Anesthesiology and Perioperative Science最新文献

Anesthesia is essential in modern surgical practice, ensuring patient comfort, immobility, and amnesia. However, its impact on the immune system has become a growing area of research, as anesthetic agents can modulate immune function in complex ways. Emerging evidence suggests that anesthetics may induce immune dysregulation, affecting both innate and adaptive immunity, with potential consequences for patient outcomes, particularly in the context of infection, inflammation and cancer. This review provides a comprehensive understanding of the immunological effects of anesthesia, exploring the molecular and cellular pathways involved. It examines how anesthetics can either suppress or modulate immune responses, depending on factors including drug type, dose and patient-specific characteristics. We discuss their influence on innate immunity, including the activity of natural killer cells, macrophages and neutrophils, as well as their impact on adaptive immunity, particularly T-cell activation, cytokine production and antigen presentation. In addition, we highlight the immunological consequences of commonly used anesthetic agents in clinical practice.

Purpose

Dexmedetomidine (DEX) has been extensively studied for its protective effects on multiple organs, primarily attributed to its anti-inflammatory and anti-apoptotic properties. However, the molecular mechanisms underlying its effects in acute hepatic damage induced by N-Nitrosodiethylamine (DEN) remain unclear. This study aims to investigate the role of DEX in mitigating DEN-induced acute hepatic damage and elucidate the involvement of the silent information regulator 1 (SIRT1)-autophagy axis in this process.

Methods

Acute hepatic damage was induced by a single intraperitoneal injection of 1% DEN (10 mg/kg). DEX (20, 40, or 80 μg/kg) was administered intraperitoneally 30 min prior to DEN exposure. Additionally, the SIRT1 inhibitor Selisistat (EX527) or the autophagy inhibitor 3-MA was administered intraperitoneally 30 min after DEN injection. Histopathological changes, inflammatory and oxidative responses were assessed 24 h post-DEN exposure. The roles of autophagy and SIRT1 were further examined using hepatocyte-specific SIRT1 knockout mice (SIRT1^f/fALB^cre+/−).

Results

A single injection of DEN significantly induced acute hepatic damage, characterized by marked elevations in serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST), hepatocyte necrosis, inflammatory cell infiltration, and increased oxidative stress burden. Dexmedetomidine pretreatment effectively attenuated hepatic damage, as evidenced by significant reductions in ALT, AST, and reactive oxygen species (ROS) accumulation. The expressions of LC3B and SIRT1 were upregulated following DEX pretreatment, with increased co-localization between the two proteins. However, the hepatoprotective effects of DEX were abolished when SIRT1 was inhibited by EX527 or genetically deleted in in SIRT1^f/fALB^cre+/– mice.

Conclusions

Dexmedetomidine significantly alleviates DEN-induced acute hepatic damage through a mechanism involving the upregulation of autophagy and SIRT1 activity. These findings suggest that DEX may be a promising therapeutic strategy for treating severe hepatic damage and other forms of acute organ injury.

Purpose

Sepsis is a life-threatening disorder marked by organ dysfunction due to infection. Transient receptor potential vanilloid 1 (TRPV1) is a non-selective, ligand-gated cation channel activated by multiple stimuli. This study investigates the role of TRPV1 in sepsis-associated encephalopathy (SAE).

Methods

The SAE models of wild-type and TRPV1 knockout (TRPV1^-/-) mice were established through intraperitoneal injection of 10 mg/kg lipopolysaccharide. Brain tissues and serum were collected 24 h post-injection for analysis. Rectal temperature was monitored at 12 and 24 h, and the 7-day survival rate was recorded. Mice were pretreated with capsaicin (CAP), and brain tissue and serum were collected for detection.

Results

TRPV1 expression was significantly elevated in the brain tissues of mice with sepsis. TRPV1^-/- aggravated SAE symptoms, as evidenced by a significant decrease in rectal temperature, a reduced 7-day survival rate, an elevated Murine Sepsis Score, and greater impairment in learning and memory. Mechanistically, TRPV1 deficiency increased NF-κB, pyroptosis-related proteins, and levels of IL-6 and TNF-α in SAE mice. CAP pretreatment significantly reduced abnormal neurons in the CA1 region, decreased NF-κB, Pro-caspase1, and Cleaved-caspase1 in brain tissues, and lowered IL-1β and IL-18 serum levels, with this effect being TRPV1-dependent.

Conclusion

In summary, TRPV1 deficiency worsens SAE-induced damage in mice, associated with activation of NF-κB and pyroptosis pathways. CAP pretreatment improved the damage caused by SAE by activating TRPV1.

Sleep architecture is frequently disrupted after major surgery, leading to acute and chronic postoperative sleep disorders that may contribute to episodic hypoxia, hemodynamic instability, postoperative fatigue, cognitive dysfunction, depression. These all have potentially detrimental impacts on disease regression. Pain is a key driver of postoperative sleep disruption and opioids are widely used for pain management due to their potent analgesic and sedative effects. Opioids are conventionally believed to induce natural sleep and reduce sleep disorders. However, available evidence suggests that opioids can disrupt sleep architecture, leading to sleep deprivation, fragmentation and restriction. This systematic review investigates the detrimental effects of opioids on postoperative sleep and explores the underlying mechanisms responsible for sleep disorders. By synthesizing current evidence wehighlight the risks associated with opioid-centric pain management strategies and advocate for a more balanced approach that optimizes pain relief while mitigating opioid-induced sleep disruption.

Purpose

Rebound pain occurs when peripheral nerve blocks (PNBs) subside and this hampers patient recovery after surgery. This study aims to determine the most effective adjuvant to mitigate rebound pain in adult surgical patients.

Methods

A comprehensive search was conducted for randomized controlled trials (RCTs) that reported rebound pain and utilized perineurally (PN) or intravenously (IV) administered adjuvants. We used multiple databases, including PubMed, Web of Science, the Cochrane Library, Embase, CNKI, Wanfang Data, SinoMed and Chinese medical journals from their inception until September 30, 2024. The primary outcome measured was the incidence of rebound pain. A network meta-analysis was performed using a frequentist approach.

Results

The meta-analysis included three RCTs examining ketamine/esketamine, eight evaluating dexamethasone and one assessing tropisetron. Compared to no adjuvant, IV dexamethasone was found to significantly reduce the incidence of rebound pain (odds ratio [OR] = 0.13, 95% confidence interval [CI]: 0.05, 0.35) and postoperative nausea and vomiting (PONV; OR = 0.33, 95% CI: 0.12, 0.85), while also prolonging the time to onset of rebound pain (mean difference [MD] = 3.95 h, 95% CI: 1.36, 6.53). PN dexamethasone extended the time to onset of rebound pain (MD = 6.57 h, 95% CI: 3.20, 9.93) but did not significantly reduce the incidence of rebound pain or PONV. Ketamine/esketamine was associated with a reduction in the incidence of rebound pain (OR = 0.30, 95% CI: 0.10, 0.89) but did not affect PONV. According to the rank order of surface under the cumulative ranking curve analysis, IV dexamethasone exhibited the lowest incidence of rebound pain and PONV compared to PN dexamethasone, ketamine/esketamine, tropisetron and no adjuvant. PN dexamethasone was most effective in prolonging the onset of rebound pain compared to IV dexamethasone, tropisetron and no adjuvant. The overall quality of evidence was rated as low or very low.

Conclusion

Current evidence, albeit of low quality, indicates that IV dexamethasone is the most effective adjuvant for the prevention of rebound pain, while PN dexamethasone is optimal for delaying its onset. Therefore, a combined approach utilizing both IV and PN dexamethasone following PNB may represent an effective strategy for managing rebound pain in adult surgical patients.