Search Results (436)

Background: Neurodevelopmental disorders span a wide spectrum of deficits, often with a known or suspected genetic basis. While some genetic determinants may indicate treatment with selective compounds, more often both the molecular cause of the disorder and the mechanism of action for the therapeutic compound are more ambiguously matched. Due to the polypharmacological nature of most neuroactive compounds, measuring gene expression changes following drug perturbation could be an effective strategy to gain insight into shared therapeutic action downstream of diversity in receptor interaction. High-throughput drug discovery platforms have effectively measured changes in gene expression following drug perturbation in cell cultures, but unfortunately, these platforms often lack specificity for neuroactive compounds, fail to capture the developmental influence of cell–cell interactions, and do not accurately model drug metabolism in an intact system. Methods: In this study, we present a high-throughput, low-cost and cell-type-specific approach for capturing transcriptional changes in neural cell populations following neuroactive compound exposure through the combined use of transgenic zebrafish, cell sorting, and bulk RNA-seq. Results: Our system captures unique transcriptional profiles between neuronal and non-neuronal cell populations and demonstrates specific drug responsiveness within our neuronal cell population. We assessed two known positive allosteric modulators (PAMs) of γ-Aminobutyric acid sub-type A receptors (GABA_AR), ivermectin and propofol, as a case study to explore shared pathway and gene expression changes following drug exposure; these chemically distinct agents share a mechanistic signature that dampens the neuronal hyperexcitability characteristic of a broad spectrum of neurodevelopmental disorders. Two shared downregulated genes reflect a core expression module for modulating GABAergic tone: SRC proto-oncogene, non-receptor tyrosine kinase (SRC), and Glutamate decarboxylase 2 (GAD2). Conclusions: We provide this methodology and analysis as a framework for exploring shared changes in gene expression following neuroactive compound exposure in vivo, leading to a more complete and nuanced understanding of therapeutic effects on neurons that can aid in drug repurposing efforts for neurodevelopmental disorders. Full article

Background: Laryngospasm is defined as glottis closure due to reflex constriction of the laryngeal muscles. It is one of the most common complications following pediatric anesthesia that can lead to hypoxemia, bradycardia, or aspiration. Laryngospasm following tracheal extubation has different reasons: presence of secretions, foreign body in the airway, or pain at the site of surgery. Propofol is usually used as an induction or maintenance agent. However, its use with the subhypnotic dose (0.5 mg/kg) is increasing nowadays for reducing the incidence of laryngospasm. This systematic review and meta-analysis aim to assess the efficacy of subhypnotic propofol in reducing the incidence of laryngospasm and respiratory complications in children following tonsillectomy or adenotonsillectomy and before extubation. Methods: We systematically searched the following databases: PubMed, Cochrane Library, Scopus, and Web of Science. Studies were included if they used propofol with a low dose (0.5 mg/kg) following tonsillectomy and before extubation. Both Randomized Controlled Trials (RCTs) and cohort studies published up until 27 December 2025 were included. We used the R software for statistical analysis. We employed a random-effects model for the analysis. Continuous outcomes were analyzed as mean differences (MD) and dichotomous data as risk ratios (RR), with 95% confidence intervals (CI). Heterogeneity was assessed using I² statistics. Results: Our review included four RCTs and one prospective cohort study with 593 participants. Our analysis showed that propofol was significantly associated with a low incidence of laryngospasm (RR = 0.25, 95% CI 0.13–0.49), cough (RR = 0.08, 95% CI 0.01–0.62), and agitation (RR = 0.15, 95% CI 0.03–0.72) compared with the control group. However, there were no significant differences regarding laryngeal occlusion (RR = 0.70, 95% CI 0.20–2.46), cyanosis (RR = 1.13, 95% CI 0.14–9.43), stridor (RR = 1.38, 95% CI 0.76–2.50), and the duration of surgery (MD = 1.81, 95% CI −0.74 to 4.36). Conclusions: Our findings state that propofol had a lower significant incidence of laryngospasm than the control. Trial sequential analysis for laryngospasm indicated that evidence is conclusive. However, regarding the other outcomes, the evidence is still inconclusive, which suggests the need for future large-scale RCTs with larger sample sizes to validate these findings. 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

Introduction: Postoperative delirium, including emergence agitation, is recognized in the post-anesthesia care unit as a fluctuating disturbance of attention and cognition. The current evidence examined suggests that both anesthetic agents and postoperative pain intensity may influence the risk of delirium. The aim of this review is to discuss the significance of pharmacological agents used during anesthesia and the relationship between the intensity of postoperative pain and the occurrence of postoperative delirium in patients undergoing surgical procedures, regardless of age. Methods: A scoping review was conducted from December 2024 to December 2025. The articles identified in each search were limited to those published between 2015 and 2025. Results: Agents such as dexmedetomidine, remimazolam, and magnesium sulfate were examined in the included trials and were reported to be associated with reducing the incidence and severity of postoperative delirium, particularly in pediatric and elderly patients. Analysis of clinical trial outcomes conducted in pediatric populations undergoing various surgical procedures suggests that dexmedetomidine (administered intranasally and intravenously) and alfentanil were associated with lower incidence and severity of emergence delirium compared to standard care or other agents (e.g., midazolam). Higher doses of dexmedetomidine (2 µg/kg) were reported to be associated with improved postoperative analgesia and reduced agitation, without prolonging recovery time or causing serious adverse effects. Propofol, due to its rapid metabolism, was suggested to contribute to shorter emergence times; however, its impact on cognitive function requires further investigation. Additionally, there remains a lack of agreed-upon and/or validated tools and strategies for pain assessment in patients experiencing delirium. Conclusions: The current evidence examined suggests that the use of intranasal dexmedetomidine at appropriate doses may be associated with reduced postoperative pain and agitation without prolonging recovery time or increasing the risk of serious adverse events. Hydromorphone was reported in the included trials to be associated with better postoperative pain control than sufentanil, whereas remimazolam, although associated with reduced delirium incidence in some trials, did not influence the length of stay in the post-anesthesia care unit. Magnesium sulfate, although not significantly affecting the incidence of delirium, was associated with alleviation of postoperative symptoms such as pain and insomnia in adult patients. Ketamine, while commonly used for analgesic therapy, did not demonstrate a consistent association with delirium prevention and, in some studies, was associated with increased neuropsychiatric events. Further research is required to more precisely define optimal perioperative delirium prevention protocols. Full article

Background/Objectives: Pupillometry offers a non-invasive method for assessing nociceptive responses during anesthesia. This study aimed to evaluate the effects of intravenous lidocaine on pupillary reflex dilation (PDR) and the Pupillary Pain Index (PPI) during general anesthesia with orotracheal intubation. Methods: In this prospective, randomized, single-blind trial, 90 ASA I–II patients aged 18–65 years, scheduled for elective surgery under general anesthesia, were enrolled. Participants were randomized into three groups: control, study (lidocaine 1.5 mg/kg), and placebo. Standardized anesthesia induction was performed using propofol, fentanyl, and rocuronium. Pupil diameter was measured using the Algiscan pupillometer. PDR was assessed during intubation, while PPI was measured five minutes post-intubation through controlled electrical stimulation. Hemodynamic parameters and BIS values were recorded throughout. Eighty-six patients completed the study. No significant differences in demographics, anesthetic drug doses, or hemodynamic parameters were noted between groups. Results: PDR during intubation showed no significant difference between the control and study groups (median dilation: 0.34 mm vs. 0.33 mm; p = 0.76), but was significantly lower in the lidocaine group compared to placebo (median dilation: 0.33 mm vs. 0.50 mm; p = 0.02). PPI scores did not differ significantly between groups (p > 0.05). A positive correlation was observed between PDR and BIS values, indicating that lighter anesthesia depth increased PDR response. No such correlation was found with PPI. Conclusions: Intravenous lidocaine attenuates the pupillary response to nociceptive stimuli during orotracheal intubation but does not influence PPI scores. Pupillometry remains a valuable adjunct for intraoperative nociceptive monitoring. Full article

Remimazolam is an ultra-short-acting benzodiazepine developed according to the “soft drug” concept and characterized by rapid onset, predictable offset, organ-independent metabolism, and the availability of a specific antagonist. Due to these pharmacological features, this drug represents a particularly attractive option for pediatric anesthesia and sedation, a field in which traditional agents are often limited by hemodynamic instability, prolonged recovery, and adverse respiratory effects. This narrative review summarizes and discusses the current evidence regarding the use of remimazolam in pediatric patients, focusing on pharmacokinetics, pharmacodynamics, clinical applications, and safety. Available data indicate that remimazolam provides effective sedation and anesthesia in children across multiple settings, including induction of general anesthesia, non-operating room anesthesia, and intensive care unit sedation. Compared with propofol and midazolam, remimazolam is generally associated with greater hemodynamic stability, rapid recovery, reduced emergence delirium, and a favorable respiratory profile, while maintaining comparable efficacy. Intranasal administration has also shown promise as a premedication strategy for reducing preoperative anxiety, although it may occasionally be associated with pain. Even if remimazolam lacks intrinsic analgesic properties, its use appears to indirectly improve postoperative comfort by attenuating stress responses and emergence agitation. Despite encouraging results, pediatric use of remimazolam remains off-label in many countries, and evidence is still limited by small sample sizes and heterogeneous protocols. Further large-scale randomized controlled trials are needed to define optimal dosing strategies, long-term safety, and their definitive role in pediatric anesthetic and sedative practice. Full article

Background: Propofol is used worldwide as a short-acting intravenous anesthetic in clinical practice; however, side effects such as injection pain and respiratory depression remain clinically relevant. Therefore, identification of safer propofol analogs is required. Method: In response to the urgent need for optimized potency and reduced side effects, a series of dihydrobenzofuran derivatives were designed as expectedly better propofol analogs through conformational restriction. A loss of righting reflex assay was conducted to evaluate the sedative/anesthetic properties of the synthesized compounds, and a respiratory depression test was performed for safety assessment. Results: Most of the designed compounds were shown to possess promising anesthetic properties as propofol analogs. The represented 53A had higher potency and a wider safety margin (ED₅₀:3.898 vs. 8.040 mg/kg in mice; 2.985 vs. 5.894 mg/kg in rats; TI (therapeutic index): 6.172 vs. 5.061 in mice; 4.362 vs. 2.580 in rats) than propofol, and fast onset and recovery times were maintained. The phosphate prodrug 56A also exhibited better efficiency and safety than fospropofol, along with a longer duration and faster recovery time in sedative profiles. Furthermore, alleviation of the adverse effects of respiratory depression has been demonstrated. Conclusions: 53A has the potential to be selected as a preclinical candidate for clinical development. Full article

Background and Objectives: The study was designed to compare the propofol-sparing effect, intraoperative haemodynamic profiles, and recovery profiles during propofol–remifentanil total intravenous anaesthesia (TIVA) with remimazolam or dexmedetomidine co-administered as an adjuvant. Materials and Methods: After the remifentanil target concentration of 5 ng/mL had been achieved and endotracheal intubation was completed, the R group was intravenously administered 1 mg remimazolam/kg/hr, the D group was given 0.5 µg dexmedetomidine/kg/hr, and the control (C) group was given 1 mL normal saline/kg/hr. The allocated experimental drug infusion was initiated immediately after intubation and maintained until termination of the two target-controlled infusions of propofol and remifentanil. The propofol-sparing effect, intraoperative haemodynamic profiles and recovery profiles were assessed in the three groups. Results: The R group had the lowest requirement of propofol and the C group had the highest requirement of propofol. Haemodynamic profiles were similar among the groups. However, the total phenylephrine dose administered to maintain haemodynamic stability was significantly lower in the R group than in the D group and C group. Recovery profiles did not significantly differ between the groups. Conclusions: The co-administration of remimazolam or dexmedetomidine as an adjuvant in propofol–remifentanil TIVA reduced propofol requirements. While recovery profiles, including recovery times, postoperative pain, and postoperative nausea and vomiting, were similar among the groups, remimazolam was associated with a reduced phenylephrine requirement despite similar haemodynamic profiles. Full article

The search for an ideal anesthetic has always been a major goal in anesthesiology. In recent years, the introduction of ciprofol has marked a major breakthrough in the pharmacological field, following the introduction of dexmedetomidine. Ciprofol has similar characteristics to propofol but with greater hemodynamic stability. Furthermore, it overcomes one of the most common discomforts associated with propofol: pain at the injection site. These characteristics make it a suitable hypnotic for pediatric use. Although studies on children are still limited, the literature on adults is now substantial and of high quality. The potential advantages of using ciprofol in pediatric anesthesia include pain-free induction, hemodynamic stability, less respiratory depression, and a lower incidence of emergence delirium. Full article

Background and Objectives: Scalp nerve block (SNB) is hypothesized to attenuate the physiological response to skull pinning more effectively than local anesthetic (LA) infiltration. This study aimed to compare the two techniques using Bispectral index (BIS) as a primary surrogate measure of cortical arousal. Materials and Methods: In this prospective observational study, patients undergoing elective craniotomy received either bilateral SNB (Group S, n = 53) or LA infiltration (Group LA, n = 35) based on anesthesiologist preference. Depth of anesthesia was monitored via BIS. The primary outcome was the change in BIS after skull pin insertion. A ΔBIS > 20% from baseline triggered rescue medication (remifentanil/propofol). Secondary outcomes included hemodynamic parameters and rescue requirements. Results: There was a significant main effect of time on BIS values (p < 0.001), indicating that BIS values changed significantly across measurement points. Post-hoc examination of parameter estimates revealed that the Group LA showed significantly greater increases in BIS values compared to the Group S at T1 (p = 0.030) and T3 (p = 0.024). No significant between-group differences in BIS changes were observed at T5, T10, or T15 time points (p > 0.05). Hemodynamic responses (mean arterial pressure and heart rate) were also transiently but significantly higher in Group LA at these time points (p < 0.001). The most clinically notable finding was that significantly more patients in Group LA required rescue medication (p < 0.001), indicating a greater frequency of clinically significant physiological trespass. Conclusions: Compared to LA infiltration, SNB was associated with statistically significant reductions in immediate BIS and hemodynamic responses to skull pinning. The key potential clinical implication is the corresponding reduction in the need for rescue anesthetic intervention. These findings support SNB as a technique for enhancing physiological stability, though the direct impact on patient-centered outcomes requires further study. BIS may serve as a useful adjunctive indicator of the cortical response to noxious stimuli. Full article

Background/Objectives: Drug-induced sleep endoscopy (DISE) is used in obstructive sleep apnea (OSA) to visualize dynamic upper airway collapse, but sedation protocols vary widely with no consensus on the optimal agent or technique. This narrative review aims to clarify current sedation strategies for DISE in OSA and their clinical implications. Methods: We systematically searched PubMed, Scopus, Web of Science, and Cochrane Library for English-language publications on DISE sedation (2000–2025). Relevant clinical studies, guidelines, and reviews were included. Data were qualitatively synthesized due to heterogeneity among studies. Results: Sedation approaches in DISE varied considerably. Propofol, dexmedetomidine, and midazolam were the primary agents identified. Propofol provided rapid, titratable sedation but increased airway collapsibility at higher doses; dexmedetomidine produced a more natural sleep-like state with minimal respiratory depression; midazolam was less favored due to prolonged effects. Use of target-controlled infusion (TCI) and pharmacokinetic–pharmacodynamic (PK–PD) models improved control of propofol sedation. Co-sedative adjuncts (e.g., opioids) reduced the required sedative dose but added risk of respiratory depression. Careful titration to the lowest effective dose-often guided by bispectral index (BIS) monitoring—was emphasized to achieve adequate sedation without artifactual airway collapse. No universal DISE sedation protocol was identified. Conclusions: Optimal DISE sedation balances adequate depth with patient safety to ensure reliable findings. Using the minimum effective dose, guided by objective monitoring (e.g., BIS), is recommended. There is a need for standardized sedation protocols and further research (e.g., in obese patients) to resolve current controversies and improve DISE’s utility in OSA management. Full article

Background and Objectives: The study aimed to evaluate the predictive significance of Shock Indices and induction agents in predicting the risk of Peri-Intubation Cardiovascular Collapse (PIC) during intubation in the ICU. Materials and Methods: A total of 130 patients were analyzed in the study after dividing them into 2 groups based on the definition of PIC as Patients with PIC and Non-PIC Patients. PIC was defined as the detection of at least SBP < 65 mmHg measured at least once within 30 min after the intubation, SBP < 90 mmHg for 30 min, initiation of norepinephrine treatment, increasing the norepinephrine dose taken before the intubation, increasing SBP to >90 mmHg with >15 mL/kg crystalloid fluid infusion, or development of cardiac arrest. The relationship between Shock Index (SI), Diastolic Shock Index (DSI), Modified Shock Index (MSI), Age Shock Index (Age-SI), and induction agents (ketamine, propofol) and PIC was evaluated. Results: The PIC was detected in 62 patients (47.7%). Age-SI showed the highest predictive performance (AUC = 0.686, p < 0.001). Ketamine provided a protective effect (OR = 0.161, p = 0.003). Propofol (OR = 2.962, p = 0.048), age (OR = 1.065, p = 0.002), lactate (OR = 1.265, p = 0.047), and DSI (OR = 2.300, p = 0.037) were identified as independent risk factors. ICU mortality was significantly higher in the PIC group (74.2% vs. 20.6%, p < 0.001). Conclusions: Age, lactate, DSI, and Age-SI are valuable predictive parameters for PIC. Ketamine reduces the risk of PIC, while propofol increases it. These results support evidence-based risk assessment and induction agent selection in ICU intubation protocols. Full article

Sheep are routinely used as orthopedic models due to their similarities to human joints. Spinal anesthesia provides adequate analgesia for these procedures, and its duration can be enhanced with adjuvant drugs. Clonidine is commonly used in human spinal anesthesia, while dexmedetomidine is a newer and more selective α-2 agonist. This study compared the duration and analgesic effect of these two drugs as adjuvants in spinal anesthesia. Thirty-nine sheep undergoing experimental pelvic limb cartilage damage surgery were enrolled. Animals were sedated with diazepam (0.4 mg kg⁻¹) and buprenorphine (10 μg kg⁻¹) intravenously. Propofol was given as needed (0.5 mg kg⁻¹) and oxygen support via face mask was continuous. Animals were positioned with the treated limb in a dependent position for the lumbosacral spinal block. Sheep were divided into three groups (n = 13), receiving lidocaine 2% (L group), lidocaine 2% + clonidine 20 μg mL⁻¹ (CL group), or lidocaine 2% + dexmedetomidine 1 μg mL⁻¹ (LD group) for spinal block (1 mL every 10 kg). Recovery times (minute) from the spinal block were recorded: anal sphincter tone (AS), recovery of sensibility (RoS), first limb movements (FMov), time of standing (ToS), and first rescue analgesia; ataxia (ATA) was also measured after standing. Dexmedetomidine increased the duration of spinal anesthesia, affecting both motor and sensory functions. 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

Background/Objectives: In recent years, it has been suggested that sedatives may cause brain damage. One possible mechanism is interference with oxidative phosphorylation of brain mitochondria, but much remains unknown. In this study, we focused on dexmedetomidine, midazolam, and propofol, essential sedatives in anesthesia and intensive care, and aimed to understand the effects of these drugs on mouse brain mitochondria. Methods: We measured changes in mitochondrial respiratory capacity and swelling rate upon exposure to these sedatives in a wide concentration range. For the sedative that demonstrated impaired mitochondrial function we explored the possible involvement of mitochondrial permeability transition pore opening using brain mitochondria from cyclophilin D knockout (CypD KO) mice and detected cytochrome c (cyt c) release by Western blot. Results: Of the three sedatives, only high concentrations of propofol exhibited reduced respiratory capacity and mitochondrial swelling, toxicity which was not prevented by CypD KO. Furthermore, propofol did not induce cyt c release. Conclusions: These results suggest that propofol-induced brain mitochondrial dysfunction is a mechanism independent of mPTP opening. Full article