1.
Randomized controlled trial of calcitriol in severe sepsis.
Leaf, DE, Raed, A, Donnino, MW, Ginde, AA, Waikar, SS
American journal of respiratory and critical care medicine. 2014;(5):533-41
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Abstract
RATIONALE Vitamin D and its metabolites have potent immunomodulatory effects in vitro, including up-regulation of cathelicidin, a critical antimicrobial protein. OBJECTIVES We investigated whether administration of 1,25-dihydroxyvitamin D (calcitriol) to critically ill patients with sepsis would have beneficial effects on markers of innate immunity, inflammation, and kidney injury. METHODS We performed a double-blind, randomized, placebo-controlled, physiologic study among 67 critically ill patients with severe sepsis or septic shock. Patients were randomized to receive a single dose of calcitriol (2 μg intravenously) versus placebo. The primary outcome was plasma cathelicidin protein levels assessed 24 hours after study drug administration. Secondary outcomes included leukocyte cathelicidin mRNA expression, plasma cytokine levels (IL-10, IL-6, tumor necrosis factor-α, IL-1β, and IL-2), and urinary kidney injury markers. MEASUREMENTS AND MAIN RESULTS Patients randomized to calcitriol (n = 36) versus placebo (n = 31) had similar plasma cathelicidin protein levels at 24 hours (P = 0.16). Calcitriol-treated patients had higher cathelicidin (P = 0.04) and IL-10 (P = 0.03) mRNA expression than placebo-treated patients 24 hours after study drug administration. Plasma cytokine levels (IL-10, IL-6, tumor necrosis factor-α, IL-1β, and IL-2) and urinary kidney injury markers were similar in calcitriol- versus placebo-treated patients (P > 0.05 for all comparisons). Calcitriol had no effect on clinical outcomes nor were any adverse effects observed. CONCLUSIONS Calcitriol administration did not increase plasma cathelicidin protein levels in critically ill patients with sepsis and had mixed effects on other immunomodulatory markers. Additional phase II trials investigating the dose and timing of calcitriol as a therapeutic agent in specific sepsis phenotypes may be warranted. Clinical trial registered with www.clinicaltrials.gov (NCT 01689441).
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Probiotics in the critically ill patient: a double blind, randomized, placebo-controlled trial.
Barraud, D, Blard, C, Hein, F, Marçon, O, Cravoisy, A, Nace, L, Alla, F, Bollaert, PE, Gibot, S
Intensive care medicine. 2010;(9):1540-7
Abstract
PURPOSE Probiotics have been shown to be able to restore a non-pathogenic digestive flora, to prevent digestive colonization by pathogenic bacteria, and to modulate immunity. The aim of this study was to assess the effects of prophylactic probiotic administration in patients ventilated for up to 2 days. METHODS This study was performed as a double-blind, concealed randomized, placebo-controlled trial in a French medical intensive care unit (ICU). Adult patients mechanically ventilated for a period of more than 48 h received enterally administered probiotics (Ergyphilus, 2 x 10(10) lactic acid bacteria, mostly Lactobacillus rhamnosus GG, once a day) or placebo until successful weaning. RESULTS A total of 167 patients were included. The two groups were comparable at baseline. The 28-day mortality rates were not different in the probiotic (25.3%) and placebo groups (23.7%). Mortality rates in ICU and at 90 days were also unaffected by the treatment. The incidence of ICU-acquired infections did not differ significantly except for that of catheter-related bloodstream infections that was lowered by probiotics. On a prespecified subgroup analysis, we found a reduction of the 28-day mortality among severe sepsis patients (total n = 101) treated with probiotics (n = 52) with an odds ratio (OR) for death at 0.38 (95% CI 0.16-0.93, p = 0.035). By contrast, probiotics were associated with a higher mortality rate in non-severe sepsis patients (OR 3.09, 95% CI 0.87-11.01, p = 0.08). CONCLUSIONS Although numerous uncertainties remain (type and the number of strains to use, delay and length of administration), and despite an acceptable safety profile, the daily prophylactic administration of probiotics cannot be encouraged in the critically ill patient.
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Effects of continuous versus bolus infusion of enteral nutrition in critical patients.
Serpa, LF, Kimura, M, Faintuch, J, Ceconello, I
Revista do Hospital das Clinicas. 2003;(1):9-14
Abstract
PURPOSE Enteral alimentation is the preferred modality of support in critical patients who have acceptable digestive function and are unable to eat orally, but the advantages of continuous versus intermittent administration are surrounded by controversy. With the purpose of identifying the benefits and complications of each technique, a prospective controlled study with matched subjects was conducted. PATIENTS AND METHODS Twenty-eight consecutive candidates for enteral feeding were divided into 2 groups (n = 14 each) that were matched for diagnosis and APACHE II score. A commercial immune-stimulating polymeric diet was administered via nasogastric tube by electronic pump in the proportion of 25 kcal/kg/day, either as a 1-hour bolus every 3 hours (Group I), or continuously for 24 hours (Group II), over a 3-day period. Anthropometrics, biochemical measurements, recording of administered drugs and other therapies, thorax X-ray, measurement of abdominal circumference, monitoring of gastric residue, and clinical and nutritional assessments were performed at least once daily. The principal measured outcomes of this protocol were frequency of abdominal distention and pulmonary aspiration, and efficacy in supplying the desired amount of nutrients. RESULTS Nearly half of the total population (46.4%) exhibited high gastric residues on at least 1 occasion, but only 1 confirmed episode of pulmonary aspiration occurred (3.6%). Both groups displayed a moderate number of complications, without differences. Food input during the first day was greater in Group II (approximately 20% difference), but by the third day, both groups displayed similarly small deficits in total furnished volume of about 10%, when compared with the prescribed diet. CONCLUSIONS Both administration modalities permitted practical and effective administration of the diet with frequent registered abnormalities but few clinically significant problems. The two groups were similar in this regard, without statistical differences, probably because of meticulous technique, careful monitoring, strict patient matching, and conservative amounts of diet employed in both situations. Further studies with additional populations, diagnostic groups, and dietetic prescriptions should be performed in order to elucidate the differences between these commonly used feeding modalities.