Sedative effects of propofol and risk factors for excessive sedation in the endoscopic treatment of biliary and pancreatic diseases.

Objectives: The safety and effectiveness of propofol in more complex endoscopic procedures, such as endoscopic retrograde cholangiopancreatography, remain unknown. Thus, we aimed to evaluate propofol sedation during endoscopic cholangiopancreatography, ultrasound-guided intervention, and gastroduodenal stenting and examine risk factors for excessive sedation. Methods: We retrospectively analyzed data from 870 patients who underwent endoscopic treatment with propofol sedation for biliary and pancreatic disease between October 2020 and September 2021. Sedation included propofol and fentanyl, with continuous monitoring of vital signs and the bispectral index. The assessed risk factors included age, complications, body mass index, treatment duration, and specialty. Results: Distal bile duct treatment (n = 367), hilar bile duct treatment (n = 197), post-small-intestinal reconstruction treatment (n = 75), endoscopic ultrasound-guided intervention (n = 140), and gastrointestinal obstruction treatment (n = 91) were performed. The rates of excessive sedation, hypoxemia, and hypotension were 7.8%, 6.0%, and 1.8%, respectively. Post-small-intestinal reconstruction treatment had the highest incidence rate of excessive sedation (16%), whereas endoscopic ultrasound-guided intervention had the lowest incidence rate (4.3%). Multivariate analysis revealed significant associations between excessive sedation and comorbid sleep apnea, obesity, and prolonged procedural time. Conclusions: Obesity, sleep apnea syndrome, and prolonged procedure time are risk factors for excessive sedation related to propofol use. Thus, sedation techniques should be tailored for these patients.

Comparison of propofol-based sedation and midazolam sedation in pediatric bidirectional endoscopy conducted by pediatric gastroenterologists.

Objectives: The effectiveness and safety of propofol-based sedation and midazolam sedation in pediatric bidirectional endoscopy were compared. Methods: We retrospectively analyzed the cases of pediatric patients (≤15 years old) who had undergone bidirectional endoscopy, esophagogastroduodenoscopy, and colonoscopy by pediatric gastroenterologists. Demographic data, indications, sedatives/dosages, clinical outcomes, endoscopic findings, adverse events, and total patient time requirements (total time in which patients stay in our hospital) were compared in the two sedation groups. Results: Ninety-one children (51 boys, 40 girls, mean age 13 years, range 9-15) treated at our hospital were enrolled. Propofol alone or in combination with midazolam and/or pentazocine was administered to 51 patients (propofol-based sedation group). Midazolam alone or in combination with pentazocine was administered to the other 40 patients (midazolam sedation group). In the propofol group, the following mean doses were used: propofol, 96 mg (range 40-145 mg); midazolam, 4.9 mg (range 3-5 mg); and pentazocine, 7.5 mg. In the midazolam group, the mean doses of midazolam and pentazocine were 6.2 mg (range 4-10 mg) and 15 mg, respectively. All procedures were successfully completed by pediatric gastroenterologists. The total procedure times and endoscopic findings were similar in the two groups, but the median patient time requirement in the propofol group was significantly shorter versus the midazolam group (7.3 h vs. 8.4 h, p < 0.001). No adverse events occurred in either group. Conclusions: Propofol-based sedation in pediatric bidirectional endoscopy was safely and effectively performed by pediatric gastroenterologists, and its patient time requirement was shorter than that for midazolam sedation.

Comparing subjective quality of recovery between remimazolam- and propofol-based total intravenous anesthesia for surgical procedures: a meta-analysis.

BACKGROUND: Remimazolam is a novel ultra-short-acting benzodiazepine that has been recently introduced as an alternative to propofol for general anesthesia. While both agents have been compared in terms of safety and efficacy, their relative effects on postoperative quality of recovery (QoR) remain unclear. Therefore, this meta-analysis aimed to compare the effects of remimazolam and propofol on subjective QoR in surgical patients who underwent general anesthesia. METHODS: Medline, Embase, Google Scholar, and the Cochrane Central Register of Controlled Trials were searched from inception to May 28, 2024 to identify randomized controlled trials comparing remimazolam and propofol in terms of postoperative QoR. The Cochrane risk-of-bias tool (RoB 2) was used to assess study quality. QoR score on postoperative day (POD) 1 (primary outcome), QoR scores on PODs 2-3, QoR dimensions, time to loss of consciousness, other recovery characteristics, and rescue analgesia requirement were evaluated using random-effects meta-analyses. RESULTS: This meta-analysis included 13 studies published between 2022 and 2024 involving 1,418 patients. QoR was evaluated using either the QoR-15 (10 studies) or QoR-40 (3 studies) questionnaire. The pooled results indicated no significant difference in the QoR scores on POD 1 (standardized mean difference: 0.02, 95% confidence interval [CI]: - 0.20, 0.23, P = 0.88, I2 = 73%) and PODs 2-3 between remimazolam and propofol. Furthermore, no significant differences were observed in QoR dimensions, length of postanesthesia care unit (PACU) stay, and time to extubation as well as in the risks of agitation and postoperative nausea and vomiting. Patients administered remimazolam exhibited slower anesthetic induction (mean difference (MD): 32.27 s) but faster recovery of consciousness (MD: - 1.60 min) than those administered propofol. Moreover, remimazolam was associated with a lower risk of rescue analgesia requirement in the PACU (risk ratio: 0.62, 95% CI: 0.43, 0.89, P = 0.009, I2 = 0%) but not in the ward. CONCLUSION: Remimazolam is a potential alternative to propofol for general anesthesia as it offers similar QoR to the latter and has advantages in terms of consciousness recovery and immediate postoperative analgesia requirement.

Impact of different doses of esketamine on the incidence of hypotension in propofol-based sedation for colonoscopy: a randomized controlled trial.

Background: Hypovolemia is common in colonoscopy due to fasting and bowel preparation, and propofol itself can reduce systemic vascular resistance, resulting in relative hypovolemia. Therefore, hypotension is not a rare event during propofol-based sedation for colonoscopy. Objectives: Our objective was to explore the efficacy of esketamine as a sedative adjuvant in reducing the incidence of hypotension during colonoscopy. Design: This was a prospective randomized trial. The trial was registered with the Chinese Clinical Trial Registry (ID: ChiCTR 2100047032). Methods: We included 100 eligible patients who planned to receive a colonoscopy and randomly divided them into 4 groups with 25 patients in each group, which were propofol 2 mg/kg (Group P), propofol 1 mg/kg with esketamine 0.2 mg/kg (Group E1), propofol 1 mg/kg with esketamine 0.3 mg/kg (Group E2), and propofol 1 mg/kg with esketamine 0.4 mg/kg (Group E3). The hemodynamic and respiratory parameters were documented at various times during the procedure, including the patient's entry into the endoscopic room (T0), the induction of sedation (T1), the insertion of the colonoscope (T2), the removal of the colonoscope (T3), and the awakening of the patient (T4). The primary outcome was the incidence of hypotension. Secondary outcomes were cardiovascular side effects other than hypotension, incidence of hypoxia, cumulative changes in cardiovascular and respiratory parameters, total propofol dosage, anesthesia recovery time, and satisfactory levels of both patients and endoscopists. Results: The incidence of hypotension in Group E1 (16%), Group E2 (16%), and Group E3 (12%) was significantly lower than in Group P (60%), with p values 0.003, 0.003, and <0.001 respectively. The cumulative changes in diastolic blood pressure and mean arterial pressure in Groups E1, E2, and E3 were significantly higher than in Group P (p = 0.024, p < 0.001, p = 0.006, respectively). Cumulative changes in systolic blood pressure in Group E3 were significantly higher than those in Group P (p = 0.012). The respiratory-related parameters were not statistically significant. Conclusions: This study showed that the application of 0.4 mg/kg esketamine in propofol-based sedation reduced the incidence of hypotension during colonoscopy while providing satisfactory sedation.

Background: When people undergo colonoscopy and are sedated with propofol, about one-third of them experience low blood pressure. This study aims to see if adding esketamine to the propofol can help prevent or lessen these episodes of low blood pressure during colonoscopy. Methods: This study examined four groups who received different doses of esketamine along with propofol. It focuses on differences in the occurrence of low blood pressure, respiratory measures, the amount of anesthetic used, and levels of satisfaction. The study analyzed the relevant data for these parameters to understand the differences between the groups. Results: The results indicated that using esketamine along with propofol for sedation during colonoscopy led to several key outcomes, such as:• Three different concentrations of esketamine effectively reduced the occurrence of low blood pressure in patients undergoing colonoscopy.• Less propofol was needed in the groups that included esketamine.• Esketamine at a dosage of 0.4 mg kg-1 showed the best respiratory parameters among the four groups. Conclusions: During colonoscopy, using esketamine along with propofol for sedation not only achieves satisfactory sedation but also lowers the occurrence of hypotension. Specifically, employing 0.4 mg kg-1 esketamine along with propofol not only reduces hypotension occurrences but also enhances respiration.

Impact of different doses of esketamine on incidence of hypotension in propofol-based sedation for colonoscopy.

Effects of acepromazine, xylazine and propofol on spinal reflexes in healthy dogs.

BACKGROUND: In the neurological examination, it is crucial to identify the possible location of the lesion in order to determine the appropriate treatment process. In aggressive animals, chemical restraint may be necessary due to their non-cooperative behaviour. However, sedatives may distort the results of examinations. Therefore, a drug should be found that has minimal impact on the examination results. OBJECTIVES: To investigate the effects of acepromazine, xylazine, and propofol on spinal reflexes in healthy dogs. METHODS: In a randomized, blinded study, ten native adult mixed-breed dogs were participated in three groups with a 1-week washout period between each group. Before performing each step, the spinal reflexes were evaluated. Then, in the first group, acepromazine (0.05 mg/kg, IM), in the second group, xylazine (1 mg/kg, IM), and in the third group, propofol (3 mg/kg, IV for initial bolus and 0.1 mg/kg/min for maintenance) were injected for sedation. The spinal reflexes were reevaluated at maximum sedation and at 15, 30, and 45 min thereafter. RESULTS: Acepromazine increased the patellar reflex and decreased the panniculus reflex. Xylazine increased the cranial tibial reflex and decreased the panniculus reflex, while propofol decreased the withdrawal, and extensor carpi radialis reflexes, and suppressed the palpebral and gag reflexes. CONCLUSIONS: The drugs used in the present study did not have a significant impact on the most important reflexes evaluated in neurological examinations. Among the drugs, acepromazine has the least effects compared to other drugs, making it a suitable choice for sedation.

Prolonged Lower Limb Dystonia and Dysphonia Following General Anesthesia in a Patient on Hydroxyzine.

We present a case of prolonged lower limb movement disorder following general anesthesia in a female patient in her early forties. She presented with vigorous, regular synchronous, rhythmic, and jerky movements during the immediate postoperative period lasting around forty minutes. Her past anesthetic history suggests varying degrees of postoperative movement disorders. Our patient was on long-term hydroxyzine for her skin condition. She had uneventful anesthetics before the prescription of hydroxyzine for her skin condition. All post-anesthetic dystonic events were reported while she was on hydroxyzine. Dystonic reactions during the perioperative period are rare and mostly occur during induction and emergence, which usually be transient. Our patient had prolonged lower limb dystonia resulting in severe muscular pain and lethargy for a few days. Further, she once developed transient aphasia and prolonged dysphonia following total intravenous anesthesia. This clinical finding could be a part of spasmodic laryngeal dystonia, which has not been reported previously. We correlate this rare postoperative dystonic reaction with propofol and possibly with the concurrent use of hydroxyzine. As differential diagnosis can widely vary, the correlation of clinical findings with movement disorders is important for the diagnosis. Alterations of anesthetic techniques avoiding propofol and holding hydroxyzine are advisable in such rare clinical situations. Early diagnosis of perioperative movement disorders will prompt specific treatments, such as anticholinergic medications, for dystonia.

Steady-state trumps accuracy: target-controlled infusion as a gain switch.

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.

The effective dose of butorphanol tartrate in patients of different ages undergoing painless gastroscopy.

OBJECTIVE: This study evaluated the 50% effective dose (ED50) and 95% effective dose (ED95) of butorphanol tartrate in patients undergoing painless gastroscopy. METHODS: Patients who underwent painless gastroscopy at Binzhou Medical University Hospital were divided into the youth, middle-aged, and older groups. The ED50 and ED95 required for successful sedation using butorphanol tartrate were measured using the Dixon up-and-down method in patients in the different age groups. Patients in each group were administered intravenous butorphanol 5 minutes before gastroscopy. Each patient was administered 2 mg/kg propofol. The ED50 and ED95 of butorphanol were calculated using probit analysis. RESULTS: In total, 95 patients were included. The ED50s of butorphanol in the youth, middle-aged, and older groups were 7.384, 6.657, and 6.364 µg/kg, respectively. The ED95s of butorphanol doses in these groups were 9.108, 8.419, and 7.348 µg/kg, respectively. CONCLUSIONS: The ED50 and ED95 varied among the age groups, indicating that the effective dose decreases with age.

Effect of quantitative consciousness index on seizure parameters during electroconvulsive therapy in patients with major depressive disorder.

BACKGROUND: Electroconvulsive therapy (ECT) is both an effective treatment for patients with major depressive disorder (MDD) and a noxious stimulus. Although some studies have explored the effect of sedation depth on seizure parameters in ECT, there is little research on the noxious stimulation response to ECT. In this study, we used two electroencephalography (EEG)-derived indices, the quantitative consciousness (qCON) index and quantitative nociceptive (qNOX) index, to monitor sedation, hypnosis, and noxious stimulation response in patients with MDD undergoing acute ECT. AIM: To evaluate the effect of anesthesia depth based on the qCON and qNOX indices on seizure parameters. METHODS: Patients with MDD (n = 24) underwent acute bilateral temporal ECT under propofol anesthesia. Before ECT, the patients were randomly divided into three groups according to qCON scores (qCON60-70, qCON50-60, and qCON40-50). Continuous qCON monitoring was performed 3 minutes before and during ECT, and the qCON, qNOX, vital signs, EEG seizure parameters, and complications during the recovery period were recorded. The 24-item Hamilton Rating Scale for Depression, Zung's Self-rating Depression Scale, and Montreal Cognitive Assessment scores were evaluated before the first ECT session, after the fourth ECT session, and after the full course of ECT. RESULTS: A total of 193 ECT sessions were performed on 24 participants. The qCON index significantly affected the EEG seizure duration, peak mid-ictal amplitude, and maximum heart rate during ECT (P < 0.05). The qNOX index significantly affected the post-ictal suppression index (P < 0.05). Age, number of ECT sessions, and anesthetic-ECT time intervals also had a significant effect on EEG seizure parameters (P < 0.05). However, there were no significant differences in complications, 24-item Hamilton Rating Scale for Depression scores, Zung's Self-rating Depression Scale scores, or Montreal Cognitive Assessment scores among the three groups (P > 0.05). CONCLUSION: Electrical stimulation at a qCON index of 60-70 resulted in better EEG seizure parameters without increasing complications in patients with MDD undergoing bilateral temporal ECT under propofol anesthesia.

Design, synthesis, and activity evaluation of water-soluble propofol derivatives as anesthetic drugs.

In this work, two series of water-soluble derivatives were designed and synthesized based on the structure of propofol as the lead compound. Furthermore, the anesthetic activities of the synthesized compounds were evaluated in vivo against mice, and the in vitro propofol release rate from five target compounds was determined. The findings of this study have shown that series II compounds which possess the structure feature of propofol + γ-hydroxybutyric acid + α-aminoacetate or γ-aminobutyrate have higher therapeutic index than that of series I compounds which possess the structure feature of propofol + α-aminoacetate or ß-aminopropionate. In addition, the rate of propofol released from series II compounds was significantly better than that of series I compounds. Among series II compounds, compound II-20 had a therapeutic index of 5.6 (propofol = 2.7), a duration time of 571 s (propofol = 57 s), and no significant toxicity was observed in vivo, which made it valuable for further development.

Effect of propofol versus midazolam on short-term outcomes in patients with sepsis-associated acute kidney injury.

Background: Propofol and midazolam are commonly used sedative drugs in mechanically ventilated patients in the Intensive Care Unit (ICU). However, there is still a lack of relevant studies exploring the influence of midazolam and propofol on the prognosis of patients with Sepsis-associated Acute Kidney Injury (S-AKI). Patients and methods: A statistical analysis was conducted on 3,745 patients with S-AKI in the Medical Information Mart for Intensive Care IV database. The patients' baseline characteristics were grouped based on the use of either propofol or midazolam as sedatives. Cox proportional hazards models, logistic regression models, and subgroup analyses were used to compare the effects of propofol and midazolam on the short-term prognosis of S-AKI patients, including 30-day mortality, ICU mortality, and duration of mechanical ventilation. Results: In the statistical analysis, a total of 3,745 patients were included, with 649 patients using midazolam and 3,096 patients using propofol. In terms of the 30-day mortality, compared to patients using midazolam, S-AKI patients using propofol had a lower ICU mortality (hazard ratio = 0.62, 95% confidence interval: 0.52-0.74, p < 0.001), lower 30-day mortality (hazard ratio = 0.56, 95% confidence interval: 0.47-0.67, p < 0.001), and shorter mechanical ventilation time (odds ratio = 0.72, 95% confidence interval: 0.59-0.88, p < 0.001). Kaplan-Meier curves showed lower survival probabilities in the midazolam group (p < 0.001). Subgroup analyses showed that propofol was strongly protective of short-term prognosis in older, male, smaller SOFA score CCI score, no heart failure, and comorbid chronic kidney disease patients with S-AKI. Conclusion: Compared to midazolam, propofol was considered a protective factor for short-term mortality risk and ICU mortality risk in S-AKI patients. Additionally, S-AKI patients using propofol had a lower risk of requiring prolonged mechanical ventilation. Overall, propofol may be more beneficial for the short-term prognosis of S-AKI patients compared to midazolam.

Comparison of Intravenous Ondansetron and Dexamethasone for Preventing Propofol-Induced Pain During Laparoscopic Cholecystectomy: A Double-Blind, Randomized Study.

Background Propofol is the most common induction agent used in current anesthesia practice. Patients receiving propofol injections commonly experience varying degrees of pain, creating an unpleasant anesthesia experience. Methods Seventy-two patients, aged between 18 and 70, scheduled for elective laparoscopic cholecystectomy under general anesthesia were randomized into two groups. Group D received 8 mg of dexamethasone, and Group O received 8 mg of ondansetron intravenously before induction. After five seconds, mid-arm venous occlusion was applied for one minute using a tourniquet. Propofol (0.5 mg/kg) was administered intravenously over five seconds, and patients rated the injection pain over the next 15 seconds. The primary outcome was pain intensity using the Verbal Rating Scale during propofol injection. Secondary outcomes included intraoperative hemodynamic changes and postoperative nausea and vomiting (PONV). Normally distributed variables were compared using the Student's t-test, non-normally distributed variables using the Mann-Whitney U-test, and qualitative data using the chi-square or Fisher's exact test. Statistical significance for the study was set at p < 0.05. Results In Group D, 30 out of 36 patients (83.3%) experienced no pain, while four patients (11.1%) reported mild pain, two patients (5.6%) reported moderate pain, and no patients (0.0%) reported severe pain. In contrast, in Group O, only 15 out of 36 patients (41.6%) experienced no pain, with 12 patients (33.3%) experiencing mild pain, seven patients (19.4%) experiencing moderate pain, and two patients (5.6%) experiencing severe pain. Overall, six out of 36 patients in Group D (16.7%) experienced some level of pain, compared to 21 out of 36 patients in Group O (58.3%), a statistically significant difference (p < 0.05). Regarding postoperative nausea, 16 out of 36 patients in Group Dexamethasone (44.44%) experienced nausea, whereas 23 out of 36 patients in Group Ondansetron (63.88%) reported this symptom, with the difference being statistically significant (p = 0.0372). Additionally, postoperative vomiting occurred in nine out of 36 patients in Group Dexamethasone (25%), compared to 18 out of 36 patients in Group Ondansetron (50%), with this difference also reaching statistical significance (p= 0.026). Conclusions Intravenous dexamethasone before propofol administration reduces injection pain and PONV in laparoscopic cholecystectomy more effectively as compared to ondansetron.

Efficacy and safety of esketamine versus propofol in electroconvulsive therapy for treatment-resistant depression: A randomized, double-blind, controlled, non-inferiority trial.

BACKGROUND: Electroconvulsive therapy (ECT) is a commonly used alternative for treatment-resistant depression (TRD). Although esketamine has a rapid pharmacological antidepressant action, it has not been studied as an ECT anesthetic. The objective of this study was to compare the efficacy and safety of esketamine with propofol when both are used as ECT anesthetic agents. METHODS: Forty patients with TRD were assigned to one of two arms in a double-blind, randomized controlled trial: esketamine or propofol anesthesia for a series of eight ECT sessions. Using a non-inferiority design, the primary outcome was the reduction in HAMD-17 depressive symptoms. The other outcomes were: rates of response and remission, anxiety, suicidal ideation, cognitive function, and adverse events. These were compared in an intention-to-treat analysis. RESULTS: Esketamine-ECT was non-inferior to propofol-ECT for reducing TRD symptoms after 8 sessions (adjusted Δ = 2.0, 95 % CI: -1.2-5.1). Compared to propofol-ECT, esketamine-ECT also had higher depression response (80 % vs. 70 %; p = .06) and remission (65 % vs. 55 %; p = .11) rates but non-inferiority was not established. In four components of cognitive function (speed of processing, working memory, visual learning, and verbal learning) esketamine-ECT was non-inferior to propofol-ECT. The results for anxiety, suicidal ideation, and adverse events (all p's > .05) were inconclusive. CONCLUSION: Esketamine was non-inferior to propofol when both are used as anesthetics for TRD patients undergoing ECT. Replication studies with larger samples are needed to examine the inconclusive results. REGISTRATION NUMBER: ChiCTR2000033715.

Novel technique of switching TIVA and sevoflurane during epilepsy surgery for combined intraoperative motor evoked potentials monitoring and electrocorticography: an illustrative case report.

BACKGROUND: During epilepsy surgery, it is equally important to record electrocorticography (ECoG) for detecting epileptogenic activity and guiding brain resection, and to evaluate neuromonitoring data, particularly motor evoked potentials (MEP), for avoidance of postoperative neurological complications. However, sevoflurane, which is commonly used during recording of ECoG, may attenuate the MEP response. It enforces anesthesiologists and neurosurgeons to select one anesthetic agent over another, facilitating either ECoG or MEP monitoring. CASE PRESENTATION: In the presented case of a 20-year-old man, who underwent surgery for temporal lobe epilepsy, a novel technique of neuroanesthesia was introduced, integrating initial induction of the total intravenous anesthesia (TIVA) with propofol (effect-site concentration, 2.3-3.0 µg/ml), its subsequent switching to sevoflurane (end-tidal concentration, 2.5%) for ECoG recording, and further change back to TIVA for MEP monitoring during brain resection. CONCLUSIONS: Intraoperative switch of anesthetic agents according to specific intraoperative requirements may be useful for cases of brain surgery requiring both ECoG recordings and MEP monitoring.

Propofol binds and inhibits skeletal muscle ryanodine receptor 1.

BACKGROUND: 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. METHODS: 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 (AziPm). Activator-mediated wild-type RyR1 opening as a function of propofol concentration was measured by Fura-2 Ca2+ imaging of human skeletal myotubes. AziPm 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. RESULTS: Both propofol and AziPm 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 AziPm. MD simulation predicted propofol KD values of 55.8 µM and 1.4 µM in the V4828 pocket in open and closed RyR1, respectively. CONCLUSIONS: Propofol demonstrated direct binding and inhibition of RyR1 at clinically plausible concentrations, consistent with the hypothesis that propofol partially mitigates MH by inhibition of induced Ca2+ flux through RyR1.

Impact of propofol versus desflurane anesthesia on postoperative hepatic and renal functions in infants with living-related liver transplantation: a randomized controlled trial.

BACKGROUND: The effects of anesthetics on liver and kidney functions after infantile living-related liver transplantation (LRLT) are unclear. This study aimed to investigate the effects of propofol-based total intravenous anesthesia (TIVA) or desflurane-based inhalation anesthesia on postoperative liver and kidney functions in infant recipients after LRLT and to evaluate hepatic ischemia-reperfusion injury (HIRI). METHODS: Seventy-six infants with congenital biliary atresia scheduled for LRLT were randomly divided into two anesthesia maintenance groups: group D with continuous inhalation of desflurane and group P with an infusion of propofol. The primary focus was to assess alterations of liver transaminase and serum creatinine (Scr) levels within the first 7 days after surgery. And the peak aminotransferase level within 72 h post-surgery was used as a surrogate marker for HIRI. RESULTS: There were no differences in preoperative hepatic and renal functions between the two groups. Upon the intensive care unit (ICU) arrival, the levels of aspartate aminotransferase (AST, P = 0.001) and alanine aminotransferase (ALT, P = 0.005) in group P were significantly lower than those in group D. These changes persisted until the fourth and sixth days after surgery. The peak AST and ALT levels within 72 h after surgery were also lower in group P than in group D (856 (552, 1221) vs. 1468 (732, 1969) U/L, P = 0.001 (95% CI: 161-777) and 517 (428, 704) vs. 730 (541, 1100) U/L, P = 0.006, (95% CI: 58-366), respectively). Patients in group P had lower levels of Scr upon the ICU arrival and on the first day after surgery, compared to group D (17.8 (15.2, 22.0) vs. 23.0 (20.8, 30.8) µmol/L, P < 0.001 (95% CI: 3.0-8.7) and 17.1 (14.9, 21.0) vs. 20.5 (16.5, 25.3) µmol/L, P = 0.02 (95% CI: 0.0-5.0) respectively). Moreover, the incidence of severe acute kidney injury was significantly lower in group P compared to that in group D (15.8% vs. 39.5%, P = 0.038). CONCLUSIONS: Propofol-based TIVA might improve liver and kidney functions after LRLT in infants and reduce the incidence of serious complications, which may be related to the reduction of HIRI. However, further biomarkers will be necessary to prove these associations.

Effects of dexmedetomidine versus propofol on outcomes in critically ill patients with different sedation depths: a propensity score-weighted cohort study.

OBJECTIVE: We explored the effects of dexmedetomidine (DEX) versus propofol on outcomes in critically ill patients and to assess whether these effects are dissimilar under different sedation depths. METHODS: A stabilized inverse probability of treatment weighting cohort study was conducted using data from the Medical Information Mart for Intensive Care IV database from 2008 to 2019. Adult intensive care unit (ICU) patients who were administered DEX or propofol as the primary sedative were identified. Various statistical methods were used to evaluate the effects of DEX versus propofol on outcomes. RESULTS: Data on 107 and 2318 patients in DEX and propofol groups, respectively, were analyzed. Compared to the propofol group, the DEX group exhibited longer ventilator-free days on day 28 and a shorter ICU stay. Conversely, it showed null associations of DEX with the risk of 90-day ICU mortality, the odds of persistent organ dysfunction on day 14 and acute kidney injury, and the duration of vasopressor-free days on day 28. Subgroup analyses revealed that DEX positively impacted persistent organ dysfunction on day 14, ventilator-free days on day 28, and ICU stay in the subgroup with a Richmond Agitation Sedation Scale (RASS) score of ≥-2. However, DEX negatively impacted 90-day ICU mortality, persistent organ dysfunction on day 14, and ventilator-free days on day 28 in the subgroup with a RASS score of <-2. CONCLUSION: Our results indicated that, compared with propofol, DEX had beneficial and adverse impacts on certain ICU outcomes in critically ill patients, and these impacts appeared to depend on sedation depths.

Comparison of the efficacy and safety of ciprofol and propofol for ERCP anesthesia in older patients: A single-center randomized controlled clinical study.

STUDY OBJECTIVES: Ciprofol is a novel agonist at the gamma-aminobutyric acid-A (GABAA) receptor, exhibiting better cardiovascular stability and rapid recovery. The objective of this study was to compare the efficacy and safety of ciprofol and propofol for endoscopic retrograde cholangiopancreatography (ERCP) anesthesia in older patients. DESIGN: A single-center, randomized, parallel controlled clinical study. SETTING: General Hospital of Northern Theater Command. PATIENTS: We recruited 284 patients and intended to conduct ERCP from November 2021 to June 2022. INTERVENTIONS: Patients scheduled for ERCP were randomly assigned to two groups (n = 142 each): ciprofol group (anesthesia induction 0.3-0.4 mg/kg, anesthesia maintenance 0.8-1.2 mg/kg/h) and propofol group (anesthesia induction 1.5-2.0 mg/kg, anesthesia maintenance 4-12 mg/kg/h). MEASUREMENTS: The primary outcome was sedation success rate, defined as the proportion of patients with successful anesthesia induction. Secondary outcomes encompassed the time of successful induction, the time of complete recovery, the time of leaving the room and the incidence rate of adverse events (hypoxemia, hypotension and injection pain). MAIN RESULTS: The success rate of sedation in both groups was 100 %. The 95 % CI of the difference of sedation success rate was (- 2.63 %, 2.63 %), and the lower limit was greater than the non-inferiority limit of -8 %.The time of successful sedation induction in ciprofol group (38.4 ± 6.5 s) was longer than that in propofol group (30.6 ± 6.2 s, p < 0.05).The time of complete recovery in ciprofol group (12.8 ± 5.8 min) was shorter than that in propofol group (16.9 ± 5.0 min, p < 0.05). The time of leaving the room in ciprofol group (21.8 ± 5.8 min) was shorter than those in propofol group (25.9 ± 5.1 min, p < 0.05). The incidence of injection pain in ciprofol group (2 %) was lower than that in the propofol group (25 %, p < 0.05). Other outcomes didn't show statistical differences. CONCLUSIONS: Compared with propofol, ciprofol exhibited a comparable level of sedation in older patients undergoing ERCP, and recovery was safe and rapid with less injection pain. TRIAL REGISTRATION: www.chictr.org.cn (Registration number ChiCTR2100053386, Registration date November 20, 2021).

Accurate Machine Learning-based Monitoring of Anesthesia Depth with EEG Recording.

General anesthesia, pivotal for surgical procedures, requires precise depth monitoring to mitigate risks ranging from intraoperative awareness to postoperative cognitive impairments. Traditional assessment methods, relying on physiological indicators or behavioral responses, fall short of accurately capturing the nuanced states of unconsciousness. This study introduces a machine learning-based approach to decode anesthesia depth, leveraging EEG data across different anesthesia states induced by propofol and esketamine in rats. Our findings demonstrate the model's robust predictive accuracy, underscored by a novel intra-subject dataset partitioning and a 5-fold cross-validation method. The research diverges from conventional monitoring by utilizing anesthetic infusion rates as objective indicators of anesthesia states, highlighting distinct EEG patterns and enhancing prediction accuracy. Moreover, the model's ability to generalize across individuals suggests its potential for broad clinical application, distinguishing between anesthetic agents and their depths. Despite relying on rat EEG data, which poses questions about real-world applicability, our approach marks a significant advance in anesthesia monitoring.