Publications

The sublingual microcirculation is globally unaltered by red blood cell transfusion in septic patients; however, it can improve in patients with altered capillary perfusion at baseline.

Many preclinical studies in critical care medicine and related disciplines rely on hypothesis-driven research in mice. The underlying premise posits that mice sufficiently emulate numerous pathophysiologic alterations produced by trauma/sepsis and can serve as an experimental platform for answering clinically relevant questions. Recently, the lay press severely criticized the translational relevance of mouse models in critical care medicine. A series of provocative editorials were elicited by a highly publicized research report in the Proceedings of the National Academy of Sciences (PNAS; February 2013), which identified an unrecognized gene expression profile mismatch between human and murine leukocytes following burn/trauma/endotoxemia. Based on their data, the authors concluded that mouse models of trauma/inflammation are unsuitable for studying corresponding human conditions. We believe this conclusion was not justified. In conjunction with resulting negative commentary in the popular press, it can seriously jeopardize future basic research in critical care medicine. We will address some limitations of that PNAS report to provide a framework for discussing its conclusions and attempt to present a balanced summary of strengths/weaknesses of use of mouse models. While many investigators agree that animal research is a central component for improved patient outcomes, it is important to acknowledge known limitations in clinical translation from mouse to man. The scientific community is responsible to discuss valid limitations without overinterpretation. Hopefully, a balanced view of the strengths/weaknesses of using animals for trauma/endotoxemia/critical care research will not result in hasty discount of the clear need for using animals to advance treatment of critically ill patients.

TAK-242 failed to suppress cytokine levels in patients with sepsis and shock or respiratory failure. Treatment with TAK-242 resulted in mild increases in serum methemoglobin levels but was otherwise well tolerated. Although observed mortality rates in patients with both shock and respiratory failure were lower with the 2.4 mg/kg/day dose, differences were not significant.

These results showed that stiripentol was a weak inhibitor of saquinavir metabolism both in vitro and in vivo. In contrast, stiripentol is a potent inhibitor of carbamazepine 10,11-epoxide formation in vitro and in vivo in epileptic patients.

In the whole study population, intra-arrest cooling initiated < 20 min from collapse compared to cooling initiated at hospital was not associated with improved favorable neurologic outcome. In the subgroup with shockable rhythms, early cooling was associated with improved favorable outcome and complete recovery.

The purpose of the study was to compare the effects of high and low dose of 6% hydroxyethyl starch solution (HES) on resuscitation for shock induced by intestinal ischemia/reperfusion (I/R) injury in rabbits. Thirty-two anesthetized rabbits were randomized into four groups of eight animals each, which was either treated with no fluid resuscitation as control, lactated Ringer's solution (LRS, 20ml/kg/h), LRS+HES (LRS 18ml/kg/h + HES 2ml/kg/h, low dose of HES) or only treated with HES (high dose of HES, 20ml/kg/h). These rabbits underwent the intestinal I/R injury developed by occluding superior mesenteric artery (SMA) with a noncrushing vascular clamp for 60min and then loosing the clamp for 240min. The fluid resuscitation began at the same time of reperfusion. Hemodynamic parameters including MAP, HR, aortic velocity (Qaorta, as CO) and SMA blood flow (Osma) were measured. Tissue oxygenation was assessed indirectly by measuring the tonometric parameters of gut, including difference between intestinal intramucosal PtCO2 and arterial PaCO2 (PCO2-gap), intestinal intramucosal pH (pHi), arterial lactate acid concentration and oxygen delivery (DO2). Mortality of the rabbits was calculated at the end. The results showed that hemodynamic parameters were significantly higher in group LRS+HES and HES than in group LRS and control (P&lt;0.05). Low dose of HES was better than high dose of HES in restoring hemodynamic parameters (P&lt;0.05). Low dose of HES could greatly decrease lactate and PCO2-gap, significantly improve pHi than other three groups (P&lt;0.05), but high dose of HES did not do so, rather, which induced oral and nasal bleeding, even death of some animals. Low dose and high dose of HES significantly improved DO2 while LRS did not (P&lt;0.05). Therefore low dose of HSE together with LRS was more effective than only high dose of HES or LRS in the resuscitation for shock induced by intestinal I/R injury in rabbits, because hemodynamic parameters increased suitably and tissue oxygenation was greatly improved.