Literature Review

November 2020 Issue

  1. Jerry W. Jones, MD Assistant Professor; Director, Acute Pain Service, University of Tennessee Health Science Center Co-author
  2. Anthony Machi, MD Assistant Professor; Fellowship Director, University of Texas Southwestern Medical Center Co-author
  3. Sudheer Potru, DO Director, Complex Pain and High-Risk Opioid Clinic; Assistant Professor, Department of Anesthesiology, Atlanta VA Medical Center; Emory School of Medicine Co-author


Editor’s note: “Literature Review” is a new feature of the ASRA News designed to provide you with brief summaries of recent articles of interest, particularly from sources that our readers might not normally consume. 


Risk of Nonunion with Nonselective NSAIDs, COX-2 Inhibitors, and Opioids

George MD, Baker JF, Leonard CE, Mehta S, Miano TA, Hennessy S. J Bone Joint Surg Am. 2020;102:1230-8. doi: 10.2106/JBJS.19.01415.

Selection and summary by Jerry Jones, MD.

Background:  The incidence of nonunion is approximately 2-10% after long bone fracture and is influenced by fracture location, energy of injury, comorbidities, and other factors. Cyclooxygenase-2 (COX-2) is important in fracture healing, and some animal studies suggest that nonsteroidal anti-inflammatory drugs (NSAIDS), particularly selective COX-2 inhibitors, may impair bone healing enough to increase the risk of nonunion. To date, the safety and clinical relevance of these medications with regards to the risk of nonunion has not been elucidated from human studies. The recognized risks of opioids increase the need to further evaluate the relative risks of utilizing COX-2 inhibitors and nonselective NSAIDS for patients at risk for nonunion.

Using a national private health insurance claims database, 339,864 episodes from 326,876 patients with an ICD-9 diagnosis of an isolated long bone extremity or clavicle fracture that met inclusion criteria were identified retrospectively. Patients with multiple fractures, fracture within the previous year, bone cancer or cancer metastatic to bone, history of malunion/nonunion, malunion/nonunion <90 days after fracture, and those with <1 year follow up or <6 months of prior records were excluded. Filled prescriptions for nonselective NSAIDS, COX-2 inhibitors, and opioids prior to and within 30 days after the fracture were analyzed along with any ICD-9 diagnosis of nonunion between 91 and 365 days after the fracture.

Results: A diagnosis of nonunion occurred in 1.6% of patients, and a procedure to treat the nonunion occurred in 0.9% of patients. Filling a single nonselective NSAID prescription after an isolated long bone fracture was not associated with a greater risk of nonunion (OR=1.07; 1.08 with procedure). Filling a prescription for a COX-2 inhibitor (OR=1.48; 1.84 with procedure) or opioid (OR=1.53; 1.69 with procedure) after an isolated long bone fracture was associated with a greater risk of nonunion. Filling a prescription in the 90 days prior to an isolated long bone fracture was associated with an increased risk of nonunion for nonselective NSAIDS (OR=1.36; 1.44 with procedure) or COX-2 inhibitors (OR=1.76; 1.60 with procedure) but not for opioids. Patients filling multiple prescriptions for nonselective NSAIDS, COX-2 inhibitors, or opioids in the 60 days after the fracture had higher nonunion rates. 

Key points:  Short term use of nonselective NSAIDS after an isolated long bone fracture is not associated with a greater risk of nonunion. Short term use of COX-2 inhibitors or opioids after an isolated long bone fracture is associated with an increased risk of nonunion. Prior exposure to NSAIDS or COX-2 inhibitors increases the risk of nonunion. Multiple prescriptions after a fracture may reflect increased injury severity which might be a confounding factor. Generalizing these results to other patient populations may not be appropriate as this population has a relatively low risk of nonunion.


Cooled Radiofrequency Ablation Compared with a Single Injection of Hyaluronic Acid for Chronic Knee Pain: A Multicenter, Randomized Clinical Trial Demonstrating Greater Efficacy and Equivalent Safety for Cooled Radiofrequency Ablation

Chen AF, Khalouf F, Zora K et al. J Bone Joint Surg Am. 2020; 102:1501-10. doi: 10.2106/JBJS.19.00935

Selection and summary by Sudheer Potru, DO

Background: Recent studies have called into question the practice of both corticosteroid and hyaluronic acid injections for treatment of knee osteoarthritis (OA). This extremely common condition can be refractory to other measures and many patients do not want to undergo operative interventions. Genicular nerve radiofrequency ablation (RFA) has been demonstrated in numerous studies to be a highly effective treatment for both knee OA pain and persistent knee pain after TKA. The cooled radiofrequency ablation technique utilizes cooling technology to allow for longer and larger lesion creation; there is some evidence that this provides longer duration of relief.

A multicenter controlled trial enrolled 175 patients with knee OA refractory to non-operative intervention. Patients were randomized to genicular cooled radiofrequency ablation (CRFA) at four sites in the knee versus a single hyaluronic acid (HA) injection.  Only one knee was treated for each patient during the study and subjects with a positive response (>50% pain reduction) to a genicular nerve block proceeded into the treatment group.  A total of 158 patients (76 CRFA and 82 HA) completed the six-month follow up. Pain scores and various measures of function (Western Ontario and McMaster Universities Osteoarthritis Index [WOMAC]) and quality of life (Global Perceived Effect [GPE]) were obtained.

Results:  In the CRFA group, 71% of the subjects had greater than 50% reduction in the numerical rating scale (NRS) (primary end point) compared with 38% in the HA group, which was highly significant. At 6 months, the mean NRS score reduction was 4.1± 2.2 for the CRFA group compared with 2.5± 2.5 for the HA group (p < 0.0001). There was also statistically significant and substantial clinical improvement in the WOMAC (48% versus 23%) and GPE (72% versus 40%) noted.

Key points: In this industry-sponsored trial, cooled genicular RFA was demonstrated to be superior to single hyaluronic acid injection for treatment of non-operative knee osteoarthritis pain. That said, it behooves the user to consider the relative cost of these therapies in treatment of knee OA, an extremely common pain condition.


Acute Postoperative Pain Is Associated With Myocardial Injury After Noncardiac Surgery

Turan A, Leung S, Bajracharya GR, et al. Anesth Analg. 2020;131: 822-29. doi: 10.1213/ane.0000000000005033

Selection and summary by Anthony Machi, MD

Background: Pain activates the sympathetic nervous system. This leads to hypertension, tachycardia, and increased myocardial contractility. These physiologic changes increase myocardial work and oxygen consumption. In addition, the autonomic stress response decreases myocardial oxygen supply via alpha-mediated coronary vasoconstriction. In the postoperative setting, there is also activation of a hypercoagulable state and the renin-aldosterone-angiotensin system. Though the combined balance of these physiologic changes are well characterized and relate to myocardial injury after noncardiac surgery (MINS), no previous study had made the direct correlation of acute postoperative pain to MINS.

The authors performed a retrospective cohort analysis of 2892 adult patients from 4 separate prospective trials who had routine postoperative troponin monitoring after noncardiac surgery under general anesthesia with or without regional anesthesia. Time-weighted average pain scores were calculated from all available pain scores at 4-hour intervals. MINS was defined as peak troponin > 0.03 ng/mL within 72 hours after surgery. A generalized linear mixed model was used to assess the association between pain and MINS.

Results: 4.5% of patients had MINS, and higher time-weighted average pain scores were associated with increased hazard of myocardial injury.

Key points: Moderate-to-severe acute postoperative pain is associated with myocardial injury after noncardiac surgery. Higher average pain scores are associated with increasingly greater risk for MINS.

Tags: opioids, radiofrequency ablation, acute postoperative pain

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