Reduced mortality with noninvasive hemodynamic monitoring of shock.

PURPOSE: This study compared clinical outcomes associated with exposure to pulmonary artery catheters (PACs), central venous catheters (CVCs), arterial pressure waveform analysis for cardiac output (APCO), or no central monitoring (NCM) in patients with shock. MATERIALS AND METHODS: We assessed 6929 consecutive patients from 2003 to 2006 within a surgical intensive care unit of a university hospital, identifying 237 mechanically ventilated patients with shock. RESULTS: Adjusted for severity of illness, use of APCO monitoring, compared with other options, was associated with reduced intensive care unit mortality (odds ratio [OR], 0.37; 95% confidence interval [CI], 0.18-0.77) and 28-day mortality (OR, 0.43; 95% CI, 0.22-0.85). Other monitors were not associated with changes of 28-day mortality (CVC: OR, 0.63; 95% CI, 0.34-1.17; PAC: OR, 0.78; 95% CI, 0.36-1.69) or were associated with increased risk (NCM: OR, 2.29; 95% CI, 1.14-4.61). There were significant differences in the fluid and vasoactive drug prescriptions among the groups. CONCLUSIONS: This study supports an association between the use of APCO monitoring and reduction in mortality in shock compared with traditional methods of monitoring. Although it is impossible to exclude the role of unrecognized/unrecorded differences among the groups, these findings may result from differences in supportive care, directed by monitor technology.

Dehydroepiandrosterone inhibits intracellular calcium release in beta-cells by a plasma membrane-dependent mechanism.

Both dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEAS) affect glucose stimulated insulin secretion, though their cellular mechanisms of action are not well characterized. We tested the hypothesis that human physiological concentrations of DHEA alter insulin secretion by an action initiated at the plasma membrane of beta-cells. DHEA alone had no effect on intracellular calcium concentration ([Ca(2+)](i)) in a rat beta-cell line (INS-1). However, it caused an immediate and dose-dependent inhibition of carbachol-induced Ca(2+) release from intracellular stores, with a 25% inhibition at zero. One nanometer DHEA. DHEA also inhibited the Ca(2+) mobilizing effect of bombesin (29% decrease), but did not inhibit the influx of extracellular Ca(2+) evoked by glyburide (100 microM) or glucose (15 mM). The steroids (androstenedione, 17-alpha-hydroxypregnenolone, and DHEAS) had no inhibitory effect on carbachol-induced intracellular Ca(2+) release. The action of DHEA depended on a signal initiated at the plasma membrane, since membrane impermeant DHEA-BSA complexes also inhibited the carbachol effect on [Ca(2+)](i) (39% decrease). The inhibition of carbachol-induced Ca(2+) release by DHEA was blocked by pertussis toxin (PTX). DHEA also inhibited the carbachol induction of phosphoinositide generation, with a maximal inhibition at 0.1 nM DHEA. Furthermore, DHEA inhibited insulin secretion induced by carbachol in INS-1 cells by 25%, and in human pancreatic islets by 53%. Taken together, this is the first report showing that human physiological concentrations of DHEA decrease agonist-induced Ca(2+) release by a rapid, non-genomic mechanism in INS-1 cells. Furthermore, these data provide evidence consistent with the existence of a specific plasma membrane DHEA receptor, mediating this signal transduction pathway by pertussis toxin-sensitive G-proteins.