"The extent and duration of catecholamine therapy and tachycardia are all independently associated with poor outcomes in critically ill patients [8, 20–22]. Concerns have been raised about the use of catecholamines in the treatment of septic shock  "
[Show abstract][Hide abstract] ABSTRACT: Beta blockers are some of the most studied drugs in the pharmacopoeia. They are already widely used in medicine for treating hypertension, chronic heart failure, tachyarrhythmias, and tremor. Whilst their use in the immediate perioperative patient has been questioned, the use of esmolol in the patients with established septic shock has been recently reported to have favourable outcomes. In this paper, we review the role of the adrenergic system in sepsis and the evidence for the use of beta stimulation and beta blockers from animal models to critically ill patients.
BioMed Research International 07/2015; · 3.17 Impact Factor
"The calcium and anti-inflammatory actions of levosimendan provide a strong biological rationale for its use in sepsis. In addition, conventional vasoactive support using catecholamines such as norepinephrine and dobutamine may result in sympathetic nervous system overstimulation and a range of adverse effects . Evidence of a lack of benefit from trials comparing different catecholamine regimens , increased mortality in patients exposed to a greater vasopressor load , the observation of higher plasma catecholamine levels in non-survivors compared to survivors of critical illness , and emerging evidence that beta-blockade may play a role if patients are receiving high-dose catecholamines  all provide further evidence of possible harm from conventional catecholamine therapy. "
[Show abstract][Hide abstract] ABSTRACT: Background
Organ dysfunction consequent to infection (‘severe sepsis’) is the leading cause of admission to an intensive care unit (ICU). In both animal models and early clinical studies the calcium channel sensitizer levosimendan has been demonstrated to have potentially beneficial effects on organ function. The aims of the Levosimendan for the Prevention of Acute oRgan Dysfunction in Sepsis (LeoPARDS) trial are to identify whether a 24-hour infusion of levosimendan will improve organ dysfunction in adults who have septic shock and to establish the safety profile of levosimendan in this group of patients.
This is a multicenter, randomized, double-blind, parallel group, placebo-controlled trial. Adults fulfilling the criteria for systemic inflammatory response syndrome due to infection, and requiring vasopressor therapy, will be eligible for inclusion in the trial. Within 24 hours of meeting these inclusion criteria, patients will be randomized in a 1:1 ratio stratified by the ICU to receive either levosimendan (0.05 to 0.2 μg.kg-1.min-1 or placebo for 24 hours in addition to standard care. The primary outcome measure is the mean Sequential Organ Failure Assessment (SOFA) score while in the ICU. Secondary outcomes include: central venous oxygen saturations and cardiac output; incidence and severity of renal failure using the Acute Kidney Injury Network criteria; duration of renal replacement therapy; serum bilirubin; time to liberation from mechanical ventilation; 28-day, hospital, 3 and 6 month survival; ICU and hospital length-of-stay; and days free from catecholamine therapy. Blood and urine samples will be collected on the day of inclusion, at 24 hours, and on days 4 and 6 post-inclusion for investigation of the mechanisms by which levosimendan might improve organ function. Eighty patients will have additional blood samples taken to measure levels of levosimendan and its active metabolites OR-1896 and OR-1855. A total of 516 patients will be recruited from approximately 25 ICUs in the United Kingdom.
This trial will test the efficacy of levosimendan to reduce acute organ dysfunction in adult patients who have septic shock and evaluate its biological mechanisms of action.
Current controlled trials ISRCTN12776039 (19 September 2013)
"Other factors recognized as leading to increased risk of infection involve invasive treatment procedures, particularly use of endotracheal tubes (with mechanical ventilation), urinary catheters, surgical drains, and IV catheter lines. An additional risk factor is now recognized as coming from the inotrope medications patients are given . This view came about because catecholamine inotropes have been shown to be involved in staphylococcal colonization of indwelling medical devices such as IV lines due to their ability to stimulate staphylococcal growth and biofilm formation [14, 51–53]. "
[Show abstract][Hide abstract] ABSTRACT: It is clear that a dialogue is occurring between microbes and their hosts and that chemical signals are the language of this interkingdom communication. Microbial endocrinology shows that, through their long coexistence with animals and plants, microorganisms have evolved sensors for detecting eukaryotic hormones, which the microbe uses to determine that they are within proximity of a suitable host and to optimally time the expression of genes needed for host colonisation. It has also been shown that some prokaryotic chemical communication signals are recognized by eukaryotes. Deciphering what is being said during the cross-talk between microbe and host is therefore important, as it could lead to new strategies for preventing or treating bacterial infections.
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