Caution Appropriate as We Investigate New Approaches to Pain Management
The dangers of chronic opioid use have rightly been at the forefront of orthopaedic practice considerations in recent years. The widespread use of regional anesthesia and periarticular-injection cocktails, targeted NSAID utilization, and strict limitations on opioid use have become standard approaches for postoperative pain management.
With the availability of cannabinoids in numerous state jurisdictions, attention has now turned to the potential of these compounds to enhance patient comfort in the postoperative period. However, as we contemplate their use, it’s imperative that we also evaluate the impact of these compounds on clinically important outcomes such as bone-healing and fusion. The track record of nicotine, NSAIDs, and other compounds in terms of the impact on bone-healing is enough to suggest caution.
In the June 2, 2021 issue of JBJS, Yun et al. provide new insight into this topic. Specifically, they evaluated the impact of cannabinoid receptor agonist WIN55 on osteogenic differentiation in vitro and bone regeneration and spinal fusion in a preclinical rat model.
They found that WIN55 had no adverse impact on osteogenic differentiation of primary bone marrow stem cells in vitro. As noted by the authors, “mRNA expression levels of Runx2 and Alp were similar among cells treated with vehicle alone and WIN55. Likewise, exposure to WIN55 did not inhibit ALP [Alkaline phosphatase] activity or bone matrix mineralization.”
In addition, no adverse impact of WIN55 on spinal fusion or bone regeneration was found. Forty-five rats (15 per group) underwent L4-L5 posterolateral spinal fusion with bilateral placement of collagen scaffolds soaked with rhBMP-2. The rats were treated with vehicle alone or 0.5 or 2.5 mg/kg WIN55 by way of daily intraperitoneal injections for 5 days. Radiography, manual palpation-based fusion scoring, microCT, and histology were used for assessment. No significant differences among the groups in the mean fusion score, fusion rate, and new bone volume were demonstrated.
These findings are intriguing, and such research helps set the stage for carefully designed in vivo research projects, eventually moving toward randomized controlled trials, before recommending widespread use of cannabinoids for post-surgical pain management.
Marc Swiontkowski, MD
JBJS Editor-in-Chief
Sustained Fevers After Spinal Fusion: A Sentinel for Infection?
Postoperative fevers occur frequently. During the first 2 to 3 days after surgery, these fevers are often due to atelectasis or the increased inflammatory response that arises from tissue injury during surgery. However, persistent postoperative fevers should be cause for concern. In the August 19, 2020 issue of The Journal, Hwang et al. examine the relationship between sustained fevers after spine instrumentation and postoperative surgical site infection.
The authors retrospectively reviewed 598 consecutive patients who underwent lumbar or thoracic spinal instrumentation. They excluded patients who underwent surgery to treat tumors or infections and those with other identified causes of fever, such as a urinary tract infection or pneumonia. Sustained fevers were defined as those that began on or after postoperative day (POD) 4 and those that started on POD 1 to 3 if they persisted until or beyond POD 5.
Sixty-eight patients (11.4%) met the criteria for a sustained fever after spinal instrumentation. Nine of those 68 (13.2%) were diagnosed with a surgical site infection. Of the 530 patients who did not have a sustained fever, only 5 (0.9%) developed a surgical site infection (p<0.001 for the between-group difference).
Further analysis revealed 3 diagnostic clues for surgical site infections among the patients with sustained fevers:
- Continuous fever (rather than cyclic or intermittent)
- Levels of C-reactive protein (CRP) >4 mg/dL after POD 7
- Increasing or stationary patterns of CRP level and neutrophil differential
In addition, the authors found that CRP levels >4 mg/dL between PODs 7 and 10 had much greater sensitivity for discriminating surgical site infection than gadolinium-enhanced magnetic resonance imaging data obtained within 1 month of the surgical procedure.
Although a vast majority (87%) of patients with sustained postoperative fevers in this study did not develop an infection, persistent fever after spine instrumentation surgery is something to be mindful of. The authors describe their findings as “tentative” and advise readers to interpret them with caution. Those caveats notwithstanding, I consider this information to be valuable because it might help prevent delays in the diagnosis of a potentially serious perioperative complication.
Matthew R. Schmitz, MD
JBJS Deputy Editor for Social Media
Owning the Bone in Spine Surgery
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.
Approximately 20% of patients who undergo spine surgery have osteoporosis, which has a significant impact on spine-surgery complications such as failure of fixation devices and collapse fractures following fusion procedures. In a recent critical analysis review, authors focus on improving outcomes by identifying and optimizing patients with osteoporosis prior to spine surgery. The multidisciplinary team involved in that process should include primary care providers, endocrinologists, physical therapists, and orthopaedic surgeons.
The predominant tool for assessing bone mineral density (BMD) is dual x-ray absorptiometry. The diagnosis is based on a T score, which represents the number of standard deviations between the patient’s BMD and that of a healthy 30-year-old woman. Standard deviations ≤─2.5 define osteoporosis. The Z score is similar to the T score but compares the patient to an age- and sex-matched individual.
A history of low-energy fracture, such as a wrist fracture following a fall from a standing height, is considered a sentinel event for suspicion of fragility fractures. The combination of a fragility fracture and low BMD is considered to be severe osteoporosis. The most common form of osteoporosis is associated with a postmenopausal decrease in mineralization, but there are other causes. These include advanced kidney disease, hypogonadism, Cushing disease, vitamin D deficiency, anorexia and/or bulimia, rheumatoid arthritis, hyperthyroidism, primary hyperparathyroidism, and some medications (e.g., anticonvulsants, corticosteroids, heparin, and proton pump inhibitors).
Forty-seven percent of patients undergoing spine deformity surgery and 64% of cervical spine surgery patients have low vitamin D levels. Postoperative bone health can be enhanced in women ≥51 years old with daily intake of 800 to 1,000 units of vitamin D and 1,200 mg of daily calcium. There is no solid evidence that pre- or postoperative bisphosphonates have a positive impact on bone healing. Conversely, some series have shown that teriparatide, an anabolic parathyroid hormone, may improve time-to-fusion and help reduce screw pull-out after lumbar fusion in postmenopausal women.
Calcitonin has been shown to reduce the incidence of vertebral compression fracture, but there is no concrete evidence that it supports spine-fusion healing. Similarly, there is no strong evidence for the use of estrogen or selective estrogen receptor modulators in this surgical scenario. There is evidence that when the human monoclonal antibody denosumab is combined with teriparatide, spine-fusion healing may be improved relative to the use of teriparatide alone. Finally, the review article identifies screw size, screw position, and other surgical considerations that can improve fixation strength.
Using the “Own the Bone” practices promulgated by the American Orthopaedic Association and the technical considerations described in this review, we should be able to mitigate osteoporosis-related postoperative complications in spine-surgery patients.
Not All Modes in Multimodal Pain Management are Effective
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
JBJS Editor-in-Chief
Vancomycin Powder May Thwart Spinal Fusion
Prompted by relatively high infection rates associated with surgical treatment of pediatric spinal conditions such as scoliosis and spinal-deformity surgery in immunocompromised adults, spine surgeons have led “deep dive” clinical research into the possible benefits of local, intrawound antibiotic therapy. Consequently, the administration of antibiotic powder around the spine’s posterior elements and internal-fixation devices has become fairly widespread. But are there possible downsides to this approach that can impact patient outcomes?
This important question is addressed in the basic-science study by Ishida et al. in the October 2, 2019 issue of The Journal. The authors analyzed the fusion-specific impact of varying concentrations of intrawound vancomycin and tobramycin in a well-characterized rat model of posterolateral fusion performed with syngeneic iliac-crest allograft plus clinical bone-graft substitute. Ishida et al. found that a high dose of vancomycin (71.5 mg/kg, about 5 times higher than spine surgeons typically use) but not tobramycin had detrimental effects on fusion-mass formation in this model, as demonstrated by micro-computed tomography and histological analysis.
We now need further clinical research from the spine community to determine the optimal doses and types of intrawound antibiotics in this setting. Based on the currently available data, power calculations should be performed when designing future trials focused on this question. There seems to be little remaining doubt that locally delivered antibiotics help limit surgical-site and deep infections in spinal surgery. The impact of antibiotics on fusion rates must now be investigated further.
Marc Swiontkowski, MD
JBJS Editor-in-Chief
What’s New in Spine Surgery
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. Click here for a collection of all OrthoBuzz Specialty Update summaries.
This month, OrthoBuzz asked Theodore Choma, MD, co-author of the June 21, 2017 Specialty Update on spine surgery, to select the five most clinically compelling findings from among the more than 40 studies cited in the article.
Biomaterials and Biologics
A multicenter randomized prospective trial compared osteogenic protein-1 (OP-1, also known as bone morphogenetic protein [BMP]-7) combined with local autograft to iliac crest autograft combined with local autograft in posterolateral lumbar fusion. Based on computed tomography (CT) scan assessments, the authors found a 54% fusion rate in the OP-1 group and a 74% fusion rate in the iliac crest group. OP-1 appears to be a poor substitute for iliac crest autograft for achieving posterolateral lumbar fusion.
Adult Spinal Deformity (ASD)
We continue to elucidate the risks and morbidity of adult degenerative spinal deformity surgery. The Scoli-Risk-1 study,1 a Level-III multicenter, prospective observational study, reported on 272 patients with ASD treated surgically. Twenty-two percent of the patients were discharged from the hospital with a decline in the lower-extremity motor score, while only 13% demonstrated improvement. However, by 6 months postoperatively, 21% demonstrated improvement, 69% demonstrated maintenance, and 11% continued to demonstrate lower-extremity motor decline.
Spinal Cord Injury
A Level-I, randomized, crossover trial2 examined whether the character of neuropathic pain following spinal cord injury determined the response to 300 mg/day of either pregabalin or oxcarbazepine. Both anticonvulsant medications significantly improved neuropathic pain in these patients. A subgroup analysis demonstrated that oxcarbazepine was more effective in patients without evoked pain and pregabalin was more effective in patients with evoked pain.
Lumbar Degenerative Spondylolisthesis
To address the consequences of fusion along with decompression in degenerative lumbar spondylolisthesis, a Level-I, randomized controlled trial3 specifically compared laminectomy only with laminectomy plus fusion among 66 patients with stable degenerative spondylolisthesis and symptomatic lumbar stenosis. Patients in the fusion group had significantly higher SF-36 scores at 2, 3, and 4 years, but the groups did not differ with respect to ODI scores at 2 years. The authors reported a significantly higher reoperation rate (34% compared with 14%) in the decompression-only group over the 4-year follow-up, but patients who underwent decompression with fusion began to have an increase in the probability of reoperation 36 months after surgery.
Osteoporotic Injuries
We have more evidence of the effectiveness of vertebral cement augmentation for osteoporotic thoracolumbar compression fractures. The authors of a level-I systematic review and meta-analysis examined randomized controlled trials comparing vertebroplasty with conservative treatment or placebo/sham and identified 11 relevant studies involving 1,048 subjects. The meta-analysis found that patients receiving percutaneous vertebroplasty (n = 531) had lower pain ratings at 1 to 2 weeks, 2 to 3 months, and 1 year. The effect size of vertebroplasty was significant and close to the minimal clinically important difference (MCID).
References
- Lenke LG, Fehlings MG, Shaffrey CI, Cheung KM, Carreon L, Dekutoski MB, Schwab FJ, Boachie-Adjei O, Kebaish KM, Ames CP, Qiu Y, Matsuyama Y, Dahl BT, Mehdian H, Pellis´e-Urquiza F, Lewis SJ, Berven SH. Neurologic outcomes of complex adult spinal deformity surgery: results of the prospective, multicenter Scoli-RISK- 1 study. Spine (Phila Pa 1976). 2016 Feb;41(3):204-12.
- Min K, Oh Y, Lee SH, Ryu JS. Symptom-based treatment of neuropathic pain in spinal cord-injured patients: a randomized crossover clinical trial. Am J Phys Med Rehabil. 2016 ;95(5):330–8
- Ghogawala Z, Dziura J, Butler WE, Dai F, Terrin N, Magge SN, Coumans JV, Harrington JF, Amin-Hanjani S, Schwartz JS, Sonntag VK, Barker FG 2nd, Benzel EC. Laminectomy plus fusion versus laminectomy alone for lumbar spondylolisthesis. N Engl J Med. 2016 Apr 14;374(15):1424-34.
JBJS Classics: Wiltse’s Paraspinal Muscle-Splitting Approach
OrthoBuzz regularly brings you a current commentary on a “classic” article from The Journal of Bone & Joint Surgery. These articles have been selected by the Editor-in-Chief and Deputy Editors of The Journal because of their long-standing significance to the orthopaedic community and the many citations they receive in the literature. Our OrthoBuzz commentators highlight the impact that these JBJS articles have had on the practice of orthopaedics. Please feel free to join the conversation by clicking on the “Leave a Comment” button in the box to the left.
Almost 50 years ago, in a classic 1968 JBJS paper, Leon Wiltse and co-authors described a novel and innovative access route to the lumbar spine. At that time, the vast majority of approaches to the lumbar spine were performed through midline incisions. Wiltse´s approach, however, utilized a more lateral access route to the spine. In this beautifully illustrated paper, the authors described a curved incision of the fascia and the skin with direct access to the transverse processes, pedicles, and the lateral masses.
The advantages of this novel access were multifold. Although wide midline laminectomies represented the gold-standard decompression technique at that time, the lateral approach served to avoid a more challenging and risky midline revision access, adding an elegant access for salvage procedures. Two goals of Wiltse’s approach were to achieve solid, posterolateral fusions and to decompress the neural structures. Graft harvest from the posterior iliac crest was easily facilitated with this approach.
Additional advantages included reduced blood loss and less muscle ischemia, and the preservation of spinous processes and intra-/supraspinous ligaments, which served to maintain the stability of the lumbar spine. The main downside was the necessity of performing two skin incisions as opposed to just one midline incision.
Since its introduction, Wiltse´s approach and the anatomic planes have been studied in great detail.1,2 Considering the vast developments in spine surgery over the last years and decades, the Wiltse approach has stood the test of time, as it still represents one of the main access routes to the lumbar spine that any skilled spine surgeon needs to master.
With the arrival of instrumentation, Wiltse´s approach was later employed in interbody fusion and minimally invasive transforaminal lumbar interbody fusion (TLIF) techniques, as it allowed direct access to the pedicles and the disc space. It has also been used for various techniques of direct pars repair.3
With the addition of some minor modifications, Wiltse´s approach still reflects the main access for minimally invasive, microsurgical treatment of foraminal and extraforaminal disc herniations, including bony decompression of the neuroforamen.4 The far lateral access permits sufficient decompression of the exiting nerve roots while preserving the facet joints, which serves to avoid more invasive fusion techniques for a considerable number of patients.
Overall, Wiltse´s innovative approach advanced spinal care by reducing access–related morbidity. Dr. Wiltse passed away at age 92 in 2005. His major achievements in spine surgery and his great accomplishments will remain in our memories and will continue to impact spine surgery over the coming decades.
Christoph J. Siepe, MD
JBJS Deputy Editor
References
- Vialle R, Court C, Khouri N, et al. Anatomical study of the paraspinal approach to the lumbar spine. Eur Spine J. 2005;14(4):366-71.
- Palmer DK, Allen JL, Williams PA, et al. Multilevel magnetic resonance imaging analysis of multifidus-longissimus cleavage planes in the lumbar spine and potential clinical applications to Wiltse’s paraspinal approach. Spine (Phila Pa 1976). 2011;36(16):1263-7.
- Xing R, Dou Q, Li X, et al. Posterior Dynamic Stabilization With Direct Pars Repair via Wiltse Approach for the Treatment of Lumbar Spondylolysis: The Application of a Novel Surgery. Spine (Phila Pa 1976). 2016;41(8):E494-502.
- Mehren C, Siepe CJ. Neuroforaminal decompression and intra-/extraforaminal discectomy via a paraspinal muscle-splitting approach. Eur Spine J. 2016.
Are Ortho Patients Getting Too Many Pain Pills?
Surgeons often prescribe more postoperative pain medication than their patients actually use. That’s partly because there is limited procedure-specific evidence-based data regarding optimal amounts and duration of postoperative narcotic use—and because every patient’s “relationship” with postoperative pain is unique. Nevertheless, physician prescribing plays a role in the current opioid-abuse epidemic, so any credible scientific information about postoperative narcotic usage will be helpful.
The Level I prognostic study by Grant et al. in the September 21, 2016 issue of The Journal of Bone & Joint Surgery identified factors associated with high opioid use among a prospective cohort of 72 patients (mean age 14.9 years) undergoing posterior spinal fusion for idiopathic scoliosis.
Higher weight and BMI, male sex, older age, and higher preoperative pain scores were associated with increased narcotic use after surgery. Somewhat surprisingly, the number of levels fused, number of osteotomies, in-hospital pain level, self-reported pain tolerance, and surgeon assessment of anticipated postoperative narcotic requirements were unreliable predictors of which patients would have higher postoperative narcotic use.
Because the authors found that pain scores returned to preoperative levels by postoperative week 4, they say, “further refills after this point should be considered with caution.” Additionally, after reviewing the cohort’s behavior around disposing of unused narcotic medication, the authors conclude, “We consider discussion of narcotic use and disposal to be an important component of the 1-month postoperative visit…This important educational opportunity could help decrease abuse of narcotics.”
Mobility of Listhesis Key in Surgical Decision Making for Spondylolisthesis
OrthoBuzz occasionally receives posts from guest bloggers. This guest post comes from Brett A. Freedman, MD, in response to two recent NEJM studies on treating spondylolisthesis.
The April 14, 2016 edition of The New England Journal of Medicine published results from two randomized clinical trials (RCTs) evaluating the benefits of laminectomy alone versus laminectomy and fusion for the treatment of specific spinal conditions in patients 50 to 80 years old, with at least 2-year follow-up. The larger study was conducted in Sweden and included 247 patients, 135 of whom had degenerative spondylolisthesis of some magnitude. In this study, the surgical technique varied and was left to the treating provider’s preference. The ultimate conclusion of this study was that adding fusion to the procedure did not result in better patient outcomes by any index measured.
Conversely, an essentially concurrent but unrelated RCT evaluating similar outcomes in a US patient population (n=66) with degenerative spondylolisthesis that measured at least 3 mm, but in which there was no instability, concluded that spinal fusion, using a standardized technique (pedicle screws and rods with iliac crest bone graft), did provide a significant clinical benefit. Specifically, this study found significant improvement in SF-36 physical-component summary scores (the primary outcome measure) and lower reoperation rates (14% vs. 34%; p=0.05) compared to decompression alone.
When two Level 1 studies published on the same day in the same high-impact journal come to divergent conclusions about the same clinical question, we must pause and look to the past. Spine surgeons have investigated decompression alone for spondylolisthesis, first by necessity (prior to the era of reliable spinal fusion) and then later in comparison to in-situ and instrumented fusion1,2. Consensus is consistent with anatomic reasoning. Dysfunctional lumbar mobile segments, especially those with preserved or excessive motion (i.e. >2 to 4 mm change on flexion-extension films), produce a mechanical pathoanatomic sequence of events that leads to critical and clinically symptomatic spinal stenosis. Addressing this first cause is paramount.
The immediate effect of surgery type is largely neutralized by the fact that the decompression component, which is common to both approaches, is principally responsible for acute improvement. Because most prospective studies are not able to reliably track patients beyond 2 to 5 years, the longer-term benefits of a solid arthrodesis of a dysfunctional spinal-motion segment compared to a simple decompression in which some of the incompetent posterior elements are further surgically removed remain largely unknown. Anecdotally, spine surgeons recognize that failures of decompression alone in mobile spondylolisthesis occur quite frequently—and that revision fusion surgery in this situation is significantly more complicated than primary decompression and fusion. That was the case in the Swedish study, where the majority of revision surgeries in the decompression-only cohort were performed at the same level as the prior surgery, versus adjacent levels in the fusion group. And, again, reoperation rates were significantly higher (>2x) in the decompression-only group in the US study.
Given conflicting data3, there likely are cofactors that need to be identified and further studied to select cases of spondylolisthesis that can be treated well with decompression alone, versus those that require the stabilizing effect of a fusion. Until then, surgeons must weigh the data available and provide the surgical option they feel is best for each individual patient.
Brett A. Freedman, MD is an orthopaedic surgeon specializing in spine trauma and degenerative spinal diseases at the Mayo Clinic in Rochester, MN
References
- Fischgrund JS, Mackay M, Herkowitz HN, Brower R, Montgomery DM, Kurz LT. Degenerative lumbar spondylolisthesis with spinal stenosis: a prospective, randomized study comparing decompressive laminectomy and arthrodesis with and without spinal instrumentation. Spine (Phila Pa 1976). 1997 Dec 15;22(24):2807-12.
- Bridwell KH, Sedgewick TA, O’Brien MF, Lenke LG, Baldus C. The role of fusion and instrumentation in the treatment of degenerative spondylolisthesis with spinal stenosis. J Spinal Disord. 1993 Dec;6(6):461-72.
- Joaquim AF, Milano JB, Ghizoni E, Patel AA. Is There a Role for Decompression Alone for Treating Symptomatic Degenerative Lumbar Spondylolisthesis?: A Systematic Review. J Spinal Disord Tech. 2015 Dec 24. [Epub ahead of print]
BMP vs Autograft for Instrumented Posterolateral Lumbar Fusion
In diligent efforts to improve osseous bridges when performing spinal fusion surgery, orthopaedists have been using harvested allograft bone for more than a century and bone morphogenetic protein (BMP) for nearly a half century. Now, a European multicenter, randomized trial by Delawi et al., in the March 16, 2016 Journal of Bone & Joint Surgery, has compared overall success (defined as a combination of CT-determined fusion rates and clinical results at 12 months) between the two approaches among 113 patients.
This was a non-inferiority trial, and the BMP formulation used (Osigraft BMP-7, known commonly as OP-1 and available in the US in a similar formulation known as OP-1 Putty) was not non-inferior to iliac crest autograft. To clarify the potentially confusing double negative: OP-1 was less successful than autograft, due primarily to lower fusion rates. There were no significant between-group differences in clinical outcomes as measured by scores on the Oswestry Disability Index, although the authors added that “our follow-up period of one year may have been too short to show differences in clinical results.”
Delawi et al. conclude that, based on their findings, “use of OP-1 in place of autologous iliac crest bone graft in instrumented posterolateral lumbar fusions cannot be recommended.” That conclusion is echoed by commentator Jeffrey Coe, MD, who sees these findings as “another bit of evidence against the use of rhBMP-7 as a substitute for [iliac crest bone grafts] in posterolateral spinal fusion.”
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