Keywords
Sepsis, vitamin D Deficiency, mortality, 1,25(OH)2D, intensive care unit, critically ill, cathelicidin
This article is included in the Datta Meghe Institute of Higher Education and Research collection.
Vitamin D functions as a prohormone that promotes bone mineralization by regulating calcium and phosphate levels in the skeletal system. It is a fat-soluble vitamin that is required for immunomodulation, cytokine regulation, and cell proliferation. As a result, Vitamin D is a powerful hormone with pleiotropic effects that improve overall health. Sepsis is the leading cause of death in critically unwell people. According to a recent study, numerous trace minerals and nutrients have the ability to alter the human body, and supplementing these nutrients can improve the prognosis of sepsis patients. A considerable number of patients in the intensive care unit (ICU) have low vitamin D levels, a frequent condition that can increase the risk of infectious diseases. According to various studies, severely ill patients admitted to the ICU who have a vitamin D deficiency are at a higher risk of requiring mechanical ventilation and facing a higher likelihood of mortality. Nonetheless, the connection between insufficient vitamin D levels and mortality in sepsis patients remains a topic of debate.
Sepsis, vitamin D Deficiency, mortality, 1,25(OH)2D, intensive care unit, critically ill, cathelicidin
Sepsis is the primary cause of mortality in critically ill patients. Recent research emphasizes the importance of early detection and intervention to reduce mortality rates. Several studies have revealed that specific trace minerals and nutrients can influence the body’s functioning and that supplementation may improve outcomes for sepsis patients. Many studies have shown that low levels of cathelicidin are associated with insufficient 25(OH) D levels. Inadequate 25(OH) D levels are linked to an increased risk of severe sepsis, the need for mechanical ventilation, and higher mortality due to low cathelicidin levels.1
It is estimated that approximately 1 billion people globally have inadequate vitamin D levels. The level of 25-hydroxyvitamin D (25(OH)D) is less than or equal to 30 ng/ml or 20 ng/ml. Another unknown factor is that vitamin D circulates in the form of 25(OH) D in the body, it is inactive and must be to the active form 1α-hydroxylase by the Renal system (endocrine) and the extra-renal (paracrine). Enzyme 1a-hydroxylase to the active hormone, 1,25-dihydroxy vitamin D (1,25(OH)2D).2
When present in its active form, 1,25(OH)2D binds to the nuclear vitamin D receptor, leading to the production of antimicrobial peptides like cathelicidin and defensin by neutrophils. This is the primary mechanism through which 1,25(OH)2D influences the body. In sepsis, both low levels of 25(OH) D and inadequate hydroxylation can significantly reduce 1,25(OH)2D levels, which have been linked to an increased risk of mortality. Numerous studies have demonstrated that low 25(OH) D levels in critically ill patients are associated with an increased risk of severe sepsis, longer hospital stays, and higher mortality rates. Few studies have investigated 1,25(OH)2D levels in sepsis patients but have found an association with poor outcomes, supporting our hypothesis. The specific cause is uncertain, although low levels of Vitamin D are known to boost endothelial adhesion molecule production, IL-6, and oxidative stress all of which play a significant role in the development of sepsis.
Sepsis is a medical condition that is caused by leaking blood vessels and an increase in the release of cytokines. Both of these conditions can be improved by 1,25(OH)2D. Additionally, 1,25(OH)2D is instrumental in regulating cathelicidin, which is responsible for fighting off invading germs. Even though numerous studies have demonstrated that Vitamin D plays a crucial role in immunological function and sepsis, The purpose of this study is to look into the relationship between Vitamin D and sepsis, as well as whether there is a link between Vitamin D levels and patient outcomes including mortality and discharge.
Another objective of this research is to determine whether vitamin D levels can predict morbidity in discharged hospitalized patients. The study also examines the correlation between various sepsis markers and vitamin D levels to investigate whether vitamin D can be used as a biomarker for sepsis.3
The study will be conducted in the Department of Medicine at Acharya Vinoba Bhave Rural Hospital (AVBRH), a tertiary care teaching hospital in Wardha District’s rural area.
This study will be a single-center assessment of patients who were brought to the emergency department with suspected sepsis and were subsequently admitted to the Medical Intensive Care Unit (MICU) and those who required mechanical ventilator assistance.
A manageable number of patients will be enrolled in the trial to uncover biomarkers linked to poor outcomes in the patients.
The duration of the studies will be between 2022 and 2024.
• To Study vitamin-D level in sepsis and its outcome in patients admitted to the medical intensive care unit
• To estimate and classify hypovitaminosis vitamin D level severity in sepsis patients.
• To correlate the level of vitamin D with outcome in terms of mortality, Intensive Care Unit stay, and need for mechanical ventilation.
1. A confirmed source of infection, as determined by the treating physician, and serum lactate level more than 2.5 mmol/L.
2. To diagnose systemic inflammatory response syndrome (SIRS), at least two of the following criteria must be met:
a) If the body temperature is greater than 38°C or less than 36°C.
b) If the respiratory rate exceeds 20 breaths per minute or if carbon dioxide partial pressure is less than 32 mmHg.
c) If the heart rate is at least 90 beats per minute.
d) Hypotension occurs when the mean arterial pressure (MAP) drops below 70 mmHg or the systolic blood pressure (SBP) is less than 90 mmHg.) despite fluid resuscitation or the need for vasopressors.
e) White blood cell count 4000/mm3 or greater than 12000/mm3 or greater than 10% immature band form.
1. Pregnant and lactating mothers.
2. Post cardiopulmonary resuscitated patient.
3. Whether the patient is taking any multivitamins or food supplements containing Vitamin D.
4. Patient with malabsorption syndromes.
5. Patients with chronic diarrhea.
6. Patients are not willing to give informed consent.
Patients suspected of having sepsis and requiring mechanical ventilator support were admitted to the medical ICU, where they received a comprehensive history and clinical review. A comprehensive laboratory examination will be performed, including a complete blood count (CBC), serum vitamin D level, liver function test, renal function test, and blood sugar levels.
α: Type I error at 5% l.o.s. = 1.96
β: Type II Error at 20% (1-β) = 0.8
Estimated Proportion (p) = 15% = 0.15 (Mortality in Patient of sepsis) (Ref article).
Each sample will be centrifuged at 2,0006 g for 10 minutes within 1 hour of collection. Without further freeze-thaw cycles, the plasma will be equally divided into 1 mL cryovials and stored at 284uC. Following that, the samples were sent to Heartland Assay LLC in Ames, Iowa in dry ice, for 25-hydroxyvitamin D (25(OH)D), 1,25-dihydroxyvitamin D (1,25(OH)2D), and 24,25-dihydroxyvitamin D (24,25(OH)2D) analysis. 25(OH)D is the abbreviation for 25-hydroxyvitamin D.
A direct, competitive chemiluminescence immunoassay (CLIA) employing the DiaSorin LIAISON 25-OH Vitamin D Total test is the FDA-approved method for testing 25(OH)D.
This assay detects 25(OH)D3 as well as 25(OH)D2. In this study, a specific
The 1,25(OH)2D assay begins with the extraction of vitamin D metabolites from blood or plasma, which is then purified using C18OH cartridges.
In a repeated RIA approach, a polyclonal antibody that can detect both 1,25(OH)2D2 and 1,25(OH)2D3 is used, and the sample, antibody, and tracer are incubated for two hours at 20–25°C. Following this, a second antibody precipitating complex is added and the mixture is incubated for another 20 minutes at the same temperature. Finally, phase separation is obtained. The binding fraction that remains in the pellet after centrifugation and decantation is counted using a gamma counter.
The values are directly computed using a calibration curve of known concentrations. The typical range of the assay is 20 to 50 pg/mL, with coefficients of variation of 12.6% and 12.6%, respectively. 9.8% and 9.8%, respectively.
A kind of vitamin D is 24,25-dihydroxy vitamin D (24,25(OH)2D). The level of 24,25(OH)2D will be determined using a modified version of the Horst et al.6 method.
Silica solid phase extraction (SPE) and high-pressure liquid chromatography (HPLC) were employed to purify plasma lipids for analysis.
The radioimmunoassay (RIA) will be utilized to examine the HPLC-purified material containing both 24,25(OH)2D2 and 24,25(OH)2D3. With 24,25(OH)2D3, the estimated losses will be determined. A novel method will be used, which will include the use of an antibody capable of detecting both 24,25(OH)2D2 and 24,25(OH)2D3. The sample, antibody, and tracer will be mixed together and incubated for 120 minutes at 20-25°C. The combination will next be treated with a second antibody to induce phase separation, which will take 20 minutes at the same temperature. During the centrifugation process, a buffer called NSB/Addition is used to reduce non-specific binding. To estimate radioactivity in the c-radiation counting method, a smooth-spline approach is employed. The assay’s normal range falls between 1 to 3 ng/mL, and its coefficients of variation are 10.0% and 8.0%, respectively, across different assays. Reference levels of serum 25 (OH)D3: 30 ng/mL
Deficient: 11-20 ng/mL
Severe deficiency:10 ng/Ml
Analysis: Descriptive statistics will be employed to compile and delineate the outcomes across various variables. Both the mean and standard deviation of the data pertaining to these variables will be scrutinized to assess normal distribution. Additionally, the interquartile range (IQR) will be calculated, and any skewed distributions will be identified using median statistics. For descriptive statistics, frequencies and percentages of categorical and binary variables will be computed. All statistical analyses will be conducted using the freely available R software. Subsequently, inferential statistics will be analyzed in accordance with the provided guidelines.
Primary outcome: to assess and categorize the extent of vitamin deficiency in patients with sepsis.
Secondary outcome: Correlate vitamin D levels with mortality, ICU stay, and ventilation needs.
Scope: nowadays most of the patients in the general population are either deficient or insufficient in vit. D.
More research is required to determine if hypovitaminosis D in sepsis patients might impact the course of hospitalization and change the morbidities encountered by vitamin D-deficient sepsis patients.
The Chi-square and Fischer exact tests will be used to analyze categorical variables, which will be reported as percentages or proportions.
Continuous variables’ mean and standard deviation will be calculated and analyzed using an unpaired t-test or ANOVA.
All data will be input and coded in Microsoft Excel, and the statistical software R Studio Version 4.3.1 will be utilized for analysis. An alpha level of 5% will be used, which means that any p-value less than 0.05 will be considered significant. Spearman’s or Pearson’s correlations will be used for the correlation.
Previous research has indicated that patients who get enough vitamin D have a higher rate of discharge and a lower percentage of expiry. The study’s primary focus is on the association between Vitamin D levels and the severity and outcome of sepsis. The active form of 1,25(OH)2D interacts with the nuclear vitamin D receptor, causing neutrophils to produce antimicrobial peptides such as cathelicidin and defensin, which are important in immune response, and Lack of it increases the risk of severe sepsis, hospitalization, and death. In the majority of studies, low 25(OH) D levels were found to be associated with low cathelicidin levels, an increased risk of severe sepsis, hospital length of stay, and death. Several studies have looked at 1,25(OH)2D levels in patients with sepsis and discovered a link to poor outcomes. This discovery strengthens our case hypothesis.
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