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Clinical practice guideline on diagnosisand treatment of hyponatraemia
Goce Spasovski, Raymond Vanholder
, Bruno Allolio
, Djillali Annane
, Steve Ball
,Daniel Bichet
, Guy Decaux
, Wiebke Fenske
, Ewout J Hoorn
, Carole Ichai
,Michael Joannidis
, Alain Soupart
, Robert Zietse
, Maria Haller
, Sabine van derVeer
on behalfof theHyponatraemia GuidelineDevelopment Group
State University Hospital Skopje, Skopje, Macedonia,
Ghent University Hospital, Ghent, Belgium,
Wu¨rzburgUniversity Hospital, Wu¨rzburg, Germany,
Raymond Poincare´ Hospital, University of Versailles Saint Quentin, Paris,France,
Newcastle Hospitals and Newcastle University, Newcastle, UK,
Sacre´-Coeur Hospital, University ofMontreal, Montreal, Quebec, Canada,
Erasmus University Hospital, Brussels, Belgium,
Erasmus Medical Centre,Rotterdam, The Netherlands,
Nice University Hospital, Nice, France,
Innsbruck University Hospital, Innsbruck,Austria,
KH Elisabethinen Linz, Linz, Austria and
Amsterdam Medical Centre, Amsterdam, The NetherlandsCorrespondenceshould be addressed toThe Editorial office, EuropeanJournal of Endocrinology;Email: eje@bioscientifica.com
Hyponatraemia, defined as a serum sodium concentration
135 mmol/l, is the most common disorder of body fluid andelectrolyte balanceencountered inclinical practice.It canlead toa widespectrumof clinical symptoms,from subtle tosevereor even life threatening, and is associated with increased mortality, morbidity and length of hospital stay in patientspresenting with a range of conditions. Despite this, the management of patients remains problematic. The prevalence ofhyponatraemia in widely different conditions and the fact that hyponatraemia is managed by clinicians with a broad varietyof backgrounds have fostered diverse institution- and speciality-based approaches to diagnosis and treatment. To obtain acommon and holistic view, the European Society of Intensive Care Medicine (ESICM), the European Society of Endocrinology(ESE) and the European Renal Association – European Dialysis and Transplant Association (ERA–EDTA), represented byEuropean Renal Best Practice (ERBP), have developed the Clinical Practice Guideline on the diagnostic approach andtreatment of hyponatraemia as a joint venture of three societies representing specialists with a natural interest inhyponatraemia. In addition to a rigorous approach to methodology and evaluation, we were keen to ensure that thedocument focused on patient-important outcomes and included utility for clinicians involved in everyday practice.
European Journal of Endocrinology 
, G1–G47
1. Foreword
Hyponatraemia is a clinical feature in 15–20% of emergency admissions to hospital. It is associated withincreased mortality, morbidity and length of hospitalstay in patients presenting with a range of conditions.Hyponatraemia is therefore both common and important.Despite this, the management of patients remainsproblematic. The prevalence of hyponatraemia underwidely different conditions and the fact that hypo-natraemia is managed by clinicians with a broad varietyof backgrounds have fostered diverse institution- andspeciality-based approaches to diagnosis and treatment.However, the paucity of well-designed, prospectivestudies in the field has limited the evidence-base tothese approaches. Previous guidance has often beenbased on experience or practice, without a systematicapproach to evaluation and lacking a clear, patient-centred focus. Clinicians using previous guidance mayhave noted a number of problems:
 Ithasbeendifficulttofollowtheguidanceinday-to-dayclinical practice, especially by doctors in training whoare managing patients in the ‘front line’. Here, therequirement is for clear, concise and practical adviceon what has to be done, including during the critical
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Clinical PracticeGuideline
G Spasovski and others Diagnosis and treatment ofhyponatraemia
2014 European Society of Endocrinology,European Society of Intensive Care Medicine,European Renal Association-European Dialysisand Transplant AssociationDOI: 10.1530/EJE-13-1020Published by Bioscientifica Ltd.The guidelines were peer reviewed by the owner societies and by external refereesprior to publication.
‘out-of-office hours’ period. Complex diagnostic algo-rithms and time-consuming investigations are realbarriers to implementation in this context.
 The guidance has been over-simplistic and does notreflect the range of clinical problems encountered inday-to-day practice.
 The guidance has been limited by a diagnosis-,mechanism- or duration-based approach to treatment,failing to recognise that establishing the diagnosis,mechanism or duration of hyponatraemia may bedifficult. Previous guidance has mostly used durationof hyponatraemia as a key point on which to basemanagement. Yet, duration can be hard to establish,especially in emergency settings. Decisions often haveto be made on limited information.
 The guidance has demonstrated an institutional orspecialty-specific bias, limiting implementation acrosssites and clinical disciplines. This is best demonstratedin institution- or speciality-specific approaches toinvestigations.
 The guidance has used a biochemical focus, failingto prioritise clinical status in decisions on treatmentoptions. Clinicians know that the degree of biochemicalhyponatraemia does not always match the clinical state of the patient. Guidance that bases management advicesimplyontheserumsodiumconcentrationmaybecountertoclinicalexperience,riskingcredibilityandengagement.Together, these factors have limited the utility of previous advice. Two emerging themes require that werevisit the area:1. Theclearrecognitionoftheimportanceofevidence-basedapproaches to patient care to enhance quality, improvesafety and establish a clear and transparent frameworkfor service development and health care provision.2. The advent of new diagnostics and therapeutics, high-lighting the need for a valid, reliable and transparentprocess of evaluation to support key decisions.To obtain a common and holistic view, the EuropeanSociety of Intensive Care Medicine (ESICM), the EuropeanSociety of Endocrinology (ESE) and the European RenalAssociation–EuropeanDialysisandTransplantAssociation(ERA–EDTA), represented by European Renal Best Practice(ERBP), have developed new guidance on the diagnosticapproach and treatment of hyponatraemia. In addition toa rigorous approach to methodology and evaluation, wewere keen to ensure that the document focused onpatient-important outcomes and included utility forclinicians involved in everyday practice.
2. Composition of the GuidelineDevelopment Group
A steering committee with representatives of all the threesocieties convened in October 2010 and decided on thecomposition oftheGuideline Development Group, takinginto account the clinical and research expertise of eachproposed candidate.
Guideline development group co-chairs
Goce Spasovski
Consultant Nephrologist, State University HospitalSkopje, Skopje, Macedonia.
Raymond Vanholder
Consultant Nephrologist, Ghent University Hospital,Ghent, Belgium.
Work Group
Bruno Allolio
ConsultantEndocrinologist,Wu¨rzburgUniversityHospital,Wu¨rzburg, Germany.
Djillali Annane
Consultant Intensivist, Raymond Poincare´ Hospital,University of Versailles Saint Quentin, Paris, France.
Steve Ball
Consultant Endocrinologist, Newcastle Hospitals andNewcastle University, Newcastle, UK.
Daniel Bichet
Consultant Nephrologist, Hospital, Montreal, Canada.
Guy Decaux
ConsultantInternalMedicine,ErasmusUniversityHospital,Brussels, Belgium.
Wiebke Fenske
Consultant Endocrinologist, Wu¨rzburg UniversityHospital, Wu¨rzburg, Germany.
Ewout Hoorn
Consultant Nephrologist, Erasmus Medical Centre,Rotterdam, The Netherlands.
Carole Ichai
Consultant Intensivist, Nice University Hospital, Nice,France.
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Clinical Practice Guideline
 G Spasovski and others Diagnosis and treatment ofhyponatraemia
Michael Joannidis
Consultant Intensivist, Innsbruck University Hospital,Innsbruck, Austria.
Alain Soupart
ConsultantInternalMedicine,ErasmusUniversityHospital,Brussels, Belgium.
Robert Zietse
Consultant Nephrologist, Erasmus Medical Centre,Rotterdam, The Netherlands.
ERBP methods support team
Maria Haller
Specialist Registrar Nephrology, KH Elisabethinen Linz,Linz, Austria.
Evi Nagler
SpecialistRegistrarNephrology,GhentUniversityHospital,Ghent, Belgium.
Wim Van Biesen
ConsultantNephrologist,ChairofERBP,GhentUniversityHospital, Belgium.
Sabine van der Veer
Implementation Specialist, Amsterdam Medical Centre,Amsterdam, The Netherlands.
3. Purpose and scope of this guideline
3.1. Why was this guideline produced?
The purpose of this Clinical Practice Guideline was toprovide guidance on the diagnosis and treatment of adult individuals with hypotonic hyponatraemia. It wasdesigned to provide information and assist in decision-making related to this topic. It was not intended to definea standard of care and should not be construed as one.It should not be interpreted as prescribing an exclusivecourse of management.This guideline was developed as a joint ventureof three societies representing specialists with a naturalinterest in hyponatraemia: the ESICM, the ESE and theERA–EDTA, represented by ERBP.All three societies agreed that there was a needfor guidance on diagnostic assessment and therapeuticmanagement of hyponatraemia. A recent systematicreview, which included three clinical practice guidelinesand five consensus statements, confirmed the lack of high-quality guidelines in this field (1). The guidance documents scored low to moderate in the six domains of the AGREEII tool scope and purpose, stakeholderinvolvement, rigour of development, clarity of presen-tation, applicability and editorial independence – and themanagement strategies proposed in the different guidancedocuments were sometimes contradictory (2).
3.2. Who is this guideline for?
This guideline was meant to support clinical decision-making for any health care professional dealing withhyponatraemia, i.e. general practitioners, internists, sur-geons and other physicians dealing with hyponatraemiain both an outpatient and an in-hospital setting. Theguideline was also developed for policymakers for inform-ing standards of care and for supporting the decision-making process.
3.3. What is this guideline about?
This section defines what this guideline intended to coverand what the guideline developers considered. The scopewas determined at a first meeting held in Barcelona inOctober 2010 with representatives of ESICM, ESE andERBP present.
3.3.1. Population
The guideline covers hyponatraemia in adults throughthe biochemical analysis of a blood sample. It does notcover hyponatraemia detected in children because theguideline development group judged that hyponatraemiain children represented a specific area of expertise. Theguidelinealsodoesnotcoverscreeningforhyponatraemia.
3.3.2. Conditions
Theguidelinespecificallycoversdiagnosisandmanagementof true hypotonic hyponatraemia. It covers the differen-tiation of hypotonic hyponatraemia from non-hypotonichyponatraemia but does not deal with the specific diag-nostic and therapeutic peculiarities in the setting of pseudohyponatraemia, isotonic or hypertonic hyponatrae-mia.Thesesituationsarenotassociatedwiththehypotonicstate responsible for the majority of symptoms attributableto true hypotonic hyponatraemia. The guideline coversdiagnosis and management of both acute and chronichypotonic hyponatraemia in case of reduced, normal andincreased extracellular fluid volume. It does not cover thediagnosisortreatmentoftheunderlyingconditionsthatcanbe associated with hypotonic hyponatraemia.
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Clinical Practice Guideline
 G Spasovski and others Diagnosis and treatment ofhyponatraemia

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