Neutrophils play a critical role in acute and chronic inflammatory processes, including myocardial ischemia/reperfusion injury, sepsis, and adult respiratory distress syndrome. Binding of formyl peptide receptor 1 (FPR1) by N-formyl peptides can activate neutrophils and may represent a new therapeutic target in either sterile or septic inflammation. Propofol, a widely used i.v. anesthetic, has been shown to modulate immunoinflammatory responses. However, the mechanism of propofol remains to be established. In this study, we showed that propofol significantly reduced superoxide generation, elastase release, and chemotaxis in human neutrophils activated by fMLF. Propofol did not alter superoxide generation or elastase release in a cell-free system. Neither inhibitors of γ-aminobutyric acid receptors nor an inhibitor of protein kinase A reversed the inhibitory effects of propofol. In addition, propofol showed less inhibitory effects in non-FPR1–induced cell responses. The signaling pathways downstream from FPR1, involving calcium, AKT, and ERK1/2, were also competitively inhibited by propofol. These results show that propofol selectively and competitively inhibits the FPR1-induced human neutrophil activation. Consistent with the hypothesis, propofol inhibited the binding of N-formyl-Nle-Leu-Phe-Nle-Tyr-Lys-fluorescein, a fluorescent analog of fMLF, to FPR1 in human neutrophils, differentiated THP-1 cells, and FPR1-transfected human embryonic kidney-293 cells. To our knowledge, our results identify, for the first time, a novel anti-inflammatory mechanism of propofol by competitively blocking FPR1 in human neutrophils. Considering the importance of N-formyl peptides in inflammatory processes, our data indicate that propofol may have therapeutic potential to attenuate neutrophil-mediated inflammatory diseases by blocking FPR1.

We have evaluated the antiemetic effect of i.v. dexamethasone compared with saline in the prevention of nausea and vomiting after laparoscopic cholecystectomy. We studied 90 patients requiring general anaesthesia for laparoscopic cholecystectomy, in a randomized, double-blind, placebo-controlled study. The dexamethasone group (n = 45) received dexamethasone 8 mg i.v. and the saline group received saline 2 ml i.v. at induction of anaesthesia. Anaesthesia was maintained with isoflurane in oxygen. We found that 10% of patients in the dexamethasone group compared with 34% in the saline group reported vomiting (P < 0.05). Of note, the total incidence of nausea and vomiting was 23% in the dexamethasone group and 63% in the saline group (P < 0.001). We conclude that dexamethasone 8 mg significantly decreased the incidence of nausea and vomiting after laparoscopic cholecystectomy.

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We sought to determine the minimum effective dose of dexamethasone in preventing postoperative nausea and vomiting in women undergoing thyroidectomy. Two hundred twenty-five women (n = 45 in each of five groups) undergoing thyroidectomy under general anesthesia were enrolled in this randomized, double-blinded, placebo-controlled study. Immediately after the induction of anesthesia, patients received IV dexamethasone at doses of 10 mg (D10), 5 mg (D5), 2.5 mg (D2.5), 1.25 mg (D1.25), or saline (S). We found that Groups D10 and D5 were significantly different from Group S in the total incidences of nausea and vomiting, more than four vomiting episodes, the proportions of patients requiring rescue antiemetics, and the incidences of complete responses. The differences between Groups D10 and D5 were not significant. Dexamethasone 2.5 mg reduced the total incidence of nausea and vomiting. Dexamethasone 1.25 mg was not effective. Dexamethasone 5 mg IV is the minimum effective dose in preventing postoperative nausea and vomiting in women undergoing thyroidectomy.