Toxicity of benzodiazepines in the treatment of insomnia disorders in older adults: a systematic literature review.

AIM: To review the literature data on the prevalence of benzodiazepines abuse and poisoning in older adults; the prevalence of polypharmacy with benzodiazepines in this demographic; and determine whether benzodiazepine anxiolytics or hypnotics were more frequently implicated in the cases of abuse and poisoning. METHODS: We searched PubMed and Scopus for relevant studies published from January 1, 2013, to May 1, 2023. Twelve studies were included in the final selection. RESULTS: The review highlights the diverse prevalence rates of benzodiazepine abuse and poisoning in the older adult population. Benzodiazepine anxiolytics were more frequently associated with negative outcomes than benzodiazepine hypnotics. Concurrent use of benzodiazepines, benzodiazepine-related medications, and opioids was reported, although these medications were not the only ones commonly used by the elderly. CONCLUSION: It is essential to increase awareness about adhering to prescribed pharmacological therapies to mitigate issues related to drug abuse and poisoning among older adults.

Effects of different doses of remimazolam on hemodynamics during general anesthesia in patients with septic shock.

OBJECTIVE: The stability of hemodynamics plays a vital role in the process of anesthesia induction for patients with septic shock. As a new-type benzodiazepine, remimazolam has numerous advantages, including rapid induction, rapid recovery, stable hemodynamics, and mild respiratory depression. Nevertheless, reports about the effects of remimazolam on hemodynamics in patients with septic shock are still limited. The study aimed to evaluate the effects that different doses of remimazolam have on hemodynamics in inducing general anesthesia in patients with septic shock. PATIENTS AND METHODS: Admitted to the intensive care unit of our hospital from January 2023 to June 2023, 75 patients with septic shock caused by acute appendicitis-induced sepsis were selected as observation subjects. They were randomly assigned to receive low-dose [0.2 mg/(kg·h)], medium-dose [0.3 mg/(kg·h)], and high-dose [0.4 mg/(kg·h)] remimazolam by using a random number table, with 25 patients in each group. Their intraoperative conditions were recorded, including operation duration, intraoperative hemorrhage volume, intraoperative transfusion volume, and decannulation time. Hemodynamic parameters, including mean arterial pressure (MAP), heart rate (HR), cardiac index (CI), and stoke volume index (SVI) were collected at seven-time points (T0: before induction; T1: before intubation; T2: after intubation; T3: the start of operation; T4: 15 min after operation; T5: 30 min after operation; T6: the end of operation). We also compared hepatic and renal function indexes, including blood urea nitrogen (BUN), serum creatinine (sCr), procalcitonin (PCT), white blood cells (WBC), tumor necrosis factor-α2 (TNF-α2), and Interleukin-6 (IL-6), of the three groups of patients before operation and 1, 3, 5, 7 days after operation. In addition, the incidence of adverse reactions in the three groups was recorded and compared. RESULTS: During remimazolam induction, the number of patients with intraoperative need for rescue remimazolam in the medium-dose and high-dose groups was significantly lower than in the low-dose group (p < 0.05). In terms of hemodynamic indexes, MAP in the high-dose group at T2 was lower than that at T0 (p < 0.05), and MAP at T2 was significantly lower in the high-dose group than that in the medium-dose group (p < 0.05). Furthermore, MAP at T4 in the medium-dose and high-dose groups declined compared with the low-dose group (p < 0.05). There were no significant differences in HR, CI, and SVI at different time points among the three groups (p > 0.05), but levels of HR and SVI decreased and CI increased after anesthesia compared with those before operation. Additionally, in comparison with the levels before operation, levels of sCR, BUN, PCT, WBC, TNF-α, and IL-6 were higher on postoperative days 1, 3 (p < 0.05) and lower on postoperative day 7 (p < 0.05). After the operation, both levels of BUN and sCR in the medium-dose and high-dose groups were lower than those in the low-dose group (p < 0.05). CONCLUSIONS: Remimazolam is safe and effective for inducing general anesthesia in patients with septic shock. Low, medium, and high doses of remimazolam can maintain a stable hemodynamic state, and the recovery of hepatic and renal function is certain to depend on the dose.

Apnea during moderate to deep sedation using continuous infusion of remimazolam compared to propofol and dexmedetomidine: A retrospective observational study.

Remimazolam's rapid onset and offset make it an innovative sedative for use during regional anesthesia. However, its respiratory safety profile is not well understood. We compared the continuous infusion of remimazolam with commonly used sedatives, propofol and dexmedetomidine, after regional anesthesia. In this retrospective study, the incidence of apnea (>10 seconds) was assessed in patients who underwent orthopedic surgery under regional anesthesia and received moderate to deep sedation using continuous infusion of remimazolam (group R: 0.1 mg/kg in 2 minutes followed by 0.5 mg/kg/hr). The incidence was compared with that of propofol (group P: 2-3 µg/mL target-controlled infusion) and dexmedetomidine (group D: 1 µg/kg in 10 minutes followed by 0.4-1 µg/kg/hr). Propensity score weighted multivariable logistic regression model was utilized to determine the effects of the sedative agents on the incidence of apnea. A total of 634 (191, 278, and 165 in group R, P, and D) cases were included in the final analysis. The incidence of apnea was 63.9%, 67.3%, and 48.5% in group R, P, and D, respectively. The adjusted odds ratios for apnea were 2.33 (95% CI, 1.50 to 3.61) and 2.50 (95% CI, 1.63 to 3.85) in group R and P, compared to group D. The incidence of apnea in patients receiving moderate to deep sedation using continuous infusion of remimazolam with dosage suggested in the current study was over 60%. Therefore, careful titration and respiratory monitoring is warranted.

Chlordiazepoxide against signalling, receptor and regulatory proteins of breast cancer: a structure-based in-silico approach.

Among the most prevalent forms of cancer are breast, lung, colon-rectum, and prostate cancers, and breast cancer is a major global health challenge, contributing to 2.26 million cases with approximately 685,000 deaths worldwide in 2020 alone, typically beginning in the milk ducts or lobules that produce and transport milk during lactation and it is becoming challenging to treat as the tissues are developing resistance, which makes urgent calls for new multitargeted drugs. The multitargeted drug design provides a better solution, simultaneously targeting multiple pathways, even when the drug resists one, it remains effective for others. In this study, we included four crucial proteins that perform signalling, receptor, and regulatory action, namely- NUDIX Hydrolases, Dihydrofolate Reductase, HER2/neu Kinase and EGFR and performed multitargeted molecular docking studies against human-approved drugs using HTVS, SP and extra precise algorithms and filtered the poses with MM\GBSA, suggested a benzodiazepine derivative chlordiazepoxide, used as an anxiolytic agent, can be a multitargeted inhibitor with docking and MM\GBSA score ranging from - 4.628 to - 7.877 and - 18.59 to - 135.86 kcal/mol, respectively, and the most interacted residues were 6ARG, 6GLU, 3TRP, and 3VAL. The QikProp-based ADMET and DFT computations showed the suitability and stability of the drug candidate followed by 100 ns MD simulation in water and MMGBSA on trajectories, resulting in stable performance and many intermolecular interactions to make the complexes stable, which favours that chlordiazepoxide can be a multitargeted breast cancer inhibitor. However, experimental validation is needed before its use.

Comparison of efficacy and safety of equivalent doses of remimazolam versus propofol for gastroscopy anesthesia in elderly patients.

Remimazolam, a novel intravenous anesthetic, has been proven to be safe and efficacious in the gastroscopy setting among the elderly. However, reports comparing the effectiveness and safety of using equivalent doses of remimazolam with propofol have not been seen. The aim of this study was to compare the sedation efficacy and safety of the 95% effective doses (ED95) of remimazolam versus propofol combined with sufentanil in the gastroscopy setting among the elderly. In the first step of this two-step study, a modified up-and-down method was used to calculate the ED95 of remimazolam and propofol when combined with 0.1 µg/kg sufentanil in inhibiting body movement of elderly patients undergoing gastroscopy. In the second step, ED95 of both agents calculated in the first step were administered, endpoints of efficacy, safety, and incidence of adverse events were compared. A total of 46 individuals completed the first step. The ED95 of remimazolam was 0.163 mg/kg (95% CI 0.160-0.170 mg/kg), and that of propofol was 1.042 mg/kg (95% CI 1.007-1.112 mg/kg). In the second step, 240 patients completed the trial. The anesthetic effective rates of the remimazolam group and the propofol group were 78% and 83%, respectively, with no statistical difference (P = 0.312). Patients in the remimazolam group had more stable circulatory functions (P < 0.0001) and a lower incidence of pain on injection (3.3% vs. 19.5%, P < 0.0001). The incidence of hypotension was low in the remimazolam versus propofol group (15.6% vs. 39.0%, P < 0.0001). Overall adverse event was low in the remimazolam versus propofol group (21.3% vs. 62.7%, P < 0.0001).In this study, we found that when anesthesia was administered to elderly gastroscopy patients based on 95% effective doses of remimazolam and propofol, remimazolam was as effective as propofol, but was safer with a lower incidence of adverse events.Study registration: Chinese Clinical Trial Registry, ChiCTR2000034234. Registered 29/06/2020, https://www.chictr.org.cn .

The Safety and Efficacy of Remimazolam Compared to Dexmedetomidine for Awake Tracheal Intubation by Flexible Bronchoscopy: A Randomized, Double-Blind, Controlled Trial.

Background: Remimazolam is a novel ultra-short-acting benzodiazepine sedative that has the potential to be an alternative for procedural sedation due to its rapid sedation and recovery, no accumulation effect, stable hemodynamics, minimal respiratory depression, anterograde amnesia effect, and specific antagonist. Here, we aimed to compare the safety and efficacy of remimazolam with dexmedetomidine for awake tracheal intubation by flexible bronchoscopy (ATI-FB). Methods: Ninety patients scheduled for ATI-FB were randomly divided into three groups, each consisting of 30 cases: dexmedetomidine 0.6 µg/kg + sufentanil (group DS), remimazolam 0.073 mg/kg + sufentanil (group R1S), or remimazolam 0.093 mg/kg + sufentanil (group R2S). The primary outcome was the success rate of sedation. Secondary outcomes were MOAA/S scores, hemodynamic and respiratory parameters, intubation conditions, intubation time, tracheal intubation amnesia, and adverse events. Results: The success rates of sedation in groups R2S and DS were higher than that in group R1S (93.3%, 86.7%, respectively, vs 58.6%; P = 0.002), and intubation conditions were better than those in group R1S (P < 0.05). Group R2S had shorter intubation times than groups R1S and DS (P = 0.003), and a higher incidence of tracheal intubation amnesia than group DS (P = 0.006). No patient in the three groups developed hypoxemia or hypotension, and there were no significant differences in oligopnea, PetCO2, or bradycardia (P > 0.05). Conclusion: In conclusion, both DS and R2S had higher success rates of sedation, better intubation conditions, and minor respiratory depression, but R2S, with its shorter intubation time, higher incidence of anterograde amnesia, and ability to be antagonized by specific antagonists, may be a good alternative sedation regimen for patients undergoing ATI-FB.

Comparison of Remimazolam and Propofol on Postoperative Delirium in Elderly Patients Undergoing Radical Resection of Colon Cancer: A Single-Center Prospective Randomized Controlled Study.

BACKGROUND We compared the effect of remimazolam and propofol intravenous anesthesia on postoperative delirium in elderly patients undergoing laparoscopic radical resection of colon cancer. MATERIAL AND METHODS One hundred patients undergoing elective radical operation of colon cancer under general anesthesia were divided into a remimazolam group (group R) and propofol group (group P) by a random number table method. During anesthesia induction and maintenance, group R was intravenously injected with remimazolam to exert sedation; however, in group P, propofol was injected instead of remimazolam. The occurrence of postoperative delirium was assessed with the Confusion Assessment Method for the Intensive Care Unit scale and postoperative pain was assessed with the visual analogue score (VAS). The primary outcome measures were the incidence and duration of delirium within 7 days following surgery. Secondary outcome measures included postoperative VAS scores, intraoperative anesthetic drug dosage, and adverse reactions, including nausea and vomiting, hypoxemia, and respiratory depression. RESULTS There was no significant difference in baseline data between the 2 groups (P>0.05). There was no statistically significant difference in the incidence and duration of postoperative delirium between the 2 groups (P>0.05). There were no significant differences in VAS scores, remifentanil consumption, and adverse reactions, including nausea and vomiting, hypoxemia, and respiratory depression between the 2 groups (P>0.05). CONCLUSIONS In elderly patients undergoing radical colon cancer surgery, remimazolam administration did not improve or aggravate the incidence and duration of delirium, compared with propofol.

Intentional benzodiazepine poisoning in older adults reported to United States Poison Centers.

INTRODUCTION: Despite known contraindications, benzodiazepines are frequently prescribed for older adults. This study utilizes poison control center data on benzodiazepine-involved cases aged 50 and above to compare the characteristics of suspected suicide attempt with other intentional misuse cases. We also examined associations of major medical outcomes (major effect/death) with demographic characteristics and other co-used substances in each group. METHODS: The study employed data from the America's Poison Center National Poison Data System from 2015-2022. Descriptive statistics and binary logistic regression models were used. RESULTS: Of the benzodiazepine-poisoning cases of intentional misuse (n = 93,245), 85 percent were suicide attempts and 15 percent were other intentional misuses. Reports to poisons centers showed a decline from 2019-2022 when compared to 2015-2016. However, the likelihood of a reported suicide attempt, compared to other intentional misuse, was greater in 2019-2022 compared to 2015-2016 and among those who co-used antidepressants, anxiolytics, atypical antipsychotics, other benzodiazepines, other analgesics, anticonvulsants, and alcohol. The odds of major effect/death in both groups were also greater in 2019-2022, with suicide attempt cases in advanced ages showing higher odds. The co-use of antidepressants, prescription opioids, atypical antipsychotics, anticonvulsants, and other analgesics were associated with a higher likelihood of major effect/death in both exposure groups. For instance, adjusted odds ratios for co-used prescription opioids were 2.20 (95 percent confidence intervals: 2.09-2.31) among suicide attempt cases and 3.51 (95 percent confidence intervals: 3.10-3.97) among other intentional misuse cases. DISCUSSION: Healthcare providers need to screen for suicidal ideation among benzodiazepine users, with special attention to an increased risk of suicide attempt among those who co-use antidepressants and opioids and to decreasing adverse outcomes in all misuse cases. Assessments of underlying mental health and substance use problems and medication regimens to minimize polypharmacy and drug interactions are needed to reduce adverse outcomes. CONCLUSIONS: Though the numbers of benzodiazepine-involved suicide attempt and other intentional misuse cases reported to United States poison centers decreased in recent years, the likelihood of major medical effect/death among these cases have increased.

Cognitive impairment following sedative overdose.

INTRODUCTION: Patients with sedative overdose may have residual cognitive impairment at the time they are deemed medically cleared for discharge. Impairment could affect the performance of high-risk activities, including driving. The Trail Making Test is an alpha-numeric assessment that can be performed at the bedside to assess cognitive function. We examined whether there were differences in cognitive function when medically cleared between patients that overdosed on sedative and non-sedative drugs. METHODS: A prospective, observational study assessed cognitive function using the Trail Making Test between 2018 and 2021. Patients (16 years and greater) completed testing upon medical clearance if they spoke English and had no previous neurological injury. Continuous covariates were compared using t-tests or Mann-Whitney U tests and multiple linear regression; binary variables were modelled using logistic regression. RESULTS: Of 171 patients enrolled, 111 (65 per cent) had sedative overdose; they were older (median 32.1 versus 22.2 years) and more likely to be male (58.6 per cent versus 36.7 per cent). Benzodiazepines and paracetamol were the commonest drug overdoses. Patients with sedative overdose performed worse on Trail Making Test part A (37.0 versus 33.1 seconds, P = 0.017) and Trail Making Test part B (112.4 versus 81.5 seconds, P = 0.004). Multiple linear regression analysis indicated that patient age (P < 0.001, 1.7 seconds slower per year, 95 per cent confidence interval: 0.9-2.6 seconds) and perception of recovery (P = 0.006, 36.4 seconds slower if perceived not recovered, 95 per cent confidence interval: 10.8-62.0 seconds) were also associated with Trail Making Test part B times. Patients with sedative overdose were more likely to be admitted to the intensive care unit (Odds Ratio: 4.9, 95 percent confidence interval: 1.1-22.0; P = 0.04). DISCUSSION: Our results are broadly in keeping with previously published work, but include a wider range of drug overdose scenarios (polypharmacy and recreational drugs). While patients demonstrated some perception of their cognitive impairment, our model could not reliably be used to provide individual discharge advice. The study design did not allow us to prove causation of cognitive impairment, or to make comparison between the strength of an overdose to the trail making test time. CONCLUSIONS: Trail Making Test results suggested that patients who had sedative drug overdoses may have significant cognitive deficits even when medically cleared. Risk of harm may be minimised with advice to avoid high-risk activities such as driving. More profound impacts seen on the Trail Making Test part B than A may mean higher-order thinking is more affected than simple cognitive function.

To Compare the Anesthetic Effect of Remimazolam and Propofol in Painless Hysteroscopic Minimally Invasive Surgery.

OBJECTIVE: Hysteroscopic surgery will stimulate the autonomic nerves innervating the uterus, causing intense discomfort and pain in the examined person, and in severe cases, it will cause blood pressure drop, heart rate slowing, arrhythmia and even cardiac arrest, so most patients need anesthetic intervention. This study to retrospectively compare the anesthetic effect of remimazolam and propofol in minimally invasive painless hysteroscopic surgery and to explore the safety and efficacy of remimazolam. METHODS: The clinical data of 110 female patients who underwent painless hysteroscopic minimally invasive surgery in our hospital from January 2023 to June 2023 were collected. The patients were divided into the remimazolam group (group R, n = 55) and the propofol group (group P, n = 55) according to the main anesthetic drugs used during the operation. The changes in heart rate (HR), mean arterial pressure (MAP), blood oxygen saturation (SpO2), and respiratory rate (RR) at the time of entry (T0), modified vigilance/sedation score (MOAA/S) 0 (T1), cervical dilation (T2), end of the operation (T3) and anesthesia recovery (T4) were compared between the two groups. Anesthesia induction time, operation time, and anesthesia recovery time were compared between the two groups, and the incidence of intraoperative and postoperative adverse reactions was compared between the two groups. RESULTS: HR, MAP, and SpO2 in group R were significantly higher than those in group P at T1, T2, T3, and T4 (p < 0.05), and there was no significant difference in RR between the two groups (p > 0.05). HR, MAP, and SpO2 at T1 and T2 were significantly lower than those at T0 in group R (p < 0.05), and RR at different time points in the group had no significant difference (p > 0.05). HR, MAP, and SpO2 at T1, T2, T3, and T4 were significantly lower than those at T0 in group P (p < 0.01), and RR at different time points in the same group had no significant difference (p > 0.05). The anesthesia induction time in group R was more prolonged than in group P, and the anesthesia recovery time in group R was shorter than in group P (p < 0.05). The incidences of hypotension, bradycardia, low oxygen saturation, respiratory depression, and injection pain in group R were significantly lower than those in group P (p < 0.05). CONCLUSION: Intravenous induction of remimazolam at 6 mg·kg-1·h-1 and maintenance of anesthesia at 1-2 mg·kg-1·h-1 have less effect on hemodynamics, faster recovery time and lower incidence of adverse reactions compared with propofol when used in minimally invasive hysteroscopic surgery. Remimazolam can be safely and effectively used in this kind of surgery.

Effect of converting from propofol to remimazolam with flumazenil reversal on recovery from anesthesia in outpatients with mental disabilities: a randomized controlled trial.

BACKGROUND: General anesthesia is often necessary for dental treatment of outpatients with mental disabilities. Rapid recovery and effective management of postoperative nausea and vomiting (PONV) are critical for outpatients. This study aimed to investigate the effect of transitioning from propofol to remimazolam with flumazenil reversal administered toward the end of surgery during propofol-based total intravenous anesthesia (TIVA) on recovery. METHODS: Adults with mental disabilities scheduled to undergo dental treatment were randomly assigned to receive either propofol-based TIVA (Group P) or propofol-remimazolam-based TIVA with flumazenil reversal (Group PR). Propofol was replaced with remimazolam 1 h before the end of surgery in Group PR; moreover, 0.5 mg of flumazenil was administered after the neuromuscular blockade reversal agent. The primary outcome was the duration of stay in the post-anesthesia care unit (PACU). The secondary outcomes included time to eye-opening, time to extubation, occurrence of PONV, and quality of recovery. RESULTS: Fifty-four patients were included in this study. The duration of stay in the PACU in Group PR was significantly shorter than that in Group P (mean difference, 8.7 min; confidence interval [95% CI], 3.3-14.2; P = 0.002). Group PR exhibited a shorter time to eye opening (mean difference, 5.4 min; 95% CI, 3.3-8.1; P < 0.001) and time to extubation (mean difference, 5.5 min; 95% CI, 3.6-7.9; P < 0.001) than Group P. Neither group required the administration of rescue analgesics, and the incidence of PONV was not reported. CONCLUSIONS: Transitioning from propofol to remimazolam 1 h before the end of surgery followed by flumazenil reversal reduced the duration of stay in the PACU and the time to eye opening and extubation without affecting the incidence of PONV and quality of recovery. TRIAL REGISTRATION NUMBER: Clinical Research Information Service (KCT0007794), Clinical trial first registration date: 12/10/2022.

Bolus administration of remimazolam was superior to midazolam for deep sedation in elderly patients undergoing diagnostic bronchoscopy: A randomized, double-blind, controlled trial.

BACKGROUND: To date, there is no standardized practice for the use of pharmacological sedatives during flexible bronchoscopy, particularly for elderly patients. This exploratory study aimed to assess the efficacy and safety of remimazolam at a single induced dose for deep sedation in elderly patients undergoing diagnostic flexible bronchoscopy (DFB), and compare with midazolam, a commonly used sedative. METHODS: A total of 100 elderly patients (age range 65-80 yr; American Society of Anesthesiologists Physical Status I-III) undergoing DFB were randomly allocated into 2 groups according to the sedatives used for induction: the remimazolam group and the midazolam group. Sedation induction was initiated by an intravenous bolus of remimazolam (0.135 mg/kg) or midazolam (0.045 mg/kg), respectively, both groups were combined with a high-dose of alfentanil (18 µg/kg), and supplemented with high-flow nasal cannula (HFNC) oxygen supply at a flow rate of 45 L/min. If the target depth of sedation was not achieved, propofol would be titrated as a rescue. The primary outcome was the success rate of sedation at a single induced dose to achieve target depth (Ramsay sedation score [RSS] = 4) during induction, intraoperative changes in vital signs, postoperative follow-up situation and incidence of post-bronchoscopy adverse events were evaluated as secondary outcomes. RESULTS: The success rate of sedation in the remimazolam group was significantly higher than that in the midazolam group (65.2% vs 39.6%, P = .013), while the incidence of extra sleep within 6 hours after procedure was lower in the remimazolam group as compared to the midazolam group (10.9% vs 31.3%, P = .016). No statistically significant differences were observed between the 2 groups regarding hemodynamic fluctuations, incidence of hypoxemia, and cough response during the procedure, as well as postoperative recall, willingness to undergo reexamination, and other post-bronchoscopy adverse events. CONCLUSIONS: Bolus administration of remimazolam offers advantages over midazolam for deep sedation in elderly patients undergoing DFB, in terms of a higher success rate of sedation and a lower incidence of extra sleep within 6 hours after procedure, though the safety profiles of both groups were favorable.

Effect of Remimazolam- versus Propofol-Based Total Intravenous General Anesthesia on Intraoperative Hemodynamic Stability for Major Spine Surgery in the Prone Position: A Randomized Controlled Trial.

Background and Objectives: Remimazolam offers advantages over propofol in terms of hemodynamic stability. However, it remains unclear whether remimazolam-based total intravenous anesthesia (TIVA) can reduce intraoperative hypotension compared to propofol-based TIVA, especially after prone positioning. In this study, we compared the effects of remimazolam- and propofol-based TIVA on intraoperative hemodynamic stability in patients undergoing surgery in the prone position. Materials and Methods: This study randomly assigned patients undergoing major spinal surgery in the prone position to the propofol or remimazolam group. Target-controlled infusion (2-3.5 µg/mL for induction and 2-3 µg/mL for maintenance) was used in the propofol group and continuous infusion (6 mg/kg/h for induction and 1-2 mg/kg/h for maintenance) was used in the remimazolam group; target-controlled infusion (3-5 ng/mL) of remifentanil was performed in both groups. The primary outcomes were the incidence of hypotensive episodes during the first hour after prone positioning. The secondary outcomes included the incidence of severe hypotension and the total amount of inotropic or vasopressor medication. Systolic and mean arterial pressure, heart rate, cardiac index and output, stroke volume, stroke volume variation, and pleth variability index were also evaluated. These variables were recorded per minute for the first 10 min after prone positioning, and every 10 min thereafter. Results: The study enrolled 94 patients (47 patients in each group). The incidence of hypotension or severe hypotension did not differ significantly between the two groups during the first hour after prone positioning. The total amount of ephedrine administered during the first hour after prone positioning was lesser (p = 0.020) and the mean arterial pressure during the initial 10 min after prone positioning was higher in the remimazolam group (p = 0.003). Conclusions: Our study uncovered no significant differences in the incidence of hypotension between remimazolam- and propofol-based TIVA in patients undergoing major spine surgery in prone position.

Anti-inflammatory potential of remimazolam: A laboratory and clinical investigation.

BACKGROUND: Anesthetic agents, particularly intravenous anesthetics, may affect immune function and tumorigenic factors. We herein investigated whether the anti-inflammatory effects of anesthetic agents are attributed to their antioxidant properties. The antioxidant and anti-inflammatory effects of remimazolam, a new anesthetic, remain unclear. We hypothesized that remimazolam exerts anti-inflammatory effects due to its antioxidant properties, which may affect the postoperative inflammatory response. This retrospective clinical study examined this hypothesis using laboratory and clinical approaches. METHODS: The antioxidant effects of remimazolam and dexmedetomidine were assessed by electron spin resonance (ESR) spectroscopy, and postoperative inflammatory responses were compared in 143 patients who underwent transcatheter aortic valve replacement at Kindai University Hospital between April 2021 and December 2022. The primary endpoint was the presence or absence of the antioxidant effects of the anesthetics themselves using ESR. RESULTS: Remimazolam at clinical concentrations exerted antioxidant effects, whereas dexmedetomidine did not. Increases in C-reactive protein (CRP) levels on POD3 from preoperative values were significantly smaller in the remimazolam group than in the dexmedetomidine group (1.33 ± 1.29 vs. 2.17 ± 1.84, p = .014). CONCLUSIONS: Remimazolam exerted stronger anti-inflammatory effects than dexmedetomidine, and these effects were enhanced by its antioxidant properties, which may have affected postoperative CRP production.

Status epilepticus: what's new for the intensivist.

PURPOSE OF REVIEW: Status epilepticus (SE) is a common neurologic emergency affecting about 36.1/100 000 person-years that frequently requires intensive care unit (ICU) admission. There have been advances in our understanding of epidemiology, pathophysiology, and EEG monitoring of SE, and there have been large-scale treatment trials, discussed in this review. RECENT FINDINGS: Recent changes in the definitions of SE have helped guide management protocols and we have much better predictors of outcome. Observational studies have confirmed the efficacy of benzodiazepines and large treatment trials indicate that all routinely used second line treatments (i.e., levetiracetam, valproate and fosphenytoin) are equally effective. Better understanding of the pathophysiology has indicated that nonanti-seizure medications aimed at underlying pathological processes should perhaps be considered in the treatment of SE; already immunosuppressant treatments are being more widely used in particular for new onset refractory status epilepticus (NORSE) and Febrile infection-related epilepsy syndrome (FIRES) that sometimes revealed autoimmune or paraneoplastic encephalitis. Growing evidence for ICU EEG monitoring and major advances in automated analysis of the EEG could help intensivist to assess the control of electrographic seizures. SUMMARY: Research into the morbi-mortality of SE has highlighted the potential devastating effects of this condition, emphasizing the need for rapid and aggressive treatment, with particular attention to cardiorespiratory and neurological complications. Although we now have a good evidence-base for the initial status epilepticus management, the best treatments for the later stages are still unclear and clinical trials of potentially disease-modifying therapies are long overdue.

Clinical Study of Flumazenil Antagonizing Remimazolam on Nausea and Vomiting After Gynecologic Day Surgery.

Purpose: To evaluate the effect of flumazenil antagonizing remimazolam on postoperative nausea and vomiting (PONV) after gynecologic day surgery. Patients and Methods: 141 cases of gynaecological daycase surgery patients in Weifang People's Hospital were selected, randomized into group F (flumazenil group, 71 cases) and group C (control group, 70 cases). Dexamethasone 5 mg, flurbiprofen axetil 50 mg, and droperidol 1 mg were given intravenously before induction of anesthesia in both groups. Anesthesia induction: Remimazolam 0.25mg / kg was injected within 1 minute. After the patient fell asleep, mivacurium chloride 0.2mg / kg was injected for 30 seconds and alfentanil 20ug / kg was injected for 30 seconds. Anesthesia maintenance: Remimazolam 1mg/kg/h and alfentanil 40ug/kg/h were continuously pumped by micro pump. Stopping the injection of remimazolam and alfentanil at the end of the operation. Flumazenil 0.2 mg was given to antagonize remimazolam in group F after 1 minute. Group C was given an equal volume of saline. The incidence of PONV in the postoperative PACU and over a 24-hour period, patient awakening time, and general patient information were recorded. Results: The incidence of PONV in both groups within 24 hours was 50.70% in group F was significantly higher than 32.86% in group C. The difference was statistically significant (P < 0.05). The incidence of PONV in the PACU was 5.6% in group F and 8.6% in group C. The difference was not statistically significant (p > 0.05). Conclusion: Flumazenil antagonism of remimazolam increases the incidence of PONV within 24 hours in gynecologic day surgery patients and has no significant effect on the incidence of PONV in the PACU.