Item does not contain fulltextSTUDY OBJECTIVE: Although anxiolytic-sedative agents are used preoperatively since the advent of anesthesia, many aspects of this treatment, including the intended effects among which anxiolysis, effectiveness, and optimal agents, remain unclear. The objective of this study was to provide insight into the preoperative use of anxiolytic-sedative agents in the Netherlands and to relate the administration of these agents to the anxiolytic-sedative state of patients. DESIGN: Questionnaire study. SETTING: University, general, and specialized hospitals in the Netherlands. PATIENTS: One anesthesiologist in each hospital was asked for details about premedication in all elective procedures, except cardiothoracic surgery, in normal weighted adults in good to fair clinical condition. INTERVENTIONS: None. MEASUREMENTS: Estimated percentage of patients receiving anxiolytic-sedative premedication, type, dose, route of administration and timing of these agents, and anxiolytic state of patients when arriving at the holding area. MAIN RESULTS: All 8 university hospitals, 69 of 82 general hospitals and 2 of 3 specialized hospitals participated in this study (response rate, 84.9%). The estimated percentage of patients that received anxiolytic-sedative agents was 46.8% for in-patients and 30.4% for day care patients (P<.0001), with large between-hospital variation. Midazolam (62.7%), oxazepam (20.2%), and temazepam (7.8%) were most frequently used and were virtually always orally administered 1 hour preoperatively. There was no relationship between use of anxiolytic-sedative agents and reduction of perceived anxiety (r=-0.09, P=.46 and r=-0.01, P=.91 for clinical and day care patients, respectively). CONCLUSIONS: Anxiolytic-sedative agents are used preoperatively in a substantial number of patients in the Netherlands, and the pharmacokinetic characteristics of many agents are not optimal of their intended use. In addition, we found no relationship with reduced anxiety. This study stresses the need for clear guidelines on preoperative use of anxiolytic-sedative agents

Background: With renewed interest in long-duration space missions, there is growing exploration into synthetic torpor as a countermeasure to mitigate physiological stressors. Sedative agents, particularly those used in clinical anesthesia, have been proposed to replicate aspects of natural torpor, including reduced metabolic rate, core temperature, and brain activity. Objectives: This systematic review aims to evaluate the potential of sedative agents to induce torpor-like states suitable for extended spaceflight. The review specifically investigates their pharmacokinetics, pharmacodynamics, and performance under space-related stressors such as microgravity and ionizing radiation. Methods: We conducted a comprehensive search across multiple databases (e.g., PubMed, Scopus, Web of Science) for studies published from 1952 to 2024. Eligible studies included experimental, preclinical, and clinical investigations examining sedative agents (especially inhalation anesthetics) in the context of metabolic suppression or space-relevant conditions. Screening, selection, and data extraction followed PRISMA guidelines. Results: Out of the screened records, 141 studies met the inclusion criteria. These were thematically grouped into seven categories, including torpor physiology, anesthetic uptake, metabolism, and inhalation anesthetics. Sedative agents showed variable success in inducing torpor-like states, with inhalation anesthetics demonstrating promising metabolic effects. However, concerns remain regarding delivery methods, safety, rewarming, and the unknown effects of prolonged use in space environments. Conclusions: Sedative agents, particularly volatile anesthetics, hold potential as tools for inducing synthetic torpor in space. Nevertheless, significant knowledge gaps and technical challenges persist. Further targeted research is required to optimize these agents for safe, controlled use in spaceflight settings.

Background The effects of sedative and anesthetic agents on sympathetic nerve activity (SNA) are poorly understood. Objective To determine the effects of commonly used sedative and anesthetic agents on SNA in ambulatory dogs and humans. Methods We implanted radiotransmitters in 6 dogs to record stellate ganglion nerve activity (SGNA), subcutaneous nerve activity (ScNA) and blood pressure (BP). After recovery, we injected dexmedetomidine (3 μg/kg), morphine (0.1 mg/kg), hydromorphone (0.05 mg/kg) and midazolam (0.1 mg/kg) in different days. We also studied 12 human patients (10 males, 68.0±9.1 years old) undergoing cardioversion for atrial fibrillation with propofol (0.77±0.18 mg/kg) or methohexital (0.65 mg/kg) anesthesia. Skin sympathetic nerve activity (SKNA) and electrocardiogram were recorded during the study. Results SGNA and ScNA were significantly suppressed immediately after administration of dexmedetomidine (p=0.000, 0.000), morphine (p=0.011, 0.014) and hydromorphone (p=0.000, 0.012), along with decreased BP and heart rate (HR) (p<0.001 for each). Midazolam had no significant effect on SGNA and ScNA (p=0.248, 0.149). However it increased HR (p=0.015) and decreased BP (p=0.004) in ambulatory dogs. In patients undergoing cardioversion, bolus of propofol administration significantly suppressed SKNA (from 1.11 ±0.25 μV to 0.77±0.15 μV, p=0.001) and the effects lasted for at least 10 min after the final cardioversion shock. Methohexital decreased chest SKNA from 1.59±0.45 μV to 1.22±0.58 μV (p=0.000) and arm SKNA from 0.76±0.43 μV to 0.55±0.07 μV (p=0.001). The effects lasted for at least 10 min after the cardioversion shock. Conclusion Propofol, methohexital, dexmedetomidine, morphine and hydromorphone suppressed, but midazolam had no significant effects on SNA.

Fractional tissue oxygen extraction (FTOE) by means of cerebral near-infrared spectroscopy (NIRS) provides information about oxygen uptake in the brain. Experimental animal data suggest that sedative agents decrease cerebral oxygen demand. The aim of the present study was to investigate the association between the cerebral FTOE and the use of pre and intraoperative sedative agents in infants aged 1–90 days. Cerebral NIRS was continuously applied during open major non-cardiac surgery in 46 infants. The main outcomes were the mean intraoperative FTOE and the percentage (%) of time of intraoperative hyperoxiaFTOE relative to the total duration of anesthesia. HyperoxiaFTOE was defined as FTOE ≤ 0.1. Cumulative doses of sedative agents (benzodiazepines and morphine), given up to 24 h preoperatively, correlated with the mean intraoperative FTOE (Spearman’s rho = −0.298, p = 0.0440) and were predictive for the % of time of intraoperative hyperoxiaFTOE (β (95% CI) 47.12 (7.32; 86.92)) when adjusted for the patients’ age, type of surgery, preoperative hemoglobin, intraoperative sevoflurane and fentanyl dose, mean intraoperative arterial blood pressure, and end-tidal CO2 by multivariate 0.75 quantile regression. There was no association with 0.5 quantile regression. We observed the suggestive positive association of decreased fractional cerebral tissue oxygen extraction and the use of sedative agents in neonates and infants undergoing surgery.

Dissertação (mestrado) - Universidade Federal de Santa Catarina, Centro de Ciências da Saúde. Programa de Pós-Graduação em Ciências MédicasObjetivo: Comparar a segurança e efetividade da clonidina com a dexmedetomidina para a sedação de pacientes críticos. Estabelecer a relação entre essas duas drogas e o desenvolvimento de Delirium bem como seu impacto no sistema imune. Método: Ensaio clínico, aberto, randomizado, aprovado pela Comissão de Ética da Instituição. Foram analisados pacientes que necessitassem de ventilação mecânica por um período mínimo de 24 horas, sem doença neurológica prévia, hipotensão ou bradiarritmia. A segurança dos fármacos foi avaliada pelo seu impacto nos níveis de pressão arterial média (PAM) e freqüência cardíaca (FC). CAM-ICU e níveis de cortisol foram avaliados no começo e 24hs após o início da infusão para mensurar impacto no Delirium e no sistema imune. A efetividade foi analisada pelo tempo em que os pacientes mantiveram-se sob sedação ideal (Ramsay2/4, RASS-3/+1). Para análise estatística foram utilizados os testes t de Student e ?2 (significante p?0,05). Resultados: Foram avaliados 29 pacientes, 14 receberam clonidina (G1) e 15 dexmedetomidina (G2). As características clínicas e demográficas foram semelhantes nesses grupos. A dose média administrada de clonidina foi 0,82µg/kg/h e de dexmedetomidina foi 0,62µg/kg/h. As duas drogas causaram redução na PAM e FC, com exceção da PAM na sexta e vigésima quarta hora do G2. Houve uma tendência que os pacientes do G2 permanecessem mais tempo com sedação ideal (Rass: G1=58,5%, G2=71,9%, Ramsay: G1=54,7%, G2=68,4%) (p=NS). Os níveis de cortisol embora elevados nos dois grupos, não sofreram variação significativa após 24hs de infusão das drogas (G1:34,0/35,2µg/dL, G2:40,9/62,0µg/dL). Houve uma tendência de que Delirium fosse mais freqüentemente diagnosticado no G2 ao final do protocolo (28,6% vs. 45,5% p=NS). Conclusão: A dexmedetomidina e a clonidina mostraram-se efetivas e seguras para a sedação dos pacientes críticos sob ventilação mecânica deste estudo

BACKGROUND Remimazolam besylate, despite being widely used in various clinical settings, lacks evidence in cardiac anesthesia. This trial compared its efficacy with propofol in elective cardiac surgery. METHODS A total of 320 adult patients undergoing elective cardiac surgery via cardiopulmonary bypass between December 2024 and March 2025 were randomized 1:1 to either propofol (1 mg/kg for induction and 1-1.5 mg/kg/h for maintenance) or remimazolam besylate (0.3 mg/kg for induction and 1 mg/kg/h for maintenance) groups. The primary outcome was the sedation success rate (ie, bispectral index 40-60 throughout surgery with predefined dosages and without rescue sedatives), with an absolute difference of 3% as a noninferiority margin. Secondary outcomes included time from drug administration to bispectral index <60 (minute) and bispectral index variation within 15 minutes after drug withdrawal. Application of vasoactive drugs during induction, time to extubation (hour), length of stay in intensive care unit (hour), and hospital (day) were recorded. RESULTS Of 320 enrolled patients, all patients completed the trial and 318 patients were analyzed eventually. The sedation success rate of the whole surgery was significantly higher in the remimazolam besylate group (159; 99.4%) than in the propofol group (130; 82.3%) (absolute difference 17.1%, 95% confidence interval 11.6%-23.9%; P < .001). No significant differences in time from drug administration to bispectral index <60 (P = .119), bispectral index variation after drug withdrawal (P = .658), time to extubation (P = .824), and length of stay in intensive care unit (P = .898) and hospital (P = .294) were observed. CONCLUSIONS Remimazolam besylate is noninferior to propofol in terms of sedation efficacy during elective cardiac procedures.

Background Behavioral management techniques are employed for children who are fearful and uncooperative. Pharmacologic sedation and anesthesia are frequently utilized to manage pain and anxiety in pediatric dental patients. Aim To evaluate the intraoperative and postoperative pain levels during dental treatment of children sedated with 1.5 μg/kg intranasal dexmedetomidine, 0.3 mg/kg intranasal midazolam, and nitrous oxide. Materials and methods In this crossover study, 24 children between the ages of five and seven years were randomly assigned to receive intranasal atomized dexmedetomidine, intranasal atomized midazolam, and inhaled nitrous oxide during three different visits. At each visit, a single pulp therapy procedure was conducted after administering the respective sedative agent, and the pain levels were documented. There was a one-week interval between each visit to allow for a washout period. The data were analyzed using IBM SPSS Statistics for Windows, Version 22.0 (Released 2013; IBM Corp, Armonk, NY, United States) using the Wilcoxon signed-rank test and Kruskal-Wallis H test (p < 0.05). Results All three sedative agents were equally effective in controlling postoperative and intraoperative pain. Although there was no statistically significant difference among the groups, clinically, midazolam showed lower intraoperative pain levels (mean 1.78 ± 1.42). Conclusion In pediatric dental patients, intranasal midazolam at a dosage of 0.3 mg/kg and intranasal dexmedetomidine at a dosage of 1.5 μg/kg demonstrate comparable effectiveness to nitrous oxide sedation in pain management. These options serve as effective alternatives for anxious children who may not tolerate nitrous oxide sedation.

Tese (doutorado) - Universidade Federal de Santa Catarina, Centro de Ciências da Saúde. Programa de Pós-Graduação em Odontologia

Multimodal general anesthesia (MMGA) is a strategy that utilizes the well-known neuroanatomy and neurophysiology of nociception and arousal control in designing a rational and clinical practical paradigm to regulate the levels of unconsciousness and antinociception during general anesthesia while mitigating side effects of any individual anesthetic. We sought to test the feasibility of implementing MMGA for seniors undergoing cardiac surgery, a high-risk cohort for hemodynamic instability, delirium, and post-operative cognitive dysfunction. Twenty patients aged 60 or older undergoing on-pump coronary artery bypass graft (CABG) surgery or combined CABG/valve surgeries were enrolled in this non-randomized prospective observational feasibility trial, wherein we developed MMGA specifically for cardiac surgeries. Antinociception was achieved by a combination of intravenous remifentanil, ketamine, dexmedetomidine, and magnesium together with bupivacaine administered as a pecto-intercostal fascial block. Unconsciousness was achieved by using electroencephalogram (EEG)-guided administration of propofol along with the sedative effects of the antinociceptive agents. EEG-guided MMGA anesthesia was safe and feasible for cardiac surgeries, and exploratory analyses found hemodynamic stability and vasopressor usage comparable to a previously collected cohort. Intraoperative EEG suppression events and postoperative delirium were found to be rare. We report successful use of a total intravenous anesthesia (TIVA)-based MMGA strategy for cardiac surgery and establish safety and feasibility for studying MMGA in a full clinical trial.Clinical Trial Number:www.clinicaltrials.gov; identifier NCT04016740 (https://clinicaltrials.gov/ct2/show/NCT04016740).</jats:p

Trabalho de Conclusão de Curso - Universidade Federal de Santa Catarina. Curso de Medicina. Departamento de Clinica Medica

Background and objective The development of modern anesthetic agents has made it possible to conduct pain-free surgical procedures. The role of the anesthetist in choosing a suitable anesthetic agent to provide a good anesthetic and sedative effect is very important in any surgical procedure. There is always a degree of risk involved as the hemodynamic parameters may be altered. This study aimed to compare the hemodynamic changes and respiratory effects between the use of etomidate and propofol for the induction of general anesthesia (GA) as well as to compare the side effects of both drugs in daycare surgeries. Methods The study was a parallel-design, randomized, double-blinded control trial conducted over a period of three years among patients undergoing elective daycare surgeries under GA. The patients were classified into two groups depending on the type of drug received: Group A or the propofol group and Group B or the etomidate group. Randomization was done by computer-generated random number generator software. A total of 174 patients were selected (87 in each group) at a ratio of 1:1. A baseline evaluation of the hemodynamic parameters was done followed by continuous monitoring. Results The age, weight, and gender distribution of the patients in both groups were comparable. Significant hemodynamic changes were observed following induction in Group A. The fall in systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial blood pressure (MABP) in Group A following induction was found to be statistically significant (p<0.00). The rise in heart rate was almost similar in both groups, with Group A demonstrating a slightly higher rate. There were fewer signs of respiratory depression in Group B. The major side effects observed after induction were myoclonus, which was more prevalent in Group B patients (21.84%), and pain at the injection site, which was observed more frequently in Group A (17.1%). Conclusion Based on our findings, etomidate is a drug with better hemodynamic stability and less pain at the site of injection compared to propofol. Hence, it may be a better induction agent in daycare surgeries.

General anesthesia is a state of unconsciousness, amnesia, analgesia and akinesia induced by drugs including opioids, hypnotic-sedative agents, muscle relaxants and antiemetics. Clinical and genetic factors are reported to influence the efficacy and side effects of these agents. Based on the evidence, clinical action is needed to improve clinical outcomes. This review summarizes the latest knowledge with regards to the pharmacogenetics of anesthetics and general anesthesia related complications. </jats:p

Background: Children undergoing complex cardiac surgery are exposed to substantial cumulative doses of sedative medications and volatile anesthetics and are more frequently anesthetized with ketamine, compared with healthy children. This study hypothesized that greater exposure to sedation and anesthesia in this population is associated with lower neurodevelopmental scores at 18 months of age. Methods: A secondary analysis was conducted of infants with congenital heart disease who participated in a prospective observational study of environmental exposures and neurodevelopmental outcomes to assess the impact of cumulative volatile anesthetic agents and sedative medications. Cumulative minimum alveolar concentration hours of exposure to volatile anesthetic agents and all operating room and intensive care unit exposures to sedative and anesthesia medications were collected before administration of Bayley Scales of Infant and Toddler Development, 3rd edition (Bayley III), at 18 months of age. Results: The study cohort included 41 (37%) single-ventricle and 69 (63%) two-ventricle patients. Exposures to volatile anesthetic agents, opioids, benzodiazepines, and dexmedetomidine were not associated with abnormal Bayley III scores. At 18-month follow-up, after adjusting for confounders, each mg/kg increase in ketamine exposure was associated with a 0.34 (95% CI, −0.64 to −0.05) point decrease in Bayley III motor scores (P = 0.024). Conclusions: Total cumulative exposures to volatile anesthetic agents were not associated with neurodevelopmental impairment in infants with congenital heart disease undergoing various imaging studies and procedures, whereas higher ketamine doses were associated with poorer motor performance. In this secondary analysis of a prospective study evaluating neurodevelopmental outcomes of pediatric patients with congenital heart disease, no association was found between total cumulative exposures to volatile anesthetics and Bayley III scores assessed at 18 months of age, whereas higher ketamine doses were associated with poorer motor performance.

Objective: We recorded the data of patients performing Percutaneous Nephro-lithotomy (PCNL) under combined spinal anesthesia with sedative mixtures of Ketamine-Propofol (KP) or Fentanyl-Propofol (FP). Background: The PCNL is usually done under General anesthesia (GA); combining spinal anesthesia with a mixture of sedative drugs has shown to provide an optimum intra and post-operative analgesic and sedative response without side effects. Patients and Methods: 100 healthy patients were enrolled for PCNL, after stabilization of the sensory block of spinal anesthesia patients were randomized into two groups; Group KP received 1 mg/Kg Ketamine and 1 mg/Kg Propofol diluted in 20 ml syringe given over 30 seconds and Group FP received 1 mic/Kg Fentanyl and 1 mg/Kg Propofol diluted in 20 ml syringe over 30 seconds; both groups will receive increment doses if the patient suffers from anxiety, pain or discomfort. Perioperative Hemodynamic data (HR, SBP, DBP, RR, and SpO2) were recorded; PACU stay time and post operative analgesia time were analyzed. Results: Sedative mixtures of FP and KP provided remarkably deep sedation levels for PCNL procedures under spinal anesthesia. Respiratory depression, hypotension and bradycardia were the major side effects reported in FP group which had mean decrease in RR of 4.63 breath/min (27.49%) with mean 3.77% drop in SpO2 levels. KP group produced significant increase in HR about 7 beats/min without reported side effects. Conclusion: Various sedation techniques may be applicable for PCNL procedures with routine premedication, mixtures of fentanyl-Propofol or Ketamine-Propofol could be used, and KP has advantages of stable hemodynamics, prolonged analgesic response intra and post-operatively with no appreciable side effects and more effective method of sedative mixture.

Dexmedetomidine is a selective α2-adrenergic receptor agonist that has emerged as an important agent for sedation and analgesia in anesthetic and critical care practice. Unlike conventional sedatives, it produces a calm, cooperative form of sedation with minimal respiratory compromise and is most commonly administered via continuous intravenous infusion. Its sedative effect is primarily mediated through inhibition of noradrenergic activity in the locus coeruleus, resulting in decreased norepinephrine release and enhanced inhibitory neuronal signaling. This mechanism produces a sleep-like sedative state in which patients remain easily arousable and interactive. In clinical practice, dexmedetomidine is increasingly adopted for procedural sedation and for sedation of mechanically ventilated patients in both adult and pediatric intensive care units. It has also demonstrated potential utility as an adjunct in the management of intracranial hypertension following neurological injury. By activating central α2-adrenoceptors, dexmedetomidine suppresses sympathetic outflow, blunts stress-related neuroendocrine and cardiovascular responses to surgery and anesthesia, and decreases the need for additional anesthetic and opioid agents. These pharmacological properties are associated with favorable clinical outcomes, including improved patient tolerance, reduced incidence of agitation and delirium, and facilitation of earlier weaning from mechanical ventilation. Consequently, dexmedetomidine has become a preferred sedative agent in the intensive care setting. In addition to sedation, it provides analgesic benefits and is increasingly employed as an adjunct in regional anesthesia, as well as in selected perioperative and psychiatric indications. Nevertheless, dexmedetomidine administration may be accompanied by hemodynamic adverse effects such as bradycardia, hypotension, and transient hypertension. Therefore, appropriate patient selection and vigilant cardiovascular monitoring are essential, particularly in individuals with compromised cardiac function. This review highlights the distinctive sedative profile and clinical advantages of dexmedetomidine, underscoring its growing significance in contemporary anesthesia and critical care management.</jats:p