Daily Anesthesiology Research Analysis
A high-quality randomized trial found no analgesic benefit of single-shot four-quadrant TAP blocks using liposomal or plain bupivacaine versus saline in major abdominal surgery, challenging routine use. A large multicenter analysis showed that moderate-to-severe pain on postoperative day 1 is independently associated with delirium within 7 days in older adults after abdominal surgery. A prospective study suggests intraoperative esketamine infusion reduces postoperative sleep disturbance, with an
Summary
A high-quality randomized trial found no analgesic benefit of single-shot four-quadrant TAP blocks using liposomal or plain bupivacaine versus saline in major abdominal surgery, challenging routine use. A large multicenter analysis showed that moderate-to-severe pain on postoperative day 1 is independently associated with delirium within 7 days in older adults after abdominal surgery. A prospective study suggests intraoperative esketamine infusion reduces postoperative sleep disturbance, with an EEG-derived slow-wave index predicting risk.
Research Themes
- De-implementation of low-value perioperative regional anesthesia
- Pain and neurocognitive outcomes in older surgical patients
- Mechanism-informed strategies for postoperative sleep and recovery
Selected Articles
1. Liposomal Bupivacaine, Plain Bupivacaine, and Saline for Transversus Abdominis Plane Blocks: The CLEVELAND Randomized Trial.
In this randomized, blinded trial (n=261), single-shot four-quadrant TAP blocks with liposomal bupivacaine, plain bupivacaine, or saline produced similar opioid requirements and pain scores at 24, 48, and 72 hours after major abdominal surgery. The findings indicate no early or sustained analgesic benefit from liposomal bupivacaine or plain bupivacaine versus placebo when used in this context.
Impact: This well-powered negative RCT challenges the routine use of pre-incision single-shot TAP blocks and the perceived advantages of liposomal bupivacaine, with substantial implications for ERAS pathways and cost-effective perioperative care.
Clinical Implications: Avoid routine pre-incision, single-shot TAP blocks in mixed major abdominal surgery populations and reconsider the use of costly liposomal bupivacaine. Emphasize multimodal systemic analgesia and consider alternative regional techniques (e.g., continuous catheters) where indicated.
Key Findings
- 24-hour opioid consumption was similar across groups: liposomal bupivacaine 26 [18,48] MME, plain bupivacaine 33 [13,75] MME, placebo 31 [17,53] MME.
- Geometric mean ratios showed no reduction with liposomal (0.86; 97.7% CI 0.60–1.24) or plain bupivacaine (0.91; 97.7% CI 0.63–1.32) versus placebo.
- Opioid use from 24–48 hours, 48–72 hours, pain scores, time to return of sensation, and other secondary outcomes were comparable among all groups.
Methodological Strengths
- Randomized, blinded, three-arm design with modified intention-to-treat analysis
- Standardized TAP technique and blinded clinical teams, reducing bias
Limitations
- Heterogeneous surgical population and procedures may dilute subgroup benefits
- Single-shot, pre-incision strategy; findings may not apply to continuous catheter techniques or postoperative timing
Future Directions: Evaluate patient selection, timing (postoperative vs pre-incision), and continuous catheter techniques; cost-effectiveness analyses to guide de-implementation and resource allocation.
BACKGROUND: Enhanced Recovery After Surgery (ERAS) pathways recommend transversus abdominis plane (TAP) blocks, but their efficacy is controversial and limited by the duration of local anesthetics. Liposomal bupivacaine is commonly used in single-injection TAP blocks to extend analgesia, though its effectiveness remains unclear. We therefore tested two co-primary hypotheses: first, that opioid consumption during the initial 24 postoperative hours is higher with saline than plain bupivacaine or liposomal bupivacaine; and second, that opioid consumption between 24 to 48 hours post-surgery is comparable or greater with saline or plain bupivacaine than with liposomal bupivacaine. METHODS: Patients having major abdominal surgery (e.g., colorectal, gynecological, hernia repairs etc.) were enrolled and randomly assigned 1:1:1 to bilateral 4-quadrant TAP blocks with liposomal bupivacaine (40 ml plain bupivacaine 0.25% with 20 ml liposomal bupivacaine and 20 ml of saline), plain bupivacaine (50 ml of plain bupivacaine 0.5% with 30 ml normal saline) and placebo (80 ml normal saline). Patient-controlled intravenous opioids were used as needed. Patients, clinicians who adjust opioid analgesia, ward nurses who evaluated pain scores, and study investigators who evaluated local anesthetic effects were blinded to treatment groups. FINDINGS: In our modified intention to treat cohort of 261 patients, opioid requirements during the first 24 hours were median [IQR] 26 [18, 48] MME (morphine milligram equivalents) for liposomal bupivacaine (n = 89), 33 [13, 75] MME for plain bupivacaine (n = 84), and 31 [17, 53] MME for placebo (n = 88). The estimated ratio of geometric means was 0.86 (97.7% CI: 0.60, 1.24; P = 0.355) between liposomal bupivacaine and placebo groups, and 0.91 (97.7% CI: 0.63, 1.32; P = 0.578) between plain bupivacaine and placebo groups. Opioid requirements between 24-48 hours were also comparable across groups. Secondary outcomes, including time to sensation return, pain scores, and opioid requirements from 48-72 hours, were similar across all groups, with no significant differences observed. CONCLUSION: Single-shot, four-quadrant TAP blocks performed with liposomal bupivacaine, plain bupivacaine, or normal saline before incision for various open and laparoscopic abdominal procedures resulted in similar postoperative opioid consumption and pain scores at 24, 48, and 72 hours. Absence of early benefit suggests that routine pre-incision, single-shot TAP blocks in this mixed surgical population provide little analgesia.
2. The effect of early postoperative acute pain on postoperative delirium in older persons undergoing abdominal surgery: a secondary analysis of multicenter prospective data.
Among 2,674 older adults undergoing elective abdominal surgery, moderate-to-severe pain on postoperative day 1 was independently associated with 7-day postoperative delirium across univariate, multivariable, and PSM analyses. The findings highlight early pain control as a modifiable target for delirium prevention.
Impact: Identifies a modifiable and common perioperative factor—early postoperative pain—linked to delirium in a large, multicenter cohort, guiding pragmatic prevention strategies.
Clinical Implications: Implement proactive multimodal analgesia and day-1 pain surveillance in older adults, integrate pain scores into delirium risk stratification, and embed early analgesic optimization within delirium prevention bundles.
Key Findings
- Postoperative delirium occurred in 13.2% within 7 days after surgery.
- Moderate-to-severe pain on POD1 was associated with delirium: unadjusted OR 1.83 (95% CI 1.445–2.319), multivariable OR 1.63 (95% CI 1.274–2.084), PSM OR 1.44 (95% CI 1.108–1.879).
- Delirium prevalence was significantly higher in the moderate-to-severe pain group (16.3% vs 9.6%, p<0.001).
Methodological Strengths
- Multicenter prospective dataset with large sample size
- Robust analyses including multivariable regression, propensity score matching, and subgroup analyses
Limitations
- Observational secondary analysis limits causal inference
- Pain assessments and analgesic regimens may vary; residual confounding possible
Future Directions: Test whether intensified day-1 multimodal analgesia reduces delirium in randomized trials; integrate pain metrics into validated delirium prediction tools.
PURPOSE: Older persons frequently experience postoperative acute pain and delirium, however, there is little clinical data on their possible interrelationships. METHODS: A secondary analysis of multicenter prospective data, including tertiary hospitals in Five Chinese Regions, from April 2020 to April 2022. Older persons (≥ 65 years) scheduled for elective abdominal surgery under general anesthesia, without auditory, visual, or cognitive impairments, who completed assessments for postoperative delirium, anxiety, and depression. The impact of early postoperative acute pain on postoperative delirium in older persons undergoing abdominal surgery was evaluated using univariate and multivariate logistic regression, propensity score matching, and subgroup analysis. RESULTS: The study cohort included 2,674 patients. The median age was 70 years, and 66.5% of the patients were male. Delirium occurred in 13.2% (n = 354) of patients in postoperative 7 days (POD 7), with a significantly higher prevalence in the moderate-to-severe pain group (unadjusted: 16.3 vs. 9.6%, p < 0.001). Moderate-to-severe pain on POD1 showed a significant association with delirium occurrence in POD 7 according to univariate logistic regression (OR 1.83, 95% CI 1.445-2.319, p < 0.001), multivariable logistic regression (OR 1.63, 95% CI 1.274-2.084, p < 0.001), and propensity score matching (PSM) model (OR 1.44, 95% CI 1.108-1.879, p = 0.006). CONCLUSION: In older persons undergoing elective abdominal surgery, moderate-to-severe pain on POD 1 was significantly associated with both delirium and depressive symptoms within 7 days of surgery. Improved early postoperative analgesic strategies may aid in preventing delirium. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT06964893 (2025-05-07).
3. The impact of intraoperative esketamine infusion on postoperative sleep in patients undergoing general surgery.
Continuous intraoperative esketamine infusion (0.3 mg/kg/h) reduced postoperative sleep disturbance on days 1 and 3 and lessened early pain. An EEG-derived slow-wave composite index (PCI) robustly predicted sleep disturbance risk, while preoperative melatonin, IL-6, anxiety, and postoperative pain were independent predictors.
Impact: Links a practical intraoperative intervention to improved postoperative sleep and identifies a mechanistic EEG biomarker (PCI) to stratify risk, advancing precision perioperative care.
Clinical Implications: Consider esketamine infusion in selected general surgery patients to reduce early postoperative sleep disturbance and pain, and explore EEG-based indices (PCI) for risk stratification; address modifiable risks (anxiety, inflammation, inadequate melatonin).
Key Findings
- Esketamine reduced postoperative sleep disturbance on POD1 (49.3% vs 25.3%, P=0.002) and POD3 (36.0% vs 18.7%, P=0.017).
- EEG slow-wave composite index (PCI) predicted PSD risk (OR 0.25; 95% CI 0.139–0.479; P<0.001).
- Independent predictors of PSD: esketamine administration (protective), lower preoperative melatonin, higher preoperative IL-6, higher anxiety (HADS-A), and higher postoperative pain.
Methodological Strengths
- Prospective design with pre-registration and mechanistic EEG monitoring
- Multivariate modeling identifying independent predictors
Limitations
- Randomization and blinding procedures are not clearly detailed in the abstract
- Single-center context and subjective sleep measure (AIS); external validation needed
Future Directions: Randomized, blinded multicenter trials to confirm efficacy; validate PCI thresholds and integrate biomarker-guided dosing; evaluate longer-term sleep and cognitive outcomes.
OBJECTIVE: Major abdominal surgery frequently induces circadian sleep-wake disturbances, characterized by increased daytime rapid eye movement (REM) sleep and prolonged nocturnal wakefulness. This study investigated the effects of perioperative continuous esketamine infusion (0.3 mg/kg/h) on postoperative sleep disturbance in patients under general anesthesia. Intraoperative electroencephalography (EEG) monitoring was implemented with focused analysis of relative wavelength frequencies. METHODS: . Patients undergoing surgery received a continuous intraoperative esketamine infusion at a dose of 0.3 mg/kg/h. Concurrent electroencephalography (EEG)monitoring was performed, with the analysis specifically focusing on relative power percentages of the EEG signal.Preoperatively, levels of melatonin (quantified using mass spectrometry), Interleukin-6 (IL-6), and C-Reactive Protein (CRP)were measured.Postoperative sleep quality was then assessed on days 1 and 3 using the Athens Insomnia Scale (AIS), where a score > 6 was defined as sleep disturbance. RESULTS: The esketamine group exhibited significantly lower rates of sleep disturbance on postoperative day 1 (37/75 [49.3%] vs. 19/75 [25.3%];P = 0.002) and day 3 (27/75 [36.0%] vs. 14/75 [18.7%];P = 0.017). Significant intergroup differences in acute postoperative pain were observed. The EEG analysis demonstrated that the slow-wave activity composite index (PCI) serves as a robust predictor for postoperative sleep disturbance risk(OR = 0.25, 95% CI:0.139-0.479;P < 0.001).Multivariate logistic regression identified independent predictors of postoperative sleep disturbance (PSD): Esketamine administration (OR 0.274; 95% CI 0.088-0.854);Preoperative melatonin levels (per-unit increase: OR 1.039; 95% CI 1.013-1.065);Preoperative HADS-A anxiety score (OR 1.396; 95% CI 1.075-1.813);preoperative IL-6 levels (OR 1.274; 95% CI 1.025-1.583);Postoperative pain score (OR 2.340; 95% CI 1.483-3.692);PC1 (OR 0.25, 95% CI: 0.139-0.479). CONCLUSION: Perioperative esketamine administration significantly reduces postoperative sleep disturbance (PSD) incidence and early postoperative pain severity. Independent risk factors for PSD include preoperative melatonin deficiency, anxiety symptoms (HADS-A), preoperative IL-6 elevation, and acute postoperative pain. Crucially, the slow-wave activity composite index (PCI)-reflecting esketamine-induced prefrontal delta synchronization (δ/α ratio + Delta power)-emerges as a robust predictor of PSD risk (OR = 0.25, 95% CI: 0.139-0.479;P < 0.001). REGISTRY: ChiCTR Trial Registration Number (TRN): ChiCTR2400092868 Registration date: 25 November 2024.