However, as with many anniversaries, we look back over the last 30 years with mixed feelings. Despite considerable technological and scientific advances, we cannot help but feel a little disappointed that our discipline has made few ground-shaking steps forward, especially Vorinostat HDAC3 in therapeutics. Nevertheless, we should be pleased with the progress and improvements that have been made, notably in the process of care.We have not made much progress in therapeutics..To be honest, there have been very few major developments in critical care in terms of specific new treatments and cures over the last 30 years.

Our success in translating the many advances in basic scientific knowledge and understanding of the pathobiology of syndromes, such as sepsis and acute respiratory distress syndrome (ARDS), to pharmacologic or biologic therapies in order to interrupt injurious processes has been minimal, and this is due in part to the complex and variable nature of these disease processes, the heterogeneous nature of the patients who are affected, and the inadequate preclinical models currently available [1]. No ‘magic bullets’ that have directly saved lives in heterogeneous groups of patients have been developed. Many prospective multicenter randomized trials have been conducted; in itself, this may be viewed as progress and evidence of increasing maturity. However, the vast majority of these trials have failed to demonstrate improved outcomes with the intervention under investigation [2].

Even the encouraging findings of single-center studies have not been reproduced in later multicenter trials: a good example of this is the concept of tight blood sugar control, in which the results from the initial singlecenter study [3] could not be reproduced by the multicenter VISEP (Volume Substitution and Insulin Therapy in Severe Sepsis) [4], Glucontrol [5], or NICESUGAR (Normoglycemia in Intensive Care Evaluation and Survival Using Glucose Algorithm Regulation) [6] studies. There are many reasons for the apparent failure of randomized controlled trials to demonstrate improved outcomes with the interventions that have been tested: for example, the interventions were simply not effective, the studies were underpowered, and the selected mortality endpoint is inadequate or inappropriate. However, the main reason is likely related to the logistics Batimastat of multicenter trials, which require the inclusion of a broad spectrum of patients and loose co-intervention controls.