Analysis of the Epidemiology, Clinical Presentation and Therapy as Well as Therapy-associated Risk of Demyelination Syndrome in Patients With Profound Hyponatremia in the Emergency Department

NCT06781710 | Completed

• 2 other identifiers: V1.0_23.09.202222-1373-retro
• Study Type: observational
• Target: 1,000
• Locations: 1 country
• Sites: 1

Brief Summary

Hyponatremia is a frequent cause for presentation to the emergency department (ED). While patients with chronic hyponatremia often exhibit minor symptoms, acute development of hyponatremia can lead to global cerebral edema, transtentorial herniation and death. The time course of hyponatremia development is usually not known to the treating physician at presentation. Hence, type and extent of therapy depend on the presence or absence of severe symptoms such as coma, seizures, obtundation or vomiting. It is believed that these are suggestive of increased cerebral pressure and indicative of cerebral edema. International guidance thus demands aggressive therapy with hypertonic saline at their occurrence. However, severe symptoms can also be found in patients with chronic hyponatremia (i.e., development in more than 48 hours) which are not at risk for developing cerebral edema due to adaptive counter measures in the brain. Although the percentage of patients with severe symptoms in chronic hyponatremia is considerably smaller than in acute hyponatremia, a higher incidence of chronic hyponatremia may lead to a larger overall number of severely symptomatic patients with chronic hyponatremia. The precise distribution of acute and chronic cases in the ED has not been established yet. In consequence, many patients with hyponatremia presenting with severe symptoms receive aggressive treatment in order to raise sodium levels, exposing them to the risk for overly rapid correction and osmotic demyelination syndrome (ODS). Current U.S. recommendations limit the sodium increase to a maximum of 8 mmol/L and 10-12 mmol/L in the first 24 hours in patients with high or low-to-moderate ODS risk, respectively. Similarly, the 2014 European Clinical Practice Guideline (ECPG) recommends a limit of 10 mmol/L in each 24h-period. These limits are often not accomplished in the real-world setting. In summary, weighing the risk of hyponatremia against complications associated with its (over-)correction constitutes a dilemma for the clinician. It will be strived to refine guidance on management of hyponatremia in patients with profound hyponatremia. Therefore, a better understanding of the proportions and characteristics of patients at risk for both cerebral edema and ODS is needed. The primary objective of this study is to determine the rate of hyponatremic patients who had already developed cerebral edema on admission and to identify patients who developed ODS during the index hospital stay. A secondary objective is a more detailed characterization of these subsets.

Conditions

Hyponatremia

Keywords

Hyponatremia; ODS; demyelination; overcorrection

Outcome Measures

Primary Outcomes (2)

• Rate of patients with cerebral edema

  The primary aim is to determine the patient´s risk to develop cerebral edema, associated with hyponatremia and osmotic demyelination as a result of therapy, respectively. Determination at admission as evidenced by imaging studies in the time period index admission in the Emergency Department until referral from the Emergency Department

  on admission and within 2 hours after admission

• rate of patients who develop osmotic demyelination syndrome (ODS)

  The primary aim is to determine the patient´s risk to develop cerebral edema, associated with hyponatremia and osmotic demyelination as a result of therapy, respectively. Determination as evidenced by imaging studies in the time period index admission until 90 days thereafter.

  on admission and 90 days after admission

Secondary Outcomes (4)

• Risk factors associated with hyponatremia

  on admission

• Risk factors associated with osmotic demyelination syndrome

  on admission

• Proportion of patients with severe symptoms and characterization of severe symptoms of hyponatremia

  on admission

• Proportion of patients, in which ODS was considered "confirmed", "highly likely" and "possible", considering clinical and/or radiological features of ODS

  at study end, 1 year after study start

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients with profound hyponatremia presenting to the emergency department

You may qualify if:

• Adult patients ≥18 years
• Plasma sodium ≤125 mmol/L in the initial blood sample after admission to the Emergency Department

You may not qualify if:

• Lack of follow-up sodium analyses within the first 24 hours after admission
• initial blood glucose \>300 mg/dL

Sponsors & Collaborators

• University of Cologne: lead

Study Sites (1)

University Hospital of Cologne

Cologne, 50937, Germany

Location

Related Publications (1)

• Burst V, Rabii R, Peto-Madew J, Persigehl T, Haneder S, Hackl MJ, Huser C, Trappe M, Cukoski S, Mollenhoff K, Suarez V. Severe Hyponatremia in the Emergency Department Incidence of Cerebral Edema and Risk of Osmotic Demyelination Syndrome. Acad Emerg Med. 2026 Jan;33(1):e70158. doi: 10.1111/acem.70158. Epub 2025 Oct 9.

  PMID: 41069084 DERIVED

MeSH Terms

Conditions

Hyponatremia; Demyelinating Diseases

Condition Hierarchy (Ancestors)

Water-Electrolyte Imbalance; Metabolic Diseases; Nutritional and Metabolic Diseases; Nervous System Diseases

Study Officials

• Volker Burst, MD

  University Hospital Cologne

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. Dr. med.

Study Record Dates

• First Submitted: December 17, 2024
• First Posted: January 17, 2025
• Study Start: November 1, 2024
• Primary Completion: December 31, 2025
• Study Completion: December 31, 2025
• Last Updated: April 30, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)