Daily Anesthesiology Research Analysis
Three standout anesthesiology papers advance opioid-sparing acute pain control, pediatric difficult airway rescue strategy, and perioperative stroke risk prediction. A nonopioid NaV1.8 inhibitor (suzetrigine) matched hydrocodone’s analgesia in two phase 3 RCTs, registry data clarify that flexible bronchoscopy may outperform videolaryngoscopy in the smallest infants after failed direct laryngoscopy, and a large externally validated model enables high-accuracy prediction of perioperative stroke af
Summary
Three standout anesthesiology papers advance opioid-sparing acute pain control, pediatric difficult airway rescue strategy, and perioperative stroke risk prediction. A nonopioid NaV1.8 inhibitor (suzetrigine) matched hydrocodone’s analgesia in two phase 3 RCTs, registry data clarify that flexible bronchoscopy may outperform videolaryngoscopy in the smallest infants after failed direct laryngoscopy, and a large externally validated model enables high-accuracy prediction of perioperative stroke after non-cardiac surgery.
Research Themes
- Opioid-sparing acute pain pharmacotherapy (NaV1.8 inhibition)
- Pediatric difficult airway rescue (videolaryngoscopy vs flexible bronchoscopy)
- Perioperative stroke risk prediction and stratification
Selected Articles
1. Suzetrigine, a Nonopioid Na V 1.8 Inhibitor for Treatment of Moderate-to-severe Acute Pain: Two Phase 3 Randomized Clinical Trials.
Across two large phase 3 RCTs in abdominoplasty and bunionectomy, suzetrigine significantly improved SPID48 vs placebo and provided analgesia similar to hydrocodone/acetaminophen, with a faster onset than placebo and mild-to-moderate adverse events. These results position a selective NaV1.8 inhibitor as a viable nonopioid option for acute postoperative pain.
Impact: A first-in-class targeted nonopioid analgesic demonstrating phase 3 efficacy comparable to an opioid could reshape postoperative pain protocols and reduce opioid exposure.
Clinical Implications: Suzetrigine could be incorporated into multimodal analgesia pathways as an opioid-sparing agent for 48-hour postoperative pain control in soft-tissue and orthopedic procedures, with monitoring for class-specific adverse events.
Key Findings
- Met primary endpoint: SPID48 improved vs placebo in both trials (LS mean difference 48.4 after abdominoplasty; 29.3 after bunionectomy).
- No superiority over hydrocodone/acetaminophen on SPID48 in either trial.
- Faster onset to ≥2-point pain reduction vs placebo (119 vs 480 min abdominoplasty; 240 vs 480 min bunionectomy).
- Adverse events were mild to moderate and consistent with postsurgical settings.
Methodological Strengths
- Two large, randomized, double-blind, placebo- and active-controlled phase 3 trials
- Standardized endpoints (SPID48) and prespecified key secondary outcomes
Limitations
- Did not demonstrate superiority to hydrocodone/acetaminophen on SPID48
- Evidence limited to 48-hour postsurgical pain in two surgical models; long-term safety and broader generalizability remain to be established
Future Directions: Head-to-head comparisons with NSAIDs and regional techniques, evaluation across diverse surgeries and ambulatory settings, longer-term safety, and opioid-sparing outcomes (consumption, adverse events) in multimodal pathways.
BACKGROUND: Opioids are effective for treating acute pain but have safety, tolerability, and addiction concerns while nonopioid analgesics have limited efficacy. Suzetrigine, an oral, nonopioid small molecule, selectively inhibits the voltage-gated sodium channel 1.8 (NaV1.8) and has potential to provide efficacious and safe relief for acute pain without addiction concerns. METHODS: To evaluate suzetrigine for treatment of acute pain, two phase 3, randomized, double-blind, placebo- and active-controlled trials were conducted in adults with moderate-to-severe acute pain on the verbal categorical rating scale and 4 or greater on the numeric pain rating scale after abdominoplasty (n = 1,118) or bunionectomy (n = 1,073). After surgery, participants were randomized to suzetrigine (100 mg, then 50 mg every 12 h), hydrocodone bitartrate/acetaminophen (5/325 mg every 6 h), or placebo for 48 h. The primary endpoint was time-weighted sum of the pain intensity difference in numeric pain rating scale from 0 to 48 h (SPID48) versus placebo. Key secondary endpoints were SPID48 versus hydrocodone bitartrate/acetaminophen and time to 2-point or greater reduction in numeric pain rating scale from baseline versus placebo. RESULTS: The primary endpoint was achieved in both trials with suzetrigine demonstrating statistically significant and clinically meaningful reduction in pain versus placebo. The least squares mean difference in SPID48 between suzetrigine and placebo was 48.4 (95% CI, 33.6 to 63.1; P < 0.0001) after abdominoplasty and 29.3 (95% CI, 14.0 to 44.6; P = 0.0002) after bunionectomy. Neither trial achieved the first key secondary endpoint of superiority of suzetrigine versus hydrocodone bitartrate/acetaminophen on SPID48. For the second key secondary endpoint of time to 2-point or greater reduction in numeric pain rating scale, suzetrigine had a more rapid onset of clinically meaningful pain relief versus placebo after abdominoplasty (119 min vs. 480 min; nominal P < 0.0001) and bunionectomy (240 min vs. 480 min; nominal P = 0.0016). Adverse events were similar to those seen in postsurgical settings. CONCLUSIONS: As compared with placebo, suzetrigine reduced moderate-to-severe acute pain over 48 h after abdominoplasty or bunionectomy. Pain reduction with suzetrigine was similar to that with hydrocodone bitartrate/acetaminophen. Suzetrigine was associated with adverse events that were mild to moderate in severity.
2. Comparing videolaryngoscopy and flexible bronchoscopy to rescue failed direct laryngoscopy in children: a propensity score matched analysis of the Pediatric Difficult Intubation Registry.
In registry cases of failed direct laryngoscopy, videolaryngoscopy was used far more often than flexible bronchoscopy, but matched cohorts showed similar overall success and complication rates. In infants <5 kg, flexible bronchoscopy achieved higher eventual success, emphasizing the need to maintain bronchoscopy proficiency for the smallest patients.
Impact: Clarifies real-world rescue strategy trade-offs after failed direct laryngoscopy and identifies a critical subgroup (infants <5 kg) where flexible bronchoscopy likely confers advantage.
Clinical Implications: For infants under 5 kg, prioritize flexible bronchoscopy as rescue after failed direct laryngoscopy and ensure training/availability; in larger children, either technique may be reasonable based on operator expertise and equipment.
Key Findings
- Videolaryngoscopy was chosen more frequently than flexible bronchoscopy after failed direct laryngoscopy (64.7% vs 7.3%).
- In propensity-matched cohorts, first-attempt and eventual success and complications did not differ overall.
- In infants <5 kg, eventual success was higher with flexible bronchoscopy (90%) than videolaryngoscopy (71%) with similar complications.
Methodological Strengths
- Multicentre registry with large time span and real-world practice data
- Propensity score matching and predefined subgroup analysis in infants <5 kg
Limitations
- Observational design with potential residual confounding and selection bias
- Device heterogeneity and operator expertise variability not fully standardized
Future Directions: Prospective comparative trials in infants, standardized rescue algorithms, and training studies to optimize device selection by age/weight and airway phenotype.
INTRODUCTION: Flexible bronchoscopy is the gold standard for difficult airway management. Clinicians are using videolaryngoscopy increasingly because it is perceived to be easier to use with high success rates. We conducted this study to compare the success rates of the two techniques when used after failed direct laryngoscopy in children with difficult tracheal intubations. METHODS: We identified cases where initial attempts at direct laryngoscopy failed in the multicentre Pediatric Difficult Intubation Registry from August 2012-September 2023. After propensity score matching, we compared success rates and complications when videolaryngoscopy and flexible bronchoscopy were used as rescue techniques in the matched cohort and in matched patients weighing < 5 kg. RESULTS: Clinicians chose videolaryngoscopy more frequently than flexible bronchoscopy when direct laryngoscopy failed (64.7%, 1426/2281 vs. 7.3%, 156/2281, p < 0.001). Propensity score matched cohorts did not differ with respect to first-attempt success, eventual success and complications. For the subgroup of infants < 5 kg, clinicians chose videolaryngoscopy more frequently than flexible bronchoscopy to rescue failed direct laryngoscopy (54.3%, 295/543 vs. 8.9%, 44/543, p < 0.001). First-attempt success was 43% (62/145) with videolaryngoscopy and 62% (18/29) with flexible bronchoscopy (odds ratio 2.19, 95%CI 0.96-4.98, p = 0.061). Eventual success was 71% (103/145) with videolaryngoscopy and 90% (26/29) with flexible bronchoscopy (odds ratio 3.53, 95%CI 1.03-12.2, p = 0.046). Complications did not differ between the techniques. DISCUSSION: Videolaryngoscopy was chosen more frequently than flexible bronchoscopy as a rescue technique in a cohort of children with difficult direct laryngoscopy, with similar success and complication rates. For small infants, flexible bronchoscopy had a higher eventual success rate, underscoring the importance of maintaining proficiency with flexible bronchoscopy.
3. Risk factor analysis and creation of an externally-validated prediction model for perioperative stroke following non-cardiac surgery: A multi-center retrospective and modeling study.
Using 223,415 non-cardiac surgical cases, the authors developed a 13-variable perioperative stroke model with AUC≈0.89–0.90 and validated it in two independent hospitals, outperforming existing tools. An online calculator (301PSRC) facilitates risk communication and targeted prevention.
Impact: Provides a robust, externally validated tool to stratify perioperative stroke risk, enabling targeted mitigation strategies across perioperative care.
Clinical Implications: Integrate the model into preoperative clinics and perioperative decision support to identify high-risk patients for optimization (hemodynamic targets, medication adjustments, monitoring) and informed consent.
Key Findings
- Identified 13 independent predictors (e.g., age, ASA class, hypertension, prior stroke, emergency surgery, surgery type/length, fibrinogen/albumin ratio).
- High discrimination: AUC 0.893 (development), 0.878 (internal validation), 0.897 and 0.895 (external validations).
- Outperformed existing prediction tools and released an online risk calculator (301PSRC).
Methodological Strengths
- Very large derivation cohort with inclusion of intraoperative variables
- External validation at two independent hospitals and comparative performance analysis
Limitations
- Retrospective design and exclusion of surgeries <1 hour may limit generalizability
- Validation limited to Chinese datasets; prospective and international validation needed
Future Directions: Prospective, multicountry validation; integration into EHRs with real-time decision support; testing whether model-driven interventions reduce perioperative stroke.
BACKGROUND: Perioperative stroke is a serious and potentially fatal complication following non-cardiac surgery. Thus, it is important to identify the risk factors and develop an effective prognostic model to predict the incidence of perioperative stroke following non-cardiac surgery. METHODS AND FINDINGS: We identified potential risk factors and built a model to predict the incidence of perioperative stroke using logistic regression derived from hospital registry data of adult patients that underwent non-cardiac surgery from 2008 to 2019 at The First Medical Center of Chinese PLA General Hospital. Our model was then validated using the records of two additional hospitals to demonstrate its clinical applicability. In our hospital cohorts, 223,415 patients undergoing non-cardiac surgery were included in this study with 525 (0.23%) patients experiencing a perioperative stroke. Thirty-three indicators including several intraoperative variables had been identified as potential risk factors. After multi-variate analysis and stepwise elimination (P < 0.05), 13 variables including age, American Society of Anesthesiologists (ASA) classification, hypertension, previous stroke, valvular heart disease, preoperative steroid hormones, preoperative β-blockers, preoperative mean arterial pressure, preoperative fibrinogen to albumin ratio, preoperative fasting plasma glucose, emergency surgery, surgery type and surgery length were screened as independent risk factors and incorporated to construct the final prediction model. Areas under the curve were 0.893 (95% confidence interval (CI) [0.879, 0.908]; P < 0.001) and 0.878 (95% CI [0.848, 0.909]; P < 0.001) in the development and internal validation cohorts. In the external validation cohorts derived from two other independent hospitals, the areas under the curve were 0.897 and 0.895. In addition, our model outperformed currently available prediction tools in discriminative power and positive net benefits. To increase the accessibility of our predictive model to doctors and patients evaluating perioperative stroke, we published an online prognostic software platform, 301 Perioperative Stroke Risk Calculator (301PSRC). The main limitations of this study included that we excluded surgical patients with an operation duration of less than one hour and that the construction and external validation of our model were from three independent retrospective databases without validation from prospective databases and non-Chinese databases. CONCLUSIONS: In this work, we identified 13 independent risk factors for perioperative stroke and constructed an effective prediction model with well-supported external validation in Chinese patients undergoing non-cardiac surgery. The model may provide potential intervention targets and help to screen high-risk patients for perioperative stroke prevention.