Modelling of the optimal bupivacaine dose for spinal anaesthesia in ambulatory surgery based on data from systematic review.

BACKGROUND: Spinal bupivacaine is used for day-case surgery but the appropriate dose that guarantees hospital discharge is unknown. OBJECTIVE: We sought to determine the spinal bupivacaine dose that prevents delayed hospital discharge in ambulatory surgery. DESIGN: Systematic review of clinical trials. DATA SOURCES: Comprehensive search in electronic databases of studies published between 1996 and 2014 reporting the use of spinal bupivacaine in ambulatory patients. Additional articles were retrieved through hyperlinks and by manually searching reference lists in original articles, review articles and correspondence published in English and French. MAIN OUTCOME MEASURES: Data were used to calculate, motor block duration and discharge time, an estimated maximal effect (Emax: maximum theoretical time of motor block) and the effective dose to obtain half of Emax (D50) with 95% confidence intervals (CIs). A simulation was performed to determine the dose corresponding to a time to recovery of 300 min for motor function, and 360 min for discharge, in 95% of the patients. RESULTS: In total, 23 studies (1062 patients) were included for analysis of the time to recovery of motor function, and 12 studies (618 patients) for the time to hospital discharge. The Emax for recovery of motor function was 268 min [95% CI (189 to 433 min)] and the D50 was 3.9 mg [95% CI (2.3 to 6.2 mg)]. A 7.5-mg dose of bupivacaine enables resolution of motor block and ambulation within 300 min in 95% of the patients. A 5-mg dose or less was associated with an unacceptable failure rate. CONCLUSION: Ambulatory surgery is possible under spinal anaesthesia with bupivacaine although the dose range that ensures reliable anaesthesia with duration short enough to guarantee ambulatory management is narrow.

Beta2-adrenergic agonist protects human endothelial cells from hypoxia/reoxygenation injury in vitro.

OBJECTIVE: Circulatory shock results in hypoxia/reoxygenation processes that lead to the release of reactive oxygen species, endothelial injury, and multiple organ failure. Previous data suggest that beta2-adrenergic agonists prevent endothelial dysfunction. The study aimed at determining whether the beta2-adrenergic agonist formoterol protects endothelial cells against hypoxia/reoxygenation injury in vitro. DESIGN: Prospective controlled trial. SETTING: University hospital research laboratory. SUBJECTS: Cultured human umbilical vein endothelial cells (HUVECs). INTERVENTIONS: Confluent HUVECs were sealed in a flow-through chamber mounted on an inverted microscope and perfused with a constant flow of Krebs medium. After 1 hr of equilibration, HUVECs underwent 2 hrs of hypoxia and 1 hr of reoxygenation. Cell death at the end of reoxygenation and reactive oxygen species formation were assessed with fluorescent probes propidium iodide and 2',7'-dichlorodihydrofluorescein diacetate, respectively. The effects of the beta2-adrenergic agonist formoterol, the beta2-adrenergic antagonist ICI 118,551 and the nitric oxide synthase inhibitor L-NNA were investigated. Statistical analysis was performed with analysis of variance followed by post hoc Fisher's test. MEASUREMENTS AND MAIN RESULTS: Hypoxia/reoxygenation increased cell death (hypoxia/reoxygenation 29 +/- 4% vs. control 1 +/- 5%, p < .05) and endothelial reactive oxygen species production (hypoxia/reoxygenation 126 +/- 4% vs. control 108 +/- 4%, p < .05). Formoterol reduced cell death in a concentration-dependent manner (EC95 = 10 mol/L) and reduced endothelial reactive oxygen species production (hypoxia/reoxygenation + formoterol EC95 109 +/- 4% vs. hypoxia/reoxygenation 126 +/- 4%, p < .05). When added to formoterol EC95, ICI 118,551 and L-NNA abolished the formoterol-induced cell protection and reduced reactive oxygen species production. CONCLUSIONS: These results indicate that formoterol reduces endothelial cell death and reactive oxygen species production in this in vitro hypoxia/reoxygenation model. These effects are beta2-adrenergic specific and are partially mediated by nitric oxide synthase.