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As the primary Ca2+ release channel in skeletal muscle sarcoplasmic reticulum (SR), mutations in type 1 ryanodine receptor (RyR1) or its binding partners underlie a constellation of muscle disorders, including malignant hyperthermia (MH). In patients with MH mutations, triggering agents including halogenated volatile anaesthetics bias RyR1 to an open state resulting in uncontrolled Ca2+ release, increased sarcomere tension, and heat production. Propofol does not trigger MH and is commonly used for patients at risk of MH. The atomic-level interactions of any anaesthetic with RyR1 are unknown. RyR1 opening was measured by [3H]ryanodine binding in heavy SR vesicles (wild type) and single-channel recordings of MH mutant R615C RyR1 in planar lipid bilayers, each exposed to propofol or the photoaffinity ligand analogue m -azipropofol (AziP m). Activator-mediated wild-type RyR1 opening as a function of propofol concentration was measured by Fura-2 Ca2+ imaging of human skeletal myotubes. AziP m binding sites, reflecting propofol binding, were identified on RyR1 using photoaffinity labelling. Propofol binding affinity to a photoadducted site was predicted using molecular dynamics (MD) simulation. Both propofol and AziP m decreased RyR1 opening in planar lipid bilayers (P <0.01) and heavy SR vesicles, and inhibited activator-induced Ca2+ release from human skeletal myotube SR. Several putative propofol binding sites on RyR1 were photoadducted by AziP m. MD simulation predicted propofol K D values of 55.8 μM and 1.4 μM in the V4828 pocket in open and closed RyR1, respectively. Propofol demonstrated direct binding and inhibition of RyR1 at clinically plausible concentrations, consistent with the hypothesis that propofol partially mitigates malignant hyperthermia by inhibition of induced Ca2+ flux through RyR1. [ABSTRACT FROM AUTHOR]

Target-controlled infusion (TCI) is a mature technology that enables the delivery of intravenous anaesthetics in the concentration domain. The accuracy of the pharmacologic models used by TCI systems is imperfect, especially regarding pharmacodynamic predictions. This shortcoming of TCI devices is not critical. That TCI systems produce steady-state effect-site concentrations at or near a specified target is a more important attribute than a high level of accuracy because anaesthesiologists titrate to a stable level of drug effect whatever the actual concentration is. In this sense, TCI functions as a 'gain switch'. Achieving a steady state is more important than perfect accuracy. [ABSTRACT FROM AUTHOR]

The Eleveld pharmacokinetic–pharmacodynamic model for propofol predicts bispectral index (BIS) processed electroencephalogram values from estimated effect-site concentrations. We investigated agreement between measured and predicted BIS values during total intravenous anaesthesia (TIVA). Forty participants undergoing lower limb surgery received TIVA using remifentanil target-controlled infusions and propofol by manually controlled, target-guided infusions based upon the Eleveld model and directed by two pharmacokinetic computer simulation applications: PKPD Tools and StelSim. We evaluated the predictive performance of the Eleveld model by calculating median prediction errors (BIS units) and by Bland–Altman analyses. We also performed |Bland-Altman analysis of supplementary data provided by the authors of the Eleveld model. Whereas median prediction errors were small (MDPE –1.9, MDAPE 10), the ranges were wide (–18.5 to 24.3 and 1.7 to 24.3). The proportion of MDAPE >10 BIS units was 47.8%. Bland–Altman analysis showed a small mean bias (–0.52 BIS units) with wide limits of agreement (–27.7 to 26.2). Each participant's limits of agreement did not meet the requirements for declaring interchangeability between the two measurements. The measurement differences depended on the BIS values, as indicated by the positive slopes of the differences vs BIS values. Bland–Altman analysis of the Eleveld model supplementary data revealed similar results. BIS predictions by the Eleveld model should be interpreted with caution. In spite of the acceptable MDPE and MDAPE, there are unacceptable degrees of both within-subject and between-subject variation during propofol target-controlled infusions. This limits the use of adjusting targeted concentrations to achieve desired simulated BIS values with confidence. [ABSTRACT FROM AUTHOR]

Postoperative sleep disturbance (PSD) is prevalent in perioperative patients，and has significant impact on postoperative recovery and prognosis. The aim of this study was to investigate the effect of desflurane maintenance on postoperative sleep quality, in order to optimize patients' perioperative sleep management. A total of 118 patients undergoing elective breast surgery were randomized to receive either desflurane-based volatile anesthesia (desflurane group) or propofol-based total intravenous anesthesia (propofol group) for anesthesia maintenance. The primary outcome was the quality of sleep, which was assessed by the Pittsburgh Sleep Quality Index (PSQI) on 3 days after operation (POD3). Secondary outcomes were PSQI on postoperative day 7 (POD7) and 30 (POD30), and postoperative anxiety, depression, and pain score, as well as objective sleep parameters including total sleep time (TST), WASO (Wakefulness after sleep onset), REM (Rapid eye movement) and NREM (Non-rapid Eye Movement) measured by Fitbit Charge 2TM during the initial 3 postoperative days. The global PSQI scores on POD3 in the desflurane group was non-inferior to that in the propofol group [mean (SD) 8.47 (3.46) vs. 7.65 (3.16); mean difference (95 % CI) 0.82 (−0.43, 2.07); p < 0.001 for non-inferiority]. There were no significant differences in PSQI scores on POD3 and POD7. In addition, the score of anxiety, depression, and pain on the 3rd, 7th, and 30th day after surgery have no significant differences between the propofol and the desflurane group, respectively. The postoperative NREM was higher in the desflurane group than that in the propofol group. The effects of desflurane-based volatile anesthesia maintenance on postoperative sleep quality is not inferior to that of propofol-based total intravenous anesthesia, and these two drugs may have different effects on the sleep structure. ClinicalTrials.gov Identifier: NCT04805775. • General anesthetics can cause postoperative sleep disturbance in patients after surgery. • The relationship between desflurane and postoperative sleep disturbance is still unknown. • The effects of desflurane on postoperative sleep quality is not inferior to propofol. [ABSTRACT FROM AUTHOR]

To compare the effects of propofol, ketamine–propofol and isoflurane, at similar anesthetic depth, on cardiopulmonary variables in unpremedictated chickens. Prospective, randomized, crossover experimental trial. A total of 10 male Leghorn domestic chickens, aged 3 months and body mass 1.4–2.0 kg. Birds were randomly assigned to each of three anesthetic protocols, 7 days apart: intravenous propofol, intravenous ketamine–propofol or isoflurane. Anesthesia was induced (indicated by loss of righting reflex and tracheal intubation) and maintained with propofol (10 mg kg–1 minute–1, then 1.1 mg kg–1 minute–1), ketamine–propofol (5 mg mL–1 ketamine and 5 mg mL–1 propofol combined; 10 mg kg–1 minute–1, then 1.1 mg kg–1 minute–1) or isoflurane [5% vaporizer setting initially, then end-tidal concentration (F e ′Iso) of 2%] for 65 minutes. Anesthesia was maintained at a similar anesthetic depth based upon positive or negative responses to toe pinch. Heart rate (HR), respiratory rate (f R), noninvasive arterial blood pressure and arterial blood gases were measured during anesthesia. Propofol or ketamine–propofol infusion rates and F e′ Iso required to prevent movement in response to a noxious stimulus and recovery times were recorded. Anesthesia induction dose was 9.0 ± 0.8 (mean ± SD) and 12.2 ± 0.3 mg kg–1 for propofol and ketamine–propofol, respectively. Propofol and ketamine–propofol infusion rates and F e′ Iso required to prevent movement in response to the noxious stimulus were 0.88 ± 0.14 mg kg–1 minute–1, 0.92 ± 0.14 mg kg–1 minute–1 and 1.45 ± 0.28%, respectively. Cardiopulmonary variables remained clinically acceptable, but ketamine–propofol was associated with a significantly higher HR (p = 0.0001) and lower f R (p = 0.0001). Time to extubation did not differ among treatments. Cardiovascular and respiratory variables were maintained within normal ranges in all treatments. Coadministration of ketamine with propofol significantly reduced the induction and maintenance dose of propofol. [ABSTRACT FROM AUTHOR]

To evaluate the propofol-sparing and hemodynamic effects of guaifenesin administered for co-induction of anesthesia in sheep. Prospective, blinded, two-way crossover experimental study. Thirteen healthy adult female sheep. Anesthesia was induced without premedication with intravenous (IV) guaifenesin 5% at 100 mg kg–1 (GGE) or an equivalent volume of physiologic saline (SAL), followed by IV propofol at a controlled rate (1 mg kg–1 min–1). Heart rate (HR), respiratory rate and oscillometric noninvasive arterial blood pressure (NIBP) were recorded at baseline after co-induction administration, following endotracheal intubation and every 2 minutes thereafter for 10 minutes. Propofol doses required to achieve intubation after each co-induction treatment were compared by independent Student's t -test. Values of p < 0.05 were considered statistically significant. The propofol dose required (mean ± standard deviation) to achieve intubation was significantly lower (p = 0.001) in the GGE treatment (3.40 ± 0.74 mg kg–1) than in the SAL treatment (5.94 ± 1.09 mg kg–1). HR was increased after anesthetic induction compared with baseline in both treatments. HR was generally lower in the GGE treatment than in the SAL treatment. NIBP did not vary between GGE and SAL treatments. Guaifenesin, when administered as a co-induction agent with propofol in sheep, reduces propofol dose requirements and maintains hemodynamic variables within a clinically acceptable range. [ABSTRACT FROM AUTHOR]

To compare the incidence of delirium and early (at 1 week) postoperative cognitive dysfunction (POCD) between propofol-based total intravenous anesthesia (TIVA) and volatile anesthesia with sevoflurane in adult patients undergoing elective coronary artery bypass graft surgery (CABG) with cardiopulmonary bypass (CPB). This was a prospective randomized single-blinded study. The study was conducted at a single institution, the Sree Chitra Tirunal Institute for Medical Sciences and Technology, a tertiary care institution and university-level teaching hospital. Seventy-two patients undergoing elective CABG under CPB participated in this study. This study was conducted on 72 adult patients (>18 years) undergoing elective CABG under CPB who were randomized to receive propofol or sevoflurane. Anesthetic depth was monitored to maintain the bispectral index between 40 and 60. Delirium was assessed using the Confusion Assessment Method for the Intensive Care Unit. Early POCD was diagnosed when there was a reduction of >2 points in the Montreal Cognitive Assessment score compared to baseline. Cerebral oximetry changes using near-infrared spectroscopy (NIRS), atheroma grades, and intraoperative variables were compared between the 2 groups. Seventy-two patients were randomized to receive propofol (n = 36) or sevoflurane (n = 36). The mean patient age was 59.4 ± 8.6 years. The baseline and intraoperative variables, including atheroma grades, NIRS values, hemoglobin, glycemic control, and oxygenation, were comparable in the 2 groups. Fifteen patients (21.7%) patients developed delirium, and 31 patients (44.9%) had early POCD. The incidence of delirium was higher with sevoflurane (n = 12; 34.2%) compared to propofol (n = 3; 8.8%) (odds ratio [OR], 1.72; 95% confidence interval [CI], 1.13-2.62; p = 0.027)*. POCD was higher with sevoflurane (n = 20; 57.1%) compared to propofol (n = 11; 32.3%) (OR, 1.63; 95% CI, 1.01-2.62; p = 0.038)*. In patients aged >65 years, delirium was higher with sevoflurane (7/11; 63.6%) compared to propofol (1/7; 14.2%) (p = 0.03)*. Propofol-based TIVA was associated with a lower incidence of delirium and POCD compared to sevoflurane in this cohort of patients undergoing CABG under CPB. Large-scale, multicenter randomized trials with longer follow-up are needed to substantiate the clinical relevance of this observation. [ABSTRACT FROM AUTHOR]

The comparative effectiveness of volatile anaesthesia and total intravenous anaesthesia (TIVA) in terms of patient outcomes after cardiac surgery remains a topic of debate. Multicentre randomised trial in 16 tertiary hospitals in China. Adult patients undergoing elective cardiac surgery were randomised in a 1:1 ratio to receive volatile anaesthesia (sevoflurane or desflurane) or propofol-based TIVA. The primary outcome was a composite of predefined major complications during hospitalisation and mortality 30 days after surgery. Of the 3123 randomised patients, 3083 (98.7%; mean age 55 yr; 1419 [46.0%] women) were included in the modified intention-to-treat analysis. The composite primary outcome was met by a similar number of patients in both groups (volatile group: 517 of 1531 (33.8%) patients vs TIVA group: 515 of 1552 (33.2%) patients; relative risk 1.02 [0.92–1.12]; P =0.76; adjusted odds ratio 1.05 [0.90–1.22]; P =0.57). Secondary outcomes including 6-month and 1-yr mortality, duration of mechanical ventilation, length of ICU and hospital stay, and healthcare costs, were also similar for the two groups. Among adults undergoing cardiac surgery, we found no difference in the clinical effectiveness of volatile anaesthesia and propofol-based TIVA. Chinese Clinical Trial Registry (ChiCTR-IOR-17013578). [ABSTRACT FROM AUTHOR]

To compare changes in oesophageal (T-Oeso) and rectal (T-Rec) temperature in dogs during general anaesthesia and premedicated with fentanyl, medetomidine–fentanyl or acepromazine–fentanyl. Prospective, randomized, blind clinical study. A total of 120 healthy dogs, aged 2–10 years and weighing 5–20 kg. Dogs were randomly allocated to one of three groups. Animals of F group were premedicated with fentanyl (0.01 mg kg–1), MF group with medetomidine (0.005 mg kg–1) and fentanyl (0.01 mg kg–1) and AF group with acepromazine (0.01 mg kg–1) and fentanyl (0.01 mg kg–1). Anaesthesia was induced with propofol and maintained with isoflurane in oxygen–air mixture. Fentanyl was administered continuously (0.01 mg kg–1 hour–1). The T-Oeso, T-Rec and ambient temperatures were recorded after induction (T0) and subsequently at 10 minute intervals for 60 minutes (T10–T60). Data were analysed using anova or their non-parametric equivalents (p < 0.05). Median T-Oeso was significantly higher in MF group between T0–T20 compared with other groups. Median T-Oeso significantly decreased in F group from 38.0 °C (T0) to 37.4 °C (T30), 37.1 °C (T40), 36.9 °C (T50) and 36.6 °C (T60), in MF group from 38.3 °C (T0) to 37.7 °C (T30), 37.5 °C (T40), 37.2 °C (T50) and 37.1 °C (T60) and in AF group from 37.7 °C (T0) to 37.3 °C (T40), 37.2 °C (T50) and 37.1 °C (T60). The T-Rec significantly decreased in F group from 38.0 °C (T0) to 37.4 °C (T40), 37.2 °C (T50) and 36.9 °C (T60), in MF group from 38.3 °C (T0) to 37.5 °C (T50) and 37.4 °C (T60) and in AF group from 38.2 °C (T0) to 37.6 °C (T40), 37.5 °C (T50) and 37.4 °C (T60). Premedication with fentanyl, medetomidine–fentanyl or acepromazine–fentanyl in the doses used decreased the T-Oeso and T-Rec. The T-Oeso at the beginning of anaesthesia was higher after premedication with medetomidine–fentanyl. However, this difference was not clinically significant. [ABSTRACT FROM AUTHOR]

The occurrence of hypotension after induction of general anaesthesia is common in geriatric patients, and should be prevented to minimise perioperative complications. Compared with propofol, remimazolam potentially has a lower incidence of hypotension. This study aimed to compare the incidence of hypotension after general anaesthesia induction with remimazolam or propofol in geriatric patients. This single-centre, double-blind, randomised trial enrolled 90 patients aged ≥80 yr who received general anaesthesia for scheduled surgery. Patients were randomised to receive remimazolam (12 mg kg−1 h−1) or propofol (0.025 mg kg−1 s−1) for anaesthesia induction, with remifentanil and sevoflurane. The presence or absence of hypertension on the ward served as the stratification factor. The incidence of hypotension after the induction of general anaesthesia, defined as a noninvasive mean arterial pressure of <65 mm Hg measured every minute from initiation of drug administration to 3 min after tracheal intubation, was the primary outcome. Subgroup analysis was performed for the primary outcome using preoperative ward hypertension, clinical frailty scale, Charlson Comorbidity Index, and age. Three subjects were excluded before drug administration, and 87 subjects were included in the analysis. The incidence of hypotension was 72.1% (31/43) and 72.7% (32/44) with remimazolam or propofol, respectively. No statistically significant differences (adjusted odds ratio, 0.96; 95% confidence interval, 0.37–2.46; P =0.93) were observed between groups. Subgroup analysis revealed no significant differences between groups. Compared with propofol, remimazolam did not reduce the incidence of hypotension after general anaesthesia induction in patients aged ≥80 yr. UMIN000042587. [ABSTRACT FROM AUTHOR]

Propofol and sevoflurane are two of the most commonly used anaesthetics for paediatric surgery. Data from some clinical trials suggest that postoperative pain incidence is lower when propofol is used for maintenance of anaesthesia compared with sevoflurane, although this is not clear. This meta-analysis compared postoperative pain following maintenance of anaesthesia with propofol or sevoflurane in paediatric surgeries. PubMed Medline, Embase, Scopus, Web of Science and Cochrane Library were searched for randomised controlled trials (RCTs) that compared postoperative pain between sevoflurane and propofol anaesthesia in children. After quality assessment, a meta-analysis was carried out using bias-adjusted inverse heterogeneity methods, heterogeneity using I 2 and publication bias using Doi plots. In total, 13 RCTs with 1174 children were included. The overall synthesis suggested nearly two-fold higher odds of overall postoperative pain in the sevoflurane group compared with the propofol group (odds ratio [OR] 1.88, 95% confidence interval [CI] 1.12–3.15, I 2=58.2%). Further, children in the sevoflurane group had higher odds of having higher pain scores (OR 3.18, 95% CI 1.83–5.53, I 2=20.9%), and a 60% increase in the odds of requiring postoperative rescue analgesia compared with propofol (OR 1.60, 95% CI 0.89–2.88, I 2=58.2%). Children maintained on inhalational sevoflurane had higher odds of postoperative pain compared with those maintained on propofol. The results also suggest that sevoflurane is associated with higher odds of needing postoperative rescue analgesia compared with propofol. The protocol for this systematic review and meta-analysis was registered on the International Prospective Register of Systematic Reviews (PROSPERO) with registration ID CRD42023445913. [ABSTRACT FROM AUTHOR]

The aim of this study was to determine what is considered a long oral surgery and conduct a cost-effective analysis of sedative agents used for intravenous sedation (IVS) and sedation protocols for such procedures. Pubmed and Google Scholar databases were used to identify human studies employing IVS for extractions and implant-related surgeries, between 2003 and July/2023. Sedation protocols and procedure lengths were documented. Sedative satisfaction, operator satisfaction, and sedation assessment were also recorded. Cost estimation was based on The British National Formulary (BNF). To assess bias, the Cochrane Risk of Bias tools were employed. This review identified 29 randomised control trials (RCT), six cohorts, 14 case-series, and one case-control study. The study defined long procedures with an average duration of 31.33 minutes for extractions and 79.37 minutes for implant-related surgeries. Sedative agents identified were midazolam, dexmedetomidine, propofol, and remimazolam. Cost analysis revealed midazolam as the most cost-effective option (<10 pence per procedure per patient) and propofol the most expensive option (approximately £46.39). Bias analysis indicated varying degrees of bias in the included studies. Due to diverse outcome reporting, a comparative network approach was employed and revealed benefits of using dexmedetomidine, propofol, and remimazolam over midazolam. Midazolam, dexmedetomidine, propofol, and remimazolam demonstrated safety and efficacy as sedative agents for conscious IVS in extended procedures like extractions or implant-related surgeries. While midazolam is the most cost-effective option, dexmedetomidine, propofol, and remimazolam offer subjective and clinical benefits. The relatively higher cost of propofol may impede its widespread use. Dexmedetomidine and remimazolam stand out as closely priced options, necessitating further clinical investigations for comparative efficacy assessment. [ABSTRACT FROM AUTHOR]

Propofol has a favourable efficacy profile in gastrointestinal endoscopic procedures, however adverse events remain frequent. Emerging evidence supports remimazolam use in gastrointestinal endoscopy. This systematic review and meta-analysis compares remimazolam and propofol, both combined with a short-acting opioid, for sedation of adults in gastrointestinal endoscopy. We searched MEDLINE, Embase, and Cochrane databases for randomised controlled trials comparing efficacy-, safety-, and satisfaction-related outcomes between remimazolam and propofol, both combined with short-acting opioids, for sedation of adults undergoing gastrointestinal endoscopy. We performed sensitivity analyses, subgroup assessments by type of short-acting opioid used and age range, and meta-regression analysis using mean patient age as a covariate. We used R statistical software for statistical analyses. We included 15 trials (4516 subjects). Remimazolam was associated with a significantly lower sedation success rate (risk ratio [RR] 0.991; 95% confidence interval [CI] 0.984–0.998; high-quality evidence) and a slightly longer induction time (mean difference [MD] 9 s; 95% CI 4–13; moderate-quality evidence), whereas there was no significant difference between the sedatives in other time-related outcomes. Remimazolam was associated with significantly lower rates of respiratory depression (RR 0.41; 95% CI 0.30–0.56; high-quality evidence), hypotension (RR 0.43; 95% CI 0.35–0.51; moderate-quality evidence), hypotension requiring treatment (RR 0.25; 95% CI 0.12–0.52; high-quality evidence), and bradycardia (RR 0.42; 95% CI 0.30–0.58; high-quality evidence). There was no difference in patient (MD 0.41; 95% CI –0.07 to 0.89; moderate-quality evidence) and endoscopist satisfaction (MD –0.31; 95% CI –0.65 to 0.04; high-quality evidence) between both drugs. Remimazolam has clinically similar efficacy and greater safety when compared with propofol for sedation in gastrointestinal endoscopies. [ABSTRACT FROM AUTHOR]

Sleep disruption is a common occurrence during medical care and is detrimental to patient recovery. Long-term sedation in the critical care setting is a modifiable factor that affects sleep, but the impact of different sedative–hypnotics on sleep homeostasis is not clear. We conducted a systematic comparison of the effects of prolonged sedation (8 h) with i.v. and inhalational agents on sleep homeostasis. Adult Sprague–Dawley rats (n =10) received dexmedetomidine or midazolam on separate days. Another group (n =9) received propofol or sevoflurane on separate days. A third group (n =12) received coadministration of dexmedetomidine and sevoflurane. Wakefulness (wake), slow-wave sleep (SWS), and rapid eye movement (REM) sleep were quantified during the 48-h post-sedation period, during which we also assessed wake-associated neural dynamics using two electroencephalographic measures: theta-high gamma phase-amplitude coupling and high gamma weighted phase-lag index. Dexmedetomidine-, midazolam-, or propofol-induced sedation increased wake and decreased SWS and REM sleep (P <0.0001) during the 48-h post-sedation period. Sevoflurane produced no change in SWS, decreased wake for 3 h, and increased REM sleep for 6 h (P <0.02) post-sedation. Coadministration of dexmedetomidine and sevoflurane induced no change in wake (P >0.05), increased SWS for 3 h, and decreased REM sleep for 9 h (P <0.02) post-sedation. Dexmedetomidine, midazolam, and coadministration of dexmedetomidine with sevoflurane reduced wake-associated phase-amplitude coupling (P ≤0.01). All sedatives except sevoflurane decreased wake-associated high gamma weighted phase-lag index (P <0.01). In contrast to i.v. drugs, prolonged sevoflurane sedation produced minimal changes in sleep homeostasis and neural dynamics. Further studies are warranted to assess inhalational agents for long-term sedation and sleep homeostasis. [ABSTRACT FROM AUTHOR]

• The number of corticocortical evoked potentials decreases under anesthesia compared to the awake state. • The N1-peak latency is increased under propofol-anesthesia. • The topology of effective networks in awake patients is preserved under anesthesia. We compared the effective networks derived from Single Pulse Electrical Stimulation (SPES) in intracranial electrocorticography (ECoG) of awake epilepsy patients and while under general propofol-anesthesia to investigate the effect of propofol on these brain networks. We included nine patients who underwent ECoG for epilepsy surgery evaluation. We performed SPES when the patient was awake (SPES-clinical) and repeated this under propofol-anesthesia during the surgery in which the ECoG grids were removed (SPES-propofol). We detected the cortico-cortical evoked potentials (CCEPs) with an automatic detector. We constructed two effective networks derived from SPES-clinical and SPES-propofol. We compared three network measures (indegree, outdegree and betweenness centrality), the N1-peak-latency and amplitude of CCEPs between the two effective networks. Fewer CCEPs were observed during SPES-propofol (median: 6.0, range: 0–29) compared to SPES-clinical (median: 10.0, range: 0–36). We found a significant correlation for the indegree, outdegree and betweenness centrality between SPES-clinical and SPES-propofol (respectively r s = 0.77, r s = 0.70, r s = 0.55, p < 0.001). The median N1-peak-latency increased from 22.0 ms during SPES-clinical to 26.4 ms during SPES-propofol. Our findings suggest that the number of effective network connections decreases, but network measures are only marginally affected. The primary network topology is preserved under propofol. [ABSTRACT FROM AUTHOR]

To evaluate the effect of oral tasipimidine on dog handling, ease of catheter placement and propofol and isoflurane requirements for anaesthesia. Placebo-controlled, randomized, blinded, experimental trial. A group of seven adult Beagle dogs weighing (mean ± standard deviation) 13.1 ± 2.7 kg with a mean age of 18.6 ± 1 months. The dogs underwent four treatments before induction of anaesthesia with propofol. PP: placebo orally (PO) 60 minutes before induction of anaesthesia followed by placebo (NaCl 0.9%) intravenously (IV). TP: tasipimidine 30 μg kg–1 (PO) 60 minutes before induction of anaesthesia followed by placebo (NaCl 0.9%) IV. TMP: tasipimidine 30 μg kg–1 PO 60 minutes before induction of anaesthesia followed by methadone 0.2 mg kg–1 IV. TMPD: tasipimidine 30 μg kg–1 PO 60 minutes before induction of anaesthesia followed by methadone 0.2 mg kg–1 and dexmedetomidine 1 μg kg–1 IV followed by a dexmedetomidine constant rate infusion of 1 μg kg–1 hour–1. Sedation, response to catheter placement, intubation quality, time to loss of consciousness, time to intubation, required dose of propofol and minimum alveolar isoflurane concentration preventing motor movement (MAC NM) were determined. A mixed-model analysis or the Friedman and Mann–Whitney test were used; p -value < 0.05. Response to catheter placement did not differ between treatments. Tasipimidine alone reduced the propofol dose by 30%. Addition of methadone or methadone and dexmedetomidine reduced the propofol dose by 48% and 50%, respectively. Isoflurane MAC NM was reduced by 19% in tasipimidine-medicated dogs, whereas in combination with methadone or methadone and dexmedetomidine, isoflurane MAC NM was reduced by 35%. An anxiolytic dose of tasipimidine induced mild signs of sedation in dogs and reduced propofol and isoflurane requirements to induce and maintain anaesthesia, which needs to be considered in an anaesthetic plan. [ABSTRACT FROM AUTHOR]

To investigate if preoperative ondansetron reduces postoperative nausea associated with laparoscopic gastropexy and castration in dogs. Prospective clinical study. Twenty client-owned, healthy male dogs. Dogs were premedicated with dexmedetomidine (2–5 mcg kg–1) and methadone (0.2–0.5 mg kg–1) intramuscularly. General anesthesia was induced with propofol and maintained with an inhalant anesthetic agent. Dogs were randomized into group S (saline 0.1 mL kg–1, intravenously) or group O (ondansetron 0.2 mg kg–1, intravenously). Plasma and serum were collected before premedication and 3 hours postextubation to measure arginine vasopressin (AVP) and cortisol concentrations. Nausea scoring occurred before and 10 minutes after premedication, immediately after extubation, and at 1, 2 and 3 hours postextubation. Data were analyzed by mixed and split-plot anova with Bonferroni adjustment for the number of group comparisons. Significance was set at p < 0.05. Nausea scores increased over time at 1 (p = 0.01) and 2 (p < 0.001) hours postextubation in both groups compared with before premedication. Median nausea score (0–100 mm) for groups S and O before premedication were 2.5 and 0.5 mm, respectively. At 1 and 2 hours postextubation, group S scored 7.5 and 4.0 mm and group O scored 6.0 and 5.0 mm, respectively. No significant differences in nausea scores within or between groups were observed before premedication and 3 hours postextubation. Cortisol concentrations increased significantly 3 hours postextubation in both groups (p < 0.001) compared with before premedication, with no differences between groups. AVP concentrations showed no significant differences within or between groups. Preoperative intravenous administration of ondansetron (0.2 mg kg–1) did not impact postoperative nausea after laparoscopic gastropexy and castration. Investigation of higher doses of ondansetron on the incidence of postoperative nausea and vomiting in dogs after surgery is warranted. [ABSTRACT FROM AUTHOR]

Although propofol is widely used for gastrointestinal endoscopic sedation, cardiopulmonary adverse events remain common. Ciprofol is a new intravenous anaesthetic agent demonstrating respiratory and hemodynamic stability. This study aimed to clarify the benefits of ciprofol combined with alfentanil in bidirectional endoscopy (esophagogastroduodenoscopy followed by colonoscopy) to reduce adverse events and improve post-endoscopic recovery. A total of 185 patients scheduled to undergo bidirectional endoscopy were randomly divided into two groups: ciprofol combined with alfentanil or propofol combined with alfentanil. All patients received 7 µg/kg alfentanil intravenously before the study drugs were administered. The propofol group received a bolus of 1.2 mg/kg (0.12 ml/kg) propofol intravenously, whereas the ciprofol group received a bolus of 0.3 mg/kg (0.12 ml/kg) ciprofol intravenously. The primary outcome was the proportion of patients with cardiopulmonary adverse events (i.e., any one of the airway obstruction, apnoea, hypotension, hypertension, bradycardia, tachycardia or arrhythmias). Compared with propofol, ciprofol reduced cardiopulmonary adverse events by 43.51 % (34.4% vs. 60.9 %, P <0.001), mitigated respiratory adverse events by 54.74 % (17.2% vs. 38.0 %, P = 0.002) overall and by 59.05 % (12.9% vs. 31.5 %, P = 0.002) during the induction period. Ciprofol can significantly decrease respiratory depression events and provides a better sedative efficacy than propofol with higher recovery quality and satisfaction. [ABSTRACT FROM AUTHOR]

The aim of this study was to describe the onset and duration of action of escalating doses of atracurium in healthy, anesthetized goats. Randomized, blinded, triple crossover study. Animals A total of eight (five males and three females) healthy goats weighing 42.7–123.5 kg and aged from 11 months to 8 years. Goats were anesthetized three times with propofol and anesthesia was maintained with isoflurane. One of three doses of atracurium was administered intravenously 30 minutes after induction: 0.25 mg kg–1 (AT25), 0.5 mg kg–1 (AT50) or 0.75 mg kg–1 (AT75). Acceleromyographic train-of-four ratio (TOFR) followed by train-of-four counts (TOFC) were recorded at 30 second intervals after atracurium administration to determine blockade onset (TOFC = 0). The TOFR followed by TOFC were recorded at 5 minute intervals until return to pre-atracurium baseline (TOFR = 1.0). Normally distributed data were analyzed with repeated measures anova and a Tukey multiple comparison test. Data not normally distributed were analyzed with a Friedman test and a Dunn's multiple comparison test. For AT50 and AT75, 100% of goats achieved TOFC = 0 after atracurium administration. For AT25, however, 87.5% of goats achieved TOFC = 0 after atracurium administration. The onset time was shorter for AT75 [1.5 (0.5–1.5) minutes; median (range)] than for AT25 [2 (1–4) minutes] (p = 0.048). The duration of action [from onset time to complete reversal (TOFR = 1.0)] was significantly shorter for AT25 (52 ± 12 minutes, mean ± SD) than for AT50 (77 ± 18 minutes) (p < 0.001) and AT75 (85 ± 16 minutes) (p < 0.001). There was no significant difference in duration between AT50 and AT75 (p = 0.238). Doses of 0.5 and 0.75 mg kg–1 atracurium may produce complete neuromuscular blockade in healthy, anesthetized goats. [ABSTRACT FROM AUTHOR]

Information integration and network science are important theories for quantifying consciousness. However, whether these theories propose drug- or conscious state-related changes in EEG during anaesthesia-induced unresponsiveness remains unknown. A total of 72 participants were randomised to receive i.v. infusion of propofol, dexmedetomidine, or ketamine at a constant infusion rate until loss of responsiveness. High-density EEG was recorded during the consciousness transition from the eye-closed baseline to the unresponsiveness state and then to the recovery of the responsiveness state. Permutation cross mutual information (PCMI) and PCMI-based brain networks in broadband (0.1–45 Hz) and sub-band frequencies were used to analyse drug- and state-related EEG signature changes. PCMI and brain networks exhibited state-related changes in certain brain regions and frequency bands. The within-area PCMI of the frontal, parietal, and occipital regions, and the between-area PCMI of the parietal–occipital region (median [inter-quartile ranges]), baseline vs unresponsive were as follows: 0.54 (0.46–0.58) vs 0.46 (0.40–0.50), 0.58 (0.52–0.60) vs 0.48 (0.44–0.53), 0.54 (0.49–0.59) vs 0.47 (0.42–0.52) decreased during anaesthesia for three drugs (P <0.05). Alpha PCMI in the frontal region, and gamma PCMI in the posterior area significantly decreased in the unresponsive state (P <0.05). The frontal, parietal, and occipital nodal clustering coefficients and parietal nodal efficiency decreased in the unresponsive state (P <0.05). The increased normalised path length in delta, theta, and gamma bands indicated impaired global integration (P <0.05). The three anaesthetics caused changes in information integration patterns and network functions. Thus, it is possible to build a quantifying framework for anaesthesia-induced conscious state changes on the EEG scale using PCMI and network science. [ABSTRACT FROM AUTHOR]

The purpose of this study is to observe the postoperative sleep quality of insomnia patients undergoing laparoscopic gynecologic oncology surgery after total intravenous anesthesia. Prospective study. We conducted a prospective, observational study in our hospital. All patients underwent propofol-remifentanil anesthesia without other sedative medications before or during the operation. Pittsburgh Sleep Quality Index (PSQI) scores of the baseline value, night-1 (the first night after surgery), night-3, night-5, and night-30 were observed. Sixty-nine female insomnia patients were allocated based on the results of the PSQI and the diagnostic criteria of insomnia. The PSQI global scores were respectively 6 (5–8), 5 (4–6), 5 (3–6), and 6 (5–7) on night-1, night-3, night-5, and night-30, significantly lower than the baseline 7 (6–8) (P < 0.05). The 5 components (subjective sleep quality, sleep latency, sleep duration, sleep efficiency and daytime dysfunction) had significant changes at different postoperative time points (P < 0.05). The daytime dysfunction could also be improved 1 month after the surgery (P < 0.05). In contrast, the variations of sleep disturbance and use of sleep medication had no statistical differences. The sleep quality of female patients with insomnia was improved on the first night after surgery in the sides of sleep latency and daytime dysfunction, and the improvement could also be obtained 1 month after propofol-remifentanil general anesthesia. [ABSTRACT FROM AUTHOR]

In this study, an electrochemical sensor for the real-time monitoring of propofol (PPF) in anesthesia was developed using molecularly imprinted polymers and reduced graphene oxide-modified glassy carbon electrodes (MIPs/rGO/GCE). To make the electrode, GO was thermally reduced into rGO, which was then electrodeposited on GCE (rGO/GCE), followed by the electropolymerization of MIPs using LiClO 4 , pyrrole, and PPF (template) solution on rGO/GCE (MIPs/rGO/GCE). The PPF was then taken out of the pyrrole polymer. X-ray Diffraction (XRD), Scanning Electron Microscopy (SEM), and X-ray Photoelectron Spectroscopy (XPS) examinations of surface composition and morphology revealed that electropolymerization MIP on rGO/GCE and reduction and deposition of rGO on GCE were both successful processes. MIPs/rGO/GCE revealed significant sensitivity and selectivity towards PPF in electrochemical tests utilizing cyclic voltammetry (CV) and amperometry. Results demonstrated a linear range from 0.5 to 250 μM that was steady and wide, with a sensitivity of 1.0776 μA/μM and a detection limit value of 0.08 μM. MIPs/rGO/GCE demonstrated outstanding electrocatalytic activity over a broad linear range and a reasonable detection limit value for PPF concentrations. To assess the method's applicability for the analysis of PPF, it was applied to real biological samples of human plasma and urine. [ABSTRACT FROM AUTHOR]

Two methods for administering general anaesthesia are widely used: propofol-based total intravenous anaesthesia (propofol-TIVA) and inhalation volatile agent-based anaesthesia. Both modalities, which have been standards of care for several decades, boast a robust safety profile. Nevertheless, the potential differential effects of these anaesthetic techniques on immediate, intermediate, and extended postoperative outcomes remain a subject of inquiry. We discuss a recently published longitudinal analysis stemming from a multicentre randomised controlled trial comparing sevoflurane-based inhalation anaesthesia with propofol-TIVA in older patients with cancer, which showed a reduced incidence of emergence and postoperative delirium, comparable postoperative complication rates within 30 days after surgery, and comparable long-term survival rates. We undertake an assessment of the trial's methodological strengths and limitations, contextualise its results within the broader scientific evidence, and explore avenues for resolving the extant controversies in anaesthetic choice for cancer surgery. We aim to pave the way for the incorporation of precision medicine paradigms into the evolving landscape of perioperative care for patients with cancer. [ABSTRACT FROM AUTHOR]

To compare the effects of volatile anesthetics and propofol on neurocognitive function after cardiac surgery. A systematic review and meta-analysis of randomized controlled trials. A literature search of PubMed, EMBASE, CENTRAL, CINAHL, Scopus, and Web of Science databases was conducted. A total of 10 randomized controlled trials comparing volatile anesthetics and propofol in cardiac surgery were included in the study. The standardized mean difference and risk ratio were calculated to estimate pooled effect sizes. The primary outcome was the postoperative neurocognitive function score, and the secondary outcome was the incidence of delirium after cardiac surgery. The analysis did not show significant differences in postoperative neurocognitive function scores (standardized mean difference − 0.06, 95% CI − 0.81-0.69; p = 0.879). The incidences of delirium (risk ratio 1.10, 95% CI 0.81-1.50) between the volatile anesthetics and propofol groups were not significant (p = 0.533). Unlike noncardiac surgery, there are no differences between volatile anesthetics and propofol regarding postoperative neurocognitive dysfunction after cardiac surgery. [ABSTRACT FROM AUTHOR]

Propofol is commonly used in ICUs, but its long-term effects have not been thoroughly studied. In vitro studies suggest it may harm mitochondrial function, potentially affecting clinical outcomes. This study aimed to investigate the association between substantial propofol sedation and clinical outcomes in critically ill patients. We conducted a single-centre cohort study of critically ill, mechanically ventilated (≥7 days) adults to compare patients who received a substantial dose of propofol (cumulative >500 mg) during the first week of ICU admission with those who did not. The primary outcome was the association between substantial propofol administration and 6-month mortality, adjusted for relevant covariates. Subanalyses were performed for administration in the early (day 1–3) and late (day 4–7) acute phases of critical illness due to the metabolic changes in this period. Secondary outcomes included tracheostomy need and duration, length of ICU and hospital stay (LOS), discharge destinations, ICU, hospital, and 3-month mortality. A total of 839 patients were enrolled, with 73.7 % receiving substantial propofol administration (substantial propofol dose group). Six-month all-cause mortality was 32.4 %. After adjusting for relevant variables, we found no statistically significant difference in 6-month mortality between both groups. There were also no significant differences in secondary outcomes. Our study suggests that substantial propofol administration during the first week of ICU stay in the least sick critically ill, mechanically ventilated adult patients is safe, with no significant associations found with 6-month mortality, ICU or hospital LOS, differences in discharge destinations or need for tracheostomy. [ABSTRACT FROM AUTHOR]

Propofol use is contraindicated in patients on ketogenic diet (KD) due to higher risk of propofol infusion syndrome (PIS). This study is intended to provide a descriptive analysis of our experience with propofol bolus and short infusions for anesthetic care in patients on the KD and to evaluate if any signs of PIS were observed. All patients on the KD who underwent anesthesia with propofol between 2012 and 2022 were reviewed. Anesthetic encounters and charts were studied for type of surgical procedure; signs of PIS, including new cardiac arrhythmias, acidosis, or rhabdomyolysis in the periprocedural period; hypoglycemia; unplanned admissions within 24 hours of the procedure; if procedure was unexpectedly aborted; and increased seizure frequency within one week. We identified 65 patients, aged from one to 20 years who underwent 165 anesthetic encounters with propofol, of which 123 were boluses and 42 were infusions. In bolus dosing, the average dose was 2.8 mg/kg (0.7 to 12.8 ± 1.8 mg/kg). Of these, four encounters developed acidosis, one developed rhabdomyolysis, and one developed increased seizures. With infusions, the average infusion rate was 9 mg/kg/hour, with mean infusion duration of 83 minutes (10 to 352 ± 75 minutes). Of these, one developed acidosis and one increased seizures. No cases of PIS were identified. None of the adverse effects were attributed to propofol. Boluses and brief infusions of propofol for anesthetic use in patients on the KD did not cause PIS in our cohort. [ABSTRACT FROM AUTHOR]

Total intravenous anesthesia with propofol can be administered by target-controlled infusion pumps, which work on the principles of pharmacokinetic modeling. While designing this model, neurosurgical patients were excluded as the surgical site and drug action site remained the same (brain). Whether the predicted set propofol concentration and the actual brain site concentration correlate, especially in neurosurgical patients with impaired blood-brain barrier (BBB), is still unknown. In this study we compared the set propofol effect-site concentration in the target-controlled infusion pump with actual brain concentration measured by sampling the cerebrospinal fluid (CSF). Consecutive adult neurosurgical patients requiring propofol infusion intraoperatively were recruited. Blood and CSF samples were collected simultaneously when patients received propofol infusion at 2 different target effect-site concentrations—2 and 4 ug/mL. To study BBB integrity, CSF-to−blood albumin ratio and imaging findings were compared. The propofol level in the CSF was compared with set concentration using the Wilcoxon signed-rank test. Fifty patients were recruited, and the data were analyzed from 43 patients. There was no correlation between propofol concentration set in TCI and propofol concentration measured in blood and CSF. Though imaging findings were suggestive of BBB disruption in 37/43 patients, the mean (±standard deviation) CSF-to−serum albumin ratio was 0.0028 ± 0.002, suggesting intact BBB integrity (ratio >0.3 was considered as disrupted BBB). CSF propofol level did not correlate with set concentration in spite of acceptable clinical anesthetic effect. Also, the CSF-to−blood albumin measurement did not provide information on the BBB integrity. [ABSTRACT FROM AUTHOR]

To compare the effects of intramuscular premedication with a novel nonanalgesic [alfaxalone–midazolam–acepromazine (AMA)] and an analgesic [ketamine–midazolam–detomidine (KMD)] protocol on sedation end points and propofol requirements for induction of anesthesia in swine. Prospective experimental study. A total of 27 Yorkshire cross gilts weighing approximately 30 kg. Two sedation protocols, AMA and KMD, were compared. Time from intramuscular injection to ataxia, recumbency and nonresponsiveness to tactile stimulation was recorded. The propofol dose requirement for induction of general anesthesia and tracheal intubation, and any adverse events (paddling, twitching), were recorded. Data were tested for normality using a Shapiro–Wilk test. Propofol requirements were compared using a Student's t test. Times from injection to sedation end points were compared using a Mood's test, and significance was confirmed using a Kaplan–Meier curve with Wilcoxon test survival analysis. Sedation end points were reached significantly faster with KMD than with AMA. Nonresponsiveness occurred in 5 (0–16) and 9.5 (5–36) minutes for KMD and AMA, respectively (p = 0.011). No significant difference (p = 0.437) was found between propofol doses used in either group (KMD; 64.38 ± 5.98 mg, AMA; 72.00 ± 7.57 mg). More adverse events were noted with AMA (11/16 pigs) than with KMD (1/11 pigs). In pigs, AMA can be used as a reliable sedation protocol. Frequency of adverse events and time to reach sedation end points between AMA and KMD differed, but the dose of propofol needed to induce general anesthesia was not significantly different. [ABSTRACT FROM AUTHOR]

To retrospectively evaluate the feasibility of a propofol infusion for anaesthetic maintenance in guinea pigs. Retrospective case series. Client-owned guinea pigs undergoing general anaesthesia. Anaesthetic records of guinea pigs anaesthetized between March 2015 and March 2018 were reviewed. Animals administered a propofol infusion for > 20 minutes were identified and evaluated. Procedure performed, pre-anaesthetic medication, preoperative and intraoperative respiratory rate (f R) and heart rates (HRs), total amount of propofol administered, total anaesthesia and recovery times were extracted from the records and analysed using descriptive statistics and Pearson correlation tests. Data are reported as mean (range). Records of 14 animals meeting the criteria were identified. Following drug combinations were administered for premedication: butorphanol 0.43 (0.3–0.5) mg kg–1, medetomidine 0.1 (0.05–0.2) mg kg–1 and midazolam 1 (0.5–2) mg kg–1 (n = 3); methadone 0.33 (0.25–0.5) mg kg–1, medetomidine 0.07 (0.01–0.1) mg kg–1 and midazolam 0.66 (0.5–1) mg kg–1 (n = 3); butorphanol 0.5 mg kg–1, medetomidine 0.05 mg kg–1 and ketamine 5 mg kg–1 (n = 2); buprenorphine 0.01 mg kg–1, medetomidine 0.07 (0.04–1) mg kg–1 and ketamine 4 (3–5) mg kg–1 (n = 3); butorphanol 0.5 mg kg–1, alfaxalone 1 mg kg–1 and midazolam 0.5 mg kg–1 (n = 1); and methadone 0.38 (0.25–0.5) mg kg–1, medetomidine 0.08 (0.06–1) mg kg–1 with midazolam 0.75 (0.5–1) mg kg–1 (n = 2). Preoperative and intraoperative HRs were 240 (160–300) and 170 (140–200) beats minute–1, respectively. Preoperative and intraoperative f R were 63 (50–86) and 37 (18–80) breaths minute–1, respectively. The propofol infusion rate was 0.45 (0.17–0.80) mg kg–1 minute–1. Total anaesthesia and recovery times were 60 (25–145) and 17 (8–60) minutes, respectively. A slight correlation was found between total propofol dose infused and recovery time (r = 0.58). Propofol infusions may be a useful alternative to inhalant anaesthetics. [ABSTRACT FROM AUTHOR]

Variability is high in predicted propofol concentrations during clinical anaesthesia titrated by target-controlled infusion (TCI) to maintain a processed EEG parameter (bispectral index [BIS]) within a specified range. We have shown that the potential for improving the pharmacokinetic model is minimal. The drug titration paradox revealed that titration challenges the classical relationship between drug dose and effect in both individuals and the population. We hypothesised that dynamic factors during surgery beyond the static genetic, epigenetic, and other factors such as age, height, and weight affect the necessary dose. We compared the variability of measured end-tidal sevoflurane concentrations with predicted effect-site propofol concentrations when titrated to a BIS range of 40–60, with the hypothesis that the variability in measured sevoflurane concentrations would not be less than the variability in estimated propofol concentrations. Clinical data from 2280 surgical procedures >1 h in duration were included in the analysis. Anaesthesia with sevoflurane or propofol was based on an institutional protocol. The titration performance for both drugs was assessed by comparing BIS values 30 min after skin incision. The variability of the required concentrations at the same time point was calculated and compared. The achieved 30-min post-incision BIS ranges were not significantly different for sevoflurane or propofol TCI (30 [99% CI: 28–33] and 31 [99% CI: 27–36], respectively). The variability of sevoflurane concentrations was not significantly different from measured predicted propofol concentrations during BIS-guided anaesthesia (normalized concentration range of 0.89 [99% CI: 0.78–0.99] and 0.93 [99% CI 0.87–1.02). Improvements in prediction accuracy of pharmacokinetic models beyond that of those already in clinical use are unlikely to reduce variability in target anaesthetic concentrations across patients in clinical practice. [ABSTRACT FROM AUTHOR]

Although procedural sedation is an established method of anesthesia for transcatheter aortic valve replacement (TAVR), reliable evidence to guide the choice of a suitable sedative agent remains scarce. Accordingly, this trial aimed to compare the effect of procedural sedation with dexmedetomidine versus propofol on postoperative neurocognitive and related clinical outcomes in patients undergoing TAVR. Prospective, randomized, double-blind clinical trial. The study was conducted at the University Medical Centre Ljubljana, Slovenia. The study enrolled 78 patients who underwent TAVR under procedural sedation between January 2019 and June 2021. Seventy-one patients randomized into the propofol group (n = 34) and dexmedetomidine group (n = 37) were included in the final analysis. Patients in the propofol group received sedation with propofol (continuous intravenous infusion of 0.5-2.5 mg/kg/h), whereas patients in the dexmedetomidine group received sedation with dexmedetomidine (loading dose of 0.5 µg/kg over 10 minutes followed by continuous intravenous infusion of 0.2-1.0 µg/kg/h). Minimental state examination (MMSE) was performed before and 48 hours after TAVR. There was no statistically significant difference in MMSE scores between groups before TAVR (p = 0.253), but the MMSE after the procedure revealed a significantly lower incidence of delayed neurocognitive recovery (p = 0.005) and thus better cognitive outcomes in the dexmedetomidine group (p = 0.022). Compared with propofol, procedural sedation with dexmedetomidine in TAVR was associated with a significantly lower incidence of delayed neurocognitive recovery. [ABSTRACT FROM AUTHOR]

Some patients experience sleep disturbances after endoscopy performed under sedation. This study aimed to evaluate the effects of propofol on sleep quality after gastrointestinal endoscopy (GE). This study was a prospective cohort study. This study enrolled 880 patients who underwent GE. Patients who chose to undergo GE under sedation received intravenous propofol, whereas the control group did not. The Pittsburgh Sleep Quality Index (PSQI) was measured before GE (PSQI-1) and 3 weeks (PSQI-2) after GE. The Groningen Sleep Score Scale (GSQS) was used before GE (GSQS-1) and 1 (GSQS-2) and 7 days (GSQS-3) after GE. There was a significant increase in GSQS scores from baseline to days 1 and 7 after GE (GSQS-2 vs GSQS-1, P <.001, GSQS-3 vs GSQS-1, P =.008). However, no significant changes were observed in the control group (GSQS-2 vs GSQS-1, P =.38, GSQS-3 vs GSQS-1, P =.66). On day 21, there were no significant changes in the baseline PSQI scores over time in either group (sedation group, P =.96; control group, P =.95). GE with propofol sedation negatively affected sleep quality for 7 days after GE but not 3 weeks after GE. [ABSTRACT FROM AUTHOR]

Sleep disorders can profoundly affect neurological function. We investigated changes in social and anxiety-related brain functional connectivity induced by sleep deprivation, and the potential therapeutic effects of the general anaesthetics propofol and sevoflurane in rats. Twelve-week-old male Sprague–Dawley rats were subjected to sleep deprivation for 20 h per day (from 14:00 to 10:00 the next day) for 4 consecutive weeks. They were free from sleep deprivation for the remaining 4 h during which they received propofol (40 mg kg–1 i.p.) or sevoflurane (2% for 2 h) per day or no treatment. These cohorts were instrumented for EEG/EMG recordings on days 2, 14, and 28. Different cohorts were used for open field and three-chambered social behavioural tests, functional MRI, nuclear magnetic resonance spectroscopy, and positron emission tomography imaging 48 h after 4 weeks of sleep deprivation. Propofol protected against sleep deprivation-induced anxiety behaviours with more time (44.7 [8.9] s vs 24.2 [4.1] s for the sleep-deprivation controls; P<0.001) spent in the central area of the open field test and improved social preference index by 30% (all P<0.01). Compared with the sleep-deprived rats, propofol treatment enhanced overall functional connectivity by 74% (P<0.05) and overall glucose metabolism by 30% (P<0.01), and improved glutamate kinetics by 20% (P<0.05). In contrast, these effects were not found after sevoflurane treatment. Unlike sevoflurane, propofol reduced sleep deprivation-induced social and anxiety-related behaviours. Propofol might be superior to sevoflurane for patients with sleep disorders who receive anaesthesia, which should be studied in clinical studies. [ABSTRACT FROM AUTHOR]

To identify which gynecologic procedures are eligible to be performed under PSA with propofol and to describe safety and effectiveness of these procedures in this setting. A systematic review of the literature was conducted in Pubmed (MEDLINE), Embase and The Cochrane Library from inception until September 21st 2022. Cohort studies and randomized controlled trials were included when they reported on clinical outcomes of gynecologic procedures under procedural sedation and analgesia in which propofol was used as an anesthetic. Studies were excluded when sedation without propofol was used, when they only mentioned the use of procedural sedation and analgesia but did not describe any clinical outcome parameters or when < 10 patients were included. The primary outcome parameter was completeness of procedure. Secondary outcome parameters were type of gynecologic procedure, intraoperative complication rate, patient satisfaction, postoperative pain, duration of hospital admission, patient's discomfort and ease of procedure as judged by the surgeon. The Cochrane risk of bias tool and the ROBINS-I tool were used for bias assessment. A narrative synthesis of the findings from the included studies was provided. Numbers and percentages were presented, as well as means with standard deviations and medians with interquartile range where applicable. Eight studies were included. A total of 914 patients underwent gynecologic surgical procedures with procedural sedation and analgesia with propofol. Gynecological procedures varied from hysteroscopic procedures, vaginal prolapse surgery and laparoscopic procedures. The percentage of complete procedures was 89.8%−100%. Complications occurred in 0–6.5% of patients. Other outcomes were measured in various ways, but overall patient satisfaction was high and postoperative pain was low. The use of PSA with propofol is promising for a wide range of gynecologic procedures, including hysteroscopic procedures, vaginal prolapse surgery and laparoscopic procedures. The use of PSA with propofol seems to be effective and safe and leads to high degree of patient satisfaction. More research is needed in order to determine for which types of procedures PSA can be used. [ABSTRACT FROM AUTHOR]

Propofol and remifentanil are frequently combined for the induction and maintenance of general anaesthesia. Both propofol and remifentanil cause vasodilation and potentially reduce arterial BP. We aimed to develop a mechanism-based model that characterises the haemodynamic interactions between remifentanil and propofol. Data from two clinical trials in healthy volunteers were analysed using remifentanil-alone, propofol-alone, and combination groups. We evaluated remifentanil effects on haemodynamics using a previously developed mechanism-based haemodynamic model of propofol. The interaction between propofol and remifentanil was explored using the principles of the general pharmacodynamic interaction (GPDI) model. Remifentanil alone increased the dissipation rate of total peripheral resistance by 50% at 3.0 ng ml−1. Additionally, the dissipation rates of HR and stroke volume were attenuated by 4.8% and 4.9% per 1 ng ml−1 increase in remifentanil concentration, respectively. The maximal effect of propofol alone in decreasing the production rate of total peripheral resistance was 78%, which decreased to 32% when combined with remifentanil 4 ng ml−1. The effects of remifentanil on HR and stroke volume were attenuated by propofol with maximum decreases of 11.9% and 21.2%, respectively. Goodness-of-fit plots and prediction-corrected visual predictive check plots showed good predictive performance of the models. The structure of the previous mechanism-based haemodynamic model for propofol was able to describe the effects of remifentanil alone on haemodynamic variables. The GPDI model provided a good framework for characterising the pharmacodynamic interaction between remifentanil and propofol on haemodynamic properties. NCT02043938; NCT03143972. [ABSTRACT FROM AUTHOR]

Anaesthetic-induced unresponsiveness and non-rapid eye movement (NREM) sleep share common neural pathways and neurophysiological features. We hypothesised that these states bear resemblance also at the experiential level. We compared, in a within-subject design, the prevalence and content of experiences in reports obtained after anaesthetic-induced unresponsiveness and NREM sleep. Healthy males (N =39) received dexmedetomidine (n =20) or propofol (n =19) in stepwise doses to induce unresponsiveness. Those rousable were interviewed and left unstimulated, and the procedure was repeated. Finally, the anaesthetic dose was increased 50%, and the participants were interviewed after recovery. The same participants (N =37) were also later interviewed after NREM sleep awakenings. Most subjects were rousable, with no difference between anaesthetic agents (P =0.480). Lower drug plasma concentrations were associated with being rousable for both dexmedetomidine (P =0.007) and propofol (P =0.002) but not with recall of experiences in either drug group (dexmedetomidine: P =0.543; propofol: P =0.460). Of the 76 and 73 interviews performed after anaesthetic-induced unresponsiveness and NREM sleep, 69.7% and 64.4% included experiences, respectively. Recall did not differ between anaesthetic-induced unresponsiveness and NREM sleep (P =0.581), or between dexmedetomidine and propofol in any of the three awakening rounds (P >0.05). Disconnected dream-like experiences (62.3% vs 51.1%; P =0.418) and memory incorporation of the research setting (88.7% vs 78.7%; P =0.204) were equally often present in anaesthesia and sleep interviews, respectively, whereas awareness, signifying connected consciousness, was rarely reported in either state. Anaesthetic-induced unresponsiveness and NREM sleep are characterised by disconnected conscious experiences with corresponding recall frequencies and content. Clinical trial registration. This study was part of a larger study registered at ClinicalTrials.gov (NCT01889004). [ABSTRACT FROM AUTHOR]

Delirium is a common and disturbing postoperative complication that might be ameliorated by propofol-based anaesthesia. We therefore tested the primary hypothesis that there is less delirium after propofol-based than after sevoflurane-based anaesthesia within 7 days of major cancer surgery. This multicentre randomised trial was conducted in 14 tertiary care hospitals in China. Patients aged 65–90 yr undergoing major cancer surgery were randomised to either propofol-based anaesthesia or to sevoflurane-based anaesthesia. The primary endpoint was the incidence of delirium within 7 postoperative days. A total of 1228 subjects were enrolled and randomised, with 1195 subjects included in the modified intention-to-treat analysis (mean age 71 yr; 422 [35%] women); one subject died before delirium assessment. Delirium occurred in 8.4% (50/597) of subjects given propofol-based anaesthesia vs 12.4% (74/597) of subjects given sevoflurane-based anaesthesia (relative risk 0.68 [95% confidence interval {CI}: 0.48–0.95]; P =0.023; adjusted relative risk 0.59 [95% CI: 0.39–0.90]; P =0.014). Delirium reduction mainly occurred on the first day after surgery, with a prevalence of 5.4% (32/597) with propofol anaesthesia vs 10.7% (64/597) with sevoflurane anaesthesia (relative risk 0.50 [95% CI: 0.33–0.75]; P =0.001). Secondary endpoints, including ICU admission, postoperative duration of hospitalisation, major complications within 30 days, cognitive function at 30 days and 3 yr, and safety outcomes, did not differ significantly between groups. Delirium was a third less common after propofol than sevoflurane anaesthesia in older patients having major cancer surgery. Clinicians might therefore reasonably select propofol-based anaesthesia in patients at high risk of postoperative delirium. Chinese Clinical Trial Registry (ChiCTR-IPR-15006209) and ClinicalTrials.gov (NCT02662257). [ABSTRACT FROM AUTHOR]

Animal studies have shown that isoflurane and propofol have differential effects on Alzheimer's disease (AD) pathology and memory, although it is unclear whether this occurs in humans. This was a nested randomised controlled trial within a prospective cohort study; patients age ≥60 yr undergoing noncardiac/non-neurological surgery were randomised to isoflurane or propofol for anaesthetic maintenance. Cerebrospinal fluid (CSF) was collected via lumbar puncture before, 24 h, and 6 weeks after surgery. Cognitive testing was performed before and 6 weeks after surgery. Nonparametric methods and linear regression were used to evaluate CSF biomarkers and cognitive function, respectively. There were 107 subjects (54 randomised to isoflurane and 53 to propofol) who completed the 6-week follow-up and were included in the analysis. There was no significant effect of anaesthetic treatment group, time, or group-by-time interaction for CSF amyloid-beta (Aβ), tau, or phospho-tau 181p levels, or on the tau/Aβ or p-tau 181p /Aβ ratios (all P >0.05 after Bonferroni correction). In multivariable-adjusted intention-to-treat analyses, there were no significant differences between the isoflurane and propofol groups in 6-week postoperative change in overall cognition (mean difference [95% confidence interval]: 0.01 [–0.12 to 0.13]; P =0.89) or individual cognitive domains (P >0.05 for each). Results remained consistent across as-treated and per-protocol analyses. Intraoperative anaesthetic maintenance with isoflurane vs propofol had no significant effect on postoperative cognition or CSF Alzheimer's disease-related biomarkers within 6 weeks after noncardiac, non-neurological surgery in older adults. NCT01993836. [ABSTRACT FROM AUTHOR]

Experimental evidence indicates that i.v. anaesthesia might reduce cancer recurrence compared with volatile anaesthesia, but clinical information is observational only. We therefore tested the primary hypothesis that propofol-based anaesthesia improves survival over 3 or more years after potentially curative major cancer surgery. This was a long-term follow-up of a multicentre randomised trial in 14 tertiary hospitals in China. We enrolled 1228 patients aged 65–90 yr who were scheduled for major cancer surgery. They were randomised to either propofol-based i.v. anaesthesia or to sevoflurane-based inhalational anaesthesia. The primary endpoint was overall survival after surgery. Secondary endpoints included recurrence-free and event-free survival. Amongst subjects randomised, 1195 (mean age 72 yr; 773 [65%] male) were included in the modified intention-to-treat analysis. At the end of follow-up (median 43 months), there were 188 deaths amongst 598 patients (31%) assigned to propofol-based anaesthesia compared with 175 deaths amongst 597 patients (29%) assigned to sevoflurane-based anaesthesia; adjusted hazard ratio 1.02; 95% confidence interval (CI): 0.83–1.26; P =0.834. Recurrence-free survival was 223/598 (37%) in patients given propofol anaesthesia vs 206/597 (35%) given sevoflurane anaesthesia; adjusted hazard ratio 1.07; 95% CI: 0.89–1.30; P =0.465. Event-free survival was 294/598 (49%) in patients given propofol anaesthesia vs 274/597 (46%) given sevoflurane anaesthesia; adjusted hazard ratio 1.09; 95% CI 0.93 to 1.29; P =0.298. Long-term survival after major cancer surgery was similar with i.v. and volatile anaesthesia. Propofol-based iv. anaesthesia should not be used for cancer surgery with the expectation that it will improve overall or cancer-specific survival. ChiCTR-IPR-15006209; NCT02660411. [ABSTRACT FROM AUTHOR]

• What is the primary question addressed by this study? Can propofol enhance slow wave sleep in geriatric patients to address core pathophysiology of depression and associated cognitive dysfunction? • What is the main finding of this study? Two older adults with treatment-resistant depression received two morning infusions of propofol. One of the two demonstrated slow wave sleep enhancement and a sustained improvement of depression. • What is the meaning of the finding? The above case series lays the groundwork for an ongoing open-label Phase I clinical trial by providing proof-of-concept of propofol-induced slow wave sleep enhancement and antidepressant response. Slow wave sleep (SWS), characterized by large electroencephalographic oscillations, facilitates crucial physiologic processes that maintain synaptic plasticity and overall brain health. Deficiency in older adults is associated with depression and cognitive dysfunction, such that enhancing sleep slow waves has emerged as a promising target for novel therapies. Enhancement of SWS has been noted after infusions of propofol, a commonly used anesthetic that induces electroencephalographic patterns resembling non-rapid eye movement sleep. This paper 1) reviews the scientific premise underlying the hypothesis that sleep slow waves are a novel therapeutic target for improving cognitive and psychiatric outcomes in older adults, and 2) presents a case series of two patients with late-life depression who each received two propofol infusions. One participant, a 71-year-old woman, had a mean of 2.8 minutes of evening SWS prior to infusions (0.7% of total sleep time). SWS increased on the night after each infusion, to 12.5 minutes (5.3% of total sleep time) and 24 minutes (10.6% of total sleep time), respectively. Her depression symptoms improved, reflected by a reduction in her Montgomery-Asberg Depression Rating Scale (MADRS) score from 26 to 7. In contrast, the other participant, a 77-year-old man, exhibited no SWS at baseline and only modest enhancement after the second infusion (3 minutes, 1.3% of total sleep time). His MADRS score increased from 13 to 19, indicating a lack of improvement in his depression. These cases provide proof-of-concept that propofol can enhance SWS and improve depression for some individuals, motivating an ongoing clinical trial (ClinicalTrials.gov NCT04680910). [ABSTRACT FROM AUTHOR]

• P2X7R in mPFC contributed to propofol-induced unconsciousness. • P2X7R in mPFC affected propofol-induced unconsciousness through synaptic neurotransmission. • P2X7R of microglia participated in the process of propofol-induced unconsciousness. Propofol infusion is processed through the wake-sleep cycle in neural connections, and the ionotropic purine type 2X7 receptor (P2X7R) is a nonspecific cation channel implicated in sleep regulation and synaptic plasticity through its regulation of electric activity in the brain. Here, we explored the potential roles of P2X7R of microglia in propofol-induced unconsciousness. Propofol induced loss of the righting reflex in male C57BL/6 wild-type mice and increased spectral power of the slow wave and delta wave of the medial prefrontal cortex (mPFC), all of which were reversed with P2X7R antagonist A-740003 and strengthened with P2X7R agonist Bz-ATP. Propofol increased the P2X7R expression level and P2X7R immunoreactivity with microglia in the mPFC, induced mild synaptic injury and increased GABA release in the mPFC, and these changes were less severe when treated with A-740003 and were more obvious when treated with Bz-ATP. Electrophysiological approaches showed that propofol induced a decreased frequency of sEPSCs and an increased frequency of sIPSCs, A-740003 decrease frequency of sEPSCs and sIPSCs and Bz-ATP increase frequency of sEPSCs and sIPSCs under propofol anesthesia. These findings indicated that P2X7R in microglia regulates synaptic plasticity and may contribute to propofol-mediated unconsciousness. [ABSTRACT FROM AUTHOR]

Although sex differences in anaesthetic sensitivity have been reported, what underlies these differences is unknown. In rodents, one source of variability in females is the oestrous cycle. Here we test the hypothesis that the oestrous cycle impacts emergence from general anaesthesia. Time to emergence was measured after isoflurane (2 vol% for 1 h), sevoflurane (3 vol% for 20 min), dexmedetomidine (50 μg kg−1 i.v., infused over 10 min), or propofol (10 mg kg−1 i.v. bolus) during proestrus, oestrus, early dioestrus, and late dioestrus in female Sprague–Dawley rats (n =24). EEG recordings were taken during each test for power spectral analysis. Serum was analysed for 17β-oestradiol and progesterone concentrations. The effect of oestrous cycle stage on return of righting latency was assessed using a mixed model. The association between righting latency and serum hormone concentration was tested by linear regression. Mean arterial blood pressure and arterial blood gases were assessed in a subset of rats after dexmedetomidine and compared in a mixed model. Oestrous cycle did not affect righting latency after isoflurane, sevoflurane, or propofol. When in the early dioestrus stage, rats emerged more rapidly from dexmedetomidine than in the proestrus (P =0.0042) or late dioestrus (P =0.0230) stage and showed reduced overall power in frontal EEG spectra 30 min after dexmedetomidine (P =0.0049). 17β-Oestradiol and progesterone serum concentrations did not correlate with righting latency. Oestrous cycle did not affect mean arterial blood pressure or blood gases during dexmedetomidine. In female rats, the oestrous cycle significantly impacts emergence from dexmedetomidine-induced unconsciousness. However, 17β-oestradiol and progesterone serum concentrations do not correlate with the observed changes. [ABSTRACT FROM AUTHOR]

Intravenous sedation with propofol in the dental treatment offers an alternative to inhalation sedation or general anesthesia. The aim of this study was to evaluate the safety and identify risk factors for intraoperative complications. Uncooperative children who could not complete dental treatment under non-pharmacological behavior management or mild-to-moderate sedation in the outpatient pediatric department were selected. Details and time of dental treatment; intraoperative vital signs data, including blood pressure, heart rate, respiratory rate, pulse oxygen saturation (SpO 2), end-tidal carbon dioxide, and electrocardiogram; and incidence of intraoperative and postoperative complications were recorded. Overall, 344 children were selected, with 342 completing dental treatment. The dental treatment time was 20–155 (median, 85; interquartile range, 70–100) min. The number of treated teeth was at least 1 and at most 13 (median, 6; interquartile range, 5–8). Among 342 children, 35 (10.2%) had their treatment interrupted temporarily due to choking cough. No serious complications occurred; the incidence rate of minor complications was 47/342 (13.7%). Tachycardia was observed in 5/342 (1.5%) cases, oxygen desaturation (SpO 2 < 95%) in 18, and hypoxemia (SpO2 ≤ 90%) in 25. The treatment duration was significant longer in cases with than without complications (P < 0.05), and children coughing during treatment were more likely to have complications (P < 0.05). Postoperative restlessness occurred in six children, but there was no vomiting, aspiration, or respiratory obstruction. Decreased oxygen saturation is the most common complications. Cough during treatment and longer treatment duration were risk factors for complications. [ABSTRACT FROM AUTHOR]

To investigate the effects of propofol and sevoflurane on neurological recovery of traumatic brain injury (TBI) patients in the early postoperative stage. We retrospectively analyzed the clinical data of TBI patients who underwent craniotomy or decompressive craniectomy. Generalized additive mixed model (GAMM) was used to analyze effects of propofol and sevoflurane on Glasgow Coma Scale (GCS) on postoperative days 1,3, and 7. Multivariate regression analysis was used to analyze effects of the two anesthetics on Glasgow Outcome Scale (GOS) at discharge. A total of 340 TBI patients were enrolled in this study. There were 110 TBI patients who underwent craniotomy including 75 in the propofol group and 35 in the sevoflurane group, and 134 patients who underwent decompressive craniectomy including 63 in the propofol group and 71 in the sevoflurane group. It showed no significant difference in GCS at admission between the propofol and the sevoflurane groups among craniotomy patients (β = 0.75, 95% CI : –0.55 to 2.05, p = 0.260). However, elevation in GCS from baseline was 1.73 points (95% CI : –2.81 to –0.66, p = 0.002) less in the sevoflurane group than that in the propofol group on postoperative day 1, 2.03 points (95% CI : –3.14 to –0.91, p < 0.001) less on day 3, and 1.31 points (95% CI : –2.43 to –0.19, p = 0.022) less on day 7. The risk of unfavorable GOS (GOS 1,2, and 3) at discharge was higher in the sevoflurane group (OR = 4.93, 95% CI : 1.05 to 23.03, p = 0.043). No significant difference was observed among two-group decompressive craniectomy patients in GCS and GOS. Compared to propofol, sevoflurane was associated with worse neurological recovery during the hospital stay in TBI patients undergoing craniotomy. This difference was not detected in TBI patients undergoing decompressive craniectomy. [ABSTRACT FROM AUTHOR]

The neuronal mechanisms underlying propofol-induced modulation of consciousness are poorly understood. Neuroimaging studies suggest a potential role for non-specific thalamic nuclei in propofol-induced loss of consciousness. We investigated the contribution of the paraventricular thalamus (PVT), a midline thalamic nucleus that has been implicated in arousal control and general anaesthesia with inhaled anaesthetics, to loss and recovery of consciousness during propofol anaesthesia. Polysomnographic recordings and righting reflex test were used to determine the transitions of loss and recovery of righting reflex, used as a measure of consciousness in mice, during propofol anaesthesia in mice under conditions mimicking clinical propofol administration. PVT neuronal activities were monitored using fibre photometry and regulated using optogenetic and chemogenetic methods. Population activities of PVT glutamatergic neurones began to decrease before propofol-induced loss of consciousness and rapidly increased to a peak at the onset of recovery of consciousness. Chemogenetic inhibition of PVT calretinin-expressing (PVTCR) neurones shortened onset (from 176 [35] to 127 [26] s; P =0.001) and prolonged return (from 1568 [611] to 3126 [1616] s; P =0.002) of righting reflex. Conversely, chemogenetic activation of PVTCR neurones exerted opposite effects. Furthermore, optogenetic silencing of PVTCR neurones accelerated transitions to loss of consciousness (from 205 [35] to 158 [44] s; P =0.027) and slowed transitions to recovery of consciousness (from 230 [78] to 370 [99] s; P =0.041). During a steady period of unconsciousness maintained with continuous propofol infusion, brief optical activation of PVTCR neurones restored cortical activity and arousal with a latency of about 5 s. The paraventricular thalamus contributes to the control of consciousness transitions in propofol anaesthesia in mice. This provides a potential neuroanatomical target for controlling consciousness to reduce anaesthetic dose requirements and side effects. [ABSTRACT FROM AUTHOR]

• We investigated temporal changes in cerebral cortex during the induction phase from awake to unconscious state. • The changes in superior parietal lobule and dorsolateral prefrontal cortex were followed by the change in angular gyrus. • The loss of consciousness results from disrupted communication with external world, followed by communication loss within self. To understand the underlying mechanism of consciousness, investigating spatiotemporal changes in the cortical activity during the induction phase of unconsciousness is important. Loss of consciousness induced by general anesthesia is not necessarily accompanied by a uniform inhibition of all cortical activities. We hypothesized that cortical regions involved in internal awareness would be suppressed after disruption of cortical regions involved in external awareness. Thus, we investigated temporal changes in cortex during induction of unconsciousness. We recorded electrocorticography data of 16 epilepsy patients and investigated power spectral changes during induction phase from awake state to unconsciousness. Temporal changes were assessed at 1) the start point and 2) the interval of normalized time between start and end of power change (Δ tnormalized). We found that the power increased at frequencies < 46 Hz, and decreased in range of 62–150 Hz, in global channels. In temporal changes of power change, superior parietal lobule and dorsolateral prefrontal cortex started to change early, but the changes were completed over a prolonged interval, whereas angular gyrus and associative visual cortex showed a delayed change and rapid completion. Loss of consciousness induced by general anesthesia results first from disrupted communication between self and external world, followed by disrupted communication within self, with decreased activities of superior parietal lobule and dorsolateral prefrontal cortex, and later, attenuated activities of angular gyrus. Our findings provided neurophysiological evidence for the temporal changes in consciousness components induced by general anesthesia. [ABSTRACT FROM AUTHOR]

To describe ketamine–propofol total intravenous anaesthesia (TIVA) following premedication with acepromazine and either medetomidine, midazolam or morphine in rabbits. Randomized, crossover experimental study. A total of six healthy female New Zealand White rabbits (2.2 ± 0.3 kg). Rabbits were anaesthetized on four occasions, each separated by 7 days: an intramuscular injection of saline alone (treatment Saline) or acepromazine (0.5 mg kg–1) in combination with medetomidine (0.1 mg kg–1), midazolam (1 mg kg–1) or morphine (1 mg kg–1), treatments AME, AMI or AMO, respectively, in random order. Anaesthesia was induced and maintained with a mixture containing ketamine (5 mg mL–1) and propofol (5 mg mL–1) (ketofol). Each trachea was intubated and the rabbit administered oxygen during spontaneous ventilation. Ketofol infusion rate was initially 0.4 mg kg–1 minute–1 (0.2 mg kg–1 minute–1 of each drug) and was adjusted to maintain adequate anaesthetic depth based on clinical assessment. Ketofol dose and physiological variables were recorded every 5 minutes. Quality of sedation, intubation and recovery times were recorded. Ketofol induction doses decreased significantly in treatments AME (7.9 ± 2.3) and AMI (8.9 ± 4.0) compared with treatment Saline (16.8 ± 3.2 mg kg–1) (p < 0.05). The total ketofol dose to maintain anaesthesia was significantly lower in treatments AME, AMI and AMO (0.6 ± 0.1, 0.6 ± 0.2 and 0.6 ± 0.1 mg kg–1 minute–1, respectively) than in treatment Saline (1.2 ± 0.2 mg kg–1 minute–1) (p < 0.05). Cardiovascular variables remained at clinically acceptable values, but all treatments caused some degree of hypoventilation. Premedication with AME, AMI and AMO, at the doses studied, significantly decreased the maintenance dose of ketofol infusion in rabbits. Ketofol was determined to be a clinically acceptable combination for TIVA in premedicated rabbits. [ABSTRACT FROM AUTHOR]

The effect of dexmedetomidine (DEX) compared with propofol on intraoperative seizures (IOSs) detected using electrocorticography during awake craniotomy for resection of brain tumors is unknown. This investigation aimed to compare IOS rate in patients receiving DEX versus propofol as sedative agent. In this retrospective single-center study, awake craniotomies performed from January 2014 to December 2019 were analyzed. All IOSs detected by electrocorticography along with vital signs were recorded. Of 168 adults enrolled in the study, 58 were administered DEX and 110 were administered propofol. IOSs occurred more frequently in the DEX group (22%) versus the propofol group (11%) (P = 0.046). A higher incidence of bradycardia was also observed in the DEX group (P < 0.001). Higher incidence of hypertension and a higher mean heart rate were recorded in the propofol group (P = 0.006 and P < 0.001, respectively). No serious adverse events requiring active drug administration were noted in either group. At univariate regression analysis, DEX demonstrated a tendency to favor IOS onset but without statistical significance (odds ratio = 2.36, P = 0.051). Patients in both groups had a similar epilepsy outcome at the 1-year postoperative follow-up. IOSs detected with electrocorticography during awake craniotomy occurred more frequently in patients receiving DEX than propofol. However, patients receiving DEX were not shown to be at a statistically significant greater risk for IOS onset. DEX is a valid alternative to propofol during awake craniotomy in patients affected by tumor-related epilepsy. [ABSTRACT FROM AUTHOR]

• The AMR was higher in deep-sedated colonoscopy than in unsedated colonoscopy;. • Adenomas in the splenic flexure and descending colon were more frequently missed;. • There was no such difference in the high-level endoscopists. Deep-sedated colonoscopy with propofol is widely used in China. However, its impact on quality metrics remains controversial. We aimed to investigate the effects of deep-sedated colonoscopy on missed adenomas, specifically in each colorectal segment. Data of 3710 individuals from seven hospitals in China who underwent an initial colonoscopy with or without propofol sedation and a second colonoscopy without sedation within six months for surveillance or polypectomy by endoscopist of the same level between October 2020 and September 2021 were retrospectively analyzed. A total of 1113 missed adenomas in 3710 patients were evaluated. The adenoma miss rate (AMR) was significantly higher in deep-sedated colonoscopy than in unsedated colonoscop [19.14% (578/3020) vs. 16.15% (535/3313), P < 0.05]. The risk of missing adenomas in deep-sedated colonoscopy was 1.229 times higher than in unsedated colonoscopy (OR, 1.229; 95% CI: 1.080–1.399). AMRs of the splenic flexure (26.02% [96/369] vs. 16.04% [47/293], P < 0.05) and descending colon (20.86% [102/489] vs. 13.37% [54/404], P < 0.05) were significantly higher in deep-sedated colonoscopy than in unsedated colonoscopy when performed by middle-level endoscopists rather than high-level endoscopists (P < 0.05). AMR was higher in deep-sedated colonoscopy than in unsedated colonoscopy. Furthermore, adenomas in the splenic flexure and descending colon were more frequently missed in deep-sedated colonoscopy than in unsedated colonoscopy, particularly when performed by less experienced endoscopists. [ABSTRACT FROM AUTHOR]