Hyponatremia natural history, complications and prognosis

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Saeedeh Kowsarnia M.D.[2]

Overview

Brain adaptive mechanisms to hyponatremia are developed over hours. Shifting of water to brain cells causes brain edema and increased intracranial pressure. Excretion of osmole from brain cells decreases osmotic gradient and brain edema. Impairment of adaptive mechanisms and acute onset of hyponatremia cause encephalopathy and brain herniation. Rapid treatment of hyponatremia will not allow adaptive mechanisms to develop and may cause in osmotic demyelination syndrome, also called central pontine demyelination.

Natural History, Complications, and Prognosis

Natural History

Serum sodium concentration is the main determinant of serum osmolality. Maintaining constant serum sodium and osmolality is essential for keeping cell volume stable. This maintenance is very crucial for brain cells and volume. In acute hyponatremia, an osmotic gradient between brain cells and serum, causing water to enter brain cells and increased brain volume, edema, intracranial pressure and risk of herniation.In chronic hyponatremia, brain cells have time to lose osmoles (amino acids, polyols) to re-equilibrate the osmolar gradient and cell volume [1].

Complications

  • Hyponatremic Encephalopathy : Clinical presentation of hyponatremic encephalopathy are associated with the degree of increased intracranial pressure and brain edema. These manifestations are ranged from nausea and vomiting which are the most common symptoms to cardiac arrest, permanent brain damage, and death [2].Pulmonary edema in hyponatremic encephalopathy named Ayus-Arieff syndrome, is a noncardiogenic edema results from increased vasoconstriction and protein permeability of pulmonary vessels. Pulmonary edema by hyponatremic encephalopathy is more common with exercise associated hyponatremia and postoperative. The treatment is to correct the underlying causes of hyponatremia and reversible. Hyponatremic encephalopathy can occur without any evidence of brain edema in CT scan. Female sex (peripubertal and pre-menopausal phase) and hypoxia increased the risk of developing severe hyponatremic encephalopathy.
Stage Clinical manifestation of hyponatremic encephalopathy
Early Anorexia, headache, nausea, vomiting, muscule cramps, weakness, confusion, altered consciousness, agitation, gait disturbances
Advanced Impaired response to verbal stimuli, impaired response to painful stimuli, bizarre (inappropriate) behavior, hallucinations (auditory or visual), asterixis, obtundation, incontinence (urinary or fecal), respiratory insufficiency
Severe Decorticate and/or decerebrate posturing, bradycardia, hyper- or hypotension, altered temperature regulation (hypo- or hyperthermia), anisocornea, papilledema, dilated pupils, seizure activity (usually grand mal), cardiac arrhythmias, myocardial ischemia, pulmonary edema, respiratory arrest, coma, polyuria (secondary to central diabetes insipidus)
  • Brain herniation :In acute hyponatremia, if the brain adaptation to hyponatremia is impaired especially solute excretion of brain cells to achieve osmotic equilibrium, it causes brain cells swelling, increased intracranial pressure, cerebral edema, and eventual tentorial herniation [3].
  • Osmotic Demyelination syndrome (Central Pontine Demyelination) :Hyponatremia, serum sodium < 135 mEq/L, causes brain edema due to shift of water from extracellular in to the brain cells. In the next 24 to 48 hours, brain starts to compensate by excreting solutes and water. If serum sodium is corrected too rapidly, brain cells do not have time to replace the solutes which results in dehydration of the brain cells named osmotic demyelination syndrome [4].
Signs and symptoms of ODS

Risk of developing Osmotic Demyelination Syndrome is increased with:

Patients with congestive heart failure present with higher rate of ventricular premature beats which are correlated to the severity of hyponatremia. there are evidence that acute severe hyponatremia may cause second-degree or complete atrioventricular (AV) block [5].

Prognosis

  • Asymptomatic hyponatremia in adults is associated with attention and gait deficit, falls and fractures, osteoporosis [6], calcium forming kidney stones [6] and increased mortality in patients with pneumonia, heart failure and liver disease [7]. Hyponatremia at hospital discharge after normal admission Na levels suggest poorer prognosis in heart failure patients admitted for decompensated heart failure. [8]
  • Preterm neonates is associated with poor development and growth, cerebral palsy, sensorineural hearing loss, and intracranial hemorrhage, increased perinatal mortality in neonates who suffered perinatal asphyxia and increased sodium intake in later life [9] [10][11]
  • Presence of hyponatremia in any clinical settings is associated with increased mortality as an independent risk [12]. Hyponatremia might predict adverse outcomes of patients under dialysis. [13]
  • More recently, in COVID 19 patients, hyponatremia was found an independent predictor of in-hospital mortality, and was associated with increased risk of encephalopathy and mechanical ventilation. [14] Hyponatremia also increased length of hospital stay in COVID 19 patients. [15]
  • Patients with Diabetes Insipidus admitted with COVID-19 have a high risk of mortality due to volume depletion. However, IV fluid replacement should be administered with caution in severe cases of COVID-19 because of the risk of pulmonary edema.

References

  1. Guillaumin, Julien; DiBartola, Stephen P. (2017). "Disorders of Sodium and Water Homeostasis". Veterinary Clinics of North America: Small Animal Practice. 47 (2): 293–312. doi:10.1016/j.cvsm.2016.10.015. ISSN 0195-5616.
  2. Moritz, Michael L.; Ayus, Juan Carlos (2009). "New aspects in the pathogenesis, prevention, and treatment of hyponatremic encephalopathy in children". Pediatric Nephrology. 25 (7): 1225–1238. doi:10.1007/s00467-009-1323-6. ISSN 0931-041X.
  3. A. I. Arieff, F. Llach & S. G. Massry (1976). "Neurological manifestations and morbidity of hyponatremia: correlation with brain water and electrolytes". Medicine. 55 (2): 121–129. PMID 1256311. Unknown parameter |month= ignored (help)
  4. King, Joshua D.; Rosner, Mitchell H. (2010). "Osmotic Demyelination Syndrome". The American Journal of the Medical Sciences. 339 (6): 561–567. doi:10.1097/MAJ.0b013e3181d3cd78. ISSN 0002-9629.
  5. M. Mouallem, E. Friedman, Y. Shemesh, H. Mayan, R. Pauzner & Z. Farfel (1991). "Cardiac conduction defects associated with hyponatremia". Clinical cardiology. 14 (2): 165–168. PMID 2044246. Unknown parameter |month= ignored (help)
  6. 6.0 6.1 Seay NW, Lehrich RW, Greenberg A (2020). "Diagnosis and Management of Disorders of Body Tonicity-Hyponatremia and Hypernatremia: Core Curriculum 2020". Am J Kidney Dis. 75 (2): 272–286. doi:10.1053/j.ajkd.2019.07.014. PMID 31606238.
  7. Benoit Renneboog, Wim Musch, Xavier Vandemergel, Mario U. Manto & Guy Decaux (2006). "Mild chronic hyponatremia is associated with falls, unsteadiness, and attention deficits". The American journal of medicine. 119 (1): 71. doi:10.1016/j.amjmed.2005.09.026. PMID 16431193. Unknown parameter |month= ignored (help)
  8. Omar, Hesham R.; Charnigo, Richard; Guglin, Maya (2017). "Prognostic Significance of Discharge Hyponatremia in Heart Failure Patients With Normal Admission Sodium (from the ESCAPE Trial)". The American Journal of Cardiology. 120 (4): 607–615. doi:10.1016/j.amjcard.2017.05.030. ISSN 0002-9149.
  9. N. A. Mir, A. M. Faquih & M. Legnain (1989). "Perinatal risk factors in birth asphyxia: relationship of obstetric and neonatal complications to neonatal mortality in 16,365 consecutive live births". Asia-Oceania journal of obstetrics and gynaecology. 15 (4): 351–357. PMID 2624578. Unknown parameter |month= ignored (help)
  10. T. Ertl, K. Hadzsiev, O. Vincze, J. Pytel, I. Szabo & E. Sulyok (2001). "Hyponatremia and sensorineural hearing loss in preterm infants". Biology of the neonate. 79 (2): 109–112. doi:10.1159/000047076. PMID 11223652. Unknown parameter |month= ignored (help)
  11. Adi Shirazki, Zalman Weintraub, Dan Reich, Edith Gershon & Micah Leshem (2007). "Lowest neonatal serum sodium predicts sodium intake in low birth weight children". American journal of physiology. Regulatory, integrative and comparative physiology. 292 (4): R1683–R1689. doi:10.1152/ajpregu.00453.2006. PMID 17170236. Unknown parameter |month= ignored (help)
  12. Upadhyay, Ashish; Jaber, Bertrand L.; Madias, Nicolaos E. (2006). "Incidence and Prevalence of Hyponatremia". The American Journal of Medicine. 119 (7): S30–S35. doi:10.1016/j.amjmed.2006.05.005. ISSN 0002-9343.
  13. Li, Jin’e; Song, Panai; Yang, Dong; Liu, Yinghong (2021). "A Systematic Review and Meta-Analysis: Hyponatremia Predicted All-Cause and Cardiovascular Mortality in Dialysis Population". Blood Purification: 1–10. doi:10.1159/000517340. ISSN 0253-5068.
  14. Frontera, Jennifer A.; Valdes, Eduard; Huang, Joshua; Lewis, Ariane; Lord, Aaron S.; Zhou, Ting; Kahn, D. Ethan; Melmed, Kara; Czeisler, Barry M.; Yaghi, Shadi; Scher, Erica; Wisniewski, Thomas; Balcer, Laura; Hammer, Elizabeth (2020). "Prevalence and Impact of Hyponatremia in Patients With Coronavirus Disease 2019 in New York City". Critical Care Medicine. 48 (12): e1211–e1217. doi:10.1097/CCM.0000000000004605. ISSN 0090-3493.
  15. Hirsch, Jamie S; Uppal, Nupur N; Sharma, Purva; Khanin, Yuriy; Shah, Hitesh H; Malieckal, Deepa A; Bellucci, Alessandro; Sachdeva, Mala; Rondon-Berrios, Helbert; Jhaveri, Kenar D; Fishbane, Steven; Ng, Jia H; Abate, Mersema; Andrade, Hugo Paz; Barnett, Richard L; Bellucci, Alessandro; Bhaskaran, Madhu C; Corona, Antonio G; Flores Chang, Bessy Suyin; Finger, Mark; Fishbane, Steven; Gitman, Michael; Halinski, Candice; Hasan, Shamir; Hazzan, Azzour D; Hirsch, Jamie S; Hong, Susana; Jhaveri, Kenar D; Khanin, Yuriy; Kuan, Aireen; Madireddy, Varun; Malieckal, Deepa; Muzib, Abdulrahman; Nair, Gayatri; Nair, Vinay V; Ng, Jia Hwei; Parikh, Rushang; Ross, Daniel W; Sakhiya, Vipulbhai; Sachdeva, Mala; Schwarz, Richard; Shah, Hitesh H; Sharma, Purva; Singhal, Pravin C; Uppal, Nupur N; Wanchoo, Rimda (2021). "Prevalence and outcomes of hyponatremia and hypernatremia in patients hospitalized with COVID-19". Nephrology Dialysis Transplantation. 36 (6): 1135–1138. doi:10.1093/ndt/gfab067. ISSN 0931-0509.

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