Daily ReportOct 5, 2026
Anesthesiology, October 5 edition
We read 36 papers and selected 3.
Summary
Today’s most impactful studies addressed opioid stewardship, anesthesia-related cognitive impairment, and regional analgesia. A randomized trial showed that individualized opioid prescribing markedly reduced unused hydromorphone without worsening pain, while a mechanistic animal study identified RAF-MAPK-MSK1/CLOCK dysregulation as a potential pathway in desflurane-associated cognitive impairment; a randomized blinded trial favored PECS-II over erector spinae plane block after mastectomy.
Research Themes
- Personalized opioid prescribing and opioid stewardship
- Mechanisms and prevention of postoperative cognitive impairment
- Comparative effectiveness of regional analgesia techniques
Selected Articles
1. Personalized Opioid Prescribing With an Individualized Tapering Protocol Following Orthognathic Surgery Reduces the Amount of Unused Opioid.
In this prospective randomized trial, 201 adults undergoing single- or double-jaw orthognathic surgery were assigned to standardized opioid prescribing or personalized prescribing based on inpatient use with individualized tapering. Among 151 completers, median unused hydromorphone was 4.0 mg with personalized prescribing versus 29.0-36.5 mg with standard prescribing, while pain scores remained similar.
Impact: This study provides a practical, randomized strategy for reducing surplus postoperative opioids without compromising analgesia. It directly addresses medication waste and potential community diversion, making it relevant to perioperative opioid stewardship.
Clinical Implications: Postoperative opioid prescriptions can be based on actual inpatient opioid requirements followed by an individualized taper rather than a fixed dose. This approach may reduce unused medication while maintaining patient comfort, but local validation and reliable follow-up are needed before broad implementation.
Key Findings
- The study enrolled 201 patients, with 151 completing the 2-week assessment.
- Median unused hydromorphone was 4.0 mg with personalized prescribing versus 36.5 mg after single-jaw surgery and 29.0 mg after double-jaw surgery with standard prescribing.
- Personalized prescribing reduced postoperative hydromorphone consumption without worsening pain; satisfaction was higher after double-jaw surgery.
Methodological Strengths
- Prospective randomized controlled design with stratification and 1:1 block randomization.
- Patient-centered primary outcome directly measured unused opioid at a prespecified 2-week time point.
- Multivariable adjustment included clinical and perioperative covariates.
Limitations
- There was 25% attrition, which may introduce attrition bias.
- The single-center design and orthognathic surgery population may limit generalizability.
- The study did not establish whether the intervention reduces long-term opioid exposure or diversion.
Future Directions: Multicenter pragmatic trials should test individualized prescribing across different surgical populations and evaluate long-term opioid use, medication disposal, patient-reported outcomes, and implementation costs.
BACKGROUND: Orthognathic surgery may result in opioid prescribing that exceeds patient need, creating surplus medication. PURPOSE: To compare unused hydromorphone after orthognathic surgery between personalized inpatient-use-based prescribing with tapering and standardized fixed-dose prescribing. STUDY DESIGN, SETTING, AND SAMPLE: Prospective single-center randomized trial (Dalhousie University, Halifax, Nova Scotia; April 2023-April 2024). Adults undergoing single- or double-jaw orthognathic surgery were stratified and then randomized by 1:1 block randomization.
2. Desflurane Increases Hippocampal RAF-MAPK-MSK1 Protein Levels and Reduces CLOCK Expression: Sorafenib Attenuates Cognitive Impairment in Aged Mice.
Using aged mice and HT22 hippocampal neurons, the study linked desflurane exposure to increased c-Raf, ERK1/2 and MSK1 protein abundance, reduced CLOCK expression, cellular senescence, synaptic excitation-inhibition imbalance and cognitive deficits. RAF knockdown restored CLOCK in vitro, while sorafenib improved CLOCK expression, hippocampal pathological markers and memory-related behavior in aged mice.
Impact: The study proposes a previously underexplored molecular connection between volatile anesthesia, circadian regulation and postoperative cognitive impairment in aging. It also identifies RAF signaling as a testable therapeutic target, although translation to patients remains preliminary.
Clinical Implications: The findings do not support clinical use of sorafenib for postoperative cognitive impairment. They provide a preclinical rationale for investigating RAF-MAPK modulation, circadian biomarkers and anesthetic strategies in older adults at risk of postoperative neurocognitive disorders.
Key Findings
- Desflurane increased c-Raf, ERK1/2 and MSK1 protein abundance while reducing CLOCK expression in HT22 cells and aged hippocampus.
- These changes were accompanied by senescence markers, altered synaptic excitation-inhibition balance and impaired contextual fear memory and spatial learning.
- RAF knockdown or sorafenib treatment restored CLOCK-related abnormalities and improved cognitive or hippocampal outcomes in the experimental models.
Methodological Strengths
- Integrated in vitro and in vivo experimental systems using aged animals of both sexes.
- Mechanistic triangulation included protein analysis, immunofluorescence, electroencephalography, patch-clamp recordings and behavioral testing.
- Bidirectional RAF manipulation in neurons strengthened the mechanistic interpretation.
Limitations
- The study used animal and cell models, so human clinical relevance remains unproven.
- Phosphorylation status of the RAF-MAPK-MSK1 pathway was not assessed.
- Sorafenib has multiple kinase targets, preventing attribution of all effects specifically to RAF inhibition.
Future Directions: Future studies should validate the pathway in human perioperative cohorts, quantify pathway phosphorylation and circadian biomarkers, compare different anesthetics and test selective RAF-pathway interventions with dose and safety assessment.
Postoperative cognitive dysfunction (POCD) is common after anesthesia and surgery in older adults, yet no targeted therapy exists, and the mechanism linking volatile anesthetic exposure to circadian dysregulation in the aged hippocampus is undefined. Here we show that RAF manipulation bidirectionally alters CLOCK protein levels in HT22 hippocampal neurons, and that RAF-MAPK-MSK1 protein abundance is inversely related to CLOCK levels in the aged hippocampus after desflurane exposure. Aged C57BL/6 mice (18 months, both sexes) were exposed to 2% desflurane for 2 h, with or without pretreatment with the multi-kinase RAF inhibitor sorafenib
3. Comparison of Modified Pectoral Nerve Block and Erector Spinae Plane Block for Postoperative Analgesia and Surgical Stress Response Following Modified Radical Mastectomy: A Prospective, Randomised, Blinded Study.
This prospective randomized blinded study assigned 42 patients undergoing modified radical mastectomy to ESPB or PECS-II using the same ropivacaine-dexmedetomidine solution. PECS-II prolonged time to first rescue analgesia, reduced 24-hour diclofenac and tramadol use, lowered pain at 6 hours, decreased cortisol, interleukin-6 and neutrophil-to-lymphocyte ratio, and improved satisfaction.
Impact: The trial directly compares two widely used regional techniques and suggests that PECS-II may provide superior analgesia and attenuation of the postoperative stress response after mastectomy. The findings are clinically actionable but require confirmation in larger trials.
Clinical Implications: For modified radical mastectomy, PECS-II may be considered as an alternative to ESPB within multimodal analgesia pathways. It may reduce rescue analgesic requirements and physiologic stress, although block selection should consider surgical extent, operator expertise and patient anatomy.
Key Findings
- Time to first rescue analgesia was longer with PECS-II than ESPB: 9.05 versus 6.95 hours.
- PECS-II reduced 24-hour diclofenac and tramadol consumption and produced lower pain scores at 6 hours.
- Postoperative cortisol, interleukin-6 and neutrophil-to-lymphocyte ratio were lower, and patient satisfaction was higher, with PECS-II.
Methodological Strengths
- Prospective randomized and blinded comparative design with trial registration.
- Both groups received the same local anesthetic and dexmedetomidine regimen, improving comparability.
- Assessment included patient-centered analgesic outcomes and exploratory biologic stress markers.
Limitations
- The sample size was small, with only 42 randomized patients.
- The study was conducted in a single surgical setting and may not generalize to other breast procedures or analgesic protocols.
- Stress-response biomarkers were secondary or exploratory outcomes and may not establish clinically meaningful benefit.
Future Directions: Larger multicenter randomized trials should compare PECS-II and ESPB using standardized block techniques, assess opioid-sparing effects over several days, evaluate functional recovery and chronic postsurgical pain, and include cost and safety outcomes.
BACKGROUND: Erector spinae plane block (ESPB) and modified pectoral nerve block (PECS-II) are being increasingly used to control pain following breast surgeries. However, evidence comparing their effects on postoperative analgesia and surgical stress response attenuation is limited. The current study compared analgesic efficacy and surgical stress response attenuation of ESPB and PECS-II in patients undergoing modified radical mastectomy (MRM). METHODS: In this prospective, randomised, comparative study, 42 patients undergoing elective MRM were randomly divided to receive either ESPB or PECS-II. Both groups received 30 mL of 0.2% ropivacaine with 0.5 μg/kg dexmedetomidine after induction of general anaesthesia (GA). The primary outcome was time to first rescue analgesia requirement.