The Effect of Intraoperative Dexmedetomidine Versus Morphine on Postoperative Morphine Requirements After Laparoscopic Bariatric Surgery.

BACKGROUND: Dexmedetomidine is an α2 receptor agonist with sedative and analgesic properties. During bariatric surgery, its use may reduce postoperative opioid requirements, reduce their side effects, and improve quality of recovery. The aim of this prospective randomized controlled trial was to compare the effect of dexmedetomidine bolus and infusion versus morphine bolus given prior to the end of laparoscopic bariatric surgery. METHODS: Sixty morbidly obese patients (BMI > 40 kg m-2) aged 18 to 60 years, undergoing laparoscopic sleeve gastrectomy, received morphine sulfate (bolus 0.08 mg kg-1 followed by a saline infusion) (group M, n = 30) or dexmedetomidine (loading dose of 1 µg kg-1 followed by 0.5 µg kg-1 h-1) (group D, n = 30) 30 min before the end of surgery. Data collected included morphine consumption in the post-anesthesia care unit (PACU) (primary outcome) and at 24 h, pain intensity, nausea, heart rate, blood pressure, vomiting, sedation, and quality of recovery. RESULTS: There was no significant difference in morphine consumption in the PACU (group D 12.2 ± 5.44 mg, group M 13.28 ± 6.64 mg, P = 0.54) or at 24 h (group D 40.67 ± 24.78 mg, group M 43.28 ± 27.79 mg, P = 0.75); when accounting for intraoperative morphine given group M had significantly higher morphine consumption when compared to group D (23.48 ± 6.22 mg vs. 12.22 ± 5.54 mg, respectively, P < 0.01). Group D patients had more cardiovascular stability. CONCLUSIONS: Dexmedetomidine given prior to end of laparoscopic sleeve gastrectomy provides the same level of postoperative analgesia as morphine with better hemodynamic profile.

Cadmium Induces Migration of Colon Cancer Cells: Roles of Reactive Oxygen Species, P38 and Cyclooxygenase-2.

BACKGROUND/AIMS: Cadmium (Cd) is a heavy metal contaminant whose toxicity is associated with colorectal cancer (CRC). However, the underlying molecular mechanisms of Cd-induced CRC malignancy remain obscure. METHODS: A monolayer scratch assay was employed to assess the migration of HT-29 human adenocarcinoma cells. Luciferase reporter assay was used to determine cyclooxygenase-2 (COX-2) transcriptional activity, and Western blotting was used to detect p38 Mitogen Activated Protein Kinase (MAPK) and Akt phosphorylation as well as COX-2 expression. Prostaglandin E2 (PGE2) levels were measured using Enzyme Linked Immunosorbent Assay (ELISA) and reactive oxygen species (ROS) formation was assessed using dihydroethidium (DHE) stain. RESULTS: Here, we show that Cd potentiates the migratory capacity of HT-29 CRC cells. Cd caused a time-dependent increase in COX-2 expression. Celecoxib, a COX-2 selective inhibitor, significantly reduced Cd-induced migration. Cd also increased levels of ROS and phosphorylated p38. Importantly, Cd-induced COX-2 expression and migration were significantly abolished by N-Acetyl-Cysteine (NAC), a ROS scavenger, or SB202190, a specific p38 inhibitor. Furthermore, Cd-induced p38 phosphorylation was inhibited by NAC. Cd (100 nM) also increased PGE2 levels, which was abrogated by NAC, SB202190, or celecoxib. Exogenous PGE2 significantly potentiated cell migration. Cd caused a significant increase in Akt phosphorylation in a ROS-mediated pathway. Moreover, Cd-induced migration was significantly attenuated by LY294 002, a phosphatidylinositol-3-kinase inhibitor. CONCLUSION: Taken together, our results suggest that exposure to low levels of Cd promotes a more migratory cancer phenotype in a ROS-p38-COX-2-PGE2 pathway as well as ROS-Akt pathway. Therefore, COX-2, PGE2 receptors or Akt represent potential targets in the treatment of CRC, particularly in patients exposed to Cd.