The Potential Role of (cid:1) 2 Agonists for Noncardiac Surgery

A CUTE pain after noncardiac surgery provokes suffering, activates the sympathetic nervous system which augments myocardial demand, delays mobilization and recovery, and may result in chronic postoperative pain. Although the last 50 yr have witnessed advances in the prevention and management of acute pain after noncardiac surgery (e.g., acute pain services, patient-controlled analgesia), postoperative pain remains common. Physicians regularly use opioids to prevent and manage acute postoperative pain. Many authors have advocated multimodal analgesia with the goal of sparing opioid use and thus presumably reducing potential opioid-related adverse effects, including respiratory depression, hypotension, nausea and vomiting, bradycardia, delirium, hypothermia, hyperalgesia, immune system compromise, and constipation. In this issue of ANESTHESIOLOGY, Blaudszun and colleagues present a systematic review and meta-analyses of randomized controlled trials addressing the important topic of whether systemic 2 agonists reduce postoperative opioid use and improve pain control in patients having noncardiac surgery. This systematic review included 1,792 randomized patients from 30 trials, of which 19 evaluated clonidine and 11 evaluated dexmedetomidine. Meta-analyses by Blaudszun and colleagues demonstrated that clonidine administration reduced average postoperative cumulative morphine equivalents by 9.8 mg at 12 h and 4.1 mg at 24 h. Meta-analyses also demonstrated that dexmedetomidine administration reduced postoperative average cumulative morphine equivalents by 6.0 mg at 12 h and 14.5 mg at 24 h. What represents a clinically important decrease in opioid sparing after noncardiac surgery? One answer is the dose that reduces opioid-related adverse effects. The investigators demonstrated that clonidine and dexmedetomidine reduced postoperative nausea but not vomiting. Other potential opioid-sparing effects were not reported, including respiratory depression, delirium, hypothermia, hyperalgesia, and immune system compromise. Meta-analyses by Blaudszun and colleagues demonstrated that clonidine administration reduced postoperative pain scores (on a 10-cm visual analog scale) by 1.5 cm at 12 h and 0.7 cm at 24 h. Meta-analyses demonstrated that dexmedetomidine administration reduced postoperative pain scores by 1.4 cm at 1 h and 0.6 cm at 24 h. What represents a clinically important change in pain scores using a visual analog scale? Studies suggest that decreases in individual pain scores of 1 cm represent minimal or little change, whereas decreases of 2 cm or more represent a substantial reduction in pain that can result in a decreased need for rescue pain-relief medication. However, what represents an important change in an individual’s pain score differs from what represents an important difference between group pain scores. Unfortunately, the 2 agonist data are reported only as differences between group scores, rather than the percentage of patients in each treatment group who experienced a clinically important change being reported. Despite this limitation, it is possible, and considering the differences between group pain scores and the opioid sparing-effects, perhaps even probable, that 2 agonists resulted in an appreciable relative increase in the number of patients experiencing a clinically important reduction in their pain scores. An alternative method for assessing the effect of 2 agonists on opioid sparing and pain scores is to compare their impact to that of other drugs. Blaudszun and colleagues compare their results to other meta-analyses and suggest 2 agonists provide greater morphine and pain-sparing effects than Photo-illustration: J. P. Rathmell.