الفهرس 
ANATOMY AND PHYSIOLOGY OF PAIN
Alternative effector mechanismsOnly 14 pages are availabe for public view
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Abstract
E
ffective pain control is essential for optimum patient care in the postoperative period. Postoperative pain differs from other types of pain in that it starts with the surgery and ends with healing. It is often ignored subjecting the patients to unnecessary suffering. The ideal postoperative analgesia is that which can provide effective pain relief with minimal side effects and high levels of patient satisfaction.
The efficacy of postoperative pain therapy is a major issue in the functional outcome of the surgery.
Epidural analgesia has been widely used to provide effective postoperative analgesia. It is usually preferred to systemic analgesia as it provides effective relief of pain, early mobilization, prevention of pulmonary complications, and improvement of surgical outcome while avoiding the undesirable side effects of systemic analgesics. Despite these beneficial effects, the use of epidural local anesthetics alone is somewhat limited by their side effects resulting from unacceptable incidence of motor blockade, hypotension, urine retention, and regression of the sensory block. The optimal concentration of a local anesthetic should provide effective analgesia, minimal motor blockade and fewer side effects.
It was found that the use of local anesthetics as a sole agent in epidural anesthesia and analgesia doesn’t provide satisfactory standard of pain killing regimen, so administration of other drugs through the epidural route in combination with local anesthetic may be needed in most circumstances.
Unfortunately, intra-spinal and epidural opioid can be associated with dose dependant side effects including nausea, vomiting, urinary retention, respiratory depression, pruritis and development of tolerance and physical dependence.
It has become common practice to use a polypharmacological approach for the treatment of postoperative pain, because no drug has yet been identified that specifically inhibits nociception without associated side effect.
Alpha2-agonist was found to produce analgesia following Intrathecal or epidural administration.
Dexmedetomidine is a very potent and a highly selective alpha 2-adrenoceptor agonist as shown by receptor binding and functional studies. Its affinity for alpha2 receptor is approximately 8 times greater than that of the prototypical alpha2 adrenoceptor agonist clonidine.
In the present study we investigated the efficiency and safety of the epidural administration of dexmedetomidine or clonidine combined with bupivacaine compared to bupivacaine alone for postoperative pain control in patients undergoing orthopedic surgery of lower extremities.
Sixty adult patients aged between 18 and 65 years, ASA physical status I–II, who were scheduled for major lower extremities orthopedic surgery were enrolled in the study
Patients were randomly allocated to the following groups immediately before the anesthetic procedure:
Group B (Bupivacaine): Epidural bupivacaine 0.125% infusion for 24 hours
Group D (Bupivacaine+ Dexmedetomidine): Epidural bupivacaine 0.125% infusion supplemented with dexmedetomidine (0.002 mg/kg/day) (dexmedetomidine hydrochloride; Precedex TM, Abott Laboratories, North Chicago, USA, 59-0852-RI) for 24 hours
Group C (Bupivacaine+Clonidine): Epidural bupivacaine 0.125% infusion supplemented with clonidine (0.004 mg/kg/day) for 24 hours
All patients in the three groups were assessed and monitored for: Postoperative pain using the VAS. The number of rescue analgesia given and total analgesic consumption (cumulative doses) of rescue analgesia were recorded for each patient as well as time for first rescue analgesia required after start of epidural infusion. Monitoring the vital signs (heart rate, arterial blood pressure, respiratory rate and temperature), blood samples for serum cortisol level was taken. During the infusion period; motor block was evaluated using a modified Bromage scale, sedation was assessed on a four-point scale, side-effects related to epidural drugs (drowsiness, respiratory depression, nausea, vomiting, pruritis), and adverse events related to Epidural catheter were recorded.
The results of the statistical analysis of the data obtained showed that Visual analogue scores were highly significant in Bupivacaine alone group than in clonidine and Dexmedetomidine groups during the time of epidural infusion.
The effectiveness of the postoperative analgesia in clonidine and dexmedetomidine groups compared to bupivacaine group was further confirmed by the lower consumption of rescue analgesia in dexmedetomidine and clonidine groups than in bupivacaine group and the longer time of the patient’s 1st analgesic requirement time for postoperative analgesia after starting of epidural infusion.
The significant decrease in VAS and rescue analgesia consumption in patients receiving dexmedetomidine or clonidine as additives to epidural bupivacaine in this clinical trial was comparable with other studies that proved that addition of dexmedetomidine or clonidine to epidural bupivacaine improves analgesia with very few side effects that was of no clinical significance.
Regarding the incidence of side effects related to epidural dexmedetomidine; none of our patients developed respiratory depression or delayed respiratory depression which makes alpha 2 agonists a better alternative additive to epidural bupivacaine than narcotics. None of our patients developed pruritis in all groups, occurrence of hypotension and bradycardia in clonidine and dexmedetomidine groups despite being statistically significant but without any clinical significance which come in agreement with other studies evaluating dexmedetomidine and clonidine usage in animal and human studies.
There are still some concerns regarding the safety of dexmedetomidine with reference to some authors but still not proved and contradicted by others and we agree that further studies are necessary to ensure the safety and benefits of dexmedetomidine application via the epidural route.