The public health crisis attributed to opioids has placed increasing emphasis on other approaches to pain management, both pharmacologic and nonpharmacologic. Although some people find the term “multimodal pain management” to be ambiguous when used in clinical research or patient care, it emphasizes the need for a broader (and multidisciplinary) approach to pain management.
On the pharmacologic side, pregabalin has been found to be a variably effective adjunctive analgesic in research involving joint arthroplasty. However, its use in adolescents and children has not been adequately explored. In the February 5, 2020 issue of The Journal, Helenius et al. investigate the impact of pregabalin on total opioid consumption and pain scores in a randomized, placebo-controlled trial of 63 adolescents undergoing posterior instrumented spinal-fusion procedures. These operations are quite invasive and often result in ICU admission because of the amount of narcotics required. In this study, induction and maintenance of anesthesia and mobilization protocols were standardized for patients in both the pregabalin and placebo groups, and the authors precisely measured opioid consumption during the first 48 hours after surgery with data from patient-controlled anesthesia systems.
According to the findings from this adequately powered trial, adjunctive pregabalin did not have a positive impact on opioid consumption or postoperative pain scores. Despite these negative findings, it is my hope that this drug and others being investigated as adjunctive “modes” in multimodal pain management will be subjected to similarly designed trials, so we can accurately determine which agents work best in limiting opioid utilization.
Marc Swiontkowski, MD
This post comes from Fred Nelson, MD, an orthopaedic surgeon in the Department of Orthopedics at Henry Ford Hospital and a clinical associate professor at Wayne State Medical School. Some of Dr. Nelson’s tips go out weekly to more than 3,000 members of the Orthopaedic Research Society (ORS), and all are distributed to more than 30 orthopaedic residency programs. Those not sent to the ORS are periodically reposted in OrthoBuzz with the permission of Dr. Nelson.
Orthopaedic surgeons may not be at the forefront of dealing with nonoperative nerve pain, but many of our patients who are not candidates for surgery suffer from spine-related nerve pain in their limbs, such as sciatica. Both gabapentin (GBP, Neurontin) and pregabalin (PGB, Lyrica) are used to treat chronic sciatica (CS).
Gamma-aminobutyric acid (GABA) is an important pain-related neurotransmitter, although neither GBP nor PGB affect the GABA receptor. Instead, both drugs associate with the ligand of the auxiliary α2δ-1 and α2δ-2 subunits of certain voltage-dependent calcium channels in nerves. Among other uses, Neurontin is prescribed to treat diabetic peripheral neuropathy, and Lyrica is commonly used to treat fibromyalgia.
Investigators reporting in JAMA Neurology sought to help guide practitioners in the initial choice of drug. Eighteen patients with MRIs corroborating single-sided nerve-root sciatic pain of at least 3 months duration were evaluated in an interim analysis as part of a randomized, double-blind, double-dummy crossover trial of PGB vs GBP (8 weeks of exposure to each drug with a 1-week washout in between). The primary outcome was pain intensity measured with a 10-point visual analog scale (VAS) at baseline and 8 weeks. Secondary outcomes included disability as measured with the Oswestry Disability Index and the severity and frequency of adverse events.
Relative to baseline, both drugs showed significant VAS pain reductions and disability-score improvements, However, head-to-head, GBP showed superior VAS pain reduction (mean [SD], GBP: 1.72 [1.17] vs PGB: 0.94 [1.09]; P = 0.035), regardless of the order in which it was given. There were no between-drug differences in disability scores, but adverse events for PGB were more frequent (PGB, 31 [81%] vs GBP, 7 [19%]; P = 0.002), especially when PGB was taken first.
The authors conclude that GBP was superior with fewer and less severe adverse events, and they suggest that gabapentin should be commenced before PGB to permit optimal crossover of medicines.
Robertson K, Marshman LAG, Plummer D, Downs E. Effect of Gabapentin vs Pregabalin on Pain Intensity in Adults WIth Chronic Sciatica: A Randomized Clinical Trial. JAMA Neurol. 2018 Oct 15. doi: 10.1001/jamaneurol.2018.3077. [Epub ahead of print] PMID: 30326006
Every month, JBJS publishes a Specialty Update—a review of the most pertinent and impactful studies published in the orthopaedic literature during the previous year in 13 subspecialties. Here is a summary of selected findings from Level I and II studies cited in the June 17, 2015 Specialty Update on spine surgery:
- A database study to determine the prevalence of venous thromboembolic events after spinal fusion found that risk factors for such events included hypercoagulability, certain medical comorbidities, older age, and male sex.
- An RCT comparing allograft alone versus allograft plus bone marrow concentrate to accomplish spine fusion in adults with spondylolisthesis found very poor union rates in both groups, although allograft with bone marrow concentrate delivered slightly better results.
- A meta-analysis of five studies (253 patients) found no pain or functional differences when unilateral percutaneous kyphoplasty was compared with bilateral (same-vertebra) kyphoplasty for osteoporotic compression fractures. The unilateral approach was associated with shorter operative times, however.
- An RCT comparing the analgesic efficacy and clinical utility of gabapentin, pregabalin, and placebo in patients undergoing spinal surgery found that pregabalin outperformed the other two interventions immediately after surgery postoperative and up to three months postoperatively.
- In an RCT comparing open-door to French-door laminoplasty for cervical compressive myelopathy, both techniques were found to be equivalent in terms of neurological recovery and perioperative complications, but patients receiving the open-door technique had more kyphosis and less cervical range of motion postoperatively.
- An update to a 2002 Cochrane review found no significant outcome differences between supervised and home-exercise rehabilitation programs after lumbar disc surgery.
- A systematic review/meta-analysis showed that radiofrequency denervation of facet joints is more effective than placebo in achieving functional improvement and pain control in patients with chronic low back pain.
- A Level II diagnostic study concluded that with a magnification of 150% and a good pair of flexion and extension radiographs following anterior cervical arthrodesis, pseudarthrosis was noted with >1 mm of motion between fused interspinous processes with 96.1% specificity and a positive predictive value of 96.9%.
- A Level I therapeutic study comparing the efficacy of intravenous tranexamic acid, epsilon-aminocaproic acid, and placebo to reduce bleeding in 125 adolescent patients undergoing posterior fusion for idiopathic scoliosis found less intraoperative and postoperative blood loss and higher hematocrit levels with the antifibrinolytics than with placebo. However, transfusion requirements were no different between the groups.
- A randomized comparison of navigated versus freehand techniques for pedicle screw insertion during lumbar procedures found that surgeon radiation exposure with freehand technique is up to 10 times greater than with use of navigation.