Effects of perioperative medication on hemodynamics and blood loss

Intraoperative hemodynamic changes and loss of blood with the associated risk of allogeneic blood transfusion are risk factors for complications in surgical patients. The use of medication in the perioperative period may influence these risk factors and consequently the frequency of complications. Perioperative medication includes both regular drugs that surgical patients receive already for comorbidity, as well as drug therapy especially initiated to optimise a patient’s condition in the perioperative period, e.g. recombinant human erythropoietin. There is scant evidence from randomized controlled trials to guide perioperative medication management. Therefore, the studies in this thesis focused on the influence of medications on clinical parameters in surgical patients. The main objectives of this thesis were to investigate the effects of antidepressant agents on intraoperative hemodynamics and blood loss in patients who continued the use of their antidepressants during surgery and to investigate the effectiveness of preoperative treatment with erythropoietin in daily clinical practice. We found that severe intraoperative hemodynamic events did not occur more frequently in patients who continued the use of monoamine oxidase inhibitors in the perioperative period compared to nonusers. Treatment with selective serotonin reuptake inhibitors (SSRIs) before surgery was associated with a briefer duration of intraoperative hypotensive episodes without introducing severe or sustained hypertensive episodes. Users of serotonergic antidepressants showed a moderate increase in blood loss during orthopedic surgery that did not result in increased transfusion requirements. The use of SSRIs was not associated with an increase in the occurrence of QT interval prolongation. The introduction of a preoperative erythropoietin protocol as part of a multifaceted blood management program reduced the transfusion rate in total hip arthroplasty patients. However, the effectiveness of preoperative erythropoietin therapy in daily clinical practice is lower than the efficacy shown in randomised clinical trials. We found that a substantial number of total hip arthroplasty patients showed a poor response to preoperative treatment with erythropoietin. This poor response was more frequent in patients using angiotensin II receptor antagonists or vitamin K antagonists, and in patients having a high BMI. As a result, poor responders more frequently required allogeneic blood transfusion. In conclusion, we showed that the use of antidepressants in the perioperative period influences hemodynamic parameters and blood loss in patients during surgery, but that the continuation of these antidepressive agents seems safe in daily clinical practice. For these studies, we used only routinely documented patient data. Further investigation should be performed to fill in knowledge gaps on the potential effects of drugs on clinical and hemodynamic parameters in the perioperative period. If routinely documented patient data in electronic medical records will be more accurately recorded as well as become more easily accessible, this will offer many opportunities for clinical research on drug effects in surgical patients. Furthermore, we showed that the effectiveness of preoperative treatment with erythropoietin in daily clinical practice does not meet its efficacy as shown in randomised clinical trials. Investigation of the effect of newly introduced drug therapies in real-life populations is necessary