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Remimazolam (Anerem ® in Japan; ByFavo™ in the USA; Aptimyda™ in the EU) is an ultra-short-acting intravenous (IV) benzodiazepine sedative/anesthetic being developed by PAION AG in conjunction with a number of commercial partners for use in anesthesia and procedural sedation. Remimazolam was approved on 23 January 2020 in Japan for use in general anesthesia in adult patients. Remimazolam is also undergoing regulatory assessment in South Korea for this indication and for use in procedural sedation in the USA, the EU and China. This article summarises the major milestones in the development of remimazolam for this first approval for the induction and maintenance of general anaesthesia, and its potential upcoming approvals in general anaesthesia and procedural sedation.

Propofol is an intravenous agent used commonly for the induction and maintenance of anesthesia, procedural, and critical care sedation in children. The mechanisms of action on the central nervous system involve interactions at various neurotransmitter receptors, especially the gamma-aminobutyric acid A receptor. Approved for use in the USA by the Food and Drug Administration in 1989, its use for induction of anesthesia in children less than 3 years of age still remains off-label. Despite its wide use in pediatric anesthesia, there is conflicting literature about its safety and serious adverse effects in particular subsets of children. Particularly as children are not “little adults”, in this review, we emphasize the maturational aspects of propofol pharmacokinetics. Despite the myriad of propofol pharmacokinetic-pharmacodynamic studies and the ability to use allometrical scaling to smooth out differences due to size and age, there is no optimal model that can be used in target controlled infusion pumps for providing closed loop total intravenous anesthesia in children. As the commercial formulation of propofol is a nutrient-rich emulsion, the risk for bacterial contamination exists despite the Food and Drug Administration mandating addition of antimicrobial preservative, calling for manufacturers’ directions to discard open vials after 6 h. While propofol has advantages over inhalation anesthesia such as less postoperative nausea and emergence delirium in children, pain on injection remains a problem even with newer formulations. Propofol is known to depress mitochondrial function by its action as an uncoupling agent in oxidative phosphorylation. This has implications for children with mitochondrial diseases and the occurrence of propofol-related infusion syndrome, a rare but seriously life-threatening complication of propofol. At the time of this review, there is no direct evidence in humans for propofol-induced neurotoxicity to the infant brain; however, current concerns of neuroapoptosis in developing brains induced by propofol persist and continue to be a focus of research.

The quality of recovery (QoR) of remimazolam-based and propofol-based total intravenous anesthesia was compared as measured by QoR-15 scores. A prospective, double-blind, randomized controlled, non-inferiority trial. An operating room, a post-anesthesia care unit (PACU), and a hospital ward. Female patients (n = 140; 20–65 years) scheduled for open thyroidectomy were enrolled and randomly assigned to the remimazolam or propofol group. The remimazolam group received continuous remimazolam infusions and effect-site target-controlled remifentanil infusions. The propofol group received effect-site target-controlled infusions of propofol and remifentanil. The primary outcome was QoR-15 on postoperative day 1 (POD1). The mean difference between the groups was compared against a non-inferiority margin of −8. Secondary outcomes were QoR-15 on POD2, hemodynamic data, time to lose and recover consciousness, sedation score upon PACU admission, pain, and postoperative nausea and vomiting profiles at the PACU and ward. Group-time interaction effects in hemodynamic data and QoR-15 were analyzed using a linear mixed model. The total QoR-15 score on POD1 in the remimazolam group was non-inferior to that in the propofol group (mean [SD] 111.2 [18.8] vs. 109.1 [18.9]; mean difference [95% CI] 2.1 [−4.2, 8.5]; p = 0.002 for non-inferiority). The QoR-15 score on POD2 was comparable between the groups, and no group-time interaction was observed. At the end of anesthesia, after extubation, and upon arrival at the PACU, mean arterial pressure was significantly higher in the remimazolam group. Remimazolam group was more sedated at the time of admission to PACU. Pain intensity and the requirement for analgesics were lower in the remimazolam group than in the propofol group. Remimazolam-based total intravenous anesthesia provided a similar QoR to propofol. Remimazolam and propofol can be used interchangeably for general anesthesia in female patients undergoing thyroid surgery. •Evidence regarding quality of recovery after remimazolam-based total intravenous anesthesia has been limited.•Remimazolam-based total intravenous anesthesia was explored in female patients undergoing open thyroidectomy.•Remimazolam-based total intravenous anesthesia demonstrated similar quality of recovery to propofol.•Hypotensive incidence at cessation of anesthetics was lower in patients administered with remimazolam compared to propofol.•Remimazolam-based total intravenous anesthesia was associated with reduced pain intensity and analgesic requirement.

Propofol has been shown to provide protection against renal ischemia/reperfusion injury experimentally, but clinical evidence is lacking. Here we studied the effect of propofol anesthesia on the occurrence of acute kidney injury following heart surgery with cardiopulmonary bypass. One hundred and twelve patients who underwent valvular heart surgery were randomized to receive either propofol or sevoflurane anesthesia, both with sufentanil. Using Acute Kidney Injury Network criteria, significantly fewer patients developed acute kidney injury postoperatively in the propofol group compared with the sevoflurane group (6 compared with 21 patients). The incidence of severe renal dysfunction was significantly higher in the sevoflurane group compared with the propofol group (5 compared with none). The postoperative cystatin C was significantly lower in the propofol group at 24 and 48h. Serum interleukin-6 at 6h after aorta cross-clamp removal, C-reactive protein at postoperative day 1, and segmented neutrophil counts at postoperative day 3 were also significantly lower in the propofol group. Thus, propofol anesthesia significantly reduced the incidence and severity of acute kidney injury in patients undergoing valvular heart surgery with cardiopulmonary bypass compared with sevoflurane. This beneficial effect of propofol may be related to its ability to attenuate the perioperative increase in proinflammatory mediators.

A national audit of accidental awareness under general anaesthesia (where a patient is aware of events despite the intention to administer general anaesthesia) identified TIVA as a risk factor, particularly when unusual techniques were used or equipment checks were incomplete.3 A Cochrane review on cognitive outcomes in older people found that postoperative cognitive dysfunction (a persistent impairment of cognition following surgery) was less likely with propofol-based TIVA,4 and a meta-analysis of randomised controlled trials found that propofol based TIVA was associated with a lower incidence of emergence agitation in children.5 At present, we deem it reasonable to consider TIVA and inhalational anaesthesia equivalent from a safety perspective; three major ongoing randomised controlled trials (Vital, expected to conclude in 2026; Vapor-C, expected to conclude in 2026; and Thrive, expected to conclude in 2029) will add further information about the relative risks and benefits of both techniques.6 Evidence for the solution Multiple studies show that TIVA has a lower carbon footprint than inhalational anaesthesia.789 The studies are based on “life cycle analyses,” using 100 year global warming potential to quantify greenhouse gas emissions. Since 2021, the UK’s Royal College of Anaesthetists has specified that anaesthetists should be trained to use TIVA for non-complex cases in the first stage of training;13 further training can be sought for more complex situations. Ce=effect site concentration; Cet=effect site concentration target Anaesthetic teams should ensure that TIVA drugs and equipment are thoroughly checked before use, to minimise the risk of errors. Pharmacokinetic models are less well validated in pregnant women and children, yet these patients arguably have much to gain from TIVA (eg, because of the uterine relaxant qualities of volatile anaesthetics, and the increased risk of postoperative nausea and vomiting and agitation on emergence in paediatric practice).1618 Uncertainties include the pharmacokinetic implications of various pathologies and stages of pregnancy, and wide pharmacokinetic and pharmacodynamic variability across the paediatric population.

To compare the incidence of postoperative cognitive dysfunction (POCD) in elderly surgical patients (>60years) receiving different anesthetics (propofol, sevoflurane, or isoflurane) and to identify potential biomarkers of POCD in this patient population. Prospective, randomized, double-blind clinical trial. University-affiliated teaching hospital. One hundred and fifty elderly patients scheduled for laparoscopic cholecystectomy. Elderly patients undergoing laparoscopic cholecystectomy were randomly assigned to receive propofol, sevoflurane, or isoflurane anesthesia. Measurements: Cognitive function was assessed using neuropsychological tests at baseline (1day before surgery [D0]), and on postoperative day 1 (D1) and day 3 (D3). Plasma S-100β and Aβ1–40 protein, IL-1β, IL-6 and TNF-α concentrations were assessed before induction of anesthesia (T0), after extubation (T1), and 1h (T2) and 24h (T3) postoperatively. The incidence of POCD was significantly lower in the propofol group compared to the isoflurane group and the sevoflurane group at D1 and D3 (propofol vs. isoflurane: D1 and D3, P<0.001; propofol vs. sevoflurane: D1, P=0.012; D3, P=0.013). The incidence of POCD was significantly lower in the sevoflurane group compared to the isoflurane group at D1 (P=0.041), but not at D3. Postoperatively, plasma S-100β and Aβ1–40 protein, IL-1β, IL-6, and TNF-α concentrations were significantly decreased in the propofol group compared to the isoflurane group. Propofol anesthesia may be an option for elderly surgical patients. •Postoperative cognitive dysfunction is commonly occurred in elderly.•Anesthesia impaired the cognitive function.•Propofol had little effect then inhaled anesthetics.

Ciprofol, a novel intravenous anesthetic, provides rapid recovery in patients undergoing colonoscopy. We aimed to examine the efficacy and safety of ciprofol in comparison with propofol for sedation or anesthesia in non-operating room settings including endoscopic submucosal dissection, endoscopic retrograde cholangiopancreatography, and flexible bronchoscopy (FB). Prospective, randomized, double-blind, parallel-group clinical trial. University-affiliated teaching hospital. We recruited 207 patients scheduled for an endoscopic procedure from October 2021 to December 2021. Patients were randomized into three groups according to the dose during induction (n = 69 each): 1) ciprofol 6 mg/kg/h, 2) ciprofol 8 mg/kg/h, or 3) propofol 40 mg/kg/h. Ciprofol or propofol was administered throughout the procedure. The primary outcome was the success rate of sedation or anesthesia for the procedures. Secondary outcomes included induction time, endoscope insertion time, recovery time, discharge time, incidence of drug-related adverse events (AEs), neurological and inflammatory outcomes. The procedure success rates in the three groups were 100%. The induction time in the 6 (3.3 ± 1.0 min) and 8 mg/kg/h (2.9 ± 0.6 min) ciprofol groups was longer than that in the propofol group (2.5 ± 0.6 min) only in patients undergoing FB (p = 0.004). The time for patients to be fully alert and discharged from the post-anesthesia care unit was comparable across the three groups (p > 0.05). The incidence of drug-related AEs in the propofol and 6 and 8 mg/kg/h ciprofol groups was 84.1%, 76.8%, and 79.7%. No pain on injection was reported by ciprofol groups. Neurological outcomes and inflammatory responses were comparable among the three groups. Ciprofol induced a level of sedation or anesthesia equivalent to that induced by propofol in non-operating room settings except for a prolonged induction time in patients undergoing FB. Ciprofol had a safety profile similar to that of propofol. No pain on injection was reported by ciprofol. •Ciprofol, a novel intravenous anesthetic, and propofol induced equivalent sedation or anesthesia in non-operating room settings.•Ciprofol had a similar safety profile to that of propofol.•No pain on injection was reported by the ciprofol groups.•Ciprofol and propofol anesthesia had similar neurological outcomes and inflammatory parameters.

Sedation during endoscopic gastrointestinal procedures is now a routine practise that can improve patient outcomes. Propofol is one of the most commonly used intravenous anaesthetics. However, despite its popularity, it has been associated with various side effects, particularly haemodynamic and respiratory complications, especially in frail patient populations. Intravenous (IV) lidocaine, used as an adjuvant, has already demonstrated its efficacy in improving certain outcomes during sedation with propofol. However, the emergence of further studies requires an update to enhance the quality of existing data and refine this anaesthetic practise. The aim of this systematic review and meta-analysis is to evaluate the efficacy of intravenous lidocaine in reducing propofol consumption, decreasing episodes of desaturation and involuntary movements during the procedure, improving awakening time, relieving post-procedure pain, and increasing endoscopist satisfaction during propofol sedation in gastrointestinal endoscopic procedures (PROSPERO registration: CRD420250651511). We included randomised controlled trials conducted in adult patients undergoing propofol sedation with IV lidocaine administered as an adjunct during gastrointestinal endoscopic procedures. A comprehensive systematic search was conducted in PubMed/MEDLINE, Scopus and Web of Science from January to February 2025 without language or time restrictions. Risk of bias was assessed using the Cochrane Risk of Bias Tool (RoB2). Seventeen randomised controlled trials (1698 patients) were selected based on full text and included in the study. Lower propofol consumption was observed with intravenous lidocaine compared with the control group (SMD: –1.36, 95 % CI: −1.67 to −1.05; p < 0.001), with consistent results in all subgroups. Awakening time was significantly shorter in the IV lidocaine group (SMD = −0.92 [95 % CI: −1.18 to −0.66]; p < 0.001), while no significant difference was observed in full recovery time. Lidocaine administration was associated with a 59 % reduction in desaturation events, 36 % reduction in hypotension events and a 57 % reduction in involuntary movements. Continuous infusion after bolus administration was required to achieve these effects. Infusion rates of 2 mg/kg/h and 4 mg/kg/h were equally effective. Intravenous lidocaine is a safe and effective adjunct to propofol sedation in gastrointestinal endoscopy, reducing anaesthetic requirements and sedation-related complications. Routine use of lidocaine may increase the safety of the procedure, especially in high-risk populations and complex procedures. •IV lidocaine reduces propofol use in adult GI procedures, with consistent effects across procedures and age groups.•Lidocaine shortens awakening, lowers desaturation risk, and improves sedation quality with fewer involuntary movements.•Clinical benefits require continuous lidocaine infusion; both 2 and 4 mg/kg/h rates are equally effective.•Older patients benefit from lidocaine like younger ones, supporting routine use to improve sedation safety in high-risk populations.

Patients undergo dilatation and evacuation for abortion or miscarriage. However, bleeding is sometimes problematic. Despite reports on the association between volatile anesthetics and increased bleeding during the procedure, firm evidence is lacking. Therefore, we conducted a systematic review and meta-analysis to compare the effects of volatile anesthetics and propofol on the amount of bleeding in patients undergoing dilatation and evacuation. We conducted a systematic search of four databases, namely PubMed, Embase, Cochrane Central Register of Controlled Trials databases, and Web of Science (Clarivate Analytics), from their respective inception to April 2021. Moreover, we searched two trial registration sites. The inclusion criterion was randomized controlled trials of patients who underwent dilatation and evacuation under general anesthesia using volatile anesthetics or propofol. The primary outcome was the amount of perioperative bleeding. The mean difference of the bleeding was combined using a random-effects model. The I2 statistic was used to assess heterogeneity. We assessed risk of bias with Cochrane domains. We controlled type I and II errors due to sparse data and repetitive testing with Trial Sequential Analysis. We assessed the quality of evidence with GRADE. Five studies were included in the systematic review. The amount of bleeding was compared in four studies and was higher in the volatile anesthetic group, with a mean difference of 164.7 ml (95% confidence interval, 43.6 to 285.7; p = 0.04). Heterogeneity was considerable, with an I2 value of 97%. Two studies evaluated the incidence of significant bleeding, which was significantly higher in the volatile anesthetic group (RR, 2.42; 95% confidence interval, 1.04-5.63; p = 0.04). Choosing propofol over volatile anesthetics during dilatation and evacuation might reduce bleeding and the incidence of excessive bleeding. However, the quality of the evidence was very low. This necessitates further trials with a low risk of bias. PROSPERO (CRD42019120873).

Pain on propofol injection (POPI) is a minor problem that all anesthetists face every day. Introduction of several new formulations and hundreds of clinical trials have failed to find its remedy with just one intervention in all patients. This article highlights the causes of POPI and interventions that are used to eliminate this pain in current practice. Relevant articles from Medline and Embase databases were searched and included in this descriptive review with the following conclusions: (1) POPI is due to irritation of venous adventitia leading to release of mediators such as kininogen from kinin cascade. (2) When two or more drugs or measures are used, the incidence of POPI decreases considerably. Hence, the approach to eliminating POPI should be multimodal. (3) Any regimen that includes a drug having local anesthetic effect combined with central sedative/analgesic and rapid injection into a large vein should definitely reduce the risk of POPI to negligible levels.