In a study of patients undergoing corrective osteotomy for hallux valgus, those who received an ankle block with a mixture of bupivacaine and long-acting liposomal bupivacaine (Exparel, Pacira) experienced relief of postoperative pain and a marked reduction in opioid consumption, compared with use of general anesthesia alone or ankle block with bupivacaine alone.
Both types of nerve blocks significantly reduced pain scores, but the block including liposomal bupivacaine reduced mean opioid consumption “quite a bit,” said author Maxine M. Kuroda, PhD, MPH, epidemiologist and biostatistician at Ziekenhuis Oost-Limburg, in Genk, Belgium. “Bupivacaine alone reduced opioid consumption by approximately 40%, whereas the addition of liposome bupivacaine facilitated ambulation and reduced opioid consumption greater than 80%, compared to general anesthesia.”
Considering the current opioid epidemic in the United States, the sizable reduction in opioid consumption using liposomal bupivacaine is “quite promising,” said Dr. Kuroda, who presented the findings at The New York School of Regional Anesthesia 2017 Annual Symposium on Regional Anesthesia, Pain and Perioperative Medicine (abstract NYS27).
Currently, liposomal bupivacaine is approved for postsurgical analgesia by administration via infiltration into soft tissue surrounding the surgical site. In this study, researchers sought to determine if the addition of liposomal bupivacaine to bupivacaine in ankle blocks could provide prolonged pain relief and reduce opioid consumption. Investigators randomly assigned 40 patients scheduled to undergo hallux valgus corrective osteotomy to one of three groups: an ankle block with the mixture (n=12; bupivacaine 2.5 mL, 0.5% plus liposomal bupivacaine 5 mL, 1.3%), an ankle block with bupivacaine alone (n=14; bupivacaine 7.5 mL, 0.5%) or general anesthesia alone (n=14).
Each treatment group received ultrasound-guided blocks to the deep peroneal and posterior tibial nerves (7.5 mL per nerve). All patients received multimodal analgesia comprising ibuprofen and acetaminophen-paracetamol; opioids were used only for breakthrough pain. Patients were assessed up to seven days postoperatively.
Using generalized estimating equations, the researchers found that the ankle blocks significantly reduced postoperative pain scores compared with general anesthesia alone (P=0.016). Additionally, through postoperative day 4, a significantly greater proportion of patients who received liposomal bupivacaine were able to ambulate (P=0.007). Duration of sensory block was longer in patients who received liposomal bupivacaine than in those who received bupivacaine alone (independent ttest, P<0.05), but duration of motor block did not differ between the two groups.
The study’s most striking findings were in opioid consumption. Mean opioid consumption was significantly lower in patients who received liposomal bupivacaine than for general anesthesia alone (8 vs. 48 mEq; P<0.001). Mean opioid consumption in the liposomal bupivacaine group also was lower than for bupivacaine alone (28 mEq), but the difference was not significant (P=0.087). Similarly, opioid consumption in patients who received bupivacaine alone was lower than for general anesthesia alone, but not significantly so (P=0.116).
The investigators concluded that the addition of liposomal bupivacaine to ankle blocks with bupivacaine reduced pain scores, decreased opioid consumption and facilitated ambulation in the first postoperative week.
Small Study, Unanswered Questions
“Two of the most important considerations when interpreting the results of this study are the lack of blinding and small sample size,” said Adam W. Amundson, MD, an anesthesiologist at Mayo Clinic, in Rochester, Minn. “Given the small number of patients, it is hard to comment on differences in postinterventional pain scores between the two bupivacaine treatment groups.”
Kenneth Cummings, MD, MS, FASA, medical director of preanesthesia clinics at the Cleveland Clinic, in Ohio, echoed those concerns. “This was a very small trial, and small studies generally tend to overestimate treatment effects.”
In response, Dr. Kuroda noted that a total of 13 patients per treatment arm would sufficiently power the study to detect a difference in pain scores on the numeric rating scale of 5 points, with an SD of 3 points. “We wished to evaluate improvement in pain scores beyond that conferred by the standard regimen [of multimodal analgesia]—that is, we considered a larger difference as important to detect [i.e., 5 vs. 3 points],” she said.
Furthermore, Dr. Kuroda noted that the anesthesiologists who administered the nerve blocks in the study, although not blinded to the type of block, did not participate in postsurgical assessments of the patients. “Surgeons and research personnel were blinded to the treatment arm, as the nerve blocks were performed in a separate room outside of the operating theater.” Moreover, the patients who received general anesthesia alone were given the same surgical dressings as the patients who received nerve blocks. In addition, the personnel who recorded block onset and offset times did not participate in postoperative assessments.
Dr. Kuroda also pointed out that the results suggest a “ relationship” between the type of nerve block that patients received and postoperative opioid consumption. “For patients who received general anesthesia, total opioid consumption was 48 mEq; for patients who received bupivacaine alone, total opioid consumption was 28 mEq; and for those who received the liposome bupivacaine mixture, total opioid consumption was 8 mEq.”
However, Dr. Cummings noted that because the study evaluated both pain and opioid use, interpreting the results is challenging. “[A figure indicated that] the pain scores for the two bupivacaine groups are similar. What is not evident, however, is the difference in opioid consumption and whether it is truly important. This is a perpetual challenge in acute pain studies: To determine if one treatment is better, we must simultaneously compare pain scores and analgesic use.”
Dr. Cummings questioned whether the reduction in opioid use in patients who received liposomal bupivacaine versus bupivacaine alone was clinically relevant. “Whether this additional reduction in opioid use would justify the increased cost of liposomal bupivacaine is an open question.”
An interesting future direction for this research, Dr. Kuroda suggested, would be the integrated assessment of pain scores and use of rescue morphine (e.g., Anesth Analg 1993;77:168-170). This kind of study would likely require the accuracy of opioids delivered via IV patient-controlled analgesia, she said, noting “this would not have been feasible in our study, as our patients were discharged from hospital within 24 hours of their procedures.”