-
1.
Dysbiosis in early sepsis can be modulated by a multispecies probiotic: a randomised controlled pilot trial.
Stadlbauer, V, Horvath, A, Komarova, I, Schmerboeck, B, Feldbacher, N, Klymiuk, I, Durdevic, M, Rainer, F, Blesl, A, Stiegler, P, et al
Beneficial microbes. 2019;(3):265-278
Abstract
The gut is hypothesised to play an important role in the development and progression of sepsis. It is however unknown whether the gut microbiome and the gut barrier function is already altered early in sepsis development and whether it is possible to modulate the microbiome in early sepsis. Therefore, a randomised, double blind, placebo-controlled pilot study to examine the alterations of the microbiome and the gut barrier in early sepsis and the influence of a concomitant probiotic intervention on dysbiosis at this early stage of the disease was conducted. Patients with early sepsis, defined as fulfilling the sepsis definition from the 2012 Surviving Sepsis Campaign guidelines but without signs of organ failure, received multispecies probiotic (Winclove 607 based on Omnibiotic® 10 AAD) for 28 days. Gut microbiome composition, function, gut barrier and bacterial translocation were studied. Patients with early sepsis had a significantly lower structural and functional alpha diversity, clustered differently and showed structural alterations on all taxonomic levels. Gut permeability was unaltered but endotoxin, endotoxin binding proteins and peptidoglycans were elevated in early sepsis patients compared to controls. Probiotic intervention successfully increased probiotic strains in stool and led to an improvement of functional diversity. Microbiome composition and function are altered in early sepsis. Probiotic intervention successfully modulates the microbiome and is therefore a promising tool for early intervention in sepsis.
-
2.
Effects of prebiotics on sepsis, necrotizing enterocolitis, mortality, feeding intolerance, time to full enteral feeding, length of hospital stay, and stool frequency in preterm infants: a meta-analysis.
Chi, C, Buys, N, Li, C, Sun, J, Yin, C
European journal of clinical nutrition. 2019;(5):657-670
-
-
Free full text
-
Abstract
BACKGROUND/OBJECTIVES Prebiotics are increasingly recognized as an effective measure to promote health and prevent adverse health outcomes in preterm infants. We aimed to systematically review the randomized controlled trials (RCTs) in this area. SUBJECTS/METHODS Relevant studies from January 2000 to June 2018 were searched and selected from PubMed, Medline, Scopus, and the Cochrane Library. RCTs were included if they involved preterm infant participants, included a prebiotic intervention group, measured incidence of sepsis, feeding intolerance, mortality, time to full enteral feeding, necrotizing enterocolitis (NEC), length of hospital stay, and stool frequency as outcomes. RESULTS Eighteen RCTs (n = 1322) were included in the final meta-analysis. Participants who took prebiotics showed significant decreases in the incidence of sepsis (with a risk ratio (RR) of 0.64, 95% CI: 0.51, 0.78), mortality (RR = 0.58. 95% CI: 0.36, 0.94), length of hospital stay (mean difference (MD): -5.18, 95% CI: -8.94, -1.11), and time to full enteral feeding (MD: -0.99, 95% CI: -1.15, 0.83). The pooled effects showed no significant differences between intervention and control groups in relation to the morbidity rate of NEC (RR = 0.79, 95% CI: 0.44, 1.44) or feeding intolerance (RR = 0.87, 95% CI: 0.52, 1.45). CONCLUSIONS The results showed that the use of prebiotics with preterm infants is safe and can decrease the incidence of sepsis, mortality, length of hospital stay, and time to full enteral feeding but not NEC.
-
3.
Role of selenium supplementation in prevention of late onset sepsis among very low birth weight neonates: a systematic review of randomized controlled trials.
Garg, BD, Bansal, A, Kabra, NS
The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians. 2019;(24):4159-4165
Abstract
Background: Neonatal sepsis is one of the most common causes of neonatal morbidity and mortality. Selenium has antioxidant and immune-modulating properties.Aim: The aim of this systematic review is to evaluate role of selenium supplementation in the prevention of late onset sepsis (LOS) among very low birth weight (VLBW) neonates.Methods: We searched literature for this review by searching the Cochrane Central Register of Controlled Trials (CENTRAL) electronic PubMed, Embase, and Google Scholar. We also searched for ongoing clinical trials.Results: This review included two randomized controlled trials (RCTs) that fulfilled inclusion criteria. There was statistically significant reduction in the incidence of LOS in the intervention group [23.7 versus 35.6%; relative risk (RR) 0.67; 95% CI 0.52-0.86; p= .001; number needed to treat (NNT) 8.4; 95% CI 5.2-20.96]. However, mortality due to any cause prior to hospital discharge was not statistically significant in between the groups (6.1% intervention group versus 6.9% control group; RR 0.88; 95% CI 0.49-1.61; p= .68).Conclusions: Evidences from current systematic review revealed that selenium supplementation has some role in the prevention of LOS. However, due to limited evidences and heterogeneity between studies, large RCTs are recommended among VLBW neonates.
-
4.
Update to the Vitamin C, Thiamine and Steroids in Sepsis (VICTAS) protocol: statistical analysis plan for a prospective, multicenter, double-blind, adaptive sample size, randomized, placebo-controlled, clinical trial.
Lindsell, CJ, McGlothlin, A, Nwosu, S, Rice, TW, Hall, A, Bernard, GR, Busse, LW, Ely, EW, Fowler, AA, Gaieski, DF, et al
Trials. 2019;(1):670
Abstract
BACKGROUND Observational research suggests that combined therapy with Vitamin C, thiamine and hydrocortisone may reduce mortality in patients with septic shock. METHODS AND DESIGN The Vitamin C, Thiamine and Steroids in Sepsis (VICTAS) trial is a multicenter, double-blind, adaptive sample size, randomized, placebo-controlled trial designed to test the efficacy of combination therapy with vitamin C (1.5 g), thiamine (100 mg), and hydrocortisone (50 mg) given every 6 h for up to 16 doses in patients with respiratory or circulatory dysfunction (or both) resulting from sepsis. The primary outcome is ventilator- and vasopressor-free days with mortality as the key secondary outcome. Recruitment began in August 2018 and is ongoing; 501 participants have been enrolled to date, with a planned maximum sample size of 2000. The Data and Safety Monitoring Board reviewed interim results at N = 200, 300, 400 and 500, and has recommended continuing recruitment. The next interim analysis will occur when N = 1000. This update presents the statistical analysis plan. Specifically, we provide definitions for key treatment and outcome variables, and for intent-to-treat, per-protocol, and safety analysis datasets. We describe the planned descriptive analyses, the main analysis of the primary end point, our approach to secondary and exploratory analyses, and handling of missing data. Our goal is to provide enough detail that our approach could be replicated by an independent study group, thereby enhancing the transparency of the study. TRIAL REGISTRATION ClinicalTrials.gov, NCT03509350. Registered on 26 April 2018.
-
5.
Procalcitonin as a biomarker for critically ill patients with sepsis: Effects of vitamin D supplementation.
Wolf, TA, Wimalawansa, SJ, Razzaque, MS
The Journal of steroid biochemistry and molecular biology. 2019;:105428
Abstract
Early diagnosis of sepsis is often difficult in clinical practice, whilst it can be vital for positive patient outcomes in sepsis management. Any delay in diagnosis and treatment may lead to significant organ failure and can be associated with elevated mortality rates. Early diagnosis and effective management of sepsis can allow for prompt antibiotic therapy and a potential reduction in mortality; it can also minimize the unnecessary use of antibiotics. Furthermore, vitamin D supplementation, which is commonly used in the intensive care units to reduce mortality, may interfere with the ability to use procalcitonin (PCT) as a means of assessing clinical progression. This paper aims to explore the diagnostic and prognostic value of serum levels of PCT as an early marker of sepsis and to assess whether it can be used as a guide for using antibiotic therapy. Several serum-based biomarkers such as C-reactive protein, lactate, presepsin, and cytokines, such as interleukin-1 (IL-1), and IL-6 have been evaluated as early indicators of sepsis but none have been proven sensitive and/or specific enough to make a definitive diagnosis. Finally the potential benefits and disadvantages of using serum levels of PCT to diagnose and monitor patients with sepsis and septic shock will be briefly discussed.
-
6.
Mitochondria in Sepsis-Induced AKI.
Sun, J, Zhang, J, Tian, J, Virzì, GM, Digvijay, K, Cueto, L, Yin, Y, Rosner, MH, Ronco, C
Journal of the American Society of Nephrology : JASN. 2019;(7):1151-1161
-
-
Free full text
-
Abstract
AKI is a common clinical condition associated with the risk of developing CKD and ESKD. Sepsis is the leading cause of AKI in the intensive care unit (ICU) and accounts for nearly half of all AKI events. Patients with AKI who require dialysis have an unacceptably high mortality rate of 60%-80%. During sepsis, endothelial activation, increased microvascular permeability, changes in regional blood flow distribution with resulting areas of hypoperfusion, and hypoxemia can lead to AKI. No effective drugs to prevent or treat human sepsis-induced AKI are currently available. Recent research has identified dysfunction in energy metabolism as a critical contributor to the pathogenesis of AKI. Mitochondria, the center of energy metabolism, are increasingly recognized to be involved in the pathophysiology of sepsis-induced AKI and mitochondria could serve as a potential therapeutic target. In this review, we summarize the potential role of mitochondria in sepsis-induced AKI and identify future therapeutic approaches that target mitochondrial function in an effort to treat sepsis-induced AKI.
-
7.
Importance of vitamin D in acute and critically ill children with subgroup analyses of sepsis and respiratory tract infections: a systematic review and meta-analysis.
Cariolou, M, Cupp, MA, Evangelou, E, Tzoulaki, I, Berlanga-Taylor, AJ
BMJ open. 2019;(5):e027666
Abstract
OBJECTIVES To estimate the prevalence of 25-hydroxyvitamin D (25(OH)D) deficiency and investigate its association with mortality in children with acute or critical conditions. DESIGN Systematic review and meta-analysis of observational studies. DATA SOURCES PubMed, OVID, Google Scholar and the Cochrane Library searched until 21 December 2018. ELIGIBILITY CRITERIA Studies of children hospitalised with acute or critical conditions who had blood 25(OH)D levels measured. DATA EXTRACTION AND SYNTHESIS We obtained pooled prevalence estimates of 25(OH)D deficiency and ORs for mortality. We calculated 95% CI and prediction intervals and investigated heterogeneity and evidence of small-study effects. RESULTS Fifty-two studies were included. Of 7434 children, 3473 (47.0%) were 25(OH)D deficient (<50 nmol/L). The pooled prevalence estimate of 25(OH)D deficiency was 54.6% (95% CI 48.5% to 60.6%, I2=95.3%, p<0.0001). Prevalence was similar after excluding smaller studies (51.5%). In children with sepsis (18 studies, 889 total individuals) prevalence was 64.0% (95% CI 52.0% to 74.4%, I2=89.3%, p<0.0001) and 48.7% (95% CI 38.2% to 59.3%; I2=94.3%, p<0.0001) in those with respiratory tract infections (RTI) (25 studies, 2699 total individuals). Overall, meta-analysis of mortality (18 cohort studies, 2463 total individuals) showed increased risk of death in 25(OH)D deficient children (OR 1.81, 95% CI 1.24 to 2.64, p=0.002, I2=25.7%, p=0.153). Four (22.0%) of the 18 studies statistically adjusted for confounders. There were insufficient studies to meta-analyse sepsis and RTI-related mortality. CONCLUSIONS Our results suggest that 25(OH)D deficiency in acute and critically ill children is high and associated with increased mortality. Small-study effects, reverse causation and other biases may have confounded results. Larger, carefully designed studies in homogeneous populations with confounder adjustment are needed to clarify the association between 25(OH)D levels with mortality and other outcomes. PROSPERO REGISTRATION NUMBER CRD42016050638.
-
8.
[A Meta-analysis of Qingre Jiedu and Liangxue Sanyu method in the treatment of sepsis].
Cheng, L, Jiang, H, Chen, M, Chen, Q, Wang, X, Lu, J
Zhonghua wei zhong bing ji jiu yi xue. 2019;(1):73-80
Abstract
OBJECTIVE To systematically review the effect of Qingre Jiedu and Liangxue Sanyu method in patients with sepsis, and to discuss its effect in the treatment of sepsis. METHODS The randomized controlled trials (RCTs) on the treatment of Qingre Jiedu and Liangxue Sanyu method for sepsis published on PubMed, Embase, Web of Science, CNKI and Wanfang database from the construction to December 31st, 2017 were searched by electronical way. Conventional treatment measures for sepsis, such as fluid resuscitation, maintenance of hemodynamic stability, anti-infection, improvement of tissue perfusion, maintenance of organ function and nutritional support were used in the control group. While traditional Chinese medicine treatment based on Qingre Jiedu and Liangxue Sanyu method were applied in the experimental group besides the conventional treatment, including Chinese patent medicine or Chinese herbal medicine. The main outcome was 28-day mortality, and the second outcome was acute physiology and chronic health evaluation II (APACHE II), coagulation function, inflammatory mediators, procalcitonin (PCT), lactic acid (Lac), and the length of intensive care unit (ICU) stay. Two researchers independently searched literatures, collected data and evaluated risk bias. The statistical analysis was completed by RevMan 5.3 and STATA 13.0 software. The funnel plot and Egger test were used to evaluate the potential publication bias of the main outcomes. RESULTS A total of 20 RCTs were enrolled in this Meta-analysis, including 1 347 patients, with 667 patients in the control group and 680 patients in the experimental group. Comprehensive risk bias assessment showed that the risk bias of 11 RCT items was unknown, and the risk bias of 9 RCT items was high. Meta-analysis results showed that compared with the control group, the 28-day mortality of the experimental group was significantly lowered [relative risk (RR) = 0.54, 95% confidence interval (95%CI) = 0.45-0.65, P < 0.000 01], the 7-day APACHE II score was significantly lowered [mean difference (MD) = -3.86, 95%CI = -4.82 to -2.90, P < 0.000 01], the 7-day prothrombin time (PT) and activated partial thromboplastin time (APTT) were significantly shortened (PT: MD = -1.72, 95%CI = -2.29 to -1.14, P < 0.000 01; APTT MD = -4.36, 95%CI = -5.81 to -2.91, P < 0.000 01), the 7-day D-dimer was slightly improved (MD = -0.13, 95%CI = -0.37-0.11, P = 0.29), the 10-day interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were significantly decreased (IL-6: MD = -40.33, 95%CI = -59.55 to -21.11, P < 0.000 1; TNF-α: MD = -7.26, 95%CI = -11.31 to -3.21, P = 0.000 4), the 7-day Lac was significantly declined (MD = -1.30, 95%CI = -1.91 to -0.68, P < 0.000 1), but no significance in PCT (MD = -1.57, 95%CI = -3.25-0.11, P = 0.07) or the length of ICU stay (MD = -4.02, 95%CI = -8.60-0.56, P = 0.09) was found. The results of publication bias assessment showed that 19 studies reported 28-day mortality were basically "funnel-shaped" distribution without potential publication bias (P = 0.336). CONCLUSIONS The Meta-analysis showed that Qingre Jiedu and Liangxue Sanyu method may reduce the release of inflammatory mediators, improve the coagulation function, and reduce the 28-day mortality in patients with sepsis.
-
9.
Persistent inflammation and anemia among critically ill septic patients.
Loftus, TJ, Mira, JC, Stortz, JA, Ozrazgat-Baslanti, T, Ghita, GL, Wang, Z, Brumback, BA, Ungaro, RF, Bihorac, A, Leeuwenburgh, C, et al
The journal of trauma and acute care surgery. 2019;(2):260-267
-
-
Free full text
-
Abstract
BACKGROUND Associations among inflammatory cytokines, erythropoietin (EPO), and anemia in critically ill septic patients remain unclear. This study tested the hypothesis that elevated inflammatory cytokines and decreased EPO would be associated with iron-restricted anemia while accounting for operative blood loss, phlebotomy blood loss, and red blood cell (RBC) transfusion volume. METHODS Prospective observational cohort study of 42 critically ill septic patients was conducted. Hemoglobin (Hb) at sepsis onset and hospital discharge were used to calculate ΔHb. Operative blood loss, phlebotomy blood loss, and RBC transfusion volume were used to calculate adjusted ΔHb (AdjΔHb) assuming that 300 mL RBC is equal to 1 g/dL Hb. Patients with AdjΔHb of greater than 0 (positive AdjΔHb, n = 18) were compared with patients with AdjΔHb of less than or equal to 0 (negative AdjΔHb, n = 24). RESULTS Plasma tumor necrosis factor α, granulocyte colony-stimulating factor, interleukin (IL)-6, IL-8, EPO, erythrocyte mean corpuscular volume, and serum transferrin receptor were measured on days 0, 1, 4, 7, and 14. Patients with negative AdjΔHb had significantly higher day 14 levels of IL-6 (37.4 vs. 15.2 pg/mL, p < 0.05), IL-8 (39.1 vs. 18.2 pg/mL, p = 0.01), and granulocyte colony-stimulating factor (101.3 vs. 60.5 pg/mL, p = 0.01), but not EPO. On linear regression analysis, lower AdjΔHb was associated with higher day 14 levels of IL-6 (r = 0.22, p < 0.01), IL-8 (r = 0.10, p = 0.04), stromal cell-derived factor 1 (r = 0.14, p = 0.02), and tumor necrosis factor α (r = 0.13, p = 0.02), but not EPO. Patients with negative AdjΔHb had significantly lower mean corpuscular volume on days 4 (89.6 vs. 93.2 fL/cell, p = 0.04), 7 (92.3 vs. 94.9 fL/cell, p = 0.04), and 14 (92.1 vs. 96.0 fL/cell, p = 0.03) but similar serum transferrin receptor levels. CONCLUSION Persistent elevation of inflammatory cytokines was associated with iron-restricted anemia among critically ill septic patients, occurring in the absence of systemic iron deficiency, independent of endogenous EPO. LEVEL OF EVIDENCE Prognostic study, level II.
-
10.
Application of dynamic pulse pressure and vasopressor tools for predicting outcomes in patients with sepsis in intensive care units.
Fang, WF, Huang, CH, Chen, YM, Hung, KY, Chang, YC, Lin, CY, Fang, YT, Chang, YT, Chen, HC, Huang, KT, et al
Journal of critical care. 2019;:156-162
-
-
Free full text
-
Abstract
PURPOSE We aimed to determine whether the combination of dynamic pulse pressure and vasopressor (DPV) use is applicable for mortality risk stratification in patients with severe sepsis. We proposed the use of the DPV tool and compared it with traditional sepsis severity indices. MATERIALS AND METHODS All adult patients who met the sepsis criteria of the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) between August 2013 and January 2017 were eligible for the study. Patients who expired within 3 days of admission to the intensive care unit (ICU) were excluded. The primary outcomes were 7-day and 28-day mortality. RESULTS The study participants included 757 consecutive adult patients. A subpopulation of 155 patients underwent immune profiling assays on days 1, 3, and 7 of ICU admission. The DPV tool had a better performance for predicting 7-day mortality (area under curve, AUC: 0.70), followed by the Sequential Organ Failure Assessment (SOFA) (AUC: 0.64), the plus pulse pressure (AUC: 0.64). For predicting 28-day mortality, the DPV tool was not inferior to the SOFA (AUC: 0.61), DPV tool (AUC: 0.59). CONCLUSIONS The DPV tool can be applied for 7-day and 28-day mortality risk prediction in patients with sepsis.