Critical care : the official journal of the Critical Care Forum
-
Vasospasm is one of the leading causes of morbidity and mortality following aneurysmal subarachnoid hemorrhage (SAH). Radiographic vasospasm usually develops between 5 and 15 days after the initial hemorrhage, and is associated with clinically apparent delayed ischemic neurological deficits (DID) in one-third of patients. The pathophysiology of this reversible vasculopathy is not fully understood but appears to involve structural changes and biochemical alterations at the levels of the vascular endothelium and smooth muscle cells. ⋯ A panoply of drugs, with different mechanisms of action, has been studied in SAH related vasospasm. Currently, the most promising are magnesium sulfate, 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors, nitric oxide donors and endothelin-1 antagonists. This paper reviews established and emerging therapies for vasospasm.
-
High-mobility group box-1 protein (HMGB1) has been known as a chromosomal protein for many years. HMGB1 has recently been shown to be a proinflammatory cytokine with a role in the immunopathogenesis of sepsis. Lipopolysaccharide-binding protein (LBP) has a central role in the innate immune response when the host is challenged by bacterial pathogens. Procalcitonin (PCT) has been suggested as a marker of severe bacterial infections and sepsis. The aim of the present study was to investigate levels of HMGB1, LBP and PCT in a well-characterised sepsis cohort. The study plan included analysis of the levels of the inflammatory markers in relation to the severity of infection, to the prognosis and to the ability to identify patients with bacteraemia. ⋯ Levels of HMGB1, PCT and LBP were higher in infected patients compared with those in healthy controls, and levels were higher in severe sepsis patients compared with those in sepsis patients. Levels of all studied inflammatory markers (HMGB1, LBP, PCT, IL-6) and infection markers (C-reactive protein, white blood cell count, neutrophils) were elevated among bacteraemic patients. PCT performed best as a diagnostic test marker for bacteraemia.
-
An evaluation of critical care outreach services was published in the previous issue of Critical Care that fails to demonstrate any important outcome benefit associated with these services. It is now time to ask some difficult questions about the future of outreach, including whether the lack of evidence should lead to disinvestment in such services.
-
Review
Clinical review: timing and dose of continuous renal replacement therapy in acute kidney injury.
The optimal management of renal replacement therapy (RRT) in acute kidney injury (AKI) remains uncertain. Although it is well accepted that initiation of RRT in patients with progressive azotemia prior to the development of overt uremic manifestations is associated with improved survival, whether there is benefit to even earlier initiation of therapy is uncertain. ⋯ Several studies have suggested that more intensive delivery of CRRT during AKI is associated with improved survival, although results of trials have been inconsistent. Two large multicenter randomized clinical trials addressing this question are currently underway and should provide more definitive data within the next two years.
-
Endothelium dysfunction is one of the hallmarks of sepsis. Looney and Mattay, in the previous issue of Critical Care, highlight the role of activated protein C (APC) as a protective endothelial drug in septic situations. Nevertheless, the results of in vivo studies are less explicit and it remains uncertain whether these properties are relevant in human septic shock. ⋯ Nevertheless, if rAPC is efficient when infused in the early phase of septic challenge, we thus need to treat our patients earlier. At the least, genetically engineered variants have been designed with greater anti-apoptotic activity and reduced anticoagulant activity relative to wild-type APC. Further studies are needed to demonstrate the usefulness of these variants in septic shock therapy.