Z Gastroenterol 2010; 48 - P110
DOI: 10.1055/s-0030-1263554

Melatonin in liver resection: first clinical data

A Nickkholgh 1, H Schneider 2, M Sobirey 3, W Venetz 4, H Nguyen 5, H Bruns 1, M Weigand 6, M Zorn 7, MW Büchler 1 P Schemmer 1, PORTAL-Study group
  • 1Ruprecht-Karl-University, Heidelberg, Dept. of General and Transplantation Surgery, Heidelberg, Germany
  • 2HealthEcon AG, Basel, Switzerland
  • 3nutri˜fit GmbH & Co KG, Mühlen, Germany
  • 4Datagen AG, Rheinfelden, Switzerland
  • 5Ruprecht-Karl-University, Heidelberg, Clinical Pharmacy, Heidelberg, Germany
  • 6Ruprecht-Karl-University, Heidelberg, Dept. of Anesthesiology, Heidelberg, Germany
  • 7Ruprecht-Karl-University, Heidelberg, Dept. of Internal Medicine, Heidelberg, Germany

Aims: Experimental data suggest that melatonin, a potent immuno-modulator and antioxidant, would decrease the inflammatory changes after major liver resection, thus positively influencing the postoperative course. This study was designed to assess its safety and tolerance given as a single preoperative oral dose.

Material and methods: A randomized controlled double blind single center pilot clinical trial on the safety and tolerance of preoperative melatonin application in patients undergoing major liver resection (PORTAL) [EudraCT number: 2006–005308–159] with two parallel study arms was performed. A total of 50 patients scheduled for major liver resection (≥3 segments) were randomized to receive a preoperative single dose of either melatonin (50mg/kg BW) or a control neutral substance through the gastric tube right after the intubation for general anesthesia. Both groups were comparable regarding demographics, operative procedures, and intraoperative data. Primary endpoints were safety and tolerance. Secondary endpoints were infectious and non-infectious complications. Data is shown as Mean±SD.

Results: Melatonin was effectively absorbed with serum concentrations of 1142.8±7.2ng/ml in contrast to 0.3±7.8ng/ml in controls (p <0.0001). Melatonin treatment resulted in lower postoperative transaminases over the study period (p=0.6). There was no serious adverse event in patients after melatonin. Monitoring of laboratory data over the first 7 postoperative days confirmed the safety of the preoperative application of melatonin prior to major liver surgery. A total of 3 infectious complications occurred in either treatment groups. Non-infectious complications occurred in 5 control patients (a total of 8 complications) vs. 3 melatonin patients (a total of 3 complications). There was a trend towards shorter ICU stay and total hospital stay after melatonin.

Conclusion: This study clearly demonstrates that a single preoperative enteral dose of melatonin is effectively absorbed and is safe and well tolerated in patients undergoing major liver surgery. A future phase III study will be performed to further assess the observed trends.