Article Item

Literature Review: November 2023

Nov 6, 2023, 00:00 AM by Jeffrey Grzybowski, MD, Monika Nanda, MBBS, MPH, Beth VanderWielen, MD, Priyanka Singla MD, and Vinita Singh, MD, MS

Cite as: Literature review—November 2023. ASRA Pain Medicine News 2023;48.

Acute Pain

Adductor Canal Blocks Are Not Associated with Improved Early Postoperative Outcomes in Patients Undergoing Total Knee Arthroplasty

Holbert SE et al. Ochsner J 2023;23(1):9-15.

Summary by Jeffrey Grzybowski, MD

Introduction: Despite the prevalence and overall success of total knee arthroplasty (TKA), approximately 60% of patients report severe pain post-surgery. This can hinder patient recovery and lead to mobility-related complications, such as decreased ability to move the knee, higher risk of deep vein thrombosis, and increased length of hospital stay (LOS). This study aims to investigate the effect of an adductor canal block (ACB) on early postoperative pain and outcomes after TKA performed under spinal anesthesia.

Methods: A retrospective analysis of all patients undergoing primary unilateral TKA at a single institution was performed. All patients received spinal anesthesia and a standard periarticular anesthetic injection (PAI) of ropivacaine and epinephrine before closure. Patients consented for peripheral nerve block had ultrasound-guided ACBs performed in the operating room prior to incision using either ropivacaine or bupivacaine. Postoperative outcomes of interest included post anesthesia care unit (PACU) nausea and pain, administration of nausea medication within 24 hours of surgery, ability to participate in the first postoperative physical therapy session, urinary retention, narcotic consumption, LOS (in hours), discharge disposition, recovery time (in hours), last PACU pain score, and 30-day readmission. Patients were grouped based on whether they received an ACB or not. Multiple logistic and linear regression was used to establish the effect of ACB on postoperative outcomes while controlling for sex, fentanyl administration, and dexamethasone administration.

Results: Of the 565 patients included in the study, 167 (29.6%) received an ACB, and 398 (70.4%) did not. After risk adjustment, a decreased likelihood of nausea in the PACU among patients in the ACB group was found (odds ratio 0.39, 0.24-0.62, P<0.001). No other significant differences in variables of interest were observed between the two groups.

Key Point: This single-center retrospective review of primary TKA performed under spinal anesthesia with PAI demonstrated limited early postoperative benefits to performance of ACB in which patients receiving the block were 61% less likely to report PACU nausea.

Intravenous Versus Perineural Dexamethasone for Reducing Rebound Pain After Interscalene Brachial Plexus Block: A Randomized Controlled Trial

Lee HJ et al. J Korean Med Sci 2023;38(24):e183.

Summary by Monika Nanda, MBBS, MPH

Introduction: Post-surgical pain is common in arthroscopic rotator cuff tear repair, and interscalene brachial plexus block (ISB) offers initial relief but might lead to rebound pain later. Dexamethasone, when administered perineurally with ISB, can prolong pain relief and decrease rebound pain, though safety concerns limit its use. This study aimed to compare the effects of perineural versus IV administration of dexamethasone on rebound pain in patients undergoing this procedure with ISB.

Methods: This prospective randomized controlled study enrolled patients scheduled for elective arthroscopic rotator cuff tear repair under general anesthesia with preoperative single-injection ISB. Patients were randomly divided into two groups, one receiving perineural dexamethasone and the other receiving intravenous dexamethasone with all involved parties blinded to the group allocations. The primary goal was to assess the difference in pain scores before and after the ISB resolution with secondary outcomes of the incidence of rebound pain, time to first analgesic request, and analgesic consumption during the first 48 hours post-surgery.

Results: In this study of 71 patients split into two groups, the perineural group had a longer analgesic duration (median 19.9 hours versus 15.1 hours, p<0.001) but experienced a higher increase in pain scores after block resolution (p=0.04), higher incidence of rebound pain, and sleep disturbances due to pain compared to the intravenous group in the first postoperative week.

Key Point: Despite the longer analgesic effect of perineural dexamethasone, intravenous dexamethasone proved to be more effective in minimizing pain escalation post-ISB resolution, rebound pain occurrence, and sleep interruptions related to pain.

Neuropathies Following an Ultrasound-Guided Axillary Brachial Plexus Block

Koh K, Tatsuki O, Sakuraba S, et al. Local Reg Anesth 2023;16:123-32.

Summary by Beth VanderWielen, MD

Introduction: All regional anesthesia approaches to the brachial plexus present a risk of nerve injury. This study compared the incidence of postoperative neurologic symptoms (PONS) after an ultrasound-guided axillary nerve block compared to other approaches (interscalene, supraclavicular, and infraclavicular) when performed under general anesthesia (GA).

Methods: In this single-center, retrospective cohort study, 143 patients received an axillary nerve block while 849 patients received a non-axillary approach to the brachial plexus. All patients had their nerve block performed while under GA with ultrasound guidance. In addition, all PONS cases were based on consensus of a neurologist, orthopedic surgeon, and anesthesiologist and defined by the presence of a new onset paresthesia, hypoesthesia, numbness, or muscle weakness occurring within 48 hours postoperatively and lasting for more than 5 days. Cases in which the cause of the nerve injury was determined not to be block related, such as original injury, surgical manipulation, surgical position or tourniquet, or undetermined etiology, were excluded.

Results: Of the 992 patients receiving brachial plexus nerve blocks under GA, there were 19 total causes of PONS of which 4 were determined to be related to the nerve block. The other 11 cases were determined to be related to surgical manipulation. Of the nerve block related injuries, three cases occurred after an axillary nerve block, and one occurred after a non-axillary approach (P = 0.005).

Key Point: Ultrasound-guided axillary nerve blocks performed under GA may have a higher incidence of PONS as compared to non-axillary approaches to the brachial plexus.

Selective Inhibition of NaV1.8 with VX-548 for Acute Pain

Jones J, Correll DJ, Lechner SM, et al. N Engl J Med 2023;389(5):393-405.

Summary by Priyanka Singla, MD

Introduction: Voltage-gated sodium channels play a role in acute pain. The aim of this study was to study the effectiveness of VX-548, a selective NaV1.8 channel inhibitor, following abdominoplasty and bunionectomy.

Methods: Pre-trail selectivity of VX- 548 for NaV1.8 channel inhibition was established in vitro followed by two Phase 2, randomized, double-blind trials in which participants undergoing abdominoplasty or bunionectomy were assigned to one of four groups. The participants received one of the four following regimens over 48 hours after abdominoplasty– high dose VX-548 (100 mg followed by 50 mg every 12 hours), middle dose VX-548 (60 mg followed by 30 mg every 12 hours), hydrocodone bitartarate-acetaminophen (5 mg - 325 mg every 6 hours), or placebo every 6 hours. In the bunionectomy trial, there was an additional group of low dose VX-548 (20 mg followed by 10 mg every 12 hours). The primary end point was the time-weighted sum of the pain-intensity difference (as recorded on the 10-point numeric pain rating scale at 19 time points) over the 48-hour period (SPID48) after the first dose between VX-548 and placebo.

Results: 303 and 274 participants were enrolled in the abdominoplasty and bunionectomy trials respectively. In both trial groups, high dose VX-548 decreased pain over 48 hours when compared with the placebo (least-squares mean difference in time-weighted SPID48 was 37.8% [95% CI 9.2 to 66.4] after abdominoplasty and 36.8 [4.6 to 69.0] after bunionectomy).

Key Point: High dose of VX-548 was more effective as compared to the placebo in reducing acute pain for 48 hours after abdominoplasty or bunionectomy.

Chronic Pain

Placebo Response and Media Attention in Randomized Clinical Trials Assessing Cannabis-Based Therapies for Pain: A Systematic Review and Meta-Analysis

Gedin F, Blomé S, Pontén M, et al. JAMA Neurol 2023;80(1):18-29.

Summary by Vinita Singh, MD, MS

Introduction: Given the changing landscape of medical cannabis and the potential for large placebo responses in pain treatment, there’s a need to understand placebo responses in medical cannabis trials for pain.

Methods: This systematic review and meta-analysis aimed to evaluate the size of placebo responses in double-blind, randomized clinical trials of medical cannabis-related products for pain treatment. The primary aim of this research study was to evaluate the size of placebo responses in double-blind, randomized clinical trials in which cannabis-based therapies were compared to placebo for pain treatment. Another aim of this study was to study the association of clinical outcomes with mass media and lay press attention. The primary outcome was a change in self-reported pain intensity measured as bias-corrected standardized mean difference (Hedges g). The secondary outcome was the association between study effect size and Crossref citations for academic context or Almetric scores for non-academic context. A modified version of the Cochrane Risk of Bias Tool 2.0 for randomized control trials was used to assess the quality of the studies.

Results: A total of 20 trials with 1,459 individuals were included in the meta-analysis. The placebo had a moderate to large effect size, and active drug (cannabinoids) had a large effect size; however, the between-group difference for active drug and placebo was not statistically significant (Hedges g [cannabinoid g – placebo g] = 0.32). The amount of media attention and dissemination was not associated with the clinical outcomes.

Key Point: The placebo contributed significantly to pain reduction seen in clinical trials of cannabis.

Jeffrey S. Grzybowski, MD, is an assistant professor in the department of Anesthesiology at the University of Wisconsin School of Medicine and Public Health System in Madison, WI.
Dr. Monika Nanda
Monika Nanda, MBBS, MPH, is an associate professor of anesthesiology at the University of North Carolina School of Medicine. 
Dr. Beth VanderWielen
Beth VanderWielen, MD, is a staff anesthesiologist and clinical adjunct assistant professor in the department of Anesthesia at the University of Wisconsin School of Medicine and Public Health, Gundersen Health System in Madison, WI.
Priyanka Singla
Priyanka Singla, MD is an assistant professor in the department of Anesthesiology at the University of Virginia in Charlottesville.
Dr. Vinita Singh
Vinita Singh, MD, MS, is board-certified in anesthesiology and pain medicine. She is the director of Cancer Pain and do-director of research for the Pain Division at Emory University in Atlanta, GA.
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