Melatonin reduces cardiac morbidity and markers of myocardial ischemia after elective abdominal aortic aneurism repair: a randomized, placebo-controlled, clinical trial.

The aim was to examine the effect of perioperative melatonin treatment on clinical cardiac morbidity and markers of myocardial ischemia in patients undergoing elective surgery for abdominal aortic aneurism. Reperfusion injury results in increased cardiac morbidity in patients undergoing surgery for abdominal aortic aneurisms (AAA). A randomized, placebo-controlled, clinical trial including patients undergoing surgery for AAA was performed. The patients received by infusion over a 2-hr period either, 50 mg melatonin or placebo intra-operatively, and 10 mg melatonin or placebo orally, the first three nights after surgery. Postoperative cardiac morbidity was registered, and blood samples for analysis of troponin-I (TpI) were collected preoperatively, and at 5 min, 6, 24, 48, 72, and 96 hr after clamp removal/recirculation of the first leg. Continuous measurement of ST-segment depression was performed by Holter monitoring. A total of 26 patients received melatonin, while 24 received placebo. A significant reduction in cardiac morbidity was seen in the melatonin-treated patients compared with those given placebo [4% versus 29% (P = 0.02)]. Five patients (19%) who received melatonin had increased TpI levels in the postoperative period compared with 12 patients (50%) who were given placebo (P = 0.036). The median number of ST-segment deviations was less in the melatonin-treated patients compared with the placebo group [median 1 (range 0-4) versus 6 (range 0-13) (P = 0.01)], but no differences were found in the duration of ST-segment deviations. Melatonin treatment in the perioperative period decreased clinical cardiac morbidity as well as the occurrence of myocardial ischemia after abdominal aortic aneurism repair.

Storage-induced increase in biomarkers of oxidative stress and inflammation in red blood cell components.

BACKGROUND: Transfusion of blood components may increase the risk of complications in relation to surgery. During storage, red blood cells (RBCs) undergo structural and functional changes that may reduce function and viability after transfusion. The aim of the study was to evaluate the quality of buffy-coat reduced red cells in SAG-M additive solution, by assessing biomarkers of oxidative and inflammatory stress during a storage period of 35 days. STUDY DESIGN AND METHODS: Ten units of RBCs were stored for 35 days. Samples were collected from the units at storage days 1, 3, 7, 14, 21, 28 and 35, respectively. The samples were analysed for various biomarkers expressing the oxidative stress and inflammation, including malondialdehyde (MDA), α-tocopherol (AT), dehydroascorbic acid (DHA), ascorbate (ASC), YKL-40 and interleukin-6 (IL-6). RESULTS: The levels ofMDA, ASC, DHA, IL-6 and YKL-40 changed significantly during the storage period (p < 0.001, p < 0.001, p < 0.001, p = 0.004 and p < 0.001 respectively). A significant change in AT levels could not be shown (p = 0.087). CONCLUSIONS: RBCs displayed significant changes in all measured indices of oxidative and inflammatory stress during a storage period of 35 days except for AT. The data suggest a possible rationale behind the observation that aging blood products may increase the risk of complications following surgery and blood transfusion.

Oxidative stress in relation to surgery: is there a role for the antioxidant melatonin?

During and after surgical procedures, there is a well defined physiological stress response that involves activation of inflammatory, endocrine, metabolic, and immunological mediators. Oxidative stress, which is defined to be a situation where the production of reactive oxygen/nitrogen species exceeds the mechanisms required to detoxify them, is believed to be an integrated part of the surgical stress response. Oxidative stress per se may be associated with complications such as myocardial injury, sepsis, pulmonary edema, kidney and liver failure, and increased mortality. Melatonin is a potent antioxidant and in many studies melatonin has been shown to be more effective than some "classical" antioxidants (e.g., vitamins E and C) in protecting against oxidative/nitrosative stress. There are numerous experimental studies in which the antioxidant properties of melatonin have been proven. In preliminary studies in newborns with asphyxia, sepsis, or respiratory distress syndrome, melatonin has proven to be a highly potent antioxidant. This review summarizes the results of animal and human studies wherein melatonin was shown to modulate oxidative stress; this discussion emphasizes the stress response related to surgery.

The effect of melatonin on sleep quality after laparoscopic cholecystectomy: a randomized, placebo-controlled trial.

BACKGROUND: In this study, we investigated whether melatonin administration could improve postoperative subjective sleep quality and reduce discomfort. METHODS: One hundred twenty-one patients scheduled for elective ambulatory laparoscopic cholecystectomy were randomized to oral 5 mg melatonin (n = 60) or placebo (n = 61) for 3 nights after surgery. Subjective sleep quality, sleep duration, sleep timing, and subjective discomfort (fatigue, general well-being, and pain) were measured. RESULTS: Sleep latency was significantly reduced in the melatonin group (mean [sd] 14 min [18]) compared with placebo (28 min [41]) on the first postoperative night (P = 0.015). The rest of the measured outcome variables did not differ between groups. CONCLUSIONS: Melatonin did not improve subjective sleep quality or discomfort compared with placebo after laparoscopic cholecystectomy.

Utility of melatonin to treat surgical stress after major vascular surgery--a safety study.

Surgery for abdominal aortic aneurysm is associated with elevated oxidative stress. As an antioxidant in animal and human studies, melatonin has the potential of ameliorating some of this oxidative stress, but melatonin has never been administered to adults during surgery for the purpose of reducing oxidative damage. The aim of this pilot study was to evaluate the safety of various doses of melatonin administered during or after surgery and to monitor the changes in biomarkers of oxidative stress and inflammation during the pre-, intra-, and postoperative period. Six patients undergoing aortic surgery received 10 (n = 2), 30 (n = 2) or 60 (n = 2) mg melatonin intravenously in the intraoperative phase and 10 mg orally for three nights after surgery. Patients were monitored for hemodynamic parameters during and after surgery. Any unexpected events during the hospitalization were registered. Blood samples were collected preoperatively and at 5 min, 6 hr and 24 hr after clamp removal or after re-circulation of the first leg and the samples were analyzed for malondialdehyde (MDA), ascorbic acid (AA), dehydroascorbic acid (DHA), and interleukin-6 (IL-6). Troponin I (TpI) and C-reactive protein (CRP) were also measured for 4 days after surgery. Melatonin administration did not change hemodynamic parameters (mean arterial pressure or pulse rate) during surgery (P = 0.499 and 0.149, respectively), but oxidative stress parameters (MDA and AA) decreased significantly (P = 0.014 and 0.001, respectively). There was a significant increase in the inflammatory parameters (IL-6 and CRP) (P = 0.001 and 0.001, respectively) and an increase in TpI (P = 0.009) as a consequence of surgery. These were not influenced by melatonin treatment. Treatment of patients undergoing major aortic surgery with melatonin intravenously up to 60 mg in the intraoperative phase was safe and without complications. Melatonin may decrease oxidative damage resulting from surgery, but randomized clinical trials are required before definitive conclusions can be drawn regarding the clinical benefit of melatonin in surgical situations.

Absence of analgesic effect of intravenous melatonin administration during daytime after laparoscopic cholecystectomy: a randomized trial.

STUDY OBJECTIVE: To investigate whether melatonin administered intraoperatively reduced pain following laparoscopic cholecystectomy. DESIGN: Randomized, placebo-controlled, double-blinded study. SETTING: Two surgical departments in Copenhagen. PATIENTS: 44 women between 18 and 70 years of age, who were surgical candidates for laparoscopic cholecystectomy. INTERVENTIONS: Patients were anesthetized by a standard protocol and received a standard multimodal postoperative analgesic regimen. Patients undergoing surgery were admitted on the day of surgery and were discharged the day after surgery. Ten mg of intravenous (IV) melatonin or placebo were administered at the time of surgical incision. MEASUREMENTS: Pain was assessed by a set of questionnaires documenting "pain at rest" using a visual analog scale (VAS). The use of rescue medication was recorded. Sleep quality and general well-being were measured on separate VAS scales. Sleepiness was assessed by the Karolinska Sleepiness Scale. MAIN RESULTS: Forty-four patients were included and randomized to the study. Three patients did not complete the study. No differences in VAS pain scores, sleep quality, general well-being, or sleepiness were found between the two groups in the postoperative period. The use of postoperative rescue medication did not differ between the groups. CONCLUSIONS: The use of 10mg of IV melatonin administered during laparoscopic cholecystectomy did not affect postoperative pain or use of analgesic medication.

Oxidative stress response after laparoscopic versus conventional sigmoid resection: a randomized, double-blind clinical trial.

Surgery is accompanied by a surgical stress response, which results in increased morbidity and mortality. Oxidative stress is a part of the surgical stress response. Minimally invasive laparoscopic surgery may result in reduced oxidative stress compared with open surgery. Nineteen patients scheduled for sigmoid resection were randomly allocated to open or laparoscopic sigmoid resection in a double-blind, prospective clinical trial. Three biochemical markers of oxidative stress (malondialdehyde, ascorbic acid, and dehydroascorbic acid) were measured at 6 different time points (preoperatively, 1 h, 6 h, 24 h, 48 h, and 72 h postoperatively). There were no statistical significant differences between laparoscopic and open surgery for any of the 3 oxidative stress parameters. Malondialdehyde was reduced 1 hour postoperatively (P<0.001) for all 19 patients. There was a significant drop in ascorbic acid at 1 hour and 6 hours after the first abdominal incision (P=0.002) for all 19 patients. Laparoscopic surgery was not found to be associated with reduced oxidative stress.

[Small-bowel ileus caused by a gold filling]. / Tyndtarmsileus forårsaget af guldtand.

A 68-years-old man was admitted to hospital with signs of intestinal obstruction. Computed tomography showed a foreign body, and the patient underwent laparotomy which revealed a gold filling in the jejunum. To our knowledge, this is the first documented case of a gold filling causing intestinal obstruction.

[Renal cell carcinoma with metachronous metastases to the gallbladder after two years]. / Renalcellekarcinom med metakron metastase til galdeblaeren efter to år.

An 80-year-old man was admitted to hospital because of haematuria. Intravenous urography verified a right-sided kidney tumour. Histological examination showed renal cell carcinoma of the clear cell type. Renal cell carcinoma is known to metastasize many years after primary tumour detection and surgical treatment. Ultrasound examination after 1 year revealed a polypoid gallbladder mass. Immunohistochemical examination confirmed the metastasis diagnosis originating from the primary kidney tumour.

[Melatonin against surgical stress]. / Melatonin mod kirurgisk stress.

Surgery is associated with oxidative stress. Oxidative stress is correlated with postoperative myocardial ischaemia. It has been shown that the endogenous hormone melatonin has antioxidant effects. A potential benefit of melatonin has been proven in experimental studies as well as in neonates. Melatonin has not been used in adult patients with acute oxidative stress. A potential beneficial effect of melatonin in patients after surgery is possible and should be investigated in the future.