IntroductionSeveral observational studies suggest that statins modulate the pathophysiology of sepsis and may prevent its progression. The aim of this study was to determine if the acute administration of atorvastatin reduces sepsis progression in statin naïve patients hospitalized with sepsis.MethodsA single centre phase II randomized double-blind placebo-controlled trial. Patients with sepsis were randomized to atorvastatin 40 mg daily or placebo for the duration of their hospital stay up to a maximum of 28-days. The primary end-point was the rate of sepsis progressing to severe sepsis during hospitalization.Results100 patients were randomized, 49 to the treatment with atorvastatin and 51 to placebo. Patients in the atorvastatin group had a significantly lower conversion rate to severe sepsis compared to placebo (4% vs. 24% p = 0.007.), with a number needed to treat of 5. No significant difference in length of hospital stay, critical care unit admissions, 28-day and 12-month readmissions or mortality was observed. Plasma cholesterol and albumin creatinine ratios were significantly lower at day 4 in the atorvastatin group (p < 0.0001 and p = 0.049 respectively). No difference in adverse events between the two groups was observed (p = 0.238).ConclusionsAcute administration of atorvastatin in patients with sepsis may prevent sepsis progression. Further multi-centre trials are required to verify these findings.Trial RegistrationInternational Standard Randomized Control Trial Registry ISRCTN64637517.

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Patients in ICUs represent a relatively small subgroup of hospitalised patients, but they account for approximately 25% of all hospital infections. Approximately 30% of ICU patients suffer from infection as a complication of critical illness, which increases the length of ICU stay, morbidity, mortality and cost. Gram-negative bacteria are the predominant cause of ICU-related infections and with the rise in multidrug-resistant strains we should focus our attention on nonantibiotic strategies in the prevention and treatment of nosocomial infections. Probiotics have been proposed as one option in this quest; however, mechanisms of action in the critically ill population require further investigation. Some of the beneficial effects appear to be associated with improvement in gastrointestinal barrier function, restoration of normal intestinal permeability and motility, modification of the balance of intestinal microbiota and immunomodulation. However, the information we have to date on the use of probiotics in the critical care setting is difficult to interpret due to small sample sizes, differences in ICU populations, the variety of probiotic combinations studied and differences in administration techniques. In this review we shall examine the use of probiotics in the critical care setting, look at some of the proposed mechanisms of action and discuss their potential benefits and drawbacks.

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Intensive care units 33 54 Patients 408 546 Received β-agonist on this admission 126 (30.8%) 103 (18.8%) UK (n=126) China (n=103) ARDS 10 (7.9%) 14 (13.6%) COPD 49 (38.9%) 57 (55.3%) Unspecified wheeze 49 (38.9%) 16 (15.5%)