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.

Propofol does not alter the protein binding and unbound concentration of lidocaine at clinically targeted plasma concentrations in vitro - A short communication.

BACKGROUND: Intravenous lidocaine is increasingly used as an analgesic adjunct during general anaesthesia. Lidocaine is highly protein-bound and changes to binding can alter drug efficacy or toxicity. We aimed to measure the effect of various propofol and lidocaine plasma concentration combinations on the protein binding and concentration of lidocaine in vitro. METHODS: Known targeted concentrations of propofol and lidocaine were added to drug-free human plasma in vitro. Samples were prepared and analysed in various clinically relevant concentration combinations; propofol at 0, 2, 4 and 6 µg/mL, and lidocaine at 1, 3 and 5 µg/mL. The total and unbound concentrations of lidocaine were measured by ultra-high performance liquid chromatography-mass spectrometry and percentage protein binding was determined. Data were presented as mean and standard deviation (SD) and differences between analysed groups. RESULTS: The overall mean protein binding of lidocaine was 68.8% (SD 5.5, range 57.5-80.9%). Beta regression analysis revealed no statistically significant difference in lidocaine percentage binding across a range of propofol and lidocaine concentration combinations. CONCLUSION: Propofol did not alter the unbound and free pharmacologically active proportion of lidocaine at different clinically targeted concentrations of propofol and lidocaine in plasma in vitro. The percentage of plasma protein binding of lidocaine in this study was consistent with previously published results.

Efficacy and safety of alfaxalone compared to propofol in canine refractory status epilepticus: a pilot study.

Introduction: Refractory status epilepticus (RSE) is defined as seizure activity that is minimally responsive to first- or second-line antiseizure medications. Constant rate infusion (CRI) intravenous propofol (PPF) is commonly used to treat RSE in dogs and cats. The antiseizure activity of alfaxalone (ALF) in RSE has been demonstrated in various experimental studies. This study compared the clinical efficacy and safety of intramuscular administration followed by CRI infusion of ALF with intravenous administration followed by CRI infusion of PPF to treat canine RSE. Materials and methods: This was a multicenter, prospective, randomized clinical trial of client-owned dogs referred for status epilepticus that did not respond to first- and second-line drugs. Animals with suspected or confirmed idiopathic or structural epilepsy were included. The dogs were randomly assigned to either the PPF or ALF treatment groups and each group received drug CRI infusions for 6 h. Drug dosages were progressively reduced by 25% every hour from the third hour until suspension after 6 h. Patients were classified as responders or non-responders based on the relapse of epileptic seizures during the 24 h therapy infusion or within 24 h of drug suspension. Univariate statistical analyses were performed. Results: Twenty dogs were enrolled in the study. Ten (10/20) dogs were randomly allocated to the PPF group and 10 (10/20) to the ALF group. Successful outcomes were obtained in six (6/10) patients in the PPF group and five (5/10) patients in the ALF group. Adverse effects were recorded in six (6/10) and three (3/10) animals in the PPF and ALF groups, respectively. No statistically significant differences in outcomes or the presence of adverse effects were observed between the groups. Discussion: The results of this preliminary study suggest that ALF can be considered a valid and safe alternative to PPF for the treatment of RSE in dogs, with the additional advantage of intramuscular administration. However, caution should be exercised when using these drugs to provide airway and hemodynamic support.

Parameters Predictive of Propofol-Associated Acute Pancreatitis in Critically Ill Patients with COVID-19 Pneumonia: A Retrospective Cohort Study.

BACKGROUND: Propofol, a commonly used agent for short- and long-term sedation, is associated with acute pancreatitis. The main indirect mechanism of propofol-associated acute pancreatitis is by inducing hypertriglyceridemia. Patients with severe coronavirus disease 2019 (COVID-19) pneumonia often require prolonged mechanical ventilation and sedation. We examined the incidence rate of acute pancreatitis among critically ill adults with COVID-19 pneumonia on mechanical ventilation receiving propofol. In addition, we attempted to determine cutoff levels of serum triglycerides and doses of propofol that are predictive of propofol-associated acute pancreatitis. METHODS: This was a multicenter retrospective cohort study using a large dataset of hospitalized patients with COVID-19. The collected data included the number of days on propofol, cumulative doses of propofol, peak levels of serum triglycerides, serum lipase levels, and abdominal imaging findings. We used receiver-operating characteristic analysis in conjunction with Youden's index to identify the optimal thresholds for propofol administration parameters and levels of triglycerides that would provide maximal sensitivity and specificity for predicting acute pancreatitis. RESULTS: Out of 499 critically ill patients with COVID-19 pneumonia, 154 met the inclusion criteria. Six (4%) patients had suspected acute pancreatitis based on elevated serum lipase levels. Cutoff values greater than 688 mg/dL for peak level of triglycerides, 4.5 days on propofol, 3007 mg/day for average daily propofol dose, and 24 113 mg for cumulative propofol dose were associated with high risk of suspected acute pancreatitis. The negative predictive values for suspected acute pancreatitis using these cutoffs ranged from 98% to 100%. CONCLUSIONS: Propofol use in critically ill COVID-19 patients is associated with a low incidence rate of acute pancreatitis. We identified cutoff values for serum triglycerides and cumulative propofol dose that are linked to higher risk of propofol-associated pancreatitis. More research is needed to examine the true incidence of propofol-associated pancreatitis and help develop optimal cutoff values for certain parameters to help guide safe propofol administration.

The effects of remimazolam combined with sufentanil on respiration, circulation and sedation level in patients undergoing colonoscopy.

BACKGROUND: The main sedative which is propofol in painless gastroenteroscopy, has a high risk of reducing blood pressure and respiratory depression. Remimazolam (a short-acting benzodiazepine) is expected to be widely used in painless gastroenteroscopy due to its rapid onset, rapid metabolism and light respiratory and circulation inhibition. METHODS: A randomized, single-blind, parallel, controlled study, 123 outpatients who were undergoing painless colonoscopy and ramdomly divided into group A, B and C, in Hangzhou First People's Hospital, July-December 2021. All patients were intravenously injected with 5 µg sufentanil for analgesic preconditioning. The group A was induced by 0.2 mg/kg remimazolam besylate. The group B was induced by 0.25 mg/kg remimazolam besylate. And the group C was inducted by 2.0 mg /kg propofol. If the patients had limb movement or MOAA/S score > 3 and so on, remimazolam besylate was added at 2.5 mg/ time in group A and B, and propofol emulsion injection was added at 0.5 mg/kg/ time in group C. During the operation, according to the actual situation, remimazolam was per added 2.5 mg in the experimental group, and propofol was 0.5 mg/kg in the control group. Heart rate (HR), non-invasive blood pressure (BP), respiratory rate (RR), pulse oxygen saturation (SpO2), and improved vigilance/sedation score (MOAA/S) of patients was recorded from entering endoscopy room to get out of the anesthesia recovery room, also including perioperative adverse events, other medications or treatments, the time of patients waking up and leaving the hospital. RESULTS: The successful rate of induction in three groups was 100%. There was no significant difference in the sedation completion rate among the three groups (Group A:90.2%, Group B: 92.7%, Group C: 92.7%, P = 1.000). The rate of adverse events after administration: group A(27.0%) and B(36.8%) both lower than group C(71.0%),P < 0.001;There was no significant difference between group A and group B, P > 0.744;The average time from the last drug administration to meet the discharge criteria of the subjects in three groups was as follows: The average time of group A(16.2 min) and Group B(16.5 min) both shorter than group C(19.6 min), P = 0.001; There was no significant difference between group A and group B, P = 0.742. CONCLUSIONS: This study revealed that remimazolam is a safe and effective medication for colonoscopy sedation, the security of remimazolam is better than propofol, and the sedative effect with the initial dose of 0.25 mg/kg of remimazolam is optimal. TRIAL REGISTRATION: China Clinical Trial Center with registration number: 2100052615,02/11/2021.

Comparison of remimazolam tosilate and propofol during induction and maintenance of general anesthesia in patients undergoing laparoscopic cholecystectomy: a prospective, single center, randomized controlled trial.

BACKGROUND: Remimazolam tosilate (RT) is a new, ultrashort-acting benzodiazepine. Here, we investigated the efficacy and safety of RT for general anesthesia in patients undergoing Laparoscopic Cholecystectomy (LC). METHODS: In this study, 122 patients undergoing laparoscopic cholecystectomy were randomly allocated to receive either remimazolam tosilate (Group RT) or propofol group (Group P). RT was administered as a slow bolus of 0.3 mg kg- 1 for induction, followed by 1.0-2.0 mg kg- 1 h- 1 for maintenance of general anesthesia. Propofol was started at 2 mg kg- 1 and followed by 4-10 mg kg- 1 h- 1 until the end of surgery. The primary outcome was the time to bispectral index (BIS) ≤ 60. The secondary outcome included the time to loss of consciousness (LoC), and the time to extubation. Adverse events were also assessed. RESULTS: A total of 112 patients were recruited for study participation. Among them, the time to BIS ≤ 60 in Group RT was longer than that in Group P (Group RT: 89.3 ± 10.7 s; Group P: 85.9 ± 9.7 s, P > 0.05). While the time to LoC comparing remimazolam and propofol showed no statistical significance (Group RT: 74.4 ± 10.3 s; Group P: 74.7 ± 9.3 s, P > 0.05). The time to extubation in Group RT was significantly longer than that in Group P (Group RT: 16.0 ± 2.6 min; Group P: 8.8 ± 4.3 min, P < 0.001). Remimazolam tosilate had more stable hemodynamics and a lower incidence of hypotension during general anesthesia. CONCLUSIONS: Remimazolam tosilate can be safely and effectively used for general anesthesia in patients undergoing Laparoscopic Cholecystectomy. It maintains stable hemodynamics during induction and maintenance of general anesthesia compared with propofol. Further studies are needed to validate the findings. TRIAL REGISTRATION: Chictr.org.cn ChiCTR2300071256 (date of registration: 09/05/2023).

Comparison of Propofol-Based Total Intravenous Anesthesia versus Volatile Anesthesia with Sevoflurane for Postoperative Delirium in Adult Coronary Artery Bypass Grafting Surgery: A Prospective Randomized Single-Blinded Study.

OBJECTIVES: 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). DESIGN: This was a prospective randomized single-blinded study. SETTING: 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. PARTICIPANTS: Seventy-two patients undergoing elective CABG under CPB participated in this study. INTERVENTIONS: 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. MEASUREMENTS & MAIN RESULTS: 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)*. CONCLUSIONS: 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.

Study on the preventive effect of dexmedetomidine on anesthetic associated sleep disturbance in young to middle-aged female patients undergoing hysteroscopy: a study protocol for a crossover randomized controlled trial.

BACKGROUND: Postoperative sleep disturbance has a potentially detrimental effect on postoperative recovery. Perioperative patients are affected by several factors. General anesthesia induces a non-physiological state that does not resemble natural sleep. Exposure to propofol/sevoflurane can lead to desynchronization of the circadian rhythm, which may result in postoperative sleep disturbance characterized by mid-cycle advancement of sleep and daytime sleepiness. Dexmedetomidine is a highly selective α2-adrenoceptor agonist with a unique sedative effect that facilitates the transition from sleep to wakefulness. Basic research has shown that dexmedetomidine induces deep sedation, similar to physical sleep, and helps maintain forebrain connectivity, which is likely to reduce delirium after surgery. The aim of this study is to evaluate the influence of exposure to the mono-anesthetic propofol on the development of postoperative sleep disturbance in young and middle-aged female patients undergoing hysteroscopy and whether prophylactic administration of dexmedetomidine influences reducing postoperative sleep disturbance. METHODS: This prospective randomized controlled trial (RCT) will include 150 patients undergoing hysteroscopy at the First Affiliated Hospital of Xiamen University. Participants will be randomly assigned to three groups in a 1:1:1 ratio. The dexmedetomidine group will have two subgroups and will receive a nasal spray of 0.2 µg/kg or 0.5 µg/kg 25 min before surgery, while the control group will receive a saline nasal spray. Three groups will undergo hysteroscopy with propofol-based TIVA according to the same scheme. Sleep quality will be measured using a wearable device and double-blind sleep assessments will be performed before surgery and 1, 3, and 7 days after surgery. SPSS 2.0 is used for statistical analysis. A χ2 test is used to compare groups, and t-test is used to determine statistical the significance of continuous variables. DISCUSSION: The purpose of this study is to investigate the incidence of propofol-associated sleep disorders and to test a combination of dexmedetomidine anesthesia regimen for the prevention of postoperative sleep disorders. This study will help to improve patients' postoperative satisfaction and provide a new strategy for comfortable perioperative medical treatment. TRIAL REGISTRATION: ClinicalTrials.gov NCT06281561. Registered on February 24, 2024.

A Comparative Study of Fixed-Dose Dexmedetomidine and Propofol Infusions on Intraoperative Desflurane Consumption During Bispectral Index-Guided Laparoscopic Surgeries: A Randomized Controlled Study.

Background Desflurane is an excellent but expensive volatile anesthetic agent. Dexmedetomidine and propofol may decrease intraoperative desflurane consumption. This study aimed to compare the desflurane-sparing effect of dexmedetomidine and propofol in patients undergoing laparoscopic surgeries under bispectral index (BIS)-guided general anesthesia (GA). Methods Sixty-two adult patients, ASA (American Society of Anesthesiologists) physical status I or II, of either sex, aged between 18 and 60 years, were randomly allocated into group D or group P. Only group D patients received an intravenous (IV) bolus of dexmedetomidine (1 mcg/kg) over 15 minutes before induction. In both groups, GA was induced following the standard protocol with propofol infusion (0.5 mg/kg/min) until the BIS value dropped below 60. For maintenance, group D and group P patients received IV dexmedetomidine infusion (0.5 mcg/kg/h) and propofol infusion (50 mcg/kg/min), respectively. In both groups, desflurane dial concentration was adjusted between 3 and 8% to maintain the BIS within the range of 45-55. An hourly bolus of IV fentanyl (0.5 mcg/kg) and a half-hourly bolus of IV vecuronium (0.02 mg/kg) were administered. The total amount of desflurane consumed, duration of pneumoperitoneum, extra aliquots of propofol used during maintenance, number of boluses of IV atropine, fentanyl, and esmolol, time to attain Ramsay Sedation Score of 2 after extubation, time to first postoperative analgesic request at Numerical Rating Scale (NRS) score ≥ 4, time to reach a Modified Aldrete Score of ≥9, and incidence of any side effects were recorded. All the data were analyzed and compared using appropriate statistical tests, and a p-value of <0.05 was considered significant. Results The final data analysis was performed on 60 patients. The mean desflurane consumption was clinically higher in group P patients than in group D, but the difference was statistically insignificant (p-value > 0.05). The mean induction dose of propofol was significantly less in group D than in group P (p-value < 0.05). After extubation, the difference in time to the first analgesic request (NRS ≥ 4) between the groups was statistically significant (p-value < 0.05). Group D patients had a residual intraoperative analgesic effect. Conclusion The effects of dexmedetomidine and propofol infusions on desflurane consumption in laparoscopic surgeries are comparable, with minimal effects on intraoperative hemodynamics and postoperative recovery profiles.

Comparison of Two Intravenous Propofol Doses after Jugular Administration for Short Non-Surgical Procedures in Red-Eared Sliders (Trachemys scripta elegans).

This study compares the effects of two different doses of propofol administered intravenously (IV), in the jugular vein, to red-eared sliders (Trachemys scripta elegans). In this crossover study, 5 or 10 mg/kg propofol was administered to six Trachemys scripta elegans after cannulation of the jugular vein. Each turtle received each dose, G1 (5 mg/kg IV) and G2 (10 mg/kg IV), after a 7-day washout period. The parameters evaluated were heart rate, palpebral reflex, cloacal reflex, muscle relaxation, ease of handling, sensitivity to anterior and posterior pinch stimuli, and possibility of intubation. Additionally, respiratory rate was measured when possible, and the times from propofol administration to full recovery and from intubation to extubation were recorded. None of the turtles in G1 could be intubated, and this dose provided little relaxation and ease of handling, with a duration of effect until full recovery of 12.16 ± 8.32 (SD) min for this group. In G2, five out of the six turtles could be intubated, and the duration of effect was 32.33 ± 5.85 (SD) min. Heart rates were influenced by manipulation for catheter placement. There were statistically significant differences (p value ≤ 0.05) between the two groups in muscle relaxation degree, handling, cloacal reflex, and possibility of intubation. The 5 mg/kg propofol dose was not sufficient to induce anesthesia, even when administered in the jugular vein, in red-eared sliders. A dose of 10 mg/kg IV or higher should be used.

Comparison of opioid-free and opioid-inclusive propofol anaesthesia for thyroid and parathyroid surgery: a randomised controlled trial.

BACKGROUND: Postoperative nausea and vomiting occur frequently following thyroid and parathyroid surgery and are associated with worse patient outcomes. We hypothesised that opioid-free propofol anaesthesia would reduce the incidence of postoperative nausea and vomiting compared with opioid-inclusive propofol anaesthesia in patients undergoing these procedures. METHODS: We conducted a randomised, double-blinded controlled trial in adult patients scheduled to undergo thyroid and parathyroid surgery at two medical centres in mainland China. Patients were allocated randomly (1:1, stratified by sex and trial site) to an opioid-free anaesthesia group (esketamine, lidocaine, dexmedetomidine and propofol) or an opioid-inclusive group (sufentanil and propofol). Propofol infusions were titrated to bispectral index 45-55. Patients received prophylaxis for nausea and vomiting using dexamethasone and ondansetron and multimodal analgesia with paracetamol and flurbiprofen axetil. The primary outcome was the incidence of postoperative nausea and vomiting in the first 48 h after surgery. RESULTS: We assessed 557 patients for eligibility and 394 completed this trial. The incidence of postoperative nausea and vomiting in the first postoperative 48 h was lower in the opioid-free anaesthesia group (10/197, 5%) compared with opioid-inclusive group (47/197, 24%) (OR (95%CI) 0.17 (0.08-0.35), p < 0.001), yielding a number needed to treat of 5.3. Additionally, opioid-free propofol anaesthesia was associated with a reduced need for rescue anti-emetics, lower rates of hypotension and desaturation after tracheal extubation, and higher patient satisfaction. Time to tracheal extubation was prolonged slightly in the opioid-free group. The two groups had similar postoperative pain scores and 30-day outcomes. DISCUSSION: Opioid-free propofol anaesthesia reduced postoperative nausea and vomiting in patients undergoing thyroid and parathyroid surgery. An opioid-free anaesthetic regimen can optimise anaesthetic care during thyroid and parathyroid surgery.

Propofol total intravenous anesthesia vs. sevoflurane inhalation anesthesia: Effects on post­operative cognitive dysfunction and inflammation in geriatric patients undergoing laparoscopic surgery.

Propofol total intravenous anesthesia (TIVA) or sevoflurane inhalation anesthesia (IA) affects post-operative cognitive dysfunction in geriatric patients undergoing laparoscopic surgery; however, relevant real-world clinical evidence on the matter is limited. The present study aimed to compare the effects of propofol TIVA and sevoflurane IA on post-operative cognitive dysfunction in the aforementioned type of patients. The present prospective study enrolled 197 geriatric patients undergoing laparoscopic surgery. Patients were assigned to the propofol TIVA group (n=97) and sevoflurane IA group (n=100) according to the actual anesthesia regimens. The mini-mental state examination (MMSE) score was assessed before surgery and on day (D)1, D3 and D7 following surgery in both groups. The MMSE score on D1 was higher in the TIVA group compared with the IA group (P=0.006). The change in the MMSE scores from before surgery to D1 (P<0.001), D3 (P=0.011) and D7 (P=0.003) was smaller in the TIVA group vs. the IA group. Multivariate linear regression analyses suggested that the anesthesia method of TIVA (vs. IA) was independently related to the increased MMSE score on D1 (b=0.803; P=0.001) and D7 (b=0.472; P=0.025). The levels of interleukin (IL)-17A, IL-6 and tumor necrosis factor-α on D1, D3 and D7 exhibited a slightly decreasing trend in the TIVA group vs. the IA group, although the difference was not statistically significant (all P>0.05). Notably, the levels of IL-17A before surgery (P=0.015), on D3 (P=0.016) and D7 (P=0.002), as well as those of IL-6 on D1 (P=0.027), were negatively associated with the MMSE score at the corresponding time points. Overall, the present study demonstrates that propofol TIVA ameliorates post-operative cognitive dysfunction on D1 compared with sevoflurane IA and exerts a potentially suppressive effect on inflammation in geriatric patients undergoing laparoscopic surgery.

Effect of desflurane maintenance on postoperative sleep quality in patients undergoing elective breast surgery: A non-inferiority randomized controlled trail.

BACKGROUND: 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. METHOD: 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. RESULTS: 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. CONCLUSION: 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. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04805775.

Propofol improves sleep deprivation-induced sleep structural and cognitive deficits via upregulating the BMAL1 expression and suppressing microglial M1 polarization.

BACKGROUND: Sleep deprivation (SD) is a growing global health problem with many deleterious effects, such as cognitive impairment. Microglia activation-induced neuroinflammation may be an essential factor in this. Propofol has been shown to clear sleep debt after SD in rats. This study aims to evaluate the effects of propofol-induced sleep on ameliorating sleep quality impairment and cognitive decline after 48 h SD. METHODS: Almost 8-12-week-old rats were placed in the SD system for 48 h of natural sleep or continuous SD. Afterwards, rats received propofol (20 mg·kg-1·h-1, 6 h) via the tail or slept naturally. The Morris water maze (MWM) and Y-maze test assessed spatial learning and memory abilities. Rat EEG/EMG monitored sleep. The expression of brain and muscle Arnt-like protein 1 (BMAL1), brain-derived neurotrophic factor (BDNF) in the hippocampus and BMAL1 in the hypothalamus were assessed by western blot. Enzyme-linked immunosorbent assay detected IL-6, IL-1ß, arginase 1 (Arg1), and IL-10 levels in the hippocampus. Immunofluorescence was used to determine microglia expression as well as morphological changes. RESULTS: Compared to the control group, the sleep-deprived rats showed poor cognitive performance on both the MWM test and the Y-maze test, accompanied by disturbances in sleep structure, including increased total sleep time, and increased time spent and delta power in non-rapid eye movement sleep. In addition, SD induces abnormal expression of the circadian rhythm protein BMAL1, activates microglia, and causes neuroinflammation and nerve damage. Propofol reversed these changes and saved sleep and cognitive impairment. Furthermore, propofol treatment significantly reduced hippocampal IL-1ß and IL-6 levels, increased BDNF, Arg1, and IL-10 levels, and switched microglia surface markers from the inflammatory M1 type to the anti-inflammatory M2 type. CONCLUSION: Propofol reduces SD-induced cognitive impairment and circadian rhythm disruption, possibly by lowering neuronal inflammation and switching the microglia phenotype from an M1 to an M2 activated state, thus exerting neuroprotective effects.

Comparison of Propofol and Sevoflurane Anaesthesia in Terms of Postoperative Nausea-Vomiting Complication in Cardiac Surgery Patients Undergoing Enhanced Recovery After Surgery Protocol: A Prospective Randomized Study.

Objective: Postoperative nausea (PN) and vomiting (PONV) in cardiac surgery increases adrenergic stimulation, limits mobilization and oral intake, and can be distressing for patients. The primary aim of our study was to investigate the effect of sevoflurane and propofol anaesthesia on the incidence of PONV in cardiac surgery patients undergoing Enhanced Recovery After Surgery (ERAS) protocol. Methods: Following ethics committee approval, 62 patients undergoing elective coronary artery bypass surgery with ERAS protocol were included in this prospective randomized study. After standard induction of anaesthesia, Group S received 1.5-2% sevoflurane and Group P received 50-100 µg kg-1 min-1 propofol infusion as maintenance anaesthetic agent with a bispectral index of 40-50. The incidence of PN and PONV between 0-6 hours (early) and 6-24 hours (late) after extubation was compared as the primary outcome. The incidence of delirium was analyzed as a secondary outcome for similar periods. Results: In the propofol group, 3 patients were excluded due to postoperative tamponade revision and prolonged mechanical ventilation. PN in the early post-extubation period (29% vs. 7.1%, P=0.031) was significantly higher in Group S. The incidence of delirium was similar between the groups in both periods. Conclusion: Propofol may reduce the incidence of PN in the first 6 hours after extubation compared with sevoflurane. We believe that this period will be beneficial for gastrointestinal tolerance as it is the period when oral intake is initiated in patients. In conclusion, propofol maintenance in cardiac surgery patients may facilitate patient rehabilitation as part of the ERAS protocol.

Successful Use of Propofol After Failed Palliative Sedation in Patients With Refractory Symptoms.

Context: Propofol is a general anesthetic used in multiple clinical scenarios. Despite growing evidence supporting its use in palliative care, propofol is rarely used in palliative sedation. Reluctance toward the adoption of propofol as a sedative agent is often associated with fear of adverse events such as respiratory arrest. Objectives: We aimed to describe efficacy and safety of palliative sedation in refractory sedation with propofol using a protocol based on low, incremental dosing. Methods: A retrospective observational study featuring inpatients receiving sedative treatment with propofol in our palliative care unit in Madrid (Spain) between March 1, 2018 and February 28, 2023, following a newly developed protocol. Results: During the study period, 22 patients underwent sedation with propofol. Propofol was used successfully to control different refractory symptoms, mainly psychoexistential suffering and delirium. All patients had undergone previous failed attempts at sedation with other medications (midazolam or lemovepromazine) and presented risk factors for complicated sedation. All patients achieved satisfactory (profound) levels of sedation measured with the Ramsay Sedation Scale, but total doses varied greatly between patients. Most patients (17, 77%) received combined therapy with propofol and other sedative medications to harness synergies. The median time between start of sedation with propofol and death was 26.0 hours. No cases of apnea or death during induction were recorded. Conclusion: A protocol for palliative sedation with propofol based on low, incremental dosing, with the option of administering an initial induction bolus, shows excellent results regarding adequate levels of sedation, without observing apnea or respiratory depression. Our results promote the use of propofol to achieve palliative sedation in patients with refractory symptoms and risk factors for complicated sedation at the end of life.

Intravenous esketamine as an adjuvant for sedation/analgesia outside the operating room: a systematic review and meta-analysis.

Background: This study was conducted to evaluate the safety and efficacy of intravenous esketamine as an adjuvant for sedation or analgesia outside the operating room in adults and children. Method: PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, and Scopus were searched for potential randomized controlled studies randomized controlled trials comparing drug combinations of esketamine to any other single or combination drug regimens for sedation or analgesia outside the operating room. Results: Twenty-five studies with a total of 3,455 participants were included in this review. The pooled results of adults showed that compared with drug regimens of the control group, intravenous esketamine combinations were significantly associated with decreased risk of oxygen desaturation (RR = 0.49, 95% CI = [0.34, 0.70]); hypotension (RR = 0.38, 95% CI = [0.31, 0.46]); bradycardia (RR = 0.23, 95% CI = [0.12, 0.43]); injection pain (RR = 0.37, 95% CI = [0.25, 0.53]); body movement (RR = 0.60, 95% CI = [0.41, 0.88]); and propofol consumption (SMD = -1.38, 95% CI = [-2.64, -0.11]), but an increased risk of psychiatric symptoms (RR = 3.10, 95% CI = [2.11, 4.54]) (RR = relative risk; CI = confidence intervals; SMD = standardized mean difference). Subgroup analysis showed that only the combination of esketamine and propofol significantly reduced the above incidence of respiratory and cardiovascular adverse events in adults. In addition, the pooled results of children showed that compared with drug regimens of the control group, esketamine and propofol co-administration significantly reduced the risk of hypotension (RR = 0.59, 95% CI = [0.37, 0.95]) but increased the risk of visual disturbance (RR = 6.62, 95% CI = [2.18, 20.13]) and dizziness (RR = 1.99, 95% CI = [1.17, 3,37]). Subgroup analysis indicated that esketamine>0.5 mg/kg significantly reduced the incidence of hypotension, but increased the risk of dizziness in children. Conclusion: Intravenous use of esketamine, particularly in combination with propofol, may improve the safety and efficacy of sedation and analgesia outside the operating room, although the potential for psychiatric side effects warrants attention. Future research is recommended to investigate the role of esketamine with agents other than propofol.

Comparison of the efficacy and safety of ciprofol and propofol in sedating patients in the operating room and outside the operating room: a meta-analysis and systematic review.

BACKGROUND: As a new type of intravenous anesthetic, ciprofol has the advantages of fast onset of action, fast recovery and high clearance rate. This study aimed to investigate the effectiveness and safety of ciprofol versus traditional propofol for anesthesia and sedation in and out of the operating room. METHODS: We searched the literature in PubMed, Web of Science, Cochrane Library, and Embase databases from January 2021 to December 2023. All clinical studies comparing the sedative effects of propofol and ciprofol, both inside and outside the operating room, were included in our trial. The main outcome measures were induction time and incidence of injection-site pain. Data are merged using risk ratio and standardized mean difference with 95% confidence interval. Subgroup analysis, meta-regression, sensitivity analysis, and publication bias were performed. The study protocol was prospectively registered with PROSPERO (CRD42023447747). RESULTS: A total of 15 randomized, controlled trials involving 2002 patients were included in this study. Compared with propofol, ciprofol has a longer induction time in the operating room but a shorter induction time in non-operating room settings. Ciprofol can effectively reduce the risk of injection-site pain and respiratory depression both inside and outside the operating room. In addition, the risk of drug-related hypotension induced with ciprofol in the operating room is lower, but the awakening time is also longer. Meta-regression analysis showed that neither age nor BMI were potential sources of heterogeneity. Funnel plot, egger and begg tests showed no significant publication bias. Sensitivity analyzes indicate that our results are robust and reliable. CONCLUSION: Ciprofol has absolute advantages in reducing the risk of injection-site pain and respiratory depression, both in and outside operating room. Intraoperative use of ciprofol reduces the risk of drug-related hypotension and may also reduce the risk of intraoperative physical movements. However, ciprofol may have longer induction and awakening time than propofol.

Targeted drug release from stable and safe ultrasound-sensitive nanocarriers.

Targeted delivery of medication has the promise of increasing the effectiveness and safety of current systemic drug treatments. Focused ultrasound is emerging as noninvasive and practical energy for targeted drug release. However, it has yet to be determined which nanocarriers and ultrasound parameters can provide both effective and safe release. Perfluorocarbon nanodroplets have the potential to achieve these goals, but current approaches have either been effective or safe, but not both. We found that nanocarriers with highly stable perfluorocarbon cores mediate effective drug release so long as they are activated by ultrasound of sufficiently low frequency. We demonstrate a favorable safety profile of this formulation in a non-human primate. To facilitate translation of this approach into humans, we provide an optimized method for manufacturing the nanocarriers. This study provides a recipe and release parameters for effective and safe drug release from nanoparticle carriers in the body part specified by focused ultrasonic waves.

Recurrence-free survival after curative resection of non-small cell lung cancer between inhalational gas anesthesia and propofol-based total intravenous anesthesia: a multicenter, randomized, clinical trial (GAS TIVA trial): protocol description.

BACKGROUND: Surgery is the primary treatment for non-small cell lung cancer (NSCLC), but microscopic residual disease may be unavoidable. Preclinical studies have shown that volatile anesthetics might suppress host immunity and promote a pro-malignant environment that supports cancer cell proliferation, migration, and angiogenesis, whereas propofol may preserve cell-mediated immunity and inhibit tumor angiogenesis. However, clinical evidence that propofol-based total intravenous anesthesia (TIVA) can reduce tumor recurrence after curative resection remains inconsistent due to the retrospective observational nature of previous studies. Therefore, we will test the hypothesis that the recurrence-free survival (RFS) after curative resection of NSCLC is higher in patients who received TIVA than volatile anesthetics (GAS) in this multicenter randomized trial. METHODS: This double-blind, randomized trial will enroll patients at 22 international sites, subject to study registration, institutional review board approval, and patient written informed consent. Eligible patients are adult patients undergoing lung resection surgery with curative intent for NSCLC. Exclusion criteria will be contraindications to study drugs, American Society of Anesthesiologists physical status IV or higher, or preexisting distant metastasis or malignant tumor in other organs. At each study site, enrolled subjects will be randomly allocated into the TIVA and GAS groups with a 1:1 ratio. This pragmatic trial does not standardize any aspect of patient care. However, potential confounders will be balanced between the study arms. The primary outcome will be RFS. Secondary outcomes will be overall survival and complications within postoperative 7 days. Enrollment of 5384 patients will provide 80% power to detect a 3% treatment effect (hazard ratio of 0.83) at alpha 0.05 for RFS at 3 years. DISCUSSION: Confirmation of the study hypothesis would demonstrate that a relatively minor and low-cost alteration in anesthetic management has the potential to reduce cancer recurrence risk in NSCLC, an ultimately fatal complication. Rejection of the hypothesis would end the ongoing debate about the relationship between cancer recurrence and anesthetic management. TRIAL REGISTRATION: The study protocol was prospectively registered at the Clinical trials ( https://clinicaltrials.gov , NCT06330038, principal investigator: Hyun Joo Ahn; date of first public release: March 25, 2024) before the recruitment of the first participant.