CTRI

Will individual participant data (IPD) be shared publicly (including data dictionaries)?

Response - NO

Opioids play a vital role in providing the analgesic component of anaesthesia during surgeries and also for postoperative pain management. They control pain by their action on multiple sites throughout the nervous system - including the brain, spinal cord, and peripheral nervous systems. Opioids are traditionally considered to be the ideal drug; however, they are associated with several undesirable side effects.

Opioid-sparing strategies can alleviate the undesirable effects of opioids by enabling the use of the lowest effective dose of opioids. Multimodal regimens involve the use of multiple medications with different mechanisms of action, as well as nonpharmacological interventions & techniques, to achieve more effective analgesia. The use of multiple analgesics thereby permits the use of lower & safer doses of each drug, which therefore minimises opioid related adverse effects

Among the drugs used in opioid-sparing strategies, ketamine is a non-selective N-methyl-D-aspartate (NMDA) receptor antagonist. It demonstrates excellent analgesic effect and decreases opioid usage even in sub-anaesthetic doses, with no unwanted side effects.

Dexmedetomidine is a highly selective Î±2-adrenergic receptor agonist providing conscious sedation, anxiolysis, analgesic and sympatholytic effects. It has been found that intravenous administration of dexmedetomidine during surgery results in reduced requirement of rescue analgesia, decreased postoperative pain, nausea & vomiting.

The goal of this study is to compare the effect of Low-dose Ketamine and Dexmedetomidine in terms of effective intraoperative opioid requirement, in patients undergoing laparoscopic surgeries.

After having met inclusion and exclusion criteria and having obtained informed consent, the eligible patients will be randomly assigned to the Low-dose Ketamine and Dexmedetomidine groups using a systematic random allocation method.

For this purpose, the first patient will be randomly assigned to one group using coin tossing and then, the next patient would be assigned to the other group. This action would be repeated until the sample size was reached. The allocations would remain

concealed to the patients.

Group K: Patients will be administered an intravenous bolus of Ketamine 0.2mg/kg followed by 0.2mg/kg/hr of Ketamine as an intravenous infusion.

Group D: Patients will be administered an intravenous bolus of Dexmedetomidine 1mcg/kg followed by 0.4mcg/kg/hr as an intravenous infusion.

A detailed Pre-Anaesthetic Evaluation will be done, one day prior to surgery. Both the group patients will be advised for NBM for 8 hours.

An 18G cannula would be secured & fluids at 5mL/kg/hr will be given to all patients in pre-operative room.

After shifting the patients to the operation theatre, all standard monitors will be connected. They will be Premedicated with Inj. Glycopyrrolate 0.005 mg/kg iv, Inj. Midazolam 0.05 mg/kg iv, Inj. Fentanyl 2mcg/kg iv and preoxygenated for 3 minutes.

Both the groups will be induced with Inj. Propofol 2mg/kg iv, Inj. Scoline 2 mg/kg iv. Upon confirming adequate muscle relaxation, an appropriate size endotracheal tube will be inserted, and the patient will be mechanically ventilated. Both groups will receive Isoflurane, along with Nitrous oxide, oxygen, Vecuronium, and controlled ventilation with a tidal volume of 6â€“8 ml/kg, and the respiratory rate will be adjusted to achieve normocapnia.

5 minutes after creation of pneumoperitoneum, Patients under Group K will receive intravenous bolus of Ketamine 0.2 mg/kg followed by 0.2 mg/kg/hr Ketamine as intravenous infusion, till the end of surgery. Patients under Group D will receive intravenous bolus of Dexmedetomidine 1mcg/kg followed by 0.4mcg/kg/hr as intravenous infusion.

During surgery, intraoperative haemodynamics including heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial blood pressure (MAP) will be recorded at 5 minutes, 10 minutes, 20 minutes, and every 30 minutes until the end of the surgery. If there were any signs of inadequate analgesia, such as an increase in MAP and HR >20% from pre-induction values, additional intraoperative Inj. Fentanyl 0.5mcg/kg would be administered to both groups.

The study drugs would be stopped at the end of pneumoperitoneum.

At the end of the procedure, Vecuronium, Nitrous oxide and Isoflurane will be discontinued. The patientsâ€™ neuromuscular blockade will be reversed with Inj. Neostigmine 0.05 mg/kg iv and Inj. Atropine 0.008 mg/kg iv. When extubation criteria is met, the endotracheal tube will be removed.

The patients will be subsequently transferred to the postanaesthesia care unit (PACU) where an initial assessment of their vital signs (HR, SBP, DBP and MAP) and the VAS will be performed, followed by repeat assessments every hour. After discharge from the PACU, the patientsâ€™ vital signs and pain will be assessed every 6 hours for 12 hours.

A standard postoperative analgesia regimen of 1g intravenous infusion of Paracetamol every 6 hours will be given during the first 24 hours to each patient. Furthermore, boluses of Inj. Fentanyl 0.5mcg/kg iv will be given when the VAS is â‰¥4 or for significant patient complaints of pain between the assessment intervals in both groups.

The primary outcome will be total Fentanyl requirement in intraoperative period and hemodynamic stability. Secondary outcomes will be Fentanyl requirement in postoperative period and postoperative nausea & vomiting.