The Effects of Initial Cortisol Levels and Vitamin D on Mortality and Hospital Infection Development in Geriatric Patients at Intensive Care Unit

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1 doi: /actamedica Acta Medica Anatolia Volume 4 Issue The Effects of Initial Cortisol Levels and Vitamin D on Mortality and Hospital Infection Development in Geriatric Patients at Intensive Care Unit Leyla Kutlucan 1, Ali Kutlucan 2 1 Department of Anesthesiology, Konya Training and Research Hospital, Konya, Turkey 2 Department of Internal Medicine, Selcuk University, School of Medicine, Konya, Turkey Abstract Introduction: Vitamin D deficiency is a common problem throughout the world. Also vitamin D deficiency has been reported in up to 82% of patients in intensive care unit (ICU). In addition, corticosteroid insufficiency is a common problem in ICU patients. In this study, we investigated the effects of initial cortisol and vitamin D levels on mortality, hospital infection development and intubation status in geriatric ICU patients. Methods: This study was conducted in a tertiary ICU. In a one-year period, 117 consecutive ICU patients older than 65 years of age were evaluated retrospectively. Looking at the first with Vitamin D and cortisol levels of the patients were collected in the first 24 hours of hospitalization. At follow up period, relationship between these data s and mortality, hospital infection, and intubation conditions were evaluated. Results: Initial Vitamin D, the morning cortisol, and albumin levels were found to be significantly lower (respectively; p <0.001, p <0.001 and p <0.001), and lactate levels were found to be significantly higher (p <0.001) in patients who died in ICU than alive patients. Development rate of hospital-acquired infection was found to be significantly higher (p = 0.025) in patients with low vitamin D levels than alive patients. Vitamin D and cortisol levels were found to be lower and lactate levels were found to be higher (respectively: p <0.001, p = 0.004, p = 0.035) in intubated patients than alive patients. Conclusion: In geriatric patients, relationship between initial vitamin D and cortisol levels and mortality, hospital infection and intubation conditions were evaluated in our study for the first time. The low level of vitamin D is seen as an important risk factor for the mortality, development of hospital-acquired infections and intubation. Also it is determined that the low cortisol creates a negative situation in terms of mortality and intubation. Keywords: Intensive Care Unit, Geriatric Patients, Vitamin D, Cortisol, Mortality, Hospital Infection. Received: Accepted: Introduction Vitamin D is a fat-soluble vitamin, is synthesized in the skin by the sunlight effect, and is taken via diet in small amounts. Vitamin D which is in a steroidal structure plays important role in bone metabolism. Vitamin D regulates inflammation, immunity, cell division, apoptosis, and angiogenesis with its pleiotropic activity (1-3). Vitamin D deficiency is a common problem all over the world, and it can be frequently observed in hospitalized patients. It has been shown that vitamin D deficiency is associated with increase in morbidity and mortality in various systemic diseases (4,5). Vitamin D deficiency has been reported to be prevalent between 26-82% in the intensive care unit (ICU) patients (6,7). As a result of that high rate of deficiency, positive pleiotropic activity of vitamin D cannot be occurred and problems about natural immunity, mucosal barrier, and endothelial dysfunction appear. It has been shown that low level of vitamin D has emerging association with severity of the disease, mortality, and short life span in the ICU patients. In some studies, it was shown to be associated with extension of mechanic ventilator dependency, increase in infection rate, and long stay in ICU (8-11). During acute stress, increase in cortisol level is a protective response against stress in order to meet the physiological requirements. This homeostasis is balanced by hypothalamic-pituitary-adrenal axis. Deficiency of corticosteroid that has positive activities is a common problem in the ICUs, particularly in the patients with sepsis and septic shock. Risk of development of adrenal insufficiency increases in the patients who stay in the ICUs for a long time. Though evaluation of adrenal insufficiency is recommended in case of clinical suspicion, it hasn t Correspondence: Leyla Kutlucan, Department of Anesthesiology, Konya Training and Research Hospital, Konya, Turkey Conflict of Interest: None leylakutlucan@hotmail.com 93

2 still been known that how often it should be done (12-17). In many studies, it has been shown that low level of albumin and high level of lactic acid have significant association with increase in mortality in the ICU patients (18-20). There are no studies available in the literature conducted on evaluation of vitamin D and cortisol parameters in a geriatric patient group that constitutes a significant number of ICU patients, and that requires a more careful monitoring and treatment. In the present study, we aimed to evaluate the association of the parameters of lactate and albumin with mortality, nosocomial infection and intubation status as well as the effects of vitamin D and cortisol that have been evaluated within 24 hours of admission in a geriatric ICU patient group. Material and Methods The present study was conducted in a third-step ICU of a university hospital. A total of 117 patients over 65 years old followed up for a year were included in the study retrospectively. The patients who had endstage malignancies, who had chemotherapy and/or radiotherapy, who stayed in ICU less than two days, who were younger than 65 years, who had taken vitamin D treatment, who had kidney insufficiency, and who had parathyroid or granulomatous disease in their history were excluded. At the first admission of the patients to ICU, their demographical characteristics and detailed medical and family histories were taken from them or their relatives. Detailed physical examination was performed for all systems. At the first admission, Acute Physiology and Chronic Health Evaluation II (APACHE) and Glasgow Coma Scale (GCS) were calculated, and hemogram, blood gas analyses and biochemical tests were conducted. Within the first 24 hours, vitamin D and cortisol tests were requested. During the intensive care follow-up, the patients that had nosocomial infection that were intubated in case of need for mechanical ventilation, and that died were recorded. Amongst the tests, 25-OH test was performed with gamma counter using Radioactive Immune Assay method, and PCT test was performed with Epoch plate reader using Enzyme Linked Immunosorbent Assay method. In the vitamin D level evaluation, the levels over 30 ng/ml were accepted as sufficient, the levels between ng/ml were accepted as insufficiency, the levels below 20 ng/ml as deficiency, and the levels below 10 ng/ml as severe deficiency. Cortisol test was performed using chemiluminescent enzyme immunoassay (Immulite 2000, Roche, USA). According to the previous studies, cortisol level below 15 μg/dl is accepted as low, and replacement is recommended (21-23). Statistical analysis was performed using the software package SPSS (Version 20.0) (SPSS Inc, Chicago, IL, USA). Examination of the dispersion was performed using Kolmogorov-Smirnov test. Values in parametric distribution were expressed as mean ± standard deviation, while the non-parametric ones were as median (minimum-maximum). In the continuous variables, statistical significance was analyzed using Student s t test for parametric variables, and using Mann-Whitney U test for non-parametrics. p <0.05 was considered statistically significant. Results A total of 63 of the patients were males, and 54 were females. The mean age of the patients was in males, in females, and overall. The mean GCS was calculated as 7.97±4.1, the mean APACHE II Score was 28.06±9.1, and expected mortality rate was 60.37% ±23.93%. After the follow-up in ICU, 51 patients were discharged, and 66 patients (56.4%) were died. Nosocomial infection occurred in 31 out of 117 (26.5%) patients followed up in ICU, and 93 patients (79.5%) had to be intubated. The mean vitamin D level was 7.1±3.71 ng/ml (3-21.5) in the patients died, and was 13.10±6.68 ng/ ml (3-37) in the discharge group, and the mean vitamin D level was found to be significantly lower in the died group (p<0.001). Cortisol levels were detected as low in a total of 23 patients consisting 21 died and 2 discharged ones. The mean morning serum cortisol level was 21.15±11.31µg/dL (4.7-84) in the died patients group, was 34.00±16.17 µg/ dl ( ) in the discharged patients, and was found to be significantly lower in the died group (p<0.001). The mean lactate level was 2.2±4.05 mmol/l (0.9-18) in the died group, was 1.5±1.05 mmol/l ( ) in the discharge group, and wa found to be significantly higher in the died group (p<0.001). The mean albumin level was 2.59±0.51 g/dl ( ), was 3.00±0.54 g/dl ( ) in the discharge group, and was found to be lower in the died group (p<0.001). No significant differences were found between the groups in terms of calcium and phosphorus levels (Table 1). The mean vitamin D level was found to be lower in the patients that nosocomial infection occurred during the ICU follow-up [8.00±6.40 ng/ml (3-32)] than the ones that nosocomial infection did not 94

3 occur [10.90±6.26 ng/ml (3-37)] (p=0.025). No significant associations were detected between nosocomial infection and serum levels of cortisol, lactate, albumin, calcium, and phosphorus (Table 2). Table 1. Effects of serum levels of vitamin D, cortisol, albumin, lactate, calcium, and phosphorus on discharge status. Discharge status (n=117) Patients died (n=66) Patients discharged (n=51) p value Vitamin D 7.15± ±6.68 p<0.001 Cortisol 21.15± ±16.17 p<0.001 Lactate 2.2± ±1.05 p<0.001 Albumin 2.59± ±0.54 p<0.001 Calcium 7.93± ±0.65 p=0.276 Phosphorus 2.90± ±1.00 p=0.511 Table 2. Effects of serum levels of vitamin D, cortisol, albumin, lactate, calcium, and phosphorus on development of nosocomial infections. Nosocomial infection (n=117) Present (n=31) Absent (n=86) p value Vitamin D 8.00± ±6.26 p<0.025 Cortisol 27.50± ±16.09 p<0.636 Lactate 1.90± ±3.66 p<0.965 Albumin 2.90± ±0.06 p<0.365 Calcium 8.10± ±0.68 p=0.453 Phosphorus 3.20± ±1.00 p=0.073 The mean vitamin D level was found to be lower in the patients who were intubated [9.00±6.36 ng/ml (3-37)] than the ones were not [13.00±5.18 ng/ml (9.7-34)] (p<0.001). The mean cortisol level was found to be lower in the intubated group [23.30±14.83 mcg/dl (4.7-84)] than the non-intubated group [30.50±17.83 mcg/dl (15-94)] (p<0.004). The mean lactate level was found to be higher in the intubated group [1.90±3.53 mmol/l (0.1-18)] than the nonintubated group [1.55±2.17 mmol/l ( )] (p<0.035) (Table 3). Discussion In the present study, we detected a significant association between vitamin D deficiency and increase in mortality in geriatric ICU patients. We also found a significant association between vitamin D deficiency and either nosocomial infection development or increase in intubation rate in the same age group. Depending to our results, the cortisol levels within the first 24 hours of admission was to be significantly lower in the geriatric patients who died in ICU than the ones discharged. Cortisol levels were found to be significantly lower in the intubated patients, and they seem to be protective against intubation. No association was detected between cortisol levels and nosocomial infection development. Amongst the parameters evaluated additionally in our study, lactate levels were found to be higher in the patients died and in the ones intubated, as expected. In addition, albumin levels were detected as low in the patients died. Table 3. Effects of serum levels of vitamin D, cortisol, albumin, lactate, calcium, and phosphorus on intubation. Present (n=93) Intubation (n=117) Absent (n=24) p value Vitamin D 9.00± ±5.18 p<0.001 Cortisol 23.30± ±17.83 p<0.004 Lactate 1.90± ±2.17 p<0.035 Albumin 2.76± ±0.41 p<0.192 Calcium 8.00± ±0.64 p=0.661 Phosphorus 2.90± ±1.12 p=0.251 The mean age of our patients was so high, and number of the patients who needed intubation was also extremely high. Expected mortality rate was found to be high in our patient population that co-morbidity rate was also high. Depending on these negative factors, died patient rate overall was detected as high. The retrospective study conducted on 42 patients about vitamin D level and ICU mortality by Lee et al. was amongst the first researches done at this topic. They reported that mortality rate was high in the patients with vitamin D deficiency. As the cause of this, they considered that vitamin D deficiency and insufficiency could affect the immune system negatively, and could cause metabolic dysfunction (9). In the study conducted on 135 ICU patients by Moraes et al., vitamin D levels were tested at the first admission, and mortality rate within 28 days was compared between the patients with vitamin D levels below and over 12 ng/ml, and they detected that mortality rate was significantly higher in the patients with low vitamin D levels. They also reported no 95

4 significant differences between the groups in terms of mechanic ventilation requirement and nosocomial infection rates. They did not evaluate cortisol levels (11). In our study, the patients were not divided into groups according to vitamin D levels, and the mean vitamin D level was quite low. In addition, there were significant association between low vitamin D levels and nosocomial infection development and high intubation rate in our study. Since our patients were in geriatric age, vitamin D levels might have been detected as low. However, susceptibility to infections and respiratorial problems might be more severe because of the same reason. Quraishi et al. measured vitamin D levels in blood samples of 100 surgery patients taken preoperatively. They reported that an association could be between 25-hydroxy vitamin D levels measured within 24 hours and rehospitalization in 90 days, 90-day-mortality rate, and the length of hospital stay. In their study, the patient group consisted of the surgery patients, and neither nosocomial infections nor cortisol levels were evaluated (24). In the study conducted with retrospective evaluation of 201 patients in ICU by Aygencel et al., association between vitamin D and mortality was researched. They found that mortality rate was significantly higher in the group with low vitamin D levels. They also reported that mechanic ventilation requirement rate was significantly higher in the patients with low vitamin D levels, however they found no significant association between vitamin D levels and nosocomial infection development rates (25). Much lower mean vitamin D level and higher mean patient age in our study in comparison to that study might have caused significantly high nosocomial infection rate. In a meta-analysis conducted on 14 researches by Haan et al., association between vitamin D levels and rates of mortality and infection was evaluated in 9715 ICU patients. Depending to that analysis, it was reported that severe infection and mortality rates were high in vitamin D deficiency. In that analysis, risk for nosocomial infection development and intubation status were not evaluated (26). In critically ill patients, increase in corticosteroid levels has been considered to be a protective mechanism against stress. However, corticosteroid levels don t increase enough in ICU patients due to insufficient immune response. There are few studies available in the literature evaluating the association between cortisol levels and either mortality or nosocomial infection (27-29). In the study conducted on 57 patients by Wu et al., cortisol levels were detected to be low in most of ICU patients. They reported that cortisol levels decreased again after replacement treatment. It was also reported that cortisol levels could cause negative results. Therefore, they recommended to re-evaluation of adrenal functions in the patients who stayed for a long time in ICU (30). In conclusion, the present study has been the first research that evaluated the serum levels of vitamin D, cortisol, albumin, lactate, calcium, and phosphorus measured within the first 24 hours of admission to ICU, and mortality, nosocomial infection, and intubation status in geriatric patients. According to these information, closely monitoring of levels of cortisol and vitamin D and replacement seem to be quite useful in the geriatric ICU patients who require close follow-up and treatment. References 1. Pramyothin P, Holick MF. Vitamin D supplementation: guidelines and evidence for subclinical deficiency. Curr Opin Gastroenterol 2012;28: Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, et al. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2011;96: Biesalski HK. Vitamin D recommendations: beyond deficiency. Ann Nutr Metab. 2011;59: Holick MF. Vitamin D: importance in the prevention of cancers, type 1 diabetes, heart disease, and osteoporosis. Am J Clin Nutr. 2004;79: Arslan MS, Sahin M. Vitamin D and Thyroid Cancer. Acta Med Anatol. 2014;2(4): Lucidarme O, Messai E, Mazzoni T, Arcade M, du Cheyron D. Incidence and risk factors of vitamin D deficiency in critically ill patients: results from a prospective observational study. Intensive Care Med 2010;36: Matthews LR, Ahmed Y, Wilson KL, Griggs DD, Danner OK. Worsening severity of vitamin D deficiency is associated with increased length of stay, surgical intensive care unit cost, and mortality rate in surgical intensive care unit patients. Am J Surg 2012;204:

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