Consequences of Perioperative Serotonin Reuptake Inhibitor Treatment during Hepatic Surgery.

Background and aims Platelet stored serotonin critically affects liver regeneration in mice and humans. Selective serotonin reuptake inhibitors (SSRI) and serotonin noradrenalin reuptake inhibitors (SNRI) reduce intra-platelet serotonin. As SSRI/SNRIs are now one of the most commonly prescribed drugs in the United States and Europe, and given serotonin's impact on liver regeneration, we aimed to evaluate if perioperative use of SSRI/SNRIs affects outcome after hepatic resection. Methods 754 consecutive patients undergoing hepatic resection were retrospectively included from prospectively maintained databases from 2 European institutions. Further, an independent cohort of 495 patients from the United States was assessed to validate our exploratory findings. Perioperative intake of SSRI/SNRIs was recorded and patients were followed up for postoperative liver dysfunction (LD), morbidity and mortality. Results Perioperative intra-platelet serotonin levels were significantly decreased in patients receiving SSRI/SNRI treatment. Patients treated with SSRI/SNRI showed a higher incidence of morbidity, severe morbidity, LD and LD requiring intervention. Associations were confirmed in the independent validation cohort. Combined cohorts documented a significant increase in deleterious postoperative outcome (morbidity odds ratio (OR): 1.56- 95% confidence interval (CI): 1.07-2.31; severe morbidity - OR: 1.86 95% CI:1.22-2.79; LD - OR:1.96 95% CI:1.23-3.06; LD requiring intervention - OR: 2.22 95% CI: 1.03-4.36). Further, multivariable analysis confirmed independent association of SSRI/SNRIs with postoperative LD, which was closely associated with postoperative 90-day mortality and one-year overall survival. Conclusions We observed a significant association of perioperative SSRI/SNRI intake with adverse postoperative outcome after hepatic resection. This indicates that SSRI/SNRIs should be avoided perioperatively in patients undergoing hepatic resections.