Automatic control of consciousness using the BIS is clinically feasible and outperforms manual control.

Proinflammatory cytokines, such as tumor necrosis factor-alpha, interleukin-6, and interleukin-8, and anti unflammatory cytokines, such as interleukin-10, may play an important role in patient responses to cardiopulmonary bypass. We sought to define whether the myocardium and the lungs serve as important sources of these cytokines under conditions of cardiopulmonary bypass. Ten patients (age 64 +/- 3 years, mean +/- standard error of the mean) undergoing elective coronary artery bypass grafting were monitored with an arterial catheter, a coronary sinus catheter, and pulmonary artery catheter. Plasma levels of tumor necrosis factor-alpha, interleukin-6, interleukin-8, and interleukin-10 were measured simultaneously in peripheral arterial blood, coronary sinus blood, and mixed venous blood before heparin administration, 1 minute before aortic crossclamping, 5 minutes after aortic declamping, and at 0.5, 1, 1.5 and 2 hours after aortic declamping. The durations of cardiopulmonary bypass and aortic crossclamping were 114 +/- 9 and 64 +/- 5 minutes, respectively. Levels of tumor necrosis factor-alpha and interleukin-6 were significantly higher in coronary sinus blood than in arterial blood after aortic declamping. Tumor necrosis factor-alpha and interleukin-6 levels were also higher in mixed venous blood than in arterial blood within 1 hour after declamping. There were no significant differences among the three sampling sites with respect to interleukin-8 and interleukin-10 levels. In one patient who had postoperative myocardial infarction, however, interleukin-8 levels were three times as high as in coronary sinus blood than in arterial blood. These data indicate that the myocardium is a major source of tumor necrosis factor-alpha and interleukin-6 in patients undergoing cardiopulmonary bypass. The lungs may consume rather than release proinflammatory cytokines in the early phase of reperfusion. The source under these conditions of the antünflammatory cytokine interleukin-10 remains to be determined.

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Kidney ischemia/reperfusion injury (I/R) is characterized by renal dysfunction and tubular damages resulting from an early activation of innate immunity. Recently, nicotine administration has been shown to be a powerful inhibitor of a variety of innate immune responses, including LPS-induced toxaemia. This cholinergic anti-inflammatory pathway acts via the α7 nicotinic acetylcholine receptor (α7nAChR). Herein, we tested the potential protective effect of nicotine administration in a mouse model of renal I/R injury induced by bilateral clamping of kidney arteries. Renal function, tubular damages and inflammatory response were compared between control animals and mice receiving nicotine at the time of ischemia. Nicotine pretreatment protected mice from renal dysfunction in a dose-dependent manner and through the α7nAChR, as attested by the absence of protection in α7nAChR-deficient mice. Additionally, nicotine significantly reduced tubular damages, prevented neutrophil infiltration and decreased productions of the CXC-chemokine KC, TNF-α and the proinflammatory high-mobility group box 1 protein. Reduced tubular damage in nicotine pre-treated mice was associated with a decrease in tubular cell apoptosis and proliferative response as attested by the reduction of caspase-3 and Ki67 positive cells, respectively. All together, these data highlight that nicotine exerts a protective anti-inflammatory effect during kidney I/R through the cholinergic α7nAChR pathway. In addition, this could provide an opportunity to overcome the effect of surgical cholinergic denervation during kidney transplantation.

Background The type of fluid and volume regimen given intraoperatively both can impact patient outcome after major surgery. This two-arm, parallel, randomized controlled, double-blind, bi-center superiority study tested the hypothesis that when using closed-loop assisted goal-directed fluid therapy, balanced colloids are associated with fewer postoperative complications compared to balanced crystalloids in patients having major elective abdominal surgery. Methods One hundred and sixty patients were enrolled in the protocol. All patients had maintenance-balanced crystalloid administration of 3 ml · kg–1 · h–1. A closed-loop system delivered additional 100-ml fluid boluses (patients were randomized to receive either a balanced-crystalloid or colloid solution) according to a predefined goal-directed strategy, using a stroke volume and stroke volume variation monitor. All patients were included in the analysis. The primary outcome was the Post-Operative Morbidity Survey score, a nine-domain scale, at day 2 postsurgery. Secondary outcomes included all postoperative complications. Results Patients randomized in the colloid group had a lower Post-Operative Morbidity Survey score (median [interquartile range] of 2 [1 to 3] vs. 3 [1 to 4], difference –1 [95% CI, –1 to 0]; P < 0.001) and a lower incidence of postoperative complications. Total volume of fluid administered intraoperatively and net fluid balance were significantly lower in the colloid group. Conclusions Under our study conditions, a colloid-based goal-directed fluid therapy was associated with fewer postoperative complications than a crystalloid one. This beneficial effect may be related to a lower intraoperative fluid balance when a balanced colloid was used. However, given the study design, the mechanism for the difference cannot be determined with certainty.