A computer generated randomisation scheme is to be used to randomise patients into one of the 3 treatment regimens: racemic ketamine/K-group (0.5mg/kg bolus followed by 250µg/kg/hr infusion), dexmedetomidine/D-group (1µg/kg bolus followed by 0.5µg/kg/hr infusion) or the placebo/ P-group. Principal investigator/ anesthesia provider, patient and nursing staff will be blinded to the treatment assignment during the entire hospital stay. An opaque sealed- envelope method will be used for allocation of the patients to different groups.

A standard anesthesia induction and maintenance protocol will be followed. The sevoflurane vapourizer will be weighed prior to starting of induction and weight recorded in grams or volume consumed measured if available on ventilator. After shifting the patient to OT standard monitors like electrocardiograph, pulse oximeter and non-invasive blood pressure will be connected and an intravenous (IV) line will be established.

After preoxygenation for 2 min, anesthesia will be induced with fentanyl 2µg/kg, propofol 2-3 mg/kg and tracheal intubation will be facilitated with rocuronium 1mg/kg. Anesthesia will be maintained using oxygen-air mixture in 40:60 ratio with fresh gas flow @1.5L/min. Muscle relaxation will be maintained with rocuronium 0.25mg/kg bolus every 40 minute and analgesia with fentanyl 1µg/kg as and when required. A bispectral index (BIS. A 2000: Aspect medical system) will be used with target BIS between 40-50 by titration of sevoflurane. Additional monitors after intubation will consist of end tidal carbon dioxide (ETCO₂), invasive blood pressure/IBP, central venous pressure (CVP), anesthetic agent, airway pressure and nasopharyngeal temperature.

Once the patient is made prone the study drug (bolus) will be administered over 10 minutes using the syringe pump (TERUMO) with 10ml syringe (i.e. 60ml/hr for 10 min). Patients in low dose ketamine group will receive 0.5mg/kg bolus while those in dexmedetomidine group will receive 0.5µg/kg. For placebo group 0.9% normal saline will be used. Heart rate (HR), blood pressure (BP) and oxygen saturation will be noted during the start and end of bolus infusion. A constant infusion rate of 10ml/hr will be started prior to skin incision which would deliver at the rate of 0.5µg/kg/hr for dexmedetomidine and 250µg/kg/hr for ketamine by varying the drug concentration in a 50ml syringe. The study drug infusions will be prepared by an anaesthesiologist based on the weight of the patient pre-operatively with random drug selection who will be a co-investigator of the trial but not involved in the management of the patient. The prepared syringe will be labelled as “study drug” with serial number. BP will be targeted to keep within 20% of baseline values with hypotension defined as 20% drop from baseline value and hypertension defined as 20% rise from baseline value for more than 1 minute.

      Hypotension will be treated with:-

      1) Increase of intravenous fluid, and/or

      2) Bolus doses of phenylephrine 0.5µg/kg

      3) For non responsive cases intravenous infusion of vasopressor will be used.

       Hypertension will be treated with:-

      1)  Bolus dose of propofol 0.5mg/kg if BIS is more than 50.

      2) If BIS ranges between 40-50, then fentanyl bolus of 0.5µg/kg will be given. Intraoperatively, bradycardia was defined as HR < 60/min accompanied with hemodynamic instability or a HR <40/min with or without hemodynamic instability while tachycardia as a 20% increase from baseline in HR.

     Bradycardia will be treated with:-

1) 0.6mg atropine intravenous bolus and repeated as required.

2) For non responders dopamine (2-10 µg/kg infusion) or adrenaline (2-10µg/min infusion) may be used.

Number of episodes of bradycardia, hypotension and hypertension is noted. End tidal sevoflurane concentration will be decreased by 50% at start of skin closure and turned off after making the patient supine. The study drug infusion will be stopped at closure of muscle layer.
After turning the patient supine residual neuromuscular blockade will be reversed with neostigmine (50µg/kg) and glycopyrollate (8-10µg/kg). The patient will be extubated on meeting the extubation criteria and time is noted. Emergence agitation if any is noted and scored based on Riker sedation agitation scale (SAS).

HR, BP, ETCO₂ and SPO₂ are to be recorded at 0min, 5min, 15 min and every 15 min starting from prone positioning till end of skin closure. Apart from demographic data, hemodynamics, total dose of fentanyl, propofol, phenylephrine used, duration of surgery (from skin incision to skin closure), blood loss, recovery time (time from stopping of sevoflurane to time of extubation) will be noted.

The patient will be shifted to ICU where IV-patient controlled analgesia (IV-PCA) will be started (bolus dose of 1µg/kg of fentanyl, lockout interval of 10 minute with no basal infusion). Fentanyl consumption via IV-PCA will be evaluated for 24 hours after surgery. The pain will be quantified with a 100mm visual analog scale (VAS). Pain scores will be recorded at rest and with movement at 1, 6, 12 and 24 hr after surgery. Adverse events such as sedation, headache, nausea/vomiting and hallucination/dreams will be recorded. For moderate to severe nausea or vomiting 4mg ondansetron will be administered.

STUDY HYPOTHESIS:- We believe that using adjuvants like ketamine and dexmedetomidine in the intraoperative period in lumbar instrumentation surgery (which are painful procedures even in the post operative period due to major tissue handling/damage) decrease the post operative analgesic/narcotic requirements (primary aim) and also decreases intraoperative analgesic and/or anesthetic requirement leading to better recovery profile( secondary aim).