Propofol is one of the main sedatives but its negative side effects limit its clinical application. Chitosan oligosaccharide (COS), a kind of natural product with anti-pain and anti-inflammatory activities, may be a potential adjuvant to propofol use. A total of 94 patients receiving surgeries were evenly and randomly assigned to two groups: 10 mg/kg COS oral administration and/or placebo oral administration before being injected with propofol. The target-controlled infusion of propofol was adjusted to maintain the values of the bispectral index at 50. All patients' pain was evaluated on a four-point scale and side effects were investigated. To explore the molecular mechanism for the functions of COS in propofol use, a mouse pain model was established. The activities of Nav1.7 were analyzed in dorsal root ganglia (DRG) cells. The results showed that the patients receiving COS pretreatment were likely to require less propofol than the patients pretreated with placebo for maintaining an anesthetic situation (p < 0.05). The degrees of injection pain were lower in a COS-pretreated group than in a propofol-pretreated group. The side effects were also more reduced in a COS-treated group than in a placebo-pretreated group. COS reduced the activity of Nav1.7 and its inhibitory function was lost when Nav1.7 was silenced (p > 0.05). COS improved propofol performance by affecting Nav1.7 activity. Thus, COS is a potential adjuvant to propofol use in surgical anesthesia.

Epidemiological evidence strongly links fish oil, which is rich in docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), with low incidences of several types of cancer. The inhibitory effects of omega-3 polyunsaturated fatty acids on cancer development and progression are supported by studies with cultured cells and animal models. Propofol (2,6-diisopropylphenol) is the most extensively used general anesthetic-sedative agent employed today and is nontoxic to humans at high levels (50 microg/ml). Clinically relevant concentrations of propofol (3 to 8 microg/ml; 20 to 50 microM) have also been reported to have anticancer activities. The present study describes the synthesis, purification, characterization and evaluation of two novel anticancer conjugates, propofol-docosahexaenoate (propofol-DHA) and propofol-eicosapentaenoate (propofol-EPA).

In Alzheimer's disease (AD) and other tauopathies, the microtubule-associated protein tau can undergo aberrant hyperphosphorylation potentially leading to the development of neurofibrillary pathology. Anesthetics have been previously shown to induce tau hyperphosphorylation through a mechanism involving hypothermia-induced inhibition of protein phosphatase 2A (PP2A) activity. However, the effects of propofol, a common clinically used intravenous anesthetic, on tau phosphorylation under normothermic conditions are unknown. We investigated the effects of a general anesthetic dose of propofol on levels of phosphorylated tau in the mouse hippocampus and cortex under normothermic conditions. Thirty min following the administration of propofol 250 mg/kg i.p., significant increases in tau phosphorylation were observed at the AT8, CP13, and PHF-1 phosphoepitopes in the hippocampus, as well as at AT8, PHF-1, MC6, pS262, and pS422 epitopes in the cortex. However, we did not detect somatodendritic relocalization of tau. In both brain regions, tau hyperphosphorylation persisted at the AT8 epitope 2 h following propofol, although the sedative effects of the drug were no longer evident at this time point. By 6 h following propofol, levels of phosphorylated tau at AT8 returned to control levels. An initial decrease in the activity and expression of PP2A were observed, suggesting that PP2A inhibition is at least partly responsible for the hyperphosphorylation of tau at multiple sites following 30 min of propofol exposure. We also examined tau phosphorylation in SH-SY5Y cells transfected to overexpress human tau. A 1 h exposure to a clinically relevant concentration of propofol in vitro was also associated with tau hyperphosphorylation. These findings suggest that propofol increases tau phosphorylation both in vivo and in vitro under normothermic conditions, and further studies are warranted to determine the impact of this anesthetic on the acceleration of neurofibrillary pathology.

No abstract available

As the adjunctive anesthesia to propofol, both dezocine and fentanyl showed some potential for gastrointestinal endoscopy. This meta-analysis aimed to compare their efficacy and safety.

We developed safe and stable mixed polymeric micelles with low lipids and free propofol for intravenous administration, to overcome the biological barrier of the reticuloendothelial system (RES), reduce pain upon injection, and complications of marketed propofol formulation. The propofol-mixed micelles were composed of distearoyl-phosphatidylethanolamine-methoxy-poly (ethylene glycol 2000) (DSPE mPEG2k) and Solutol HS 15 and were optimized using Box Behnken design (BBD). The optimized formulation was evaluated for globule size, zeta potential, loading content, encapsulation efficiency, pain on injection, histological evaluation, hemolysis test, in vivo anesthetic action, and pharmacokinetics, in comparison to the commercialized emulsion Diprivan. The optimized micelle formulation displayed homogenous particle sizes, and the free drug concentration in the micelles was 60.9% lower than that of Diprivan. The paw-lick study demonstrated that propofol-mixed micelles significantly reduced pain symptoms. The anesthetic action of the mixed micelles were similar with the Diprivan. Therefore, we conclude that the novel propofol-mixed micelle reduces injection-site pain and the risk of hyperlipidemia due to the low content of free propofol and low-lipid constituent. It may be a more promising clinical alternative for anesthetic.

To systematically evaluate the efficacy and safety of alfentanil plus propofol versus propofol only for painless gastrointestinal endoscopy.

Propofol is an intravenous hypnotic drug that is used for induction and maintenance of sedation and general anaesthesia. It exerts its effects through potentiation of the inhibitory neurotransmitter γ-aminobutyric acid (GABA) at the GABAA receptor, and has gained widespread use due to its favourable drug effect profile. The main adverse effects are disturbances in cardiopulmonary physiology. Due to its narrow therapeutic margin, propofol should only be administered by practitioners trained and experienced in providing general anaesthesia. Many pharmacokinetic (PK) and pharmacodynamic (PD) models for propofol exist. Some are used to inform drug dosing guidelines, and some are also implemented in so-called target-controlled infusion devices, to calculate the infusion rates required for user-defined target plasma or effect-site concentrations. Most of the models were designed for use in a specific and well-defined patient category. However, models applicable in a more general population have recently been developed and published. The most recent example is the general purpose propofol model developed by Eleveld and colleagues. Retrospective predictive performance evaluations show that this model performs as well as, or even better than, PK models developed for specific populations, such as adults, children or the obese; however, prospective evaluation of the model is still required. Propofol undergoes extensive PK and PD interactions with both other hypnotic drugs and opioids. PD interactions are the most clinically significant, and, with other hypnotics, tend to be additive, whereas interactions with opioids tend to be highly synergistic. Response surface modelling provides a tool to gain understanding and explore these complex interactions. Visual displays illustrating the effect of these interactions in real time can aid clinicians in optimal drug dosing while minimizing adverse effects. In this review, we provide an overview of the PK and PD of propofol in order to refresh readers' knowledge of its clinical applications, while discussing the main avenues of research where significant recent advances have been made.

No abstract available

Using functional magnetic resonance imaging in human participants, we show that sedation by propofol to the point of lost overt responsiveness during the performance of an auditory verbal memory task unexpectedly increases functional connectivity of the precuneus with cortical regions, particularly the dorsal prefrontal and visual cortices. After recovery of consciousness, functional connectivity returns to a pattern similar to that observed during the wakeful baseline. In the context of a recent proposal that highlights the uncoupling of consciousness, connectedness, and responsiveness in general anesthesia, the increased precuneus functional connectivity under propofol sedation may reflect disconnected endogenous mentation or dreaming that continues at a reduced level of metabolic activity.

Propofol is a rapidly acting water-insoluble non-barbiturate anesthetic agent that is widely used as an intravenous sedative-hypnotic agent. Anecdotal evidence indicates that propofol may be effective at terminating intractable migraine headache. Cortical spreading depression (CSD) is believed to be the neural correlate of migraine aura and may be a trigger for migraine pain. Agents that block the induction or slow the spread of CSD may be of utility in treating migraine. Here we examined the ability of propofol hemisuccinate (PHS), a water-soluble prodrug of propofol, to affect CSD in mice. For comparison, we examinined dizocilpine, an NMDA receptor antagonist, that is well recognized to inhibit CSD. When administered 15min prior to activation of CSD by KCl application to the cortex, intraperitoneal PHS at doses of 120 and 200mg/kg decreased the number of CSD deflections without an effect on CSD amplitude, and at 200mg/kg caused a 77% reduction in CSD velocity. The minimally-effective dose of PHS (120mg/kg) did not cause sedation or motor impairment and while some animals receiving 200mg/kg did demonstrate motor impariment none exhibited loss-of-righting reflex (anesthesia). Dizocilpine produced comparable inhibition of CSD at doses of 0.5 and 2.5mg/kg. We conclude that acute PHS treatment inhibits CSD. Our results indicate that propofol, or its prodrug PHS, are worthy of further investigation as a treatment for migraine.

Although dental treatment with sedation is performed increasingly in special needs patients, data on adding midazolam to intravenous propofol sedation are very limited for this group. The purpose of this study was to identify the factors and procedure time associated with the use of intravenous sedation with propofol alone or propofol combined with midazolam in dental patients with special needs.This was a retrospective data analysis. The sedation medications and relevant covariates, including demographic parameters, disability levels, oral health conditions, dental procedures, treatment time, and side effects, of 718 patients with special needs were collected between April 2013 and September 2014. The unfavorable side effects by sedation types were reported. Factors associated with procedure time and the sedation medications were assessed with multiple logistic regression analyses.Of 718 patients, 8 patients experienced unfavorable side effects (vomiting, sleepiness, or emotional disturbance) after the dental procedures; the rate was 0.6% in the 509 patients who received propofol only. In 209 patients who received propofol and midazolam, 2.4% experienced the side effects. Sedation time was associated with body mass index (BMI) < 25 (adjusted odds ratio [aOR] = 1.45, 95% confidence interval [CI]: 1.04-2.04) and the performance of multiple dental procedures (aOR = 1.44, 95% CI: 1.06-1.97) but not associated with the sedation types. A significant odds ratio for the combined use of propofol and midazolam was shown for adolescents (aOR = 2.22, 95% CI: 1.28-3.86), men (aOR = 2.05, 95% CI: 1.41-2.98), patients with cognitive impairment (aOR = 1.99, 95% CI: 1.21-3.29), and patients undergoing scaling procedures (aOR = 1.64, 95% CI: 1.13-2.39).With the acceptable side effects of the use of propofol alone and propofol combined with midazolam, multiple dental procedures increase the sedation time and the factors associated with the combined use of propofol and midazolam are younger age, male sex, recognition problems, and the type dental procedure in the dental treatment of patients with special needs.

In South Korea, as in many other countries, propofol sedation is performed by practitioners across a broad range of specialties in our country. However, this has led to significant variation in propofol sedation practices, as shown in a series of reports by the Korean Society of Anesthesiologists (KSA). This has led the KSA to develop a set of evidence-based practical guidelines for propofol sedation by non-anesthesiologists. Here, we provide a set of recommendations for propofol sedation, with the aim of ensuring patient safety in a variety of clinical settings. The subjects of the guidelines are patients aged ≥ 18 years who were receiving diagnostic or therapeutic procedures under propofol sedation in a variety of hospital classes. The committee developed the guidelines via a de novo method, using key questions created across 10 sub-themes for data collection as well as evidence from the literature. In addition, meta-analyses were performed for three key questions. Recommendations were made based on the available evidence, and graded according to the modified Grading of Recommendations Assessment, Development and Evaluation system. Draft guidelines were scrutinized and discussed by advisory panels, and agreement was achieved via the Delphi consensus process. The guidelines contain 33 recommendations that have been endorsed by the KSA Executive Committee. These guidelines are not a legal standard of care and are not absolute requirements; rather they are recommendations that may be adopted, modified, or rejected according to clinical considerations.

The aim of this study is to investigate the characteristics of propofol abuse based on the results of a survey analysis of abusers among non-healthcare professionals in Korea.

Direct current cardioversion is a low-risk and standard procedure to restore normal sinus rhythm in patients with tachyarrhythmias. It requires sedation to facilitate the procedure, as it is painful and distressful. The preferred anesthetic drug must be short acting, producing conscious sedation, to enable rapid recovery after the procedure. In this sense, this narrative review focuses on the critical analysis of recent randomized studies and presents about the safety and effectiveness of propofol, comparing it with other established sedatives, mainly etomidate and midazolam. The research was performed on MEDLINE database with Propofol and Cardioversion keywords. In most cases, propofol comes to be the best option, with a quick recovery time and low rates of side effects. Different studies have demonstrated no inferiority when comparing to other drugs and, when these adverse events happened, they were easily and quickly handled. Exceptions in this scenario are those patients, particularly the elderly, with baseline important structural heart disease, in which etomidate with fentanyl has been pointed to lead to better hemodynamic stability.

The anesthetic propofol elicits many different spectral properties on the EEG, including alpha oscillations (8-12 Hz), Slow Wave Oscillations (SWO, 0.1-1.5 Hz), and dose-dependent phase-amplitude coupling (PAC) between alpha and SWO. Propofol is known to increase GABAA inhibition and decrease H-current strength, but how it generates these rhythms and their interactions is still unknown. To investigate both generation of the alpha rhythm and its PAC to SWO, we simulate a Hodgkin-Huxley network model of a hyperpolarized thalamus and corticothalamic inputs. We find, for the first time, that the model thalamic network is capable of independently generating the sustained alpha seen in propofol, which may then be relayed to cortex and expressed on the EEG. This dose-dependent sustained alpha critically relies on propofol GABAA potentiation to alter the intrinsic spindling mechanisms of the thalamus. Furthermore, the H-current conductance and background excitation of these thalamic cells must be within specific ranges to exhibit any intrinsic oscillations, including sustained alpha. We also find that, under corticothalamic SWO UP and DOWN states, thalamocortical output can exhibit maximum alpha power at either the peak or trough of this SWO; this implies the thalamus may be the source of propofol-induced PAC. Hyperpolarization level is the main determinant of whether the thalamus exhibits trough-max PAC, which is associated with lower propofol dose, or peak-max PAC, associated with higher dose. These findings suggest: the thalamus generates a novel rhythm under GABAA potentiation such as under propofol, its hyperpolarization may determine whether a patient experiences trough-max or peak-max PAC, and the thalamus is a critical component of propofol-induced cortical spectral phenomena. Changes to the thalamus may be a critical part of how propofol accomplishes its effects, including unconsciousness.

Propofol is a short and rapidly acting intravenous anesthetic extensively used for the induction and maintenance of general anesthesia. It is a lipid emulsion that contains soybean oil, purified egg phosphatide, and egg lecithin. Therefore, the package leaflet indicates that its administration is contraindicated in patients allergic to soy, eggs, or peanuts. Our study aimed to determine whether patients with proven food allergies are allergic to propofol.

The brain is possibly the most complex system known to mankind, and its complexity has been called upon to explain the emergence of consciousness. However, complexity has been defined in many ways by multiple different fields: here, we investigate measures of algorithmic and process complexity in both the temporal and topological domains, testing them on functional MRI BOLD signal data obtained from individuals undergoing various levels of sedation with the anaesthetic agent propofol, replicating our results in two separate datasets. We demonstrate that the various measures are differently able to discriminate between levels of sedation, with temporal measures showing higher sensitivity. Further, we show that all measures are strongly related to a single underlying construct explaining most of the variance, as assessed by Principal Component Analysis, which we interpret as a measure of "overall complexity" of our data. This overall complexity was also able to discriminate between levels of sedation and serum concentrations of propofol, supporting the hypothesis that consciousness is related to complexity - independent of how the latter is measured.

In our study we aimed to investigate whether the use of bispectral index (BIS) monitoring would decrease total propofol consumption during the transvaginal oocyte retrieval procedure. This was a prospective, randomized, controlled, parallel-group clinical trial. The study was conducted in the operating room, and postoperative recovery room. One hundred and thirty, American Society of Anesthesiologists (ASA) I-II patients, over age 18, undergoing transvaginal oocyte retrieval were included in this study. All patients were administered 2 μg/kg fentanyl, and 2 mg/kg propofol for the induction of anesthesia. The patients were divided into two groups. Patients in the group bolus were given 0.5 mg/kg of propofol when necessary, according to the observer's range of motion. Patients in the group BIS were given 10 mg/kg/h propofol infusion adjusted to keep the BIS value between 40 and 60. The primary outcome was the total dose of propofol administered per patient. The secondary outcomes were the time to reach the value of 5 on the Modified Observer's Assessment of Alertness Sedation Scale (MOASs), the time to reach Post Anesthetic Discharge Scoring System (PADSS) ≥ 9 of the patients, satisfaction of the patient, and the gynecologist. The amount of total propofol was higher in the group BIS than in the group bolus administered according to the patient's clinic. There was no difference in the time to reach the value of 5 on the MOASs between the groups. The time to reach PADSS ≥ 9 was longer in the group BIS than in the group bolus. There was no difference between the two groups in terms of the satisfaction of the patient and the gynecologist. Administration of propofol as an infusion with BIS monitoring did not reduce the amount of propofol administered to patients during transvaginal oocyte retrieval.Clinical trial registration number: NCT05631925-30/11/2022.

Propofol infusion syndrome (PRIS) is a potentially lethal consequence of long-term propofol administration. Children are vulnerable and cardiac involvement is often prominent and associated with mortality. We aimed to determine the mechanism of propofol toxicity in newborn mice, hypothesizing that propofol would induce discrete defects within immature cardiac mitochondria.