Intra-operative norepinephrine administration and cancer-related outcomes following radical cystectomy for bladder cancer: A cohort study.

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 2 µg kg BW h 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 2 µg kg BW h 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 2 µg kg BW h norepinephrine slightly increased tumour recurrence (hazard ratio: 1.47, 95% CI 0.98 to 2.21; P = 0.061). After adjustment for intra-operative variables, and year of surgery hazard ratios were 1.82 (95% CI 1.13 to 2.91, P = 0.013) and 1.85 (95% CI 1.12 to 3.07, P = 0.017), respectively. Overall mortality (with or without tumour recurrence) was not affected by norepinephrine (hazard ratio: 0.84, 95% CI 0.65 to 1.08, P = 0.170). CONCLUSION: Continuous administration of more than 2 µg kg BW h 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.