Comparison of postoperative sleep quality with dexmedetomidine versus ketamine in obese patients undergoing elective gynaecological surgery under central neuraxial block : A randomized controlled trial

The study will be conducted after approval from the Institutional Ethics Committee and will be registered with Clinical Trials Registry India. Patients fulfilling the inclusion criteria will be recruited for the study. A detailed pre-anaesthetic check-up and investigations will be done for all patients. The spine will be examined for any evidence of vertebral column anomalies, skin infection, bony landmarks and previous operations. A written informed voluntary consent will be obtained for anaesthesia, surgery and participation in the study after carefully explaining the procedure, including its benefits and risks in the patient’s own language. Patients will be randomised to one of the two groups in the operating room prior to giving anaesthesia and results of the allocation will be concealed and delivered in a sealed opaque envelope mentioning the code and the group number. The envelope will be opened and the test drugs will be prepared based on the assigned group by an anaesthesiologist who will be blinded to the study group.

Patients will be kept nil per oral for at least 8 hours for solid foods prior to surgery as per standard guidelines. All patients will be pre medicated with tablet alprazolam 0.25 mg and tablet pantoprazole 40 mg night before surgery. Richards-Campbell Sleep Questionnaire which is a subjective measure for sleep quality will be administered by an independent observer in the morning of surgery. It consists of five questions, each scored from 0 to 100, with 0 being worst and 100 the best. The five questions consist of the following , sleep depth ( whether it was light sleep or deep sleep ), sleep latency ( time taken to fall asleep), awakenings ( number of times the patient woke up at night), returning to sleep ( how long after waking up did the patient go back to sleep) and overall sleep quality as assessed by the patient. After arrival in the operating room, an 18G or 20G peripheral intravenous 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.

Central neuraxial anaesthesia will be administered by combined spinal epidural (CSE) technique which will be performed by an experienced anaesthesiologist.The procedure will be carried out under all aseptic precautions with the patient sitting on the operating table with buttocks at the edge. A CSE kit (B Braun Espocan®) will be used for the procedure.Local anaesthetic (1ml of 2 percent lignocaine) will be administered at the desired vertebral interspace for local analgesia. The 18-gauge Tuohy needle will be introduced and a loss of resistance to air will be used to confirm the epidural space. Dural puncture will be performed with the 27-gauge Whitacre spinal needle by needle through needle technique. An appropriate dose of 0.5 percent hyperbaric inj. bupivacaine plus inj. fentanyl 25 mcg  will be administered intrathecally after the free flow of cerebrospinal fluid is confirmed. The 20 gauge epidural catheter will be inserted through the epidural needle , 3-4 cm into the epidural space. The Tuohy needle will be removed, the catheter will be firmly fixed to the skin and covered with antiseptic dressing. The patient will be made supine, dermatomal level will be checked and the patient will be handed over for surgery. Subsequent anaesthesia and analgesia will be maintained by administering aliquots of inj. bupivacaine 0.5 percent through the epidural catheter as deemed clinically appropriate. Inj. dexmedetomidine for infusion (5µg/mL) will be prepared using 2 vials (1 mL each), each containing 100 µg of the drug, and diluting it with 38 mL of 0.9 percent normal saline solution in a 50 mL syringe. Similarly, inj. ketamine for infusion (3 mg/mL) will be prepared by mixing 3mL (50 mg/mL) with 47 mL of 0.9 percent normal saline solution in a 50 mL syringe. Patients in group D will be administered a loading dose of inj. dexmedetomidine 0.5 mcg/Kg IV followed by a maintenance dose of  0.2-0.7 mcg/Kg/h using an infusion pump (Helmier mquip SP 12). Patients in group K will be administered a loading dose of inj. Ketamine 0.3mg/Kg IV followed by a maintenance dose of  0.2-0.5 mg/Kg/h using an infusion pump (Helmier mquip SP 12).

Sedation will be maintained according to Ramsay sedation scale less than equal to 3 (Ramsay sedation scale: 1-patient anxious, agitated, or restless, 2-patient cooperative, oriented, and tranquil alert, 3-patient responds to commands, 4- asleep, but with brisk response to light glabellar tap or loud auditory stimulus, 5- asleep, sluggish response to light glabellar tap or loud auditory stimulus and 6-asleep, no response to glabellar tap or loud auditory stimulus). The occurrence of intraoperative hemodynamic events, including bradycardia, tachycardia, hypertension, hypotension and respiratory depression will be recorded by an independent observer. Bradycardia will be defined as HR less than 60 bpm; tachycardia as HR more than 100 bpm; hypertension as systolic blood pressure (SBP) more than equal to 160 mmHg or more than 20 percent increase above baseline; hypotension as SBP less than equal to 90mmHg or decrease of more than 20 percent of baseline, and desaturation as SpO2less than 94 percent  . These parameters will be treated appropriately as per standard clinical guidelines. Post operative nausea and vomiting will also be observed 1 hour, 3 hour, 6 hour, 12 hour and 24 hour after the surgery where 0 -no nausea and vomiting, 1 - nausea alone, 2 -vomiting once in 30 min or more, 3 - persistent nausea or vomiting two or more times within a 30 min period . Patients who experience vomiting will receive intravenous inj. ondansetron 0.1mg/Kg repeated 8 hourly if needed. Analgesia will be maintained in the postoperative period with infusion of 0.125 percent inj. bupivacaine at 4-5mL/h through an elastomeric pump (Elaspump 275 mL) to maintain a VAS score less than equal to 4 . The Visual Analogue Scale (VAS), represented by a straight horizontal line 10 cm (100 mm) in length, anchored by two verbal descriptors at each end, representing extremes of the symptom, will be used to assess postoperative pain at 1hour, 3 hour, 6 hour, 12 hour and 24 hour after the surgery. Inj. diclofenac sodium 1.5 mg/Kg (max 75 mg) will be administered intravenously for rescue analgesia, repeated 8 hourly if needed in the first 24 hour postoperatively and will be noted.

Polysomnography (PSG) will be performed on the first night after surgery from 9:00 PM to 6:00 AM by an independent observer trained to use the PSG machine using an ambulatory polysomnograph (OxymedTM Sleep Fairy SF-A40S). The polysomnogram will include six-channel electroencephalograms (F3, F4, C3, C4, O1, O2), two-channel electrooculograms and two-channel chin electromyogram. Total sleep time (TST) which is the total amount of time a person actually spends asleep will be recorded. It excludes time spent awake and will be calculated as TST - time spent in NREM plus REM. Sleep efficiency Index (SEI) defined as the percentage of time the person is actually asleep that is time from lights off to first awakening will be recorded. Arousal index (AI) which is the number of arousals per hour of sleep will be recorded. An arousal will be defined as a brief shift from deeper to lighter stages of sleep or wakefulness, lasting at least 3 seconds. Richards-Campbell Sleep Questionnaire will be administered again in the morning following the first night after surgery.