To compare the efficacy of oral Melatonin, Gabapentine, Clonidine and Placebo in attenuating hemodynamic response during laryngoscopy and intubation in patients undergoing surgery under General Anaesthesia , A four armed Randomized Double blinded clinical trial.

•        After obtaining written informed consent, the patients will be divided into four groups (20 patients each) with computer generated table of random numbers in opaque sealed envelops.

•        All patients will be subjected to routine pre-anesthetic checkup in the preoperative period. All routine investigations as appropriate for the surgeries will be obtained and optimised.

•        Group M will receive oral melatonin 6mg, Group C will receive oral clonidine100mcg,Group G 100mg gabapentin, Group P a multivitamin tablet 120 minutes prior to surgery with sips of water. Tablets will be removed from envelope by other  post graduate student and handed over to anesthesiologist for administration to the patient.

•        The post graduate student will not be involved in the trial.  Two anesthesiologists will be  involved in the study—one will administer the drug while the other will conduct the case and record the data.

•        All patients will be kept undisturbed, wear black blindfolds and the rooms will be kept calm and silent. Patients will be shifted to the operation theater ten minutes prior to surgery.

•        To ensure double blinding, both the anesthesiologists and the patients will be kept unaware of group allocation.

•        Before shifting patient to oT baseline heart rate and blood pressure will be recorded.

•      In the operating room, standard monitoring (heart rate, non-invasive measurement of systolic, diastolic and mean blood pressure oxygen saturation, electrocardiography) will be applied, and recorded.

•        Intravenous line will be secured with 18 G cannula and infusion of injection Ringer Lactate commenced at the rate of 10 ml/kg/hr.•        After three minutes of pre-oxygenation with 100% oxygen, inj.Emeset 0.15mg/kg,

•        Inj.glycopyrrolate 0.01mg/kg , inj.fentanyl 2 μg/kg will be administered to all patients.

•        Patients will be induced with Inj.propofol 2mg/kg given slowly over 1 minute till there was loss of response to verbal commands ,loss of eye lash reflex or transient apnea .With this dose of propofol required for induction will be determined.

•        After ensuring mask ventilation all patients will be given  Inj. vecuronium 0.1 mg/kg intravenously to facilitate endotracheal intubation.

       Anesthesia will be maintained with isoflurane 1%–1.5% in oxygen Nâ‚‚O mixture (1:1), initially with mechanical ventilation with tidal volume of 6–8 mL/kg, respiratory rate of 12–

•        14 per minute maintaining end�’tidal carbon dioxide (EtCO2) between 30 and 35 mmHg and to maintain HR and BP within 20% of the baseline values.•      Heart rate (HR) and mean arterial pressures (MAPs) will be recorded before premedication, before induction of anesthesia, immediately after induction and then at 1,2,3,4,5and 10 minutes after intubation.

•    An increase in HR >20% from baseline, if associated with hypotension, will be treated with 250mL intravenous Ringer’s lactate bolus initially. If increase in HR did not respond or was associated with increase in MAP >20% from baseline, isoflurane concentration will be increased to 1.5%–2%.

•        If the hemodynamic response would not controlled, incremental boluses of fentanyl 0.5 μg/kg will be given to a maximum of 1 μg/kg in one hour.

•        Reduction in MAP <20% from baseline value was taken as hypotension and will be treated with 250 mL intravenous fluid bolus; if not responding, incremental doses of phenylephrine 50 μg will be given.

•        Isoflurane concentration will be reduced to 0.5% at beginning of skin suturing and discontinued at completion of suturing.

•        Total duration of the surgery and  average percentage of the dial setting on the Tec 7 vaporizer will be noted. Total amount of the isoflurane required is calculated using the formula

EISENKRAFT FORMULA:-

CONSUMPTION=3×FGF×Set concentration.

•        Neuromuscular blockade will then reversed and extubation will be done when patient will be opening eyes on command and generating adequate tidal volume with return of protective airway reflexes.

 Expected duration of the subject participation: 24 hours