A step-by-step guide for the diagnosis and management of hyponatraemia in patients with stroke

Hyponatraemia is common in patients with stroke and associated with adverse outcomes and increased mortality risk. The present review presents the underlying causes and provides a thorough algorithm for the diagnosis and management of hyponatraemia in stroke patients. Concomitant diseases and therapies, such as diabetes, chronic kidney disease and heart failure, along with diuretics, antidepressants and proton pump inhibitors are the most common causes of hyponatraemia in community. In the setting of acute stroke, the emergence of hyponatraemia might be attributed to the administration of hypotonic solutions and drugs (ie. mannitol and antiepileptics), poor solute intake, infections, as well as stroke-related conditions or complications, such as the syndrome of inappropriate secretion of antidiuretic hormone, cerebral salt wasting syndrome and secondary adrenal insufficiency. Diagnostically, the initial step is to differentiate hypotonic from non-hypotonic hyponatraemia, usually caused by hyperglycaemia or recent mannitol administration in patients with stroke. Determining urine osmolality, urine sodium level and volume status are the following steps in the differentiation of hypotonic hyponatraemia. Of note, specific parameters, such as fractional uric acid and urea excretion, along with plasma copeptin concentration, may further improve the diagnostic yield. Therapeutic options are based on the duration and symptoms of hyponatremia. In the case of acute or symptomatic hyponatraemia, hypertonic saline administration is recommended. Hypovolaemic chronic hyponatremia is treated with isotonic solution administration. Although fluid restriction remains the first-line treatment for the rest forms of chronic hyponatraemia, therapies increasing renal free water excretion may be necessary. Loop diuretics and urea serve this purpose in patients with stroke, whereas sodium-glucose transport protein-2 inhibitors appear to be a promising therapy. Nevertheless, it is yet unclear whether the appropriate restoration of sodium level improves outcomes in such patients. Randomized trials designed to compare therapeutic strategies in managing hyponatraemia in patients with stroke are required.

[1]  P. Deedwania SGLT2 Inhibitors: The Dawn of a New Era in Cardio-Metabolic Therapeutics , 2021, American Journal of Cardiovascular Drugs.

[2]  Correction to: 2021 Guideline for the Prevention of Stroke in Patients With Stroke and Transient Ischemic Attack: A Guideline From the American Heart Association/American Stroke Association. , 2021, Stroke.

[3]  H. Kamel,et al.  2021 Guideline for the Prevention of Stroke in Patients With Stroke and Transient Ischemic Attack: A Guideline From the American Heart Association/American Stroke Association. , 2021, Stroke.

[4]  H. Milionis,et al.  Sodium-Glucose Cotransporter-2 Inhibitors and Protection Against stroke in Patients with type 2 Diabetes and Impaired Renal Function: A Systematic Review and Meta-Analysis. , 2021, Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association.

[5]  O. Takahashi,et al.  Prognostic Significance of Hyponatremia in Acute Stroke: A Systematic Review and Meta-Analysis , 2020, Cerebrovascular Diseases.

[6]  M. Christ-Crain,et al.  A Randomized Trial of Empagliflozin to Increase Plasma Sodium Levels in Patients with the Syndrome of Inappropriate Antidiuresis. , 2020, Journal of the American Society of Nephrology : JASN.

[7]  A. Batra,et al.  Hyponatremia in the Neurologically Ill Patient: A Review , 2020, The Neurohospitalist.

[8]  Correction to: Guidelines for the Early Management of Patients With Acute Ischemic Stroke: 2019 Update to the 2018 Guidelines for the Early Management of Acute Ischemic Stroke: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association. , 2019, Stroke.

[9]  H. Milionis,et al.  Hyponatremia in Acute Stroke Patients: Pathophysiology, Clinical Significance, and Management Options , 2019, European Neurology.

[10]  Guixia Wang,et al.  Inappropriate Antidiuretic Hormone Secretion and Cerebral Salt-Wasting Syndromes in Neurological Patients , 2019, Front. Neurosci..

[11]  W. Powers,et al.  Guidelines for the Early Management of Patients With Acute Ischemic Stroke: 2019 Update to the 2018 Guidelines for the Early Management of Acute Ischemic Stroke: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association. , 2019, Stroke.

[12]  H. Milionis,et al.  Hyponatremia in Acute Stroke: To Treat or Not to Treat? , 2019, Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association.

[13]  Panayotis K. Vlachakis,et al.  SGLT2 Inhibitors: A Review of Their Antidiabetic and Cardioprotective Effects , 2019, International journal of environmental research and public health.

[14]  Zhongyun Chen,et al.  Association of Hyponatremia and Risk of Short- and Long-Term Mortality in Patients with Stroke: A Systematic Review and Meta-Analysis. , 2019, Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association.

[15]  Jinhui Wang,et al.  Improvement of hyponatremia is associated with lower mortality risk in patients with acute decompensated heart failure: a meta-analysis of cohort studies , 2018, Heart Failure Reviews.

[16]  A. Peri,et al.  Hyponatremia, falls and bone fractures: A systematic review and meta‐analysis , 2018, Clinical endocrinology.

[17]  E. Kim,et al.  Heart Failure as a Risk Factor for Stroke , 2018, Journal of stroke.

[18]  M. Christ-Crain,et al.  Empagliflozin Increases Short-Term Urinary Volume Output in Artificially Induced Syndrome of Inappropriate Antidiuresis , 2017, International journal of endocrinology.

[19]  C. Tzeng,et al.  Risk of stroke in patients with newly diagnosed multiple myeloma: a retrospective cohort study , 2017, Hematological oncology.

[20]  Liguang Sun,et al.  Association of serum sodium and risk of all-cause mortality in patients with chronic kidney disease: A meta-analysis and sysematic review , 2017, Scientific Reports.

[21]  Liguang Sun,et al.  Association of serum sodium and risk of all-cause mortality in patients with chronic kidney disease: A meta-analysis and sysematic review , 2017, Scientific Reports.

[22]  M. Elisaf,et al.  Hyponatremia in the elderly: challenges and solutions , 2017, Clinical interventions in aging.

[23]  H. Kamel,et al.  Association Between Cirrhosis and Stroke in a Nationally Representative Cohort , 2017, JAMA neurology.

[24]  K. Shu,et al.  Hyponatremia and increased risk of dementia: A population-based retrospective cohort study , 2017, PloS one.

[25]  J. Kalita,et al.  Cerebral Salt Wasting Is the Most Common Cause of Hyponatremia in Stroke. , 2017, Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association.

[26]  R. Zietse,et al.  Diagnosis and Treatment of Hyponatremia: Compilation of the Guidelines. , 2017, Journal of the American Society of Nephrology : JASN.

[27]  M. van der Jagt Fluid management of the neurological patient: a concise review , 2016, Critical Care.

[28]  M. Elisaf,et al.  Ten pitfalls in the proper management of patients with hyponatremia , 2016, Postgraduate medicine.

[29]  H. Milionis,et al.  Statins decrease the risk of stroke in individuals with heterozygous familial hypercholesterolemia: A systematic review and meta-analysis. , 2015, Atherosclerosis.

[30]  L. Snell,et al.  Arginine-Vasopressin Receptor Blocker Conivaptan Reduces Brain Edema and Blood-Brain Barrier Disruption after Experimental Stroke in Mice , 2015, PloS one.

[31]  J. Verbalis,et al.  Hyponatremia Improvement Is Associated with a Reduced Risk of Mortality: Evidence from a Meta-Analysis , 2015, PloS one.

[32]  S. Zainudin,et al.  Relative adrenal insufficiency amongst hospitalized mild to moderate acute ischemic stroke patients. , 2015, Archives of Iranian medicine.

[33]  E. Liberopoulos,et al.  Diabetes mellitus and electrolyte disorders. , 2014, World journal of clinical cases.

[34]  L. McCullough,et al.  Hyponatremia in the prognosis of acute ischemic stroke. , 2014, Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association.

[35]  S. Kloska,et al.  Hyponatremia Is an Independent Predictor of In-Hospital Mortality in Spontaneous Intracerebral Hemorrhage , 2014, Stroke.

[36]  A. Alleman Osmotic demyelination syndrome: central pontine myelinolysis and extrapontine myelinolysis. , 2014, Seminars in ultrasound, CT, and MR.

[37]  J. Verbalis,et al.  Moderate Hyponatremia Is Associated with Increased Risk of Mortality: Evidence from a Meta-Analysis , 2013, PloS one.

[38]  J. Radhakrishnan,et al.  Prevalence of hyponatremia and association with mortality: results from NHANES. , 2013, The American journal of medicine.

[39]  S. Lang,et al.  Analysis of Risk Factors for First Seizure after Stroke in Chinese Patients , 2013, BioMed research international.

[40]  F. Barkas,et al.  Spurious Electrolyte Disorders: A Diagnostic Challenge for Clinicians , 2013, American Journal of Nephrology.

[41]  A. Hofman,et al.  Electrolyte disorders in community subjects: prevalence and risk factors. , 2013, The American journal of medicine.

[42]  T. Egberts,et al.  Prevalence of hyponatremia on geriatric wards compared to other settings over four decades: A systematic review , 2013, Ageing Research Reviews.

[43]  N. Nahar,et al.  Electrolyte changes in stroke. , 2012, Mymensingh medical journal : MMJ.

[44]  T. Peng,et al.  Association of Hyponatremia in Acute Stroke Stage with Three-Year Mortality in Patients with First-Ever Ischemic Stroke , 2012, Cerebrovascular Diseases.

[45]  H. Milionis,et al.  Hyponatremia in patients with infectious diseases. , 2011, The Journal of infection.

[46]  H. Milionis,et al.  Endocrine disorders: Causes of hyponatremia not to neglect , 2011, Annals of medicine.

[47]  G. Robertson Vaptans for the treatment of hyponatremia , 2011, Nature Reviews Endocrinology.

[48]  G. Biessels,et al.  Hyperglycemia in acute ischemic stroke: pathophysiology and clinical management , 2010, Nature Reviews Neurology.

[49]  J. Verbalis,et al.  Conivaptan: Evidence supporting its therapeutic use in hyponatremia , 2009, Core evidence.

[50]  L. Lisabeth,et al.  Acute Stroke Symptoms: Comparing Women and Men , 2009, Stroke.

[51]  A. Shorr,et al.  Epidemiology, clinical and economic outcomes of admission hyponatremia among hospitalized patients* , 2008, Current medical research and opinion.

[52]  R. Zietse,et al.  Hyponatremia Revisited: Translating Physiology to Practice , 2008, Nephron Physiology.

[53]  Adnan I. Qureshi,et al.  Guidelines for the Early Management of Adults With Ischemic Stroke , 2007 .

[54]  T. Berl,et al.  Tolvaptan, a selective oral vasopressin V2-receptor antagonist, for hyponatremia. , 2006, The New England journal of medicine.

[55]  N. Madias,et al.  Incidence and prevalence of hyponatremia. , 2006, The American journal of medicine.

[56]  R. Glass,et al.  JAMA patient page. Adrenal insufficiency. , 2005, Journal of the American Medical Association (JAMA).

[57]  H. Milionis,et al.  The hyponatremic patient: a systematic approach to laboratory diagnosis. , 2002, CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne.

[58]  A. Meinders,et al.  Hyponatremia in intracranial disorders. , 2001, The Netherlands journal of medicine.

[59]  C. Warlow,et al.  Complications after acute stroke. , 1996, Stroke.

[60]  S. Massry,et al.  NEUROLOGICAL MANIFESTATIONS AND MORBIDITY OF HYPONATREMIA: CORRELATION WITH BRAIN WATER AND ELECTROLYTES , 1976, Medicine.

[61]  H. Milionis,et al.  Hyponatremia-Inducing Drugs. , 2019, Frontiers of hormone research.

[62]  M. H. Ensom,et al.  Prevention and Treatment of Hyponatremia in Patients with Subarachnoid Hemorrhage: A Systematic Review. , 2018, World neurosurgery.

[63]  K. Pennypacker,et al.  The Effects of Clinically Relevant Hypertonic Saline and Conivaptan Administration on Ischemic Stroke. , 2016, Acta neurochirurgica. Supplement.

[64]  R. Sterns Disorders of plasma sodium--causes, consequences, and correction. , 2015, The New England journal of medicine.

[65]  D. Annane,et al.  Clinical practice guideline on diagnosis and treatment of hyponatraemia , 2014, Intensive Care Medicine.

[66]  H. Adams,et al.  Cerebral infarction in patients with nephrotic syndrome. , 1991, Stroke.