Melatonin premedication and the induction dose of propofol

Melatonin (N-acetyl-5-methoxytryptamine) is the main indolamine secreted by the pineal gland. Many studies showed that premedication with melatonin is associated with preoperative anxiolysis and sedation without impairment of cognitive and psychomotor skills and without prolonging recovery. We hypothesized that melatonin decreases the amount of propofol required to produce an adequate depth of hypnosis at induction time.

After approval from the research committee of the anaesthesia department, informed written consent was taken from 45 adult patients undergoing different surgical procedures. They were allocated randomly into three groups according to the premedication. At 100 min preoperatively, premedication was given in the form of oral melatonin 3 mg (M3 group), oral melatonin 5 mg (M5 group) or no premedication (P group). After preoxygenation an anaesthesiologist who was blinded to the premedication injected propofol 10 mg over 5 s every 15 s until the bispectral index (BIS) score fell to 45. The total dose of propofol required to achieve a BIS score of 45 was recorded. Response to verbal commands and eyelash reflex was evaluated and correlated to the BIS score and propofol dosage. When a BIS score of 45 was reached, tracheal intubation was accomplished after administration of a narcotic and muscle relaxant.

The mean (standard devitation (SD)) induction dose of propofol producing a BIS score of 45 was 134 (25) mg in the placebo group vs. 115 (19.5) and 114 (20.9) mg in the M3 and M5 groups, respectively (P < 0.05). The propofol dose required to achieve loss of eyelash reflex and loss of response to verbal commands was more in the placebo group. Anxiety score as assessed by visual analogue scale (VAS) scored more in the placebo group than both melatonin groups. Time spent in the recovery room did not differ between the three groups.

Melatonin premedication, in an oral dose of either 3 or 5 mg, reduced the required dose of propofol to achieve a BIS score of 45, reflecting a sufficient level of hypnosis for tracheal intubation without prolongation of postoperative recovery room stay.