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1.
High dose intravenous vitamin C treatment in Sepsis: associations with acute kidney injury and mortality.
McCune, TR, Toepp, AJ, Sheehan, BE, Sherani, MSK, Petr, ST, Dodani, S
BMC nephrology. 2021;(1):387
Abstract
BACKGROUND The effects of vitamin C on clinical outcomes in critically ill patients remain controversial due to inconclusive studies. This retrospective observational cohort study evaluated the effects of vitamin C therapy on acute kidney injury (AKI) and mortality among septic patients. METHODS Electronic medical records of 1390 patients from an academic hospital who were categorized as Treatment (received at least one dose of 1.5 g IV vitamin C, n = 212) or Comparison (received no, or less than 1.5 g IV vitamin C, n = 1178) were reviewed. Propensity score matching was conducted to balance a number of covariates between groups. Multivariate logistic regressions were conducted predicting AKI and in-hospital mortality among the full sample and a sub-sample of patients seen in the ICU. RESULTS Data revealed that vitamin C therapy was associated with increases in AKI (OR = 2.07 95% CI [1.46-2.93]) and in-hospital mortality (OR = 1.67 95% CI [1.003-2.78]) after adjusting for demographic and clinical covariates. When stratified to examine ICU patients, vitamin C therapy remained a significant risk factor of AKI (OR = 1.61 95% CI [1.09-2.39]) and provided no protective benefit against mortality (OR = 0.79 95% CI [0.48-1.31]). CONCLUSION Ongoing use of high dose vitamin C in sepsis should be appraised due to observed associations with AKI and death.
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Administration of parenteral nutrition during therapeutic hypothermia: a population level observational study using routinely collected data held in the National Neonatal Research Database.
Gale, C, Jeyakumaran, D, Longford, N, Battersby, C, Ojha, S, Oughham, K, Dorling, J
Archives of disease in childhood. Fetal and neonatal edition. 2021;(6):608-613
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BACKGROUND Parenteral nutrition is commonly administered during therapeutic hypothermia. Randomised trials in critically ill children indicate that parenteral nutrition may be harmful. OBJECTIVE To examine the association between parenteral nutrition during therapeutic hypothermia and clinically important outcomes. DESIGN Retrospective, population-based cohort study using the National Neonatal Research Database; propensity scores were used to create matched groups for comparison. SETTING National Health Service neonatal units in England, Scotland and Wales. PARTICIPANTS 6030 term and near-term babies, born 1/1/2010 and 31/12/2017, who received therapeutic hypothermia; 2480 babies in the matched analysis. EXPOSURE We compared babies that received any parenteral nutrition during therapeutic hypothermia with babies that did not. MAIN OUTCOME MEASURES Primary outcome: blood culture confirmed late-onset infection; secondary outcomes: treatment for late onset infection, necrotising enterocolitis, survival, length of stay, measures of breast feeding, hypoglycaemia, central line days, time to full enteral feeds, discharge weight. RESULTS 1475/6030 babies (25%) received parenteral nutrition. In comparative matched analyses, the rate of culture positive late onset infection was higher in babies that received parenteral nutrition (0.3% vs 0.9%; difference 0.6; 95% CI 0.1, 1.2; p=0.03), but treatment for presumed infection was not (difference 0.8%, 95% CI -2.1 to 3.6, p=0.61). Survival was higher in babies that received parenteral nutrition (93.1% vs 90.0%; rate difference 3.1, 95% CI 1.5, 4.7; p<0.001). CONCLUSIONS Receipt of parenteral nutrition during therapeutic hypothermia is associated with higher late-onset infection but lower mortality. This finding may be explained by residual confounding. Research should address the risks and benefits of parenteral nutrition in this population.
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Serum Coenzyme Q10 Levels are Decreased in Critically-Ill Septic Patients: Results From a Preliminary Study.
Vassiliou, AG, Mastora, Z, Jahaj, E, Keskinidou, C, Pratikaki, ME, Kampisiouli, E, Orfanos, SE, Kotanidou, A, Dimopoulou, I
Biological research for nursing. 2021;(2):198-207
Abstract
BACKGROUND The increased oxidative stress resulting from the inflammatory responses in sepsis initiates changes in mitochondrial function which may result in organ damage, the most common cause of death in the intensive care unit (ICU). Deficiency of coenzyme Q10 (CoQ10), a key cofactor in the mitochondrial respiratory chain, could potentially disturb mitochondrial bioenergetics and oxidative stress, and may serve as a biomarker of mitochondrial dysfunction. Hence, we aimed to investigate in initially non-septic patients whether CoQ10 levels are decreased in sepsis and septic shock compared to ICU admission, and to evaluate its associations with severity scores, inflammatory biomarkers, and ICU outcomes. METHODS Observational retrospective analysis on 86 mechanically-ventilated, initially non-septic, ICU patients. CoQ10 was sequentially measured on ICU admission, sepsis, septic shock or at ICU discharge. CoQ10 was additionally measured in 25 healthy controls. Inflammatory biomarkers were determined at baseline and sepsis. RESULTS On admission, ICU patients who developed sepsis had lower CoQ10 levels compared to healthy controls (0.89 vs. 1.04 µg/ml, p < 0.05), while at sepsis and septic shock CoQ10 levels decreased further (0.63 µg/ml; p < 0.001 and 0.42 µg/ml; p < 0.0001, respectively, from admission). In ICU patients who did not develop sepsis, admission CoQ10 levels were also lower than healthy subjects (0.81 µg/ml; p < 0.001) and were maintained at the same levels until discharge. CONCLUSION CoQ10 levels in critically-ill patients are low on ICU admission compared to healthy controls and exhibit a further decrease in sepsis and septic shock. These results suggest that sepsis severity leads to CoQ10 depletion.
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Factors Disrupting Melatonin Secretion Rhythms During Critical Illness.
Maas, MB, Lizza, BD, Abbott, SM, Liotta, EM, Gendy, M, Eed, J, Naidech, AM, Reid, KJ, Zee, PC
Critical care medicine. 2020;(6):854-861
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Abstract
OBJECTIVES The circadian system modulates many important physiologic processes, synchronizing tissue-specific functions throughout the body. We sought to characterize acute alterations of circadian rhythms in critically ill patients and to evaluate associations between brain dysfunction, systemic multiple organ dysfunction, environmental stimuli that entrain the circadian rhythm (zeitgebers), rest-activity rhythms, and the central circadian rhythm-controlled melatonin secretion profile. DESIGN Prospective study observing a cohort for 24-48 hours beginning within the first day of ICU admission. SETTING Multiple specialized ICUs within an academic medical center. PATIENTS Patients presenting from the community with acute onset of either intracerebral hemorrhage as a representative neurologic critical illness or sepsis as a representative systemic critical illness. Healthy control patients were studied in using modified constant routine in a clinical research unit. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS Light, feeding, activity, medications, and other treatment exposures were evaluated along with validated measures of encephalopathy (Glasgow Coma Scale), multiple organ system function (Sequential Organ Failure Assessment score), and circadian rhythms (profiles of serum melatonin and its urinary metabolite 6-sulphatoxymelatonin). We studied 112 critically ill patients, including 53 with sepsis and 59 with intracerebral hemorrhage. Environmental exposures were abnormal, including light (dim), nutritional intake (reduced or absent and mistimed), and arousal stimuli (increased and mistimed). Melatonin amplitude and acrophase timing were generally preserved in awake patients but dampened and delayed with increasing encephalopathy severity. Melatonin hypersecretion was observed in patients exposed to catecholamine vasopressor infusions, but unaffected by sedatives. Change in vasopressor exposure was the only factor associated with changes in melatonin rhythms between days 1 and 2. CONCLUSIONS Encephalopathy severity and adrenergic agonist medication exposure were the primary factors contributing to abnormal melatonin rhythms. Improvements in encephalopathy and medical stabilization did not rapidly normalize rhythms. Urinary 6-sulphatoxymelatonin is not a reliable measure of the central circadian rhythm in critically ill patients.
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Severe infections in patients with anti-neutrophil cytoplasmic antibody-associated vasculitis: a retrospective cohort study with a clinical phenotype approach.
Caballero-Islas, AE, Hoyo-Ulloa, I, García-Castro, A, Hinojosa-Azaola, A
Rheumatology international. 2020;(10):1657-1666
Abstract
Severe infections are common in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). We aimed to describe the characteristics of patients with AAV and severe infections according to clinical phenotype. Retrospective cohort study including patients with granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA). Baseline characteristics were compared between patients with and without at least one severe infection. Demographics, comorbidities, clinical characteristics, laboratory and treatment were retrieved at diagnosis and at every infectious event. One hundred and eight patients were included (57 with and 51 without infections). Patients with an infection had received more frequently methylprednisolone boluses at AAV diagnosis than patients without infections (OR 2.6, 95% CI 1.1-5.9, p = 0.01). There were a total of 108 severe infections in 57 patients (median follow-up 18 months). Thirty-two patients (56%) had an infectious complication within the first year of AAV diagnosis, 43 (75%) had pulmonary involvement during the first infection. The most frequent type of infection was pneumonia. Phenotypes were: Non-severe AAV (n = 11), severe PR3-AAV (n = 30), severe MPO-AAV (n = 9); the number of infectious events in each group was 11, 69, 18, respectively. Patients with severe MPO phenotype were older and required more frequently ICU stay compared to other phenotypes. Positive correlation was found between total of infections and pulmonary infiltrates due to vasculitis (ρ = 0.40, p = 0.003), endobronchial involvement (ρ = 0.40, p = 0.003), and alveolar hemorrhage (ρ = 0.34, p = 0.015). Severe infections, most commonly pneumonia, were frequent in this cohort, especially during the first year after diagnosis, in patients with pulmonary involvement and severe PR3 phenotype who received methylprednisolone boluses.
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Serum trace element and heavy metal levels in patients with sepsis.
Akkaş, İ, Ince, N, Sungur, MA
The aging male : the official journal of the International Society for the Study of the Aging Male. 2020;(3):222-226
Abstract
Background and objectives: Sepsis is defined as a life-threatening organ dysfunction syndrome, which occurs when the body's immune response to infection is impaired. The aim of the present study was to investigate serum Iron, Copper, Zinco, Cobalt, Chromium, Selenium, Vanadium, Nickel, Cadmium, and Aliminium levels in patients with sepsis.Materials and methods: This prospective and observational study was conducted at a tertiary care university hospital of Turkey from 2015 to 2016, and comprised patients with sepsis. Serum concentrations of 10 elements were analyzed using inductively coupled plasma mass spectrometry. Analyses were performed at the laboratory of Düzce University Scientific and Technological Research Application and Research Center. A total of 87 participants (52 men, 35 women; average age, 74.11 ± 14.26) were enrolled.Results: When evaluated in terms of trace elements, a significant difference was noted between the sepsis and control groups in terms of the levels of the five elements. Chromium, Iron, Nickel, Copper, and Cadmium levels were significantly higher in the sepsis group.Conclusion: Our study indicated in particular, Iron, Copper, Chromium, Nickel, and Cadmium levels were elevated in patients with sepsis.
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Stool Short-Chain Fatty Acids in Critically Ill Patients with Sepsis.
Valdés-Duque, BE, Giraldo-Giraldo, NA, Jaillier-Ramírez, AM, Giraldo-Villa, A, Acevedo-Castaño, I, Yepes-Molina, MA, Barbosa-Barbosa, J, Barrera-Causil, CJ, Agudelo-Ochoa, GM
Journal of the American College of Nutrition. 2020;(8):706-712
Abstract
Objective: To determine the concentration of stool short-chain fatty acids (SCFAs) in critically ill patients with sepsis and to compare the results between the critically ill patient and the control group.Methods: This descriptive, multicenter, observational study was conducted in five health institutions. Over a 6-month study period, critically ill patients with sepsis who were admitted to the intensive care unit (ICU) and met the inclusion criteria were enrolled, and a control, paired by age and sex, was recruited for each patient. A spontaneous stool sample was collected from each participant and a gas chromatograph coupled to a mass spectrometer (Agilent 7890/MSD 5975 C) was used to measure the concentrations SCFAs.Results: The final sample included 44 patients and 45 controls. There were no differences in the age and sex distributions between the groups (p > 0.05). According to body mass index (BMI), undernutrition was more prevalent among critically ill patients, and BMI in control subjects was most frequently classified as overweight (p = 0.024). Propionic acid, acetic acid, butyric acid, and isobutyric acid concentrations were significantly lower in the critically ill patient group than in the control group (p = 0.000). No association with outcome variables (complications, ICU stay, and discharge condition) was found in the patients, and patients diagnosed with infection on ICU admission showed significant decreases in butyric and isobutyric acid concentrations with respect to other diagnostic criteria (p < 0.05).Conclusions: The results confirm significantly lower concentrations of stool SCFAs in critically ill patients with sepsis than in control subjects. Due to its role in intestinal integrity, barrier function, and anti-inflammatory effect, maintaining the concentration of SCFAs may be important in the ICU care protocols of the critical patient.
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[Diagnostic and prognostic value of peripheral lymphocyte subtyping for invasive candidiasis infection in critically ill patients with non-neutropenic sepsis].
Han, W, Wang, H, Cui, N, Zhang, JH, Bai, GX, Chen, JW, Long, Y
Zhonghua nei ke za zhi. 2020;(12):968-975
Abstract
Objective: To assess the diagnostic and prognostic value of lymphocyte subtyping for invasive candidiasis infection (ICI) in critically ill patients with non-neutropenic sepsis. Methods: A prospective observational cohort study was performed at Peking Union Medical College Hospital (PUMCH), 377 patients with non-neutropenic sepsis admitted to Department of Critical Care Medicine from January 2017 to November 2019 were enrolled. There were 9.0% (34/377) patients diagnosed as ICI. Vital signs, supportive care therapy and microbiological specimens were collected. Peripheral blood lymphocyte subtypes, serum globulin, complements, inflammatory factors such as interleukin(IL)-6, IL-8, IL-10 and tumor necrosis factor were detected within 24 hours after sepsis was diagnosed. The receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value and prognostic significance of immunological indicators for ICI. Multiple logistic regression was used to analyze the independent risk factors for ICI. Kaplan-Meier analysis was used to analyze survival. Results: The acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) score was 17.0 (13.0, 21.0) in all 377 patients. The sequential organ failure score (SOFA) was 11.0 (8.0, 13.0), and the 28-day mortality rate was 27.6% (104/377). Peripheral blood CD8+absolute T lymphocyte count≤177 cells/μl, CD28+CD8+T-cell count≤81 cells/μl and 1, 3-β-D-glucan (BDG) ≥88.20 ng/L were closely correlated with the diagnosis of ICI (AUC=0.793,95%CI 0.749-0.833,P<0.000 1;AUC=0.892,95%CI 0.856-0.921, P<0.000 1;AUC=0.761, 95%CI 0.715-0.803,P<0.000 1, respectively), with sensitivity of diagnosis 94.12%, 100.00%, and 88.24%; the specificity of diagnosis 81.34%, 62.39%, 63.56% respectively. Multivariate logistic regression analysis identified CD8+T-cell count≤139 cells/μl (OR=7.463, 95%CI 1.300-42.831, P=0.024) and CD28+CD8+T-cell counts≤52 cells/μl (OR=57.494, 95%CI 3.986-829.359, P=0.003) as independent risk factors for higher mortality. Kaplan-Meier survival analysis suggested that CD8+T-cell count ≤139 cells/μl (P=0.0159) and CD28+CD8+T-cell count≤52 cells/μl (P=0.000 1) were associated with higher mortality within 28 days (68.8%, 91.7%). Conclusions: Low CD28+CD8+T cell count in peripheral blood is closely related to the development and clinical outcome of ICI in sepsis patients, which could be used as an effective indicator for the diagnosis and prognosis prediction of ICI.
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Muscle degradation, vitamin D and systemic inflammation in hospitalized septic patients.
Borges, RC, Barbeiro, HV, Barbeiro, DF, Soriano, FG
Journal of critical care. 2020;:125-131
Abstract
PURPOSE To date, the relationship between systemic inflammation and muscle changes observed by ultrasonography in septic patients in clinical studies is not known. Furthermore, the role of vitamin D on muscle changes in these patients needs to be investigated. MATERIALS AND METHODS Forty-five patients admitted to the ICU due to severe sepsis or septic shock. Blood samples were collected to evaluate systemic inflammation (interleukin (IL)-10, IL-1β, IL-1α, IL-6, IL-8 and tumor necrosis factor-α(TNF-α)) and vitamin D. Muscle mass was evaluated by ultrasound during hospitalization. Clinical tests of muscle strength (Medical Research Council (MRC) scale and handgrip) were performed after the awakening of patients. RESULTS There was a reduction in day 2 values to hospital discharge on TNF-alpha, IL-8, IL-6 and IL-10 (p < .05). The muscle mass showed a significant decline from day 6 of the ICU. After awakening, the patients had a significant increase in muscle strength (p < .05). There was a positive association between muscle mass variation (day 2 - ICU) with absolute values of IL-8 (r = 0.38 p = .05). For muscle strength, there was a negative association between handgrip strength with IL-8 (r = -0.36 p < .05) on ICU discharge. The vitamin D showed a positive association with the handgrip strength of the day 1 of the awakening (r = 0.51 p < .05). CONCLUSIONS In septic patients, there is an association between inflammation and changes in muscle mass and strength during ICU stay, which is similar to those observed in experimental studies. In addition, there was an association of vitamin D with recovery of muscle strength during hospitalization.
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A novel prediction equation of resting energy expenditure for Japanese septic patients.
Takemae, A, Takazawa, T, Kamiyama, J, Kanamoto, M, Tobe, M, Hinohara, H, Kunimoto, F, Saito, S
Journal of critical care. 2020;:236-242
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Estimating nutrient consumption and administering appropriate nutritional therapy is essential for improving clinical outcomes in critically ill patients. Various equations, such as the Harris-Benedict equation, have been developed to estimate the required calories. Previous equations, however, targeted Westerners, whose physical characteristics are likely different from those of Asians. Hence, it is unclear whether these equations can be used for Asian patients. This study focused specifically on sepsis patients admitted to a single Japanese ICU, and aimed to develop novel equations to estimate their total energy expenditure. A total of 95 sepsis patients were included in this study. We measured resting energy expenditure (REE) by using indirect calorimetry, and created equations to calculate basal metabolic rate (BMR) using height, weight and age as variables. REE was predicted by multiplying BMR by the novel equation with the stress factor of 1.4. The prediction error of our novel equations were smaller than those of other conventional equations. We further confirmed the accuracy of our equations and that they were unaffected by patient age and disease severity by using data obtained from another patient group. The current study suggested that these equations might allow accurate estimation of the total energy expenditure and proper management of nutritional therapy in Asian sepsis patients.