Critical care medicine
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Critical care medicine · Aug 2002
Randomized Controlled Trial Comparative Study Clinical TrialC1-inhibitor in patients with severe sepsis and septic shock: beneficial effect on renal dysfunction.
To investigate the efficacy and the safety of the parenteral administration of C1-inhibitor to patients with severe sepsis or septic shock. ⋯ C1-inhibitor administration attenuated renal impairment in patients with severe sepsis or septic shock.
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Critical care medicine · Aug 2002
Randomized Controlled Trial Comparative Study Clinical TrialImproved resuscitation minimizes respiratory dysfunction and blunts interleukin-6 and nuclear factor-kappa B activation after traumatic hemorrhage.
We hypothesized that modifying resuscitation would alter hemorrhagic shock-induced respiratory dysfunction and correlate with nuclear factor-kappa B and cytokine expression. ⋯ Group II demonstrated the least improvement in serum lactate after resuscitation, the most significant acute lung injury, and the greatest interleukin-6 and nuclear factor-kappa B response. Group IV mice had the least acute lung injury, with no detectable interleukin-6 response. Improved resuscitation with crystalloid and shed blood minimized acute lung injury. The reduction in pulmonary dysfunction after improved resuscitation may be attributable to a blunting of the nuclear factor-kappa B and interleukin-6 responses to hemorrhage.
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Critical care medicine · Aug 2002
Review Randomized Controlled Trial Clinical TrialActivated protein C in normal human pregnancy and pregnancies complicated by severe preeclampsia: a therapeutic opportunity?
Given the efficacy and safety of recombinant human activated protein C (rhAPC) in the systemic inflammatory response syndrome, this study was designed to review the evidence for a role for APC in the pathogenesis of preeclampsia. Preeclampsia is a proinflammatory and procoagulant state, and it is a pregnancy-specific condition that mimics the systemic inflammatory response syndrome. rhAPC reduces mortality in patients with systemic inflammatory response syndrome and could potentially have a role as disease-modifying therapy in preeclampsia. To determine which patients would be offered rhAPC, the literature pertaining to fetal/neonatal outcomes for preeclampsia remote from term, transplacental transport of protein C, and pregnancy experience with the compound were reviewed. ⋯ Sufficient data exist to support the use of rhAPC in phase II clinical studies for women with either early onset preeclampsia or severe or deteriorating postpartum disease.
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Critical care medicine · Aug 2002
Comparative Study Clinical TrialStatistical evaluation of ventilator-free days as an efficacy measure in clinical trials of treatments for acute respiratory distress syndrome.
Trials of potential new therapies in acute lung injury are difficult and expensive to conduct. This article is designed to determine the utility, behavior, and statistical properties of a new primary end point for such trials, ventilator-free days, defined as days alive and free from mechanical ventilation. Describing the nuances of this outcome measure is particularly important because using it, while ignoring mortality, could result in misleading conclusions. ⋯ Use of ventilator-free days as a trial end point allows smaller sample sizes if it is assumed that the treatment being tested simultaneously reduces the duration of ventilation and improves mortality. It is unlikely that a treatment that led to higher mortality could lead to a statistically significant improvement in ventilator-free days. This would be especially true if the treatment were also required to produce a nominal improvement in mortality.
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Critical care medicine · Aug 2002
Comparative StudyIncreased neutrophil migratory activity after major trauma: a factor in the etiology of acute respiratory distress syndrome?
Neutrophil infiltration of the lung is characteristic of early posttraumatic acute respiratory distress syndrome (ARDS). This study examines the ability of neutrophils isolated (over the first 24 hrs) from the peripheral blood of patients admitted after major trauma to migrate in response to interleukin-8. Interleukin-8 is elevated in the lung within 2 hrs of major trauma in patients who later develop ARDS, and thus it plays a central role in the recruitment of neutrophils to the lung and their subsequent activation. We hypothesized that enhanced interleukin-8-mediated neutrophil migratory activity in the early postinjury phase, before the development of ARDS, may be a crucial factor in the etiology of ARDS. ⋯ These data indicate that major blunt trauma enhances the migratory capacity of circulating neutrophils. This is manifest within 2 hrs of admission and may be attributable to alteration in interleukin-8 receptor expression, affinity, or downstream signaling. In patients who later develop ARDS, initially elevated circulating neutrophil counts decrease rapidly, over the same time course. Early enhanced neutrophil migratory activity coupled with elevated pulmonary concentrations of interleukin-8 may be central to the establishment of the neutrophil infiltration that is characteristic of ARDS.