Comparison of the postoperative sleep quality with oral zolpidem versus oral melatonin in adult patients undergoing elective surgery under general anaesthesia: A randomized controlled trial

Study will be conducted after approval from the institutional ethical committee IEC and will be registered with Clinical Trial Registry India CTRI. A detailed pre anaesthetic checkup, detailed history, physical examination and baseline investigations as per clinical requirements will be performed. A written and informed voluntary consent will be obtained from the patient.

Quality assurance mechanism Recruitment of the subjects, sampling strategy, methods of data collection and subsequent data handling will be predefined. All the procedures to be performed will be standardized and training will be provided to reduce variability in outcome measurement.

Trial monitoring mechanism The rights and well being of subjects will be protected. The reported trial data will be accurate, complete and verifiable from source document. The conduct of the trial will be in compliance with the protocol, good clinical practice and with the applicable regulatory requirements. Trial recruitment and outcome measurement process will be kept uniform throughout the study.

Clinical equipoise Before randomly assigning patients to both the competing groups, investigator involved in both groups will be free of any treatment preferences and the subjects involved will not be devoid of any treatment care if needed.

A thorough pre anaesthetic examination will be performed prior to the procedure. A written informed voluntary consent will be obtained from the patient after carefully explaining the procedure including its benefits and risks in the patients own language. Patients will be kept nil per oral NPO for at least 8 hours for solid foods prior to surgery as per standard guidelines. All patients will be premedicated with tablet pantoprazole 40 mg on the night before surgery.

Randomization A computer generated unique randomization code will be generated and with the help of sealed envelope technique, patients will be randomized into two groups as follows

Group A Zolpidem group patients who will receive oral zolpidem 5 mg at 9 PM the night before surgery.

Group B Melatonin group patients who will receive oral melatonin 5 mg at 9 PM the night before surgery.

Allocation concealment The results of the allocation will be concealed and delivered in a sealed opaque envelope mentioning the code and the group number in the morning of the surgery.

Blinding The patient and the observer data collector will not know the premedication oral zolpidem or oral melatonin being given to the patient.

Sleep Quality Assessment The Richards Campbell Sleep Questionnaire which is a subjective measure for sleep quality will be administered by an independent observer in the preoperative period in the morning 6 AM of the surgery. At the same time, VAS scoring for assessment of anxiety will be performed using a 10 cm scale in which 0 signifies absence of anxiety and 10 signifies maximum anxiety.

After arrival in the operating room, an 18G or 20G peripheral intravenous IV catheter will be inserted. Standard monitoring will be applied including non invasive blood pressure NIBP, electrocardiograph ECG with heart rate HR, pulse oximetry SpO2 and temperature.

Induction of anesthesia will be performed using injection fentanyl 1 to 2 microgram per kg IV and injection propofol 2 to 2.5 mg per kg IV. Muscle paralysis will be achieved with non depolarizing muscle relaxant injection rocuronium 0.6 mg per kg IV followed by intermittent positive pressure ventilation with oxygen and sevoflurane and endotracheal intubation after 3 minutes.

Anesthesia shall be maintained with oxygen and sevoflurane along with top up doses of injection rocuronium. Intraoperative hemodynamics will be managed according to surgical procedure and blood loss. Trachea shall be extubated as per standard protocol using injection neostigmine 0.05 mg per kg IV and injection glycopyrrolate 0.01 mg per kg IV.

Intraoperative adverse reactions including hypertension, hypotension, bradycardia and tachycardia will be recorded. Postoperative pain management will be provided with injection diclofenac sodium 75 mg every 8 hours and injection paracetamol 1 g every 8 hours to maintain a VAS score of 4 or less. Rescue analgesia shall be provided with injection tramadol 50 mg.

Patients shall receive another dose of tablet melatonin or tablet zolpidem as per the allocated group at 9 PM on the night following surgery POD 0. Sleep quality will be re evaluated in the first postoperative night POD 0 using polysomnography performed from 10 PM to 6 AM and the Richards Campbell Sleep Questionnaire RCSQ and VAS A scoring for assessment of anxiety on the next morning POD 1.

Polysomnographic monitoring will be performed by an independent observer trained to use the PSG machine. Total sleep time TST which is the total amount of time a person actually spends asleep will be noted. It excludes time spent awake and will be calculated as time spent in NREM plus REM. Sleep efficiency SE defined as the percentage of time the person is actually asleep that is time from lights off to first awakening will be recorded. It will be calculated as total sleep time divided by total time in bed multiplied by 100. Arousal index AI which is the number of arousals per hour of sleep will be noted. An arousal will be defined as a brief shift from deeper to lighter stages of sleep or wakefulness lasting at least 3 seconds. It will be calculated as total number of arousals divided by total sleep time in hours.