Sedative Agents Research Articles

Three cases of difficulty in achieving definitive loss of consciousness with remimazolam

BackgroundRemimazolam is a novel, ultra-short-acting benzodiazepine used for general anesthesia. Because remimazolam is an emerging drug, the tolerance to remimazolam in benzodiazepine-taking patients has been unclear. Also, the efficacy of remimazolam in different races is not fully elucidated so far.Case presentationHere we experienced three cases in which high dose of remimazolam was needed for attempting to achieve appropriate anesthetic depth. Two of the three cases were of preoperatively benzodiazepine-taking patients. The other was a case of a Chinese patient. In all three cases, conversion to general anesthesia with propofol was necessitated.ConclusionsWhen signs of inadequate sedative effect of remimazolam are observed in patients of benzodiazepine users or of different races, conversion to another sedative agent such as propofol should be considered.

Intravenous dexmedetomidine, morphine, or a combination can result in gallbladder wall thickening; with no significant association with plasma histamine concentrations.

The gallbladder is routinely evaluated during ultrasonographic examinations in dogs. However, published studies describing the effects of sedative agents on gallbladder wall thickness are currently lacking. The aims of this prospective, blinded, randomized crossover pilot study were to test hypotheses that IV morphine would result in gallbladder wall thickening, that morphine administration would increase plasma histamine concentrations, and that combining IV morphine with dexmedetomidine would potentiate gallbladder wall thickening. Six healthy Beagle dogs were sedated with intravenous (IV) morphine 0.4mg/kg (group M), dexmedetomidine 7 μg/kg (group D), or a combination of the two (group MD). Physiologic parameters were measured at baseline and at regular intervals until the last ultrasonographic scan. Ultrasonographic scans were performed at baseline, 90 s, and at 5, 15, 30, 45, 60, 90, and 120 min. Plasma histamine samples were taken at baseline, 90 s, and 5 and 60 min. Cochran's Q-test was used to compare gallbladder wall thickening between groups, while the association between histamine plasma concentration and gallbladder wall thickness was compared with a mixed-effects model. Baseline gallbladder wall thickness was not significantly different between groups. Six of 18 treatments/dogs (33%) developed gallbladder thickening, with no difference between groups. There was no significant difference in baseline plasma histamine concentrations between groups, and no association between plasma histamine concentration and gallbladder wall thickness. Gallbladder wall thickening was observed in at least one dog in each group, therefore caution is recommended for gallbladder wall thickness ultrasonographic interpretation in dogs when these drugs have been administered.

Endotracheal intubation sedation in the intensive care unit.

Endotracheal intubation is one of the most common, yet most dangerous procedure performed in the intensive care unit (ICU). Complications of ICU intubations include severe hypotension, hypoxemia, and cardiac arrest. Multiple observational studies have evaluated risk factors associated with these complications. Among the risk factors identified, the choice of sedative agents administered, a modifiable risk factor, has been reported to affect these complications (hypotension). Propofol, etomidate, and ketamine or in combination with benzodiazepines and opioids are commonly used sedative agents administered for endotracheal intubation. Propofol demonstrates rapid onset and offset, however, has drawbacks of profound vasodilation and associated cardiac depression. Etomidate is commonly used in the critically ill population. However, it is known to cause reversible inhibition of 11 β-hydroxylase which suppresses the adrenal production of cortisol for at least 24 h. This added organ impairment with the use of etomidate has been a potential contributing factor for the associated increased morbidity and mortality observed with its use. Ketamine is known to provide analgesia with sedation and has minimal respiratory and cardiovascular effects. However, its use can lead to tachycardia and hypertension which may be deleterious in a patient with heart disease or cause unpleasant hallucinations. Moreover, unlike propofol or etomidate, ketamine requires organ dependent elimination by the liver and kidney which may be problematic in the critically ill. Lately, a combination of ketamine and propofol, “Ketofol”, has been increasingly used as it provides a balancing effect on hemodynamics without any of the side effects known to be associated with the parent drugs. Furthermore, the doses of both drugs are reduced. In situations where a difficult airway is anticipated, awake intubation with the help of a fiberoptic scope or video laryngoscope is considered. Dexmedetomidine is a commonly used sedative agent for these procedures.

Resilience State Security and the Role Sedative Agents in Military Pharmacy for State Defense in Future War

National defense is closely related to the role of an intelligence officer who is strong and capable of safeguarding the country's sovereignty. Intelligence covers many fields. One of those is medical intelligence. Mitragynine can be used as a sedative agent in a medical intelligence operation. To analyze a sedative agent in intelligent medical purposing of military aspect. This paper determines the role of Military Pharmacy in medical intelligence to support national defense using natural substances that contain a sedative agent. This research used narrative review method for this study obtained from Crossref, google scholar, PubMed, and Scopus range 2010 to 2021 in the English language, using the following terms: "National defense," "Medical intelligence," "Kratom" Mitragynine "Sedative agent" but we did not exclude out older works that were often cited and significant. Mitragynine binds to three types of receptors with varying affinities, with the highest affinity for μ, K, and δ-opioid receptors, which can be used as sedatives in medical intelligence to support national defense. Kratom is a plant endemic to Southeast Asia; this plant has a sedative effect at high doses. Kratom leaves contain thirty-seven alkaloid compounds. Both alkaloid compounds are Mitragynine and 7-hydroxymitragynine, both of which are included in the indole alkaloid compound, the main kratom compound. Plants that are used when facing the battlefield in maintaining national defense are very complex owned by the Indonesian state, that is the kratom plant which has a chance to strengthening people defense and security state facing of sixth generation war. This study needs to validate with more rigorous human clinical studies in the future.

Anaesthetic and Haemodynamic Effects of Dexmedetomidine vs Midazolam used as Premedication in Minor Obstetrics and Gynaecological ProceduresA Prospective Interventional Study

Introduction: Preoperative anxiety for any surgery is a frequent condition. It may lead to high catecholamine levels which increases blood pressure, heart rate and oxygen consumption. Various agents have been used for anxiolysis and sedation as premedicants. Aim: To compare the anaesthetic and haemodynamic effects of injection Dexmedetomidine and injection Midazolam used as premedication in minor Obstetrics and Gynaecological procedures. Materials and Methods: This was a prospective interventional study conducted from July 2016 to September 2017, on total number of 60 patients of American Society of Anaesthesiologist Physical Status (ASA PS I and II) enrolled for the study. They were randomised in two groups: Group A (n=30) for Injection (Inj.) Midazolam 0.04 mg/kg and Group B (n=30) for injection Dexmedetomidine 1mcg /kg injected over a period of 10 minutes prior to General Anaesthesia. After appropriate monitoring like, Heart Rate (HR), Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), Mean arterial Pressure (MAP), Peripheral oxygen saturation (SpO2 ), Respiratory Rate (RR) were noted during the procedure at interval of 5 minutes till 30 minutes and, Ramsay Sedation Score (RSS) and Visual Analogue Scale (VAS) in postoperative period for 1 hour at interval of 15 minutes. The significance between all variables and amongst the two groups was calculated by Chi-square test, Repeated measure Analysis of Variance (ANOVA) test and Independent sample t test. Results: It was observed that mean HR, SBP (p<0.05), DBP (p<0.05) and MAP (p<0.05 ) decreased significantly in group B. The RR (p<0.05) was significantly decreased in group B. There was no significant difference in SpO2 (p=0.4) value in both the groups. VAS (p<0.05) of group B patients was significantly reduced in the postoperative period but there was no significant difference in RSS score (p=0.1) at 45 and 60 minutes in both the groups. Conclusion: Dexmedetomidine is more effective as a sedative agent than injection Midazolam when used in minor gynaecological procedures. Though Dexmedetomidine caused significant reduction in SBP, DBP and HR, it maintained haemodynamic stability well without causing any adverse effects.

Insights into the medicinal chemistry of heterocycles integrated with a pyrazolo[1,5-a]pyrimidine scaffold.

Pyrazolo[1,5-a]pyrimidines are the dominant motif of many drugs; for instance, zaleplon and indiplon are sedative agents and ocinaplon was identified as an anxiolytic agent. The importance of this class of compounds lies in its varied and significant biological activities, and accordingly, considerable methods have been devised to prepare these compounds. Hence, other derivatives of this class of compounds were prepared by substitution reactions with different nucleophiles exploiting the activity of groups linked to the ring carbon and nitrogen atoms. The methods used vary through the condensation reactions of the aminopyrazoles with 1,2-allenic, enaminonitriles, enaminones, 1,3-diketones, unsaturated nitriles, or unsaturated ketones. Alternatively, these compounds are prepared through the reactions of acyclic reagents, as these methods were recently developed efficiently with high yields. The current review highlighted the recent progress of the therapeutic potential of pyrazolo[1,5-a]pyrimidines as antimicrobial, anticancer, antianxiety, anti-proliferative, analgesic, and antioxidant agents, carboxylesterase, translocator protein and PDE10A inhibitors, and selective kinase inhibitors.

Hemodynamic and ventilatory changes in pediatric patients with special needs: A comparative clinical study.

Very limited data are available on the hemodynamic and ventilatory changes during sedation and general anesthesia using bispectral index (BIS) monitoring in intellectually disabled children. The purpose was to determine the hemodynamic and ventilatory changes after propofol and sevoflurane administration in children with special needs (CSN) versus healthy children (HC) during dental treatment. Forty pediatric patients needing dental treatment were allocated into two groups: children without systemic disease (healthy children [HC]) and mentally disabled children (children with special needs [CSN]). Sevoflurane in oxygen (100% oxygen, 5 l/min) and continuous propofol infusion (target-controlled infusion [TCI], 2 µg/ml) were used as sedative agents, and 2% lidocaine with 1:80,000 adrenaline was used as local anesthesia in both groups. Heart rate (HR), oxygen saturation (SaO2), respiratory rate (RR), exhaled carbon dioxide (CO2), blood pressure (BP) and bispectral monitoring (BIS) values were recorded during the entire dental treatment procedure. A statistically significant decrease in systolic BP, diastolic BP and RR was observed, with no significant differences between the healthy and disabled groups. In contrast, the HR and BIS values were lower in the CSN group than in the healthy patients (p ≤ 0.05). Patients with special needs had lower HR and BIS values than healthy patients, while BP, SaO2 and exhaled CO2 showed similar results in both groups. Key words:Bispectral index, hemodynamic changes, ventilatory changes, pediatric patients, special needs.

Efficacy of nitrous oxide-oxygen inhalation versus oral midazolam-promethazine as sedative agents in pediatric patients: a comparative study

Background Managing difficult and uncooperative pediatric dental patients is a challenging task. Conscious sedation has been propagated as a pharmacological means for handling such situations.Objective To evaluate the effects of sedation using nitrous oxide-oxygen inhalation versus oral midazolam-promethazine in pediatric patients.Patients and methods A total of 100 pediatric patients were selected and divided into two equal categories: group 1 (midazolam-promethazine) and group 2 (N2O-O2). Ethical committee approval was obtained, and patients were assessed. Data collected were analyzed using an unpaired t test.Results Duration of sedation was found to be statistically significant, and a higher duration was found for group 1. No significant differences were noted in the behavior rating scale with either of the combinations and in pulse oximeter readings.Conclusion Midazolam/promethazine is better in inducing longer sedation than N2O/O2.

Psychiatric management of Patients in intensive care units.

Psychiatric management of Patients in intensive care units.

A hypothetic review on “HELIOX: The medium for conscious sedation in severely ill patients”

The uncooperativeness on behalf of the child has been conceptualized in different ways from time to time in the field of dentistry. The early signs of dental phobia are denoted by dental fear and dental anxiety which influence the daily living and resultin prolonged avoidance oftreatment. Thus, an obstacle to the success and quality of dental care. Various behavioral techniques are applied for management of a young, fearful, and uncooperative pediatric dental patients. However, there exist a portion of pediatric patients who are febrile andunable to tolerate the fearful circumstances and may require alternative approaches, such as conscious sedation or general anesthesia. General anesthesia being the most common modality for management of the uncooperative children but, the risk of morbidity and mortality associated are considerably higher compared to conscious sedation. The aim of this review is to provide a hypothetic view on use of HELIOX as an agent for conscious sedation.

Awake craniotomy with dexmedetomidine during resection of brain tumours located in eloquent regions.

An awake craniotomy (AC) is the gold standard for the resection of supra-tentorial brain tumours in eloquent areas. Intraoperative monitoring "on-demand" of essential eloquent brain functions and the increasing need to preserve higher intellectual functions during surgery requires aunique anaesthetic approach during AC. Dexmedetomidine is considered the first-choice pharmacological agent for sedation during AC. Twenty-six patients with asingle brain tumour located in areas of eloquent brain function were enrolled in this prospective study. The patients underwent AC under conscious sedation. Motor-evoked potentials and brainstem-evoked auditory potentials were measured using neurophysiological tests during surgery to assess brain potentials. Intraoperative brain relaxation was reached using amodified Bristow scale. Neuromonitoring and psychological tests were maintained until meningeal closure. All operations were carried out successfully, and no reoperations were needed. No significant impact on circulatory and respiratory parameters was observed during conscious sedation based on dexmedetomidine. Neither instrumental airway support nor conversion to general anaesthesia was necessary. Brain relaxation was good in 84% of cases. Intraoperative epileptic episodes were observed in 15% of the patients. Neuro-logical and psychological monitoring was satisfactory. Unaltered muscle force was observed postoperatively in 88% of the patients. AC performed under conscious sedation, and dexmedetomidine infusion without instrumental airway support, was safe and well-tolerated by patients with comfortable physiological sleep for most of the procedure. This approach to AC was associated with minimal risk of perioperative adverse events and may be particularly beneficial in patients with severe comorbidities.

Investigation of the nephroprotective effect of dexmedetomidine on colistin-induced nephrotoxicity in rats.

There are very few studies in the literature focusing on whether dexmedetomidine exerts a protective effect on colistin nephrotoxicity. Our study aims to investigate the nephroprotective effect of dexmedetomidine in an experimental model of nephrotoxicity in rats. The control group was administered saline (SF) intraperitoneally twice a day. The colistin group received an intraperitoneal (ip) injection of 10 mg/kg of colistin twice a day. The DX10 group received 10 mg/kg of colistin 20 minutes after the intraperitoneal injection of 10 mcg/kg of dexmedetomidine. The DX20 group received 10 mg/kg of colistin 20 minutes after the intraperitoneal injection of 20 mcg/kg of dexmedetomidine. Applications were continued for 7 days, twice a day. All rats were sacrificed on the 8th day after blood and kidney tissue samples were taken. BUN, Creatine, KIM-1 and Endothelin-1 were studied in blood samples. There was a significant difference in the median values of Urea, BUN and Creatine between the groups (p<0.001, p<0.001, p<0.001, respectively). There was a significant difference in the median values of KIM-1 and Endothelin-1 between the groups (p=0.009, p=0.001, respectively). A significant difference was observed between the histopathological scores of the groups (p<0.001). Dexmedetomidine significantly decreased the elevated levels of BUN, Creatinine, KIM-1, and Endothelin-1 induced by colistin. Dexmedetomidine, at both doses, histopathologically prevented apoptosis and reduced the number of necrotic cells in the kidneys. Dexmedetomidine provides renoprotective effects, therefore it is a valuable sedation agent for clinicians working in intensive care units (Tab. 2, Fig. 4, Ref. 19). Text in PDF www.elis.sk Keywords: rat, colistin, nephrotoxicity, dexmedetomidine.

COMPARISON OF ORAL PREMEDICATION BETWEEN MIDAZOLAM AND CLONIDINE FOR GENERALANAESTHESIA IN ELECTIVE OPEN ABDOMINAL SURGERY

Anxiety is common in patients undergoing even minor surgery and it increases as the surgical event approaches. Treating anxiety not only improves patient satisfaction but it also decreases the hospital stay and offers good recovery. It decreases the surgical stress response, incidences of postoperative nausea and vomiting. The most commonly used agents for anxiolysis in Premedication are Benzodiazepines and Alpha 2 agonists. This study is a double blinded comparison of oral Midazolam and Clonidine as anxiolytic and sedative agent for general anaesthesia in elective open abdominal surgery. Laryngoscopy and intubation cause intense sympatho-adrenal stimulation resulting in tachycardia, rise of systolic BP, diastolic BP, Mean Arterial Blood Pressure, decrease in coronary perfusion due to decrease in diastole duration, increase in various cardiac dysrhythmias. In cardiac compromised patients this stress reaction may result in myocardial infarction and heart failure. Also there is a chance of bleeding in brain following rupture of any pre-existing cerebral aneurysm. The multi modal approach of GA encompasses use of anti-anxiety medication, opioids, volatile anaesthetics, local anaesthetics (locally , intravenously, regionally), vasodilators, CCB, Beta 1 adrenoceptor blocker, Alpha 2 adrenoceptor agonists, in combination, with varying degrees of success. METHOD: In this randomized prospective double blinded comparative study 80 patients were randomly divided into 2 groups namely Group M and Group C. Group M received Tablet Midazolam 7.5 mg while Group C received Tablet Clonidine 150 mcg, given orally, preoperatively 90 minutes before induction. Group M showed better sedation after induction, however, Group C showed better hemodynamic stability therefore had better attenuation of sympatho-adrenal response. Conclusion: Considering all parameters, it was observed that Group C was signicantly more efcacious in attenuation of sympatho-adrenal response whereas Group M showed signicantly better sedation.

Midazolam But not Propofol for Sedation Impairs Long Term Spatial Memory in Mice

Aim and Background: Sedation may alter memory and learning. This study is designed to investigate the effects of short-acting sedative agents, propofol and midazolam, on learning and memory in mice. Materials and Methods: Thirty male, adult Swiss-albino mice were randomly assigned into three groups as control, midazolam and propofol groups (n=10, for each). Experiments on learning and memory were started 72 hours after the intraperitoneal injections. Learning and short term memory development in mice were evaluated by Morris Water Maze conducted for five consecutive days, and on the 19th day long term memory formation was evaluated by the same experimental set up. Time for the mice to find the escape platform (latency), total distance covered and swimming speed were recorded and evaluated statistically. Results: Propofol and midazolam administrations were found to increase the latency. In addition, midazolam was found to impair memory development, when compared to other two groups (p &lt; 0,01). Swimming speed and distance covered as indicators of the motor activity decreased gradually from the beginning, however there was no statistically difference between the groups (p &gt; 0.05). Conclusion: Use of midazolam and propofol prolonged the latency on the first three days. Midazolam was also found to affect the memory development negatively.

Comparison of Intra and Post-operative Sedation Efficacy of Dexmedetomidinemidazolam and Dexmedetomidine-propofol for Major Abdominal Surgery.

The effectiveness and side effects of dexmedetomidine (DEX) in combination with midazolam and propofol have not been comparatively studied in a single clinical trial as sedative agents to general anesthesia before. The objective of this study is to compare intra and post-operative sedation between DEX-Midazolam and DEX-Propofol in patients who underwent major abdominal surgery on the duration of general anesthesia, hemodynamic and sedation effect. This prospective, randomized, double-blinded clinical trial included 50 patients who were 20 to 60 years of age and admitted for major abdominal surgery. The patients were randomly assigned by a computer-generated random numbers table to sedation with DEX plus midazolam (DM group) (n=25) or DEX plus propofol (DP group) (n=25). In the DM group, patients received a bolus dose of 0.1 mg/kg of midazolam and immediately initiated the intravenous (i.v.) infusion of DEX 1 μg/kg over a 10 min and 0.5 μg/kg/hr by continuous i.v. infusion within operation period. In the DP group, patients received pre-anesthetic i.v. DEX 1 μg/kg over 15 min before anesthesia induction and 0.2-1 μg/kg/hr by continuous i.v. infusion during the operative period. After preoxygenation for at least 2 min, during the surgery, patients received propofol infusion dose of 250 μg/kg/min for 15 min then a basal infusion dose of 50 μg/kg/min. The bispectral index (BIS) value, as well as mean arterial pressure (MAP), heart rate (HR), respiratory rate (RR), oxygen saturation (SaO2), percutaneous arterial oxygen saturation (SpO2) and end-tidal carbon dioxide tension (ETCO2) were recorded before anesthesia (T0), during anesthesia (at 15-min intervals throughout the surgical procedure), by a blinded observer. Evidence of apnea, hypotension, hypertension and hypoxemia were recorded during surgery. The hemodynamic changes, including HR, MAP, BIS, VT, SaO2, and RR had a downward tendency with time, but no significant difference was observed between the groups (P>0.05). However, the two groups showed no significant differences in ETCO2 and SPO2 values in any of the assessed interval (P>0.05). In this study, the two groups showed no significant differences in the incidence of nausea, vomiting, coughing, apnea, hypotension, hypertension, bradycardia and hypoxemia (P>0.05). Respiratory depression and serious adverse events were not reported in either group. Extubation time after surgery was respectively 6.3 ± 1.7 and 5.8 ± 1.4 hr. in the DM and DP groups and the difference was not statistically significant (P= 0.46). Our study showed no significant differences between the groups in hemodynamic and respiratory changes in each of the time intervals. There were also no significant differences between the two groups in the incidence of complication intra and post-operative. Further investigations are required to specify the optimum doses of using drugs which provide safety in cardiovascular and respiratory system without adverse disturbance during surgery.

Cyclic Vomiting Syndrome in Pediatric Patients: A Review of Therapeutics.

Cyclic vomiting syndrome (CVS) is a functional gastrointestinal disorder that can present quite a challenge to clinicians caring for children with this complex disease. Different therapeutic interventions are recommended for prophylaxis and acute abortive therapy for a CVS attack. The aim of this review is to summarize therapeutic treatment recommendations from the 2008 North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHN) Consensus Statement on the Diagnosis and Management of Cyclic Vomiting Syndrome and discuss studies contemporary to this expert recommendation. After an extensive search of medical databases, 8 studies that evaluated therapeutic treatments for CVS were identified. Amitriptyline and cyproheptadine remain the standard of care for prophylaxis. Nutritional supplements such as carnitine and coenzyme Q10 have shown efficacy in decreasing episodes and severity in small studies with high tolerability among patients. The combination of ondansetron and sumatriptan are recommended for abortion of an acute vomiting episode, but other agents such as aprepitant and sedative agents can be considered when vomiting is refractory to initial treatments.

Nocturnal dexmedetomidine alleviates post\u2013intensive care syndrome following cardiac surgery: a prospective randomized controlled clinical trial

BackgroundDexmedetomidine is a sedative agent that may have the potential to reduce the risk of post-intensive care syndrome (PICS). This study aimed to establish whether prophylactic nocturnal dexmedetomidine safely reduces postoperative PICS incidence and to develop an easy-to-use model for predicting the risk of PICS following cardiac surgery.MethodsThis was a single-center, double-blind, randomized, prospective, placebo-controlled trial. Patients undergoing cardiac surgery were randomly assigned (1:1) to dexmedetomidine or placebo (normal saline) groups between January 2019 and July 2020. Dexmedetomidine or a similar volume of saline was administered, with an infusion rate up to 1.2 μg/kg/h until the RASS remained between − 1 and 0. The primary study endpoint was PICS incidence at 6 months follow-up, as defined by cognitive, physical, or psychological impairments.ResultsWe assessed 703 individuals for eligibility, of whom 508 were enrolled. Of these, there were 251 in the dexmedetomidine group and 257 in the placebo group that received the trial agent, forming a modified intention-to-treat population. PICS incidence at 6-month follow-up was significantly decreased in the dexmedetomidine group (54/251, 21.5%) relative to the placebo group (80/257, 31.1%) (odds ratio [OR] 0.793, 95% CI 0.665–0.945; p = 0.014). Psychological impairment was significantly reduced in the dexmedetomidine group relative to the placebo group (18.7% vs. 26.8%, OR 0.806, CI 0.672–0.967, p = 0.029). However, dexmedetomidine treatment was associated with a higher rate of hypotension. A nomogram revealed that age, education, a medical history of diabetes and smoking, dexmedetomidine treatment, postoperative atrial fibrillation, and sequential organ failure assessment scores at 8 h post-surgery were independent predictors of PICS.ConclusionsProphylactic nocturnal dexmedetomidine administration significantly reduced PICS incidence by a marked reduction in psychological impairment within a 6-month follow-up period.Trial registrationChiCTR, ChiCTR1800014314. Registered 5 January 2018, http://www.chictr.org.cn/index.aspx

Use of advanced intravenous conscious sedation techniques in complex oral surgery procedures: Comparison of midazolam, midazolam‐propofol and midazolam‐propofol‐alfentanil combinations

AbstractAimThis retrospective observational study evaluates the safety and efficacy of intravenous sedation using midazolam only or combinations of two or three drugs including propofol and alfentanil for complex dental surgery such as implant placement or sinus augmentations.MethodsThe study analyses 60 patients aged 42–79 who required advanced sedation techniques for complex oral surgery procedures. Twenty patients had midazolam only (M), 10 patients a 2‐drug combination of midazolam and propofol (MP) and a third group of 30 patients had the combination of midazolam, propofol and alfentanil (MAP). The last two regimens were carried out under the supervision of a dedicated consultant anaesthetist.ResultsHigher mean minimum heart rate (beats/min) was observed in the midazolam group compared to the group sedated with the three‐drug regimen (p &lt; 0.05). The time between the last drug administration (LDA) and end of surgery (EOS) was significantly longer (p &lt; 0.005) in group M (≤45 mins) compared to the other two sedation groups MP and MAP (≤15 min). The final titration of midazolam of 11.2 ± 4 mg (5–20 mg) was significantly greater in group M than in either of group MP or MAP (p &lt; 0.05).ConclusionIn patients requiring conscious sedation to undergo complex and lengthy oral surgery, a combination of agents (midazolam, propofol and alfentanil) can provide a predictable steady state of sedation up to the end of the surgery resulting in better operating conditions for the surgeon and improved patient co‐operation. The shorter duration of action drugs propofol and alfentanil improved haemodynamic stability, sedation quality and reduce the final doses of each sedative agent.

Abstract 9112: Dexmedetomidine Reduces Incidences of Ventricular Arrhythmias in Adults

Introduction: Ventricular arrhythmias, including ventricular tachycardia (VT) and ventricular fibrillation (VF), are associated with high mortality and morbidity. Sedation through agents like benzodiazepines, propofol, and opiates are mainstays of treatment but are limited by side effects. Dexmedetomidine is a α2-presynaptic receptor agonist with a safe and efficacious sedative profile. Furthermore, it has been recently proposed as a sedative agent in VT due its additional antiarrhythmic properties. Methods: A systemic literature review was conducted of MEDLINE, EMBASE, Cochrane, and Scopus. Randomized controlled trials comparing the incidence of ventricular arrhythmias of dexmedetomidine with placebo or an alternative sedative agent were included. Two researchers independently extracted the data and performed quality assessments. Results: We identified 6 studies that met the selection criteria. Our meta-analysis demonstrated significant reduction of the overall risk of ventricular arrhythmias in patients receiving dexmedetomidine (RR 0.35, 95% CI 0.16, 0.76). Furthermore, there was no significant difference in risk of mortality (RR 0.59 95% CI 0.12, 3.02). Dexmedetomidine also significantly increased the risk of bradycardia (RR 2.78 95% CI 2.00, 3.87). There was no significant difference in risk of tachycardia (RR 0.59 95% CI 0.12, 3.02) or hypotension (RR 1.07 95% CI 0.64, 1.81). Conclusions: Our study demonstrates that the dexmedetomidine reduces the risk of VA by 65% compared to control. Further prospective research is necessary to clarify the antiarrhythmic and sedative properties of dexmedetomidine and its potential effect on patient outcomes.

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.