Daily Anesthesiology Research Analysis

BACKGROUND: The prognostic relevance of perioperative myocardial injury/infarction (PMI) in older patients undergoing major noncardiac surgery remains unclear, as high comorbidity burden may lessen its impact. METHODS: Older patients (defined as age ≥70 years with ≥3 comorbidities, or ≥80 years) enrolled in a multicentre, prospective study of patients at increased cardiovascular risk undergoing major noncardiac surgery were analysed. The primary endpoint, all-cause mortality at 1 year, was analysed using Cox proportional hazards regression. Secondary endpoints included major adverse cardiac events (MACE) (cardiovascular death, acute myocardial infarction, life-threatening arrhythmia and acute heart failure), analysed using Fine-Grey hazard regression. All models were adjusted for prespecified confounders with PMI as a time-varying exposure. RESULTS: Amongst 4634 older patients (median age 80 years; 42.9% women), PMI occurred in 892 patients (19.2%), which was higher than in younger patients (P < .0001). The distribution of PMI aetiologies was comparable between groups. At 1 year, all-cause mortality was 26.2% in patients with PMI and 13.2% in patients without PMI, and MACE occurred in 30% versus 13%, respectively. After multivariable adjustment, the hazard ratio of PMI was highest on postoperative day 1 (all-cause mortality: 10.5 [95% CI 4.5-24.5]; MACE: 4.4 [95% CI 3.2-5.9]), declined by day 90 (1.4 [95% CI 1.0-1.9] and 2.2 [95% CI 1.7-2.7], respectively), and persisted through 1 year. CONCLUSIONS: PMI was very common amongst older patients and associated with substantially higher 1-year risks of all-cause mortality and MACE, with greatest vulnerability observed during the initial 90 postoperative days.

Postoperative cognitive dysfunction (POCD) in the elderly is a serious clinical concern. Although microglial phagocytosis is known to depend on mitochondrial metabolism, and its dysregulation can lead to abnormal synaptic pruning and neuronal injury, the molecular link between these processes in POCD pathogenesis requires further elucidation. In this study, we established a POCD animal model of aged mice using isoflurane exposure and partial hepatectomy to investigate how anesthesia and surgery impacted synaptic plasticity via microglial phagocytosis. Our findings demonstrated that anesthesia and surgery significantly reduced hippocampal peroxisome proliferators-activated receptor γ coactivator-1α (PGC-1α) expression, leading to impaired mitochondrial energy metabolism, abnormal microglial phagocytosis and excessive synaptic pruning, which was associated with synaptic deficits and cognitive dysfunction. Importantly, the treatment with the PGC-1α activator ZLN005 or AAV-mediated overexpression of PGC-1α not only successfully restored PGC-1α level in the hippocampus of aged mice, but also effectively ameliorated mitochondrial dysfunction, reversed abnormal microglia-mediated synaptic pruning, restored synaptic plasticity, and improved POCD. Our findings identify microglial PGC-1α as a critical mediator in the pathogenesis of POCD, linking mitochondrial energy metabolism with microglia-mediated synaptic pruning, and highlight the potential of microglial PGC-1α as a promising therapeutic target for prevention and treatment of POCD.

PURPOSE: Oxycodone is a dual μ/κ-opioid receptor agonist effective in managing both somatic and visceral pain. We compared the effect of oxycodone-based versus sufentanil-based multimodal regimens on early gastrointestinal recovery and pain control following laparoscopic colorectal cancer surgery. METHODS: In this single-center, prospective, randomized, double-blind trial, 76 patients undergoing elective laparoscopic colorectal cancer surgery were allocated to the oxycodone group (Group O) or the sufentanil group (Group S). Both groups received standardized multimodal analgesia with preoperative TAP block, postoperative PCIA, and flurbiprofen axetil for rescue. The primary endpoint was time to first flatus; secondary outcomes included other recovery indicators, pain and sedation scores, opioid and PCIA use, adverse effects, PACU stay, and hospital length of stay. RESULTS: Group O shortened time to first flatus (43.7±7.9 h vs 48.4±8.7 h, mean difference -4.8 h; 95% CI -8.6 to -1.0; P = 0.015) and time to ambulation (47.3±5.1 h vs 50.0±3.8 h, mean difference -2.7 h; 95% CI -4.8 to -0.7; P = 0.010). Group O reduced PCIA demands (median 0 vs 2), rescue analgesia (7.9% vs 26.3%), PONV (7.9% vs 31.6%), PACU stay (median 55 vs 60 min), and remifentanil use (2.8±0.4 vs 3.1±0.5 mg) (all P < 0.05). Postoperative sedation at 4 h was better in group O. Visceral pain scores at 12 h and 48 h were lower with oxycodone, whereas incisional pain and solid-food tolerance did not differ; length of stay was similar. CONCLUSION: Oxycodone-based multimodal analgesia was associated with improved early gastrointestinal recovery indicators, better visceral pain control, and fewer opioid-related adverse effects than the sufentanil-based regimen, but did not reduce hospital length of stay. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR2500100676).