Unfortunately, only activated protein C (aPC) has actually been licensed for use in such patients, and the efficacy of this drug has been challenged. Numerous other antisepsis therapies have been tested, many Volasertib mw in large multicenter phase III studies, yet have failed to show overall effectiveness in improving patient outcomes. Much has been said about the importance of early diagnosis of sepsis and the potential role of biomarkers, but we remain frustrated in our attempts to identify biomarkers that are specific for sepsis and that can be used for diagnosis, therapeutic guidance, or prognostication. The role of immunomodulatory nutritional solutions has also not been clarified. Whether specialized nutrients, such as glutamine or omega-3 fatty acids, are beneficial remains uncertain.

Apart from the effects of selenium on the reduction of secondary bacterial infection, no consistent effect has been shown for other drugs, such as glutamine (Peter Andrews, SIGNET [Scottish Intensive Care Glutamine or Selenium Evaluative Trial], personal communication).? Respiratory failure and ARDS: Progress has been made in the use of noninvasive mechanical ventilation, which is now widely employed and for which indications have been more clearly defined. Arguably, we have made major progress in the ventilatory treatment of patients with ARDS over the past 30 years through the recognition and avoidance of iatrogenic ventilator induced lung injury (VILI) by limiting tidal volumes and airway pressures [7]. However, we still have much to learn about the optimal ventilatory management of patients with ARDS.

Less aggressive ventilation has clearly resulted in a reduced incidence of barotrauma, yet debate persists over the best lung protective ventilation strategy and how to optimally apply positive end-expiratory pressure (PEEP). We now have some evidence, albeit not strong, that fluid balance is an important determinant of outcome in patients with acute lung injury (ALI), although our ability to accurately define a level of preload to which fluid therapy should be titrated remains elusive. Turning patients to the prone position also appears to be associated with reduced mortality rates in the most severe cases. Disappointingly, no specific pharma cologic intervention showing clear outcome benefit has been forthcoming, with approaches ranging from inhaled surfactant or nitric oxide to systemic administration of antioxidants or anti-inflammatory agents.

Although most studies do not show a clear benefit of steroids in ARDS, their Carfilzomib precise role remains controversial in these patients. Even though mortality rates may be decreasing [8], we are still left with many unanswered questions.? Cardiovascular diseases: There has been considerable progress in the management of acute myocardial infarction with early thrombolysis and percutaneous coronary intervention, although these are often applied outside the ICU.