Critical care : the official journal of the Critical Care Forum
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Angiopoietin-1 (Angpt1), the natural agonist ligand for the endothelial Tie2 receptor, is a non-redundant endothelial survival and vascular stabilization factor that reduces endothelial permeability and inhibits leukocyte-endothelium interactions. Here we evaluate the efficacy of a novel polyethylene glycol (PEG)-clustered Tie2 agonist peptide, Vasculotide (VT), to protect against vascular leakage and mortality in a murine model of polymicrobial abdominal sepsis. ⋯ We provide proof of principle in support of the efficacious use of PEGylated VT, a drug-like Tie2 receptor agonist, to counteract microvascular endothelial barrier dysfunction and reduce mortality in a clinically relevant murine sepsis model. Further studies are needed to pave the road for clinical application of this therapeutic concept.
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The rapid institution of therapeutic hypothermia after cardiac arrest has become an accepted practice. In the previous issue of Critical Care, Haugk and colleagues present a retrospective analysis of 13 years of experience with therapeutic hypothermia at their center that suggests an association between rate of cooling and less favorable neurological outcomes. The association most likely reflects easier cooling in patients more severely brain injured by their initial cardiac arrest, and should not lead clinicians to abandon or slow their efforts to achieve post-resuscitative cooling.
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Perioperative haemodynamic optimisation of high-risk surgical patients has long been documented to improve both short-term and long-term outcomes, as well as to reduce the rate of postoperative complications. Based on the evidence, cardiac output monitoring and fluid resuscitation, combined with the use of inotropes, would seem to be the gold standard of care for these difficult surgical cases. However, clinicians do not universally apply these techniques and principles in their everyday practice. By exploring the reasons why this is so, perhaps we could move forward in the standardisation of care and the application of evidence-based practice.
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Protocols using high levels of positive end-expiratory pressure (PEEP) in combination with low tidal volumes have been shown to reduce mortality in patients with severe acute respiratory distress syndrome (ARDS). However, the optimal method for setting PEEP is yet to be defined. It has been shown that respiratory system reactance (Xrs), measured by the forced oscillation technique (FOT) at 5 Hz, may be used to identify the minimal PEEP level required to maintain lung recruitment. The aim of the present study was to evaluate if using Xrs for setting PEEP would improve lung mechanics and reduce lung injury compared to an oxygenation-based approach. ⋯ In a lavage model of lung injury a PEEP optimization strategy based on maximizing Xrs attenuated the signs of ventilator induced lung injury. The respiratory system reactance measured by FOT could thus be an important component in a strategy for delivering protective ventilation to patients with ARDS/acute lung injury.
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Editorial Comment
Defining the adequate arterial pressure target during septic shock: not a 'micro' issue but the microcirculation can help.
The Surviving Sepsis Campaign guidelines suggest targeting a mean arterial pressure of at least 65 mm Hg to maintain organ perfusion pressure during septic shock. However, the optimal mean arterial pressure can be higher in patients with a history of hypertension or other vascular comorbidities or in those with increased abdominal pressure. ⋯ Near-infrared spectroscopy and sidestream dark field imaging have emerged as promising technologies for monitoring the microcirculation at the bedside. These new methods could provide additional clues to help define the adequate blood pressure to target during the resuscitation phase of septic shock.