Jenny E. Han

High dose vitamin D administration in ventilated intensive care unit patients: A pilot double blind randomized controlled trial

Highlights • First double blind RCT of vitamin D therapy in mechanically ventilated patients.• Treatment with placebo, 250,000 IU or 500,000 IU enteral vitamin D3 was well tolerated.• Significant increase in plasma 25(OH)D from baseline to day 7.• Significant decrease in hospital length of stay for vitamin D3 treated subjects.• No change in plasma LL-37 according to treatment group.

Vitamin D and sepsis: An emerging relationship

Vitamin D insufficiency and sepsis are both highly prevalent worldwide problems and this article reviews the emerging science that is defining the intersections of these conditions. The importance of vitamin D’s role in skeletal health has long been understood but recent evidence is beginning to highlight its role in the functioning of other physiologic systems of the body. Basic science data reveal its integral role in local immune responses to pathogens and the systemic inflammatory pathways of sepsis. Furthermore, clinical scientists have found associations with respiratory infections, critical illness and sepsis but the causal relationship and its clinical impact have yet to be clearly defined. The article ends with speculations on the connections between racial disparities and seasonal differences in sepsis and vitamin D insufficiency.

A novel mRNA binding protein complex promotes localized plasminogen activator inhibitor-1 accumulation at the myoendothelial junction

Objective—Plasminogen activator inhibitor-1 (PAI-1) has previously been shown to be key to the formation of myoendothelial junctions (MEJs) in normal and pathological states (eg, obesity). We therefore sought to identify the mechanism whereby PAI-1 could be selectively accumulated at the MEJ. Methods and Results—We identified PAI-1 protein enrichment at the MEJ in obese mice and in response to tumor necrosis factor (TNF-&agr;) with a vascular cell coculture. However, PAI-1 mRNA was also found at the MEJ and transfection with a PAI-1–GFP with TNF-&agr; did not demonstrate trafficking of the protein to the MEJ. We therefore hypothesized the PAI-1 mRNA was being locally translated and identified serpine binding protein-1, which stabilizes PAI-1 mRNA, as being enriched in obese mice and after treatment with TNF-&agr;, whereas Staufen, which degrades PAI-1 mRNA, was absent in obese mice and after TNF-&agr; application. We identified nicotinamide phosphoribosyl transferase as a serpine binding protein-1 binding partner with a functional &tgr;-like microtubule binding domain. Application of peptides against the microtubule binding domain significantly decreased the number of MEJs and the amount of PAI-1 at the MEJ. Conclusion—We conclude that PAI-1 can be locally translated at the MEJ as a result of a unique mRNA binding protein complex.

Vitamin D Supplementation in Sepsis and Critical Illness: Where Are We Now?

There is growing recognition that vitamin D deficiency is very common in critically ill adults and children, with or without sepsis (1–10). Low serum concentrations of the biomarker of vitamin D status, 25-hydroxyvitamin D (25[OH]D), when documented at intensive care unit (ICU) admission, remain unchanged or significantly decrease during the subsequent 7- to 10-day period without adequate vitamin D supplementation (2–5). Several studies have variously demonstrated a significant association between vitamin D deficiency (blood 25[OH]D levels < 15–20 ng/ml] in the ICU and adverse clinical outcomes (e.g., length of hospital stay, readmission rates, and mortality) (4–10). For example, in a retrospective observational study in 1,325 patients, Braun and colleagues found that serum 25(OH)D levels ≤ 15 ng/ml obtained within 7 days before or after initiation of critical care were associated with higher 30-, 60-, and 365-day mortality, even after multivariate adjustment (6). Large retrospective cohort studies indicate that low serum levels of 25(OH)D obtained at time points within 1 year prior to ICU admission are associated with higher rates of sepsis, bloodstream infection, and mortality (11, 12). The reasons for the high rate of vitamin D deficiency in the ICU is likely multifactorial. Decreased exposure to sunlight and/or dietary intake of vitamin D prior to ICU admission may occur, and inflammation, decreased synthesis of vitamin D–binding protein (VDBP; which may result in urinary loss of 25[OH]D), interstitial extravasation, and hemodilution due to fluid loads may play a role after admission (1, 13).

High-Dose Vitamin D3 Administration Is Associated With Increases in Hemoglobin Concentrations in Mechanically Ventilated Critically Ill Adults A Pilot Double-Blind, Randomized, Placebo-Controlled Trial

BACKGROUND Anemia and vitamin D deficiency are highly prevalent in critical illness, and vitamin D status has been associated with hemoglobin concentrations in epidemiologic studies. We examined the effect of high-dose vitamin D therapy on hemoglobin and hepcidin concentrations in critically ill adults. MATERIALS AND METHODS Mechanically ventilated critically ill adults (N = 30) enrolled in a pilot double-blind, randomized, placebo-controlled trial of high-dose vitamin D3 (D3 ) were included in this analysis. Participants were randomized to receive placebo, 50,000 IU D3 , or 100,000 IU D3 daily for 5 days (totaling 250,000 IU D3 and 500,000 IU D3 , respectively). Blood was drawn weekly throughout hospitalization for up to 4 weeks. Linear mixed-effects models were used to assess change in hemoglobin and hepcidin concentrations by treatment group over time. RESULTS At enrollment, >75% of participants in all groups had plasma 25-hydroxyvitamin D (25(OH)D) concentrations <30 ng/mL, and >85% of participants across groups were anemic. In the 500,000-IU D3 group, hemoglobin concentrations increased significantly over time (Pgroup × time = .01) compared with placebo but did not change in the 250,000-IU D3 group (Pgroup × time = 0.59). Hepcidin concentrations decreased acutely in the 500,000-IU D3 group relative to placebo after 1 week (P = .007). Hepcidin did not change significantly in the 250,000-IU D3 group. CONCLUSION In these critically ill adults, treatment with 500,000 IU D3 was associated with increased hemoglobin concentrations over time and acutely reduced serum hepcidin concentrations. These findings suggest that high-dose vitamin D may improve iron metabolism in critical illness and should be confirmed in larger studies.

Effect of Electronic Health Record Implementation in Critical Care on Survival and Medication Errors

Background: Electronic health records (EHR) with computerized physician order entry have become exceedingly common and government incentives have urged implementation. The purpose of this study was to ascertain the effect of EHR implementation on medical intensive care unit (MICU) mortality, length of stay (LOS), hospital LOS and medication errors. Materials and Methods: Prospective, observational study from July 2010‐June 2011 in MICU at an urban teaching hospital in Atlanta, Georgia of 797 patients admitted to the MICU; 281 patients before the EHR implementation and 516 patients post‐EHR implementation. Results: Compared with the preimplementation period (N = 43 per 281), the mortality risk at 4 months post‐EHR implementation (N = 41 per 247) and at 8 months post‐EHR implementation (N = 26 per 269) significantly decreased (P < 0.001). In addition, the mean MICU LOS statistically decreased from 4.03 ± 1.06 days pre‐EHR to 3.26 ± 1.06 days 4 months post‐EHR and to 3.12 ± 1.05 days 8 months post‐EHR (P = 0.002). However, the mean hospital LOS was not statistically decreased. Although medication errors increased after implementation (P = 0.002), this was attributable to less severe errors and there was actually a decrease in the number of severe medication errors (both P < 0.001). Conclusions: We report a survival benefit following the implementation of EHR with computerized physician order entry in a critical care setting and a concomitant decrease in the number of severe medication errors. Although overall hospital LOS was not shortened, this study proposes that EHR implementation in a busy urban hospital was associated with improved ICU outcomes.

Evaluating Simulation-Based ACLS Education on Patient Outcomes: A Randomized, Controlled Pilot Study

BACKGROUND Simulation training is widely accepted as an effective teaching tool, especially for dealing with high-risk situations. OBJECTIVE We assessed whether standardized, simulation-based advanced cardiac life support (ACLS) training improved performance in managing simulated and actual cardiac arrests. METHODS A total of 103 second- and third-year internal medicine residents were randomized to 2 groups. The first group underwent conventional ACLS training. The second group underwent two 2 1/2-hour sessions of standardized simulation ACLS teaching. The groups were assessed by evaluators blinded to their assignment during in-hospital monthly mock codes and actual inpatient code sheets at 3 large academic hospitals. Primary outcomes were time to initiation of cardiopulmonary resuscitation, time to administration of first epinephrine/vasopressin, time to delivery of first defibrillation, and adherence to American Heart Association guidelines. RESULTS There were no differences in primary outcomes among the study arms and hospital sites. During 21 mock codes, the most common error was misidentification of the initial rhythm (67% [6 of 9] and 58% [7 of 12] control and simulation arms, respectively, P  =  .70). There were no differences in primary outcome among groups in 147 actual inpatient codes. CONCLUSIONS This blinded, randomized study found no effect on primary outcomes. A notable finding was the percentage of internal medicine residents who misidentified cardiac arrest rhythms.

Rational or rationalized choices in fluid resuscitation

The war between colloids and crystalloids wages on. In a large multinational survey of fluid prescribing practices in critically ill patients, we have a new and intriguing snapshot of global fluid resuscitation practices. Colloids are more often used for impaired perfusion or low cardiac output, and the choice of colloid or crystalloid varies enormously between countries. Why are some ICUs prescribing colloids more often than crystalloids when there is little convincing evidence that colloids are superior for fluid resuscitation? Are colloids advantageous in certain diseases, or in specific regional patient populations that have not yet been elucidated? Perhaps we should look inwards: the answer may not be more randomized clinical trials, but better adherence to current guidelines and treatment recommendations.

Oxidative stress in critically ill ventilated adults: effects of vitamin D 3 and associations with alveolar macrophage function

Background/objectivesDisruptions in redox balance lead to oxidative stress, a promoter of morbidity in critical illness. This study aimed to: (1) characterize the plasma and alveolar thiol/disulfide redox pools, (2) examine their associations with alveolar macrophage phagocytosis, and (3) determine the effect of high dose vitamin D3 on plasma thiol/disulfide redox.Subjects/methodsSubjects were 30 critically ill, ventilated adults in a double-blind randomized trial of high-dose (250 000 or 500 000 IU) vitamin D3 or placebo. Baseline bronchoalveolar lavage fluid (BALF) samples were analyzed for determination of alveolar phagocytosis index (PI) and for concentrations of glutathione (GSH), glutathione disulfide (GSSG), cysteine (Cys), cystine (CySS), and their respective redox potentials (EhGSSG and EhCySS). Plasma redox outcomes were assessed at baseline and days 7 and 14.ResultsBaseline plasma Cys was inversely associated with alveolar PI (ρ = −0.69, P = 0.003), and EhCySS was positively associated with PI (ρ = 0.61, P = 0.01). Over time, among all subjects there was an increase in plasma GSH levels and a decrease in EhGSSG (P < 0.01 for both), with no difference by treatment group. Vitamin D3 decreased oxidized plasma GSSG to a more normal state (P for group x time = 0.009).ConclusionsOxidative stress indicators were positively associated with alveolar macrophage phagocytic function in acutely ill ventilated adults. High-dose vitamin D3 decreased plasma GSSG concentrations, which suggests that vitamin D can possibly improve the oxidative stress environment.

Evaluation of medication errors with implementation of electronic health record technology in the medical intensive care unit

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