European Journal of Cardiovascular Medicine

Dysnatremia poses a significant challenge in critically ill patients. Although the incidence of hyponatremia has decreased by half in recent years, the occurrence of hypernatremia has doubled [1-4]. Hypernatremia is primarily caused by water loss, with sodium (Na) excess being a less common factor [5,6]. It affects approximately 6%-42% of ICU patients and is generally associated with a 50%-60% increase in short-term mortality. Even mild hypernatremia (Na <150 mmol/L) is linked to more than a 20% 30-day mortality rate [7].

Sodium is the primary extracellular fluid cation, crucial for maintaining extracellular tonicity and water movement across cell membranes. The clinical manifestations of hypernatremia predominantly result from fluid shift from intracellular to extracellular spaces due to osmotic imbalances. Symptoms vary depending on severity and onset speed and may include thirst, muscle weakness, lethargy, restlessness, irritability, confusion, seizures, and altered consciousness levels. Severe cases can lead to intracranial blood vessel stretching and rupture [8,9].

In critical care, hypernatremia can be categorized as ICU-acquired (IAH) or preadmission (PAH) hypernatremia. PAH is more common in infants and the elderly, while IAH is prevalent in ICU settings compared to general wards. ICU hypernatremia ranges from 6%-42%, usually appearing within the first week of admission, while pre-ICU admission hypernatremia is lower at about 4% [10-13]. Both IAH and PAH independently predict mortality and longer ICU stays [14-16], with PAH showing a stronger association [17,18]. Hospital-acquired hypernatremia is often due to inadequate fluid intake compounded by ongoing losses and solute intake from medications and nutrition [19,20]. Factors like high APACHE II scores, low GCS scores, organ dysfunction, and blood transfusions are associated with IAH [13].

There's limited data on ICU hypernatremia from India and other developing nations. Thus, this study aimed to assess hypernatremia's prevalence, contributing factors, and outcomes in an academic hospital ICU in India.

The retrospective study involved reviewing ICU charts of patients admitted to the adult general ICU at a tertiary-level academic hospital. Serum sodium (Na) and electrolyte concentrations were routinely measured at least once daily for all ICU patients. Hypernatremia was defined as having two consecutive serum Na levels >145 mmol/L, while hyponatremia was defined as having two consecutive serum Na levels <135 mmol/L. Patients with neither hypernatremia nor hyponatremia were categorized as normonatremic. Hypernatremia severity was further classified as mild (serum Na 146-149 mmol/L), moderate (serum Na 150-155 mmol/L), or severe (serum Na >155 mmol/L). Acute kidney injury (AKI) was defined based on specific criteria related to serum creatinine levels and urine output.

ICU charts of all patients during the study period were retrieved, excluding those with missing medical records. Data collection included patient demographics, altered mental status, APACHE II score, serum Na levels, hypernatremia severity and duration, AKI, interventions such as hemodialysis and mechanical ventilation, length of ICU stay, and ICU mortality. Patient identities were protected, and data was stored securely.

Data analysis was performed using Microsoft Excel and EPiInfo software. Categorical variables were described using frequencies and percentages, compared using Pearson’s chi-square test. Continuous data were compared using the Kruskal-Wallace test due to non-normal distribution. ICU mortality comparisons were made using odds ratios (OR) and 95% confidence intervals (CI), with significance set at p = 0.05.

The astudy sample comprised 235 patients. Among them, 147 individuals were classified as having normal sodium levels (normonatremia), while 88 patients (37.44%) had hypernatremia. Within the hypernatremia group, 41 patients (17.44%) had increased absolute hypernatremia (IAH), and 47 (20%) exhibited pseudohypernatremia (PAH). Table 1 details and contrasts the various characteristics of the study cohort. The median age of participants was 45 years, with a slightly higher representation of females. Noteworthy, there were no significant differences observed among the three groups concerning age, gender distribution, median duration of hypernatremia during intensive care unit (ICU) stay, or need for hemodialysis.

Regarding hypernatremia severity, mild cases were notably more prevalent in the IAH group, whereas moderate and severe cases were notably more frequent in the PAH cohort (p <0.05). Comparing IAH and PAH groups, individuals with IAH showed a significantly higher requirement for mechanical ventilation, longer mechanical ventilation duration, and extended ICU stay duration (p <0.05). Conversely, those with PAH had significantly higher rates of altered mental status and median Acute Physiology and Chronic Health Evaluation II (APACHE II) scores (p <0.05), with no notable differences in mortality rates (p >0.05).

When comparing IAH with normonatremia, the IAH group exhibited significantly elevated rates of altered mental status, median APACHE II scores, mechanical ventilation necessity, longer mechanical ventilation duration, inotropic/vasopressor support requirement, extended ICU stay duration, and ICU mortality (p <0.05).

Similarly, when comparing PAH with normonatremia, the PAH group demonstrated significantly higher rates of altered mental status, median APACHE II scores, acute kidney injury (AKI), mechanical ventilation necessity, longer mechanical ventilation duration, inotropic/vasopressor support requirement, extended ICU stay duration, and ICU mortality (p <0.05).

Table 2 delineates ICU mortality concerning hypernatremia severity. Notably, compared to normonatremic subjects, there was a progressively elevated likelihood (odds ratio) of ICU mortality with increasing hypernatremia severity. Specifically, the odds of ICU mortality were 5.81 times higher among those with severe hypernatremia (p <0.01) compared to normonatremic individuals.

Table 1: Comparison of demographic and clinical characteristics between study groups

Table 2: Correlation of ICU mortality with degree of hypernatremia

In this study, hypernatremia was prevalent in 37.44% of cases. Notably, hypernatremia correlated significantly (p <0.05) with heightened rates of altered mental status, elevated APACHE II scores, increased need and duration of mechanical ventilation, greater reliance on inotropic/vasopressor support, extended ICU stays, and elevated ICU mortality rates. These associations highlight hypernatremia's link to increased illness severity and poorer ICU outcomes. Comparison between ICU-acquired hypernatremia (IAH) and preadmission hypernatremia (PAH) groups revealed higher rates of altered mental status and median APACHE II scores in the PAH group, while the need for mechanical ventilation and longer ICU stays were more pronounced in the IAH group (p <0.05). However, there were no significant differences in mortality rates between the two groups, indicating that hypernatremia's presence, regardless of origin, is associated with unfavorable ICU outcomes.

Contrasting these findings, a multicenter study in Austria reported a much lower hypernatremia prevalence of 6.9%, with corresponding mortality likelihoods for mild, moderate, and severe hypernatremia at 1.48 (1.36-1.61), 2.32 (1.98-2.73), and 3.64 (2.88-4.61) times higher, respectively [12]. Another multicenter study in France reported an ICU-acquired hypernatremia prevalence of 15.3%, associating both mild and moderate to severe hypernatremia with increased mortality rates [21]. A study in the USA found that 7% of ICU patients developed IAH, leading to older age, higher illness severity scores, longer ICU stays, and higher mortality rates compared to normonatremic patients [22]. A study in Sri Lanka reported 42.5% of ICU patients developing IAH, associated with higher APACHE II scores, lower GCS scores, increased organ dysfunction, more blood transfusions, longer ICU stays, and higher ICU mortality rates [13]. However, unlike our study, a study in the Netherlands found significantly higher mortality rates in IAH compared to PAH patients [18].

Our study, conducted in India, revealed a higher hypernatremia prevalence compared to other regions, potentially reflecting differences in patient severity between low-middle-income and higher-income countries. Future studies should investigate interventions to reduce hypernatremia prevalence by addressing underlying illnesses early and managing Na intake and fluid administration meticulously. Limitations of this study include its single-center nature, lack of data on total hypernatremia days and their correlation with outcomes, absence of data on Na intake and fluid deficits' role in hypernatremia development and patient outcomes, and lack of distinction between preadmission hypernatremia sources among PAH patients.

The study revealed a hypernatremia prevalence, considerably higher than what is typically reported in higher-income countries. This condition was significantly linked to various adverse outcomes, including a heightened rate of altered mental status, elevated APACHE II scores, increased rates and duration of mechanical ventilation, a greater need for inotropic/vasopressor support, extended ICU stays, and elevated ICU mortality rates. Furthermore, the severity of hypernatremia correlated with a notable increase in mortality rates. Future investigations should delve into discerning the contributions of sodium overload/water deficit versus illness severity in the development of hypernatremia within ICU settings.

1. Oude Lansink-Hartgring A, Hessels L, Weigel J, et al. Long-term changes in dysnatremia incidence in the ICU: a shift from hyponatremia to hypernatremia. Ann Intensive Care. 2016;6:22. DOI: 10.1186/s13613-016-0124-x.
2. Sterns RH. Disorders of plasma sodium--causes, consequences, and correction. N Engl J Med. 2015;372:55-65. DOI: 10.1056/NEJMra1404489.
3. Eghtesadi-Araghi P, Rasouli MR, Mokhtari M. Two devils: hypernatremia and hyponatremia can show faces to the same patient in the intensive care unit. Crit Care. 2009;13:404. DOI: 10.1186/cc7722.
4. Stelfox HT, Ahmed SB, Khandwala F, Zygun D, Shahpori R, Laupland K. The epidemiology of intensive care unit-acquired hyponatraemia and hypernatraemia in medical-surgical intensive care units. Crit Care. 2008;12. DOI: 10.1186/cc7162.
5. Muhsin SA, Mount DB. Diagnosis and treatment of hypernatremia. Best Pract Res Clin Endocrinol Metab. 2016;30:189-203. DOI: 10.1016/j.beem.2016.02.014.
6. Adrogué HJ, Madias NE. Hypernatremia. N Engl J Med. 2000;342:1493-9.
7. Qian Q. Hypernatremia. Clin J Am Soc Nephrol. 2019;14:432-4. DOI: 10.2215/CJN.12141018.
8. What Is hypernatremia? [Internet]. 2021. Available from: https://www.webmd.com/a-to-zguides/what-is-hypernatremia.
9. Sakr Y, Santos C, Rother S. Sodium in critical illness: an overview. In: Vincent JL (ed). Annual Update in Intensive Care and Emergency Medicine. Springer, Cham; 2014. p. 595-611.
10. Jung WJ, Lee HJ, Park S, et al. Severity of community acquired hypernatremia is an independent predictor of mortality. Intern Emerg Med. 2017;12:935-40.
11. Lindner G, Funk GC. Hypernatremia in critically ill patients. J Crit Care. 2013;28:216.e11-216.e20.
12. Funk GC, Lindner G, Druml W, Metnitz B, Schwarz C, Bauer P, Metnitz PG. Incidence and prognosis of dysnatremias present on ICU admission. Intensive Care Med. 2010;36:304-11.
13. Premaratne S, Jagoda H, Ikram MM, Abayadeera A. Acquired hypernatraemia in the intensive care units. Open Anesthesiol J. 2016;10:1-7.
14. Alansari MA, Abdulmomen A, Hussein M, Zubaidi AM, Alswaiti JT. Acquired hypernatremia in a general surgical Intensive Care Unit: Incidence and prognosis. Saudi J Anaesth. 2016;10:409-13.
15. Hu B, Han Q, Mengke N, He K, Zhang Y, Nie Z, Zeng H. Prognostic value of ICU-acquired hypernatremia in patients with neurological dysfunction. Medicine (Baltimore). 2016;95