• Lukas M Löffel, Marc A Furrer, Aline Favre, Dominique Engel, Brigitta Gahl, Fiona C Burkhard, and Patrick Y Wuethrich.
• From the Department of Anaesthesiology and Pain Medicine, Inselspital (LML, MAF, DE, PYW), Department of Urology, Inselspital, Bern University Hospital, Bern (MAF, FCB), Division of Anaesthesiology, Department of Anaesthesiology, Clinical Pharmacology and Intensive Care Medicine, Geneva University Hospitals, Geneva (AF) and Statistics & Methodology, Clinical Trials Unit CTU Bern, University of Bern, Bern, Switzerland (BG).
• Eur J Anaesthesiol. 2020 May 1; 37 (5): 377-386.

BackgroundThe impact of anaesthetic techniques on recurrence of cancers is controversial. Elevated plasma catecholamine levels have been implicated in angiogenesis and metastasis in various cancers.ObjectivesTo 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.DesignRetrospective observational cohort study.SettingSingle tertiary centre, from 2000 to 2017.PatientsWe 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 MeasuresThe 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.ResultsThe 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).ConclusionContinuous 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 RegistrationNot applicable.

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