Effect of Nebulized Magnesium Sulfate on Post-intubation Stress Response in Patients Undergoing Laparoscopic Cholecystectomy

This randomized controlled double blinded study will be carried out on 140 patients underwent elective fit laparoscopic cholecystectomy at El-Rajhi Assiut University Hospital. Inclusion criteria: * 20-50 years old. * Both sexes. * American society of anesthesiologists (ASA) physical status I-II. * Elective fit laparoscopic cholecystectomy Exclusion criteria: * Patient refusal. * Patients with history of hypersensitivity to magnesium sulfate. * Patients with coronary ischemic disease, atrioventricular block of any degree, known cardiac arrhythmias, heart failure on beta blockers or calcium channel blockers expected difficult intubation (Mallampati 4). * Body mass index (BMI) \> 40 kg/m2. An online randomization program (http://www.randomizer.org) will be used to generate a random list and each patients' code will be kept in an opaque sealed envelope. Patients will be randomly allocated with 1:1 allocation ratio into two equal groups in a parallel manner: * Group A: (N=70) Patients will receive nebulized magnesium sulfate in 5 ml (250 mg) over 15 min. * Group B: (N=70) Patients received nebulized normal saline in 5 ml over 15 min, ending 5 min before the induction of anesthesia. A. Preoperative assessment: All patients will be subjected to the followings: 1. Demographic data collection (age, weight, height, BMI, and ASA). 2. Complete clinical examination. 3. Routine Laboratory investigations: * Random blood sugar. * Blood sample withdrawal for cortisol level at baseline 2ml intravenously. The sample will be sent to be centrifugated within 30 minutes and the serum will be separated and stored in -20°C till time of cortisol level by ELIZA technique.

B. Intraoperatively: SBP, DBP, HR, and blood glucose level will be measured at the following intervals: Baseline (before induction), after premedication (sedation), after induction, after ETT intubation, 3 min later, 6 min later. Full monitoring data (Blood pressure every 3 minutes, ECG, Nanogram, and pulse oximeter) will be collected till 6 minutes then every 5 minutes. Random blood sugar will be tested 5 minutes pre-intubation, 3minutes and 5 minutes after intubation and recorded. After end of nebulization, sedation with 2 mg midazolam and IV fluids (10 ml/kg) were infused to avoid tachycardia of dehydration and fear of surgery. Then, we proceed on general anesthesia through Propofol titration + fentanyl 100 mcg + Cis-atracurium 0.15 mg/kg. Endotracheal intubation with cuffed tube and mechanical ventilation with mild increase in respiratory rate 14-16/min to overcome CO2 peritoneal insufflation. All patients will receive intraoperatively, nalbuphine 0.1 mg/kg + ketorolac 60 mg + paracetamol IV 1 g. Dexamethasone 4mg + Ondansetron 4mg will receive to all patients for prophylaxis against postoperative nausea and vomiting. After 10 minutes of intubation, a second 2ml IV blood sample will be withdrawn for cortisol level. The centrifugation, serum separation, storage and ELIZA analysis will be done as the baseline sample described above. C. Postoperative: After end of surgery, cessation of inhalational anesthesia and reversal of muscle relaxation with neostigmine 2.5 mg+ Atropine 1mg is done. Consumption of isoflurane intraoperatively is recorded. Post operative assessment for pain using Visual Analogue Scale (VAS) will be assessed 2 hours after recovery. VAS is presented as a website10 cm straight line ruler reflecting the extremes of "no pain" equals 0 and "worst pain at the other end(at 10cm), while in between the intensity of pain is represented by corresponding facies. Time for recovery after stop of isoflurane is estimated. Hypertension is considered when the BP values are 20% above baseline values or SBP \> 140 mmHg. Hypotension is considered when BP values are lower than 20% of baseline or SBP \< 90 mmHg and will be treated with 10-20 mg ephedrine. Tachycardia will be considered when HR is higher than 20% of baseline or HR \> 100 bpm. Bradycardia is considered when HR values are lower than 50 bpm, treated by I.V. atropine 0.02 mg/kg respiratory depression (the SpO2 \< 95% and need O2 supplementation), and postoperative nausea and vomiting (PONV) is treated by ondansetron 0.1 mg/kg IV. Measurements: * Demographic data. * Hemodynamics variables like SBP, DBP, HR, and blood glucose level are measured at the following intervals: Baseline (before induction), after premedication (sedation), after induction, after ETT intubation, 3 min later, 6 min later. * Visual Analog Scale (VAS) is assessed. * Side effects are recorded