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A Population-Based Cohort Study on the Drug-Specific Effect of Statins on Sepsis Outcome.
Lee, CC, Lee, MG, Hsu, TC, Porta, L, Chang, SS, Yo, CH, Tsai, KC, Lee, M
Chest. 2018;(4):805-815
Abstract
BACKGROUND Whether statin treatment, proved by recent experimental studies to have an antimicrobial activity, exerts a drug- or a class-specific effect in sepsis remains unknown. METHODS Short-term mortality in patients with sepsis was analyzed using data from the National Health Insurance Research Database. Use of statins was defined as the cumulative use of a specific statin (atorvastatin, simvastatin, or rosuvastatin) for > 30 days prior to the index sepsis admission. We determined the association between statin and sepsis outcome by multivariate-adjusted Cox models and propensity score (PS)-matched analysis, using a 1:1:1 PS matching technique. RESULTS A total of 52,737 patients with sepsis fulfilled the inclusion criteria, of which 1,855 were prescribed atorvastatin, 916 were prescribed simvastatin, and 732 were prescribed rosuvastatin. Compared with nonusers, simvastatin (hazard ratio [HR], 0.72; 95% CI, 0.58-0.90) and atorvastatin (HR, 0.78; 95% CI, 0.68-0.90) were associated with an improved 30-day survival, whereas rosuvastatin was not (HR, 0.87; 95% CI, 0.73-1.04). Using rosuvastatin as the reference, atorvastatin (HR, 0.79; 95% CI, 0.64-0.99) and simvastatin (HR, 0.77; 95% CI, 0.59-0.99) had superior effectiveness in preventing mortality. CONCLUSIONS Compatible with in vitro experimental findings, our results suggest that the drug-specific effect of statins on sepsis is not correlated to their lipid-lowering potency.
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High-Dose Versus Conventional-Dose Continuous Venovenous Hemodiafiltration and Patient and Kidney Survival and Cytokine Removal in Sepsis-Associated Acute Kidney Injury: A Randomized Controlled Trial.
Park, JT, Lee, H, Kee, YK, Park, S, Oh, HJ, Han, SH, Joo, KW, Lim, CS, Kim, YS, Kang, SW, et al
American journal of kidney diseases : the official journal of the National Kidney Foundation. 2016;(4):599-608
Abstract
BACKGROUND Soluble inflammatory mediators are known to exacerbate sepsis-induced acute kidney injury (AKI). Continuous renal replacement therapy (CRRT) has been suggested to play a part in immunomodulation by cytokine removal. However, the effect of continuous venovenous hemodiafiltration (CVVHDF) dose on inflammatory cytokine removal and its influence on patient outcomes are not yet clear. STUDY DESIGN Prospective, randomized, controlled, open-label trial. SETTING & PARTICIPANTS Septic patients with AKI receiving CVVHDF for AKI. INTERVENTION Conventional (40mL/kg/h) and high (80mL/kg/h) doses of CVVHDF for the duration of CRRT. OUTCOMES Patient and kidney survival at 28 and 90 days, circulating cytokine levels. RESULTS 212 patients were randomly assigned into 2 groups. Mean age was 62.1 years, and 138 (65.1%) were men. Mean intervention durations were 5.4 and 6.2 days for the conventional- and high-dose groups, respectively. There were no differences in 28-day mortality (HR, 1.02; 95% CI, 0.73-1.43; P=0.9) or 28-day kidney survival (HR, 0.96; 95% CI, 0.48-1.93; P=0.9) between groups. High-dose CVVHDF, but not the conventional dose, significantly reduced interleukin 6 (IL-6), IL-8, IL-1b, and IL-10 levels. There were no differences in the development of electrolyte disturbances between the conventional- and high-dose groups. LIMITATIONS Small sample size. Only the predilution CVVHDF method was used and initiation criteria were not controlled. CONCLUSIONS High CVVHDF dose did not improve patient outcomes despite its significant influence on inflammatory cytokine removal. CRRT-induced immunomodulation may not be sufficient to influence clinical end points.
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Platelet mitochondrial dysfunction in critically ill patients: comparison between sepsis and cardiogenic shock.
Protti, A, Fortunato, F, Artoni, A, Lecchi, A, Motta, G, Mistraletti, G, Novembrino, C, Comi, GP, Gattinoni, L
Critical care (London, England). 2015;(1):39
Abstract
INTRODUCTION Platelet mitochondrial respiratory chain enzymes (that produce energy) are variably inhibited during human sepsis. Whether these changes occur even during other acute critical illness or are associated with impaired platelet aggregation and secretion (that consume energy) is not known. The aims of this study were firstly to compare platelet mitochondrial respiratory chain enzymes activity between patients with sepsis and those with cardiogenic shock, and secondly to study the relationship between platelet mitochondrial respiratory chain enzymes activity and platelet responsiveness to (exogenous) agonists in patients with sepsis. METHODS This was a prospective, observational, case-control study. Platelets were isolated from venous blood of 16 patients with severe sepsis or septic shock (free from antiplatelet drugs) and 16 others with cardiogenic shock, within 48 hours from admission to Intensive Care. Platelet mitochondrial respiratory chain enzymes activity was measured with spectrophotometry and expressed relative to citrate synthase activity, a marker of mitochondrial density. Platelet aggregation and secretion in response to adenosine di-phosphate (ADP), collagen, U46619 and thrombin receptor activating peptide were measured with lumiaggregometry only in patients with sepsis. In total, 16 healthy volunteers acted as controls for both spectrophotometry and lumiaggregometry. RESULTS Platelets of patients with sepsis or cardiogenic shock similarly had lower mitochondrial nicotinamide adenine dinucleotide dehydrogenase (NADH) (P < 0.001), complex I (P = 0.006), complex I and III (P < 0.001) and complex IV (P < 0.001) activity than those of controls. Platelets of patients with sepsis were generally hypo-responsive to exogenous agonists, both in terms of maximal aggregation (P < 0.001) and secretion (P < 0.05). Lower mitochondrial NADH (R (2) 0.36; P < 0.001), complex I (R (2) 0.38; P < 0.001), complex I and III (R (2) 0.27; P = 0.002) and complex IV (R (2) 0.43; P < 0.001) activity was associated with lower first wave of aggregation with ADP. CONCLUSIONS Several platelet mitochondrial respiratory chain enzymes are similarly inhibited during human sepsis and cardiogenic shock. In patients with sepsis, mitochondrial dysfunction is associated with general platelet hypo-responsiveness to exogenous agonists. TRIAL REGISTRATION ClinicalTrials.gov NCT00541827 . Registered 8 October 2007.
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Early enteral immunonutrition vs. parenteral nutrition in critically ill patients without severe sepsis: a randomized clinical trial.
Radrizzani, D, Bertolini, G, Facchini, R, Simini, B, Bruzzone, P, Zanforlin, G, Tognoni, G, Iapichino, G
Intensive care medicine. 2006;(8):1191-8
Abstract
OBJECTIVES We compared early parenteral nutrition (PN) and early enteral immunonutrition (iEN) in critically ill patients, distinguishing those with and without severe sepsis or septic shock (SS) on admission to intensive care units (ICUs). DESIGN AND SETTING Multicenter, randomized, unblinded clinical trial in 33 Italian general ICUs. PATIENTS AND PARTICIPANTS The study included 326 patients, 287 of whom did not have SS on ICU admission. Eligibility criteria excluded the two tails in the spectrum of critical conditions, i.e., patients either too well or too ill. Of the patients recruited 160 were randomized to iEN (142 without SS) and 166 to PN (145 without SS). INTERVENTIONS Patients were randomized to two arms: early iEN or early PN. MEASUREMENTS AND RESULTS Primary endpoint was 28-day mortality for all patients and the occurrence of SS during ICU stay for patients admitted without such condition. While 28-day mortality did not differ between iEN and PN (15.6% vs. 15.1%), patients without SS who received iEN had fewer episodes of severe sepsis or septic shock (4.9% vs. 13.1%). ICU length of stay was 4 days shorter in patients given iEN. CONCLUSIONS Compared to parenteral nutrition iEN appears to be beneficial in critical patients without severe sepsis or septic shock. Parenteral nutrition in these patients should be abandoned, at least when enteral nutrition can be administered, even at an initial low caloric content.
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Effect of polymyxin B-immobilized fiber on bone resorption in patients with sepsis.
Nakamura, T, Kawagoe, Y, Matsuda, T, Koide, H
Intensive care medicine. 2004;(9):1838-41
Abstract
OBJECTIVE To analyze the effects of polymyxin B-immobilized fiber (PMX-F) on bone resorption in septic patients. DESIGN AND SETTING Observational prospective study in intensive care units of a general hospital. PATIENTS AND PARTICIPANTS 25 patients with severe sepsis and 20 healthy controls. MEASUREMENTS AND RESULTS Septic patients were randomly assigned to two groups: PMX-F treatment group (n=15) and conventional treatment group (n=10). Total pyridinium crosslink pyridinoline (PYD) and deoxypyridinoline (DPD) in urine were determined by modified high-performance liquid chromatography. Nitric oxide production was assessed by measuring the ratio of the nitric oxide breakdown products to urinary creatinine (NOx/Cr). Plasma endotoxin levels were determined by endospecy test. The blood albumin, ionized calcium, and parathyroid hormone were also measured. PMX-F treatment was performed twice separated by 24 h. Urinary NOx/Cr, PYD/Cr, and DPD/Cr were significantly increased in septic patients compared with those in healthy controls. Blood ionized calcium in septic patients was lower than in healthy controls, while parathyroid hormone levels in septic patients were higher than in healthy controls (P<0.01). PMX-F treatment reduced plasma endotoxin, urinary NOx/Cr, PYD/Cr, DPD/Cr, and serum parathyroid hormone levels and increased blood ionized calcium significantly; however, conventional treatment did not affect these levels. CONCLUSIONS Septic patients increased nitric oxide production and bone resorption, and PMX-F treatment is effective in reducing nitric oxide levels and bone resorption markers.
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6.
Total parenteral nutrition: potion or poison?
Jeejeebhoy, KN
The American journal of clinical nutrition. 2001;(2):160-3
Abstract
The role of nutritional support in clinical care has burgeoned over the past 40 y. Initially, total parenteral nutri-tion (TPN) was considered to be the standard of care. Later, the concept that enteral nutrition (EN) promoted gut function and prevented the translocation of intestinal bacteria resulted in EN becoming the standard of care. Furthermore, TPN was consid-ered to be a dangerous form of therapy. Critical review of the data suggests that, in humans, TPN does not cause mucosal atrophy or increase bacterial translocation. Increased sepsis with TPN can be ascribed to overfeeding; the dangers of TPN-induced complications have been exaggerated. TPN is an equally effective alternative to EN when a risk of malnutrition is present and EN is not tolerated or when gut failure is present.