RESUMO
BACKGROUND: The impact of anaesthetic techniques on recurrence of cancers is controversial. Elevated plasma catecholamine levels have been implicated in angiogenesis and metastasis in various cancers. OBJECTIVES: To assess the potential association between continuous intra-operative norepinephrine administration and tumour-related outcome in muscle-invasive bladder cancer patients undergoing radical cystectomy with urinary diversion. DESIGN: Retrospective observational cohort study. SETTING: Single tertiary centre, from 2000 to 2017. PATIENTS: We included a consecutive series of 1120 urothelial carcinoma patients undergoing radical cystectomy and urinary diversion, including 411/1120 patients (37%) who received a continuous intra-operative administration of more than 2âµgâkgâBWâh norepinephrine. MAIN OUTCOME MEASURES: The primary outcome was time to tumour recurrence within 5 years after surgery, with death as competing outcome. We used inverse probability of treatment weighting to adjust for imbalances between treatment groups, one having received more than 2âµgâkgâBWâh norepinephrine and the other having received less. We furthermore adjusted for intra-operative variables or years of surgery as sensitivity analyses. RESULTS: The continuous administration of more than 2âµgâkgâBWâh norepinephrine slightly increased tumour recurrence (hazard ratio: 1.47, 95% CI 0.98 to 2.21; Pâ=â0.061). After adjustment for intra-operative variables, and year of surgery hazard ratios were 1.82 (95% CI 1.13 to 2.91, Pâ=â0.013) and 1.85 (95% CI 1.12 to 3.07, Pâ=â0.017), respectively. Overall mortality (with or without tumour recurrence) was not affected by norepinephrine (hazard ratio: 0.84, 95% CI 0.65 to 1.08, Pâ=â0.170). CONCLUSION: Continuous administration of more than 2âµgâkgâBWâh norepinephrine was associated with a slightly increased hazard ratio for tumour recurrence if adjusted for intra-operative variables and year of surgery. This observation could reflect a low potential pro-oncogenic effect of norepinephrine during the intra-operative period. TRIAL REGISTRATION: Not applicable.