Hyponatremia - Complications, Prognosis, Epidemiology in Finnish Tertiary Care

Clinical Significance of Hyponatremia

Study Objectives and Hypothesis

To determine the incidence of hyponatremia at TYKS and the factors associated with it.

To assess how rapidly hyponatremia was corrected and how the rate of correction affected patient prognosis.

To evaluate treatment modalities and their impact on patient prognosis, length of hospital stay, and their appropriateness in comparison with national and international treatment guidelines.

To determine the incidence of osmotic demyelination at TYKS and the factors associated with it.

To assess other complications and their clinical significance.

To evaluate the impact of hyponatremia on various endpoints, such as mortality, length of hospital stay, seizures, confusion, and similar outcomes.

Study Overview

• Status: Active, not recruiting
• Conditions: Hyponatremia; Alcohol Use Disorder; Osmotic Demyelination Syndrome

Detailed Description

Clinical Significance of Hyponatremia (Study Protocol)

Investigators: Tyko Hellsten, Anssi Mustonen, Ilpo Nuotio

Background of the Study General Background

Hyponatremia is a common electrolyte disorder occurring in approximately 15-30% of hospitalized patients (3,4). Most cases are mild and minimally symptomatic. The most clinically significant cases are rapidly developing severe hyponatremia, which may cause neurological emergencies and death, and chronic severe hyponatremia, in which overly rapid correction may lead to permanent neurological injury and, in the most severe cases, death (3,4). Hyponatremia is not an independent disease but a consequence of underlying illnesses, adverse drug effects, inappropriate fluid therapy, or, rarely, lifestyle-related factors.

Hyponatremia is classified as mild when serum sodium is 130-134 (-138) mmol/L. Although mild hyponatremia has been associated with increased hospital visits, prolonged hospital stays, sarcopenia, falls, fractures, and increased mortality, it is not typically an active target of treatment, and there are no reports on the effectiveness of its treatment.

Rapidly developing severe hyponatremia presenting with neurological symptoms, cerebral edema, or seizures requires an initial rapid increase in serum sodium followed by slower correction (1). In chronic severe hyponatremia, correction must be slow from the beginning to avoid neurological complications (1). Since the rate of development is often unknown, practical guidance recommends an initial rapid increase of 5-6 mmol/L in patients with neurological symptoms, while sodium should be corrected slowly in minimally symptomatic patients.

Hyponatremia is also classified according to serum osmolality into pseudo-, hypertonic, isotonic, and hypotonic hyponatremia. Pseudohyponatremia and hypertonic/isotonic hyponatremia are most commonly caused by hyperglycemia or, rarely, by fluids used in operative settings. This study focuses on hypotonic hyponatremia, its prevalence, associated diseases, clinical significance in acute care, and treatment.

Classification, Etiology and Diagnostics

Hyponatremia is classified as:

Mild: 130-134 (-138) mmol/L

Moderate: 120 (-125) to 130 mmol/L

Severe: <120-125 mmol/L (1)

Based on duration:

Acute hyponatremia develops within 48 hours (e.g., postoperative fluid therapy with increased ADH secretion, polydipsia in psychiatric patients or endurance athletes) (1,3,4).

Chronic hyponatremia develops over more than 48 hours, has an unclear duration, or develops outside hospital settings (1,3,4).

Based on volume status, hypotonic hyponatremia is classified as:

Hypovolemic

Euvolemic

Hypervolemic

Hypovolemic hyponatremia presents with clinical signs of dehydration and is caused by gastrointestinal losses or renal losses (e.g., diuretics, mineralocorticoid deficiency) (4).

Euvolemic hyponatremia, the most common type, is often due to SIADH (syndrome of inappropriate antidiuretic hormone secretion), associated with medications, stress, CNS and pulmonary diseases, and malignancies. Other causes include hypothyroidism, adrenal insufficiency, and abnormal dietary habits (4).

Hypervolemic hyponatremia results from decreased effective arterial blood volume, leading to reactive water retention (4), as seen in liver cirrhosis, heart failure, nephrotic syndrome, and polydipsia.

Assessment of vasopressin activity is commonly based on the urine-to-serum osmolality ratio (U-osmolality > S-osmolality or U-osmolality 100-300) (6), since direct vasopressin measurement is unreliable and copeptin is not routinely used.

Treatment and Associated Risks

Treatment depends on the rate of onset, symptom severity, and etiology. Current guidelines are largely consistent.

If there is a high risk of osmotic demyelination syndrome (ODS) (Na <105 mmol/L, alcoholism, hypokalemia, malnutrition, liver disease), correction should not exceed 4-6 mmol/L per 24 hours (3). Otherwise, up to 8 mmol/L in the first 24 hours is considered safe. In confirmed acute cases (<24-48 hours), correction may proceed more rapidly (3).

Rapid-onset hyponatremia causes cerebral edema due to water movement into brain cells (4). Chronic hyponatremia allows osmotic adaptation, reducing cellular swelling (4).

Known intracranial pathology increases herniation risk, and hypertonic 3% saline should be considered early (1). Sodium levels should be monitored every 4-6 hours, or hourly in severe cases (3).

In Finland, national acute care guidelines recommend fluid restriction for slowly developing, mildly symptomatic hyponatremia. Hypertonic 3% saline is reserved for severe neurological symptoms (8).

After acute correction, hyponatremia may not require further specific treatment if the underlying cause has been addressed. SIADH is often chronic; first-line treatment is fluid restriction and correction of underlying causes (4). Tolvaptan is rarely used due to cost and limited reimbursement. Oral sodium chloride may be considered in SIADH if fluid restriction is insufficient (1).

Complications and Prognosis

Hyponatremia is the most common cause of ODS, particularly in chronic cases with overly rapid correction (2). Clinical manifestations include central pontine and extrapontine myelinolysis (2). Symptoms range from dysarthria and dysphagia to spastic tetraparesis and extrapyramidal features.

MRI is essential in diagnosis. Imaging findings do not directly correlate with prognosis (2).

There is no specific treatment for ODS; prevention through cautious correction is key (1,3). Prognosis has improved substantially compared to the 1980s (2).

Study Objectives and Hypotheses

To determine the incidence of hyponatremia and associated factors at TYKS (Turku University Hospital).

To evaluate correction rates and their impact on prognosis.

To assess treatment modalities, hospital length of stay, outcomes, and adherence to guidelines.

To determine the incidence and risk factors of ODS at TYKS.

To identify other complications and their significance.

To evaluate the impact of hyponatremia on mortality, hospital stay, seizures, confusion, and other endpoints.

The first study will assess incidence and associated factors (2016-2020). The second will evaluate sodium levels and mortality across diagnosis groups. The third will assess ODS incidence and associated factors. The fourth will focus on management of severe hyponatremia.

Materials and Methods

A registry-based study will include all patients with hyponatremia and all cases of osmotic demyelination syndrome treated at TYKS between January 1, 2016, and December 31, 2020.

Data will be analyzed using statistical software (SAS, SPSS, R) by study investigators.

Results will be published in international medical journals and presented at national and international conferences.

Significance of the Study

Hyponatremia is a common clinical challenge in emergency and inpatient care. Controlled correction requires monitored care. This study aims to clarify:

At which sodium levels monitored correction is necessary

What constitutes a safe correction rate

The frequency of complications with rapid correction

Whether patients are overtreated

The impact of hyponatremia and comorbidities on prognosis and mortality

The goal is to clarify diagnostic and therapeutic strategies for hyponatremia.

Ethical Considerations

This is a registry-based study. Separate ethical approval is not required. Data will be anonymized before analysis.

Study Timeline

Study planning: from January 1, 2022 Research permits and data retrieval: from May 1, 2022

• Study Type: Observational
• Enrollment (Actual): 10000

Contacts and Locations

Study Locations

• Finland
  • Southwest Finland
    • Turku, Southwest Finland, Finland, 20300
      • University of Turku

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

The study design was to enroll as general population that are hospitalized as possible. From this population the main focus group of hyponatremia and ODS patients were selected and formed case-control groups.

Description

Inclusion Criteria:

• Two sodium measurements in Tyks laboratories between 12-36 hours.

Exclusion Criteria:

-

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prevalence of ODS in hyponatremia patients	The primary variable is dichotomous. It is defined based on radiologists' reports and confirmed by an expert panel.	From enrollment to the end of the treamtent period. Usually 2-21 days.
Osmotic demyelination syndrome	Dichotomic 0/1, outcome defined from radiology reports.	During the study period 1.1.2010-31.12.2020 wiht recorded sodium values.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Epidemiology and correction rates of hyponatremia	The prevalence of severe, and moderate hyponatremia in Tyks. The medium and maximal correction rate during any 24-hour period during the treatment period.	During any 24-hour period during the treatment period.
Prognosis linked to severe or moderate hyponatremia	To assess 1, 6 and 12 month mortality and hospitalization duration compared to normal sodium values at enrollment.	1, 6 and 12 months after enrollment

Collaborators and Investigators

• Sponsor: University of Turku

Publications and helpful links

General Publications

• Kalampokini S, Artemiadis A, Zis P, Hadjihannas L, Parpas G, Kyrri A, Hadjigeorgiou GM. Osmotic demyelination syndrome improving after immune-modulating treatment: Case report and literature review. Clin Neurol Neurosurg. 2021 Sep;208:106811. doi: 10.1016/j.clineuro.2021.106811. Epub 2021 Jul 24.
• Baek SH, Jo YH, Ahn S, Medina-Liabres K, Oh YK, Lee JB, Kim S. Risk of Overcorrection in Rapid Intermittent Bolus vs Slow Continuous Infusion Therapies of Hypertonic Saline for Patients With Symptomatic Hyponatremia: The SALSA Randomized Clinical Trial. JAMA Intern Med. 2021 Jan 1;181(1):81-92. doi: 10.1001/jamainternmed.2020.5519.
• Verbalis JG, Goldsmith SR, Greenberg A, Schrier RW, Sterns RH. Hyponatremia treatment guidelines 2007: expert panel recommendations. Am J Med. 2007 Nov;120(11 Suppl 1):S1-21. doi: 10.1016/j.amjmed.2007.09.001.
• Verbalis JG, Goldsmith SR, Greenberg A, Korzelius C, Schrier RW, Sterns RH, Thompson CJ. Diagnosis, evaluation, and treatment of hyponatremia: expert panel recommendations. Am J Med. 2013 Oct;126(10 Suppl 1):S1-42. doi: 10.1016/j.amjmed.2013.07.006.
• Lambeck J, Hieber M, Dressing A, Niesen WD. Central Pontine Myelinosis and Osmotic Demyelination Syndrome. Dtsch Arztebl Int. 2019 Sep 2;116(35-36):600-606. doi: 10.3238/arztebl.2019.0600.

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2023
• Primary Completion (Actual): January 1, 2026
• Study Completion (Estimated): December 31, 2028

Study Registration Dates

• First Submitted: February 17, 2026
• First Submitted That Met QC Criteria: February 17, 2026
• First Posted (Actual): February 24, 2026

Study Record Updates

• Last Update Posted (Actual): February 24, 2026
• Last Update Submitted That Met QC Criteria: February 17, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: epidemiology; hyponatremia; Osmotic Demyelination Syndrome; Alchol use disorder
• Additional Relevant MeSH Terms: Mental Disorders; Metabolic Diseases; Substance-Related Disorders; Chemically-Induced Disorders; Alcohol-Related Disorders; Water-Electrolyte Imbalance; Nutritional and Metabolic Diseases; Alcoholism; Hyponatremia
• Other Study ID Numbers: T194/2022-1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Current Finnish legislation does not permit the sharing of individual participant data (IPD).

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No