Intravenous Sedative Agents Research Articles

Ciprofol alleviates remifentanil-induced hyperalgesia by regulating α2GABAARs, NR2B, and P-CaMKIIα levels in the spinal cord and hippocampus.

Several studies have shown that propofol administration during surgery effectively attenuates remifentanil-induced hyperalgesia (RIH). Ciprofol, a novel intravenous sedative agent analogous to propofol, has not yet been proven efficacious in alleviating RIH. The present study aimed to investigate the effect of ciprofol on RIH and the possible mechanisms involved. The RIH model was established by an infusion of remifentanil (1 μg·kg-1·min-1) 60 min in rats with incisional pain. Ciprofol (0.1, 0.25, and 0.4 mg·kg-1·min-1) was simultaneously infused to evaluate its effect on RIH. The antinociception of ciprofol was verified by measured paw withdrawal mechanical threshold (PWMT) and paw withdrawal thermal latency (PWTL). γ-aminobutyric acid type A receptor α2 subunit (α2GABAAR), N-methyl-d-aspartate receptor NR2B subunit (NR2B), calcium/calmodulin-dependent protein kinase II α (CaMKIIα), and phosphorylated CaMKIIα (P-CaMKIIα) in the spinal cord and hippocampus of rats were assessed by western blotting and immunohistochemistry. The results showed that ciprofol dose-dependently increased PWMT and PWTL values in RIH rats. Moreover, ciprofol upregulated α2GABAAR and downregulated NR2B and P-CaMKIIα in the rat spinal cord and hippocampus. Ciprofol alleviates RIH effectively, and the anti-hyperalgesic mechanisms may involve increasing α2GABAAR levels and decreasing NR2B and P-CaMKIIα levels in the spinal cord and hippocampus.

Comparison of the recovery time of remimazolam besylate and propofol for gastrointestinal endoscopy sedation in elderly patients.

Background: Recovery time is a crucial factor in ensuring the safety and effectiveness of both patients and endoscopy centers. Propofol is often preferred due to its fast onset and minimal side effects. Remimazolam is a new intravenous sedative agent, characterized by its rapid onset of action, quick recovery and organ-independent metabolism. Importantly, its effect can be specifically antagonized by flumazenil. The primary goal of this study is to compare the recovery time of remimazolam besylate and propofol anesthesia during endoscopic procedures in elderly patients. Methods: 60 patients aged 65-95 years who underwent gastrointestinal endoscopy were randomly and equally assigned to two groups: the remimazolam group (Group R) and the propofol group (Group P). The primary measure was the recovery time, defined as the time from discontinuing remimazolam or propofol until reaching an Observer's Assessment of Alertness and Sedation scale (OAA/S) score of 5 (responds readily to name spoken in normal tone). The time required to achieve an OAA/S score of 3 (responds after name spoken loudly or repeatedly along with glazed marked ptosis) was also recorded and compared. Results: The recovery time for Group R (2.6 ± 1.6 min) was significantly shorter than that for Group P (10.8 ± 3.0 min), with a 95% confidence interval (CI): 6.949-9.431 min, p <0.001. Similarly, the time to attain an OAA/S score of 3 was significantly less in Group R (1.6 ± 0.9 min) compared to Group P (9.6 ± 2.6 min), with a 95% CI: 6.930-8.957 min, p <0.001. Conclusion: Our study demonstrated that remimazolam anesthesia combined with flumazenil antagonism causes a shorter recovery time for elderly patients undergoing gastrointestinal endoscopy compared to propofol. Remimazolam followed by flumazenil antagonism provides a promising alternative to propofol for geriatric patients, particularly during gastrointestinal endoscopy.

Use of volatile anesthetics for sedation in the ICU during the COVID-19 pandemic: A national survey in France (VOL'ICU 2 study).

The COVID-19 pandemic has increased the number of patients in ICUs leading to a worldwide shortage of the intravenous sedative agents obligating physicians to find alternatives including inhaled sedation. Inhaled sedation in French ICU has been previously explored in 2019 (VOL'ICU study). This survey was designed to explore the use of inhaled sedation two years after our first survey and to evaluate how the COVID-19 pandemic has impacted the use of inhaled sedation. We designed a national survey, contacting medical directors of French ICUs between June and October 2021. Over a 50-item questionnaire, the survey covered the characteristics of the ICU, data on inhaled sedation, and practical aspects of inhaled ICU sedation for both COVID-19 and non-COVID-19 patients. Answers were compared with the previous survey, VOL'ICU. Among the 405 ICUs contacted, 25% of the questionnaires were recorded. Most ICU directors (87%) knew about the use of inhaled ICU sedation and 63% of them have an inhaled sedation's device in their unit. The COVID-19 pandemic increased the use of inhaled sedation in French ICUs. The main reasons said by the respondent were "need for additional sedative" (62%), "shortage of intravenous sedatives" (38%) and "involved in a clinical trial" (30%). The main reasons for not using inhaled ICU sedation were "device not available" (76%), "lack of familiarity" (60%) and "no training for the teams" (58%). More than 70% of respondents were overall satisfied with the use of inhaled sedation. Almost 80% of respondents stated that inhaled sedation was a seducing alternative to intravenous sedation for management of COVID-19 patients. The use of inhaled sedation in ICU has increased fastly in the last 2 years, and is frequently associated with a good satisfaction among the users. Even if the COVID-19 pandemic could have impacted the widespread use of inhaled sedation, it represents an alternative to intravenous sedation for more and more physicians.

Propofol suppresses cell proliferation in gastric cancer cells through NRF2‐mediated polyol pathway

Propofol, a widely used short‐acting intravenous sedative agent, has gradually gained attention due to the tumour‐suppressing role and non‐anaesthetic effect. Dysfunction of metabolic reprogramming has been recognised as a well‐documented factor for tumour progression. The aim of this study is to explore the effect of propofol on the polyol pathway in gastric cancer cells. In this study, we found that propofol treatment led to a significant downregulation of cell proliferation in BGC823 and GES‐1 cells, which was attributed to the decreased AR‐mediated polyol pathway. Both aldo‐keto reductase family 1, member B1 (AKR1B1) and AKR1B10 were significantly reduced in BGC823 and GES‐1 cells in response to propofol stimulation, leading to decreased AR activity and sorbitol level. Addition of sorbitol could reverse the inhibitory effect of propofol on cell proliferation. Mechanically, propofol treatment drastically inhibited phosphorylation and nuclear translocation of nuclear factor (erythroid‐derived 2)‐like 2 (NRF2), subsequently decreased the binding of NRF2 to AR promoter. Overexpression of NRF2 resulted in the recovery of AR expression in gastric cancer cell with propofol treatment. Taken together, these finding showed that propofol suppressed cell proliferation in BGC823 and GES‐1 cell through NRF2‐mediated polyol pathway, which would aid the selection of sedation for patients with gastric cancer.

Antiviral Efficacy of the Anesthetic Propofol against Dengue Virus Infection and Cellular Inflammation.

Propofol, 2,6-diisopropylphenol, is a short-acting intravenous sedative agent used in adults and children. Current studies show its various antimicrobial as well as anti-inflammatory effects. Dengue virus (DENV) is an emerging infectious pathogen transmitted by mosquitoes that causes mild dengue fever and progressive severe dengue diseases. In the absence of safe vaccines and antiviral agents, adjuvant treatments and supportive care are generally administered. This study investigated the antiviral effects of propofol against DENV infection and cellular inflammation by using an in vitro cell model. Treatment with propofol significantly inhibited DENV release 24 h postinfection in BHK-21 cells. Furthermore, it also blocked viral protein expression independent of the translational blockade. Propofol neither caused inhibitory effects on endosomal acidification nor prevented dsRNA replication. Either the proinflammatory TNF-α or the antiviral STAT1 signaling was reduced by propofol treatment. These results provide evidence to show the potential antiviral effects of the sedative propofol against DENV infection and cellular inflammation.

Characteristics of Intravenous Midazolam Sedation with Nitrous Oxide in Pediatric Dental Treatment

Midazolam is a short-acting benzodiazepine that is widely used in pediatric dental sedation. However, its clinical effectiveness as an intravenous sedative agent in children has not been widely documented. A retrospective study was conducted to evaluate the efficacy and safety of intravenous midazolam and nitrous oxide inhalation sedation in pediatric dental treatment.&lt;br/&gt;The subjects were 115 patients (118 cases) who received dental treatment under intravenous midazolam and nitrous oxide inhalation sedation. Demographic factors, general health status, sedation time, midazolam and nitrous oxide dosage, and success rate of sedation were evaluated from electronic medical records.&lt;br/&gt;Behavioral management was the main reason of choosing sedation. Mean duration of sedation was 56.7 minutes for surgical treatment, and 74.4 minutes for restorative treatment. The initial dosage of intravenous midazolam was 0.051 ± 0.019 mg/kg. In 34 cases (28.8%), additional midazolam of 0.036 ± 0.057 mg/kg was delivered during the treatment. The concentration of nitrous oxide was maintained between 40% and 50%. The success rate of sedation was 99% (n = 117). In 1 case, laryngospasm occurred and the patient was reversed with benzodiazepine antagonist, flumazenil.&lt;br/&gt;Intravenous midazolam sedation with nitrous oxide was shown to be clinically effective for the dental treatment in children, if administered by trained personnel and patients are carefully selected in accordance with guidelines.

COMPARATIVE STUDY OF INTRAVENOUS DEXMEDETOMIDINE AND MIDAZOLAM AS A PREOPERATIVE SEDATION UNDER SPINAL ANESTHESIA

INTRODUCTION: Preoperative anxiety is a frequent condition. Comfortable anesthesia induction and maintenance can be achieved by controlling anxiety. Various agents are used to relieve anxiety and provide sedation. We conducted this study to compare the sedative effects of dexmedetomidine versus midazolam for patients undergoing spinal anesthesia. AIMS AND OBJECTIVES : To compare the sedative effect of both drugs and observe intraoperative and postoperative comfort level, cardiovascular and respiratory changes and side effects of both drugs. MATERIALS AND METHODS: Sixty patients between 18-65 years of age requiring spinal anaesthesia for their procedures were selected randomly and division was done in 2 groups (Each group having 30 patients). Group D was given Inj. Dexmedetomidine at the dose of 1 mcg/kg within 10 mins in 100 ml NS and group M was given Inj Midazolam at the dose of 0.04 mg/kg in 100 ml NS within 10 mins. DISCUSSION: Anxiety is more common among young patients, women, and people with negative experience of anesthesia or fear that arises just before the operation and anesthesia my lead to psychological trauma. Various agents such as phenothiazines, bezodiazepines, barbiturates, opioids, propofol, ketamine, dexmedetomidine or clonidine and antihistamines are used to relieve anxiety and provide sedation. Midazolam is a benzodiazepine,commonly used as an intravenous sedative agent for pre-operative sedation. Dexmedetomidine is an alpha-2 agonist which acts on adrenoreceptors in many tissues including the nervous, cardiovascular and respiratory systems. Unlike midazolam, dexmedetomidine does not affect the ventilatory response to carbon dioxide, it also produces analgesia which could potentially alleviate pain.

COMPARATIVE STUDY OF INTRAVENOUS DEXMEDETOMIDINE AND MIDAZOLAM AS A PREOPERATIVE SEDATION UNDER SPINAL ANESTHESIA

INTRODUCTION: Preoperative anxiety is a frequent condition. Comfortable anesthesia induction and maintenance can be achieved by controlling anxiety. Various agents are used to relieve anxiety and provide sedation. We conducted this study to compare the sedative effects of dexmedetomidine versus midazolam for patients undergoing spinal anesthesia. AIMS AND OBJECTIVES : To compare the sedative effect of both drugs and observe intraoperative and postoperative comfort level, cardiovascular and respiratory changes and side effects of both drugs. MATERIALS AND METHODS: Sixty patients between 18-65 years of age requiring spinal anaesthesia for their procedures were selected randomly and division was done in 2 groups (Each group having 30 patients). Group D was given Inj. Dexmedetomidine at the dose of 1 mcg/kg within 10 mins in 100 ml NS and group M was given Inj Midazolam at the dose of 0.04 mg/kg in 100 ml NS within 10 mins. DISCUSSION: Anxiety is more common among young patients, women, and people with negative experience of anesthesia or fear that arises just before the operation and anesthesia my lead to psychological trauma. Various agents such as phenothiazines, bezodiazepines, barbiturates, opioids, propofol, ketamine, dexmedetomidine or clonidine and antihistamines are used to relieve anxiety and provide sedation. Midazolam is a benzodiazepine,commonly used as an intravenous sedative agent for pre-operative sedation. Dexmedetomidine is an alpha-2 agonist which acts on adrenoreceptors in many tissues including the nervous, cardiovascular and respiratory systems. Unlike midazolam, dexmedetomidine does not affect the ventilatory response to carbon dioxide, it also produces analgesia which could potentially alleviate pain.

Sedation During Neurocritical Care

AbstractSedation is an essential therapeutic strategy in the care of neurocritical patients. Intravenous sedative agents are the most widely used, with promising alternatives (dexmedetomidine, ketamine, and volatile agents) to propofol and midazolam arising. Studies designed to evaluate superiority and avoid biases are required. A neurological awakening test is safe in most patients. Potential risks and benefits of limiting deep sedation and daily interruption of sedation in these patients remain unclear. The aim of this review was to report recent clinical evidence on sedation in this subgroup of patients, focusing on its effects on clinical prognosis.

Evaluation of the Antibacterial Activities of the Agents Used for Sedation in Intensive Care Unit In Vitro Method

Objective Sedation in the intensive care unit is used for the treatment of anxiety and agitation. This study aims to investigate the in vitro antimicrobial activity of propofol, ketamine, thiopental, dexmedetomidine and midazolam doses used in practice for sedation purposes in the intensive care unit. Material and Methods In vitro antimicrobial activities of intravenous sedative agents were investigated by using the microdilution technique. Microorganisms used in the test were as follows: Escherichia coli (ATCC 25922), Yersinia pseudotuberculosis (ATCC 911), Pseudomonas aeruginosa (ATCC 27853), Enterococcus faecalis (ATCC 29212), Staphylococcus aureus (ATCC 25923), Bacillus cereus 709 ROMA, Mycobacterium smegmatis (ATCC 607), Candida albicans (ATCC 60193), Candida tropicalis (ATCC 13803) and Saccharomyces cerevisiae RSKK 251. Antibacterial experiments were performed in Mueller-Hinton Broth with a pH of 7.3, and antifungal analyses were carried out in buffered Yeast Nitrogen Base with a pH of 7.0. Results Only the preparation with ketamine showed antimicrobial activity, whereas no antimicrobial activity was detected in the preparations with the other agents. Conclusion Ketamine has antimicrobial activity in vitro on microorganisms frequently seen in the intensive care unit practice. However, there is a need for in vivo studies to evaluate the antimicrobial efficacy of ketamine in clinical use, its potential contribution to antibiotic therapy, and how well it can eliminate intensive care unit infections or benefit the patients with sepsis.

Physicochemical compatibility of dexmedetomidine with total parenteral nutrition

Rationale: Dexmedetomidine (DEX) is an α2-agonist used as an intravenous sedative agent in the intensive care setting. In certain cases, simultaneous administration of DEX and total parenteral nutrition (TPN) may be required. The aim of this study was to evaluate the physicochemical compatibility of DEX with TPN during simulated Y-site administration.

Considerations for submucosal midazolam administration in combination with oral and inhaled medications for sedation of pediatric dental patients.

Sedation allows patients to maintain their airway independently and respond appropriately to physical stimulation and verbal command while maintaining a minimum depressed level of consciousness. Drugs commonly used for sedation of pediatric dental patients include a combination of chloral hydrate, hydroxyzine, and nitrous oxide-oxygen. Midazolam is a benzodiazepine and currently one of the most commonly used intravenous sedative agents. It can be easily titrated to provide a wide range of sedation, from conscious sedation to deep sedation, and exhibits a wide safety margin without severe respiratory and circulatory depression. At an appropriate dose, it also decreases patient anxiety and induces amnesia. We found that the submucosal administration of midazolam combined with chloral hydrate provided increased sedative effects and decreased the postoperative vomiting response compared with conventional chloral hydrate administration, with no significant difference in physiological responses. The depth of sedation can be titrated using this technique.

Survey on choice of intravenous sedative agent at department of dental anesthesiology, Tokyo Dental College Chiba Hospital between 2010 and 2011.

Use of intravenous sedation is increasing in the management of dental patients in consideration of accompanying diseases and patient demand for comfort and safety. We surveyed choice of sedative agent and dosage on the basis of accompanying diseases or conditions in patients receiving treatment at the Department of Dental Anesthesiology, Tokyo Dental College Chiba Hospital between 2010 and 2011. A total of 5,256 patients were reviewed and divided into the following categories: 1) medically compromised patients (MC); 2) minor oral surgery (OS); 3) cerebral palsy (CP); 4) mental retardation (MR); 5) mental disorder (MD); and 6) dental phobia with/without gag reflex. The investigated variables were sex, age, weight, duration of sedation, and dosage of agent. Dosage of midazolam (M), M plus propofol (MP), and P alone was investigated. A total of 2,336 patients were managed by intravenous sedation during the study period. The combination of MP was used in approximately 63-79% of patients in all categories, except MC. Midazolam was used in approximately 47% in the MC group. Propofol was used in approximately 32% of patients in the MR group. Other agents (minor tranquilizers, analgesics, and so on) were used in approximately 12% in the OS group. The dose of M was approximately 0.05-0.06 mg/kg. When MP was administered, the dose of M showed no difference among groups. The dose of P, however, tended to be lower in the MC and CP groups than in the other groups. These results suggest that MP is chosen for intravenous sedation in most types of dental treatment.

A review of the practice of sedation with inhalational anaesthetics in the intensive care unit with the AnaConDa® device

The intensive care unit (ICU) environment is often perceived to be hostile and frightening by patients due to unfamiliar surroundings coupled with presence of numerous personnel, monitors and other equipments as well as a loss of perception of time. Mechanical ventilation and multiple painful procedures that often need to be carried out in these critically ill patients add to their overall anxiety. Sedation is therefore required not only to allay the stress and anxiety, but also to allow for mechanical ventilation and other invasive therapeutic and diagnostic procedures to be performed. The conventional intravenous sedative agents used in ICUs suffer from problems of over sedation, tachyphylaxis, drug accumulation, organ specific elimination and often lead to patient agitation on withdrawal. All this tend to prolong the ventilatory as well as ICU and hospital discharge time, which increase the risk for infection and add to the overall increase in morbidity, mortality and hospital costs. In 2005, the anaesthetic conserving device (AnaConDa®) was marketed for ICU sedation with volatile anaesthetic agents. A number of trials have shown the effectiveness of using volatile anaesthetic agents for ICU sedation with the AnaConDa device. Compared with intravenous sedatives, use of volatile anaesthetic agents have resulted in shorter wake up and extubation time, lesser duration of mechanical ventilation and faster discharge from hospitals. This review shall focus on the benefits, technical pre-requisites and status of sedation with volatile anaesthetic agents in ICUs with the AnaConDa® device.

Sedation of the Agitated, Critically Ill Patient Without an Artificial Airway

One of the most demanding and stressful situations is management of the agitated, unintubated, critically ill patient. Sedation often must be provided without a specific diagnosis, and the need for rapid airway control must be anticipated. No predictably safe and effective techniques are proven. The experience and skill of the physician managing the patient during sedation are the predictive factors for the best outcome. Even in expert hands, airway compromise and cardiovascular decompensation often occur in these very ill patients. Many techniques for sedation have been described. Treatment of pain followed by small boluses of intravenous sedative agents is a reasonable initial approach. Benzodiazepines have a good safety record and provide good amnesia. Other agents have been used, by themselves or in combination. Haloperidol may have a therapeutic advantage in the disoriented, agitated patient. Prolonged need for significant sedative medication usually mandates a secure airway. Once this is accomplished, the requirement for a continuously present airway expert at the bedside is removed. The standard for sedating a patient without an artificial airway requires a higher level of expertise than sedating a critically ill patient with an artificial airway.

A Comparative Evaluation of Propofol and Midazolam as Sedative Agents in Fiberoptic Bronchoscopy

Propofol, a new intravenous sedative agent, was investigated in 41 asthmatic patients undergoing day-case (outpatient) fiberoptic bronchoscopy. The study design was a randomized comparison between propofol and midazolam, which is a well-established intravenous sedative agent. The age, weight, and American Society of Anesthesiologists physical status and lung function of the two groups were not significantly different. Mean (SD) induction dose of propofol was 104.7 (30.1) mg with a maintenance dose of 121.9 (38.5) mg. Corresponding values of midazolam were 9.3 (3.1) mg and 3.7 (2.3) mg. The required level of sedation was achieved significantly faster with propofol, mean (SD) 125.4 (39.8) s, compared with midazolam, 179.4 (55.2) s (p < 0.001). Significantly faster recovery was noted with propofol compared with midazolam in terms of time to recall name and date of birth 2.3 (1.7) min vs 6.3 (8.6) min, (p < 0.045). Alertness scored with the digital symbol substitution test (DSST) returned to prebronchoscopy values in the propofol group at 30 min, DSST score = 35.9 (18.2) vs 13.4 (9.1), in the midazolam group (p < .0001) and was still significantly higher at 90 min-39.4 (17.9) and 23.1 (13.8) (p < 0.01). We conclude that propofol is a useful sedating agent in fiberoptic bronchoscopy with similar efficacy to midazolam but with a faster onset of action and a more rapid recovery. These represent significant advantages for day-case procedures.

Physostigmine reversal of drug-induced paradoxical excitement

Paradoxical excitement associated with intravenous conscious-sedation in a patient undergoing dental surgery was successfully reversed with 1.0 mg physostigmine. Physostigmine is felt to have exerted this effect by 2 mechanisms: (1) the re-establishment of homeostasis in the CNS via augmented cholinergic pathways with the net result being thalamacocortical excitation, and (2) cholinergically-mediated increase in cerebral blood flow increasing the rate of redistribution of the intravenous sedative agents used. The most commonly encountered side-effects of physostigmine used to reverse parodoxical excitement, emergence delirium, or prolonged narcosis are bradycardia, nausea, and/or vomiting. The incidence of these side-effects is low in doses, below 2.0 mg/70 kg. body weight.

Sédation par voie intraveineuse pour gastroscopie : comparaison midazolam-diazépam

Benzodiazepines are often used as premedication or intravenous sedative agents for endoscopies. The present study included 74 patients. It compared the sedative and amnestic properties of midazolam and diazepam, their relative potencies as well as the comfort of both the patient and the endoscopist during gastroscopy. The comparison has shown some statistically significant differences, allowing the following conclusions : 1) amnesia was more frequent with midazolam; 2) the dose requirement (in mg · kg −1) for adequate sedation was more important with diazepam, confirming the greater potency of midazolam; 3) generally speaking, sedation was excellent with both drugs.