
==== Front
Acta Clin Croat
Acta Clin Croat
ACC
Acta Clinica Croatica
0353-9466
1333-9451
Sestre Milosrdnice University Hospital and Institute of Clinical Medical Research, Vinogradska cesta c. 29 Zagreb

acc-62-510
10.20471/acc.2023.62.03.13
Original Scientific Papers
GLUCOSE AND SODIUM LEVELS AS DISEASE OUTCOME PREDICTORS IN CRITICALLY ILL PATIENTS
Dragila Željka 1
Dorokazi Andrea 2
Mihić Damir 3
Loinjak Domagoj 3
Šram Miroslav 4
Bačun Tatjana 5 6
1 Osijek University Hospital Center, Osijek, Croatia;
2 Slavonija Polyclinic, Osijek, Croatia;
3 Intensive Care Unit, Department of Internal Medicine, Osijek University Hospital Center, Osijek, Croatia;
4 Division of Cardiology, Department of Internal Medicine, Osijek University Hospital Center, Osijek, Croatia;
5 Faculty of Medicine in Osijek, Josip Juraj Strossmayer University of Osijek, Osijek, Croatia;
6 Division of Endocrinology, Department of Internal Medicine, Osijek University Hospital Center, Osijek, Croatia
Correspondence to: Tatjana Bačun, MD, Division of Endocrinology, Department of Internal Medicine, Osijek University Hospital Center, Ulica Josipa Hutlera 4, HR-31000 Osijek, Croatia, E-mail: tbacun@gmail.com, Received July 13, 2022, accepted February 14, 2023 February 1, 2023
11 2023
11 2023
62 3 510518
Sestre Milosrdnice University Hospital
2023
Sestre Milosrdnice University Hospital
https://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives (CC BY-NC-ND) 4.0 License.
SUMMARY

The main aim of this study was to examine the association of glucose and sodium level with diagnosis and disease outcome of critically ill patients. Glucose and sodium concentrations of 283 patients admitted in critical condition to the Intensive Care Unit of the Department of Internal Medicine in a period from November 1, 2015 to February 28, 2017 were reviewed. The most common diagnoses in critically ill patients were acute kidney injury (26.1%) and sepsis (including septic shock, 22.3%). Significantly lower glucose concentration was observed in patients with acute kidney injury (p=0.02), whereas patients in sepsis and septic shock had a significantly higher sodium concentration (p=0.04). Higher glucose level was related to higher mortality rate (p=0.001). On the other hand, sodium level was not significantly associated with survival. Higher mortality, as well as higher glucose concentration were more common in patients older than 65 years (p<0.001). Study results showed significantly lower glucose concentrations in patients with acute kidney injury, whereas in patients older than 65, glucose concentration was significantly higher. Patients in sepsis and septic shock had significantly higher sodium concentrations. Higher concentration of glucose was connected with higher mortality in the elderly, whereas sodium concentration did not show connection with mortality.

Key words:

Critical illness
Glucose
Intensive care unit
Sodium
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pmcIntroduction

Patients admitted to the intensive care unit (ICU) are a heterogeneous population which differs in admission diagnoses and comorbidities. The most common indications for admission to the ICU are hemodynamic instability, respiratory failure, and sepsis. About 50% of patients admitted to the ICU have a fatal outcome, of which 80% die within 15 days of admission (1). Mortality of patients in the ICU depends on the patient general condition, age, length of stay, immobility, comorbidities, the need to use mechanical ventilation and vasopressor drugs, etc. (2). Electrolyte disturbances and insulin use have been shown to be associated with increased mortality of patients in the ICU, indicating the importance of monitoring glucose and sodium levels in these patients (3).

Glucose is the most important source of energy for human metabolism. Impaired glucose levels, whether hyperglycemia or hypoglycemia, have been associated with poor outcomes of patients in the ICU (4, 5). These patients have stress hyperglycemia, which is defined as a transient increase in glucose concentration in response to an acute condition, i.e., disease. In most cases, these patients do not have diabetes. However, stress hyperglycemia can also occur in patients with diabetes in whom glucose concentrations are mostly higher than 13.9 mmol/L. According to the American Diabetes Association, in patients without diabetes, stress hyperglycemia is defined as a glucose concentration higher than 7.8 mmol/L in the presence of acute disease. Glycosylated hemoglobin (HbA1c) levels help distinguish patients with stress hyperglycemia (HbA1c <6.5%) from those with undiagnosed diabetes (HbA1c >6.5%) (6).

Stress hyperglycemia and insulin resistance are mechanisms preserved through evolution that enable survival in periods of great stress for the body. In ischemic conditions such as sepsis, glucose passes from the bloodstream through the interstitial space into the cell due to concentration gradient. Elevated blood glucose levels in stress hyperglycemia facilitate the transfer of glucose down the concentration gradient and thus allow adequate cell nutrition while avoiding hyperosmolarity of extracellular fluid. Furthermore, acute hyperglycemia may protect the cell by promoting pathways that inhibit apoptosis and promote angiogenesis (4).

Hormones that oppose insulin action (catecholamines, glucagon, growth hormone and cortisol), adipokines and inflammatory cytokines are involved in the pathophysiology of stress hyperglycemia. They lead to excessive glucose production in the liver and insulin resistance. Glucose is a proinflammatory mediator which can lead to a vicious circle in which hyperglycemia leads to even more severe hyperglycemia (7). To avoid these consequences of severe stress hyperglycemia, glucose monitoring and treatment of hyperglycemia is intensified. However, strict control of glucose levels has been shown to often lead to moderate and severe hypoglycemia associated with higher mortality in critically ill patients. Hypoglycemia leads to reduced glucose availability to glucose-dependent cells and tissues such as the brain and macrophages. Hypoglycemia may also occur as a consequence of the underlying disease and thus may serve as a marker for identification of diseases that lead to increased mortality in the ICU (5).

Sodium is the main extracellular cation. Disorders of sodium concentration are one of the most common electrolyte disturbances in the ICU. About one-third of patients are admitted to the ICU with sodium disorders and another third of patients will develop the disorder during hospitalization (8, 9).

According to previous research, hyponatremia is present in 15%-30% of patients admitted to the ICU, most often with slightly reduced sodium levels. The mortality of patients with hyponatremia is up to three times higher than that of patients with normal sodium concentration. All degrees of hyponatremia are associated with increased mortality in critically ill patients (10, 11). Factors influencing the occurrence of hyponatremia are old age, renal failure, adrenal and thyroid insufficiency, diuretic use, chronic heart failure, and central nervous system diseases (8). Hyponatremia leads to a decrease in the extracellular fluid osmolarity leading to intracellular edema which is particularly dangerous in the brain. If hyponatremia is corrected too quickly, a sudden increase in extracellular fluid osmolarity will lead to dehydration of brain cells and consequent demyelination (12). Disruption of sodium concentration alone may not lead to higher mortality in these patients but may serve as a marker of the severity of the underlying disease, especially if sodium levels are extremely low (13).

On admission to the ICU, hypernatremia is present in 2% to 6% of patients, while between 6% and 26% of patients will develop hypernatremia during their hospital stay. Hypernatremia is associated with increased patient mortality regardless of its severity. Studies have shown that mild hypernatremia is associated with twice the mortality and severe with three times the mortality compared with patients with normal sodium levels (14). Hypernatremia can occur due to fever (sepsis and pneumonia), uncontrolled diabetes, osmotic diarrhea, and excessive use of furosemide with inadequate water intake. Hypernatremia leads to insulin resistance, prevents hepatic breakdown of lactate, reduces left ventricular contractility, and leads to neurological consequences (8, 9).

The aim of this study was to examine the effect of different glucose and sodium concentrations on patient outcome in the ICU.

Patients and Methods

The research was organized as a cross-sectional study with historical data. It was approved by the Ethics Committee of the Faculty of Medicine Osijek, Josip Juraj Strossmayer University in Osijek. Data were collected by searching medical records of the Department of Internal Medicine, Osijek University Hospital Center. All patients admitted to the ICU of the Department of Internal Medicine, Osijek University Hospital Center in the period from November 1, 2015 to February 28, 2017 were included in the study. The research included 283 patients of both genders.

On searching the documentation, patient age, gender, diagnosis at admission, and disease outcome were recorded. Of laboratory findings, data on the concentrations of glucose and sodium at patient admission to the ICU were monitored. According to the outcome of the disease, patients were divided into two groups, i.e., transfer and death. Patients were divided into groups according to glucose and sodium concentrations into those who had low, normal and high values. Glucose values ​​were further divided into categories as follows: mild (4.0-4.3 mmol/L), moderate (2.0-3.9 mmol/L) and severe (<2.0 mmol/L) hypoglycemia, normal values ​​4.4-6.4 mmol/L; and mild (6.5-10.0 mmol/L), moderate (10.1-15.0 mmol/L), severe (15.1-25.0 mmol/L) and extreme (>25.0 mmol/L) hyperglycemia. Sodium values ​​were further divided into categories as follows: mild (130-134 mmol/L), moderate (125-129 mmol/L) and severe (<125 mmol/L) hyponatremia, normal values 135-145 mmol/L; and mild (146-155 mmol/L), moderate (156-160 mmol/L) and severe (>160 mmol/L) hypernatremia. Data on glucose concentration at admission were available for 282 patients.

Statistical analysis

Categorical data were expressed as absolute and relative frequencies. Numerical data were described by the median and interquartile range. The normality of distribution of numerical variables was examined by the Shapiro-Wilk test. Differences in category variables were examined with the χ2-test and, if necessary, with Fisher exact test. For testing differences between numerical data, the Mann Whitney U test was used (15). All p values were two-tailed. The significance level was set to Alpha=0.05. MedCalc Statistical Software version 14.12.0 (MedCalc Software bvba, Ostend, Belgium; 2014) was used on statistical analysis.

Results

The research included 283 patients, of which 144 (50.9%) were men and 139 (49.1%) were women. Their median age was 73 years (interquartile range, 63 to 80 years) ranging from 19 to 93 years. The most common diagnoses on admission were acute kidney injury (n=74, 26%) and sepsis (including septic shock, n=63, 22.3%). The largest number of patients had elevated glucose values ​​(n=204, 72.3%), whereas sodium values ​​were mostly normal (n=166, 58.7%). Fatal outcome was reported in 175 (61.8%) patients (Table 1).

Table 1 Basic characteristics of patients admitted to the Intensive Care Unit

	    n (%)	
    Gender	    Male	    144 (50.9)	
    Female	    139 (49.1)	
    Age	    <65 years	    89 (31.4)	
    ≥65 years	    194 (68.6)	
    Diagnosis	    Acute kidney injury	    74 (26.1)	
    Sepsis, septic shock	    63 (23.3)	
    Coronary artery disease	    28 (9.9)	
    Heart failure	    24 (8.5)	
    Pneumonia	    20 (7.1)	
    Drug intoxication	    20 (7.1)	
    Glucose*	    Low	    19 (6.7)	
    Normal	    59 (20.9)	
    High	    204 (72.3)	
    Sodium	    Low	    76 (26.9)	
    Normal	    166 (58.7)	
    High	    41 (14.5)	
    Outcome	    Transfer	    108 (38.2)	
    Death	    175 (61.8)	
    Total	    283 (100)	
*Data available on 282 patients

Patients with acute kidney injury were significantly more likely to have elevated glucose values ​​(p=0.02, χ2-test). Sodium values ​​were significantly higher in subjects with sepsis and septic shock (p=0.04, χ2-test). No significant differences in glucose and sodium concentrations were found compared to other diagnoses (Table 2).

Table 2 Glucose and sodium levels in relation to diagnosis at admission to the Intensive Care Unit

	    n (%)	    p	
    Low	    Normal	    High	
    Acute kidney injury					
    Glucose	    7 (9.5)	    8 (10.8)	    59 (79.7)	    0.02*	
    Sodium	    13 (17.6)	    44 (59.5)	    17 (23)	    0.53*	
    Sepsis, septic shock					
    Glucose	    4 (6.3)	    17 (27)	    42 (66.7)	    0.38*	
    Sodium	    7 (11.1)	    31 (49.2)	    25 (39.7)	    0.04*	
    Coronary artery disease					
    Glucose	    0	    6 (21.4)	    22 (78.6)	    0.42†	
    Sodium	    6 (21.4)	    17 (60.7)	    5 (17.9)	    0.35*	
    Heart failure					
    Glucose	    0	    3 (13)	    20 (87)	    0.28†	
    Sodium	    2 (8.3)	    18 (75)	    4 (16.7)	    0.27†	
    Pneumonia					
    Glucose	    2 (10)	    3 (15)	    15 (75)	    0.18†	
    Sodium	    1 (5)	    16 (80)	    3 (15)	    0.72†	
    Drug intoxication					
    Glucose	    2 (10)	    6 (30)	    12 (60)	    0.32†	
    Sodium	    2 (10)	    12 (60)	    6 (30)	    0.85†	
*χ2-test; †Fisher exact test

Glucose concentrations differed significantly between the two age groups observed. The largest number of patients older than 65 had elevated glucose values ​​(80.4%; p<0.001, χ2-test). In this age group, 13.4% of patients had normal glucose values, in contrast to the age group younger than 65, where 38% of patients had normal glucose values. No significant differences in sodium concentration were found according to age. In both age groups, the majority of patients had normal sodium values ​​(Table 3).

Table 3 Glucose and sodium levels in relation to age of patients admitted to the Intensive Care Unit

	    n (%)	    p*	
    Low	    Normal	    High	
    Glucose					
    <65 years	    7 (8)	    33 (38)	    48 (55)	    <0.001	
    ≥65 years	    12 (6.2)	    26 (13.4)	    156 (80.4)	
    Sodium					
    <65 years	    9 (10.1)	    51 (57.3)	    29 (32.6)	    0.2	
    ≥65 years	    32 (16.5)	    115 (59.3)	    47 (24.2)	
*χ2-test

Significant difference in glucose concentration was observed according to treatment outcome (p=0.001, Fisher exact test). Patients who had normal glucose values ​​were more likely to have a positive treatment outcome, i.e., they were transferred from the ICU. On the other hand, patients with elevated glucose levels and those with moderately and significantly reduced values ​​were more likely to have fatal outcome (Table 4). The median glucose value was 7.3 mmol/L (interquartile range 5.7-11.8 mmol/L) in patients who were transferred and 10.6 mmol/L (interquartile range 7.1-15.4 mmol/L) in patients who died, yielding a significant difference (p<0.001, Mann Whitney U test).

Table 4 Glucose levels in relation to outcome of patients admitted to the Intensive Care Unit

    Glucose (mmol/L)	    n (%)	    p*	
    Transfer	    Death	    Total	
    Severe hypoglycemia (<2.0)	    2 (40)	    3 (60)	    5 (1.8)	    0.001	
    Moderate hypoglycemia (2.0-3.9)	    1 (14.3)	    6 (85.7)	    7 (2.5)	
    Mild hypoglycemia (4.0-4.3)	    4 (57.1)	    3 (42.9)	    7 (2.5)	
    Euglycemia (4.4-6.4)	    36 (61)	    23 (39)	    59 (20.9)	
    Mild hyperglycemia (6.5-10.0)	    33 (38.8)	    52 (61.2)	    85 (30.1)	
    Moderate hyperglycemia (10.1-15.0)	    15 (26.8)	    41 (73.2)	    56 (19.9)	
    Severe hyperglycemia (15.1-25.0)	    11 (22.9)	    37 (77.1)	    48 (17)	
    Extreme hyperglycemia (>25.0)	    5 (33.3)	    10 (66.7)	    15 (5.3)	
    Total	    107 (37.9)	    175 (62.1)	    282 (100)		
*Fisher exact test

No significant difference in sodium concentration was observed according to patient outcome (p=0.12, Fisher exact test). The greatest difference was observed in patients with moderately low (125-129 mmol/L) and slightly elevated (146-155 mmol/L) sodium levels. These patients were more likely to have fatal outcome (Table 5). The median sodium concentration was 138 mmol/L (interquartile range 135-141 mmol/L) in patients who were transferred and 137 mmol/L (interquartile range 133-142 mmol/L) in patients who died, which did not make a significant difference (p=0.79, Mann Whitney U test).

Table 5 Sodium levels in relation to outcome of patients admitted to the Intensive Care Unit

    Sodium (mmol/L)	    n (%)	    p*	
    Transfer	    Death	    Total	
    Severe hyponatremia (<125)	    5 (55.6)	    4 (44.4)	    9 (3.2)	    0.12	
    Moderate hyponatremia (125-129)	    5 (22.7)	    17 (77.3)	    22 (7.8)	
    Mild hyponatremia (130-135)	    15 (33.3)	    30 (66.7)	    45 (15.9)	
    Eunatremia (136-145)	    73 (44)	    93 (56)	    166 (58.7)	
    Mild hypernatremia (146-155)	    9 (25)	    27 (75)	    36 (12.7)	
    Moderate hypernatremia (156-160)	    0	    1 (100)	    1 (0.4)	
    Severe hypernatremia (>160)	    1 (25)	    3 (75)	    4 (1.4)	
    Total	    108 (38.2)	    175 (61.8)	    283 (100)		
*Fisher exact test

There were no significant differences between men and women in relation to survival (p=0.14, Fisher exact test). Older age was significantly associated with fatal outcome (p<0.001, Fisher exact test). Death was reported in 70.1% of patients over 65 years of age and in 43.8% of patients under 65 years of age (Table 6).

Table 6 Outcome in relation to gender and age of patients admitted to the Intensive Care Unit

	    n (%)	    p*	
    Transfer	    Death	    Total	
    Gender	    Male	    61 (42.4)	    83 (57.6)	    144 (50.9)	    0.14	
    Female	    47 (33.8)	    92 (66.2)	    139 (49.1)	
    Age	    <65 years	    50 (56.2)	    39 (43.8)	    89 (31.4)	    <0.001	
    ≥65 years	    58 (29.9)	    136 (70.1)	    194 (68.6)	
    Total	    108 (38.2)	    175 (61.8)	    283 (100)		
*Fisher exact test

Discussion

Glucose and sodium disorders are extremely common in patients admitted to the ICU. Due to their important roles in maintaining homeostasis of the body, it is necessary to examine their impact on survival. These disorders are often asymptomatic and great attention should be paid to their early detection and initiation of treatment in order to improve the outcomes of critically ill patients. The study was conducted on 283 patients admitted to the ICU over a period of 16 months. Glucose and sodium concentrations were recorded on admission and their impact on survival of these patients was examined, i.e., whether these patients were transferred from the ICU or had a fatal outcome. Glucose values ​​significantly affected survival. On the other hand, sodium values ​​did not show significant association with survival of critically ill patients.

All degrees of hyperglycemia were significantly associated with poorer outcome. It is known that glucose stimulates the production of proinflammatory mediators and thus stimulates the inflammatory process. Acute hyperglycemia causes vasoconstriction and consequent hypoperfusion of organs by reduced nitric oxide synthesis in the endothelium. Furthermore, hyperglycemia increases the risk of infection, causes glucotoxicity in immune cells, promotes lymphocyte apoptosis, reduces neutrophil activity, and by glycosylation of immunoglobulins and complement reduces their activity (6). Blood glucose levels above 10.0 mmol/L exceed the renal glucose threshold and lead to osmotic diuresis causing hypovolemia (4). All these factors contribute to higher mortality of critically ill patients and explain the result obtained in our study. Zhang et al. investigated the impact of hyperglycemia on the outcome of 7895 critically ill patients. The group of patients with a glucose concentration higher than 11.1 mmol/L had higher 30-day and 90-day mortality and had a longer stay in the ICU compared to normoglycemic patients, which is in line with our results (16).

In our study, 6.7% of patients had low glucose levels on admission to the ICU. These patients had higher mortality compared with patients who had normal glucose values. Patients with hypoglycemia are older, have diabetes, need mechanical ventilation, stay longer in the ICU and have higher mortality, which is in line with the results of our study (17). Increased mortality is due to a number of side effects of hypoglycemia, e.g., dysfunction of the autonomic nervous system, release of inflammatory mediators and cytokines, leukocyte activation, QT prolongation (and consequent predisposition to fatal arrhythmias), and impaired brain function. Complications (renal, cardiac, hepatic, and bacteremia) are more common in patients with hypoglycemia during their stay in the ICU (18). The NICE-SUGAR study on 6026 critically ill patients also showed a negative effect of hypoglycemia on outcome (5).

Numerous studies have shown that hyponatremia is an independent predictive factor for mortality in critically ill patients. In a study by Funk et al., hyponatremia was present in 17.7% of patients admitted to the ICU, which is slightly less than in our study (26.9%). In their study, there were more neurological patients who may have had concomitant syndrome of inappropriate antidiuretic hormone secretion causing hyponatremia. All degrees of hyponatremia were associated with increased mortality, which is not consistent with the results of our study (10). In our study, patients with severe hyponatremia were more likely to be transferred from the ICU. Chawla et al. examined the potential reasons for better survival of patients with severe hyponatremia compared to patients with mild and moderate hyponatremia. They believe that patients with moderate hyponatremia are more likely to have more severe underlying disease and/or comorbidities and thus higher mortality. On the other hand, patients with severe hyponatremia were more likely to be admitted to the ICU primarily due to severe disorder in sodium concentration rather than due to severe underlying disease. This is supported by the fact that patients with severe hyponatremia who survived were more likely to have drug-induced hyponatremia (thiazide diuretics and selective serotonin reuptake inhibitors) and had no severe comorbidities (13). It is not entirely clear why decreased sodium values ​​are associated with higher mortality. Hoorn and Zietse propose three scenarios, as follows: 1) hyponatremia is the direct cause of death; 2) the severity of the underlying disease is the cause of death and hyponatremia, which does not contribute to mortality but is a marker of the severity of the underlying disease; and 3) hyponatremia leads to organ dysfunction and thus indirectly leads to death (19). In our study, no significant association was found between hyponatremia and mortality. A possible explanation is the small number of subjects and inclusion of only those patients who had hyponatremia at admission. For the same reason, no significant results were obtained on the association of hypernatremia and higher mortality. All degrees of hypernatremia were associated with poorer outcome, which is consistent with other studies. Hypernatremia leads to organ dysfunction by affecting metabolism, central nervous system, cardiovascular system and muscles (may cause rhabdomyolysis) (14, 20). Darmon et al. studied the effect of sodium disturbance on admission on the mortality of 11,125 patients. Hypernatremia was present in 17.6% of patients, which is in line with the results of our study (15%). All degrees of hypernatremia were associated with increased mortality (9).

The most common diagnoses of patients admitted to the ICU were acute kidney injury, sepsis and septic shock, coronary artery disease, heart failure, pneumonia, and drug intoxication. Patients with acute kidney injury were significantly more likely to have elevated glucose levels.

Acute kidney injury is a clinical syndrome that develops within a few hours to 7 days and is characterized by sharp decrease in renal function. It is defined as an increase in creatinine level ≥0.3 mg/dL within 48 hours or increase in creatinine level 1.5 times higher than normal within 7 days or urine volume <0.5 mL/kg/h over 6 hours. The incidence of this condition in the ICU ranges from 20% to 40%, which is in line with the results of our study (26.1%). Mortality of patients with acute renal failure is about 50% (21). The association between hyperglycemia and acute kidney injury has been investigated in a number of studies. Gordillo et al. showed that with each increase of 0.55 mmol/L (10.0 mg/dL) in the maximum glucose measurement, the risk of developing acute kidney injury increases by 12%. Hyperglycemia leads to tissue damage due to increased formation of free oxygen radicals in mitochondria. The proximal tubule is particularly sensitive to free oxygen radicals. In hyperglycemic rabbits, higher creatinine levels, decreased renal cortex perfusion and severe morphological damage to the kidneys were observed (22, 23). Important risk factors for the development of acute kidney injury are old age and accompanying comorbidities, especially hypertension and diabetes. In recent years, the average age of patients admitted to the ICU has increased. It is estimated that in the United States, every second bed in the ICU is occupied by a patient older than 65. In our study, 68.6% of patients were older than 65, reflecting a higher proportion of elderly population in Croatia than in the United States. In the elderly, the kidney is more susceptible to prerenal failure due to changes in the tone of renal blood vessels in which vasoconstriction predominates. Fluid loss (vomiting, diarrhea, diuretics), decreased cardiac output, and drugs with negative effect on renal perfusion (nonsteroidal anti-inflammatory drugs and angiotensin-converting enzyme inhibitors) also contribute to decreased renal plasma flow. In our study, it was found that patients older than 65 were more likely to have elevated glucose levels (80.4% had elevated glucose levels), which by the above mentioned mechanisms participate in the development of acute kidney injury. Comorbidities such as hypertension and diabetes are more common in people over 65 years and are a risk factor for acute kidney injury and death in these patients (21). This explains the significant association between acute kidney injury and elevated glucose levels, as well as the significantly higher mortality in patients over 65 years of age recorded in our study.

Disorders of glucose and sodium concentrations have consequences for the whole body. In the case of critically ill patients treated in the ICU who have impaired homeostasis and need numerous medications and invasive life support techniques, the accompanying impairment of glucose and sodium concentrations further impairs their body’s ability to defend itself and leads to increased mortality in these patients. In order to improve the outcome of these patients, attention and effort should be focused on their early recognition and appropriate treatment.

A disadvantage of this research is that glucose and sodium concentrations ​​were not monitored during the stay in the ICU but only at admission. Furthermore, patients were not followed-up after transfer from the ICU. Our study was of a cross-sectional nature and prospective studies are needed to conduct further research on this topic.

Conclusion

The most common diagnoses in patients admitted to the ICU were acute kidney injury, sepsis and septic shock, coronary artery disease, heart failure, pneumonia, and drug intoxication. Acute kidney injury was associated with lower glucose levels while sepsis and septic shock were associated with higher sodium levels. Elevated glucose levels, as well as older age (≥65 years) increased mortality in critically ill patients. Sodium concentration did not have a significant impact on survival in critically ill patients.
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References

1 Unal AU Kostek O Takir M Caklili O Uzunlulu M Oguz A . Prognosis of patients in a medical intensive care unit. North Clin Istanb. 2015;2 (3 ):189–95. 10.14744/nci.2015.79188 28058366
2 Akavipat P Thinkhamrop J Thinkhamrop B Sriraj W . Acute Physiology And Chronic Health Evaluation (APACHE) II score – the clinical predictor in neurosurgical intensive care unit. Acta Clin Croat. 2019 March;58 (1 ):50–6. 10.20471/acc.2019.58.01.07 31363325
3 Soares Pinheiro FG de M Santana Santos E Barreto ÍD de C Weiss C Vaez AC Oliveira JC . Mortality predictors and associated factors in patients in the intensive care unit: a cross-sectional study. Crit Care Res Pract. 2020;2020 :1483827. 10.1155/2020/1483827 32802502
4 Marik PE Bellomo R . Stress hyperglycemia: an essential survival response! Crit Care. 2013 March 6;17 (2 ):305. 10.1186/cc12514 23470218
5 NICE-SUGAR Study InvestigatorsFinfer S Liu B Chittock DR Norton R Myburgh JA . Hypoglycemia and risk of death in critically ill patients. N Engl J Med. 2012 September 20;367 (12 ):1108–18. 10.1056/NEJMoa1204942 22992074
6 Mifsud S Schembri EL Gruppetta M . Stress-induced hyperglycaemia. Br J Hosp Med (Lond). 2018 November 2;79 (11 ):634–9. 10.12968/hmed.2018.79.11.634 30418830
7 Lheureux O Prevedello D Preiser J-C . Update on glucose in critical care. Nutrition. 2019 March;59 :14–20. 10.1016/j.nut.2018.06.027 30415158
8 Pokaharel M Block CA . Dysnatremia in the ICU. Curr Opin Crit Care. 2011 December;17 (6 ):581–93. 10.1097/MCC.0b013e32834cd388 22027406
9 Darmon M Diconne E Souweine B Ruckly S Adrie C Azoulay E Prognostic consequences of borderline dysnatremia: pay attention to minimal serum sodium change. Crit Care. 2013 January 21;17 (1 ):R12. 10.1186/cc11937 23336363
10 Funk G-C Lindner G Druml W Metnitz B Schwarz C Bauer P Incidence and prognosis of dysnatremias present on ICU admission. Intensive Care Med. 2010 February;36 (2 ):304–11. 10.1007/s00134-009-1692-0 19847398
11 Radulović B Potočnjak I Dokoza Terešak S Trbušić M Vrkić N Huršidić Radulović A Cholesterol and chloride in acute heart failure. Acta Clin Croat. 2019 June;58 (2 ):195–201. 10.20471/acc.2019.58.02.01 31819314
12 Buffington MA Abreo K . Hyponatremia: a review. J Intensive Care Med. 2016 May;31 (4 ):223–36. 10.1177/0885066614566794 25592330
13 Chawla A Sterns RH Nigwekar SU Cappuccio JD . Mortality and serum sodium: do patients die from or with hyponatremia? Clin J Am Soc Nephrol. 2011 May;6 (5 ):960–5. 10.2215/CJN.10101110 21441132
14 Lindner G Funk G-C . Hypernatremia in critically ill patients. J Crit Care. 2013 April;28 (2 ):216.e11–20. 10.1016/j.jcrc.2012.05.001 22762930
15 Petz B, Kolesari ÊV, Ivanec D. Petzova statistika. Osnovne statistiËke metode za nematematiËare [Internet]. 2012 [cited Dec 10, 2020]. Available from: https://www.bib.irb.hr/649813 (in Croatian)
16 Zhang L Wang Z Xu F Han D Li S Yin H Effects of stress hyperglycemia on short-term prognosis of patients without diabetes mellitus in coronary care unit. Front Cardiovasc Med. 2021;8 :683932. 10.3389/fcvm.2021.683932 34095265
17 Krinsley JS Schultz MJ Spronk PE Harmsen RE van Braam Houckgeest F van der Sluijs JP Mild hypoglycemia is independently associated with increased mortality in the critically ill. Crit Care. 2011 July 25;15 (4 ):R173. 10.1186/cc10322 21787410
18 Park S Kim D-G Suh GY Kang JG Ju Y-S Lee Y-J Mild hypoglycemia is independently associated with increased risk of mortality in patients with sepsis: a 3-year retrospective observational study. Crit Care. 2012 October 12;16 (5 ):R189. 10.1186/cc11674 23062226
19 Hoorn EJ Zietse R . Hyponatremia and mortality: how innocent is the bystander? Clin J Am Soc Nephrol. 2011 May;6 (5 ):951–3. 10.2215/CJN.01210211 21493744
20 Chi C Patel S Cheung NW . Admission sodium levels and hospital outcomes. Intern Med J. 2021 January;51 (1 ):93–8. 10.1111/imj.14777 32043721
21 Infante B Franzin R Madio D Calvaruso M Maiorano A Sangregorio F Molecular mechanisms of AKI in the elderly: from animal models to therapeutic intervention. J Clin Med. 2020 August 8;9 (8 ):E2574. 10.3390/jcm9082574 32784471
22 Gordillo R Ahluwalia T Woroniecki R . Hyperglycemia and acute kidney injury in critically ill children. Int J Nephrol Renovasc Dis. 2016;9 :201–4. 10.2147/IJNRD.S115096 27601931
23 Mendez CE Der Mesropian PJ Mathew RO Slawski B . Hyperglycemia and acute kidney injury during the perioperative period. Curr Diab Rep. 2016 January;16 (1 ):10. 10.1007/s11892-015-0701-7 26792142
