Invited commentary: Role of alpha-2 agonists for postoperative pain relief.

Acute postoperative pain is a complex and difficult problem to manage in the perioperative period. In addition to causing patient discomfort, it stimulates the sympathetic nervous system, increases myocardial oxygen demand, delays mobilization, impairs the immune system, and may potentially lead to chronic pain. Multimodal analgesia appears to be a very attractive method for postoperative pain management, as it decreases opioid requirements and thus associated complications such as nausea, emesis, and respiratory depression. The use of alpha-2 agonists for multimodal analgesia in the postoperative period has several potential benefits and is worth investigating. Several studies have looked at the risks and benefits associated with the use of dexmedetomidine, an alpha-2 agonist, for postoperative pain. A recent meta-analysis demonstrated that postoperative dexmedetomidine administration reduced the average cumulative morphine equivalents by 6.0 mg at 12 hours and 14.5 mg at 24 hours, as well as pain scores by 1.4 at 1 hour and 0.6 at 24 hours. The same study showed that dexmedetomidine was more effective than acetaminophen but less effective than ketamine or nonsteroidal antiinflammatory medications. Alpha-2 agonists also seem to decrease postoperative nausea and vomiting, presumably by reducing the sympathetic tone; it has been suggested that postoperative nausea and vomiting may be triggered by high catecholamine concentrations. The main risk for using dexmedetomidine was the increased risk of postoperative bradycardia (1, 2). An animal study showed that a single intraperitoneal dose of dexmedetomidine had a long-term antinociceptive effect on acute heat pain (tail-flick test) and on carrageenan-induced inflammatory thermal hyperalgesia (paw withdrawal test) (3). In addition, the use of low-dose intravenous dexmedetomidine (1 mcg/kg) in elderly patients prior to spinal anesthesia with 1.2 mL of 0.5% bupivacaine prolonged the duration of spinal anesthesia and improved postoperative analgesia. Adverse effects, however, consisted of an increased incidence of sedation, desaturation, and bradycardia (4, 5). In this issue, Ramsay et al set up a prospective double-blinded trial to investigate the analgesic effects of dexmedetomidine (0.1–0.5 mcg/kg/h) administered for 24 to 48 hours in patients who underwent lateral thoracotomies (6). Although the dexmedetomidine group used 41% less opioids, they had similar pain scores when compared to the placebo group. This study is unique as, to our knowledge, it is the first trial that continued the dexmedetomidine infusion for 48 hours postoperatively for pain relief. The two main limitations of this study are the small population size and the need for intensive care monitoring in the postoperative period while the patients were on a dexmedetomidine infusion. The requirement for intensive postoperative monitoring might not be available in other institutions. Thoracic epidural analgesia is still considered the gold standard for pain relief after thoracotomies; however, its effectiveness and safety profile have been challenged. The failure rate of thoracic epidurals may be up to 50%. In addition, with the increased use of low-molecular-weight heparin for deep venous thrombosis prophylaxis, there has been an increase in the incidence of epidural hematoma, primarily in elderly patients (7). A survey of Australian anesthesiologists showed that 82% of them had inserted fewer epidural catheters due to the fear of litigation and a lack of evidence for beneficial effects (8). A good alternative to thoracic epidural analgesia for thoracotomies is paravertebral blocks due to a lower incidence of complications (9). The use of the novel alpha-2 agonist fadolmidine for paravertebral blocks in addition to local anesthetics might prove to be an attractive use of alpha-2 agonists for postoperative analgesia (10). The study by Ramsey in this issue as well as other publications highlight the need for a large well-powered study to better evaluate the value of alpha-2 agonists in postoperative pain management.