To assess the effect of perioperative Dexmedetomidine infusion on Interleukin 6 and cortisol level in patients undergoing general anesthesia for total abdominal hysterectomy

Following the departmental research committee approval and informed patient's consent, 52 patients, undergoing abdominal hysterectomy in Suez Canal University Hospital, will be randomly assigned to one of the two groups (Dexmedetomidine and Placebo) using a table of random numbers.

Patients will be fasting for 6 - 8 hours. All patients will receive oral Midazolam (7.5 mg), and oral Ranitidine (150mg) administered 90 min before arrival in the operating room with a sip of water.

All patients will receive before induction, normal saline 10 ml/kg body weight over 10-15 minutes. Subsequently, intravenous fluid administration will be done according to the need of each patient.

All operations will start between 08:30 am and 09:30 am, to minimize variations in cortisol level.

All patients will receive the Drug of study 10 minutes before induction of anesthesia till the start of wound closure in the form of:

Group (D): Dexmedetomidine 1 mcg/kg over 10 min followed by 0.4 mcg/kg/hr. Group (C): Normal saline prepared in a syringe with the same volume as Dexmedetomidine to assure blinding.

Doses will be calculated, diluted in 50 ml of normal saline and given intravenously by a syringe pump over 10 minutes initially and then over 1 hour till the start of wound closure.

All drugs of the study will be prepared by an independent anesthesiologist who will not share in the study and then selected and given by another one blinded for the content of each syringe.

Airway devices, anesthesia machine, ventilator, flowmeters and monitors will be checked promptly.

Another wide-bore I.V cannula will be inserted in case of blood transfusion.

Monitoring equipment's (Datex-Ohmeda™) will be attached to the patient including 3-leads ECG, non-invasive arterial blood pressure, pulse oximeter and capnograph after tracheal intubation.

The depth of anesthesia will be monitored with Entropy device. The Entropy electrodes will be placed on the forehead and on the lateral angle of orbit and connected to (Datex-Ohmeda™). The target Entropy range will be 40-60 for surgical anesthesia.

Induction of anesthesia will be performed by Propofol 2 mg/kg followed by cis-atracurium 0.15 mg/kg and fentanyl 1 mcg/kg given intravenously after pre-oxygenation with 100% oxygen for at least 3 minutes.

Patients will be manually ventilated with 100% oxygen till intubation after 2 min and with Entropy value of 60 to 40 by Macintosh laryngoscope and appropriate size endotracheal tube.

Maintenance of anesthesia will be carried out by isoflurane varying its end tidal concentration to keep Entropy in the range of 55 to 40 with Air:Oxygen mixture 0.3 fraction of oxygen and flow rate of 2 liters/minute in completely closed circuit.

Cis-atracurium 0.03 mg/kg guided by neuromuscular monitor Train Of Four (TOF) will be used for muscle relaxation.

Hemodynamics (mean arterial blood pressure and heart rate) will be maintained within 25 % of baseline measures.

Any increase of MAP or HR more than 25% of baseline measures on two consecutive readings within 2-3 min will be managed by I.V bolus of Fentanyl 0.5 mcg/kg and any decrease of MAP or HR less than 25 % on two consecutive readings within 2-3 min will be managed by I.V bolus of ephedrine 5 mg or atropine 0.5 mg respectively.

The infusion of study medication will be discontinued if the hypotension persisted > 5 minutes after these interventions upon return of the MAP or HR to within 25% of the baseline value, the study medication infusion will be resumed at 50% of the initial infusion rate and then gradually increased to the initial infusion rate.

The infusion of study medication will be discontinued at the start of wound closure. Upon completion of wound closure, isoflurane will be discontinued and the flow rate will be increased to 5 L/min of 100% Oxygen and residual neuromuscular block will be reversed with neostigmine, 0.05 mg/kg IV, and atropine 0.25 mg/kg IV. The trachea will be extubated when the patient is fully awake. Transfer to the recovery room will be done when the patient scored 7 and above using the modified Aldrete scoring system.

On emergence from anesthesia and immediately in post anesthesia care unit, analgesic regimen, consisting of intravenous patient-controlled morphine analgesia (bolus 1mg, 10-min lockout, maximum dose 5 mg / h), will be used in all groups.

The whole technique and anesthetic procedures will be performed by the same anesthesiologist to avoid as much as possible the inter-individual skill variations.

Inclusion Criteria:

• American Society of Anesthesiology physical status Grade I = (normal healthy patients)
• American Society of Anesthesiology physical status Grade II = (patients with mild systemic disease and no functional limitations)
• Patients scheduled for abdominal hysterectomy.

Exclusion Criteria:

• Pre-operative regular medication with opioids and benzodiazepines, alcohol abuse, known sleep disturbance, known endocrine disease.
• Known allergy to Dexmedetomidine.
• Heart block greater than first degree.
• Medication known to affect the sympathetic response or hormonal secretion.
• Smokers