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Vitamin D status and its influence on outcomes following major burn injury and critical illness.

ABSTRACT: Vitamin D deficiency is common among the general population. It is also observed in up to 76% of critically ill patients. Despite the high prevalence of hypovitaminosis D in critical illness, vitamin D is often overlooked by medical staff as the clinical implications and consequences of vitamin D deficiency in acute contexts remain to be fully understood. Vitamin D has a broad range of pleotropic effects on various processes and systems including the immune-inflammatory response. 1?,25-dihydroxyvitamin D (1,25(OH)2D), has been shown to promote a tolerogenic immune response limiting deleterious inflammatory effects, modulation of the innate immune system, and enhancement of anti-microbial peptides. Vitamin D deficiency is frequently observed in critically ill patients and has been related to extrinsic causes (i.e., limited sunlight exposure), magnitude of injury/illness, or the treatment started by medical doctors including fluid resuscitation. Low levels of vitamin D in critically ill patients have been associated with sepsis, organ failure, and mortality. Despite this, there are subpopulations of critical illness, such as burn patients, where the literature regarding vitamin D status and its influence on outcomes remain insufficient. Thermal injury results in damage to both burned and non-burned tissues, as well as induces an exaggerated and persistent immune-inflammatory and hypermetabolic response. In this review, we propose potential mechanisms in which burn injury affects the vitamin D status and summarizes current literature investigating the influence of vitamin D status on outcomes. In addition, we reviewed the literature and trials investigating vitamin D supplementation in critically ill patients and discuss the therapeutic potential of vitamin D supplementation in burn and critically ill patients. We also highlight current limitations of studies that have investigated vitamin D status and supplementation in critical illness. Thermal injury influences vitamin D status. More studies investigating vitamin D depletion in burn patients and its influence on prognosis, via standardized methodology, are required to reach definitive conclusions and influence clinical practice.

SUBMITTER: Al-Tarrah K

PROVIDER: S-EPMC5910591 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Vitamin D status and its influence on outcomes following major burn injury and critical illness.

Al-Tarrah Khaled K Hewison Martin M Moiemen Naiem N Lord Janet M JM

Burns & trauma 20180416

Vitamin D deficiency is common among the general population. It is also observed in up to 76% of critically ill patients. Despite the high prevalence of hypovitaminosis D in critical illness, vitamin D is often overlooked by medical staff as the clinical implications and consequences of vitamin D deficiency in acute contexts remain to be fully understood. Vitamin D has a broad range of pleotropic effects on various processes and systems including the immune-inflammatory response. 1α,25-dihydroxy ...[more]

PMID: 29721511

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Project description:BackgroundMetabolic homeostasis is substantially disrupted in critical illness. Given the pleiotropic effects of vitamin D, we hypothesized that metabolic profiles differ between critically ill patients relative to their vitamin D status.MethodsWe performed a metabolomics study on biorepository samples collected from a single academic medical center on 65 adults with systemic inflammatory response syndrome or sepsis treated in a 20-bed medical ICU between 2008 and 2010. To identify key metabolites and metabolic pathways related to vitamin D status in critical illness, we first generated metabolomic data using gas and liquid chromatography mass spectroscopy. We followed this by partial least squares-discriminant analysis to identify individual metabolites that were significant. We then interrogated the entire metabolomics profile using metabolite set enrichment analysis to identify groups of metabolites and pathways that were differentiates of vitamin D status. Finally we performed logistic regression to construct a network model of chemical-protein target interactions important in vitamin D status.ResultsMetabolomic profiles significantly differed in critically ill patients with 25(OH)D ≤ 15 ng/ml relative to those with levels >15 ng/ml. In particular, increased 1,5-anhydroglucitol, tryptophan betaine, and 3-hydroxyoctanoate as well as decreased 2-arachidonoyl-glycerophosphocholine and N-6-trimethyllysine were strong predictors of 25(OH)D >15 ng/ml. The combination of these five metabolites led to an area under the curve for discrimination for 25(OH)D > 15 ng/ml of 0.82 (95% CI 0.71-0.93). The metabolite pathways related to glutathione metabolism and glutamate metabolism are significantly enriched with regard to vitamin D status.ConclusionVitamin D status is associated with differential metabolic profiles during critical illness. Glutathione and glutamate pathway metabolism, which play principal roles in redox regulation and immunomodulation, respectively, were significantly altered with vitamin D status.

Project description:Vitamin D plays a key role in immune function. Deficiency may aggravate the incidence and outcome of infectious complications in critically ill patients. We aimed to evaluate the prevalence of vitamin D deficiency and the correlation between serum 25-hydroxyvitamin D (25(OH) D) and hospital mortality, sepsis mortality and blood culture positivity.In a single-center retrospective observational study at a tertiary care center in Graz, Austria, 655 surgical and nonsurgical critically ill patients with available 25(OH) D levels hospitalized between September 2008 and May 2010 were included. Cox regression analysis adjusted for age, gender, severity of illness, renal function and inflammatory status was performed. Vitamin D levels were categorized by month-specific tertiles (high, intermediate, low) to reflect seasonal variation of serum 25(OH) D levels.Overall, the majority of patients were vitamin D deficient (<20 ng/ml; 60.2%) or insufficient (?20 and <30 ng/dl; 26.3%), with normal 25(OH) D levels (>30 ng/ml) present in only 13.6%. The prevalence of vitamin D deficiency and mean 25(OH) D levels was significantly different in winter compared to summer months (P <0.001). Hospital mortality was 20.6% (135 of 655 patients). Adjusted hospital mortality was significantly higher in patients in the low (hazard ratio (HR) 2.05, 95% confidence interval (CI) 1.31 to 3.22) and intermediate (HR 1.92, 95% CI 1.21 to 3.06) compared to the high tertile. Sepsis was identified as cause of death in 20 of 135 deceased patients (14.8%). There was no significant association between 25(OH) D and C-reactive protein (CRP), leukocyte count or procalcitonin levels. In a subgroup analysis (n?=?244), blood culture positivity rates did not differ between tertiles (23.1% versus 28.2% versus 17.1%, P?=?0.361).Low 25(OH) D status is significantly associated with mortality in the critically ill. Intervention studies are needed to investigate the effect of vitamin D substitution on mortality and sepsis rates in this population.

Project description:OBJECTIVE:Hospital-level variations in structure and process may affect clinical outcomes in ICUs. We sought to characterize the organizational structure, processes of care, use of protocols, and standardized outcomes in a large sample of U.S. ICUs. DESIGN:We surveyed 69 ICUs about organization, size, volume, staffing, processes of care, use of protocols, and annual ICU mortality. SETTING:ICUs participating in the United States Critical Illness and Injury Trials Group Critical Illness Outcomes Study. SUBJECTS:Sixty-nine intensivists completed the survey. MEASUREMENTS AND MAIN RESULTS:We characterized structure and process variables across ICUs, investigated relationships between these variables and annual ICU mortality, and adjusted for illness severity using Acute Physiology and Chronic Health Evaluation II. Ninety-four ICU directors were invited to participate in the study and 69 ICUs (73%) were enrolled, of which 25 (36%) were medical, 24 (35%) were surgical, and 20 (29%) were of mixed type, and 64 (93%) were located in teaching hospitals with a median number of five trainees per ICU. Average annual ICU mortality was 10.8%, average Acute Physiology and Chronic Health Evaluation II score was 19.3, 58% were closed units, and 41% had a 24-hour in-house intensivist. In multivariable linear regression adjusted for Acute Physiology and Chronic Health Evaluation II and multiple ICU structure and process factors, annual ICU mortality was lower in surgical ICUs than in medical ICUs (5.6% lower [95% CI, 2.4-8.8%]) or mixed ICUs (4.5% lower [95% CI, 0.4-8.7%]). We also found a lower annual ICU mortality among ICUs that had a daily plan of care review (5.8% lower [95% CI, 1.6-10.0%]) and a lower bed-to-nurse ratio (1.8% lower when the ratio decreased from 2:1 to 1.5:1 [95% CI, 0.25-3.4%]). In contrast, 24-hour intensivist coverage (p = 0.89) and closed ICU status (p = 0.16) were not associated with a lower annual ICU mortality. CONCLUSIONS:In a sample of 69 ICUs, a daily plan of care review and a lower bed-to-nurse ratio were both associated with a lower annual ICU mortality. In contrast to 24-hour intensivist staffing, improvement in team communication is a low-cost, process-targeted intervention strategy that may improve clinical outcomes in ICU patients.

Project description:OBJECTIVES:Acute kidney injury frequently complicates critical illness and is associated with high morbidity and mortality. Frailty is common in critical illness survivors, but little is known about the impact of acute kidney injury. We examined the association of acute kidney injury and frailty within a year of hospital discharge in survivors of critical illness. DESIGN:Secondary analysis of a prospective cohort study. SETTING:Medical/surgical ICU of a U.S. tertiary care medical center. PATIENTS:Three hundred seventeen participants with respiratory failure and/or shock. INTERVENTIONS:None. MEASUREMENTS AND MAIN RESULTS:Acute kidney injury was determined using Kidney Disease Improving Global Outcomes stages. Clinical frailty status was determined using the Clinical Frailty Scale at 3 and 12 months following discharge. Covariates included mean ICU Sequential Organ Failure Assessment score and Acute Physiology and Chronic Health Evaluation II score as well as baseline comorbidity (i.e., Charlson Comorbidity Index), kidney function, and Clinical Frailty Scale score. Of 317 patients, 243 (77%) had acute kidney injury and one in four patients with acute kidney injury was frail at baseline. In adjusted models, acute kidney injury stages 1, 2, and 3 were associated with higher frailty scores at 3 months (odds ratio, 1.92; 95% CI, 1.14-3.24; odds ratio, 2.40; 95% CI, 1.31-4.42; and odds ratio, 4.41; 95% CI, 2.20-8.82, respectively). At 12 months, a similar association of acute kidney injury stages 1, 2, and 3 and higher Clinical Frailty Scale score was noted (odds ratio, 1.87; 95% CI, 1.11-3.14; odds ratio, 1.81; 95% CI, 0.94-3.48; and odds ratio, 2.76; 95% CI, 1.34-5.66, respectively). In supplemental and sensitivity analyses, analogous patterns of association were observed. CONCLUSIONS:Acute kidney injury in survivors of critical illness predicted worse frailty status 3 and 12 months postdischarge. These findings have important implications on clinical decision making among acute kidney injury survivors and underscore the need to understand the drivers of frailty to improve patient-centered outcomes.

Project description:Background:Sepsis, trauma, and burn injury acutely depress systolic and diastolic cardiac function; data on long-term cardiac sequelae of pediatric critical illness are sparse. This study evaluated long-term systolic and diastolic function, myocardial fibrosis, and exercise tolerance in survivors of severe pediatric burn injury. Methods:Subjects at least 5 years after severe burn (post-burn:PB) and age-matched healthy controls (HC) underwent echocardiography to quantify systolic function (ejection fraction[EF%]), diastolic function (E/e'), and myocardial fibrosis (calibrated integrated backscatter) of the left ventricle. Exercise tolerance was quantified by oxygen consumption (VO2) and heart rate at rest and peak exercise. Demographic information, clinical data, and biomarker expression were used to predict long-term cardiac dysfunction and fibrosis. Findings:Sixty-five subjects (PB:40;HC:25) were evaluated. At study date, PB subjects were 19±5 years, were at 12±4 years postburn, and had burns over 59±19% of total body surface area, sustained at 8±5 years of age. The PB group had lower EF% (PB:52±9%;HC:61±6%; p=0.004), E/e' (PB:9.8±2.9;HC: 5.4±0.9;p<0.0001), VO2peak (PB:37.9±12;HC: 46±8.32 ml/min/kg; p=0.029), and peak heart rate (PB:161±26;HC:182±13bpm;p=0.007). The PB group had moderate (28%) or severe (15%) systolic dysfunction, moderate (50%) or severe diastolic dysfunction (21%), and myocardial fibrosis (18%). Biomarkers and clinical parameters predicted myocardial fibrosis, systolic dysfunction, and diastolic dysfunction. Interpretation:Severe pediatric burn injury may have lasting impact on cardiac function into young adulthood and is associated with myocardial fibrosis and reduced exercise tolerance. Given the strong predictive value of systolic and diastolic dysfunction, these patients might be at increased risk for early heart failure, associated morbidity, and mortality. Funding:Conflicts of Interest and Sources of Funding: The authors do not have any conflicts of interest to declare. This work was supported by NIH (P50 GM060338, R01 GM056687, R01 HD049471, R01 GM112936, R01-GM56687 and T32 GM008256), NIDILRR (H133A120091, 90DP00430100), Shriners Hospitals for Children (84080, 79141, 79135, 71009, 80100, 71008, 87300 and 71000), FAER (MRTG CON14876), and the Department of Defense (W81XWH-14-2-0162 and W81XWH1420162). It was also made possible with the support of UTMB's Institute for Translational Sciences, supported in part by a Clinical and Translational Science Award (UL1TR000071) from the National Center for Advancing Translational Sciences (NIH).

Dataset Information

Vitamin D status and its influence on outcomes following major burn injury and critical illness.

Publications

Vitamin D status and its influence on outcomes following major burn injury and critical illness.

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