Abdallah, Faraj W.

Background: The use of spinal cord stimulation (SCS) for managing severe refractory chronic pain has expanded considerably due to positive statistical evidence regarding its use; however, the statistical robustness of the underlying randomized controlled trials (RCTs) requires further scrutiny. One such tool that can be used for this purpose is the fragility index, which quantifies how many individual outcome events must be altered for an outcome to lose statistical significance. Thus the index can be used quantitatively to assess the stability and robustness of an RCT’s conclusions, with higher values indicating increased trial stability. This study assesses the fragility of pain outcomes across RCTs investigating SCS for chronic pain to better understand the quality and robustness of evidence. Methods: A systematic search was conducted for RCTs assessing SCS for any chronic pain indication. The primary outcome was an evaluation of the trial-specific fragility index for the prespecified pain primary outcomes of RCTs. Secondary outcomes included an evaluation of fragility for (1) specified indications for SCS therapy, (2) reported pain outcomes appearing in three or more RCTs, (3) the presence/absence of a conflict of interest, and (4) comparisons of SCS to conservative management or different SCS waveform modalities. Results: A total of 30 RCTs were included. The median (interquartile range [IQR]) fragility index across the primary outcome of all trials was 5.45 (3.00 to 11.45). There was no statistical difference between the (1) types of outcomes (dichotomous vs. continuous; P = 0.710), (2) primary versus secondary pain outcomes ( P = 0.771), or (3) presence versus absence of trial conflict of interest ( P = 0.753). Indications with a median (IQR) fragility score greater than three included persistent spinal pain syndrome type 2 with a score of 8.00 (2.80 to 12.60), painful diabetic neuropathy with a score of 6.00 (3.00 to 11.80), complex regional pain syndrome with a score of 7.20 (4.62 to 81.50), mixed etiologies with a score of 9.00 (3.00 to 38.00), and other etiologies with a score of 3.00 (1.00 to 8.55). Conclusions: This study suggests that the majority of RCTs investigating primary pain outcomes after SCS therapy are robust with relatively high fragility scores. Reporting the fragility of outcomes in trials can provide a more comprehensive assessment of trial robustness and can further aid clinicians in interpreting trial results and making informed treatment decisions.

Background: Periarticular local infiltration analgesia has become an important mainstay of multimodal analgesia after elective total hip arthroplasty (THA). However, the role of novel motor-sparing fascial plane blocks—with or without periarticular local infiltration analgesia—has not been fully elucidated for patients undergoing THA. The authors conducted a network meta-analysis evaluating the relative analgesic effectiveness of motor-sparing fascial plane blocks (quadratus lumborum, erector spinae, and pericapsular nerve group blocks) and periarticular local infiltration analgesia for adult patients undergoing THA. Methods: Randomized trials examining single-injection quadratus lumborum, erector spinae, or pericapsular nerve group blocks, or periarticular local infiltration analgesia, for THA were sought. The primary outcome was area under the curve (AUC) rest pain scores during the period from 0 to 24 h. Secondary outcomes included rest pain scores at 0, 6, 12, and 24 h; postoperative function at 6, 12, and 24 h; analgesic consumption at 0 to 24 h; incidence of opioid-related side effects; and incidence of block-related complications. Network meta-analysis was performed using a frequentist approach. Results: A total of 44 trials (3,579 patients) evaluating the quadratus lumborum block, erector spinae block, pericapsular nerve group block, or periarticular local infiltration analgesia for THA were considered. Network meta-analysis was used to derive the probability of each intervention being the most effective as compared to the others (P score). For AUC 0 to 24 h rest pain, periarticular local infiltration analgesia was the most effective intervention, as demonstrated by a P score of 89%. For postoperative analgesic consumption, the quadratus lumborum block was the most effective intervention, with a P score of 88%. This was followed by the pericapsular nerve group block (74%), the erector spinae block (38%), and periarticular local infiltration analgesia (42%). Conclusions: Periarticular local infiltration analgesia alone provides the most consistent improvements in postoperative rest pain, analgesic consumption, and functional recovery after THA. The addition of a quadratus lumborum block or pericapsular nerve group block to periarticular local infiltration may further improve analgesic outcomes.

Background: Both perineural and intravenous dexamethasone have been proposed as effective adjuncts that prolong the duration of peripheral nerve blocks. The authors sought to explore whether combining systemic with perineural dexamethasone yields any additive or synergistic effect on the characteristics and analgesic effects of peripheral nerve blocks. Methods: Adult patients having distal radius open reduction and internal fixation and/or carpometacarpal arthroplasty under supraclavicular block were randomized to intravenous dexamethasone, a combination of perineural plus intravenous dexamethasone, or no dexamethasone (control). Sensory block duration was set as the primary outcome. Secondary outcomes included motor block duration; postoperative rebound pain scores as well as worst pain at 8, 16, 24, 32, 40, and 48 h; opioid consumption at 0 to 24 and 25 to 48 h; incidence of nausea/vomiting; and presence of burning sensation in the blocked limb at 24 and 48 h. The null hypothesis was lack of difference in sensory block duration between the three groups. Results: A total of 104 patients were included in the analysis (intravenous dexamethasone, 37; intravenous plus perineural dexamethasone, 34; control, 33). Compared to intravenous dexamethasone alone, adding perineural dexamethasone did not yield any incremental benefits in any of the outcomes examined. The mean ± SD of sensory block duration was 21.3 ± 7.3 h in the intravenous dexamethasone group, 20.6 ± 6.1 h in the perineural plus intravenous group, and 16.8 ± 6.8 h in the control group. The mean difference (95% CI) of sensory block duration was significantly prolonged by 4.5 h (95% CI, 1.3 to 7.7; P = 0.006) in the intravenous dexamethasone group and 3.8 h (95% CI, 0.8 to 6.8; P = 0.015) in the perineural plus intravenous dexamethasone group compared to control; however, no difference was observed when the two dexamethasone groups were compared to each other (0.7 h [95% CI, –2.5 to 3.9]; P = 0.670). Compared to control, both intravenous and intravenous plus perineural dexamethasone similarly reduced 24-h pain scores and opioid consumption and decreased incidence of rebound pain. Conclusions: The authors’ findings suggest that intravenous dexamethasone alone is sufficient to improve analgesic outcomes for patients receiving supraclavicular block for upper extremity surgery. Combining the intravenous and perineural dexamethasone routes does not yield an additive or synergistic effect on the characteristics and analgesic effects of supraclavicular block.

Summary Non‐steroidal anti‐inflammatory drugs (NSAIDs) are one of the mainstays of multimodal pain management. While effective for acute pain control, recent pre‐clinical evidence has raised concerns regarding an association between NSAIDs and chronic pain and potential opioid use. Our objective was to explore the association between peri‐operative use of prescription NSAIDs and the need for continued opioid prescriptions lasting 90–180 days in previously opioid‐naïve patients undergoing total knee arthroplasty. A database of health claims in the USA was used to identify all opioid‐naïve adult patients who underwent primary knee arthroplasty between January 2010 and October 2021. We evaluated the magnitude of association between peri‐operative prescription NSAID claims and claims for opioids at 90 days postoperatively using multivariable logistic regression models. Secondary outcomes included: the magnitude of association between peri‐operative NSAID prescription and claims for opioids at 180 days postoperatively; and identifying other potential factors associated with opioid claims at 90 days postoperatively. After risk adjustment using multivariable logistic regression models in the 789,736‐patient cohort, the adjusted odds ratio (95%CI) for a continuous claim of opioids at 90 and 180 days postoperatively among patients with a peri‐operative NSAID prescription within 30 days was 1.32 (1.30–1.35), p < 0.001; and 1.12 (1.10–1.15), p < 0.001, respectively. This estimate of effect remained robust at 90 days after accounting for known potential confounders, including pre‐existing knee pain and acute postoperative pain severity. Similar analysis of other pain medications (e.g. paracetamol) did not detect such an association. This population‐based cohort study suggests that peri‐operative prescription NSAID use may be associated with continued opioid prescription claims at 90 and 180 days after knee arthroplasty, even after adjusting for other observed covariates for continuous opioid claims. These novel findings can inform clinical decision‐making for post‐surgical pain management, risk–benefit discussions with patients and future research.

Background The analgesic effectiveness of contemporary motor-sparing nerve blocks used in combination for analgesia in total knee arthroplasty is unclear. This network meta-analysis was conducted to evaluate the analgesic effectiveness of adding single-injection or continuous adductor canal block (ACB) with or without infiltration of the interspace between the popliteal artery and the capsule of the posterior knee (iPACK) to intraoperative local infiltration analgesia (LIA), compared to LIA alone, after total knee arthroplasty. Methods Randomized trials examining the addition of single-injection or continuous ACB with or without single-injection block at the iPACK to LIA for total knee arthroplasty were considered. The two primary outcomes were area-under-the-curve pain scores over 24 to 48 h and postoperative function at greater than 24 h. Secondary outcomes included rest pain scores at 0, 6, 12, and 24 h; opioid consumption (from 0 to 24 h and from 25 to 48 h); and incidence of nausea/vomiting. Network meta-analysis was conducted using a frequentist approach. Results A total of 27 studies (2,317 patients) investigating the addition of (1) single-injection ACB, (2) continuous ACB, (3) single-injection ACB and single-injection block at the iPACK, and (4) continuous ACB and single-injection block at the iPACK to LIA, as compared to LIA alone, were included. For area-under-the-curve 24- to 48-h pain, the addition of continuous ACB with single-injection block at the iPACK displayed the highest P -score probability (89%) of being most effective for pain control. The addition of continuous ACB without single-injection block at the iPACK displayed the highest P -score probability (87%) of being most effective for postoperative function. Conclusions The results suggest that continuous ACB, but not single-injection ACB and/or single-injection block at the iPACK, provides statistically superior analgesia when added to LIA for total knee arthroplasty compared to LIA alone. However, the magnitude of these additional analgesic benefits is clinically questionable. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New