Hypotonic Hyponatremia: Criteria for the Correct Classification of Its Etiology and of Patient Volume Status

NCT04402190 | Completed DMC

• 1 other identifier: IPSO-URG
• Study Type: observational
• Target: 123
• Locations: 1 country
• Sites: 1

Brief Summary

Hyponatremia is the most frequent electrolyte disorder encountered in clinical practice. The patient approach, however, is still problematic, above all because hyponatremia is a manifestation correlated to various pathological conditions, with complex etiopathogenesis. Even though some algorithms have been proposed to correctly assess hyponatremia subtype classification and patient volume status, there is no single parameter that has proven to be able alone to perfectly achieve this result.

Conditions

Hyponatremia; Hyponatremia With Extracellular Fluid Depletion; Hyponatremia With Normal Extracellular Fluid Volume; Hyponatremia With Excess Extracellular Fluid Volume

Keywords

Hyponatremia; Hyponatremia with Extracellular Fluid Depletion; Hyponatremia with Normal Extracellular Fluid Volume; Hyponatremia with Excess Extracellular Fluid Volume; Hypotonic Hyponatremia; Volume Status; Intravascular Volume Status; Extracellular Fluid Volume Status; Copeptin

Outcome Measures

Primary Outcomes (22)

• Subtype classification of hypotonic hyponatremia according to the overall judgment of the clinical case by the point-of-care clinician

  The point-of-care clinician was asked to provide a subtype classification of hypotonic hyponatremia according to his/her overall judgment of the clinical case (using Kumar and Berl classification classes as a reference frame). This will be compared to the gold standard reference (as defined in the "Study Description" Section). The strength of agreement (by Cohen's kappa) and the accuracy will thus be evaluated.

  At ED admission

• Subtype classification of hypotonic hyponatremia according to the overall judgment of the clinical case by the point-of-care clinician

  The point-of-care clinician was asked to provide a subtype classification of hypotonic hyponatremia according to his/her overall judgment of the clinical case (using Kumar and Berl classification classes as a reference frame). This will be compared to the gold standard reference (as defined in the "Study Description" Section). The strength of agreement (by Cohen's kappa) and the accuracy will thus be evaluated.

  At hospital ward admission

• Physical Examination (PE) as a tool for the assessment of Extra-Cellular Fluid (ECF) Volume Status

  Elements of PE relevant for ECF Volume Status assessment were recorded (blood pressure, heart rate, pulmonary crepitations/rales, jugular vein distension, peripheral edema, dry mucous membranes). The overall evaluation of ECF Volume Status based on PE alone will be compared to the gold standard reference (as defined in the "Study Description" Section).

  At ED admission

• Physical Examination (PE) as a tool for the assessment of Extra-Cellular Fluid (ECF) Volume Status

  Elements of PE relevant for ECF Volume Status assessment were recorded (blood pressure, heart rate, pulmonary crepitations/rales, jugular vein distension, peripheral edema, dry mucous membranes). The overall evaluation of ECF Volume Status based on PE alone will be compared to the gold standard reference (as defined in the "Study Description" Section).

  At hospital ward admission

• Inferior Vena Cava (IVC) ultrasound evaluation as a tool for the assessment of Extra-Cellular Fluid (ECF) Volume Status

  IVC diameter and collapsibility were recorded. The overall evaluation of ECF Volume Status based on IVC ultrasound evaluation alone will be compared to the gold standard reference (as defined in the "Study Description" Section).

  At ED admission

• Inferior Vena Cava (IVC) ultrasound evaluation as a tool for the assessment of Extra-Cellular Fluid (ECF) Volume Status

  IVC diameter and collapsibility were recorded. The overall evaluation of ECF Volume Status based on IVC ultrasound evaluation alone will be compared to the gold standard reference (as defined in the "Study Description" Section).

  At hospital ward admission

• Serum creatinine as a tool for the assessment of Extra-Cellular Fluid (ECF) Volume Status

  Serum creatinine (mg/dl) will be used to estimate GFR (ml/min) according to CKD-EPI formula. eGFR will then be compared between three main groups of interest (i.e. hypovolemic, euvolemic and hypervolemic patients). As already previously described, these groups will be identified by the gold standard reference defined in the "Study Description" Section.

  At ED admission

• Serum urea as a tool for the assessment of Extra-Cellular Fluid (ECF) Volume Status

  Serum urea (mg/dl) will be compared between three main groups of interest (i.e. hypovolemic, euvolemic and hypervolemic patients). As already previously described, these groups will be identified by the gold standard reference defined in the "Study Description" Section.

  At ED admission

• Serum urea / serum creatinine ratio as a tool for the assessment of Extra-Cellular Fluid (ECF) Volume Status

  Serum urea / serum creatinine ratio will be compared between three main groups of interest (i.e. hypovolemic, euvolemic and hypervolemic patients). As already previously described, these groups will be identified by the gold standard reference defined in the "Study Description" Section.

  At ED admission

• Urine sodium as a tool for the assessment of Extra-Cellular Fluid (ECF) Volume Status

  Urine sodium (mmol/L), evaluated on a spot sample, will be compared between three main groups of interest (i.e. hypovolemic, euvolemic and hypervolemic patients). As already previously described, these groups will be identified by the gold standard reference defined in the "Study Description" Section.

  At ED admission

• Urine sodium / urine osmolality ratio as a tool for the assessment of Extra-Cellular Fluid (ECF) Volume Status

  Urine sodium / urine osmolality ratio will be compared between three main groups of interest (i.e. hypovolemic, euvolemic and hypervolemic patients). As already previously described, these groups will be identified by the gold standard reference defined in the "Study Description" Section.

  At ED admission

• Urine sodium / plasma osmolality ratio as a tool for the assessment of Extra-Cellular Fluid (ECF) Volume Status

  Urine sodium / plasma osmolality ratio will be compared between three main groups of interest (i.e. hypovolemic, euvolemic and hypervolemic patients). As already previously described, these groups will be identified by the gold standard reference defined in the "Study Description" Section.

  At ED admission

• Serum NT-proBNP as a tool for the assessment of Extra-Cellular Fluid (ECF) Volume Status

  Serum NT-proBNP (pg/ml) will be compared between three main groups of interest (i.e. hypovolemic, euvolemic and hypervolemic patients). As already previously described, these groups will be identified by the gold standard reference defined in the "Study Description" Section.

  At ED admission

• Serum NT-proBNP / urine sodium ratio as a tool for the assessment of Extra-Cellular Fluid (ECF) Volume Status

  Serum NT-proBNP / urine sodium ratio will be compared between three main groups of interest (i.e. hypovolemic, euvolemic and hypervolemic patients). As already previously described, these groups will be identified by the gold standard reference defined in the "Study Description" Section.

  At ED admission

• Serum creatinine as a tool for the assessment of Extra-Cellular Fluid (ECF) Volume Status

  Serum creatinine (mg/dl) will be used to estimate GFR (ml/min) according to CKD-EPI formula. eGFR will then be compared between three main groups of interest (i.e. hypovolemic, euvolemic and hypervolemic patients). As already previously described, these groups will be identified by the gold standard reference defined in the "Study Description" Section.

  At hospital ward admission

• Serum urea as a tool for the assessment of Extra-Cellular Fluid (ECF) Volume Status

  Serum urea (mg/dl) will be compared between three main groups of interest (i.e. hypovolemic, euvolemic and hypervolemic patients). As already previously described, these groups will be identified by the gold standard reference defined in the "Study Description" Section.

  At hospital ward admission

• Serum urea / serum creatinine ratio as a tool for the assessment of Extra-Cellular Fluid (ECF) Volume Status

  Serum urea / serum creatinine ratio will be compared between three main groups of interest (i.e. hypovolemic, euvolemic and hypervolemic patients). As already previously described, these groups will be identified by the gold standard reference defined in the "Study Description" Section.

  At hospital ward admission

• Urine sodium as a tool for the assessment of Extra-Cellular Fluid (ECF) Volume Status

  Urine sodium (mmol/L), evaluated on a spot sample, will be compared between three main groups of interest (i.e. hypovolemic, euvolemic and hypervolemic patients). As already previously described, these groups will be identified by the gold standard reference defined in the "Study Description" Section.

  At hospital ward admission

• Urine sodium / urine osmolality ratio as a tool for the assessment of Extra-Cellular Fluid (ECF) Volume Status

  Urine sodium / urine osmolality ratio will be compared between three main groups of interest (i.e. hypovolemic, euvolemic and hypervolemic patients). As already previously described, these groups will be identified by the gold standard reference defined in the "Study Description" Section.

  At hospital ward admission

• Urine sodium / plasma osmolality ratio as a tool for the assessment of Extra-Cellular Fluid (ECF) Volume Status

  Urine sodium / plasma osmolality ratio will be compared between three main groups of interest (i.e. hypovolemic, euvolemic and hypervolemic patients). As already previously described, these groups will be identified by the gold standard reference defined in the "Study Description" Section.

  At hospital ward admission

• Plasma renin activity (PRA) as a tool for the assessment of Extra-Cellular Fluid (ECF) Volume Status

  PRA (ng/ml/h) will be compared between three main groups of interest (i.e. hypovolemic, euvolemic and hypervolemic patients). As already previously described, these groups will be identified by the gold standard reference defined in the "Study Description" Section.

  At hospital ward admission

• Uric acid as a tool for the assessment of Extra-Cellular Fluid (ECF) Volume Status

  Uric acid (mg/dl) will be compared between three main groups of interest (i.e. hypovolemic, euvolemic and hypervolemic patients). As already previously described, these groups will be identified by the gold standard reference defined in the "Study Description" Section.

  At hospital ward admission

Secondary Outcomes (4)

• Plasma copeptin as a tool for the assessment of Extra-Cellular Fluid (ECF) Volume Status

  At ED admission

• Plasma copeptin / urine sodium ratio as a tool for the assessment of Extra-Cellular Fluid (ECF) Volume Status

  At ED admission

• Plasma copeptin as a tool for the assessment of Extra-Cellular Fluid (ECF) Volume Status

  At hospital ward admission

• Plasma copeptin / urine sodium ratio as a tool for the assessment of Extra-Cellular Fluid (ECF) Volume Status

  At hospital ward admission

Other Outcomes (2)

• Length of hospitalization

  Up to 6 months after ED admission

• Overall mortality

  Up to 6 months after ED admission

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

All consecutive patients admitted at the emergency department (ED) of our hospital in the time frames specified in the inclusion criteria with a detection, at the time of ED access, of moderate-severe hyponatremia (defined as serum sodium \< 130 mmol/L at blood gas analysis).

You may qualify if:

• Access to the emergency department (ED) of our hospital from Monday to Thursday, between 8 am and 6 pm (time constraint needed so that all the necessary laboratory analyzes could be correctly completed)
• Detection at the time of ED access of moderate-severe hyponatremia, defined as serum sodium \< 130 mmol/L at blood gas analysis (BGA)
• Need for hospitalization

You may not qualify if:

• Programmed hospitalization that did not include access through the ED

Sponsors & Collaborators

• A.O.U. Città della Salute e della Scienza: lead

Study Sites (1)

AOU Città della Salute e della Scienza

Turin, Piedmont, 10126, Italy

Location

Related Publications (8)

• Spasovski G, Vanholder R, Allolio B, Annane D, Ball S, Bichet D, Decaux G, Fenske W, Hoorn EJ, Ichai C, Joannidis M, Soupart A, Zietse R, Haller M, van der Veer S, Van Biesen W, Nagler E; Hyponatraemia Guideline Development Group. Clinical practice guideline on diagnosis and treatment of hyponatraemia. Eur J Endocrinol. 2014 Feb 25;170(3):G1-47. doi: 10.1530/EJE-13-1020. Print 2014 Mar.

  PMID: 24569125 BACKGROUND

• Fenske W, Maier SK, Blechschmidt A, Allolio B, Stork S. Utility and limitations of the traditional diagnostic approach to hyponatremia: a diagnostic study. Am J Med. 2010 Jul;123(7):652-7. doi: 10.1016/j.amjmed.2010.01.013.

  PMID: 20609688 BACKGROUND

• Fenske W, Stork S, Blechschmidt A, Maier SG, Morgenthaler NG, Allolio B. Copeptin in the differential diagnosis of hyponatremia. J Clin Endocrinol Metab. 2009 Jan;94(1):123-9. doi: 10.1210/jc.2008-1426. Epub 2008 Nov 4.

  PMID: 18984663 BACKGROUND

• Christ-Crain M, Morgenthaler NG, Fenske W. Copeptin as a biomarker and a diagnostic tool in the evaluation of patients with polyuria-polydipsia and hyponatremia. Best Pract Res Clin Endocrinol Metab. 2016 Mar;30(2):235-47. doi: 10.1016/j.beem.2016.02.003. Epub 2016 Feb 16.

  PMID: 27156761 BACKGROUND

• Sailer CO, Winzeler B, Nigro N, Suter-Widmer I, Arici B, Bally M, Schuetz P, Mueller B, Christ-Crain M. Characteristics and outcomes of patients with profound hyponatraemia due to primary polydipsia. Clin Endocrinol (Oxf). 2017 Nov;87(5):492-499. doi: 10.1111/cen.13384. Epub 2017 Jul 7.

  PMID: 28556237 BACKGROUND

• Boursier G, Almeras M, Buthiau D, Jugant S, Daubin D, Kuster N, Dupuy AM, Ribstein J, Klouche K, Cristol JP. CT-pro-AVP as a tool for assessment of intravascular volume depletion in severe hyponatremia. Clin Biochem. 2015 Jul;48(10-11):640-5. doi: 10.1016/j.clinbiochem.2015.03.013. Epub 2015 Mar 28.

  PMID: 25828045 BACKGROUND

• Nigro N, Winzeler B, Suter-Widmer I, Schuetz P, Arici B, Bally M, Blum CA, Nickel CH, Bingisser R, Bock A, Huber A, Muller B, Christ-Crain M. Evaluation of copeptin and commonly used laboratory parameters for the differential diagnosis of profound hyponatraemia in hospitalized patients: 'The Co-MED Study'. Clin Endocrinol (Oxf). 2017 Mar;86(3):456-462. doi: 10.1111/cen.13243. Epub 2016 Oct 7.

  PMID: 27658031 BACKGROUND

• Kumar S, Berl T. Sodium. Lancet. 1998 Jul 18;352(9123):220-8. doi: 10.1016/S0140-6736(97)12169-9.

  PMID: 9683227 BACKGROUND

MeSH Terms

Conditions

Hyponatremia; Diabetes Insipidus

Condition Hierarchy (Ancestors)

Water-Electrolyte Imbalance; Metabolic Diseases; Nutritional and Metabolic Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Pituitary Diseases; Endocrine System Diseases

Study Officials

• Ezio Ghigo, MD

  AOU Città della Salute e della Scienza Torino

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Medical Doctor, Full Professor in Endocrinology

Study Record Dates

• First Submitted: May 20, 2020
• First Posted: May 26, 2020
• Study Start: June 1, 2018
• Primary Completion: August 31, 2019
• Study Completion: February 28, 2020
• Last Updated: May 26, 2020

Record last verified: 2020-05

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)