PORTAL: Pilot study on the safety and tolerance of preoperative melatonin application in patients undergoing major liver resection: a double-blind randomized placebo-controlled trial

Schemmer, Peter; Nickkholgh, Arash; Schneider, H; Sobirey, Michael; Weigand, Markus; Koch, Moritz; Weitz, Jürgen; Büchler, Markus W.

doi:10.1186/1471-2482-8-2

Cited by 21 publications

(12 citation statements)

References 29 publications

(28 reference statements)

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“…The PORTAL study (pilot study on the safety and tolerance of preoperative melatonin application in patients undergoing major liver resection; EudraCT number: 2006‐005308‐15) is a randomized controlled, double‐blind, single‐center clinical pilot trial [12]. The study protocol, the patient information sheet, and the informed consent form were approved by the independent Ethics Committee of the Faculty of Medicine at the Ruprecht‐Karls University of Heidelberg.…”

Section: Methodsmentioning

confidence: 99%

“…In clinical liver surgery, melatonin enhances neutrophil apoptosis in vitro after partial hepatectomy, which causes liver ischemia and reperfusion [10], thus eliminating the consequent active inflammatory response due to surgical injury [11]. Within the context of the current knowledge of the immunomodulatory effects of melatonin and its role in the gastrointestinal physiology, especially considering the high‐affinity binding sites in hepatocyte nuclei, the rationale of this study was to meet the need for a randomized controlled trial to evaluate the safety and efficacy, and the possible benefits of oral administration of melatonin in liver surgery [12]. Preliminary results have been published elsewhere [13].…”

Section: Introductionmentioning

confidence: 99%

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The use of high‐dose melatonin in liver resection is safe: first clinical experience

Nickkholgh

Schneider²,

Sobirey³

et al. 2011

Journal of Pineal Research

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101

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Experimental data suggest that melatonin decreases inflammatory changes after major liver resection, thus positively influencing the postoperative course. To assess the safety of a preoperative single dose of melatonin in patients undergoing major liver resection, a randomized controlled double-blind pilot clinical trial with two parallel study arms was designed at the Department of General and Transplantation Surgery, Ruprecht-Karls-University, Heidelberg. A total of 307 patients, who were referred for liver surgery, were screened. One hundred and thirteen patients, for whom a major liver resection (≥3 segments) was scheduled, were eligible. Sixty-three eligible patients refused to participate, and therefore, 50 patients were randomized. A preoperative single dose of melatonin (50 mg/kg BW) dissolved in 250 mL of milk was administered through the gastric tube after the intubation for general anesthesia. Controls were given the same amount of microcrystalline cellulose. Primary endpoint was safety. Secondary endpoints were postoperative complications. Melatonin was effectively absorbed with serum concentrations of 1142.8 ± 7.2 ng/mL (mean ± S.E.M.) versus 0.3 ± 7.8 ng/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 treatment. A total of three infectious complications occurred in either group. A total of eight noninfectious complications occurred in five control patients, whereas three noninfectious complications occurred in three patients receiving preoperative melatonin (P = 0.3). There was a trend toward shorter ICU stay and total hospital stay after melatonin treatment. Therefore, a single preoperative enteral dose of melatonin is effectively absorbed and is safe and well tolerated in patients undergoing major liver surgery.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The use of high‐dose melatonin in liver resection is safe: first clinical experience

Nickkholgh

Schneider²,

Sobirey³

et al. 2011

Journal of Pineal Research

Self Cite

101

View full text Add to dashboard Cite

show abstract

“…To bring this experimental knowledge into clinical use, a pilot study was initiated by Schemmer et al [183] in Germany to evaluate the use of melatonin in patients undergoing major liver resections. Should this investigation be successful, this would open the door for yet another important indication for the use of melatonin in human liver surgery: as an adjunct to reduce ischemia/reperfusion injury in liver transplantation.…”

Section: From Bench To Bedsidementioning

confidence: 99%

Hepatoprotective actions of melatonin: Possible mediation by melatonin receptors

Mathes¹

2010

WJG

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Melatonin, the hormone of darkness and messenger of the photoperiod, is also well known to exhibit strong direct and indirect antioxidant properties. Melatonin has previously been demonstrated to be a powerful organ protective substance in numerous models of injury; these beneficial effects have been attributed to the hormone's intense radical scavenging capacity. The present report reviews the hepatoprotective potential of the pineal hormone in various models of oxidative stress in vivo, and summarizes the extensive literature showing that melatonin may be a suitable experimental substance to reduce liver damage after sepsis, hemorrhagic shock, ischemia/reperfusion, and in numerous models of toxic liver injury. Melatonin's influence on hepatic antioxidant enzymes and other potentially relevant pathways, such as nitric oxide signaling, hepatic cytokine and heat shock protein expression, are evaluated. Based on recent literature demonstrating the functional relevance of melatonin receptor activation for hepatic organ protection, this article finally suggests that melatonin receptors could mediate the hepatoprotective actions of melatonin therapy.

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“…No references were identified through scanning reference lists of the identified RCTs. Of the 48 references, 24 were excluded as they represented non‐randomized studies, 30–43 a quasi‐randomized study which did not report adverse outcomes related to the pharmacological intervention, 44 a protocol of a study 45 or studies that did not use vascular flow occlusion during liver resection 46–53 . A total of 24 references describing 18 RCTs fulfilled the inclusion criteria 54–77 .…”

Section: Resultsmentioning

confidence: 99%

Systematic review of randomized controlled trials of pharmacological interventions to reduce ischaemia-reperfusion injury in elective liver resection with vascular occlusion

Abu‐Amara

Gurusamy

Hori

et al. 2010

HPB

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PORTAL: Pilot study on the safety and tolerance of preoperative melatonin application in patients undergoing major liver resection: a double-blind randomized placebo-controlled trial

Cited by 21 publications

References 29 publications

The use of high‐dose melatonin in liver resection is safe: first clinical experience

The use of high‐dose melatonin in liver resection is safe: first clinical experience

Hepatoprotective actions of melatonin: Possible mediation by melatonin receptors

Systematic review of randomized controlled trials of pharmacological interventions to reduce ischaemia-reperfusion injury in elective liver resection with vascular occlusion

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