Project description:Hyperglycemia frequently occurs with acute medical illness, especially among patients with cardiovascular disease, and has been linked to increased morbidity and mortality in critically ill patients. Even patients who are normoglycemic can develop hyperglycemia in response to acute metabolic stress. An expanding body of literature describes the benefits of normalizing hyperglycemia with insulin therapy in hospitalized patients. As a result, both the American Diabetes Association and the American College of Endocrinology have developed guidelines for optimal control of hyperglycemia, specifically targeting critically ill, hospitalized patients. Conventional blood glucose values of 140-180 mg/dL are considered desirable and safely achievable in most patients. More aggressive control to <110 mg/dL remains controversial, but has shown benefits in certain patients, such as those in surgical intensive care. Intravenous infusion is often used for initial insulin administration, which can then be transitioned to subcutaneous insulin therapy in those patients who require continued insulin maintenance. This article reviews the data establishing the link between hyperglycemia and its risks of morbidity and mortality, and describes strategies that have proven effective in maintaining glycemic control in high-risk hospitalized patients.
Project description:Active vitamin D metabolites, including 25-hydroxyvitamin D (25D) and 1,25-dihydroxyvitamin D (1,25D), have potent immunomodulatory effects and attenuate acute kidney injury (AKI) in animal models. We conducted an NIH-funded, phase 2, randomized, double-blind, multiple-dose, 3-arm clinical trial comparing oral calcifediol (25D), calcitriol (1,25D), and placebo among critically ill adult patients at high-risk of moderate-to-severe AKI. The primary end point was a hierarchical composite of death, kidney replacement therapy, and kidney injury (baseline-adjusted mean change in serum creatinine), each assessed within 7 days following enrollment using a rank-based procedure. We also performed transcriptomic analyses on circulating CD14+ monocytes collected immediately prior to randomization and two days later using RNA sequencing. The global rank score for the primary end point was similar among calcifediol vs. placebo treated patients (P=0.85) and for calcitriol vs. placebo-treated patients (P=0.58). Calcitriol upregulated more individual genes and pathways in circulating monocytes than did calcifediol, including pathways involving interferon (IFN)-alpha, IFN-gamma, oxidative phosphorylation, DNA repair, and heme metabolism. In summary, treatment with calcifediol or calcitriol in critically ill adults did not attenuate AKI, but calcitriol upregulated multiple genes and pathways involving immunomodulation, DNA repair, and heme metabolism.
Project description:IntroductionThiamine (Vitamin B1) is an essential micronutrient and is classically considered a co-factor in energy metabolism. The association between thiamine status and whole-body metabolism in critical illness has not been studied.ObjectivesTo determine association between whole blood thiamine pyrophosphate (TPP) concentrations and plasma metabolites and connected metabolic pathways using high resolution metabolomics (HRM) in critically ill patients.MethodsCross-sectional study performed at Erciyes University Hospital, Kayseri, Turkey and Emory University, Atlanta, GA, USA. Participants were critically ill adults with an expected length of intensive care unit stay longer than 48 h and receiving chronic furosemide therapy. A total of 76 participants were included. Mean age was 69 years (range 33-92 years); 65% were female. Blood for TPP and metabolomics was obtained on the day of ICU admission. Whole blood TPP was measured by HPLC and plasma HRM was performed using liquid chromatography/mass spectrometry. Data was analyzed using regression analysis of TPP levels against all plasma metabolomic features in metabolome-wide association studies (MWAS). MWAS using the highest and lowest TPP concentration tertiles was performed as a secondary analysis.ResultsSpecific metabolic pathways associated with whole blood TPP levels in regression and tertile analysis included pentose phosphate, fructose and mannose, branched chain amino acid, arginine and proline, linoleate, and butanoate pathways.ConclusionsPlasma HRM revealed that thiamine status, determined by whole blood TPP concentrations, was significantly associated with metabolites and metabolic pathways related to metabolism of energy, carbohydrates, amino acids, lipids, and the gut microbiome in adult critically ill patients.
Project description:Background: Thiamine deficiency is common in patients with heart failure, and thiamine supplement can benefit these patients. However, the association between thiamine administration and prognosis among critically ill patients with heart failure remains unclear. Thus, this study aims to prove the survival benefit of thiamine use in critically ill patients with heart failure. Methods: A retrospective cohort analysis was performed on the basis of the Medical Information Mart of Intensive Care-Ⅳ database. Critically ill patients with heart failure were divided into the thiamine and non-thiamine groups depending on whether they had received thiamine therapy or not during hospitalization. The association between thiamine supplement and in-hospital mortality was assessed by using the Kaplan-Meier (KM) method and Cox proportional hazard models. A 1:1 nearest propensity-score matching (PSM) and propensity score-based inverse probability of treatment weighting (IPW) were also performed to ensure the robustness of the findings. Results: A total of 7,021 patients were included in this study, with 685 and 6,336 in the thiamine and non-thiamine groups, respectively. The kaplan-meier survival curves indicated that the thiamine group had a lower in-hospital mortality than the none-thiamine group. After adjusting for various confounders, the Cox regression models showed significant beneficial effects of thiamine administration on in-hospital mortality among critically ill patients with heart failure with a hazard ratio of 0.78 (95% confidence interval: 0.67-0.89) in the fully adjusted model. propensity-score matching and probability of treatment weighting analyses also achieved consistent results. Conclusion: Thiamine supplement is associated with a decreased risk of in-hospital mortality in critically ill patients with heart failure who are admitted to the ICU. Further multicenter and well-designed randomized controlled trials with large sample sizes are necessary to validate this finding.
Project description:BackgroundMyocardial infarction (MI) is a common cardiovascular disease (CVD) in critically ill patients, leading to 17% mortality in the intensive care unit (ICU) setting. Patients with CVD frequently suffer from thiamine insufficiency, thereby thiamine supplements may be helpful. Unfortunately, the relationship between thiamine treatment and survival outcomes in ICU patients with MI is still unknown. The purpose of the research is to demonstrate the survival advantage of thiamine application in these patients.MethodsThe Medical Information Mart of Intensive Care-IV database served as the foundation for this retrospective cohort analysis. Depending on whether patients were given thiamine therapy during the hospital stay, critically ill MI patients were split into the thiamine and non-thiamine groups. The Kaplan-Meier (KM) method and Cox proportional hazard models were used to evaluate the relationship between thiamine use and the risk of in-hospital, 30-day, and 90-day mortality. To validate the results, a 1:2 closest propensity-score matching (PSM) was also carried out.ResultsThis study included 1782 patients for analysis with 170 and 1,612 individuals in the thiamine and non-thiamine groups, respectively. The KM survival analyses revealed that the risk of in-hospital, 30-day, and 90-day mortality was significantly lower in the thiamine group than the none-thiamine group. After modifying for a variety of confounding factors, the Cox regression models demonstrated substantial positive impacts of thiamine use on in-hospital, 30-d, and 90-d mortality risk among critically ill patients with MI with hazard ratio being 0.605 [95% confidence interval (CI): 0.397-0.921, p = 0.019], 0.618 (95% CI: 0.398-0.960, p = 0.032), and 0.626 (95% CI: 0.411-0.953, p = 0.028), respectively, in the completely modified model. PSM analyses also obtained consistent results.ConclusionThiamine supplementation is related to a decreased risk of mortality risk in critically ill patients with MI who are admitted to the ICU. More multicenter, large-sample, and well-designed randomized controlled trials are needed to validate this finding.
Project description:BackgroundThiamine is a precursor of the essential coenzyme thiamine pyrophosphate required for glucose metabolism; it improves the immune system function and has shown to reduce the risk of several diseases. The role of thiamine in critically ill septic patient has been addressed in multiple studies; however, it's role in COVID-19 patients is still unclear. The aim of this study was to evaluate the use of thiamine as an adjunctive therapy on mortality in COVID-19 critically ill patients.MethodsThis is a two-center, non-interventional, retrospective cohort study for critically ill patients admitted to intensive care units (ICUs) with a confirmed diagnosis of COVID19. All patients aged 18 years or older admitted to ICUs between March 1, 2020, and December 31, 2020, with positive PCR COVID-19 were eligible for inclusion. We investigated thiamine use as an adjunctive therapy on the clinical outcomes in critically ill COVID-19 patients after propensity score matching.ResultsA total of 738 critically ill patients with COVID-19 who had been admitted to ICUs were included in the study. Among 166 patients matched using the propensity score method, 83 had received thiamine as adjunctive therapy. There was significant association between thiamine use with in-hospital mortality (OR = 0.39; 95% CI 0.19-0.78; P value = 0.008) as well as the 30-day mortality (OR = 0.37; 95% CI 0.18-0.78; P value = 0.009). Moreover, patients who received thiamine as an adjunctive therapy were less likely to have thrombosis during ICU stay [OR (95% CI) 0.19 (0.04-0.88), P value = 0.03].ConclusionThiamine use as adjunctive therapy may have potential survival benefits in critically ill patients with COVID-19. Additionally, it was associated with a lower incidence of thrombosis. Further interventional studies are required to confirm these findings.
Project description:Background & aimsVitamin D's pleiotropic effects include immune modulation, and its supplementation has been shown to prevent respiratory tract infections. The effectivity of vitamin D as a therapeutic intervention in critical illness remains less defined. The current study analyzed clinical and immunologic effects of vitamin D levels in patients suffering from coronavirus disease 2019 (COVID-19) induced acute respiratory distress syndrome (ARDS).MethodsThis was a single-center retrospective study in patients receiving intensive care with a confirmed SARS-CoV-2 infection and COVID-19 ARDS. 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D serum levels, pro- and anti-inflammatory cytokines and immune cell subsets were measured on admission as well as after 10-15 days. Clinical parameters were extracted from the patient data management system. Standard operating procedures included the daily administration of vitamin D3 via enteral feeding.ResultsA total of 39 patients with COVID-19 ARDS were eligible, of which 26 were included in this study as data on vitamin D status was available. 96% suffered from severe COVID-19 ARDS. All patients without prior vitamin D supplementation (n = 22) had deficient serum levels of 25-hydroxyvitamin D. Vitamin D supplementation resulted in higher serum levels of 25-hydroxyvitamin D but not did not increase 1,25-dihydroxyvitamin D levels after 10-15 days. Clinical parameters did not differ between patients with sufficient or deficient levels of 25-hydroxyvitamin D. Only circulating plasmablasts were higher in patients with 25-hydroxyvitamin D levels ≥30 ng/ml (p = 0.029). Patients with 1,25-dihydroxyvitamin D levels below 20 pg/ml required longer mechanical ventilation (p = 0.045) and had a worse acute physiology and chronic health evaluation (APACHE) II score (p = 0.048).ConclusionThe vast majority of COVID-19 ARDS patients had vitamin D deficiency. 25-hydroxyvitamin D status was not related to changes in clinical course, whereas low levels of 1,25-dihydroxyvitamin D were associated with prolonged mechanical ventilation and a worse APACHE II score.
Project description:Oxygen consumption may be impaired in critically ill patients.To evaluate the effect of intravenous thiamine on oxygen consumption ([Formula: see text]o2) in critically ill patients.This was a small, exploratory open-label pilot study conducted in the intensive care units at a tertiary care medical center. Critically ill adults requiring mechanical ventilation were screened for enrollment. Oxygen consumption ([Formula: see text]o2) and cardiac index (CI) were recorded continuously for 9 hours. After 3 hours of baseline data collection, 200 mg of intravenous thiamine was administered. The outcome was change in [Formula: see text]o2 after thiamine administration.Twenty patients were enrolled and 3 were excluded because of incomplete [Formula: see text]o2 data, leaving 17 patients for analysis. There was a trend toward increase in [Formula: see text]o2 after thiamine administration (16.3 ml/min, SE 8.5; P?=?0.052). After preplanned adjustment for changes in CI in case of a delivery-dependent state in some patients (with exclusion of one additional patient because of missing CI data), this became statistically significant (16.9 ml/min, SE 8.6; P?=?0.047). In patients with average CI greater than our cohort's mean value of 3 L/min/m(2), [Formula: see text]o2 increased by 70.9 ml/min (±16; P?<?0.0001) after thiamine. Thiamine had no effect in patients with reduced CI (<?2.4 L/min/m(2)). There was no association between initial thiamine level and change in [Formula: see text]o2 after thiamine administration.The administration of a single dose of thiamine was associated with a trend toward increase in [Formula: see text]o2 in critically ill patients. There was a significant increase in [Formula: see text]o2 in those patients with preserved or elevated CI. Further study is needed to better characterize the role of thiamine in oxygen extraction. Clinical trial registered with www.clinicaltrials.gov (NCT01462279).