Local anaesthetic adjuncts for peripheral regional anaesthesia: a narrative review

Medications which bind to opioid receptors are increasingly being prescribed for the treatment of multiple and diverse chronic painful conditions. Their use for acute pain or terminal pain is well accepted. Their role in the long-term treatment of chronic noncancer pain is, however, controversial for many reasons. One of the primary reasons is the well-known phenomenon of psychological addiction that can occur with the use of these medications. Abuse and diversion of these medications is a growing problem as the availability of these medications increases and this public health issue confounds their clinical utility. Also, the extent of their efficacy in the treatment of pain when utilized on a chronic basis has not been definitively proven. Lastly, the role of opioids in the treatment of chronic pain is also influenced by the fact that these potent analgesics are associated with a significant number of side effects and complications. It is these phenomena that are the focus of this review. Common side effects of opioid administration include sedation, dizziness, nausea, vomiting, constipation, physical dependence, tolerance, and respiratory depression. Physical dependence and addiction are clinical concerns that may prevent proper prescribing and in turn inadequate pain management. Less common side effects may include delayed gastric emptying, hyperalgesia, immunologic and hormonal dysfunction, muscle rigidity, and myoclonus. The most common side effects of opioid usage are constipation (which has a very high incidence) and nausea. These 2 side effects can be difficult to manage and frequently tolerance to them does not develop; this is especially true for constipation. They may be severe enough to require opioid discontinuation, and contribute to under-dosing and inadequate analgesia. Several clinical trials are underway to identify adjunct therapies that may mitigate these side effects. Switching opioids and/or routes of administration may also provide benefits for patients. Proper patient screening, education, and preemptive treatment of potential side effects may aid in maximizing effectiveness while reducing the severity of side effects and adverse events. Opioids can be considered broad spectrum analgesic agents, affecting a wide number of organ systems and influencing a large number of body functions.

Severe pain after surgery remains a major problem, occurring in 20-40% of patients. Despite numerous published studies, the degree of pain following many types of surgery in everyday clinical practice is unknown. To improve postoperative pain therapy and develop procedure-specific, optimized pain-treatment protocols, types of surgery that may result in severe postoperative pain in everyday practice must first be identified. This study considered 115,775 patients from 578 surgical wards in 105 German hospitals. A total of 70,764 patients met the inclusion criteria. On the first postoperative day, patients were asked to rate their worst pain intensity since surgery (numeric rating scale, 0-10). All surgical procedures were assigned to 529 well-defined groups. When a group contained fewer than 20 patients, the data were excluded from analysis. Finally, 50,523 patients from 179 surgical groups were compared. The 40 procedures with the highest pain scores (median numeric rating scale, 6-7) included 22 orthopedic/trauma procedures on the extremities. Patients reported high pain scores after many "minor" surgical procedures, including appendectomy, cholecystectomy, hemorrhoidectomy, and tonsillectomy, which ranked among the 25 procedures with highest pain intensities. A number of "major" abdominal surgeries resulted in comparatively low pain scores, often because of sufficient epidural analgesia. Several common minor- to medium-level surgical procedures, including some with laparoscopic approaches, resulted in unexpectedly high levels of postoperative pain. To reduce the number of patients suffering from severe pain, patients undergoing so-called minor surgery should be monitored more closely, and postsurgical pain treatment needs to comply with existing procedure-specific pain-treatment recommendations.

The current study was designed to test the hypothesis that high-dose dexmedetomidine added to local anesthetic would increase the duration of sensory and motor blockade in a rat model of sciatic nerve blockade without causing nerve damage. Thirty-one adult Sprague-Dawley rats received bilateral sciatic nerve blocks with either 0.2 ml bupivacaine, 0.5%, and 0.5% bupivacaine plus 0.005% dexmedetomidine in the contralateral extremity, or 0.2 ml dexmedetomidine, 0.005%, and normal saline in the contralateral extremity. Sensory and motor function were assessed by a blinded investigator every 30 min until the return of normal sensory and motor function. Sciatic nerves were harvested at either 24 h or 14 days after injection and analyzed for perineural inflammation and nerve damage. High-dose dexmedetomidine added to bupivacaine significantly enhanced the duration of sensory and motor blockade. Dexmedetomidine alone did not cause significant motor or sensory block. All of the nerves analyzed had normal axons and myelin at 24 h and 14 days. Bupivacaine plus dexmedetomidine showed less perineural inflammation at 24 h than the bupivacaine group when compared with the saline control. The finding that high-dose dexmedetomidine can safely improve the duration of bupivacaine-induced antinociception after sciatic nerve blockade in rats is an essential first step encouraging future studies in humans. The dose of dexmedetomidine used in this study may exceed the sedative safety threshold in humans and could cause prolonged motor blockade; therefore, future work with clinically relevant doses is necessary.