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        "titulo" => "Medicina de precisi&#243;n&#58; &#171;Point of Care Ultrasound&#187; &#40;PoCUS&#41; en el abordaje diagn&#243;stico del paciente con hiponatremia"
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Hyponatremia is defined as a plasma sodium concentration<span class="elsevierStyleHsp" style=""></span>&#8804;<span class="elsevierStyleHsp" style=""></span>135<span class="elsevierStyleHsp" style=""></span>mEq&#47;l&#46; It affects about 6&#37;&#8211;7&#37; of the general population and up to 15&#37;&#8211;30&#37; of hospitalized adult patients&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#8211;3</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Its significance rests in the fact that it has been shown to be independently associated with increased mortality&#44; increase in days of hospitalization&#44; gait disturbances&#44; falls&#44; osteoporosis and a significant deterioration in quality of life&#46;<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4&#44;5</span></a> Therefore&#44; its correct identification together with an adequate diagnosis and an appropriate therapeutic approach is essential&#59; however and in some cases it continues to be an unmet medical demand&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">Plasma sodium concentration depends on the content of exchangeable sodium in relation to total body water&#46; Hyponatremia is related to a relative excess of water compared to extracellular sodium &#40;most common&#41; or an absolute loss of sodium &#40;uncommon&#41;&#46; Antidiuretic hormone &#40;ADH&#41; is the main regulator of renal water excretion&#44; being elevated in most clinical scenarios of hyponatremia&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a></p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Clinical case</span><p id="par0020" class="elsevierStylePara elsevierViewall">A 71-year-old woman with clinical history tobacco use up to 2 years ago &#40;exposure 29 pack-years&#41;&#44; dyslipidemia&#44; and bilateral gonarthrosis&#46; Her treatment was only atorvastatin 20<span class="elsevierStyleHsp" style=""></span>mg&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">She went to the emergency room because during the last 2 months she had progressive asthenia&#44; loss of appetite&#44; weakness&#44; and progressive swelling of both lower extremities&#46; On physical examination&#44; he was afebrile&#44; the blood pressure was 135&#47;86<span class="elsevierStyleHsp" style=""></span>mmHg&#44; heart rate of 85 beats per minute&#44; and oxygen saturation of 96&#37;&#46; Hypoventilation at base of the right lung and bilateral pitting edema up to the root of the lower limbs&#46; In the blood chemistry it was found hyponatremia of 122<span class="elsevierStyleHsp" style=""></span>mEq&#47;l &#40;we do not have previous analysis controls in the last year&#44; but it was known that somewhat earlier her serum sodium was normal&#41;&#44; glucose an renal function were normal&#46; Low plasma osmolality 252 mOsm&#47;kg consistent with hypoosmolar hyponatremia&#46; N-terminal B-type natriuretic peptide &#40;NT-proBNP 745<span class="elsevierStyleHsp" style=""></span>pg&#47;mL&#46; Urine Na and K were &#60;20<span class="elsevierStyleHsp" style=""></span>mmol&#47;L&#44; and 36<span class="elsevierStyleHsp" style=""></span>mmol&#47;l respectively with an urinary osmolarity of 295<span class="elsevierStyleHsp" style=""></span>mOsm&#47;kg&#46; Chest x-ray showed the presence of right pleural effusion &#40;no previous chest imaging studies were available&#41; with a normal cardiothoracic index&#44; without clear condensations&#44; masses&#44; or signs of vascular redistribution&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Diagnostic approach</span><p id="par0030" class="elsevierStylePara elsevierViewall">The diagnostic approach most commonly used in clinical practice is based on 3 questions &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#58;<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">1</span><p id="par0035" class="elsevierStylePara elsevierViewall">What is the plasma osmolality&#63; It allows differentiating hypotonic hyponatremias from pseudohyponatremias &#40;hyperlipidemia or hyperproteinemia&#41; and hyponatremias with normal or increased osmolality &#40;hyperglycemia&#44; administration of parenteral substances with osmolar power such as mannitol&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">2</span><p id="par0040" class="elsevierStylePara elsevierViewall">What is the urinary osmolality or electrolyte-free water clearance &#40;Na<span class="elsevierStyleInf">u</span> and K<span class="elsevierStyleInf">o</span>&#41;&#63; It allows to distinguish between hyponatremias in which the kidney eliminates free water adequately and hyponatremias in which the renal response is inadequate&#44; usually due to an excess of circulating ADH&#46;</p></li><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">3</span><p id="par0045" class="elsevierStylePara elsevierViewall">How is the extracellular volume &#40;ECV&#41;&#63; This provides an indication of the ultimate cause that has triggered hyponatremia&#46;</p></li></ul></p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0050" class="elsevierStylePara elsevierViewall">For this purpose&#44; it is essential to know the plasma Osm&#44; urinary Osm&#44; the main ions in urine &#40;Na<span class="elsevierStyleInf">u</span>&#44; K<span class="elsevierStyleInf">u</span>&#41; and to estimate ECV&#44; this last point being sometimes a real challenge for the clinician&#46; Unfortunately&#44; isolated physical examination using parameters such as the degree of mucosal hydration or skin turgor&#44; ocular tone&#44; or the presence or absence of pulmonary crackles and edema&#44; has a low sensitivity and in some cases it is associated with an incorrect diagnosis&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> Chung et al&#46; demonstrated in a study including 58 patients&#44; all with hyponatremia &#40;Na<span class="elsevierStyleInf">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>130<span class="elsevierStyleHsp" style=""></span>mEq&#47;l&#41;&#44; that they only adequately identified 47&#37; of hypovolemic patients and 48&#37; of euvolemic patients&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> This fact highlights the need for the use of other tools for a more accurate assessment of ECV&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">In recent years&#44; the concept of multiparametric assessment of congestion has emerged in which the use of serum biomarkers of congestion has been proposed&#44; such as NT-proBNP produced in response to the stress to which myocardiocytes are subjected by volume and&#47;or pressure overload&#44; and is currently the most widely used biomarker for the diagnosis and prognosis of HF&#46; Its elevation predominates in patients with left ventricular &#40;LV&#41; diastolic dysfunction&#46; Factors such as age and glomerular filtration rate&#44; among others&#44; influence circulating levels of NT-proBNP&#44; therefore its use is limited in a high number of patients&#46; Another novel biomarker&#44; recently described&#44; is carbohydrate antigen 125 &#40;CA 125&#41;&#44; which is produced in serosal cells such as the pleura&#44; peritoneum and pericardium in response to increased tissue hydrostatic pressures and&#47;or inflammation&#44; and which shows a stronger association than NT-proBNP with the rest of the congestion parameters in addition it is not influenced by glomerular filtration&#46; Despite this&#44; it seems reasonable that its combined use could provide complementary information&#44; with NT-proBNP being a &#8220;biochemical window to the left heart&#8221;&#44; while CA 125 both a &#8220;window to the right heart&#8221; in HF and a marker of congestion in other hydropic states&#46;<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">9&#8211;11</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">Including insonation&#44; as the fifth pillar of the physical examination&#44;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> improves the sensitivity and specificity in determining ECV&#46; The ultrasound study includes echocardioscopy for the morphological and functional assessment of the heart&#44; in addition it allows an assessment of the stroke volume and cardiac output&#46; The <span class="elsevierStyleItalic">Venous Excess UltraSound</span> &#40;VExUS&#41; allows phenotyping and grading of venous congestion&#44; and finally&#44; it evaluates the presence of free fluid&#44; both in lungs by lung ultrasound &#40;<span class="elsevierStyleItalic">Lung Ultrasound</span> &#91;LUS&#93;&#41; and in the abdomien&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> For this reason&#44; in recent years different works have been published emphasizing the usefulness of bedside ultrasound &#40;<span class="elsevierStyleItalic">Point-of-Care Ultrasound</span> &#91;PoCUS&#93;&#41; in patients with hyponatremia&#46;<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">14&#8211;18</span></a></p><p id="par0065" class="elsevierStylePara elsevierViewall">Thus&#44; we suggest the implementation of PoCUS in the routine evaluation of the patient with hyponatremia&#44; as well as an update in the diagnostic algorithm for hyponatremia &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#44; bearing in mind that not all ultrasound findings are always present and that hyponatremia often has a multifactorial origin&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0070" class="elsevierStylePara elsevierViewall">Furthermore&#44; although a description of the basic principles of VExUS in the determination of ECV is not the subject of this review&#44; it is important to recognize its main limitations in order to minimize errors both in the acquisition of images and in their correct interpretation &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>&#41;&#46;</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Non-congestive phenotype</span><p id="par0075" class="elsevierStylePara elsevierViewall">In the presence of hypovolemia it is common to identify an A-line pattern &#40;horizontal artifacts&#44; parallel to the pleural line&#41; by LUS&#44; accompanied by decreased systolic volume measured by determining the size LV outflow tract and the integral of the velocity with respect to time calculated at that point&#44; in addition to a preserved right ventricle&#47;LV ratio in the parasternal plane short axis and the presence of a non-dilated inferior vena cava &#40;IVC&#41; with collapsibility &#60;50&#37; &#40;low right atrial pressure&#41;&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">The presence of an IVC of normal diameter and collapsibility&#44; in the absence of free fluid&#44; indicates the absence of venous congestion&#46; However&#44; as a general rule&#44; it does not allow per se to differentiate hypovolemic patients from those with euvolemia&#44; although extreme findings such as a completely collapsed IVC should guide us to the first scenario of hypovolemia&#46; In this situation&#44; the estimation of stroke volume is helpful&#44; being decreased in case of hypovolemia as mentioned above&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Congestive phenotype</span><p id="par0085" class="elsevierStylePara elsevierViewall">In case of congestion&#44; depending on where this predominates&#44; it will be possible to find pleural effusion or the presence of B lines or &#8220;pleural comets&#8221; on lung ultrasound and&#47;or ascites on abdominal insonation&#44; a dilated IVC with collapsibility &#60;50&#37;&#44; plus presence of venous congestion with pathological VExUS and by echocardioscopy a LV systolic and&#47;or diastolic dysfunction &#40;if the etiology is HF&#41; both with low cardiac output &#40;if systolic HF&#41;&#44; or normal-high cardiac output&#44; right ventricular dilatation and&#47;or flattening of the interventricular septum &#40;predominance in diastole if volume overload and in systole-diastole if there is pressure overload&#41;&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Redistributive phenotype</span><p id="par0090" class="elsevierStylePara elsevierViewall">Although congestion and volume overload often go hand in hand&#44; they are not synonymous&#46; Sometimes there is a redistribution of fluid from a venous reservoir such as the splanchnic bed&#44; with increased secondary cardiac output and B lines &#40;only in the case of increased LV filling pressures&#41;&#44; with an adequate variability of ICV&#44; without an initial increase in ECV&#44; as can be seen in certain scenarios of heart failure&#44; in the early phase of hepatorenal syndrome or in the septic patient&#46; If the condition that has precipitated the development of this scenario is not reversed&#44; the elevated sodium and water avidity in the renal tubule&#44; as well as the imbalance between the hydrostatic and oncotic pressures of the intravascular and interstitial compartment&#44; would lead to a more gradual increase in ECV&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Special scenarios</span><p id="par0095" class="elsevierStylePara elsevierViewall">Both hypothyroidism and adrenal insufficiency have been discarded from the algorithm because they present a complex pathophysiological basis in which&#44; depending on the predominant mechanism&#44; congestion may or may not be observed&#44; with its different phenotypes&#44; as well as a variable systolic volume&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">In patients with myxedema&#44; the accumulation of mucopolysaccharides in the interstitium favors the accumulation of water at this level&#44; a low intravascular volume and the consequent non-osmotic release of ADH&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a> In acute severe hypothyroidism&#44; as occurs after discontinuation of thyroid hormone treatment prior to iodine administration in patients with thyroid cancer&#44; decreased glomerular filtration rate and the reduced capacity to excrete free water seem to be the predominant mechanism&#46; In chronic hypothyroidism&#44; non-osmotic ADH release secondary to decreased cardiac output is postulated as the main mechanism&#44; although it is not the only one&#46; However&#44; hypothyroidism outside myxedema is being increasingly discussed as a cause of hypothyroidism&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">In adrenal insufficiency&#44; the low levels of aldosterone&#44; a priori&#44; would favor natriuresis with the development of hypovolemia and secondary release of ADH&#46; However&#44; many times the reduction of volemia is modest&#44; added to the fact that other factors such as the increase in angiotensin II or norepinephrine increase renal sodium reabsorption&#46; Furthermore&#44; glucocorticoid deficiency induces a reduction in blood pressure and cardiac output with non-osmotic release of ADH&#59; in addition&#44; the increase in Corticotrophin-releasing hormone &#40;CRH&#41; levels will act&#44; per se&#44; as an ADH secretagogue&#46;<a class="elsevierStyleCrossRefs" href="#bib0100"><span class="elsevierStyleSup">20&#8211;22</span></a></p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Resolution of the clinical case</span><p id="par0110" class="elsevierStylePara elsevierViewall">The PoCUS study demonstrated the presence of a collapsed&#44; filiform IVC&#44; with a VExUS SCORE of 0 points&#46; At the lung level there was a right pleural effusion without significant B lines&#46; Finally&#44; we should highlight the presence of a discrete amount of free abdominal fluid&#44; as well as a pelvic mass suggestive of tumor&#46; Expanding the study with an urgent thoracic&#44; abdominal and pelvic CT&#44; the presence of a uterine mass with compression of both iliac territories was confirmed&#44; as well as a right pleural effusion and a lung lesion at the right base suggestive of metastasis&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">With all this and despite the presence of pleural effusion&#44; edema and low sodium in urine&#44; which could have been interpreted as hypervolemic hyponatremia with the establishment of diuretic treatment&#46; Instead&#44; fluid therapy was started with 0&#46;9&#37; physiological saline solution with normalization of the serum sodium levels 72<span class="elsevierStyleHsp" style=""></span>h after admission&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">This case illustrates the usefulness of PoCUS in situations in which clinical and biochemical data do not clearly guide the diagnosis&#46; The clearance of electrolyte-free water estimated by the elimination of cations and the osmolar clearance estimated by urinary osmolality provide a contradictory information&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Key concepts</span><p id="par0150" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="lis0010"><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">-</span><p id="par0125" class="elsevierStylePara elsevierViewall">Hyponatremia is not a diagnosis&#44; but the result of a gain of free water due to a reduce excretion&#44; caused by a series of very varied pathologies that may coexist&#46;</p></li><li class="elsevierStyleListItem" id="lsti0025"><span class="elsevierStyleLabel">-</span><p id="par0130" class="elsevierStylePara elsevierViewall">The assessment of ECV is fundamental in the diagnostic approach of hyponatremia&#46; However&#44; the determination of ECV solely based of classical tools relatively often leads to erroneous diagnostic and an incorrect therapeutic approach&#46;</p></li><li class="elsevierStyleListItem" id="lsti0030"><span class="elsevierStyleLabel">-</span><p id="par0135" class="elsevierStylePara elsevierViewall">Bedside ultrasound or PoCUS has become a very useful tool to complement the physical examination and analytical parameters in the patient with hyponatremia&#46;</p></li><li class="elsevierStyleListItem" id="lsti0035"><span class="elsevierStyleLabel">-</span><p id="par0140" class="elsevierStylePara elsevierViewall">The use of PoCUS answers a specific question quickly&#44; noninvasively and reproducibly&#46; However&#44; its performance and interpretation is not without limitations&#44; so it is considered necessary to increase its presence in the different training programs of the specialty and in the scientific societies of Nephrology&#46;</p></li></ul></p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Conflict of interests</span><p id="par0145" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflict of interest&#46;</p></span></span>"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Hyponatremia is a multifactorial disorder defined as a decrease in plasma sodium concentration&#46; Its differential diagnosis requires an adequate evaluation of the extracellular volume &#40;ECV&#41;&#46; However&#44; ECV determination&#44; simply based on the clinical history&#44; vital signs&#44; physical examination&#44; and laboratory findings can leads to misdiagnosis and inappropriate treatment&#46; The use of Point-of-Care Ultrasound &#40;POCUS&#41;&#44; through the combination of Lung Ultrasound &#40;LUS&#41;&#44; Venous Excess UltraSound &#40;VExUS&#41; and Focused Cardiac Ultrasound &#40;FoCUS&#41;&#44; allows a much more accurate holistic assessment of the patient&#39;s ECV status in combination with the other parameters&#46;</p></span>"
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        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">La hiponatremia es un trastorno multifactorial definido como una disminuci&#243;n en la concentraci&#243;n plasm&#225;tica de sodio&#46; Su diagn&#243;stico diferencial requiere una evaluaci&#243;n adecuada del volumen extracelular&#46; Sin embargo&#44; la determinaci&#243;n del volumen extracelular&#44; simplemente basada en la historia cl&#237;nica&#44; las constantes vitales&#44; el examen f&#237;sico y los hallazgos de laboratorio&#44; conducen en ocasiones a un diagn&#243;stico err&#243;neo por lo que el enfoque terap&#233;utico puede ser equivocado&#46; El empleo de ecograf&#237;a a pie de cama &#40;<span class="elsevierStyleItalic">Point-of-Care Ultrasound</span> &#91;PoCUS&#93;&#41;&#44; mediante la combinaci&#243;n de ecograf&#237;a pulmonar &#40;<span class="elsevierStyleItalic">Lung Ultrasound</span> &#91;LUS&#93;&#41;&#44; <span class="elsevierStyleItalic">Venous Excess UltraSound</span> &#40;VExUS&#41; y la ecocardioscopia &#40;<span class="elsevierStyleItalic">Focused Cardiac Ultrasound</span> &#91;FoCUS&#93;&#41; permiten&#44; en combinaci&#243;n con el resto de los par&#225;metros&#44; una valoraci&#243;n hol&#237;stica mucho m&#225;s precisa del estado del volumen extracelular del paciente&#46;</p></span>"
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Brief review
Precision medicine: “Point of Care Ultrasound” (PoCUS) in the diagnostic approach to the patient with hyponatremia
Medicina de precisión: «Point of Care Ultrasound» (PoCUS) en el abordaje diagnóstico del paciente con hiponatremia
Jaime Mazón Ruiza,
Corresponding author
jaimemruiz92@gmail.com

Corresponding author.
, Eduardo Josue Banegasa, Jose Luis Pérez Cangab, Luis Bravo González-Blasa, Natalia Menéndez Garcíaa, Adriana Cavada Bustamantea, Mara Serrano Sotoc,d, Emilio Sánchez Álvareze, Roberto Alcázar Arroyof, Gregorio A. Romero-Gonzálezd,g
a Servicio de Nefrología, Hospital Universitario Central de Asturias, Oviedo, Spain
b Servicio de Nefrología, Hospital Universitario San Agustín, Avilés, Spain
c Servicio de Nefrología, Hospital Universitario Marqués de Valdecilla, Santander, Spain
d International Renal Research Institute Vicenza, Vicenza, Italy
e Servicio de Nefrología, Hospital Universitario de Cabueñes, Gijón, Spain
f Servicio de Nefrología, Hospital Universitario Infanta Leonor, Madrid, Spain
g Servicio de Nefrología, Hospital Universitari Germans Trias i Pujol, Badalona, Spain
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Hyponatremia is defined as a plasma sodium concentration<span class="elsevierStyleHsp" style=""></span>&#8804;<span class="elsevierStyleHsp" style=""></span>135<span class="elsevierStyleHsp" style=""></span>mEq&#47;l&#46; It affects about 6&#37;&#8211;7&#37; of the general population and up to 15&#37;&#8211;30&#37; of hospitalized adult patients&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#8211;3</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Its significance rests in the fact that it has been shown to be independently associated with increased mortality&#44; increase in days of hospitalization&#44; gait disturbances&#44; falls&#44; osteoporosis and a significant deterioration in quality of life&#46;<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4&#44;5</span></a> Therefore&#44; its correct identification together with an adequate diagnosis and an appropriate therapeutic approach is essential&#59; however and in some cases it continues to be an unmet medical demand&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">Plasma sodium concentration depends on the content of exchangeable sodium in relation to total body water&#46; Hyponatremia is related to a relative excess of water compared to extracellular sodium &#40;most common&#41; or an absolute loss of sodium &#40;uncommon&#41;&#46; Antidiuretic hormone &#40;ADH&#41; is the main regulator of renal water excretion&#44; being elevated in most clinical scenarios of hyponatremia&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a></p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Clinical case</span><p id="par0020" class="elsevierStylePara elsevierViewall">A 71-year-old woman with clinical history tobacco use up to 2 years ago &#40;exposure 29 pack-years&#41;&#44; dyslipidemia&#44; and bilateral gonarthrosis&#46; Her treatment was only atorvastatin 20<span class="elsevierStyleHsp" style=""></span>mg&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">She went to the emergency room because during the last 2 months she had progressive asthenia&#44; loss of appetite&#44; weakness&#44; and progressive swelling of both lower extremities&#46; On physical examination&#44; he was afebrile&#44; the blood pressure was 135&#47;86<span class="elsevierStyleHsp" style=""></span>mmHg&#44; heart rate of 85 beats per minute&#44; and oxygen saturation of 96&#37;&#46; Hypoventilation at base of the right lung and bilateral pitting edema up to the root of the lower limbs&#46; In the blood chemistry it was found hyponatremia of 122<span class="elsevierStyleHsp" style=""></span>mEq&#47;l &#40;we do not have previous analysis controls in the last year&#44; but it was known that somewhat earlier her serum sodium was normal&#41;&#44; glucose an renal function were normal&#46; Low plasma osmolality 252 mOsm&#47;kg consistent with hypoosmolar hyponatremia&#46; N-terminal B-type natriuretic peptide &#40;NT-proBNP 745<span class="elsevierStyleHsp" style=""></span>pg&#47;mL&#46; Urine Na and K were &#60;20<span class="elsevierStyleHsp" style=""></span>mmol&#47;L&#44; and 36<span class="elsevierStyleHsp" style=""></span>mmol&#47;l respectively with an urinary osmolarity of 295<span class="elsevierStyleHsp" style=""></span>mOsm&#47;kg&#46; Chest x-ray showed the presence of right pleural effusion &#40;no previous chest imaging studies were available&#41; with a normal cardiothoracic index&#44; without clear condensations&#44; masses&#44; or signs of vascular redistribution&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Diagnostic approach</span><p id="par0030" class="elsevierStylePara elsevierViewall">The diagnostic approach most commonly used in clinical practice is based on 3 questions &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#58;<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">1</span><p id="par0035" class="elsevierStylePara elsevierViewall">What is the plasma osmolality&#63; It allows differentiating hypotonic hyponatremias from pseudohyponatremias &#40;hyperlipidemia or hyperproteinemia&#41; and hyponatremias with normal or increased osmolality &#40;hyperglycemia&#44; administration of parenteral substances with osmolar power such as mannitol&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">2</span><p id="par0040" class="elsevierStylePara elsevierViewall">What is the urinary osmolality or electrolyte-free water clearance &#40;Na<span class="elsevierStyleInf">u</span> and K<span class="elsevierStyleInf">o</span>&#41;&#63; It allows to distinguish between hyponatremias in which the kidney eliminates free water adequately and hyponatremias in which the renal response is inadequate&#44; usually due to an excess of circulating ADH&#46;</p></li><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">3</span><p id="par0045" class="elsevierStylePara elsevierViewall">How is the extracellular volume &#40;ECV&#41;&#63; This provides an indication of the ultimate cause that has triggered hyponatremia&#46;</p></li></ul></p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0050" class="elsevierStylePara elsevierViewall">For this purpose&#44; it is essential to know the plasma Osm&#44; urinary Osm&#44; the main ions in urine &#40;Na<span class="elsevierStyleInf">u</span>&#44; K<span class="elsevierStyleInf">u</span>&#41; and to estimate ECV&#44; this last point being sometimes a real challenge for the clinician&#46; Unfortunately&#44; isolated physical examination using parameters such as the degree of mucosal hydration or skin turgor&#44; ocular tone&#44; or the presence or absence of pulmonary crackles and edema&#44; has a low sensitivity and in some cases it is associated with an incorrect diagnosis&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> Chung et al&#46; demonstrated in a study including 58 patients&#44; all with hyponatremia &#40;Na<span class="elsevierStyleInf">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>130<span class="elsevierStyleHsp" style=""></span>mEq&#47;l&#41;&#44; that they only adequately identified 47&#37; of hypovolemic patients and 48&#37; of euvolemic patients&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> This fact highlights the need for the use of other tools for a more accurate assessment of ECV&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">In recent years&#44; the concept of multiparametric assessment of congestion has emerged in which the use of serum biomarkers of congestion has been proposed&#44; such as NT-proBNP produced in response to the stress to which myocardiocytes are subjected by volume and&#47;or pressure overload&#44; and is currently the most widely used biomarker for the diagnosis and prognosis of HF&#46; Its elevation predominates in patients with left ventricular &#40;LV&#41; diastolic dysfunction&#46; Factors such as age and glomerular filtration rate&#44; among others&#44; influence circulating levels of NT-proBNP&#44; therefore its use is limited in a high number of patients&#46; Another novel biomarker&#44; recently described&#44; is carbohydrate antigen 125 &#40;CA 125&#41;&#44; which is produced in serosal cells such as the pleura&#44; peritoneum and pericardium in response to increased tissue hydrostatic pressures and&#47;or inflammation&#44; and which shows a stronger association than NT-proBNP with the rest of the congestion parameters in addition it is not influenced by glomerular filtration&#46; Despite this&#44; it seems reasonable that its combined use could provide complementary information&#44; with NT-proBNP being a &#8220;biochemical window to the left heart&#8221;&#44; while CA 125 both a &#8220;window to the right heart&#8221; in HF and a marker of congestion in other hydropic states&#46;<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">9&#8211;11</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">Including insonation&#44; as the fifth pillar of the physical examination&#44;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> improves the sensitivity and specificity in determining ECV&#46; The ultrasound study includes echocardioscopy for the morphological and functional assessment of the heart&#44; in addition it allows an assessment of the stroke volume and cardiac output&#46; The <span class="elsevierStyleItalic">Venous Excess UltraSound</span> &#40;VExUS&#41; allows phenotyping and grading of venous congestion&#44; and finally&#44; it evaluates the presence of free fluid&#44; both in lungs by lung ultrasound &#40;<span class="elsevierStyleItalic">Lung Ultrasound</span> &#91;LUS&#93;&#41; and in the abdomien&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> For this reason&#44; in recent years different works have been published emphasizing the usefulness of bedside ultrasound &#40;<span class="elsevierStyleItalic">Point-of-Care Ultrasound</span> &#91;PoCUS&#93;&#41; in patients with hyponatremia&#46;<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">14&#8211;18</span></a></p><p id="par0065" class="elsevierStylePara elsevierViewall">Thus&#44; we suggest the implementation of PoCUS in the routine evaluation of the patient with hyponatremia&#44; as well as an update in the diagnostic algorithm for hyponatremia &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#44; bearing in mind that not all ultrasound findings are always present and that hyponatremia often has a multifactorial origin&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0070" class="elsevierStylePara elsevierViewall">Furthermore&#44; although a description of the basic principles of VExUS in the determination of ECV is not the subject of this review&#44; it is important to recognize its main limitations in order to minimize errors both in the acquisition of images and in their correct interpretation &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>&#41;&#46;</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Non-congestive phenotype</span><p id="par0075" class="elsevierStylePara elsevierViewall">In the presence of hypovolemia it is common to identify an A-line pattern &#40;horizontal artifacts&#44; parallel to the pleural line&#41; by LUS&#44; accompanied by decreased systolic volume measured by determining the size LV outflow tract and the integral of the velocity with respect to time calculated at that point&#44; in addition to a preserved right ventricle&#47;LV ratio in the parasternal plane short axis and the presence of a non-dilated inferior vena cava &#40;IVC&#41; with collapsibility &#60;50&#37; &#40;low right atrial pressure&#41;&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">The presence of an IVC of normal diameter and collapsibility&#44; in the absence of free fluid&#44; indicates the absence of venous congestion&#46; However&#44; as a general rule&#44; it does not allow per se to differentiate hypovolemic patients from those with euvolemia&#44; although extreme findings such as a completely collapsed IVC should guide us to the first scenario of hypovolemia&#46; In this situation&#44; the estimation of stroke volume is helpful&#44; being decreased in case of hypovolemia as mentioned above&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Congestive phenotype</span><p id="par0085" class="elsevierStylePara elsevierViewall">In case of congestion&#44; depending on where this predominates&#44; it will be possible to find pleural effusion or the presence of B lines or &#8220;pleural comets&#8221; on lung ultrasound and&#47;or ascites on abdominal insonation&#44; a dilated IVC with collapsibility &#60;50&#37;&#44; plus presence of venous congestion with pathological VExUS and by echocardioscopy a LV systolic and&#47;or diastolic dysfunction &#40;if the etiology is HF&#41; both with low cardiac output &#40;if systolic HF&#41;&#44; or normal-high cardiac output&#44; right ventricular dilatation and&#47;or flattening of the interventricular septum &#40;predominance in diastole if volume overload and in systole-diastole if there is pressure overload&#41;&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Redistributive phenotype</span><p id="par0090" class="elsevierStylePara elsevierViewall">Although congestion and volume overload often go hand in hand&#44; they are not synonymous&#46; Sometimes there is a redistribution of fluid from a venous reservoir such as the splanchnic bed&#44; with increased secondary cardiac output and B lines &#40;only in the case of increased LV filling pressures&#41;&#44; with an adequate variability of ICV&#44; without an initial increase in ECV&#44; as can be seen in certain scenarios of heart failure&#44; in the early phase of hepatorenal syndrome or in the septic patient&#46; If the condition that has precipitated the development of this scenario is not reversed&#44; the elevated sodium and water avidity in the renal tubule&#44; as well as the imbalance between the hydrostatic and oncotic pressures of the intravascular and interstitial compartment&#44; would lead to a more gradual increase in ECV&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Special scenarios</span><p id="par0095" class="elsevierStylePara elsevierViewall">Both hypothyroidism and adrenal insufficiency have been discarded from the algorithm because they present a complex pathophysiological basis in which&#44; depending on the predominant mechanism&#44; congestion may or may not be observed&#44; with its different phenotypes&#44; as well as a variable systolic volume&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">In patients with myxedema&#44; the accumulation of mucopolysaccharides in the interstitium favors the accumulation of water at this level&#44; a low intravascular volume and the consequent non-osmotic release of ADH&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a> In acute severe hypothyroidism&#44; as occurs after discontinuation of thyroid hormone treatment prior to iodine administration in patients with thyroid cancer&#44; decreased glomerular filtration rate and the reduced capacity to excrete free water seem to be the predominant mechanism&#46; In chronic hypothyroidism&#44; non-osmotic ADH release secondary to decreased cardiac output is postulated as the main mechanism&#44; although it is not the only one&#46; However&#44; hypothyroidism outside myxedema is being increasingly discussed as a cause of hypothyroidism&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">In adrenal insufficiency&#44; the low levels of aldosterone&#44; a priori&#44; would favor natriuresis with the development of hypovolemia and secondary release of ADH&#46; However&#44; many times the reduction of volemia is modest&#44; added to the fact that other factors such as the increase in angiotensin II or norepinephrine increase renal sodium reabsorption&#46; Furthermore&#44; glucocorticoid deficiency induces a reduction in blood pressure and cardiac output with non-osmotic release of ADH&#59; in addition&#44; the increase in Corticotrophin-releasing hormone &#40;CRH&#41; levels will act&#44; per se&#44; as an ADH secretagogue&#46;<a class="elsevierStyleCrossRefs" href="#bib0100"><span class="elsevierStyleSup">20&#8211;22</span></a></p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Resolution of the clinical case</span><p id="par0110" class="elsevierStylePara elsevierViewall">The PoCUS study demonstrated the presence of a collapsed&#44; filiform IVC&#44; with a VExUS SCORE of 0 points&#46; At the lung level there was a right pleural effusion without significant B lines&#46; Finally&#44; we should highlight the presence of a discrete amount of free abdominal fluid&#44; as well as a pelvic mass suggestive of tumor&#46; Expanding the study with an urgent thoracic&#44; abdominal and pelvic CT&#44; the presence of a uterine mass with compression of both iliac territories was confirmed&#44; as well as a right pleural effusion and a lung lesion at the right base suggestive of metastasis&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">With all this and despite the presence of pleural effusion&#44; edema and low sodium in urine&#44; which could have been interpreted as hypervolemic hyponatremia with the establishment of diuretic treatment&#46; Instead&#44; fluid therapy was started with 0&#46;9&#37; physiological saline solution with normalization of the serum sodium levels 72<span class="elsevierStyleHsp" style=""></span>h after admission&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">This case illustrates the usefulness of PoCUS in situations in which clinical and biochemical data do not clearly guide the diagnosis&#46; The clearance of electrolyte-free water estimated by the elimination of cations and the osmolar clearance estimated by urinary osmolality provide a contradictory information&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Key concepts</span><p id="par0150" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="lis0010"><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">-</span><p id="par0125" class="elsevierStylePara elsevierViewall">Hyponatremia is not a diagnosis&#44; but the result of a gain of free water due to a reduce excretion&#44; caused by a series of very varied pathologies that may coexist&#46;</p></li><li class="elsevierStyleListItem" id="lsti0025"><span class="elsevierStyleLabel">-</span><p id="par0130" class="elsevierStylePara elsevierViewall">The assessment of ECV is fundamental in the diagnostic approach of hyponatremia&#46; However&#44; the determination of ECV solely based of classical tools relatively often leads to erroneous diagnostic and an incorrect therapeutic approach&#46;</p></li><li class="elsevierStyleListItem" id="lsti0030"><span class="elsevierStyleLabel">-</span><p id="par0135" class="elsevierStylePara elsevierViewall">Bedside ultrasound or PoCUS has become a very useful tool to complement the physical examination and analytical parameters in the patient with hyponatremia&#46;</p></li><li class="elsevierStyleListItem" id="lsti0035"><span class="elsevierStyleLabel">-</span><p id="par0140" class="elsevierStylePara elsevierViewall">The use of PoCUS answers a specific question quickly&#44; noninvasively and reproducibly&#46; However&#44; its performance and interpretation is not without limitations&#44; so it is considered necessary to increase its presence in the different training programs of the specialty and in the scientific societies of Nephrology&#46;</p></li></ul></p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Conflict of interests</span><p id="par0145" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflict of interest&#46;</p></span></span>"
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        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">La hiponatremia es un trastorno multifactorial definido como una disminuci&#243;n en la concentraci&#243;n plasm&#225;tica de sodio&#46; Su diagn&#243;stico diferencial requiere una evaluaci&#243;n adecuada del volumen extracelular&#46; Sin embargo&#44; la determinaci&#243;n del volumen extracelular&#44; simplemente basada en la historia cl&#237;nica&#44; las constantes vitales&#44; el examen f&#237;sico y los hallazgos de laboratorio&#44; conducen en ocasiones a un diagn&#243;stico err&#243;neo por lo que el enfoque terap&#233;utico puede ser equivocado&#46; El empleo de ecograf&#237;a a pie de cama &#40;<span class="elsevierStyleItalic">Point-of-Care Ultrasound</span> &#91;PoCUS&#93;&#41;&#44; mediante la combinaci&#243;n de ecograf&#237;a pulmonar &#40;<span class="elsevierStyleItalic">Lung Ultrasound</span> &#91;LUS&#93;&#41;&#44; <span class="elsevierStyleItalic">Venous Excess UltraSound</span> &#40;VExUS&#41; y la ecocardioscopia &#40;<span class="elsevierStyleItalic">Focused Cardiac Ultrasound</span> &#91;FoCUS&#93;&#41; permiten&#44; en combinaci&#243;n con el resto de los par&#225;metros&#44; una valoraci&#243;n hol&#237;stica mucho m&#225;s precisa del estado del volumen extracelular del paciente&#46;</p></span>"
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ISSN: 20132514
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