Bupivacaine inhibits the TLR4- and TLR2-Myd88/NF-κB pathways in human leukocytes.

Local anesthetics have anti-inflammatory effects. Because most previous experiments were performed with supra-therapeutic concentrations, we measured the effects of clinically relevant concentrations of bupivacaine on the Toll like receptor 4 (TLR4)- and TLR2-myeloid differentiation primary response 88 (MyD88)-nuclear factor kappa-light-chain-enhancer of activated B cell (NF-κB) pathways. We measured tumor necrosis factor alpha (TNF-α) and prostaglandin E2 (PGE2) release, p38 mitogen-activated protein kinase (MAP-kinase) phosphorylation and translocation of NF-κB in human peripheral blood mononuclear cells (hPBMCs) and human monocytes challenged with lipopolysaccharide (LPS) or tripalmitoylated lipopeptide Pam3CysSerLys4 (Pam3CSK4) in the presence or absence of bupivacaine. Similarly, we measured the effect of bupivacaine on HEK293 cells expressing the hTLR4 and the hTLR2 genes and challenged with LPS or Pam3CSK4. Finally, molecular docking simulations of R(+)- and S(-)-bupivacaine binding to the TLR4-myeloid differentiation protein 2 (MD-2) complex and to the TLR2/TLR1 heterodimer were performed. In PBMCs, bupivacaine from 0.1 to 100 µM inhibited LPS-induced TNF-α and PGE2 secretion, phosphorylation of p38 and nuclear translocation of NF-κB in monocytes. Bupivacaine similarly inhibited the effects of Pam3CSK4 on TNF-α secretion. Bupivacaine inhibited the effect of LPS on HEK293 cells expressing the human TLR4 receptor and the effect of Pam3CSK4 on HEK293 cells expressing the human TLR2 receptor. Molecular docking showed that bupivacaine binds to the MD-2 co-receptor of TLR4 and to the TLR2 receptor. Contrary to numerous experiments performed with supratherapeutic doses, our results were obtained with concentrations of bupivacaine as low as 0.1 µM. We conclude that bupivacaine modulates the inflammatory reactions such as those observed after surgery or trauma, at least partly by inhibiting the TLR4- and TLR2-NF-κB pathways.

Are standard intra-abdominal pressure values different during pregnancy?

BACKGROUND: Measurement of intra-abdominal pressure (IAP) is an important parameter in the surveillance of intensive care unit patients. Standard values of IAP during pregnancy have not been well defined. The aim of this study was to assess IAP values in pregnant women before and after cesarean delivery. METHODS: This prospective study, carried out from January to December 2011 in a French tertiary care centre, included women with an uneventful pregnancy undergoing elective cesarean delivery at term. IAP was measured through a Foley catheter inserted in the bladder under spinal anaesthesia before cesarean delivery, and every 30 minutes during the first two hours in the immediate postoperative period. RESULTS: The study included 70 women. Mean IAP before cesarean delivery was 14.2 mmHg (95%CI: 6.3-23). This value was significantly higher than in the postoperative period: 11.5 mmHg (95%CI: 5-19.7) for the first measurement (p = 0.002). IAP did not significantly change during the following two postoperative hours (p = 0.2). Obese patients (n = 25) had a preoperative IAP value significantly higher than non-obese patients: 15.7 vs. 12.4; p = 0.02. CONCLUSION: In term pregnancies, IAP values are significantly higher before delivery than in the post-partum period, where IAP values remain elevated for at least two hours at the level of postoperative classical abdominal surgery. The knowledge of these physiological changes in IAP values may help prevent organ dysfunction/failure when abdominal compartment syndrome occurs after cesarean delivery.

General anesthesia for intussusception reduction by enema.

OBJECTIVES: Intussusception is the most frequent cause of bowel obstruction in children. Although enema is usually used as the initial treatment, surgery may be required in more than 50% of patients. General anesthesia (GA) has been suggested to increase the rate of enema success. The purpose of this study was to evaluate whether GA increases the success rate of reduction by air enema. METHODS: In this retrospective single-center study from 1989 to the end of June 2008, patients receiving air enema for intussusception reduction were studied. Multivariable analysis using propensity score was performed to compare the success rate between patients receiving sedation or GA. RESULTS: The success rate of air enema increased from 72% in 1989 to the current rate of 90%. When time elapsed between first symptoms and enema was >12 h, the success rate decreased significantly (Odds Ratio 0.67 [0.56-0.81], P < 0.0001). When patients were matched by propensity score, GA significantly increased the likelihood of success (OR 5.66 [2.85-12.89], P = 0.013). CONCLUSIONS: Air enema performed under GA allows intussusception reduction in more than 90% of patients.