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

Sponsor

Azienda Ospedaliera Città della Salute e della Scienza di Torino (Other)

Overall Status

Completed

CT.gov ID

NCT04402190

Collaborator

(none)

123

Enrollment

Location

20.9

Actual Duration (Months)

5.9

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Hyponatremia Hyponatremia With Extracellular Fluid Depletion Hyponatremia With Normal Extracellular Fluid Volume Hyponatremia With Excess Extracellular Fluid Volume

Detailed Description

Hyponatremia is the most frequent electrolyte disorder encountered in clinical practice and is often associated with increased mortality, morbidity and risk of hospitalization. The patient approach, however, is still problematic, above all because hyponatremia is a manifestation correlated to various pathological conditions, with complex etiopathogenesis.

The most commonly used classification of hypotonic hyponatremia is, nowadays, the one described in a famous review by Kumar and Berl (see Bibliography). Probably the most crucial point in this classification is represented by the correct assessment of Extracellular Fluid Volume Status (i.e. hypovolemia, euvolemia, hypervolemia).

In the current study, the reference test (gold standard) for the definitive assessment of hyponatremia subtype classification and patient volume status was a post-discharge re-evaluation of all the available evidence (with the exception of plasma copeptin levels) carried out by two independent neuroendocrinologists with specific expertise in sodium disorders. In case of disagreement, the experts proceeded to a discussion and comparison of their opinions, in order to produce a shared one.

Using this gold standard, the main aims of this observational prospective study were:

to estimate the diagnostic accuracy of the clinicians in identifying the subtype of hyponatremia at the first evaluation of the patients in the ED and then at the admission to the wards;
to evaluate the diagnostic accuracy of the most important methods suggested by the literature (clinical, imaging, biochemical) for the assessment of Extracellular Fluid Volume.

In addition to this, in recent years copeptin has been shown to be a promising parameter for the evaluation of sodium disorders and water imbalances, but its diagnostic role in the setting of hyponatremic patients is still largely unknown. Therefore, a secondary objective of the study was to specifically evaluate the utility of copeptin (whose values - as specified before - were hidden to the neuroendocrinologists in charge of defining the gold standard diagnoses for each patient) for the assessment of hyponatremia subtype classification and patient volume status.

Study Design

Study Type:

Observational

Actual Enrollment :

123 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

Hypotonic Hyponatremia: Criteria for the Correct Classification of Its Etiology and of Patient Volume Status at the Access in the Emergency Department and at the Subsequent Re-evaluation in Hospital Wards

Actual Study Start Date :

Jun 1, 2018

Actual Primary Completion Date :

Aug 31, 2019

Actual Study Completion Date :

Feb 28, 2020

Outcome Measures

Primary Outcome Measures

Subtype classification of hypotonic hyponatremia according to the overall judgment of the clinical case by the point-of-care clinician [At ED admission]
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.
Subtype classification of hypotonic hyponatremia according to the overall judgment of the clinical case by the point-of-care clinician [At hospital ward admission]
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.
Physical Examination (PE) as a tool for the assessment of Extra-Cellular Fluid (ECF) Volume Status [At ED admission]
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).
Physical Examination (PE) as a tool for the assessment of Extra-Cellular Fluid (ECF) Volume Status [At hospital ward admission]
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).
Inferior Vena Cava (IVC) ultrasound evaluation as a tool for the assessment of Extra-Cellular Fluid (ECF) Volume Status [At ED admission]
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).
Inferior Vena Cava (IVC) ultrasound evaluation as a tool for the assessment of Extra-Cellular Fluid (ECF) Volume Status [At hospital ward admission]
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).
Serum creatinine as a tool for the assessment of Extra-Cellular Fluid (ECF) Volume Status [At ED admission]
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.
Serum urea as a tool for the assessment of Extra-Cellular Fluid (ECF) Volume Status [At ED admission]
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.
Serum urea / serum creatinine ratio as a tool for the assessment of Extra-Cellular Fluid (ECF) Volume Status [At ED admission]
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.
Urine sodium as a tool for the assessment of Extra-Cellular Fluid (ECF) Volume Status [At ED admission]
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.
Urine sodium / urine osmolality ratio as a tool for the assessment of Extra-Cellular Fluid (ECF) Volume Status [At ED admission]
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.
Urine sodium / plasma osmolality ratio as a tool for the assessment of Extra-Cellular Fluid (ECF) Volume Status [At ED admission]
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.
Serum NT-proBNP as a tool for the assessment of Extra-Cellular Fluid (ECF) Volume Status [At ED admission]
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.
Serum NT-proBNP / urine sodium ratio as a tool for the assessment of Extra-Cellular Fluid (ECF) Volume Status [At ED admission]
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.
Serum creatinine as a tool for the assessment of Extra-Cellular Fluid (ECF) Volume Status [At hospital ward admission]
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.
Serum urea as a tool for the assessment of Extra-Cellular Fluid (ECF) Volume Status [At hospital ward admission]
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.
Serum urea / serum creatinine ratio as a tool for the assessment of Extra-Cellular Fluid (ECF) Volume Status [At hospital ward admission]
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.
Urine sodium as a tool for the assessment of Extra-Cellular Fluid (ECF) Volume Status [At hospital ward admission]
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.
Urine sodium / urine osmolality ratio as a tool for the assessment of Extra-Cellular Fluid (ECF) Volume Status [At hospital ward admission]
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.
Urine sodium / plasma osmolality ratio as a tool for the assessment of Extra-Cellular Fluid (ECF) Volume Status [At hospital ward admission]
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.
Plasma renin activity (PRA) as a tool for the assessment of Extra-Cellular Fluid (ECF) Volume Status [At hospital ward admission]
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.
Uric acid as a tool for the assessment of Extra-Cellular Fluid (ECF) Volume Status [At hospital ward admission]
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.

Secondary Outcome Measures

Plasma copeptin as a tool for the assessment of Extra-Cellular Fluid (ECF) Volume Status [At ED admission]
Plasma copeptin (pmol/L) 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.
Plasma copeptin / urine sodium ratio as a tool for the assessment of Extra-Cellular Fluid (ECF) Volume Status [At ED admission]
Plasma copeptin / 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.
Plasma copeptin as a tool for the assessment of Extra-Cellular Fluid (ECF) Volume Status [At hospital ward admission]
Plasma copeptin (pmol/L) 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.
Plasma copeptin / urine sodium ratio as a tool for the assessment of Extra-Cellular Fluid (ECF) Volume Status [At hospital ward admission]
Plasma copeptin / 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.

Other Outcome Measures

Length of hospitalization [Up to 6 months after ED admission]
The length of hospitalization will be compared across subgroups according to hyponatremia subtype classification. As already previously described, these subgroups will be identified by the gold standard reference defined in the "Study Description" Section.
Overall mortality [Up to 6 months after ED admission]
All deaths occurring during hospitalization and/or within 6 months after hospital discharge will be registered. The overall mortality will be compared across subgroups (using a survival analysis model) according to hyponatremia subtype classification. As already previously described, these subgroups will be identified by the gold standard reference defined in the "Study Description" Section.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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