Clinical profile of hyponatraemia in critically ill patients: A retrospective study

INTRODUCTION

Hyponatraemia is a common electrolyte abnormality found in hospitalised patients. Irrespective of the cause, hyponatraemia is associated with substantial morbidity and mortality. Hyponatraemia is clinically defined by a serum sodium level of <135 mEq/L.

It is classified as mild (130–134 mmol/L), moderate (125–129 mmol/L) and severe (<125 mmol/L) depending on the serum sodium level. Hyponatraemia is classified as hypovolemic, euvolemic and hypervolemic hyponatraemia depending on the fluid volume status.^[1] Hyponatraemia develops mainly from solute dilution, solute depletion or a combination of both. Solute dilution results from overconsumption of water or the failure of the kidneys to excrete water, whereas solute depletion results from low salt intake or increased excretion of sodium by the kidneys. Hyponatraemia usually develops as a complication of cardiac, renal, endocrine, neurological or respiratory diseases. It also results from the use of medications such as diuretics or antidepressants. Thiazide-induced hyponatraemia, occurs due to increased water intake, reduction in diluting ability and water excretion in the distal tubule. Sodium plus potassium concentration in urine exceeds that in the plasma, which directly lowers plasma sodium concentration. Loop diuretics cause inhibition of sodium chloride transport in the loop of Henle, which prevents the generation of the counter-current gradient and therefore restricts water retention by antidiuretic hormone (ADH). Hence, hyponatraemia is not common with loop diuretics.^[2]

Sodium ion is one of the essential electrolytes that play a significant role in various body functions by maintaining water balance, providing proper transmission of nerve signals and regulating muscle function. Thus, hyponatraemia can result in health-related problems that range from nausea, malaise, to lethargy, headache, altered level of consciousness, seizures and coma. Majority of the hyponatraemic patients present without symptoms, making it difficult to diagnose with physical assessment only.^[3]

Critical illness is a state of ill health with vital organ dysfunction, a high risk of imminent death if care is not provided, and the potential for reversibility. Critical care is the identification, monitoring and treatment of patients with critical illness through the initial and sustained support of vital organ functions.^[3] Severity of critically ill patient is assessed by scoring systems such as logistic organ dysfunction system, simplified acute physiology score, acute physiology and chronic health evaluation (APACHE)-I, APACHE-II, APACHE III, APCHE-IV, sequential organ failure assessment, quick sequential organ failure assessment. APACHE II introduced in 1985, is a modification of the original APACHE developed in 1981.

II has three domains: ‘Acute Physiology’, ‘Chronic Health Evaluation’ and ‘Age’ reflected by the acronym APACHE. The first domain relates to acute physiological changes within the first 24 h. Total maximum score will be 71 calculated as 12 physiological variables (12 × 4), temperature, mean arterial blood pressure, heart rate, respiratory rate, arterial oxygenation, arterial pH, serum sodium, serum potassium, serum creatinine, haematocrit and total leucocyte count and glasgow coma scale (0–12) and chronic health problems (0–5) including severe organ insufficiency or immunocompromised and Age^[4] (0–6).

Several studies across the world, including India, have revealed hyponatraemia being more prevalent in elderly patients with cardiovascular disease, endocrinal disorders and drug usage. The common symptoms are altered sensorium, vomiting and seizure and the most common aetiology is syndrome of inappropriate secretion of antidiuretic hormone (SIADH). Hence, this study is planned in the Tertiary Care Centre in Rural South Karnataka at Sri Siddhartha Medical College, Hospital and Research Centre, Tumakuru, to characterise the severity distribution of hyponatraemia, associated clinical manifestations, underlying comorbidities and evaluate the correlation between APACHE II score and in-hospital mortality in critically ill adult patients with hyponatraemia.

AIMS AND OBJECTIVES

The aim of this study is to evaluate the clinical profile of hyponatraemia in critically ill adult patients admitted to a tertiary care centre, with specific objectives to assess the severity distribution of hyponatraemia, describe the associated clinical manifestations, identify common comorbidities, and evaluate the correlation between APACHE II scores and in-hospital mortality among patients with hyponatraemia.

MATERIAL AND METHODS

A retrospective observational study conducted between January and December 2023 included patients admitted to the Department of General Medicine, Sri Siddhartha Medical College Hospital and Research Centre, aged more than 18 years. All critically ill patients with confirmed hyponatraemia (serum sodium <135 mEq/L) were included. Those with a history of recent administration of Mannitol, IV immunoglobulin, recent prostate surgery were excluded. Patient demographic details, clinical features, comorbidities, drug history, serum sodium level, diagnosis, duration of intensive care unit (ICU) stay, need for ventilator support and cause of death were obtained from the case records and recorded in a prescribed pro forma. APACHE II score calculated using online calculator of Clincalc.com (https://clincalc.com/IcuMortality/APACHEII.aspx) was also recorded in the pro forma. Patients were classified into mild, moderate and severe hyponatraemia categories. Data were entered into Microsoft Excel sheet and analysed using the Statistical Package for the Social Sciences software. Institutional Scientific clearance and Institutional ethical approval were obtained.

RESULTS

During the study, 562 patients were admitted between January and December 2023. Among 562, there were 209 patients (37.1%) with hyponatraemia. Out of 209 patients, 127 (60.7%) are mild hyponatraemia, 42 (20%) are moderate hyponatraemia and 40 (19.1%) are severe hyponatraemia [Figure 1 and Table 1].

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Figure 1:

Severity of hyponatraemia.

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There was a male preponderance with 124 patients (59.3%) in mild (59.8%) and moderate (73.8%), while female preponderance in severe hyponatraemia (57.5%). The maximum patients were in the age group over 60 years, 112 (53.5%), followed by 84 (40%) in the age group of 30–59 years, 13 (6%) in the age group of 18–29 years [Table 2 and Figure 2].

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Figure 2:

Age and sex distribution.

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There were 115 (55%) Asymptomatic and 94 (45%) Symptomatic patients.

Among the asymptomatic 70 (60.8%) were in Mild, 27 (23.4%) in, moderate and 18 (15.6%) in Severe hyponatraemia [Table 3].

Among the symptomatic patients, nausea and vomiting were the most common presenting symptoms, observed in 60 patients (64%), followed by altered sensorium in 37 patients (39%) and seizures in 6 patients (7%) [Table 4].

Commonly observed comorbidities were diabetes mellitus 91 (43%), hypertension 86 (41.1%), coronary artery disease 28 (13.3%), hypothyroidism 6 (2%), chronic obstructive pulmonary disease (COPD) 19 (9%), bronchial asthma 9 (4%), tuberculosis 12 (5%), chronic kidney disease 20 (9%) and chronic liver disease 14 (6%). A history of consumption of diuretics was observed in 28 (13.3%), with 24 (86%) taking thiazides and an atypical antipsychotic in 1 [Table 5 and Figure 3].

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Figure 3:

Commonly observed comorbidities.

COPD: Chronic obstructive pulmonary disease, CKD: Chronic kidney disease, CLD: Chronic liver disease, CAD: Coronary artery disease.

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During the study, 41 (19.6%) required ICU stay, and 29 (13.8%) required ventilator support. APACHE II score varied from 02 to 44 with a mean of 14.8. The majority, 89 (42.5%), had an APACHE II score of 11–20, followed by 75 (35.8%) with 0–10 points, 32 (15.3%) with 21–30 points and 13 (6%) with more than 30 points [Figure 4 and Table 6].

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Figure 4:

Acute physiology and chronic health evaluation II score.

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Among 13 patients with a score of >30, 12 patients died, and 1 survived [Figure 5].

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Figure 5:

Acute physiology and chronic health evaluation II score among non survivors.

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During the study, there were 20 (9%) deaths, with 13 (65%) male and 7 (35%) female. Out of 20 deaths, 12 patients had an APACHE score of more than 30.

The most common cause of death was Sepsis in 9 (45%), respiratory failure in 7 (35%), cardiovascular disease in 3 (15%) and pulmonary embolism in 1 (5%) [Table 7].

DISCUSSION

Hyponatraemia is a common electrolyte abnormality found in hospitalised patients. Irrespective of the cause, hyponatraemia is associated with substantial morbidity and mortality. Etiological evaluation of the risk factors associated with the development of hyponatraemia is important in preventing recurrent episodes. In this centre, the prevalence of Hyponatraemia was 37.1% compared to 22% by Sundar et al.^[4] Therefore, routine monitoring of serum sodium in high-risk hospitalised patients can help prevent overlooked or recurrent hyponatraemia.

The prevalence of mild hyponatraemia was 60.7% compared to 46% by Sundar et al., to 20% by Singh et al. Prevalence of moderate hyponatraemia was 20% compared to 35% by Sundar et al., 20% in Singh et al. The prevalence of severe hyponatraemia was 19.1% compared to 19% by Sundar et al. and 60% by Singh et al.^[4,5] Early identification of patients progressing from mild to moderate or severe hyponatraemia may allow timely corrective measures and prevent complications.

As age increases, the prevalence of hyponatraemia also increases. Majority of patients 53.5% were above 60 years compared to 52.2% by Singh et al., 21% by Sundar et al., followed by 40% in 30–59 years compared to 69% by Sundar et al., 34% in 40–59 years by Singh et al. and only 6% in 18–29 years compared to 10% by Sundar et al.^[4,5] Since prevalence increases with age, regular electrolyte assessment in elderly patients is important.

Male preponderance of 59.3% in hyponatraemia is consistent with 57% by Sundar et al. and 60% by Singh et al.^[4,5]

Male preponderance of 59.8% was also observed in mild hyponatraemia, compared to 58.6% by Sundar et al. and 60% by Singh et al. Moderate hyponatraemia of 73.8% compared to 57.1% by Sundar et al. and 64% by Singh et al. Female preponderance of 57.5% was observed in severe hyponatraemia compared to 47% by Sundar et al., 41% by Singh et al.^[4,5] Awareness of gender-specific susceptibility can aid in early recognition and prevention of severe hyponatraemia.

There were 45% symptomatic compared to 38% by Rai et al., 86% by Sundar et al. The common symptoms observed were nausea/vomiting in 64% compared to 37% by Singh et al., 38% by Rai et al., 28% by Babliche et al., 19% by Sundar et al., followed by altered sensorium in 40% compared to 43% by Rai et al., 48% by Babaliche et al., 57% by Singh et al., 15% by Sundar et al., and seizures in 6% compared to 6.6% by Singh et al., 6% by Rai et al., 9% by Babaliche et al., 5% by Sundar et al.^[4-7] Educating clinicians to promptly evaluate nonspecific symptoms such as nausea and altered sensorium can help prevent further sodium decline and its complications.

Comorbidities such as diabetes mellitus and hypertension had a significant impact on the severity of hyponatraemia. Diabetes mellitus, as an endocrine disorder, causes increased glucose glomerular filtration, which leads to an increase in fluid excretion by osmotic diuresis, resulting in hypovolemia and hyponatraemia. Diabetes mellitus was observed in 43% and hypothyroidism in 2% in this study, compared to 36% diabetes mellitus by Singh et al., 29% diabetes mellitus by Babaliche et al., and 30% diabetes mellitus and 13% Hypothyroidism by Sundar et al.^[4,5,7] Good control of endocrine comorbidities and routine electrolyte checks in such patients is essential.

A well-known mechanism of hyponatraemia due to cardiovascular diseases has been attributed to an impairment in the excretion of diluted urine, which disturbs water balance and leads to an increase in extracellular fluid, causing hyponatraemia.

Hyponatraemic hypertensive syndrome is a well-known entity wherein the most common association is in patients with essential hypertension receiving diuretics, which interfere with the metabolism of a variety of electrolytes and cause electrolyte imbalance.^[7] Hypertension was observed in 41.1% and coronary artery disease in 13.3% in this study, comparable with 48.5% hypertension and 6% chronic heart failure by Singh et al., 49% hypertension by Babaliche et al. and 31% Hypertension by Sundar et al.^[4,5,7]

Hyponatraemia can occur in COPD patients as a manifestation of secondary water retention in comorbidities such as heart or renal failure. In addition, as in other lung diseases, hyponatraemia can appear as a consequence of different drug treatments, adrenal insufficiency (i.e. corticosteroid withdrawal) or SIADH.^[8] In this study, COPD was seen in 9%; bronchial asthma in 4%; tuberculosis in 5% compared to 4.5% bronchial asthma by Singh et al., 9% respiratory disease by Babaliche et al., followed by chronic kidney disease in 13.3% compared to 12% by Sundar et al., 17% renal failure by Rai et al., 15% renal disease by Babaliche et al., 10% chronic kidney disease by Singh et al., chronic liver disease in 5% compared to 7% liver failure by Sundar et al., 21% abdominal disease by Babaliche et al., 14% chronic liver disease by Singh et al., 6% cirrhosis of liver by Rai et al., 7% liver failure by Sundar et al.^[4-7]

Thiazide-induced hyponatraemia occurs due to increased water intake, reduction in diluting ability and water excretion in the distal tubule. Sodium plus potassium concentration in urine exceeds that in the plasma, which directly lowers plasma sodium concentration. Loop diuretics cause inhibition of sodium chloride transport in the loop of Henle, which prevents the generation of the counter-current gradient and therefore restricts water retention by ADH. Hence, hyponatraemia is not common with loop diuretics.^[2] During our study history of consumption of diuretics was observed in 13.3% compared to 14.9% by Rai et al., 30.7% by Singh et al., 15% drug intake, including diuretics by Sundar et al. Consumption of thiazide diuretics was seen in 86% of the 28 cases with a diuretic history in this study, comparable with 66% thiazide diuretics use observed by Singh et al.^[4-6] Judicious prescribing of thiazide diuretics with periodic sodium monitoring is essential to prevent thiazide-induced hyponatraemia.

Mortality of 9% compared to 15.2% by Singh et al. and 6% by Babaliche et al., 13% by Sundar et al.^[4,5,7] Maximum mortality (60%) was observed in patients with APACHE II score of more than 30. This finding was consistent with a study by Sadaka et al, which showed that APACHE II scores of more than 30 were associated with higher mortality.^[9] Early and accurate identification and treatment of hyponatraemia will help in decreasing morbidity and mortality.

This study also has some limitations. Being a retrospective study from a single centre, data collected included only inpatients from internal medicine. Subtypes of hyponatraemia (euvolemic, hyper/hypovolemic) were not discussed. Future studies incorporating volume-status-based preventive strategies may help refine early interventions and reduce disease burden.

CONCLUSION

Hyponatraemia was frequently observed among critically ill elderly patients, with mild hyponatraemia being the most common severity category. Nearly half of the patients were symptomatic, with nausea/vomiting and altered sensorium being the predominant clinical manifestations, particularly in moderate-to-severe hyponatraemia. Diabetes mellitus and hypertension were the most commonly associated comorbidities. Higher APACHE II scores were strongly associated with increased mortality, with the majority of deaths occurring in patients with scores above 30. Routine serum sodium monitoring and early risk stratification using APACHE II scoring in high-risk patients may help in early identification and prevention of adverse outcomes associated with hyponatraemia.