Critical care : the official journal of the Critical Care Forum
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Protein C plays an important role in the coagulopathy associated with sepsis and probably also in the pathogenesis of sepsis-induced organ dysfunction. Plasma levels of protein C strongly correlate with clinical outcome in patients with severe sepsis. The RESPOND (Research Evaluating Serial Protein C Levels in Severe Sepsis Patients on Drotrecogin Alfa [Activated]) study shows that administration of recombinant human activated protein C in patients with severe sepsis with alternative dose regimens adjusted to plasma levels of protein C results in higher plasma levels of protein C. This may potentially translate to a better clinical outcome in patients with severe sepsis, although that was not directly shown in this trial.
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Terblanche and colleagues add to the ongoing controversy over the role, if any, for statins in patients with sepsis. The authors note that statins fail to prevent progression to organ dysfunction in critically ill patients. However, like most publications, the study is retrospective and stimulates the controversy but fails to resolve it. The time has come for robust randomized controlled clinical trials.
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Three pulse contour systems for monitoring cardiac output - LiDCO Plus™, PiCCO Plus™ and FloTrac™ - were compared in postcardiac surgery patients. None of the three methods demonstrated good trending ability according to concordance analysis. Pulse contour systems remain unreliable in the haemodynamically unstable patient.
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The study by Dr Peiniger and colleagues in a recent issue of Critical Care indicates that transfusion strategies using an early and more balanced ratio between fresh frozen plasma and red blood cell transfusions provide a survival benefit in patients with acute traumatic coagulopathy requiring massive transfusion within the first 24 hours of hospitalization. However, this topic has never been explored in depth in patients with concomitant severe traumatic brain injury. While the study is retrospective and certainly not a substitute for a well-designed prospective trial, the authors nonetheless should be commended for addressing this issue with their current work. Currently, the optimum fluid resuscitation paradigm for patients with both severe traumatic brain injury and other injuries requiring significant volume resuscitation is not clear.
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In the previous issue of Critical Care, Tang and colleagues offer a very novel systematic review of 12 studies of gene expression in blood of human sepsis. The review concludes that there is no discernable transition from a pro- to an anti-inflammatory expression phenotype in blood in human sepsis. The authors found that upregulation of pathogen recognition receptors and signal transduction pathways was a consistent theme in expression studies. ⋯ The balance of pro- to anti-inflammatory gene expression is difficult to quantify. Sample size is highly variable in studies (n = 12 to 176). These limitations require a leap of faith to suggest that the paradigm of sepsis as a pro-inflammatory phenotype that shifts to an anti-inflammatory phenotype is flawed: the absence of evidence in expression studies is not the same as having well-conducted studies with clear negative evidence.