Search Results (102)

Background and Objectives: With the rising number of geriatric surgical patients, postoperative cognitive dysfunction (POCD) has become a major concern, linked to impairments in memory, attention, and executive function. POCD increases morbidity, prolongs hospitalization, and diminishes quality of life. This review examines the mechanisms underlying POCD, with emphasis on neuroinflammation, blood–brain barrier (BBB) disruption, and oxidative stress, and evaluates the impact of anesthetic techniques on cognitive outcomes in the elderly. Materials and Methods: This narrative review used a targeted literature search to identify relevant clinical, translational, and mechanistic evidence on POCD in older surgical patients. The evidence was synthesized qualitatively, with attention to heterogeneity in study populations, anesthetic techniques, cognitive assessment methods, and follow-up duration. Results: Neuroinflammation, BBB compromise, oxidative stress, perioperative stress responses, and patient vulnerability appear to contribute to POCD. Evidence comparing anesthetic techniques remains heterogeneous. Some studies suggest associations between general anesthesia, volatile agents, and early postoperative cognitive changes, whereas other comparative and randomized studies do not demonstrate consistent long-term cognitive differences between general, regional, neuraxial, volatile, and intravenous anesthetic approaches. Regional and neuraxial techniques may reduce anesthetic or opioid exposure in selected patients, but they should not be interpreted as definitively superior for POCD prevention. Adjunctive and multimodal strategies, including dexmedetomidine and non-opioid analgesics, show potential benefits, although evidence remains variable. Conclusions: Individualized anesthetic planning, early risk stratification, avoidance of excessive anesthetic depth, hemodynamic optimization, multimodal analgesia, and postoperative recovery strategies may help reduce modifiable contributors to POCD. Current evidence does not support a definitive hierarchy of anesthetic techniques for preventing POCD, and further high-quality studies are needed. Full article

Background and Objectives: Sevoflurane, a widely used volatile anesthetic, can induce oxidative stress and apoptosis, but the underlying mechanisms in human cardiomyocytes remain unclear. This study investigated the role of transient receptor potential vanilloid 1 (TRPV1) channels in sevoflurane-induced cardiotoxicity and the potential mitigating effect of ascorbic acid. Materials and Methods: Human cardiomyocytes were exposed to sevoflurane (5.1%, 6 h) and/or ascorbic acid (1 mM, 30 min), with or without the TRPV1 channel antagonist capsazepine and with the TRPV1 channel agonist Capsaicin. Intracellular calcium, reactive oxygen species (ROS), apoptosis, mitochondrial membrane potential, and caspase-3/9 activities were assessed. Results: Sevoflurane significantly increased intracellular calcium levels, ROS production, mitochondrial depolarization, apoptosis, and caspase-3/9 activity compared with controls (p < 0.001). These effects were attenuated by capsazepine, suggesting a role for TRPV1 involvement. Ascorbic acid pretreatment significantly reduced sevoflurane-induced elevations in all parameters (p < 0.001). Combined ascorbic acid and capsazepine treatment yielded further reductions in calcium, ROS, apoptosis, and caspase activities compared to ascorbic acid alone (p < 0.05). Conclusions: Sevoflurane induces apoptosis in human cardiomyocytes via ROS-mediated activation of the TRPV1 channel, leading to calcium overload, mitochondrial dysfunction, and caspase-dependent cell death. Ascorbic acid exerts mitigating effects by reducing oxidative stress and modulating TRPV1 channel activity, suggesting a potential therapeutic strategy for myocardial protection during sevoflurane anesthesia. Full article

Background: Rocuronium onset time shows interindividual variability, yet its hemodynamic determinants remain incompletely characterized. The peripheral perfusion index (PI), derived non-invasively from pulse oximetry, reflects integrated cardiac output and peripheral vascular tone. We hypothesized that early PI dynamics during anesthesia induction are associated with rocuronium onset time. Methods: This single-center retrospective observational cohort study included 1377 adults who received rocuronium 0.6 mg/kg under a standardized induction protocol with quantitative electromyographic train-of-four monitoring. Baseline PI was categorized as low-PI (PI < 0.7), intermediate-PI (0.7 ≤ PI < 1.4), or normal-PI (PI ≥ 1.4), and patients were further stratified by anesthetic method (TIVA or volatile anesthesia), yielding six subgroups. The 60 s PI change after propofol bolus (ΔPI₆₀) was selected as the primary dynamic variable and classified into equal-frequency tertiles (Slow-Rise, Mid-Rise, Fast-Rise). Sequential multivariable linear regression model was used to quantify independent contributions of induction-phase variables on onset time. Results: In the overall cohort, onset time differed significantly across baseline PI groups (p = 0.033), though this was not replicated within either anesthetic subgroup (TIVA: p = 0.200; volatile: p = 0.137). In contrast, ΔPI₆₀ tertile was significantly associated with onset time in both subgroups (both p < 0.001), with median onset times of 211, 183, and 170 s in the Slow-Rise, Mid-Rise, and Fast-Rise groups, respectively. In the regression model, ΔPI₆₀ tertile produced the largest single increment in model fit (adjusted R² Δ0.060, p < 0.001); Slow-Rise and Mid-Rise groups had 32.7% and 18.8% longer onset times relative to Fast-Rise, respectively. Conclusions: ΔPI₆₀ was most strongly associated with rocuronium onset time among the variables examined, independent of baseline characteristics and anesthetic method. These findings provide hypothesis-generating evidence that induction-phase PI dynamics may serve as a physiologically grounded, non-invasive marker of rocuronium delivery conditions, warranting prospective validation. Full article

Background and Objectives: While liver transplantation (LT) is a definitive treatment for hepatocellular carcinoma (HCC), tumor recurrence remains a major clinical concern. Although volatile anesthetics influence oncological outcomes, direct comparison between sevoflurane and desflurane remains scarce. This study aimed to investigate the impact of the recipient’s volatile anesthetic choice (sevoflurane vs. desflurane) on HCC recurrence following living donor liver transplantation (LDLT). Materials and Methods: This retrospective cohort study included adult patients who underwent LDLT for HCC. Patients were then divided into sevoflurane and desflurane groups, and propensity score matching (PSM) was used to balance baseline variables. The primary outcome was HCC recurrence, and the secondary outcomes were overall survival (OS) and postoperative C-reactive protein (CRP) levels as a marker for the postoperative systemic inflammatory response. Results: After PSM, 373 matched pairs (n = 746) were analyzed. HCC recurrence was significantly higher in the sevoflurane group compared to the desflurane group (19.6% vs. 13.1%, p = 0.023). Kaplan–Meier analysis also demonstrated that cumulative recurrence of HCC was significantly higher in recipients who received sevoflurane anesthesia than in those who received desflurane (log-rank p = 0.0018). In multivariate Cox proportional hazards regression analysis, the use of sevoflurane for anesthesia maintenance was an independent risk factor forHCC recurrence (Hazard Ratio, 1.66; 95% Confidence Interval, 1.15–2.39; p = 0.007). Regarding OS, no significant difference was observed between the two groups (log-rank p = 0.1123). Postoperative CRP levels were significantly higher in the sevoflurane group compared to the desflurane group, suggesting a more intense systemic inflammatory response associated with sevoflurane maintenance. Conclusions: For HCC patients undergoing LDLT, anesthesia maintenance with desflurane is associated with a reduced risk of tumor recurrence compared to sevoflurane, without a significant impact on overall survival. Full article

Post-reperfusion syndrome (PRS) remains a critical complication in living donor liver transplantation (LDLT). While sevoflurane is recognized for its organ-protective properties, the impact of the donor’s anesthetic choice on recipient outcomes has not been clearly established. This study evaluated whether donor sevoflurane anesthesia reduces the incidence of PRS in recipients compared to desflurane. We retrospectively analyzed 5006 adult LDLT recipients whose donors received either sevoflurane or desflurane. Propensity score matching was employed to minimize selection bias, resulting in 941 matched pairs. The incidence of PRS was significantly lower in the sevoflurane group (64.0%) compared to the desflurane group (71.8%; p < 0.001). Multivariable logistic regression identified donor sevoflurane as an independent protective factor against PRS (odds ratio 0.47; 95% confidence interval 0.41–0.55; p < 0.001). Furthermore, recipients in the sevoflurane group exhibited significantly lower rates of prolonged intensive care unit stay, along with superior recovery of liver enzymes and inflammatory markers. Our findings suggest a potential association between donor sevoflurane anesthesia and more favorable early recipient outcomes, including a reduced incidence of PRS and enhanced recovery. Full article

Background/Objectives: Alterations in excitation/inhibition (E/I) balance, involving both inhibitory and excitatory signaling, have been implicated in the pathophysiology of autism spectrum disorder (ASD). Volatile anesthetics, including sevoflurane, act on multiple molecular and network targets, and anesthetic sensitivity may therefore differ in ASD. This study investigated whether sevoflurane sensitivity is altered in BTBR T+Itpr3tf/J (BTBR) mice, a widely used mouse model of ASD. Methods: Sevoflurane sensitivity was compared between BTBR mice and C57BL/6J (B6) control mice using behavioral and electroencephalographic (EEG) analyses. The minimum alveolar concentration required to abolish nociceptive responses (MACsevo) and the sevoflurane concentration associated with recovery of the righting reflex (RRsevo) were measured. Dose-dependent EEG changes, including burst suppression and theta power distribution, were also evaluated. Results: MACsevo did not differ significantly between BTBR and B6 mice. However, RRsevo was significantly lower in BTBR mice (1.10 ± 0.10%) compared with B6 mice (1.65 ± 0.13%; p < 0.001). EEG analyses demonstrated that burst suppression occurred at lower sevoflurane concentrations in BTBR mice (2.0%) than in B6 mice (2.4%). In addition, topographical mapping revealed distinct theta power dynamics between the two strains during anesthesia. Conclusions: BTBR mice exhibit increased sensitivity to sevoflurane during emergence from anesthesia and show distinct EEG patterns compared with control mice. These findings suggest altered anesthetic responsiveness in a mouse model of ASD and support the possibility that network-level neurophysiological differences may influence anesthetic responses. Further studies are needed to clarify whether similar alterations are present across other ASD models and human ASD populations. Full article

Isoflurane is a widely used volatile anesthetic with context-dependent effects on neuronal survival, particularly in neurodegenerative conditions. Increasing evidence suggests that brief, sublethal stress exposure can induce adaptive cellular responses through hormesis-based preconditioning mechanisms. In this study, we investigated whether isoflurane preconditioning enhances neuronal tolerance to amyloid-β (Aβ)-induced toxicity and explored the underlying redox-dependent molecular pathways. Using HT-22 murine hippocampal neuronal cells, we demonstrate that short-term exposure to low-dose isoflurane induces a delayed neuroprotective phenotype characterized by improved cell viability, reduced apoptotic signaling, and maintained mitochondrial membrane potential following Aβ challenge. Mechanistically, isoflurane preconditioning elicited a mild and transient increase in intracellular reactive oxygen species (ROS), which is critical for the activation of the PI3K/Akt signaling pathway. Pharmacological scavenging of reactive oxygen species abolished Akt phosphorylation and reduced the protective effects of preconditioning, supporting a hormetic signaling model rather than direct antioxidant action. Following Akt activation, isoflurane preconditioning promoted the inhibitory phosphorylation of glycogen synthase kinase-3β (GSK-3β), decreased Keap1 protein levels, and facilitated nuclear translocation and transcriptional activation of nuclear factor erythroid 2-related factor 2 (Nrf2). Consequently, the expression of Nrf2-regulated antioxidant genes, including heme oxygenase-1, NAD(P)H quinone dehydrogenase 1 (NQO1), superoxide dismutase 1 and 2 (SOD1/2), and catalase, was significantly upregulated. Collectively, these findings indicate that isoflurane preconditioning confers neuroprotection through hormesis-like mild oxidative signaling and coordinated activation of endogenous antioxidant defenses rather than via direct antioxidant scavenging. Full article

Volatile anesthetics have steadily become more popular in intensive care units for sedation for reasons related to their beneficial pharmacokinetic and pharmacodynamic properties. Common anesthetics such as isoflurane and sevoflurane rapidly reach sedative levels in the body, but they are also rapidly eliminated, allowing for quick recovery. These agents have minimal impact on the liver and kidneys, which makes them attractive options when compared to other agents including opioids, benzodiazepines, ketamine, and propofol. Use of delivery systems like AnaConDa^® (Anaesthetic Conserving Device; Sedana Medical AB, Danderyd, Sweden) has enabled providers to easily use these agents in the Intensive Care Unit (ICU). In this regard, they have recently provided additional beneficial consideration during intravenous drug shortages seen during the COVID-19 pandemic and at other times. These agents have shown organ-protective effects in the kidneys and lungs, which may even reduce the total time spent in the ICU. Pharmacodynamically, these anesthetics mediate their effects through central nervous system ion channels to exert analgesic and anxiolytic actions, thereby minimizing effects in the kidneys and lungs. These agents are primarily eliminated via exhalation, which makes them potential options for those with liver or kidney failure. This narrative review examines current efficacy and risks of using volatile anesthetics for sedation in the ICU setting and clinical roles for the future. Full article

Introduction: Severe traumatic brain injury (sTBI) frequently coexists with polytrauma and often necessitates damage control neurosurgery (DCNS), where rapid decompression and temporary stabilization take precedence over definitive reconstruction. Within this context, anesthetic management must balance cerebral protection with ongoing resuscitation, yet high-quality DCNS-specific evidence remains limited. Materials and Methods: A comprehensive search of PubMed, Scopus, and Google Scholar (2015–2025) was conducted using MeSH terms and keywords related to neurotrauma, anesthesia, intracranial pressure, and perioperative management. Studies were included if they examined anesthetic or hemodynamic strategies in severe TBI or DCNS and reported relevant clinical or physiologic outcomes. Results: Nineteen articles addressing perioperative strategies for optimizing DCNS outcomes were analyzed. Discussion: Preoperative care emphasizes hemodynamic stabilization and permissive hypertension, damage control resuscitation including massive transfusion protocols, optimization of cerebral perfusion pressure (CPP) and neuromonitoring, and the use of hyperosmolar therapy. Transexamic acid can be used in sTBI safely but with unclear improvement in outcomes. Intraoperatively, propofol-based total intravenous anesthesia is generally preferred over volatile agents due to favorable effects on intracranial pressure (ICP), cerebral blood flow (CBF), autoregulation, and emergence. While historically contraindicated, ketamine and etomidate are now increasingly used as hemodynamically protective induction agents. Analgesic and sedative strategies prioritize dexmedetomidine and carefully titrated opioids to minimize respiratory depression and reduce postoperative complications. CPP and ICP-directed management relies on individualized blood pressure targets, vasopressor selection, lung-protective ventilation, and strict temperature control. Conclusions: Emerging evidence has suggested the benefit of DCNS for patient survival. Overall, perioperative care is guided largely by physiology and extrapolation, highlighting the need for standardized protocols. Full article

Background: Interest in inhalational anesthesia in cardiac surgery has resurged as volatile anesthetics exert biological effects extending beyond hypnosis. Sevoflurane and desflurane activate mitochondrial cytoprotective signaling pathways, modulate inflammatory and endothelial responses and may attenuate ischemia–reperfusion injury during cardiopulmonary bypass, potentially influencing postoperative organ function and recovery. Methods: This narrative review critically examines experimental and clinical evidence on the use of volatile anesthetics in cardiac anesthesia. The current literature was analyzed to elucidate mechanistic foundations of myocardial and extracardiac organ protection, hemodynamic and metabolic effects, and the influence of patient-specific vulnerability profiles on perioperative outcomes. Results: Preclinical studies consistently demonstrate that volatile anesthetics trigger mitochondrial protective pathways, including K-ATP channel activation, controlled reactive oxygen species signaling and inhibition of the mitochondrial permeability transition pore. Clinical studies suggest potential benefits in myocardial protection and modulation of systemic inflammatory and microcirculatory responses. However, translation into consistent clinical outcome improvement remains heterogeneous, influenced by variability in surgical procedures, anesthetic protocols and patient risk stratification. Conclusions: Volatile anesthetics exhibit mechanistic properties supporting a potential role in organ protection during cardiac surgery. Nevertheless, clinical evidence remains inconclusive, underscoring the need for refined patient stratification and precision-based perioperative strategies. Identifying knowledge gaps and research priorities may facilitate rational, individualized integration of inhalational anesthesia into contemporary cardiac surgical practice. Full article

Background/Objectives: Volatile anesthetic dosing during cardiopulmonary bypass (CPB) is poorly standardized. We estimated the end-tidal sevoflurane (ETsevo) concentration required to maintain adequate anesthesia during CPB and investigated the effects of age and body temperature. Methods: This study is a PRISMA-compliant, PROSPERO-registered meta-analysis. PubMed, Embase, and the Cochrane Library were searched. Prospective studies of adults who underwent cardiac surgery with CPB and receiving sevoflurane were included. Primary outcome was mean ETsevo concentration when bispectral index (BIS) was 40–60. Three-level random-effects meta-analytic models with robust variance estimation were used to pool repeated measurements within studies. Age and body temperature were then examined as study-level moderators. Risk of bias was determined using ROBINS-I. Results: Five studies (n = 129) fulfilled the criteria. Pooled ETsevo during CPB was 0.88 vol% (95% confidence interval [CI] 0.29 to 1.46; p = 0.02) with substantial heterogeneity (I² = 87.6%). Body temperature was not a significant moderator (difference 0.26 vol%; 95% CI −1.12 to 1.64; p = 0.27). Higher mean age was associated with lower ETsevo, evidenced by the finding that patients with a mean age of >62.0 years required 0.45 vol% less ETsevo (95% CI −0.78 to −0.13; p = 0.01), and sensitivity analysis revealed a 0.05 vol% decrease per additional year. Conclusions: To maintain BIS at 40–60 during CPB, the estimated ETsevo requirement is 0.88 vol% (minimum alveolar concentration 0.53–0.58 in patients in their 60s). Requirements decreased with age, and body temperature exerted no detectable effect. Full article

Damage-associated molecular patterns (DAMPs) are endogenous molecules released during cellular stress or injury that trigger sterile inflammation. In perioperative settings, common triggers include surgical trauma, ischemia–reperfusion injury, cardiopulmonary bypass, blood transfusion, and mechanical ventilation. When released extracellularly, DAMPs activate innate immune receptors such as Toll-like receptors (TLRs) and the receptor for advanced glycation end products (RAGE), initiating signaling cascades that amplify inflammation, disrupt endothelial integrity, and promote coagulation and metabolic imbalance. This sterile inflammatory response may extend local tissue injury into systemic organ dysfunction, manifesting clinically as acute lung injury, acute kidney injury, myocardial dysfunction, disseminated intravascular coagulation, and perioperative neurocognitive disorders. Recognizing the central role of DAMPs reframes these complications as predictable consequences of endogenous danger signaling rather than solely as results of infection or hemodynamic instability. This understanding supports the use of established strategies such as protective ventilation and restrictive transfusion to minimize DAMP release. Emerging evidence also suggests that anesthetic agents may influence DAMP-mediated inflammation: propofol and dexmedetomidine appear to exert anti-inflammatory effects, whereas volatile anesthetics show variable results. Although clinical data remain limited, anesthetic choice and perioperative management may significantly affect systemic inflammatory burden and recovery. Future research validating DAMPs as biomarkers and therapeutic targets may inform precision anesthetic strategies aimed at modulating sterile inflammation, ultimately enhancing perioperative outcome. Full article

Ethyl chloride, a volatile anesthetic with high abuse potential, remains forensically undercharacterized postmortem. In an inhalation model (n = 30), male Wistar rats were exposed to 86,000 ppm ethyl chloride under real-time PID monitoring; blood, lung, liver and brain (plus exploratory adipose, kidney, muscle) were sampled at 0, 2, 4, 6 and 12 h postmortem. A matrix-matched HS-GC-FID method was validated (Eurochem): linearity (R² = 0.9947–0.9965), LOD 0.01–0.02 ng/μL, LOQ 0.04–0.06 ng/μL, precision RSD 3.9–5.1%, recovery 90–104%, full selectivity against common volatiles. Lung yielded the highest concentrations overall; a significant decline occurred in lung between 2 h and 4 h (Pillai’s Trace p = 0.034). Concentrations became increasingly irregular ≥6 h across tissues. Early autopsy sampling, preferably within ≤6 h, optimizes ethyl chloride detectability. The validated matrix-matched HS-GC-FID protocol provides a cost-effective, robust alternative to MS platforms for volatile screening in routine forensic practice and supports prioritizing lung for analysis. Full article

Malignant hyperthermia (MH) is a rare pharmacogenetic disorder triggered by volatile anesthetics and succinylcholine, most often linked to pathogenic variants in RYR1, CACNA1S, and STAC3. The advent of next-generation sequencing (NGS) has transformed MH diagnostics, offering new opportunities for perioperative risk assessment as caffeine–halothane contracture testing declines. However, challenges remain, including incomplete penetrance, variable pathogenicity of variants, limited access to functional confirmatory testing, and cost. Genetic testing also raises important questions. What is the clinical utility of finding a variant of unknown significance? What are the broader implications of MH susceptibility beyond the operating room? Emerging evidence connects MH susceptibility loci to exertional heat illness (EHI), exertional rhabdomyolysis (ERM), and heat-related mortality, highlighting the need for a broader framework for genetic risk assessment. This review synthesizes historical advances, current consensus, and future directions concerning MH to guide anesthesiologists and perioperative clinicians in leveraging molecular diagnostics for personalized care and improved patient safety. Full article

Postoperative infections represent the most frequent complication after surgery. Anesthetic agents, while essential during surgical procedures to ensure unconsciousness, are becoming increasingly recognized as modulators of immune function. Volatile anesthetics have been identified as being able to attenuate the inflammatory response in diverse experimental models. Propofol, a widely used intravenous anesthetic, has also been described to exhibit strong anti-inflammatory mechanisms. This review synthesizes current cellular, experimental, and clinical evidence on the immunomodulatory effects of anesthetic agents, highlighting their impact on host defense mechanisms and postoperative infections. By exploring mechanistic properties and clinical outcomes, it underscores the importance of anesthetic choice in enhancing immune function and postoperative recovery. Full article