Pathophysiology, Evaluation, and Treatment of Hypernatremia
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  • 1 Duke University Medical Center, Department of Medicine, Division of Nephrology, Durham, North Carolina
  • 1

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    Zimmerman CA, Leib DE, Knight ZA: Neural circuits underlying thirst and fluid homeostasis. Nat Rev Neurosci 18: 459469, 2017 PubMed

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    Ranjan R, Lo SC, Ly S, Krishnananthan V, Lim AKH: Progression to severe hypernatremia in hospitalized general medicine inpatients: An observational study of hospital-acquired hypernatremia. Medicina (Kaunas) 56: E358, 2020 PubMed

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  • 11

    Shirazy M, Omar I, Abduljabbar D, Bousselmi K, Alkhaja M, Chaari A, Kauts V, Hakim K: Prevalence and prognostic impact of hypernatremia in sepsis and septic shock patients in the intensive care unit: A single centre experience. J Crit Care Med (Targu-Mures) 6: 5258, 2020 PubMed

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  • 12

    Breen T, Brueske B, Sidhu MS, Murphree DH, Kashani KB, Barsness GW, Jentzer JC: Abnormal serum sodium is associated with increased mortality among unselected cardiac intensive care unit patients. J Am Heart Assoc 9: e014140, 2020 PubMed

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    Bissell BD, Laine ME, Thompson Bastin ML, Flannery AH, Kelly A, Riser J, Nehra JA, Potter J, Morris PE: Impact of protocolized diuresis for de-resuscitation in the intensive care unit. Crit Care 24: 70, 2020 PubMed

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  • 15

    Imaizumi T, Nakatochi M, Fujita Y, Yamamoto R, Watanabe K, Maekawa M, Hamawaka T, Katsjjno T, Maruyama S: Glucocorticoid treatment is associated with ICU-acquired hypernatremia: A nested case-control study. Clin Exp Nephrol 25: 131139, 2021 PubMed

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  • 16

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  • 17

    Imai N, Shibagaki Y: The prevalence of dysnatremia in the elderly patients without CKD. Am J Emerg Med 37: 499501, 2019 PubMed

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    Begg DP: Disturbances of thirst and fluid balance associated with aging. Physiol Behav 178: 2834, 2017 PubMed

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  • 20

    Brennan M, Murray O, O'Shea PM, Mulkerrin EC. Increased rates of hypernatraemia during modest heatwaves in temperate climates. QJM: monthly journal of the Association of Physicians. 2020;113:266270.

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  • 21

    Imai N, Sumi H, Shibagaki Y: Impact of age on the seasonal prevalence of hypernatremia in the emergency department: A single-center study. Int J Emerg Med 12: 29, 2019 PubMed

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  • 22

    Blohm E, Goldberg A, Salerno A, Jenny C, Boyer E, Babu K: Recognition and management of pediatric salt toxicity. Pediatr Emerg Care 34: 820824, 2018 PubMed

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  • 23

    Hancher J, Fisher J, Shenvi C. Severe hypernatremia and gastric dilation from chronic eating disorder and intentional salt ingestion. AmJ Emerg Med. 2020;38:1700.e11700.e03.

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  • 24

    Park MS, Park HJ, Choi HS, Kim CS, Bae EH, Ma SK, Kim SW, Kim M: Extremely severe hypernatremia caused by wrong belief in a patient with cervical cancer. Electrolyte Blood Press 18: 1618, 2020 PubMed

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  • 25

    Sakamoto A, Hoshino T, Boku K, Hiraya D, Inoue Y: Fatal acute hypernatremia resulting from a massive intake of seasoning soy sauce. Acute Med Surg 7: e555, 2020 PubMed

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  • 26

    Lipman GS, Burns P, Phillips C, Jensen J, Little C, Jurkiewcz C, Jarrett B, Walker A, Mansfield N, Krabak BJ: Effect of sodium supplements and climate on dysnatremia during ultramarathon running. Clin J Sport Med 31: e327e334, 2020 PubMed

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  • 27

    Martinez-Cano JP, Cortes-Castillo V, Martinez-Villa J, Ramos JC, Uribe JP: Dysnatremia among runners in a half marathon performed under warm and humid conditions. BMJ Open Sport Exerc Med 4: e000351, 2018 PubMed

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  • 28

    Thongprayoon C, Cheungpasitporn W, Petnak T, Ghamrawi R, Thirunavukkarasu S, Chewcharat A, Bathini T, Vallabhajosyula S, Kashani KB: The prognostic importance of serum sodium levels at hospital discharge and one-year mortality among hospitalized patients. Int J Clin Pract 74: e13581, 2020 PubMed

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  • 29

    Gao XP, Zheng CF, Liao MQ, He H, Liu YH, Jing CX, Zeng FF, Chen QS: Admission serum sodium and potassium levels predict survival among critically ill patients with acute kidney injury: A cohort study. BMC Nephrol 20: 311, 2019 PubMed

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  • 30

    Chi WC, Patel S, Cheung NW: Admission sodium levels and hospital outcomes. Intern Med J 51: 9398, 2021 PubMed

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    Castello LM, Gavelli F, Baldrighi M, Salmi L, Mearelli F, Fiotti N, Patrucco F, Bellan M, Sainaghi PP, Ronzoni G, Di Somma S, Lupia E, Muiesan ML, Biolo G, Avanzi GC: Hypernatremia and moderate-to-severe hyponatremia are independent predictors of mortality in septic patients at emergency department presentation: a sub-group analysis of the need-speed trial. Eur J Intern Med 83: 2127,2020 PubMed

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  • 32

    Chewcharat A, Thongprayoon C, Cheungpasitporn W, Mao MA, Thirunavukkarasu S, Kashani KB: Trajectories of serum sodium on in-hospital and 1-year survival among hospitalized patients. Clin J Am Soc Nephrol 15: 600607, 2020 PubMed

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  • 33

    Tsipotis E, Price LL, Jaber BL, Madias NE: Hospital-associated hypernatremia spectrum and clinical outcomes in an unselected cohort. Am J Med 131: 7282.e1, 2018 PubMed

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  • 34

    Grangeon-Chapon C, Dodoi M, Esnault VL, Favre G: Osmotic stress and mortality in elderly patients with kidney failure: A retrospective study. Clin Interv Aging 14: 225229, 2019 PubMed

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  • 35

    Seo MS, Hwang IC, Jung J, Lee H, Choi JH, Shim JY: Hypernatremia at admission predicts poor survival in patients with terminal cancer: A retrospective cohort study. BMC Palliat Care 19: 94, 2020 PubMed

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  • 36

    Vicent L, Alvarez-Garcia J, Gonzalez-Juanatey JR, Rivera M, Segovia J, Worner F, Bover R, Pascual-Figal D, Vázquez R, Cinca J, Fernandez-Aviles FF, Sellés MM: Prognostic impact of hyponatremia and hypernatremia at admission and discharge in heart failure patients with preserved, mid-range, and reduced ejection fraction. Intern Med J 51: 930938, 2020

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  • 38

    Mangat HS: Hypertonic saline infusion for treating intracranial hypertension after severe traumatic brain injury. Crit Care 22: 37, 2018 PubMed

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  • 39

    Tsaousi G, Stazi E, Cinicola M, Bilotta F: Cardiac output changes after osmotic therapy in neurosurgical and neurocritical care patients: A systematic review of the clinical literature. Br J Clin Pharmacol 84: 636648, 2018 PubMed

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  • 40

    Hoffman H, Jalal MS, Chin LS: Effect of hypernatremia on outcomes after severe traumatic brain injury: A nationwide inpatient sample analysis. World Neurosurg 118: e880e886, 2018 PubMed

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  • 41

    Ditch KL, Flahive JM, West AM, Osgood ML, Muehlschlegel S: Hyperchloremia, not concomitant hypernatremia, independently predicts early mortality in critically ill moderate-severe traumatic brain injury patients. Neurocrit Care 33: 533541, 2020 PubMed

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  • 42

    Roquilly A, Lasocki S, Moyer JD, Huet O, Perrigault PF, Dahyot-Fizelier C, et al.; COBI group: COBI (COntinuous hyperosmolar therapy for traumatic Brain-Injured patients) trial protocol: A multicentre randomised open-label trial with blinded adjudication of primary outcome. BMJ Open 7: e018035, 2017 PubMed

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  • 43

    Fülöp T, Zsom L, Rodríguez RD, Chabrier-Rosello JO, Hamrahian M, Koch CA: Therapeutic hypernatremia management during continuous renal replacement therapy with elevated intracranial pressures and respiratory failure. Rev Endocr Metab Disord 20: 6575, 2019 PubMed

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    Ott M, Forssén B, Werneke U: Lithium treatment, nephrogenic diabetes insipidus and the risk of hypernatraemia: A retrospective cohort study. Ther Adv Psychopharmacol 9: 2045125319836563, 2019 PubMed

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    Fotso Soh J, Torres-Platas SG, Beaulieu S, Mantere O, Platt R, Mucsi I, Saury S, Renaud S, Levinson A, Andreazza AC, Mulsant BH, Müller D, Schaffer A, Dols A, Cervantes P, Low NC, Herrmann N, Christensen BM, Trepiccione F, Rajji T, Rej S: Atorvastatin in the treatment of lithium-induced nephrogenic diabetes insipidus: The protocol of a randomized controlled trial. BMC Psychiatry 18: 227, 2018 PubMed

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    Honore PM, De Bels D, Barreto Gutierrez L, Redant S, Gallerani A, Boer W: Sevoflurane and nephrogenic diabetes insipidus on the rise: Copeptin to the rescue? Crit Care 23: 304, 2019 PubMed

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    Rana H, Ferguson N, Dicpinigaitis PV: Diabetes insipidus after discontinuation of vasopressin infusion for septic shock. J Clin Pharm Ther 43: 287290, 2018 PubMed

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    Refardt J, Winzeler B, Christ-Crain M: Copeptin and its role in the diagnosis of diabetes insipidus and the syndrome of inappropriate antidiuresis. Clin Endocrinol (Oxf) 91: 2232, 2019 PubMed

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    Nigro N, Winzeler B, Suter-Widmer I, Schuetz P, Arici B, Bally M, Refardt J, Betz M, Gashi G, Urwyler SA, Burget L, Blum CA, Bock A, Huber A, Müllwe V, Christ-Crain M: Copeptin levels and commonly used laboratory parameters in hospitalised patients with severe hypernatraemia - The “Co-MED study”. Crit Care 22: 33, 2018 PubMed

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    Fenske W, Refardt J, Chifu I, Schnyder I, Winzeler B, Drummond J, Ribeiro-Oliveira A Jr, Drescher T, Bilz S, Vogt DR, Malzahn U, Kroiss M, Henzen CE, Fischli S, Tonjes A, Mueller B, Schopohl J, Flitsch J, Brabant G, Fassnacht M, Christ-Crain M: A copeptin-based approach in the diagnosis of diabetes insipidus. N Engl J Med 379: 428439, 2018 PubMed

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    Winzeler B, Cesana-Nigro N, Refardt J, Vogt DR, Imber C, Morin B, Popovic M, Steinmetz M, Sailer CO, Szinnai G, Chifu I, Fassnacht M, Christ-Crain M: Arginine-stimulated copeptin measurements in the differential diagnosis of diabetes insipidus: a prospective diagnostic study. Lancet 394: 587595, 2019 PubMed

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  • 53

    Sterns RH: Evidence for managing hypernatremia: is it just hyponatremia in reverse? Clin J Am Soc Nephrol 14: 645647, 2019 PubMed

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    Jongejan M, Vleming LJ: Time to speed up-the rate at which we correct hypernatremia. Eur J Intern Med 83: 105106, 2020 PubMed

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    Chauhan K, Pattharanitima P, Patel N, Duffy A, Saha A, Chaudhary K, Debnath N, Van Vleck T, Chan L, Nadkarni GN, Coca SG: Rate of correction of hypernatremia and health outcomes in critically ill Patients. Clin J Am Soc Nephrol 14: 656663, 2019 PubMed

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  • 57

    Huang C, Liu Y, Li L, Liu H, Zhang P: Continuous veno-venous hemofiltration in the treatment of severely burned patients with acute hypernatremia: A retrospective study of 13 cases. Int J Artif Organs 43: 416421, 2020 PubMed

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  • 58

    Zhao L, Ma F, Yu Y, Li Y, Wang Y, He L, Zhou M, Tian X, Jing R, Li L, Li L, Huang C, Bai M, Sun S: Regional citrate anticoagulation versus no-anticoagulation for continuous venovenous hemofiltration in acute severe hypernatremia patients with increased bleeding risk: A retrospective cohort study. Blood Purif 49: 4454, 2020 PubMed

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  • 59

    Sánchez-Hidalgo JM, Rodríguez-Ortiz L, Arjona-Sánchez A, Ruiz-Rabelo J, Salamanca-Bustos JJ, Rodríguez-Benot A, Márquez-López FJ, Briceño-Hidalgo J: Pancreas donor hypernatremia: Is it really a risk factor for simultaneous pancreas-kidney transplantation? Transplant Proc 50: 676678, 2018 PubMed

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  • 60

    Aliabadi-Zuckermann AZ, Gökler J, Kaider A, Riebandt J, Moayedifar R, Osorio E, Haberi T, Angleitner P, Laufer G, Forsythe J, Knezevic I, Skoric B, Erasmus M, van Cleemput J, Caliskan K, De Jonge N, Szabolcs Z, Prodán Z, Wasler A, Bara C, Udovičić M, Sandhaus T, Garbade J, Ruhparwar A, Schoenrath F, Hirt S, Antretter H, Schulz U, Richter M, Thul J, Barten MJ, Haneya A, Aleksic I, Efiert S, Berchtold-Herz M, Smits J, Zuckermann AO: Donor heart selection and outcomes: An analysis of over 2,000 cases. J Heart Lung Transplant 37: 976984, 2018 PubMed

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  • 61

    Finger MA, Cipullo R, Rossi Neto JM, Dos Santos CC, Contreras CA, Chaccur P, Dinkhuysen JJ, de Souza R, Dias França JI, Lin-Wang HT: Donor hypernatremia and smoking addiction contribute to primary graft failure in heart transplantation. Clin Transplant 33: e13693, 2019 PubMed

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  • 62

    Mihaylov P, Nagai S, Ekser B, Mangus R, Fridell J, Kubal C: Prognostic impact of peritransplant serum sodium concentrations in liver transplantation. Ann Transplant 24: 418425, 2019 PubMed

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  • 63

    Zhou ZJ, Chen GS, Si ZZ, Li Q, Bin YY, Qi HZ, Li J-Q: Prognostic factors influencing outcome in adult liver transplantation using hypernatremic organ donation after brain death. Hepatobiliary Pancreat Dis Int 19: 371377, 2020 PubMed

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  • 64

    Oude Lansink-Hartgring A, Hessels L, de Vries AJ, van der Bij W, Verschuuren EAM, Erasmus ME, Nijsten MWN: Donor hypernatremia is not related with the duration of postoperative mechanical ventilation, primary graft dysfunction, or long-term outcome following lung transplantation. Ann Transplant 23: 500506, 2018 PubMed

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  • 65

    Basmaji J, Hornby L, Rochwerg B, Luke P, Ball IM: A systematic review of donor serum sodium level and its impact on transplant recipients. Int J Organ Transplant Med 11: 4354, 2020 PubMed

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