Daily Anesthesiology Research Analysis
Three studies stand out today for anesthesiology and perioperative care: a randomized trial showed that nociception-guided intraoperative analgesia (NOX) reduced early postoperative delirium in elderly total knee arthroplasty patients; a large GWAS identified genomic loci associated with postoperative sepsis and surgical site infection; and a 5-year pooled analysis demonstrated durable pain, function, and opioid-sparing benefits after basivertebral nerve ablation for vertebrogenic low back pain.
Summary
Three studies stand out today for anesthesiology and perioperative care: a randomized trial showed that nociception-guided intraoperative analgesia (NOX) reduced early postoperative delirium in elderly total knee arthroplasty patients; a large GWAS identified genomic loci associated with postoperative sepsis and surgical site infection; and a 5-year pooled analysis demonstrated durable pain, function, and opioid-sparing benefits after basivertebral nerve ablation for vertebrogenic low back pain.
Research Themes
- Perioperative brain health and delirium prevention via nociception-guided analgesia
- Precision perioperative risk stratification using genomics for sepsis/SSI
- Durable interventional pain therapies with opioid-sparing outcomes
Selected Articles
1. Influence of Intraoperative Pain Management on Postoperative Delirium in Elderly Patients: A Prospective Single-Center Randomized Controlled Trial.
In elderly TKA patients with sedation guided by BIS in both groups, NOX-guided intraoperative analgesia reduced day-1 postoperative delirium (7% vs 16%) and required higher remifentanil dosing. This supports nociception-index guidance as a modifiable intraoperative factor for delirium prevention.
Impact: This RCT identifies intraoperative nociception-guided analgesia as a practical strategy to lower postoperative delirium, a major driver of morbidity in older surgical patients.
Clinical Implications: Incorporating nociception monitoring (e.g., NOX) to titrate intraoperative opioids while keeping sedation depth constant may reduce early postoperative delirium in older adults undergoing TKA.
Key Findings
- NOX-guided analgesia reduced day-1 postoperative delirium (7% vs 16%; P=0.041).
- Remifentanil dose was higher with NOX guidance (mean 927 vs 882 mg; P=0.002).
- Sedation depth was standardized with BIS in both groups, isolating the analgesia effect.
Methodological Strengths
- Prospective randomized controlled design with standardized sedation using BIS
- Clinically relevant outcome assessed with CAM over 3 postoperative days
Limitations
- Single-center study may limit generalizability
- Delirium reduction demonstrated on postoperative day 1; longer-term cognitive outcomes not reported
Future Directions: Multicenter trials testing NOX-guided analgesia across procedures and exploring optimal opioid titration to balance pain control and delirium risk are warranted.
INTRODUCTION: Intraoperative analgesia and sedation are closely related to postoperative delirium. Depth of sedation based on bispectral index (BIS) guidance has been shown to reduce the occurrence of postoperative delirium (POD). However, the correlation between intraoperative analgesia levels and POD is unclear. The aim of this study was to investigate the effect of intraoperative analgesic management guided by the nociceptive stimulus index (NOX) on postoperative delirium. METHODS: In this prospective single-center randomized controlled study, elderly patients aged 65 and above, who are scheduled to undergo unilateral total knee arthroplasty (TKA), were allocated into two groups: the routine monitoring group (group R), which solely monitored patient sedation levels using BIS; and the NOX monitoring group (group N), which monitored patient analgesic levels using NOX based on BIS-monitored sedation levels. The primary outcome was the incidence of postoperative delirium within 3 days after surgery, using the confusion assessment method (CAM). RESULTS: From May 2022 to December 2022, a total of 240 patients were randomized; 12 were excluded because of failure to meet experimental conditions or were lost to follow-up. Patients in group N had a lower incidence rate (%) of POD on the first day compared to those in group R (8 (7%) vs 18 (16%), P = 0.041). The dosage of remifentanil administered in group N was significantly higher than that in group R (927.07 ± 268.09 vs 882.32 ± 187.91 mg, P = 0.002). CONCLUSIONS: Appropriate intraoperative analgesia guided by NOX is associated with POD. When sedation levels were consistent, the incidence of POD was significantly reduced in older patients with NOX-guided analgesic management during unilateral TKA surgery.
2. Genomic analysis of surgical patients to identify patients at risk for postoperative sepsis and surgical site infection.
A large EMR-linked GWAS (n=59,755) identified significant loci on chromosomes 9 (rs9413988) and 14 (rs35407594) associated with postoperative sepsis, with similar variants linked to SSIs. These findings suggest genetic predisposition contributes to postoperative infection risk and could inform precision perioperative risk stratification.
Impact: This study opens a genomics-based pathway for identifying surgical patients at elevated infection risk, potentially enabling targeted prophylaxis and monitoring.
Clinical Implications: Perioperative teams could integrate genetic risk markers, once validated, into preoperative assessment to tailor infection prevention strategies and surveillance.
Key Findings
- GWAS in 59,755 surgical patients identified rs9413988 (chr9) and rs35407594 (chr14) associated with postoperative sepsis at genome-wide significance.
- Similar SNPs were associated with surgical site infections, suggesting shared genetic risk.
- Lead loci map near PGM5P2/ZNGF1 (transcriptional regulation) and OR11 family, warranting functional studies.
Methodological Strengths
- Large-scale GWAS with stringent genome-wide significance threshold
- Use of EMR-linked biobank enabling precise case-control phenotyping
Limitations
- Findings require replication in independent, diverse cohorts and functional validation
- Potential residual confounding from population stratification or phenotype misclassification
Future Directions: Replication across ancestries, fine-mapping, and mechanistic studies, followed by integration of polygenic risk into perioperative risk models.
BACKGROUND: Early and accurate diagnosis of sepsis and the ensuing organ dysfunction remain a challenge in the postoperative setting. Susceptibility to infections, as well as the subsequent immunological response, are driven to some extent by the genetic predisposition of the patient. The purpose of this study was to identify novel genetic variants associated with postoperative sepsis (POS) and surgical site infections (SSIs). METHODS: We conducted genome-wide association studies for POS and SSIs in the Electronic Medical Records and Genomics Network database. All patients with surgical and genomic information in Electronic Medical Records and Genomics were identified. Patients with a new diagnosis of sepsis/SSIs after surgery were classified as cases, and those without as controls. Analyses were performed using PLINK 2.0's logistic regression function. A p value of <5 × 10 -8 was considered statistically significant. RESULTS: A total of 59,755 participants were included in the analysis. Genetic regions on chromosomes 9 and 14 reached statistical significance for POS ( p < 5 × 10 -8 ). The most significant single-nucleotide polymorphisms (SNPs) were rs9413988 ( p = 5.59 × 10 -12 ) on chromosome 9 and rs35407594 ( p = 1.43 × 10 -10 ) on chromosome 14. The rs9413988 region is downstream to the phosphoglucomutase 5 pseudogene ( PGM5P2 ) and Zn-regulated GTPase metalloprotein activator 1F ( ZNGF1 ) and likely plays a role in transcription regulation, while rs35407594 corresponds to the olfactory receptor gene family, OR11 . Similar SNPs were also associated with SSIs. CONCLUSION: We have identified two genetic regions containing SNPs associated with POS and SSIs. These findings provide new avenues for investigation, which may help identify and guide point-of-care management for at-risk patients. LEVEL OF EVIDENCE: Prognostic and Epidemiological; Level III.
3. Intraosseous basivertebral nerve ablation: A 5-year pooled analysis from three prospective clinical trials.
Across three prospective trials, 249 BVNA-treated patients with vertebrogenic CLBP completing 5-year follow-up showed sustained improvements in pain (mean NPS −4.32) and disability (ODI −28), with 32% pain-free, 65% discontinuing opioids, 58% fewer spinal injections, and no serious device-related adverse events.
Impact: Provides durable, 5-year evidence that BVNA yields substantial and sustained clinical benefit with opioid-sparing, informing long-term expectations and payer decisions for vertebrogenic low back pain.
Clinical Implications: For MRI-confirmed vertebrogenic CLBP (Modic 1/2), BVNA offers durable pain and functional improvements and may reduce opioid use and interventional healthcare utilization.
Key Findings
- Mean NPS improved by 4.32 points and ODI by 28 points over a mean 5.6-year follow-up.
- 32.1% of patients were pain-free at 5 years; 65.2% discontinued opioids.
- Healthcare utilization decreased: spinal injections down 58.1%; same-level reintervention 13.2% (fusion 6.0%); no serious device-related AEs.
Methodological Strengths
- Prospective trials with harmonized eligibility and outcomes enabling pooled long-term analysis
- High follow-up participation (78%) and multiple clinically meaningful endpoints
Limitations
- Five-year analyses are single-arm follow-ups of treated cohorts without concurrent controls
- Potential attrition and selection bias; heterogeneity across original trials
Future Directions: Comparative effectiveness and cost-effectiveness versus other spine interventions, identification of predictors of long-term response, and broader real-world registries.
BACKGROUND: Vertebrogenic pain is a documented source of anterior column chronic low back pain (CLBP) that stems from damaged vertebral endplates. Nociceptive signals are transmitted by the basivertebral nerve (BVN) and endplate damage is observed as Type 1 or Type 2 Modic changes (MC) on magnetic resonance imaging (MRI). The clinical impact and safety of intraosseous radiofrequency ablation of the BVN (BVNA) for the treatment of vertebrogenic pain has been demonstrated in three prospective clinical trials (two randomized and one single-arm study). OBJECTIVE: Report aggregate long-term BVNA outcomes at five years from three studies. METHODS: Pooled results at 5-years post-BVNA are reported for three clinical trials with similar inclusion/exclusion criteria and outcomes measurements: 1) a prospective, open label, single-arm follow-up of the treatment arm of a randomized controlled trial (RCT) comparing BVNA to sham ablation (SMART); 2) a prospective, open label, single-arm follow-up of the treatment arm of an RCT comparing BVNA to standard care (INTRACEPT); and 3) a prospective, open label, single-arm long-term follow-up study of BVNA-treated participants (CLBP Single-Arm). Paired datasets (baseline and 5-years) for mean changes in Oswestry disability index (ODI) and numeric pain scores (NPS) were analyzed using a two-sided paired