Sedative Agents Research Articles

Abstract 16861: Early Sedation With Dexmedetomidine in Patients With Acute Myocardial Infarction Who Require Mechanical Ventilation

Background: Patients with acute myocardial infarction (AMI) who require mechanical ventilation (MV) are a critically ill population which require sedatives and analgesia for comfort. However, clinical trials, including those for dexmedetomidine, exclude or poorly represent patients with AMI. Research Question: Is early sedation with dexmedetomidine associated with lower hospital mortality compared to usual-care sedation in patients with AMI who require MV? Methods: We utilized the Vizient® Clinical Data Base to identify patients aged ≥18 years who were admitted between 2015 and 2019 with a primary diagnosis of AMI and required MV within 7 days of admission. Patients were assigned to the early dexmedetomidine group if they received dexmedetomidine on the first day of MV; the remaining patients were assigned to the usual care group. Inverse probability of treatment weighting (IPTW) was used to estimate adjusted risk differences between groups. Results: Of the 21,303 patients included in the study, 1,620 (7.6%) received early dexmedetomidine ( Table ). Patients who received early dexmedetomidine were younger (66 vs 67 years) and less likely to be female (29.3% vs 33.8%) (both, P <0.05). Median ventilator days for early dexmedetomidine vs usual care was 4 and 3 days, respectively ( P <0.001). Patients who received early dexmedetomidine had lower hospital mortality compared to usual care (33.0% vs 46.0%, P <0.001) despite higher prevalence of cardiogenic shock. After IPTW, the early dexmedetomidine group had a 16.2% (95% confidence interval [CI]: 13.6%-18.7%) lower mortality. The early dexmedetomidine group had more ventilator-free days (13.6 vs 9.7, P <0.001), which persisted after IPTW (mean difference: +4.9 days, 95% CI: 4.2-5.5 days). Conclusion: Early sedation with dexmedetomidine may be associated with lower mortality compared to usual care in patients with AMI who require MV. A randomized controlled trial of sedative agents in this population is warranted.

In vitro evaluation of cytotoxic potential of essential oil extracted from leaves of Croton heliotropiifolius Kunth in human tumor cells

ABSTRACT Croton heliotropiifolius Kunth, popularly known as “velame,” is a shrub that resides in northeastern Brazil. The essential oil of C. heliotropiifolius contains high concentrations of volatile compounds in the leaves and is widely used in folk medicine for many purposes as an antiseptic, analgesic, sedative, and anti-inflammatory agent. Due to the apparent limited amount of information, the aim of this study was to determine the cytotoxic potential of essential oil extracted from leaves of C. heliotropiifolius, utilizing different human cancer cell lines (HL-60, leukemia; HCT-116, colon; MDA-MB435, melanoma; SF295, glioblastoma) and comparison to murine fibroblast L929 cell line. The chemical characterization of the essential oil revealed the presence of large amounts of monoterpenes and sesquiterpenes, the majority of which were aristolene (22.43%), germacrene D (11.38%), ɣ-terpinene (10.85%), and limonene (10.21%). The essential oil exerted significant cytotoxicity on all cancer cells, with low activity on murine L929 fibroblasts, independent of disruption of cell membranes evidenced by absence of hemolytic activity. The cytotoxicity identified was associated with oxidative stress, which culminated in mitochondrial respiration dysfunction and direct or indirect DNA damage (strand breaks and oxidative damage), triggering cell death via apoptosis. Our findings suggest that extracts of essential oil of C. Heliotropiifolius may be considered as agents to be used therapeutically in treatment of certain cancers.

Melatonin Use in Infants Admitted to Intensive Care Units.

Sleep deprivation is a risk factor for delirium development, which is a frequent complication of intensive care unit admission. Melatonin has been used for both delirium prevention and treatment. Melatonin safety, efficacy, and dosing information in neonates and infants is lacking. The purpose of this study was to describe melatonin use in infants regarding indication, dosing, efficacy, and safety. This descriptive, retrospective study included infants <12 months of age admitted to an intensive care unit receiving melatonin. Data collection included demographics, melatonin regimen, sedative and analgesic agents, antipsychotics, and delirium-causing medications. The primary objective was to identify the melatonin indication and median dose. The secondary objectives included change in delirium, pain, and sedation scores; change in dosing of analgesic and sedative agents; and adverse event identification. Wilcoxon signed rank tests and linear mixed models were employed with significance defined at p < 0.05. Fifty-five patients were included, with a median age of 5.5 months (IQR, 3.9-8.2). Most (n = 29; 52.7%) received melatonin for sleep promotion. The median body weight-based dose was 0.31 mg/kg/dose (IQR, 0.20-0.45). There was a statistical reduction in cumulative morphine equivalent dosing 72 hours after melatonin administration versus before, 17.1 versus 21.4 mg/kg (p = 0.049). No adverse events were noted. Most patients (n = 29; 52.7%) received melatonin for sleep promotion at a median dose was 0.31 mg/kg/dose. Initiation of melatonin was associated with a reduction of opioid exposure; however, there was no reduction in pain/sedation scores.

Efficacy and safety of remimazolam besilate for sedation in outpatients undergoing impacted third molar extraction: a prospective exploratory study

BackgroundDental treatments often cause anxiety, fear, and stress in patients. Intravenous sedation is widely used to alleviate these concerns, and various agents are employed for sedation. However, it is important to find safer and more effective sedation agents, considering the adverse effects associated with current agents. This study aimed to investigate the efficacy and safety of remimazolam besilate (hereinafter called “remimazolam”) and to determine the optimal dosages for sedation in outpatients undergoing dental procedures.MethodsThirty-one outpatients aged 18–65 years scheduled for impacted third molar extraction were included in the study. Remimazolam was administered as a single dose of 0.05 mg/kg followed by a continuous infusion at a rate of 0.35 mg/kg/h, with the infusion rate adjusted to maintain a sedation level at a Modified Observer’s Assessment of Alertness/Sedation (MOAA/S) score of 2–4. The primary endpoint was the sedation success rate with remimazolam monotherapy, and the secondary endpoints included induction time, recovery time, time until discharge, remimazolam dose, respiratory and circulatory dynamics, and frequency of adverse events.ResultsThe sedation success rate with remimazolam monotherapy was 100%. The remimazolam induction dose was 0.08 (0.07–0.09) mg/kg, and the anesthesia induction time was 3.2 (2.6–3.9) min. The mean infusion rate of remimazolam during the procedure was 0.40 (0.38–0.42) mg/kg/h. The time from the end of remimazolam administration to awakening was 8.0 (6.7–9.3) min, and the time from the end of remimazolam administration to discharge was 14.0 (12.5–15.5) min. There were no significant respiratory or circulatory effects requiring intervention during sedation.ConclusionsContinuous intravenous administration of remimazolam can achieve optimal sedation levels without significantly affecting respiratory or circulatory dynamics. The study also provided guidance on the appropriate dosage of remimazolam for achieving moderate sedation during dental procedures. Additionally, the study findings suggest that electroencephalogram monitoring can be a reliable indicator of the level of sedation during dental procedural sedation with remimazolam.Trial registrationThe study was registered in the Japan Registry of Clinical Trials (No. jRCTs061220052) on 30/08/2022.

Anesthetic effect and acute toxicity of Citrus sinensis essential oil in betta

This study investigated the use of Citrus sinensis essential oil (EOCS) in Betta splendens, evaluating toxicity, induction and recovery times to anesthesia, its action on agonist behavior, and on male collective transport. To toxicity, fish were exposed to EOCS at different concentrations during 48 h. The induction test was performed to evaluate sedation, anesthesia, and recovery under different concentrations. To assess agonist behavior, male subjects were maintained with different dosages of EOCS, assessing opercular beat and fin expansion, while exposed to untreated animals. In the mass transport study, males were divided into two treatments with two levels of EOCS, for 6 h, also analyzing gill histometry at the end of transport. The results obtained show that the mean lethal concentration in 48 h of exposure to EOCS was calculated at 49.17 μL·L−1. The shortest anesthesia induction time was at 300 μL·L−1 EOCS. EOCS was able to reduce agonist behavior in males individual. Histometric analyzes revealed a reduction in the height of gill filaments in fish transported with 20 μL·L-1 EOCS. EOCS can be used as a sedative and anesthetic agent for B. splendens.

Tratamento da intoxicação por zolpidem com flumazenil em um gato

This report aims to describe the case of a cat intoxicated with zolpidem that was treated with flumazenil. Flumazenil is an imidazodiazepine that effectively reverses the central effects of benzodiazepines. In humans, it is used to treat zolpidem poisoning. Zolpidem is a sedative hypnotic agent, non-benzodiazepine, that is used to treat patients with insomnia. A 2-year-old Bengal cat weighing 2.5 kg showed signs of ataxia, incoordination and diarrhea after accidental ingestion of 10 mg zolpidem (Stilnox®). The cat was administered with 0.1 mg/kg of flumazenil intravenously, and after 20 minutes all clinical signs disappeared. To our knowledge, this is the first report of the use of flumazenil for the treatment of zolpidem poisoning in cats. Discussion regarding the treatment of zolpidem poisoning is necessary owing to the increased prescription of this drug in humans and, consequently, to a greater possibility of accidental poisoning in domestic animals.

Neonatal Surgical Procedures in the Intensive Care Unit versus the Operating Room.

With advancements in neonatal care, the survival rates of preterm infants have increased, leading to a higher incidence of comorbidities and need for surgical interventions. Neonatologists, pediatric anesthesiologists, and pediatric surgeons are thus increasingly confronted with the decision of whether to perform surgical procedures on critically ill neonates and preterm infants in the operating room (OR) or the NICU. Although certain bedside procedures have been commonly described in the literature, a paucity of research exists regarding ideal patient selection and anesthetic management. In this review, we will examine the decision-making process for providing anesthetic care in the OR versus the NICU as well as investigate appropriate sedation agents for procedures occurring in the NICU. Ultimately, the location of the surgery should be determined by the circumstances of each patient and involve collaboration of the entire perioperative team.

Protocols and procedures for safe administration of nitrous oxide–oxygen inhalational minimal sedation for anxiolysis in pediatric dentistry: A case series

Abstract Fear and anxiety related to dental treatment are the most important causes of avoidance of oral care among pediatric patients. The majority of pediatric dental patients are managed with only behavior management techniques, without any pharmacological intervention. However, several pediatric dental patients, owing to noncooperation or the extent of surgery required may require pharmacological means of management, such as sedation or general anesthesia. Children with mild-to-moderate anxiety are suitable for management with inhalational sedation agents, such as nitrous oxide and oxygen (N2O–O2). An inhalational mixture of N2O–O2 has been used in this setting for over a century and has a high index of safety. With the advent of newer failsafe equipment for the delivery of these agents and the availability of trained dental and anesthesiology teams, this modality of sedation for behavior management of children while rendering dental treatment is gaining more acceptability. Proper case selection, informed consent from parents/guardians before the procedure, preprocedure and preprocedure counseling, and anesthetic evaluation of the child are important steps in the successful administration of sedation. The awareness of guidelines, alertness regarding adverse events, and preemptive preparation to manage any critical incident are essential for the safe administration of this inhalational mixture; thus, providing oral care to pediatric patients with the least amount of discomfort.

Impact on Psychomotor Functions by Sedative Agents Used During Daycare Surgeries: A Randomized Controlled DoubleBlinded Study of Dexmedetomidine Versus Midazolam Fentanyl

Background: Sedative agents are used during surgeries to reduce stress and anxiety and discomfort of the patient. An ideal sedation agent should provide a rapid onset of action and faster recovery. Almost all commonly used sedative agents in daycare surgeries affect the cognitive and psychomotor functions. The research question of this study was to find out which of the commonly used sedative agents- Dexmedetomidine or Midazolam-Fentanyl combination produces less impact on the psychomotor functions of the patients. Materials and Methods: Seventy two patients who were undergoing tympanoplasty under local anesthesia, were randomly divided into two equal groups - Group D (dexmedetomidine) and Group MF (midazolam and fentanyl) using a computer-based randomization scheme. Group D received dexmedetomidine till an adequate sedation score was achieved (Ramsay sedation scale =3). Group MF patients received midazolam and fentanyl till an adequate sedation score was achieved. Baseline psychomotor assessment and delirium assessment was done 30 minutes prior to the shifting of the patient to operation theatre. All the scores were compared at 30 minutes, 1 hour, 2 hours, 4 hours and 8 hours by using MMSE test and stroop color word interference test for psychomotor assessment and short-CAM &amp; Short-CAM severity test for delirium assessment. Statistical analysis was done by applying paired t-test and repeated measure ANOVA for intra-group comparison and for intergroup comparison, independent t-test was applied. Results: There was a significant decline in MMSE score and stroop color word interference score at post-operative period as compared to the baseline values in both the groups up to 4 hours. No such significant difference was seen at 8 hours post-operative period. In both groups, more patients in MF group had mild cognitive dysfunction at 1 hour post-op period, as compared to patient in D group. None of the patients showed severe cognitive impairment. In Group MF, the total number of patients showing signs of delirium was more as compared to group D at Post-op 1 hour. But no signs of delirium were found in any patient in later readings. When presented, the severity of delirium was assessed by Short CAM severity test score. It was observed that all patients who had delirium had CAM severity score of 1 only. Conclusion: The present study concluded that drug dexmedetomidine causes less cognitive decline and less chances of producing post-op delirium as compared to midazolam-fentanyl combination when used for sedation at the time of surgery.

Comparison of the Sedative Effects of Dexmedetomidine and Remifentanil in Vitrectomy Surgery: A Retrospective Study.

Background Vitrectomy surgery is a painful and lengthy procedure. Therefore, administering sedation to reduce patient agitation provides both surgical comfort and hemodynamic stability. However, various complications can arise during the perioperative period depending on the sedation agent used. In our study, we aimed to evaluate the effects of dexmedetomidine and remifentanil sedation applications on patient hemodynamics and perioperative complications in vitrectomy surgery. Methods Our retrospective study included patients aged 18-70 who underwent vitrectomy surgery between 2021 and 2022 with complete file data and ASA scores of 1-3 after obtaining approval from our hospital's ethics committee. Patients were classified into two groups based on the sedation agent used: Group D for dexmedetomidine and Group R for remifentanil. Demographic data of patients, heart rate, mean arterial pressure, oxygen saturation, and bispectral index values during perioperative monitoring, operation duration, and complications such as perioperative nausea, vomiting, and low saturation were recorded. The data of both groups were statistically evaluated, with p<0.05 values considered statistically significant. Results Because of missing data in 18 out of 58 patient files, these cases were excluded from the study. A total of 40 patients were included in the study, with 20 in Group D and 20 in Group R. The mean age of the patients was 64. Among them, 18 (45%) were male, and 22 (55%) were female. The mean operation duration was 61.8 ± 24.1 minutes in Group D and 56.3 ± 17.2 minutes in Group R. The heart rate in Group D was statistically significantly lower than in Group R, starting from the 20th minute of the perioperative period. There were no significant differences between the groups in terms of mean arterial pressure, oxygen saturation, and bispectral index values. One case of bradycardia occurred in Group D, requiring intervention. Conclusion In vitrectomy surgery, both dexmedetomidine and remifentanil infusions can be used for sedation, but caution is advised regarding bradycardia in Group D. Anticipating potential complications with an experienced anesthesia team is crucial for both patient and surgical comfort.

Norepinephrine modulates calcium dynamics in cortical oligodendrocyte precursor cells promoting proliferation during arousal in mice.

Oligodendrocytes, the myelinating cells of the central nervous system (CNS), are generated from oligodendrocyte precursor cells (OPCs) that express neurotransmitter receptors. However, the mechanisms that affect OPC activity in vivo and the physiological roles of neurotransmitter signaling in OPCs are unclear. In this study, we generated a transgenic mouse line that expresses membrane-anchored GCaMP6s in OPCs and used longitudinal two-photon microscopy to monitor OPC calcium (Ca2+) dynamics in the cerebral cortex. OPCs exhibit focal and transient Ca2+ increases within their processes that are enhanced during locomotion-induced increases in arousal. The Ca2+ transients occur independently of excitatory neuron activity, rapidly decline when OPCs differentiate and are inhibited by anesthesia, sedative agents or noradrenergic receptor antagonists. Conditional knockout of α1A adrenergic receptors in OPCs suppresses spontaneous and locomotion-induced Ca2+ increases and reduces OPC proliferation. Our results demonstrate that OPCs are directly modulated by norepinephrine in vivo to enhance Ca2+ dynamics and promote population homeostasis.

The efficacy of non-anesthesiologist-administered propofol sedation with a target-controlled infusion system during double-balloon endoscopic retrograde cholangiopancreatography

BackgroundThe sedation method used during double-balloon endoscopic retrograde cholangiopancreatography (DB-ERCP) differs among countries and/or facilities, and there is no established method. This study aimed to evaluate the efficacy of non-anesthesiologist-administered propofol (NAAP) sedation using a target-controlled infusion (TCI) system during DB-ERCP.MethodsThis retrospective study was conducted between May 2017 and December 2020 at an academic center. One hundred and fifty-six consecutive patients who underwent DB-ERCP were sedated by gastroenterologists using diazepam (n = 77) or propofol with a TCI system (n = 79), depending on the period. The primary endpoint was a comparison of poor sedation rates between the two groups. Poor sedation was defined as a condition requiring the use of other sedative agents or discontinuation of the procedure. Secondary endpoints were sedation-related adverse events and risk factors for poor sedation.ResultsPoor sedation occurred significantly more often in the diazepam sedation group (diazepam sedation, n = 12 [16%] vs. propofol sedation, n = 1 [1%]; P = 0.001). Vigorous body movements (3 or 4) (diazepam sedation, n = 40 [52%] vs. propofol sedation, n = 28 [35%]; P = 0.038) and hypoxemia (< 85%) (diazepam sedation, n = 7 [9%] vs. propofol sedation, n = 1 [1%]; P = 0.027) occurred significantly more often in the diazepam sedation group. In the multivariate analysis, age < 70 years old (OR, 10.26; 95% CI, 1.57–66.98; P = 0.015), BMI ≥ 25 kg/m2 (OR, 11.96; 95% CI, 1.67–85.69; P = 0.014), and propofol sedation (OR, 0.06; 95% CI, 0.01–0.58; P = 0.015) were associated factors for poor sedation.ConclusionsNAAP sedation with the TCI system during DB-ERCP was safer and more effective than diazepam sedation.

Comparison of Propofol versus Midazolam Infusion for Conscious Sedation during Spinal Anaesthesia in Patients Undergoing Inguinal Hernia Repair

Abstract Background The operating room is an anxiety provoking environment. Supplemental sedation with an intravenous agent is often required to allay fear and anxiety in patients subjected to spinal anaesthesia. Sedation is a valuable tool to make surgery under regional anaesthesia convenient for the patient, the anaesthetist and the surgeon. Conscious sedation is a minimally depressed level of consciousness that retains the patient’s ability to maintain his or her airway independently and continuously and to respond appropriately to physical stimulation and verbal commands, produced by pharmacologic or non-pharmacologic methods alone or in combination. Aim of the Work This study will be designed to compare Propofol and Midazolam with regard to their suitability as sedative agents during spinal anaesthesia in terms of onset &amp; recovery from sedation, haemodynamic stability, dosage and side effects of both the drugs. Patients and Methods This Interventional clinical study (Randomized double blinded study was conducted in Ain Shams University Hospital’s operating rooms through 3 months on 50 patients. After obtaining approval from the medical ethical committee in Ain Shams University Hospital’s operating rooms, a written informed consent was obtained from every patient after explaining the procedure. Results Based on this study the following conclusions have been made: Cardiovascular parameters and respiration were well maintained in both the study groups, no incidence of apnea was noticed in both the study groups, pain during the injection of propofol was a side effect noticed, onset of action was faster in the propofol group, propofol group was less co-operative than midazolam group but this was clinically insignificant, midazolam group showed slower recovery than propofol group restricting and wasting the productive time of the patient, qualities such as short plasma half-life period, absence of postoperative nausea and vomiting, make propofol a better choice for sedation and thus propofol is a fast acting, safe and easily controllable sedative with rapid recovery. This offered the advantage of early patient discharge and better patient compliance. Conclusion When given as a sedative adjunct to spinal I, both propofol and midazolam in equisedative infusions offer good anxiolysis and good cardio respiratory stability. Propofol has the advantage of providing faster onset of sedation, a rapid clear headed recovery from the same and lesser postoperative impairment of recall while midazolam offers better intraoperative amnesia.

Neuropharmacological Effects of the Dichloromethane Extract from the Stems of Argemone ochroleuca Sweet (Papaveraceae) and Its Active Compound Dihydrosanguinarine.

Argemone ochroleuca Sweet (Papaveraceae) is used in folk medicine as a sedative and hypnotic agent. This study aimed to evaluate the anxiolytic-like, sedative, antidepressant-like, and anticonvulsant activities of a dichloromethane extract of A. ochroleuca stems (AOE), chemically standardized using gas chromatography-mass spectrometry (GC-MS), and its active compound dihydrosanguinarine (DHS). The anxiolytic-like, sedative, antidepressant-like, and anticonvulsant activities of the AOE (0.1-50 mg/kg p.o.) and DHS (0.1-10 mg/kg p.o.) were evaluated using murine models. A possible mechanism for the neurological actions induced by the AOE or DHS was assessed using inhibitors of neurotransmission pathways and molecular docking. Effective dose 50 (ED50) values were calculated by a linear regression analysis. The AOE showed anxiolytic-like activity in the cylinder exploratory test (ED50 = 33 mg/kg), and antidepressant-like effects in the forced swimming test (ED50 = 3 mg/kg) and the tail suspension test (ED50 = 23 mg/kg), whereas DHS showed anxiolytic-like activity (ED50 = 2 mg/kg) in the hole board test. The AOE (1-50 mg/kg) showed no locomotive affectations or sedation in mice. A docking study revealed the affinity of DHS for α2-adrenoreceptors and GABAA receptors. The anxiolytic-like and anticonvulsant effects of the AOE are due to GABAergic participation, whereas the antidepressant-like effects of the AOE are due to the noradrenergic system. The noradrenergic and GABAergic systems are involved in the anxiolytic-like actions of DHS.

Safety of geriatric patients undergoing endobronchial ultrasound-guided transbronchial needle aspiration with deep sedation: a retrospective study

BackgroundEndobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) can be performed in a wide range, from minimal sedation to general anesthesia. Advanced age increases perioperative risks related to anesthesia and is also associated with many pathological processes that further increase morbidity and mortality. The ideal sedation protocol for EBUS-TBNA has yet to be determined in geriatric patients. Deep sedation (DS) may increase the safety and performance of the procedure. There are limited studies evaluating the effectiveness and safety of EBUS-TBNA under DS in elderly patients.Methods280 patients who underwent EBUS-TBNA under DS were included in this retrospective study. 156 patients aged 65 years and over (Group 1) and 124 patients under 45 (Group 2) were compared. Demographic data, comorbidities, pulmonary function tests (PFTs), hemodynamic measurements, and peripheral oxygen saturation (SpO2) before the procedure were evaluated. In addition, the duration of the EBUS-TBNA procedure, sedation agents and dosages, recovery time, and complications related to the procedure in the 24 h and applied medications and treatments were recorded.ResultsThere was no difference in body mass index, EBUS-TBNA procedure duration, and recovery time between geriatric and young patients(p > 0.05). The proportion of female patients, pre-anesthesia SpO2, and PFTs were found to be significantly lower in geriatric patients(p < 0.05). ASA classification, frequency of comorbidities, and initial mean arterial pressure were found to be significantly higher in the geriatric group(p < 0.05). The propofol-ketamine combination was the most preferred sedative in both groups. The dose of propofol used in the regimen in which propofol was administered alone was found to be lower in the elderly group (p < 0.05). The increase in the HR was significant in Group 2 in the T4 and T5 periods with respect to T1 when the differences were compared (p < 0.05). As a complication, the frequency of high blood pressure during the procedure was higher in the elderly group (p < 0.05).ConclusionsThe EBUS-TBNA procedure performed under DS was safe in elderly and young patients. Our study showed that the procedure and recovery times were similar in the elderly and young groups. The incidence of temporary high blood pressure during the procedure was higher in the elderly patients. The other complication rates during the procedure were similar in groups. Decreased propofol dose in the regimen using propofol alone has shown us that anesthetists are more sensitive to the administration of sedative agents in geriatric patients, taking into account comorbidities and drug interactions.

Dexmedetomidine versus propofol: An effective combination with ketamine for adult procedural sedation: A randomized clinical trial

BackgroundRecently, drug combination protocols have been preferred over single drugs in procedural sedation and analgesia (PSA). This study aimed to compare the effectiveness and hemodynamic profile of ketamine-dexmedetomidine (ketodex) and ketofol as drug combinations with ketamine as a single medication for PSA in the emergency department (ED). MethodsThis prospective, randomized, double-blind clinical trial was performed among adult patients (≥18 years) requiring PSA for a painful procedure in the ED. 135 patients were enrolled and assigned into three equal groups to receive either ketodex, ketofol, or ketamine. Additional ketamine was used as a rescue agent for inadequate sedation in three groups. Oxygen saturation, heart rate, and blood pressure were recorded from baseline until 120 min after induction of PSA. Adverse events, hemodynamic variables, induction, and recovery time were recorded and compared between groups. ResultsThe mean age of the patients was 38.16 ± 19.09 years and no differences were observed between the three groups in terms of demographic variables, pain scores, and procedures between the three groups. Respiratory events had similar incidences between the three groups. The O2 reduction was less in the Ketodex group in comparison with Ketofol and Ketamine groups (1.9%, 6.5%, and 3.8%, P = 0.015). No patient needed endotracheal intubation. Changes in mean arterial pressure from the baseline in Ketamine and Ketofol groups compared to Ketodex was higher (difference was 12.9 mmHg [95% CI, 9.5 to 20.3] and 8.6 mmHg [95% CI, 3.4 to 13.7]. Tachycardia in the Ketamine group had a significantly higher incidence. The recovery time was statistically shorter in the Ketofol group in comparison with other groups. The differences between Ketofol with Ketamine and Ketodex groups were 9.8 min (95% CI, [2.5 to 17.1]) and 8.3 min (95% CI, [1.5 to 15.1]). ConclusionKetodex, as well as ketofol, were effective and safe combinations with good recovery profiles and hemodynamic stability for adult PSA in ED.

Impact of Dexmedetomidine Infusion on Opioid and Benzodiazepine Doses in Ventilated Pediatric Patients in the Cardiac Intensive Care Unit.

Dexmedetomidine (DEX) is frequently used as an adjunct agent for prolonged sedation in the intensive care unit (ICU), though its effect on concomitant opioids or benzodiazepines infusions is unclear. We explored the impact of DEX on concomitant analgosedation in a cohort of ventilated pediatric patients in a cardiac ICU, with stratification of patients according to duration of ventilation (< 5 versus ≥ 5 days) following DEX initiation. We conducted a retrospective analysis on ventilated patients receiving a DEX infusion ≥ 24 h and at least one other sedative/analgesic infusion (January 2011-June 2021). We evaluated trends of daily doses of opioids and benzodiazepines from 24 h before to 72 h following DEX initiation, stratifying patients based on ventilation duration after DEX initiation (< 5 versus ≥ 5 days). After excluding 1146 patients receiving DEX only, 1073 patients were included [median age 234 days (interquartile range 90, 879)]. DEX was associated with an opioid infusion in 99% of patients and a benzodiazepine infusion in 62%. Among patients ventilated for < 5 days (N = 761), opioids increased in the first 24 h following DEX initiation [+ 1.12 mg/kg/day (95% CI 0.96, 1.23), P < 0.001], then decreased [- 0.90 mg/kg/day (95% CI - 0.89, - 0.71), P < 0.001]; benzodiazepines slowly decreased [- 0.20 mg/kg/day (95% CI - 0.21, - 0.19), P < 0.001]. Among patients ventilated for ≥ 5 days (N = 312), opioid administration doubled [+ 2.09 mg/kg/day (95% CI 1.82, 2.36), P < 0.001] in the first 24 h, then diminished minimally [- 0.18 mg/kg/day (95% CI - 0.32, - 0.04), P = 0.015] without returning to baseline; benzodiazepine administration decreased minimally [- 0.03 mg/kg/day (95% CI - 0.05, - 0.01), P = 0.010]. Similar trends were confirmed when adjusting for age, gender, surgical complexity, recent major invasive procedures, duration of mechanical ventilation before DEX initiation, extubation within 72 h following DEX initiation, mean hourly DEX dose, and use of neuromuscular blocking infusion. While in patients ventilated < 5 days opioids initially increased and then quickly decreased in the 72 h following DEX initiation, among patients ventilated ≥ 5 days opioids doubled, then decreased only minimally; benzodiazepines decreased minimally in both groups, although more slowly in the long-ventilation cohort. These findings may inform decision-making on timing of DEX initiation in ventilated patients already being treated with opioid or benzodiazepine infusions.

Influence of Regional Nerve Block in Addition to General Anesthesia on Postoperative Delirium, Pain, and In-hospital Stay in Patients Undergoing Cardiothoracic Surgery: A Meta-analysis.

This study aims to investigate whether venous injection of sedative agent or regional nerve block in alliance with major anesthesia could decrease the risk of postoperative delirium occurrence in patients receiving cardiothoracic surgery. Electronic academic databases were retrieved for related publications, and statistical software was used for data pooling and analysis. Forest plot was used to show the pooled sensitivity, specificity, and diagnostic odds ratio. Combined receiver operating characteristic curve was used to show the area under the curve of complex data. Seven studies were included for analysis. The risk of occurrence of delirium still showed no difference (risk rate = 0.93, 95% CI, 0.85-1.03) between the intervention group and placebo group. Postoperative pain feeling was more alleviated in patients with prophylactic application of regional nerve block. In addition, prophylactic application of regional nerve block could decrease the risk of postoperative in-hospital stay (risk rate = 0.28, 95% CI, 0.02-0.54). Our study demonstrated that, in elderly patients or pediatric patients undergoing cardiac surgery, prophylactic application of regional nerve block failed to decrease the incidence of postoperative delirium. However, the option of regional nerve block could decrease the duration of in-hospitalization stay and alleviate the acute pain during the postoperative period after open-heart surgery.

On-chip modeling of physiological and pathological blood-brain barrier microenvironment for studying glial responses to neuroinflammation

The blood-brain barrier (BBB), a unique multicellular physical structure, maintains the central nervous system (CNS) homeostasis, and its disruption along with neurotoxic blood-derived molecules deposition is involved in various neurodegenerative diseases. Studying how the biological reactions of glial cells exacerbate the brain injury in the leaky BBB upon the insult of neuroinflammation is in urgent need for an in vitro physiologically relevant BBB-mimetic model. Here, we developed a microfluidic BBB chip model comprised of endothelial cells, astrocytes and microglia co-culture, which could innovatively recapitulate the physiological and pathological states when combined with particular hydrogels. Glia cells in the functional BBB with Matrigel as the matrix composition underwent significant activation by lipopolysaccharide (LPS) and specific aberrant protein aggregates stimulation, manifesting as astrocyte reactivity, higher microglial migration speed and the upregulated expression of activation marker, while the fibrin-mediated pathological extracellular microenvironment primed the glial cells to exhibit blunted responses to inflammatory irritation. We further verified the neuroprotective effect of the clinically sedative agent dexmedetomidine against neuroinflammation utilizing our BBB chip model. The BBB-on-a-chip may facilitate the elucidation of sophisticated cell-cell interactions in the progression of brain neurodegenerative diseases and the evaluation of preclinical drug efficacy.

The impact of sedative and vasopressor agents on cerebrovascular reactivity in severe traumatic brain injury

BackgroundThe aim of this study is to evaluate the impact of commonly administered sedatives (Propofol, Alfentanil, Fentanyl, and Midazolam) and vasopressor (Dobutamine, Ephedrine, Noradrenaline and Vasopressin) agents on cerebrovascular reactivity in moderate/severe TBI patients. Cerebrovascular reactivity, as a surrogate for cerebral autoregulation was assessed using the long pressure reactivity index (LPRx). We evaluated the data in two phases, first we assessed the minute-by-minute data relationships between different dosing amounts of continuous infusion agents and physiological variables using boxplots, multiple linear regression and ANOVA. Next, we assessed the relationship between continuous/bolus infusion agents and physiological variables, assessing pre-/post- dose of medication change in physiology using a Wilcoxon signed-ranked test. Finally, we evaluated sub-groups of data for each individual dose change per medication, focusing on key physiological thresholds and demographics.ResultsOf the 475 patients with an average stay of 10 days resulting in over 3000 days of recorded information 367 (77.3%) were male with a median Glasgow coma score of 7 (4–9). The results of this retrospective observational study confirmed that the infusion of most administered agents do not impact cerebrovascular reactivity, which is confirmed by the multiple linear regression components having p value > 0.05. Incremental dose changes or bolus doses in these medications in general do not lead to significant changes in cerebrovascular reactivity (confirm by Wilcoxon signed-ranked p value > 0.05 for nearly all assessed relationships). Within the sub-group analysis that separated the data based on LPRx pre-dose, a significance between pre-/post-drug change in LPRx was seen, however this may be more of a result from patient state than drug impact.ConclusionsOverall, this study indicates that commonly administered agents with incremental dosing changes have no clinically significant influence on cerebrovascular reactivity in TBI (nor do they impair cerebrovascular reactivity). Though further investigation in a larger and more diverse TBI patient population is required.