The prospective observational cross-sectional study was carried out at the Critical Care Unit of Shri Bhikhibai Kanjibhai Shah Medical Institute and Research Hospital, Piparia, Waghodia, Gujarat, over a one-month duration in November 2024. Ethical approval was obtained from the Sumandeep Vidhyapeeth Institutional Ethics Committee (SVIEC/ON/Medi/RP/OCT/24/25). The study adhered to the ethical standards outlined in the Declaration of Helsinki and the Indian Council of Medical Research.

Sample size calculation:

n=Z²×p×q/e²

Z=1.96 at a 95% Confidence Interval (CI)

p=prevalence of hyponatremia in sepsis patients admitted to the Critical Care Department, taken as 30% (0.3). The prevalence of hyponatremia in sepsis patients in the ICU, as observed by DeVita MV et al., is around 30-40% [3].

q=1-p=0.7 e=margin of error=10%.

The calculated sample size is 80, and by adding a 10% non response rate, the total sample size is 88.

Inclusion criteria: Sepsis patients aged over 18 years admitted to the critical care unit who met the Sepsis-3 guidelines were included [9].

Exclusion criteria: Patients with hyperlipidemia, paraproteinemia, hyperglycemia, hypernatremia, or those receiving mannitol or radiographic contrast agents were excluded.

The study included 88 patients who were admitted to the critical care unit over a one-month period and met the Sepsis-3 guidelines. Participants were selected based on the inclusion and exclusion criteria, and written informed consent was obtained. A standard protocol of history-taking and clinical examination was conducted. Blood samples for routine tests were collected upon admission. Investigations necessary for the study, including ABG analysis (PaO₂/FiO₂), serum bilirubin, platelet count, serum creatinine, and serum sodium, were performed as part of standard procedures. The SOFA score was calculated upon admission to the critical care unit, and the risk of mortality was predicted [Table/Fig-1] [10,11].

Hyponatremia: Sodium level is equal to or less than 135 mmol/L.

Mild hyponatremia: 130-135 mmol/L

Moderate hyponatremia: 125-129 mmol/L

Severe hyponatremia: <125 mmol/L [4,12].

The appropriate statistical tests were applied to determine the prevalence and associations within the data. A Chi-square test with a p-value of less than 0.05 was considered statistically significant.

The average age of study patients with hyponatremia was 50.74 years, with a standard deviation of 16.49 years, indicating a moderately wide age distribution among the participants. The gender-wise distribution of the study subjects with hyponatremia (n=69) revealed that the majority were male, comprising 43 (62.32%) participants, while females accounted for 26 (37.68%) participants [Table/Fig-2]. This indicates a higher representation of males in the study population with hyponatremia.

Among the study participants (n=88), 19 (21.6%) patients had normal sodium levels. The prevalence of hyponatremia was notably high, with 78.4% exhibiting varying degrees of the condition [Table/Fig-3]. These findings highlight the significant burden of hyponatremia among patients admitted to the critical care Department.

The most common aetiological diagnoses in participants with hyponatremia were as follows: lower respiratory tract infection, which was the most frequent, affecting 23% of cases (16 patients). This was followed by decompensated CLD in 6 (9%) cases, ischaemic stroke with aspiration pneumonia in 4 (6%) patients, and urosepsis in of cases 4 (6%) patients [Table/Fig-4]. Other significant etiological causes of hyponatremia in the remaining cases included acute haemorrhagic stroke in 4 (5.5%) patients, acute cardiogenic shock in 4 (5.5%) patients, decompensated heart failure in 3 (5%) patients, acute encephalitis in 3 (5%) patients, acute kidney injury on chronic kidney disease in 3 (5%) patients, and Central Nervous System (CNS) malignancy in 3 (4%) patients. The other causes include acute gastroenteritis, viral fever, Chronic Obstructive Pulmonary Disease (COPD) exacerbation, Guillain-Barré syndrome, and cerebral venous thrombosis. These findings highlight the various underlying conditions contributing to hyponatremia in critically-ill sepsis patients.

The most frequent SOFA score in hyponatremic patients was two, observed in 19 (27.5%) patients. Higher SOFA scores were less common, with 6 (6.8%) patients having scores of 8 and 5 (7.2%) patients with a score of nine. The mean SOFA score among 69 patients with hyponatremia was 4.42, with a standard deviation of 2.34. These findings illustrate that the majority of patients had lower SOFA scores, reflecting milder organ dysfunction, although a significant proportion had moderate to severe scores, correlating with higher mortality risks.

The analysis of the association between SOFA scores and the severity of hyponatremia revealed a statistically significant relationship, as indicated by the Chi-square test result (p<0.05) [Table/Fig-5].

A significant association was found between platelet count and serum creatinine with hyponatremia severity, as evidenced by a Chi-square test (p-value of 0.03 and p-value <0.05, respectively). Patients with normal platelet counts showed higher frequencies of normal sodium levels (16) and mild hyponatremia (22), while those with abnormal platelet counts had fewer severe cases. Abnormal serum creatinine levels were more common in participants with severe hyponatremia, suggesting a link between kidney function and sodium disturbances [Table/Fig-6].

Sepsis, a dysregulated host reaction to an infection, is a major cause of hospitalisation and Intensive Care Unit (ICU) mortality [13]. In the Intensive Care across Nations (ICON) audit, 10,069 patients older than 16 years who were hospitalised in the ICU were prospectively included from Europe (54.1%), Asia (19.2%), America (17.1%), and other continents (9.6%). The incidence of sepsis ranged from 13.6 to 39.3%, and the mortality rate in intensive care was 25.8% [14].

The average age of study patients with hyponatremia was 50.74 years, with a standard deviation of 16.49 years [Table/Fig-2]. This was higher than the average age reported in the study by Kumar S et al., which was 44 years [7]. Among the study subjects with hyponatremia, 62.32% were male, and 37.68% were female. This contrasts with the findings of the study by Padhi R et al., where 56.5% of hyponatremic patients were female and 43.5% were male [8].

In present study, the prevalence of hyponatremia was notably high at 78.4%, with 39.8% classified as mild, 25% as moderate, and 13.6% as severe [Table/Fig-3]. In contrast, the study by Parajuli S et al., reported a significantly lower prevalence of hyponatremia, observed in 20.59% of their 102 patients [15].

In present study, the most common causes of hyponatremia were lower respiratory tract infections (18.2%), followed by decompensated liver disease (6.8%), ischaemic stroke with aspiration pneumonia as a complication (4.5%), and urosepsis (4.5%) [Table/Fig-4]. In contrast, the study by Padhi R et al., reported that the Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH) due to pneumonia (36.25%) was the most frequent cause, followed by severe sepsis (21.51%) and trauma (21.11%) [8]. Similar results were observed in the study by Nair V et al., which found that pneumonia is frequently associated with hyponatremia at the time of admission, leading to severe illness, prolonged hospitalisation, and increased mortality [16].

In present study, decompensated liver disease was the second most common cause of hyponatremia, observed in 6.8% of hyponatremic patients. This is significantly lower compared to the findings of a study by Bhandari A and Chaudhary A, where a high prevalence of hyponatremia (41.22%) was reported among patients with CLD. In their study of 114 patients, 47 were found to have hyponatremia, with a 95% confidence interval ranging from 32.18% to 50.25% [17].

In present study, ischaemic stroke accounted for 4.5% of hyponatremia cases, which is considerably lower than the 35% reported in the study by Saleem S et al., [18]. In their study, the most common causes of hyponatremia in stroke patients were identified as SIADH and Cerebral Salt Wasting syndrome (CSW). Overall, hyponatremia was found to negatively impact stroke outcomes, highlighting the importance of closely monitoring serum sodium levels to prevent mortality [18].

The SOFA score assesses the severity of illness using straightforward measurements of major organ function based on routine tests. It requires only six variables, enabling quick evaluation. The scores are calculated 24 hours after ICU admission and subsequently every 48 hours. This scoring system has been validated in both medical and surgical ICUs, demonstrating that higher SOFA scores are associated with lower survival rates [19].

In present study, the most frequent SOFA score observed in sepsis patients with hyponatremia was two, recorded in 19 patients (27.5%). Higher SOFA scores were less frequent, with six patients (6.8%) having scores of eight and five patients having a score of nine. The mean SOFA score was 4.42, with a standard deviation of 2.34. This contrasts with the study by Jones AE et al., where the average SOFA score at admission to the Emergency Department was 7.1±3.6 points [6]. Similarly, in the study by Kumar S et al., the mean SOFA score at the time of admission was 6.18±2.38 points, which is also higher than present findings [7].

In present study, the association between SOFA scores and the severity of hyponatremia showed a statistically significant result, as demonstrated by the Chi-square test (p<0.05) [Table/Fig-5]. This suggests that the predicted mortality risk based on the SOFA score is higher in sepsis patients with hyponatremia, indicating they are at an increased risk of mortality [Table/Fig-1]. Thus, the SOFA score is a valuable tool for triaging patients and prioritising treatment.

Similar results supporting the findings of present study have been reported in the following studies. A retrospective study by Nzerue CM et al., which included 168 patients with severe hyponatremia, found that 89 patients (52.9%) displayed symptoms, with a significant mortality rate of 20.2% (34 patients) [20]. In line with this, the study by Padhi R et al., showed that patients with hyponatremia experienced longer ICU stays, prolonged mechanical ventilation, and a higher mortality rate [8]. Like-wise, Shakhe J et al., observed greater mortality, prolonged ICU stays, and higher ventilator usage in ICU patients with hyponatremia [21]. Additionally, Funk GC et al., conducted a large retrospective study involving 151,486 adults across 77 ICUs in Austria over a 10-year period, finding that all forms and severities of dysnatremia were linked to higher mortality rates [22].

In contrast to present study, Kumar S et al., found no significant association between the overall SOFA score for sepsis and the severity or presence of hyponatremia, suggesting differing findings in terms of the predictive value of SOFA scores in their study [7].

The present study found a significant association between platelet count and the severity of hyponatremia, as demonstrated by a Chi-square test (p-value of 0.03) [Table/Fig-6]. Patients with normal platelet counts exhibited a higher frequency of normal sodium levels and mild hyponatremia, whereas those with abnormal platelet counts had a lower frequency of normal sodium levels and a higher occurrence of mild and moderate hyponatremia.

In present study, the association between serum creatinine levels and the severity of hyponatremia was statistically significant, as evidenced by the Chi-square test (p-value of <0.05) [Table/Fig-6]. Abnormal serum creatinine levels were more common among participants with severe hyponatremia, suggesting a link between kidney function and sodium disturbances. The present study results contrast with those observed in the study conducted by Kumar S et al., where no correlation was found between the individual components of the SOFA score and hyponatremia [7].

The study is conducted at a single Institution, which may limit generalisability to other populations or settings. Additionally, the study does not include the endpoint of mortality in sepsis patients; therefore, only the predicted mortality rate is considered to evaluate the prognosis.

The association between hyponatremia and the SOFA score in sepsis patients holds significant clinical relevance. Hyponatremia, a frequent electrolyte imbalance in critically-ill individuals, reflects illness severity and may exacerbate organ dysfunction. It aids in risk stratification, guides targeted interventions, and helps predict mortality risk in sepsis patients. This relationship facilitates early intervention, minimises complications, and improves patient outcomes in sepsis management.