Search Results (78)

Anxiety disorders are characterized by dysregulation of monoaminergic signaling and remain a significant therapeutic challenge due to limitations associated with current pharmacological treatments. In this context, the essential oil of Morisonia flexuosa (Capparaceae) seeds was chemically characterized and evaluated for anxiolytic-like activity in adult zebrafish. Chemical profiling by GC–MS and GC–FID revealed a predominance of isothiocyanates, particularly butyl isothiocyanate (42.60%) and isobutyl isothiocyanate (42.28%). Acute toxicity assessment demonstrated no lethality at the tested doses. Behavioral analyses showed a significant increase in light preference in the light/dark paradigm, with moderate locomotor reduction insufficient to account for the behavioral shift solely by sedation. Pharmacological antagonism assays indicated that the anxiolytic-like effect was predominantly mediated by 5-HT1 and 5-HT2A/2C receptors. Chemometric analyses (PCA, HCA, and heatmap) revealed statistical association between compound abundance and behavioral endpoints, supporting the contribution of major isothiocyanates within the tested model. Notably, the strongest behavioral response was observed at the lowest concentration, suggesting an ideal effective concentration range. Collectively, these findings provide the first evidence that an isothiocyanate-rich essential oil from M. flexuosa exerts serotonergic-involved anxiolytic-like effects in zebrafish and supports further mechanistic investigation of its neuropharmacological potential. Full article

Background and Objectives: Conventional EEG-derived sedation targets for Entropy monitoring (State Entropy SE 40–60) were established in the context of general anaesthesia and may not be directly applicable to procedural sedation for endoscopic retrograde cholangiopancreatography (ERCP). This study aimed to characterize SE and Response Entropy (RE) trajectories during propofol-based sedation for ERCP and to evaluate their relationships with clinical sedation depth, patient characteristics, and procedural outcomes. Materials and Methods: In this prospective, single-center observational study, 50 consecutive adult patients undergoing elective ERCP under propofol-based sedation were enrolled. SE and RE were recorded at baseline and at serial intra-procedural timepoints. Time-in-zone analysis classified SE values into predefined ranges. Correlations between Entropy indices and MOAA/S scores, patient factors, Aldrete recovery scores, and adverse events were assessed using Spearman’s rank correlation. Results: The median patient age was 72.5 years (IQR 65.0–79.0), and the median ASA score was 3 (IQR 2–3). Following induction, SE declined from a baseline mean of 89.3 ± 1.5 to a mean of 68.8 ± 5.3 at 10 min, the lowest group-level value recorded; the mean individual SE nadir across patients was 67.2 ± 5.3. No SE values below 40 were observed at any timepoint. Mean time spent within the conventional SE 40–60 target range was 3.7% ± 10.6, while mean time within SE 60–85 was 80.7% ± 8.3. SE at 3 min correlated moderately with MOAA/S at 3 min (Spearman rho = 0.430, p = 0.002), with substantial within-category variability. Age showed a strong negative correlation with SE at 3 min (rho = −0.612, p < 0.001), an effect that persisted at 5 min, consistent with deeper early EEG suppression in older patients, which may reflect increased pharmacodynamic sensitivity, age-related changes in spectral substrate, or both. ASA score was associated with SE at 15 min only (rho = −0.299, p = 0.035). Patients who experienced adverse events demonstrated higher SE instability, though differences did not reach statistical significance. Recovery was rapid, with a median Aldrete score of 10 at 15 min. Conclusions: During propofol sedation for ERCP, observed SE values operated predominantly between 60 and 85, well above the conventional general anaesthesia target of 40–60. Older age was the strongest predictor of early sedation depth. These findings suggest that in elderly, high-ASA patients receiving propofol-based multi-drug sedation for ERCP, numerical SE values differ systematically from conventional general anaesthesia-derived target ranges. Whether this reflects true procedure-specific sedation requirements or cohort-specific spectral substrate differences warrants prospective outcome-anchored investigation. Full article

Background/Objectives: The utility and safety of EBUS-TBNA in the general population are well-documented in the scientific literature, but data on elderly patients, particularly those over 80 years old, are limited. Methods: We retrospectively investigated patients aged 80 and over who underwent EBUS-TBNA under moderate sedation, without anesthesiologic assistance, over a period of seven years at a single Italian hospital. The primary outcome was the safety of the procedure assessed by evaluating the complication rate occurring during the procedure and up to one week afterward. Secondary outcomes included the rate of procedures with successful sampling, the percentage of procedure repeated with anesthesiologic assistance, specimen adequacy, overall diagnostic yield, type of diagnosis, malignancy rate and the percentage of patients who underwent active treatment after obtaining an oncological diagnosis. Results: A total of 141 patients were enrolled in the study; the mean age was 82.6 ± 2.2 years. The incidence of complications was 11.3% (16/141); most adverse events were mild (9.9% 14/141). Two patients (1.4%) experienced major complications requiring hospitalization. Regarding the secondary endpoints, sampling was successfully performed in 99.3% of cases (140/141); in one case, it was necessary to repeat the procedure with anesthesiologic assistance (0.7% 1/141). Specimens were adequate in 96.4% of cases (135/140); the overall diagnostic rate was 85.7% (120/140); the malignancy rate was 52.9% (74/140) and among these, 78.4% (58/74) were treated. Conclusions: EBUS-TBNA performed under moderate sedation is a safe and diagnostically effective procedure in patients older than 80 years of age, supporting its use in this growing population. Full article

Background: Pain assessment in critically ill, mechanically ventilated pediatric patients is highly complex owing to communication barriers and the frequent use of sedation. A standardized, rapid, and objective tool such as the Behavioral Pain Scale (BPS) is urgently needed in Japanese pediatric intensive care units (PICUs), particularly in mixed adult–pediatric settings, to ensure consistent, multidisciplinary assessment. This study aimed to evaluate the clinical applicability, validity, and reliability of the Japanese version of the BPS in critically ill mechanically ventilated pediatric patients. Methods: This single-center, prospective cross-sectional observational study was conducted between October 2021 and March 2023. The final analysis included 70 observations from 37 pediatric patients who needed mechanical ventilation (MV). Concurrent and convergent validity were assessed using Spearman’s rank correlation coefficients (ρ) between the BPS; the Face, Legs, Activity, Cry, Consolability (FLACC) scale; and the COMFORT-Behavior (COMFORT-B) scale. Interrater reliability was evaluated using intraclass correlation coefficients (ICCs) and weighted kappa values among the three independent observers. The sample size (52 observations) was calculated based on the kappa coefficient estimation. The impact of sedation depth (assessed using the Richmond Agitation–Sedation Scale [RASS]) and the observers’ prior clinical experience with the evaluations were also analyzed. Results: Concurrent and convergent validity were high, showing strong correlations with the FLACC (ρ = 0.49–0.91) and COMFORT-B (ρ = 0.69–0.87) scales. The total BPS score showed moderate interrater reliability (ICC = 0.66, 95% CI = 0.55–0.76; weighted κ = 0.63–0.71). However, deep sedation (defined as a median RASS score ≤ −4 across observers), present in 68.6% of the observations, caused a pronounced floor effect that suppressed behavioral responses, even during painful procedures. Consequently, the reliability of fine motor subscales like “upper limb movement” (κ = 0.08) was slight and for “facial expression” (κ = 0.38), it was fair. Furthermore, the correlation strength with the FLACC scale varied significantly with observer experience, with the strongest correlation (ρ = 0.91) achieved by the observer with extensive adult ICU experience. Conclusions: As an initial validation, the Japanese version of the BPS has demonstrated acceptable validity and moderate reliability in mechanically ventilated pediatric patients. However, its clinical application requires careful interpretation because of the pronounced floor effect under deep sedation. Furthermore, accurate assessment depends heavily on specific training and familiarity with the adult-derived scale. With adequate training, the BPS has the potential to serve as an alternative tool and a valuable common multidisciplinary language in mixed intensive care settings. Future research should investigate whether implementing this tool improves multidisciplinary communication and clinical outcomes. Full article

In this study, the degree and characteristics of sedation were assessed using the Grint scale for azaperone and acepromazine in 24 dogs, with the effects on heart rate and systemic blood pressure evaluated simultaneously using oscillometry. Posture, palpebral reflex, eye position, relaxation, response, postural resistance, attitude, systolic pressure, diastolic pressure, mean arterial pressure, and heart rate were analyzed using linear mixed-effects models to evaluate the effects of treatment, time, and their interaction. Significant effects of time were observed for all variables (p < 0.001), including systolic, diastolic, and mean arterial pressure, whereas heart rate was not significantly affected by treatment. Based on these results, we conclude that azaperone produces moderate sedation at 20 min after administration, and it does not induce bradycardia or clinically significant hypotension. Full article

Sedation and anesthesia are integral components of modern gastrointestinal endoscopy, enhancing patient comfort and procedural success while adding risks such as respiratory and cardiovascular complications. Accurate monitoring of sedation depth is essential to balance safety and procedural efficacy. This narrative literature review synthesizes current evidence on monitoring depth of anesthesia during endoscopic procedures, including clinical assessment scales, capnography, and processed electroencephalogram (pEEG)-based technologies. The effects of commonly used sedative agents on monitoring parameters and the impact of different monitoring strategies on clinical outcomes are also discussed. Current evidence indicates that clinical assessment remains the cornerstone of monitoring during moderate sedation, while capnography improves early detection of respiratory compromise during deep sedation. pEEG-based monitoring may provide additional value in selected high-risk or prolonged procedures but should complement, not replace, clinical evaluation. A multimodal monitoring approach tailored to sedation depth and patient risk profile is likely to be the most effective strategy for optimizing patient safety. Future research should focus on standardizing monitoring protocols and identifying populations most likely to benefit from advanced monitoring techniques. Full article

Background: Delirium is a frequent and serious complication in intensive care units (ICUs), associated with increased mortality, prolonged mechanical ventilation, extended length of stay, and long-term cognitive impairment. This study aimed to assess ICU nurses’ knowledge and practices regarding delirium management in Cyprus and to identify predictors of knowledge. Methods: A cross-sectional study was conducted among nurses working in adult ICUs in Cyprus. Data were collected using a structured self-administered questionnaire that included demographic characteristics, sedation and analgesia practices, and an adapted Delirium Knowledge Questionnaire incorporating ICU-specific items. Results: A total of 70 ICU nurses participated, most of whom were female (60%) with a mean ICU experience of 5.1 years. Only 27.1% reported daily delirium screening, although 65.2% perceived delirium as frequent. Sedation protocols were reported by 34.3%, sedation scales were used by 44.3%, and daily sedation interruption by 61.4%. Only 15.7% had received formal delirium training, while 87.1% expressed the need for further education. Knowledge scores were moderate to high (68.5–84.0%), with higher scores among nurses with prior training and female nurses (p = 0.003). Hospital type was associated with sedation practices, with greater use of sedation scales in public ICUs (p < 0.001) and propofol more commonly used as first-line sedation compared with midazolam in private ICUs (p = 0.018). Conclusions: Although ICU nurses demonstrated moderate knowledge of delirium, systematic screening and protocolized management remain suboptimal. Structured education and standardized implementation strategies are required to strengthen patient safety in critical care settings. Full article

The objective of this study was to evaluate, in client-owned dogs, the postoperative analgesic efficacy of the centrally acting analgesic tramadol following femoral head and neck excision (FHNE). Thirty-eight dogs were diagnosed with coxofemoral disease and underwent FHNE. The sample was randomly divided into two groups. Postoperatively, dogs in Group A received robenacoxib (2 mg kg⁻¹ bodyweight, sid, per os) until they achieved final weight-bearing of the operated limb, whereas dogs in Group B received the same regimen of robenacoxib in combination with tramadol (5 mg kg⁻¹ bodyweight, tid, per os) for fifteen days. All animals were premedicated, sedated, and anesthetized following the same standardized protocol to ensure consistency between groups. Postoperative evaluations were conducted on days 15 and 30, and subsequently at monthly intervals, until full weight-bearing of the affected limb was achieved. Clinical assessments included observation of pain-related behaviors, lameness scoring, and time to initial weight-bearing (TIWB) and time to final weight-bearing (TFWB). Data normality was assessed using the Shapiro–Wilk test, and differences between groups were evaluated using the independent samples T-test (p = 0.05). Statistical analysis revealed no significant differences between the two groups regarding time to initial (p = 0.087) or final weight-bearing. However, a moderate effect size (d = 0.570) was observed for TIWB, suggesting a clinically interesting trend toward faster early recovery in the multimodal group. These findings indicate that while adding tramadol did not confer a statistically significant additional advantage in this study, the observed clinical trend warrants further investigation in larger, higher-powered cohorts to determine its definitive clinical impact. Full article

Background/Objectives: Behavior management is a major challenge in pediatric dentistry, particularly during the first dental visit, when anxiety, fear, and negative expectations can compromise cooperation and clinical outcomes. While evidence-based behavior guidance techniques are well established, their effectiveness depends on early identification of behavioral risk and individualized planning. This study aimed to develop and clinically evaluate a parent-completed digital pre-visit tool to support individualized behavior management and targeted use of digital distraction in pediatric dentistry. Methods: A web-based application was developed using HTML, CSS, and JavaScript. It was applied to a prospective observational cohort of 90 pediatric patients aged 4–8 years (mean 6.1 ± 1.2), including 48 girls and 42 boys. Parents completed a pre-visit questionnaire covering four domains: child’s age, previous dental experiences, reactions to unfamiliar situations, and individual interests, including stimuli to avoid. Based on predefined decision rules, the tool generated recommended clinical approaches, including behavior guidance techniques, digital distraction, and inhalation sedation. Results: Over 90% of children were successfully managed during their first visit. Children in low- and moderate-risk groups had significantly higher odds of treatment success compared to high-risk children. Low-risk children almost universally completed treatment at the first visit, while a substantial portion of moderate-risk children were successfully managed without an adaptation visit. Digital distraction, particularly when tailored to individual interests, enhanced cooperation and tolerance of procedures. Conclusions: The digital pre-visit tool enables early identification of behavioral risk and supports targeted application of digital distraction and sedation. This approach can improve child cooperation, reduce anxiety, optimize clinical efficiency, and contribute to positive early dental experiences. Full article

Background: 22q11.2 deletion syndrome (22q11.2 DS) is a rare genetic syndrome characterized by high phenotypic variability, with an incidence of approximately 1:4000 live births. Most of the existing literature consists of case reports or case series, making it challenging to obtain large cohorts for data comparison and drawing generalizable conclusions. Aim: The aim of this article is to share the clinical experience of patients with 22q11.2 DS who were previously evaluated by Child Neuropsychiatry and underwent odontoiatric procedures at the Dental Unit of the Policlinico di Bari. Methods: We report three clinical cases of pediatric patients with 22q11.2 DS who were managed at the University Dental Unit of the Policlinico di Bari for dental procedures, including pre/post-treatment images and child neuropsychiatric characteristics. Results: Cleft lip and cleft palate are the most commonly encountered facial malformations. Enamel hypoplasia and hypomineralizations, caries, dental agenesis, and hypodontia are reported with variable frequency in almost all studies considering the oral health of these patients. Our experience is coherent with the data present at the moment. The clinical examinations showed diffuse hypomineralization and several caries, concordant with the literature. One patient received moderate sedation and another received general anesthesia; oral prophylaxis, fluoride application, pulp therapy, extractions of hopeless teeth and restorations of carious and hypomineralized teeth were performed. Conclusions: 22q11.2 DS is a genetic condition with a variable prognosis, but current trends show that patients often reach adulthood, primarily due to advancements in cardiology, which was previously the leading cause of mortality in these patients. From this perspective, collaboration among various medical specialties is crucial to implement holistic patient management programs and early interventions. Full article

Effective pain management is central to anesthesia, critical care, and perioperative medicine, and opioids remain essential agents for moderate-to-severe pain despite ongoing concerns regarding their safety and misuse. This narrative review synthesizes the current knowledge on opioid mechanisms, clinical indications, safety considerations, and evolving strategies aimed at optimizing their use. Opioids exert their analgesic effects primarily through μ-, δ-, and κ-opioid receptors, which modulate central and peripheral nociceptive pathways. They maintain a well-established role in acute postoperative and cancer-related pain, whereas their use in chronic non-cancer pain remains controversial. Contemporary evidence suggests that physiological dependence and addiction are less frequent in appropriately selected and monitored patients, although the risk increases in the presence of psychological comorbidity, prior substance use, or adverse social determinants of health. Unequal access, prescribing variability, and persistent disparities further complicate global opioid management strategies. Recent advances, including partial agonists such as buprenorphine, dual-mechanism agents such as tapentadol, individualized titration, opioid rotation, and the integration of multimodal analgesia, support safer and more tailored prescribing. Non-pharmacological interventions, including behavioral and physical therapies, increasingly complement pharmacological strategies to minimize opioid exposure and improve functional outcomes. Clinicians must balance analgesic efficacy with adverse effects, such as tolerance, opioid-induced hyperalgesia, sedation, and respiratory depression, particularly in perioperative and critically ill populations. Opioids remain indispensable for selected indications but should be incorporated into a comprehensive, patient-centered, multimodal analgesic approach that prioritizes safety, ongoing reassessment, and individualized risk mitigation. Full article

In acute respiratory distress syndrome (ARDS), spontaneous breathing is often encouraged to preserve lung function, yet excessive patient-generated inspiratory effort can paradoxically worsen injury, a phenomenon termed patient self-inflicted lung injury (P-SILI). In mechanically heterogeneous lungs, uncontrolled effort amplifies regional stress, strain, and mechanical power, driving alveolar overdistension, cyclic recruitment–derecruitment, pendelluft, and inflammation. Cardiovascular consequences include elevated right ventricular afterload, impaired left ventricular filling, and exacerbation of pulmonary edema. While moderate spontaneous breathing may improve aeration in mild injury, evidence shows that vigorous effort in severe ARDS accelerates histological damage and regional lung stress. Early bedside assessment of respiratory drive and inspiratory effort identifies patients at highest risk, enabling targeted interventions. Strategies to preserve protective spontaneous breathing while limiting injurious effort include individualized positive end-expiratory pressure, titrated sedation, prone positioning, and short-term neuromuscular blockade. By integrating continuous physiological monitoring with personalized ventilatory management, clinicians can mitigate P-SILI, protect the diaphragm, and optimize outcomes. Future studies are needed to test physiology-guided interventions and establish evidence-based approaches to safely harness the benefits of spontaneous breathing in ARDS. Full article

Opioids play a central role in pain management and sedation in Intensive Care Units (ICUs), where critically ill patients frequently experience moderate-to-severe pain due to illness and invasive procedures or devices. Uncontrolled pain exacerbates stress responses, contributing to clinical deterioration and adverse outcomes. Although analgesics and sedatives can mitigate these effects, their use must be carefully individualized to avoid complications such as delirium, prolonged mechanical ventilation, and increased mortality. Evidence now shows that excessive or poorly controlled analgosedation can prolong ICU length of stay and delay recovery. Current guidelines recommend opioids as first-line agents for severe acute pain in the ICU, preferably within a multimodal analgesia framework to optimize pain control while minimizing adverse effects. Opioids are also essential for improving tolerance to invasive and noninvasive mechanical ventilation. Modern ICU practice emphasizes an analgesia-first or “analgosedation” strategy, prioritizing pain control with intravenous opioids before adding sedatives. This approach aims to achieve light sedation, reduce ventilator days, and improve overall outcomes. Commonly used opioids include fentanyl, morphine, hydromorphone, sufentanil, and remifentanil, with short-acting agents favored when rapid titration is required. Our narrative review aims to evaluate the clinical impact of opioid use in critically ill patients, including post-ICU outcomes, and to explore the role of opioid stewardship in optimizing patient care. Full article

Background: Long-term cognitive impairment is common among ICU patients who required invasive mechanical ventilation (IMV). Its etiology is likely multifactorial. This preregistered study examined the association between the duration of IMV and cognitive function post-ICU, as well as the moderating effects of age and cognitive reserve. Methods: A secondary analysis was conducted using data from a published study of COVID-19 ICU survivors. One year after discharge, participants underwent a neuropsychological assessment. Linear regression models were used to evaluate associations between the variables. Results: Among patients who received IMV via endotracheal intubation, ventilation duration was not significantly associated with cognitive performance. In contrast, among tracheostomized patients, longer IMV duration was associated with better cognitive outcomes (Cohen’s f² = 0.21). Age had a small negative main effect; in combination with IMV duration, f² increased to 0.31. Cognitive reserve showed a strong positive association with cognitive outcome; in combination with IMV duration, f² increased to 0.67. The interaction terms were negligible in both cases. Conclusions: We hypothesize that, compared to endotracheal intubation, IMV via tracheostoma may not only reduce the need for sedation, but also provide a more efficient respiratory support, therefore contributing to positive cognitive outcomes. However, IMV via tracheostomy still represents a form of positive pressure ventilation (PPV), which carries risks, such as ventilator-induced lung injury and reduced cardiac output and brain perfusion. These concerns about PPV, combined with our findings, indicate that alternative, non-invasive modes, such as negative pressure ventilation (NPV), warrant evaluation in future trials. Full article

Background/Objectives: Flexible bronchoscopy (FB) enables airway exploration and diagnosis of various respiratory pathologies, but the sedation and instrumentation required during the procedure raise oxygen demand while reducing ventilation, which can lead to hypoxemia. Conventional oxygen therapy (COT) may not adequately prevent desaturations in high-risk groups, as patients with moderate respiratory deficiency. High-flow nasal cannula (HFNC) can deliver heated, humidified oxygen at high flow rates, generating low-level positive airway pressure, improving oxygenation, reducing dead-space, and enhancing procedure tolerance. Prior studies have shown that HFNC can improve gas exchange and reduce desaturations during bronchoscopy. However, evidence remains limited for patients with moderate respiratory deficiency, who are particularly vulnerable. Evaluating the feasibility and safety of HFNC in this population is essential to guide safe procedural practice. Methods: A retrospective observational study including patients undergoing FB with HFNC support between January and May 2025. Inclusion criteria were BMI between 18 and 30; age > 18 years old; moderate respiratory dysfunction, defined by pulse oximetry, Pulmonary Functional Tests (PFTs) and Arterial Blood Gas (ABG) analysis. Exclusion criteria were intolerance/contraindication to HFNC. Procedures were performed under basic monitoring. Primary outcome was occurrence of severe hypoxemia (SpO2 < 90%). Secondary outcomes were needed for rescue maneuvers, interruption for conversion to other ventilatory strategies, and hemodynamic instability. Results: No severe desaturations were recorded, all procedures were completed without rescue maneuvers or other ventilatory strategies, and no hypoxemia occurred. Mean duration of the procedure was 9 min. Vital parameters were maintained within the normal ranges, with a mean SpO₂ during bronchoscopy of 98%. Conclusions: HFNC enables oxygenation and ventilation without adverse events in sedations for FB in patients with moderate respiratory deficiency. Full article