Daily Anesthesiology Research Analysis
Top findings span mechanistic pain science, perioperative risk prediction, and airway induction pharmacology. A Science Advances study uncovers a female-specific mechanism for bortezomib neuropathic pain via ICAM-1–mediated perivascular macrophage infiltration and CCL1 signaling. In perioperative care, a large, externally validated mortality model for pediatric congenital heart surgery outperforms legacy scores, and a meta-analysis shows ketamine and etomidate yield similar 30-day survival for R
Summary
Top findings span mechanistic pain science, perioperative risk prediction, and airway induction pharmacology. A Science Advances study uncovers a female-specific mechanism for bortezomib neuropathic pain via ICAM-1–mediated perivascular macrophage infiltration and CCL1 signaling. In perioperative care, a large, externally validated mortality model for pediatric congenital heart surgery outperforms legacy scores, and a meta-analysis shows ketamine and etomidate yield similar 30-day survival for RSI but with different safety trade-offs.
Research Themes
- Sex-specific mechanisms in chemotherapy-induced neuropathic pain
- Perioperative risk prediction for pediatric congenital heart surgery
- Induction agent choice for rapid sequence intubation: survival equivalence with distinct adverse profiles
Selected Articles
1. Earlier onset of chemotherapy-induced neuropathic pain in females by ICAM-1-mediated accumulation of perivascular macrophages.
Using clinical data and mechanistic mouse experiments, the authors show that bortezomib-associated neuropathic pain manifests earlier in females via ICAM-1–driven perivascular monocyte/macrophage accumulation in the spinal cord and CCL1-mediated neuronal activation. This sex-specific pathway provides actionable targets for prevention or early intervention in female patients.
Impact: Reveals a first-in-class sex-specific mechanism linking ICAM-1, perivascular macrophages, and CCL1 to chemotherapy neuropathy onset, bridging immunology and neurobiology.
Clinical Implications: For anesthesiologists and pain specialists, peri-chemotherapy strategies could incorporate ICAM-1/CCL1 pathway modulation or macrophage trafficking blockade to prevent early neuropathic pain in women receiving bortezomib. Risk stratification and sex-specific monitoring protocols may reduce chronic pain burden.
Key Findings
- Peripheral sensory disorders occurred earlier in female patients than in males after bortezomib treatment.
- BTZ elevated ICAM-1 and promoted perivascular monocyte/macrophage infiltration in female mouse spinal cord.
- Macrophage-derived CCL1 directly and indirectly (via astrocytes) activated neurons, accelerating neuropathic pain onset in females.
Methodological Strengths
- Integrated retrospective clinical observations with mechanistic in vivo experiments for convergent evidence.
- Identified a concrete molecular pathway (ICAM-1–macrophage–CCL1) with cell-type specificity in the spinal cord.
Limitations
- Clinical component is retrospective and limited to bortezomib-treated populations; causality in humans not proven.
- Translational gap remains regarding pharmacologic targeting of ICAM-1/CCL1 in patients.
Future Directions: Prospective human studies stratified by sex to validate biomarkers (ICAM-1, CCL1) and trials of macrophage trafficking or CCL1 antagonism to prevent chemotherapy neuropathy in women.
Sex differences in the pathogenesis of a variety of diseases have drawn increasing attention. However, it remains unclear whether such differences exist in chemotherapy-induced neuropathic pain. Here, we conducted a retrospective analysis of clinical case data and found that peripheral sensory disorders occurred earlier in females than in males following bortezomib (BTZ) treatment in patients with multiple myeloma. BTZ treatment led to an early elevation of intercellular adhesion molecule-1, which triggered the infiltration of peripheral monocytes into the perivascular region of the spinal cord in female mice. The CC-chemokine ligand 1 released by infiltrating macrophages directly activated neurons or indirectly activated neurons by enhancing the astrocyte activity, ultimately leading to the earlier onset of BTZ-induced neuropathic pain in females. Together, clarifying the mechanism underlying the earlier onset of BTZ-induced neuropathic pain will contribute to the precise treatment of multiple myeloma in females.
2. Development and External Validation of a Novel In-hospital Mortality Model after Pediatric Congenital Heart Surgery: A Multicenter Retrospective Cohort Study.
In 21,855 development and 5,221 external validation cases, legacy pediatric cardiac surgery mortality scores performed only moderately. A new six-variable model (age, height, oxygen support, prior cardiac operation, emergency surgery, STAT categories) achieved AUROCs of 0.864 (development) and 0.860 (external), with low Brier scores, indicating strong calibration and discrimination.
Impact: Provides a validated, parsimonious perioperative mortality model tailored to contemporary Chinese pediatric populations, likely to influence risk stratification and quality benchmarking.
Clinical Implications: Integrating the six-variable model into preoperative assessment can improve resource allocation, ICU planning, and informed consent discussions in pediatric congenital heart surgery.
Key Findings
- Traditional scores (ABC, RACHS-1, STAT score/categories) showed only moderate AUROCs (0.685–0.808).
- Adding preoperative covariates improved AUROCs across models to 0.844–0.864.
- A new six-variable model achieved AUROC 0.864 (development) and 0.860 (external validation) with low Brier scores (0.00977 and 0.00654).
Methodological Strengths
- Very large development cohort with independent external validation from a second center.
- Transparent model composition with clinically interpretable predictors and strong discrimination/calibration metrics.
Limitations
- Retrospective design may introduce residual confounding and center-specific practice patterns.
- Model derived and validated within China; generalizability to other healthcare systems requires testing.
Future Directions: Prospective, multicountry validation and integration into clinical decision support; assessment of model impact on outcomes via implementation studies.
BACKGROUND: The applicability of four major traditional in-hospital mortality models in the Chinese setting is unclear due to disease spectrum and population heterogeneity. This study aimed to test the performance of these models in the Chinese setting and to construct and externally validate a novel model. METHODS: A total of 21,855 consecutive pediatric patients who underwent congenital heart surgery from January 2015 to December 2021 in Shanghai Children's Medical Center were enrolled. For external validation, the study additionally pooled 5,221 consecutive pediatric patients who underwent this surgical treatment from January 2020 to December 2021 in Beijing Fuwai Hospital. The performance of the Aristotle Basis Complexity (ABC) score, Risk Adjustment for Congenital Heart Surgery (RACHS)-1 categories, Society of Thoracic Surgeons-European Association for Cardiothoracic Surgery (STAT) score, and STAT categories was tested. Independent predictors were used to develop a model. The area under the receiver operating characteristic curves (AUROCs) and Brier score were used to examine the model performance. RESULTS: The AUROCs were 0.778 for ABC score, 0.685 for RACHS-1 categories, 0.808 for STAT score, and 0.784 for STAT categories. When preoperative covariates were added to the four models, the AUROCs improved: ABC score (AUROC = 0.860), RACHS-1 categories (AUROC = 0.844), STAT score (AUROC = 0.856), and STAT categories (AUROC = 0.864). The best-performing model incorporated six variables, including age, height, oxygen support, previous cardiac operation, emergency surgery, and STAT categories. The AUROCs and Brier score were 0.864 and 0.00977 in the development cohort and 0.860 and 0.00654 in the external validation cohort. CONCLUSIONS: The four major traditional models were only moderately effective in predicting in-hospital mortality after congenital heart surgery in the Chinese setting. The novel model founded on the STAT categories in combination with preoperative covariates can serve as a useful and effective tool for predicting the risk of in-hospital mortality after congenital heart surgery in the Chinese setting.
3. Etomidate versus ketamine for in-hospital rapid sequence intubation: a systematic review and meta-analysis.
Across 14 RCTs/CCTs (n=23,926), etomidate and ketamine yielded similar 30-day survival for in-hospital RSI. Trade-offs were identified: etomidate increased adrenal insufficiency risk, whereas ketamine was linked to greater post-intubation vasopressor requirements and more ICU-free days.
Impact: Clarifies survival equivalence and delineates distinct adverse effect profiles for two widely used induction agents, informing protocolized RSI choices in ED/ICU.
Clinical Implications: Choice between ketamine and etomidate can be individualized: avoid etomidate when adrenal suppression is concerning; anticipate higher vasopressor needs with ketamine. Protocols should incorporate monitoring for adrenal insufficiency and hemodynamic support strategies.
Key Findings
- No significant difference in 30-day survival between etomidate and ketamine in RCTs and CCTs.
- Etomidate associated with higher adrenal insufficiency (OR 2.43, 95% CI 1.67–3.53).
- Ketamine associated with higher post-intubation vasopressor use (favoring etomidate; OR 0.71, 95% CI 0.53–0.96) and more ICU-free days.
Methodological Strengths
- Comprehensive search across multiple databases and registries with inclusion of RCTs and controlled trials.
- Large aggregated sample size (n=23,926) enabling precise effect estimates for key outcomes.
Limitations
- Heterogeneity in patient populations, dosing, and peri-intubation care across included studies.
- Adrenal insufficiency definitions and assessment timing may vary; potential residual confounding in CCTs.
Future Directions: Head-to-head pragmatic RCTs stratified by shock phenotype and adrenal axis status; standardized definitions for adrenal insufficiency and hemodynamic endpoints.
Rapid sequence intubation (RSI) is a critical procedure in emergency and intensive care settings. Etomidate has been favored for its hemodynamic stability; however, concerns about adrenal insufficiency have prompted interest in ketamine as an alternative induction agent. This systematic review and meta-analysis aimed to compare the effects of etomidate vs ketamine on 30-day survival and other clinical outcomes in critically ill patients undergoing in-hospital RSI. A comprehensive literature search was conducted until 1 November 2024, across PubMed, Embase, Web of Science, Cochrane databases, and clinical trial registries. Eligible studies included randomized controlled trials (RCTs) and controlled clinical trials (CCTs) assessing etomidate vs ketamine for RSI. The primary outcome was 30-day survival. Secondary outcomes encompassed intubation difficulty, post-intubation vasopressor use, cardiovascular collapse, Sequential Organ Failure Assessment score, systemic steroid use, organ support-free days, and adrenal insufficiency. Fourteen studies comprising 23 926 patients (19 288 receiving etomidate; 4638 receiving ketamine) met the inclusion criteria. Pooled analyses of RCTs and CCTs revealed no significant difference in 30-day survival between the two agents [RCTs: odds ratio (OR) = 0.92, 95% confidence interval (CI): 0.68-1.24, P = 0.58; CCTs: OR = 1.16, 95% CI: 0.92-1.45, P = 0.58]. Ketamine was associated with a higher requirement for post-intubation vasopressor support (OR = 0.71, 95% CI: 0.53-0.96, P = 0.03) and an increase in ICU-free days. Etomidate use correlated with a significantly higher incidence of adrenal insufficiency (OR = 2.43, 95% CI: 1.67-3.53, P < 0.001). No significant differences were observed in intubation difficulty, cardiovascular collapse, or systemic steroid use between the groups. Ketamine and etomidate showed no significant difference in 30-day survival among critically ill patients undergoing RSI. However, etomidate was associated with a higher incidence of adrenal insufficiency, while ketamine required more post-intubation vasopressor support. Provenance and peer review: Not commissioned, externally peer-reviewed.