Comparison of oral melatonin and clonidine as premedication on isoflurane consumption and postoperative analgesia in patients undergoing general anaesthesia– A randomised controlled trial

Although there are significant improvements in peri-operative pain management, fear and anxiety are still the major hurdles that prevent several patients from undergoing surgical interventions. There are many drugs used orally to reduce anxiety preoperatively like midazolam, clonidine, melatonin, gabapentin, etc .  Midazolam is known to cause postoperative cognitive and pschycomotor impairment (1). Gabapentin causes nausea, vomiting and higher levels of sedation(2). Hence a drug without these side effects is preferred.

Melatonin is a hormone secreted by the pineal gland(3). Melatonin exerts an effect on sleep by amplifying day/night differences in alertness and sleep quality. Melatonin has several functions that make it an attractive option for premedication including the regulation of circadian rhythm sedative, analgesic, anti inflammatory and antioxidant effects(4). Melatonin interacts with  multiple receptor sites including opioidergic, benzodiazepinergic, muscarinic, nicotinic, serotonergic, α1, α2 adrenergic and most importantly MT1/MT2 melatonergic receptors present in the dorsal horn of the spinal cord as well  in the central nervous system(5).

Clonidine is an α-2 adrenoreceptor agonist which produces analgesia by its central action(6,7). It is rapidly absorbed after oral administration. It reaches a peak plasma concentration within 60-90mins. Clonidine stimulates alpha 2 adrenergic neurons in the medullary vasomotor centre causing a decrease in the sympathetic nervous system outflow from the Central nervous system to the peripheral tissues and central activation of non adrenergic imidazoline preferring receptors. Decreased sympathetic activity is manifested as peripheral vasodilatation, hypotension, decrease in heart rate and cardiac output.

Some studies have proved that melatonin is an effective alternative to clonidine used in premedication especially in patients with low blood pressure. But they have used melatonin 5mg and clonidine 150µg (8). Some studies have shown that melatonin has similar efficacy compared to clonidine in reducing postoperative pain and narcotic consumption. Some studies have used 6mg of melatonin and 200 µg of clonidine (9) . There are some studies which have inferred that clonidine reduces the requirement of intraoperative isoflurane concentration (10) , but there are very few studies which have compared the anaesthetic consumption when melatonin or clonidine is given as premedication.

Hence we have undertaken this study to compare the effects of oral melatonin 3mg and clonidine 100µg as premedication on isoflurane consumption and postoperative analgesia in patients undergoing GA.