Daily Anesthesiology Research Analysis
Analyzed 61 papers and selected 3 impactful papers.
Summary
Top findings span perioperative pharmacology and critical care. A first-in-human trial of LL10, a novel long-acting local anesthetic, prolonged femoral nerve block versus levobupivacaine with acceptable safety. Hemodynamic subphenotypes of septic shock revealed phenotype-specific harm from positive fluid balance. In frail older adults, remimazolam-based anesthesia was prospectively associated with lower postoperative delirium than conventional techniques.
Research Themes
- Novel long-acting local anesthetics for prolonged regional blockade
- Hemodynamic subphenotyping to personalize fluid therapy in septic shock
- Sedative selection to mitigate postoperative delirium in frail elders
Selected Articles
1. Phase 1 single-centre, placebo and levobupivacaine controlled study in healthy volunteers to assess the safety, tolerability, efficacy, and pharmacokinetics of LL10, a novel long-acting local anaesthetic.
In healthy volunteers, LL10 (QX-OH 1.26% + levobupivacaine 0.325%) produced significantly longer femoral nerve block duration than levobupivacaine alone, with linear pharmacokinetics and no severe adverse events. Dose-related transient systemic symptoms occurred after TAP blocks but resolved spontaneously.
Impact: This first-in-human study introduces a new long-acting local anesthetic that prolongs block duration versus an established agent, addressing a key unmet need in regional anesthesia.
Clinical Implications: If efficacy and safety are confirmed in surgical populations, LL10 could reduce rescue dosing, prolong analgesia, and potentially improve recovery pathways in regional anesthesia.
Key Findings
- LL10 (1.26%/0.325%) prolonged femoral nerve block duration versus levobupivacaine 0.325% (median 25.0 h vs 15.5 h; P=0.021).
- No severe adverse events among 137 participants; TAP block produced dose-dependent transient systemic symptoms that resolved.
- LL10 exhibited linear pharmacokinetics across tested routes and doses.
Methodological Strengths
- Prospective first-in-human controlled design with both active (levobupivacaine) and placebo comparators
- Multi-route assessment (s.c., femoral nerve block, TAP block) with pharmacokinetics and objective sensory/motor testing
Limitations
- Single-centre, healthy volunteer study; not powered for clinical analgesic outcomes in surgical patients
- Randomization and blinding procedures are not detailed; short-term safety window
Future Directions: Conduct Phase 2/3 randomized trials in surgical populations comparing LL10 to current standards (including liposomal bupivacaine), evaluating analgesia duration, functional recovery, and safety (e.g., neurotoxicity, systemic toxicity).
BACKGROUND: LL10 is a novel long-acting local anaesthetic composed of QX-OH 1.26% and levobupivacaine hydrochloride 0.325%. This first-in-human trial assessed the safety, tolerability, efficacy, and pharmacokinetic profile of LL10. METHODS: We investigated three administration routes: s.c. infiltration, femoral nerve block (FNB), and transversus abdominis plane block (TAPB), with levobupivacaine as a positive control (n=18 total, six per route). For s.c. infiltration, 40 subjects received concentration escalation of LL10 (4 ml, seven cohorts); for FNB, 30 received LL10 at escalating concentrations (20 ml, six cohorts); and for TAPB, 49 received 1.26%/0.325% LL10 at escalating volumes (25-55 ml, seven cohorts). Each LL10 cohort included a placebo control (n=20). Safety evaluations included vital signs, adverse events (AEs), physical examinations, and laboratory tests. Sensory block was evaluated using pinprick, mechanical pain thresholds, and transcutaneous electrical stimulation. Motor block was evaluated via lower limb muscle strength grading. Plasma pharmacokinetics of QX-OH and levobupivacaine were investigated. RESULTS: None of the 137 enrolled subjects developed severe AEs. Dose-dependent systemic AEs including dizziness, perioral and tongue numbness, and cardiovascular symptoms were observed after TAPB; all resolved spontaneously. LL10 showed linear pharmacokinetics. The 1.26%/0.325% LL10 demonstrated prolonged FNB duration compared with levobupivacaine 0.325% (median, 25.0 [21.8-29.5] h vs 15.5 [6.0-21.2] h; P = 0.021). CONCLUSIONS: The 1.26%/0.325% LL10 was tolerated in healthy volunteers at doses up to 40 ml (equivalent to 7/1.81 mg kg
2. Hemodynamic subphenotypes in septic shock and their different responses to fluid balance in relation to ICU mortality.
Using PiCCO-derived parameters, four septic shock hemodynamic subphenotypes were identified. Overall 48-hour fluid balance was not linked to ICU mortality, but in the preserved-hemodynamics phenotype higher fluid balance independently correlated with increased ICU mortality.
Impact: This work advances precision resuscitation by demonstrating phenotype-specific harm from positive fluid balance, challenging one-size-fits-all fluid strategies in septic shock.
Clinical Implications: In patients with preserved hemodynamics, clinicians should be cautious with fluid accumulation within 48 hours. Integrating advanced monitoring to phenotype patients may guide individualized fluid targets.
Key Findings
- Four PiCCO-based hemodynamic subphenotypes of septic shock were identified (hyperdynamic, high preload, hypodynamic, preserved).
- Overall, 48-hour fluid balance was not associated with ICU mortality across all patients.
- In the preserved hemodynamic phenotype, higher 48-hour fluid balance increased ICU mortality (OR 1.24, 95% CI 1.05–1.46; p=0.011).
Methodological Strengths
- Large single-centre cohort with comprehensive invasive hemodynamic profiling (PiCCO)
- Robust latent profile modeling with interaction analysis between phenotype and fluid balance
Limitations
- Retrospective, single-centre design with potential confounding and device-specific generalizability (PiCCO)
- No external validation cohort and similar fluid balances across phenotypes may limit causal inference
Future Directions: Prospective multicentre validation and randomized trials testing phenotype-guided fluid strategies versus usual care, including non-PiCCO platforms.
BACKGROUND: Hemodynamically unstable septic patients often require aggressive fluid resuscitation, but limited evidence exists on which hemodynamic subphenotypes benefit most. METHODS: The retrospective cohort study conducted in a tertiary hospital of China. Patients with septic shock who underwent pulse index continuous cardiac output (PiCCO) monitoring within 24 h were included from November 2013 to January 2024. We applied latent profile modelling to identify subphenotypes using all hemodynamic parameters monitored via PiCCO. We then tested the association of 48-h fluid balance with ICU mortality in different subphenotypes using logistic regression. RESULT: A total of 691 patients were included. Latent profile models indicated that a four-profile model was the best fit. Hyperdynamic subphenotype (phenotype1) was characterized by highest cardiac output and lowest systemic vascular resistance index (SVRI); high preload subphenotype (phenotype 2) was characterized by highest preload; hypodynamic subphenotype (phenotype 3) was characterised by lowest cardiac output, highest SVRI, lung function, as well as inotropic score; preserved subphenotype (phenotype 4) was presented with relative normal hemodynamic parameters. No significant difference was observed in 24- and 48-hour fluid balance among subphenotypes, and overall, no significant correlation was found between 48-hour fluid balance and ICU mortality. However, a significant interaction existed between 48-hour fluid balance and phenotype 4; in this group, higher fluid balance at 48 h was associated with increased ICU mortality (OR 1.24, 95% CI 1.05 to 1.46; p = 0.011). CONCLUSION: Four hemodynamic subphenotypes in septic shock was identified. The impact of 48-hour fluid balance on ICU mortality varied by subphenotype, with increased mortality observed only in the preserved hemodynamic group.
3. The effect of remimazolam versus conventional anesthesia on postoperative delirium in frail patients: a prospective, controlled cohort study.
In a prospective controlled cohort of 606 frail elderly undergoing elective non-cardiac surgery, remimazolam-based anesthesia was associated with a lower incidence of postoperative delirium compared to conventional general anesthesia. Anesthetic choice emerges as a modifiable factor to improve neurologic outcomes in this high-risk group.
Impact: Addresses a major geriatric outcome with a scalable intervention—switching anesthetic agent—to reduce postoperative delirium.
Clinical Implications: Consider remimazolam as part of a delirium-sparing anesthetic strategy in frail patients, while awaiting randomized trials to confirm causality and define protocols.
Key Findings
- Prospective controlled cohort of 606 frail elderly (Clinical Frailty Scale ≥5) undergoing elective non-cardiac surgery.
- Remimazolam-based anesthesia was associated with a lower incidence of postoperative delirium than conventional general anesthesia.
- Findings support anesthetic choice as a modifiable delirium risk factor in frail patients.
Methodological Strengths
- Prospective design with a sizeable frail cohort focused on a clinically meaningful outcome (postoperative delirium)
- Real-world comparison of anesthetic strategies in elective non-cardiac surgery
Limitations
- Non-randomized controlled cohort with potential selection and confounding biases
- Incomplete reporting of dosing, co-interventions, and blinding; single-setting generalizability uncertain
Future Directions: Conduct multicentre randomized trials to confirm delirium reduction, delineate dosing/monitoring protocols, and assess broader outcomes (cognition, length of stay).
BACKGROUND: Frail elderly patients are at high risk for postoperative delirium (POD), a serious complication associated with poor outcomes. The choice of anesthetic agent may represent a modifiable risk factor. This study aimed to compare the effect of anesthesia involving remimazolam versus conventional general anesthesia without remimazolam on the incidence of POD in this vulnerable population. METHODS: We enrolled frail elderly patients (defined as Clinical Frailty Scale ≥ 5) scheduled for elective non-cardiac surgery. Patients received either anesthesia involving remimazolam (R group, RESULTS: Between June 2024 and June 2025, a total of 606 patients were enrolled and analyzed (R group: CONCLUSION: In this cohort of frail elderly patients, the use of remimazolam for general anesthesia was associated with a lower incidence of postoperative delirium compared to conventional anesthesia. This choice represents a promising, modifiable strategy for improving neurological outcomes in this high-risk group.