Direct laryngoscopy and endotracheal intubation during general anesthesia acts as a powerful noxious stimulus which causes stimulation of sympathetic nervous system. This leads to various responses in various physiological systems of the body such as tachycardia, hypertension, arrythmia, bronchospasm, increased intracranial pressure, elevation in intraocular pressure, etc. [1,2] The hemodynamic changes are transient and can cause serious complications in patients with cardiovascular, cerebrovascular, and endocrine disorders. These changes also disrupt the balance between oxygen supply and demand of myocardium thereby causing significant myocardial ischemia in patients with coronary artery disease [3,4]. Some researchers have reported an increase of 35–45 % in both systolic and diastolic blood pressure values in comparison to control levels. Also, an increase in heart rate of 20%–60 % is observed after endotracheal intubation [[5], [6], [7]]. These hemodynamic changes usually peak at one to 2 min following laryngoscopy and tracheal intubation, and persists for 5–10 min [[6], [7], [8]].

A variety of interventions have been evaluated in the past for smoother airway evaluation and for attenuating the hemodynamic response of direct laryngoscopy and endotracheal intubation. These include use of intravenous lignocaine, beta blockers, benzodiazepines, magnesium sulfate, propacetamol, pregabalin, nitroglycerine, dexmedetomidine, barbiturates, calcium channel blockers, sodium nitroprusside, and superior laryngeal nerve block [2,3,9,10]. The use of these drugs has several associated adverse effects such as tachyarrhythmia, bradyarrhythmia, respiratory depression, hypotension, rebound hypertension, etc. [2] Therefore, a safer drug is needed for effective suppression of hemodynamic changes during general anesthesia.

Melatonin is a natural substance produced mainly in the pineal gland of all mammals and vertebrates. Its secretion is high during night and low during day. Small amounts of Melatonin when used several hours before sleep shift the circadian clock earlier according to the phase response curve for Melatonin in humans thereby promote earlier sleep onset and morning awakening. Melatonin is rapidly distributed and eliminated after intravenous administration. After oral administration, plasma concentration peaks after 60 min and is then eliminated [11,12]. Melatonin also acts as a high-capacity free radical scavenger within mitochondria. It exerts its hypnotic effects through the activation of the MT1 and MT2 Melatonin receptors. The central effects involve modulation of the GABA receptor activity thereby facilitating GABAergic transmission [12,13]. Melatonin has shown potent analgesic effects in a dose dependent manner in experimental studies. But the physiological mechanism behind its analgesic effect has not been clarified. Melatonin has a mild hypotensive effect. Melatonin may bind to specific Melatonin receptors in the blood vessels and interfere with the vascular response to catecholamines [[11], [12], [13]]. It may interfere with the peripheral and central autonomic system and cause a reduction in adrenergic outflow and catecholamine levels. Melatonin may induce relaxation of the arterial wall smooth muscle by increasing nitric oxide levels. Therefore, premedication with sublingual/oral Melatonin is associated with pre-operative anxiolysis and sedation without impairment of orientation, psychomotor skills, or impact on quality of recovery. Also, it attenuates the hemodynamic stress response to laryngoscopy and tracheal intubation [13,14].

Clonidine is a centrally acting antihypertensive agent available as tablets for oral administration in three dosage strengths: 0.1 mg, 0.2 mg and 0.3 mg. The 0.1 mg tablet is equivalent to 0.087 mg of the free base [15]. It is rapidly absorbed after oral administration and its bioavailability is nearly 100 %. Peak plasma concentration is reached within 60–90 min and maximal effects are observed 1–3 h after an oral dose. The elimination half-life is between 6 and 24 h (mean 12 h) and 50 % of the drug is metabolized in the liver into active metabolites while the rest is excreted unchanged by the kidney [15,16]. Major site of action for this sedative/hypnotic drug is locus ceruleus situated in the upper brainstem in the floor of the fourth ventricle. It hyperpolarizes the neurons of locus ceruleus via potassium channels. It produces a potent analgesic response involving both supraspinal and spinal sites. Clonidine produces hypotension and bradycardia due to inhibition of sympathetic outflow and potentiation of parasympathetic activity by acting on a-2 receptor present over tractus solitarius. Clonidine has various properties like sedation, anxiolysis, antisialogogue, potentiates the anesthetic action of the drugs and reduces their requirements during surgery and attenuation of stress response to noxious stimuli on tracheal intubation. It is used as a preanesthetic medication [4,17].

There are several factors which influence the outcome of study such as ambient temperature of operating room, anesthesiologist's expertise, difficult airway, morbid obesity, difficult mask ventilation, preoperative anxiety, young age group, and female gender.

However, there are very few studies in India about the role of oral Melatonin and oral Clonidine as premedication in achieving hemodynamic stability during intubation. Hence this study intended to evaluate and compare the role of oral Melatonin and oral Clonidine as premedication in terms of attenuation of hemodynamic response to direct laryngoscopy and endotracheal intubation, and their safety and efficacy in various patients of different ages, sex, and cultures at random as compared to control group.