included ICU admission, mechanical ventilation, dialysis-requiring acute kidney injury (AKI), and in-hospital mortality. Length of hospital stay (in days) were evaluated using comprehensive data from the EHR.Results: Hyponatremia (median Na = 133 mmol/L) was present on admission in 366 (45.8%). Hyponatremic patients had higher hsCRP (median 10.3 [IR 4.8–18.4] mg/dl vs. 6.6 [IR 1.6–14.0] mg/dl, p < 0.01) and ferritin levels (median 649 [IQR 492–1,168] ng/dl vs. 393 [IQR 156–1,440] ng/dl, p = 0.02) than normonatremic patients. Hyponatremia was associated with higher odds of an abnormal hsCRP (unadjusted OR 5.03, 95%CI: 2.52–10.03), and remained significant after adjustment for potential confounders (adjusted OR 4.70 [95%CI: 2.33–9.49], p < 0.01). Hyponatremic patients had increased mortality on unadjusted (HR 3.05, 95%CI: 2.14–4.34) and adjusted (HR 2.76, 95%CI:1.88–4.06) in Cox proportional hazard models. Crude 30-day survival was lower for patients with hyponatremia at admission (mean [SD] survival 22.1 [0.70] days) compared with patients who were normonatremic (mean [SD] survival 27.2 [0.40] days, p < 0.01).Conclusion: Mild hyponatremia on admission is common, is associated with systemic inflammation and is an independent risk factor for hospital mortality.Clinical Trial Registration:www.ClinicalTrials.gov, identifier NCT04493268.

show abstract

“…Since IL-6 is able to induce vasopressin secretion by a direct hypothalamic stimulation and by inducing alveolar basement membrane injury and pulmonary hypoxia and vasoconstriction [ 44 , 45 , 46 , 47 ], the pro-inflammatory cytokine may represent the common denominator of both acute respiratory insufficiency and syndrome of inappropriate antidiuresis (SIAD)-related hyponatremia. A very recent metanalysis of 8 studies and 11,493 patients showed a correlation of hyponatremia with COVID-19 poor outcomes (a composite of mortality, prolonged hospitalization and severe COVID-19, defined as severe pneumonia and/or needing intensive care unit support/invasive mechanical ventilation; OR 2.65 [1.89, 3.72], p < 0.001; I2: 67.2%, p = 0.003), with a 37% sensitivity and 82% specificity; while normal serum [Na + ] is associated with a 16% post-test probability of a worse prognosis, the presence of hyponatremia increases this probability up to 33% [ 48 ].…”

Section: Hyponatremia and Healthmentioning

confidence: 99%

Hyponatremia and Oxidative Stress

et al. 2021

View full text Add to dashboard Cite

Hyponatremia, i.e., the presence of a serum sodium concentration ([Na+]) < 136 mEq/L, is the most frequent electrolyte imbalance in the elderly and in hospitalized patients. Symptoms of acute hyponatremia, whose main target is the central nervous system, are explained by the “osmotic theory” and the neuronal swelling secondary to decreased extracellular osmolality, which determines cerebral oedema. Following the description of neurological and systemic manifestations even in mild and chronic hyponatremia, in the last decade reduced extracellular [Na+] was associated with detrimental effects on cellular homeostasis independently of hypoosmolality. Most of these alterations appeared to be elicited by oxidative stress. In this review, we focus on the role of oxidative stress on both osmolality-dependent and -independent impairment of cell and tissue functions observed in hyponatremic conditions. Furthermore, basic and clinical research suggested that oxidative stress appears to be a common denominator of the degenerative processes related to aging, cancer progression, and hyponatremia. Of note, low [Na+] is able to exacerbate multiple manifestations of senescence and to decrease progression-free and overall survival in oncologic patients.

show abstract

The Prognostic Value of Hyponatremia for Predicting Poor Outcome in Patients With COVID-19: A Systematic Review and Meta-Analysis

Cited by 30 publications

References 31 publications

Sodium alterations impair the prognosis of hospitalized patients with COVID-19 pneumonia

Sodium alterations impair the prognosis of hospitalized patients with COVID-19 pneumonia

Hyponatremia, Inflammation at Admission, and Mortality in Hospitalized COVID-19 Patients: A Prospective Cohort Study

Hyponatremia and Oxidative Stress

Contact Info

Product

Resources

About