Comparison Between the Effects of Intravenous Morphine, Tramadol and Ketorolac on Stress and Immune Responses in Patients Undergoing Modified Radical Mastectomy

Sixty patients aged (20-60 years), weighting (50 -75 Kg), with American Society of Anesthesiologists (ASA) physical status I or II scheduled for modified radical mastectomy surgery under general anesthesia were enrolled in this prospective clinical study. The Ethics Committee of South Egypt Cancer Institute (SECI), assuit University, assuit, Egypt approved the study. Informed written consent was obtained from each patient to be enrolled in this study.

Patients with known allergy to opioids or Non Steroidal Anti-inflammatory drugs NSAIDs, with gastric or duodenal ulcer, on radiotherapy or chemotherapy, received blood transfusion before the surgery or preoperative NSAIDs, steroid or opioid medications 48 hours prior to operation were excluded.

All patients were taught how to evaluate their own pain intensity using the visual analogue scale (VAS) scored from 0 to 10 (where 0 = no pain and 10 = the worst pain imaginable). Both the patient and the anesthetist involved in the study were kept blinded to group assignment. Randomization codes were not decoded till the end.

No pre-medications were given. Basic monitoring probes (ECG, non invasive blood pressure, end-tidal carbon dioxide, pulse oximetry and temperature) were applied. base line VAS, sedation score, systolic and diastolic blood pressure, heart rate, respiratory rate and oxygen saturation were assessed before the beginning of surgery. Venous blood sample was taken for assessment of the base line stress hormones (cortisol, prolactin) and immune response (cluster of differentiation (CD) 3, 4, 8 and 56), General anesthesia was induced with I.V. fentanyl 1 μg/kg, thiopental 5mg/kg. Endotracheal intubation was facilitated by cis-atracurium 0.15 mg/kg, and was maintained with isoflurane 1.5-1.7 MAC, cis-atracurium 0.03 mg/kg and controlled ventilation in a ventilation parameters that maintain normocapnia (35- 45 mmHg). Neuromuscular block was antagonized by neostigmine 50µg/kg and atropine 20µg/kg. Venous blood sample was taken for assessment of stress hormones (cortisol, prolactin) and immune response (CD3, CD4, CD8 and CD56) immediately postoperatively after extubation in the operative room before the analgesic drug administration. VAS, sedation score, systolic and diastolic blood pressure, heart rate, respiratory rate and oxygen saturation were also assessed. Patients were allocated according to computer-generated randomization tables into one of three groups of 20 patients each to receive:

Group I: (n=20) received IV 0.1mg/kg morphine sulphate (morphine sulfate ®, Misr CO Pharma).