الفهرس 
INTRODUCTIONOnly 14 pages are availabe for public view
 |  | from | 158 |  |  |
| | | from | 158 | | |
Abstract
The stress response to surgery is the name given to the hormonal and metabolic changes following injury or trauma. It is a major neuroendocrine and cytokine response to surgical trauma, characterized by increases in catecholamine and steroid hormones, with predictable metabolic consequences. If the stress response is prolonged, the continuous hyper-metabolic state may result in exhaustion of essential components of the body causing loss of weight, fatigue, decreased resistance, delayed ambulation and increased morbidity and mortality. A normal, balanced, well controlled inflammatory response in previously healthy patients almost always results in an uneventful recovery. However, some patients may develop an exaggerated high or insufficient response. A suppressed response or prolonged illness may result in compromised organ function that requires exogenous support.
Cytokines are immune mediators that direct the inflammatory response to sites of injury and infection and are essential for wound healing. An exaggerated production of proinflammatory cytokines from the primary site of injury, however, can manifest systemically as haemodynamic instability or metabolic derangements. IL-6 is a main proinflammatory cytokine produced as early as two to four hours after tissue damage. Circulating IL-6 levels appear to be proportional to the extent of tissue injury during an operation.
The metabolic effects of cortisol are directed to overcome the stressful state. Cortisol has widespread effects on the metabolism and utilization of glucose, amino acids and fatty acids in hepatic and extra-hepatic tissues.
Dexmedetomidine is an α2-adrenergic agonist which is the pharmacologically active dextroisomer of medetomidine. It activates receptors in the medullary vasomotor center, reducing norepinephrine turnover and decreasing central sympathetic outflow, resulting in alterations in sympathetic function. Dexmedetomidine has significant analgesic qualities and has been labeled as ”analgesia-sparing” by the FDA. Because dexmedetomidine has no depressant effects on ventilation, its analgesic effect may offer a significant advantage for patients at risk for respiratory decompensation. Alpha-2 agonists as dexmedetomidine are widely used now for prevention of PONV.
The aim of this work was to study the effect of intravenous dexmedetomidine infusion on plasma level of interleukin-6, plasma cortisol level, blood glucose, recovery profile, postoperative pain, haemodynamic changes, and postoperative nausea and vomiting in patients undergoing major abdominal surgery.
After approval of the medical ethics committee, an informed written consent was obtained from all patients. This present double blind study was carried out on 30 adult patients admitted to the surgery department of the Alexandria Main University Hospital belonging to American Society of Anaesthesiologists (ASA) physical status grade I-III, scheduled for elective major abdominal surgery under general anaesthesia.
Patients were randomly classified using closed envelope technique into two equal groups according to the drug infused intraoperatively. Dexmedetomidine group (Group D); received loading dose of intravenous dexmedetomidine infusion of 1 µg/kg IV over 10 minutes followed by maintenance dose of 0.5 µg/kg/hr till the end of surgery and placebo group (Group P); received intravenous infusion of normal saline 0.9 % over 10 minutes followed by continuous infusion till the end of surgery.
Measurements
• Heart rate, mean arterial pressure, O2 saturation, and central venous pressure were recorded intra- and postoperatively every 6 hours during the first 24 hours.
• Arterial blood gases were measured intra- and postoperatively.
• Blood glucose level, plasma level of interleukin-6 and plasma cortisol level were measured before induction, after complete recovery and first day postoperatively at 8:00 am.
• Recovery profile was assessed by measuring tracheal extubation time, time to eye opening and time to following verbal commands.
• Postoperative pain was assessed using visual analogue scale (VAS) recorded at 10, 30, 60, 90 and 120 minutes and at 6, 12, 18 and 24 hours postoperatively.
• Sedation status was assessed using Ramsay sedation scale and Observer Assessment of Alertness/Sedation [OAA/S] scale. Both scales were recorded at 10, 30, 60, 90 and 120 minutes and at 6, 12, 18 and 24 hours postoperatively.
• Incidence of postoperative nausea and vomiting was observed in both groups.
The results of the present study showed that:
There were no statistically significant differences between both groups as regards age, sex, body weight and durations of surgery and anaesthesia.
In the present study, the basal readings of HR and MAP were within normal physiological ranges and with no significant difference between both groups. Intraoperatively, the HR and MAP were significantly lower with haemodynamic stability, in group D relative to group P during most of the intra- and postoperative periods. Dexmedetomidine was able to blunt the increase in HR and MAP associated with endotracheal intubation.
There were no significant differences between the 2 groups as regards oxygen saturation, CVP and ABG during the intra- and postoperative periods.
There was no statistically significant difference between both groups as regards the basal level of blood glucose, interleukin-6 and cortisol. After complete recovery and at the first day postoperative, they increased in both groups but were significantly lower in group D relative to group P. Dexmedetomidine attenuated stress response and suppressed the postoperative rise of IL-6.
Tracheal extubation time, time to eye opening and time to following verbal commands were slightly longer in group D relative to group P but with no statistically significant difference between both groups.
VAS for pain score was less in group D relative to group P and postoperative ketorolac requirement was significantly less in group D relative to that in group P. There were no significant differences between both groups during most of the postoperative periods as regarding both sedation scales.
There was significant decrease in postoperative nausea and vomiting in patients of group D relative to those in group P.
from the present study we concluded that:
• Dexmedetomidine administration resulted in lower levels of heart rate and MAP but with haemodynamic stability throughout intra- and postoperative period. Dexmedetomidine was effective in blunting the increase in heart rate and arterial blood pressure associated with laryngoscopy and intubation.
• Dexmedetomidine administration attenuated the postoperative rise of the proinflammatory cytokines especially IL-6 and resulted in lower levels of stress response markers to surgery as cortisol, and blood glucose.
• Dexmedetomidine provides sedation and analgesia with no accompanying respiratory depression and without delaying recovery from anaesthesia.
• Dexmedetomidine reduced the postoperative pain score and diminished the amount of rescued analgesic requirements.
• Dexmedetomidine administration resulted in significant decrease in incidence of postoperative nausea and vomiting after abdominal surgery.