-
Anaesthesia Jan 2018It is commonly assumed that loss of responsiveness and recovery of responsiveness occur at similar concentrations of propofol. However, the 'conscious' and...
It is commonly assumed that loss of responsiveness and recovery of responsiveness occur at similar concentrations of propofol. However, the 'conscious' and 'anaesthetised' conditions produced by general anaesthetics may behave as two bistable states. We hypothesised that loss of responsiveness and recovery of responsiveness occur at different propofol concentrations. Propofol was administered to 19 healthy volunteers by effect-site target-controlled infusion using increasing and decreasing stable concentration steps of 7 min. Propofol serum concentrations were measured from venous blood samples at the end of each 7-min step. A long step of 14 min was performed at loss of responsiveness. At this step, propofol concentrations were measured at 7 and 14 min. Propofol concentrations measured at loss of responsiveness and recovery of responsiveness were 2.6 (1.2-4.7) μg.ml and 1.6 (0.6-3.3) μg.ml , respectively (p < 0.001). Propofol plasma concentration and the corresponding bispectral index values measured at minute 7 and minute 14 of the long step performed at loss of responsiveness were 2.6 (1.2-4.7) vs. 2.6 (1.3-4.3) at recovery of responsiveness, (p = 0.96) and 61.2 (49.0-77.0) vs. 58.4 (45.0-74.0), (p = 0.058), respectively. Loss of responsiveness and recovery of responsiveness appear to occur at different propofol concentrations. However, it is possible that, if equilibration was not achieved between plasma and effect-sites at the end of each 7-min step, the higher concentrations found at loss of responsiveness compared with those observed during recovery of responsiveness could be explained by a possible bias in estimations of the effect-site concentrations of propofol by the Schnider model, rather than neural inertia.
Topics: Adult; Anesthetics, Intravenous; Consciousness; Dose-Response Relationship, Drug; Electroencephalography; Female; Humans; Male; Propofol; Reference Values
PubMed: 28872658
DOI: 10.1111/anae.14009 -
CNS Neuroscience & Therapeutics 2008Propofol (2,6-diisopropylphenol) is a versatile, short-acting, intravenous (i.v.) sedative-hypnotic agent initially marketed as an anesthetic, and now also widely used... (Review)
Review
Propofol (2,6-diisopropylphenol) is a versatile, short-acting, intravenous (i.v.) sedative-hypnotic agent initially marketed as an anesthetic, and now also widely used for the sedation of patients in the intensive care unit (ICU). At the room temperature propofol is an oil and is insoluble in water. It has a remarkable safety profile. Its most common side effects are dose-dependent hypotension and cardiorespiratory depression. Propofol is a global central nervous system (CNS) depressant. It activates gamma-aminobutyric acid (GABA A) receptors directly, inhibits the N-methyl-d-aspartate (NMDA) receptor and modulates calcium influx through slow calcium-ion channels. Furthermore, at doses that do not produce sedation, propofol has an anxiolytic effect. It has also immunomodulatory activity, and may, therefore, diminish the systemic inflammatory response believed to be responsible for organ dysfunction. Propofol has been reported to have neuroprotective effects. It reduces cerebral blood flow and intracranial pressure (ICP), is a potent antioxidant, and has anti-inflammatory properties. Laboratory investigations revealed that it might also protect brain from ischemic injury. Propofol formulations contain either disodium edetate (EDTA) or sodium metabisulfite, which have antibacterial and antifungal properties. EDTA is also a chelator of divalent ions such as calcium, magnesium, and zinc. Recently, EDTA has been reported to exert a neuroprotective effect itself by chelating surplus intracerebral zinc in an ischemia model. This article reviews the neuroprotective effects of propofol and its mechanism of action.
Topics: Anesthetics, Intravenous; Animals; Humans; Neuroprotective Agents; Propofol
PubMed: 18482023
DOI: 10.1111/j.1527-3458.2008.00043.x -
Anaesthesia Dec 2020Target-controlled infusion systems are increasingly used to administer intravenous anaesthetic drugs to achieve a user-specified plasma or effect-site target... (Comparative Study)
Comparative Study Observational Study
Target-controlled infusion systems are increasingly used to administer intravenous anaesthetic drugs to achieve a user-specified plasma or effect-site target concentration. While several studies have investigated the ability of the underlying pharmacokinetic-dynamic models to predict plasma concentrations, there are no data on their performance in predicting drug concentrations in the human brain. We assessed the predictive performance of the Marsh propofol model and Minto remifentanil model for plasma and brain tissue concentrations. Plasma samples were obtained during neurosurgery from 38 patients, and brain tissue samples from nine patients. Propofol and remifentanil concentrations were measured using gas chromatography mass spectrometry and liquid chromatography tandem mass spectrometry. Data were analysed from the nine patients in whom both plasma and brain samples were simultaneously obtained. For the Minto model (five patients), the median performance error was 72% for plasma and -14% for brain tissue concentration predictions. The model tended to underestimate plasma remifentanil concentrations, and to overestimate brain tissue remifentanil concentrations. For the Marsh model (five patients), the median prediction errors for plasma and brain tissue concentrations were 12% and 81%, respectively. However, when the data from all blood propofol assays (36 patients) were analysed, the median prediction error was 11%, with overprediction in 15 (42%) patients and underprediction in 21 (58%). These findings confirm earlier reports demonstrating inaccuracy for commonly used pharmacokinetic-dynamic models for plasma concentrations and extend these findings to the prediction of effect-site concentrations.
Topics: Adult; Aged; Brain; Drug Delivery Systems; Female; Humans; Infusions, Intravenous; Male; Middle Aged; Models, Biological; Propofol; Prospective Studies; Remifentanil
PubMed: 32506561
DOI: 10.1111/anae.15125 -
International Journal of Clinical... Apr 2023Ciprofol is a novel 2, 6-disubstituted phenolic derivative anesthetic that binds to the gamma-aminobutyric acid-A receptor.
BACKGROUND
Ciprofol is a novel 2, 6-disubstituted phenolic derivative anesthetic that binds to the gamma-aminobutyric acid-A receptor.
AIM
To determine the equally potent dose of ciprofol compared with propofol as an induction agent for general anesthesia in patients undergoing selective surgery, and to assess its safety.
METHOD
A total of 109 patients undergoing selective non-emergency, non-cardiothoracic or non-neurosurgical surgery requiring tracheal intubation for general anesthesia were enrolled. Ten patients per group were assigned to ciprofol-0.3, 0.4 and 0.5 mg/kg, and propofol-2.0 or 2.5 mg/kg groups, respectively to receive an intravenous bolus dose. An additional 20 patients were enrolled in the ciprofol-0.3, 0.5 or propofol-2.0 mg/kg groups. The primary outcome was the success rate of induction defined as a Modified Observer's Assessment of Alertness/Sedation (MOAA/S) ≤ 1 after the initial bolus dose. The secondary outcomes included the time to reach MOAA/S ≤ 1, the time to loss of the eyelash reflex, the incidences and severity of adverse events (AEs).
RESULTS
The success rates were 100% for all 5 groups. The mean time to MOAA/S ≤ 1 and the time to loss of the eyelash reflex were not different among the 5 groups, regardless of whether a top-up dose was needed. There were no significant differences in the incidences and severity of AEs in the dose ranges investigated of ciprofol vs. propofol.
CONCLUSION
The efficacy and safety of a single bolus dose of ciprofol-0.5 mg/kg for the general anesthesia induction in selective surgery patients was comparable to that of propofol-2.0 mg/kg.
TRIAL REGISTRATION
Clinicaltrials.gov, NCT03698617, retrospectively registered.
Topics: Humans; Adult; Propofol; Anesthesia, General
PubMed: 36680620
DOI: 10.1007/s11096-022-01529-x -
Digestion 2010The present article describes the recommendations regarding the use of propofol by non-anesthesiologists from published guidelines. Furthermore, safety and efficacy data... (Review)
Review
The present article describes the recommendations regarding the use of propofol by non-anesthesiologists from published guidelines. Furthermore, safety and efficacy data regarding the use of propofol in the hands of gastroenterologists are also reviewed. Although there are no studies comparing the safety and efficacy of propofol administration by anesthesiologists versus non-anesthesiologists for sedation during endoscopy, there is strong evidence that propofol administration by non-anesthesiologists is safe and efficacious for the majority of patients undergoing routine endoscopic procedures.
Topics: Endoscopy, Gastrointestinal; Gastroenterology; Health Personnel; Humans; Hypnotics and Sedatives; Nurses; Practice Guidelines as Topic; Propofol
PubMed: 20407257
DOI: 10.1159/000285554 -
Journal of Clinical Pharmacy and... Apr 2021Propofol is the most commonly used intravenous anaesthetic worldwide and is considered to be safe for all ages. However, there have been some reports that propofol...
WHAT IS KNOWN AND OBJECTIVE
Propofol is the most commonly used intravenous anaesthetic worldwide and is considered to be safe for all ages. However, there have been some reports that propofol induces severe atrioventricular (AV) blocks in humans and some studies demonstrated that propofol suppressed the cardiac conduction system in animals. A precise mechanism by which the block is induced has not been elucidated yet in humans. The objective of this study was to investigate the effects of propofol on the cardiac conduction system and the cardiac autonomic nervous balance in children.
METHODS
We enrolled 23 paediatric patients (age: 6-15 years; males: 16, females: 7) who were scheduled to undergo radiofrequency catheter ablation (RFCA) under general anaesthesia. Anaesthesia was induced with 2 mg/kg propofol and 0.5 µg/kg/min remifentanil, and tracheal intubation was performed with the aid of 1 mg/kg rocuronium. Anaesthesia was maintained with 5-7 mg/kg/h propofol and 0.2 µg/kg/min remifentanil during the RFCA. After the completion of the RFCA, anaesthesia was further maintained with 5 mg/kg/h propofol and 0.2 µg/kg/min remifentanil for at least 10 min (LC: low propofol concentration state), followed by the injection of 2 mg/kg propofol and the infusion of 10 mg/kg/h propofol for 10 min (HC: high propofol concentration state). The sinus node recovery time (SNRT), sinoatrial conduction time (SACT), atrial-His (AH) interval and the His-ventricular (HV) interval were measured at the end of both the LC and HC. Cardiac autonomic regulation was simultaneously assessed based on heart rate variability.
RESULTS AND DISCUSSION
Propofol significantly suppressed intrinsic cardiac HV conduction, but did not affect the SNRT, SACT or the AH interval. As HV blocks, which occur below the His bundle, are often life-threatening, the HV conduction delay may be a cause of severe AV blocks induced by propofol. Propofol directly suppressed parasympathetic nerve activity, and sympathetic nerve activity was also suppressed.
WHAT IS NEW AND CONCLUSION
These results indicate that propofol suppresses the HV conduction and might help to elucidate the mechanism by which propofol causes lethal AV blocks.
Topics: Adolescent; Anesthetics, Intravenous; Catheter Ablation; Child; Female; Heart Conduction System; Heart Rate; Humans; Male; Propofol; Remifentanil
PubMed: 33098128
DOI: 10.1111/jcpt.13302 -
PloS One 2023General anesthesia can disturb the hormone levels in surgical patients. Hormone deficiency is one of the major symptoms of craniopharyngioma (CP) in pediatric patients.... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
General anesthesia can disturb the hormone levels in surgical patients. Hormone deficiency is one of the major symptoms of craniopharyngioma (CP) in pediatric patients. The aim of this prospective randomized controlled clinical study is to evaluate whether propofol and sevoflurane influence the perioperative hormone levels in these patients and to determine which anesthesia technique causes less impact on hormone levels.
MATERIALS
Sixty-four ASA I and II pediatric patients with CP undergoing elective neurosurgery were randomly divided into the sevoflurane group (S group, n = 32) and the propofol group (P group, n = 32). Anesthesia was maintained with sevoflurane and propofol until the end of the operation. Demographic information, operation information and hemodynamic variables were recorded. The levels of hormones were evaluated preoperatively as the baseline (T0), 1h after the beginning of the operation (T1), immediately at the end of the operation (T2) and 72 h postoperatively (T3).
RESULTS
There were no significant differences in the two groups in terms of patients' demographics and intraoperative information, such as operation duration, blood loss and transfusion volumes, and fluid infusion volume (P>0.05). In both groups, compared to those at T0, the levels of TSH, FT3, TT3 and ACTH at T1, T2 and T3 were significantly lower. The levels of FSH, PRL and GH at T3 were also significantly lower (P<0.05). The FT3 and TT3 levels of both groups at T2 and T3 were significantly lower than those at T1, but the ACTH level was significantly increased (P<0.05). Compared to the levels at T2, the TSH, FT3, FT4 and ACTH levels of the two groups at T3 were significantly reduced (P<0.05). The baseline hormone levels of both groups were similar (P>0.05). At T1, the FT3, TT3, FT4, TT4 and ACTH levels in the P group were significantly lower than those in the S group (P<0.05). At T2, the TT3 and ACTH levels of the P group were significantly lower than those of the S group (P<0.05) At T3, the TT4 level in the P group was significantly lower than that of the S group (P<0.05).
CONCLUSION
Propofol and sevoflurane could reduce the levels of hormones intraoperatively and postoperatively in pediatric patients with craniopharyngioma. However, propofol reduced hormone levels more intensively, mainly intraoperatively. Postoperatively, propofol and sevoflurane had similar inhibition effects on the shift in hormone levels. Therefore, in pediatric patients with craniopharyngioma undergoing neurosurgery, sevoflurane might be the preferred anesthetic because it causes less interruption of hormone levels. However, because of their similar postoperative effects, which long-term effects of sevoflurane or propofol could produce optimal clinical situations? Thus more extensive clinical studies are needed.
TRIAL REGISTRATION
Clinical trial registration. This trail was registered at Chinese Clinical Trial Registry (http://www.chictr.org.cn, Jun Xiong) on 28/12/2021, registration number was ChiCTR2100054885.
Topics: Humans; Child; Propofol; Sevoflurane; Craniopharyngioma; Anesthesia, General; Pituitary Neoplasms; Adrenocorticotropic Hormone; Thyrotropin; Methyl Ethers; Anesthetics, Inhalation
PubMed: 37506116
DOI: 10.1371/journal.pone.0288863 -
Pain Physician Nov 2023Remimazolam is a novel ultrashort-effect benzodiazepine. In 2020, the US Food and Drug Administration approved it for procedural sedation. Remimazolam is beneficial for... (Meta-Analysis)
Meta-Analysis
Hemodynamic Influences of Remimazolam Versus Propofol During the Induction Period of General Anesthesia: A Systematic Review and Meta-analysis of Randomized Controlled Trials.
BACKGROUND
Remimazolam is a novel ultrashort-effect benzodiazepine. In 2020, the US Food and Drug Administration approved it for procedural sedation. Remimazolam is beneficial for consistent sedation and quick recovery in painless gastrointestinal endoscopy. Propofol is one of the most commonly used intravenous anesthetics in clinical practice. Recently, only a few studies have compared propofol with remimazolam for general anesthesia induction.
OBJECTIVES
The purpose of our systematic review and meta-analysis was to compare the hemodynamic effects of remimazolam and propofol during the induction of general anesthesia.
STUDY DESIGN
Systematic review and meta-analysis of randomized, controlled trials.
METHODS
The authors retrieved the PubMed, Embase, Cochrane Library, and Web of Science databases for studies published through September 30, 2022, which reported relevant prospective randomized controlled trials (RCTs) comparing remimazolam with propofol for general anesthesia. The primary outcome was hemodynamic changes, including the absolute value of fluctuation of mean arterial pressure (delta MAP) and heart rate delta HR). The secondary outcomes were the following 2 indicators: the occurrence of total adverse events and the quality of recovery from general anesthesia at 24 hours postsurgery. RevMan 5.4.1 (The Nordic Cochrane Centre for The Cochrane Collaboration) and trial sequential analysis were used to execute the statistical analyses. The different domains of bias were judged by the Cochrane risk of the bias assessment tool.
RESULTS
The authors identified 189 papers in PubMed, Embase, Cochrane Library, and Web of Science. Eight articles with 964 patients were selected. The included studies had moderate quality. For primary outcomes, the lower delta HR (mean difference [MD] = -4.99; 95% CI, -7.97 to -2.00; I² = 41.6%; P = 0.001] and delta MAP (MD = -5.91; 95% CI. -8.57 to -3.24; I² = 0%; P < 0.0001) represent more stable hemodynamic characteristics in the remimazolam group. Regarding secondary outcomes, a considerably lower incidence of total adverse events was noted in the remimazolam group than that for the propofol group (odds ratio [OR] = 0.40; 95% CI, 0.28 to 0.58; I² = 63%; P < 0.00001). In comparison to the propofol group, remimazolam achieved an advantage score of quality of recovery -15 in 24 hours postsurgery (MD = 5.31, 95% CI, 1.51 to 9.12; I² = 87%; P = 0.006).
LIMITATION
Firstly, there are only a handful of published RCTs on the administration of remimazolam in general anesthesia. In addition, due to patient privacy, we could not extract individual patient data, therefore we could not combine and assess any variations in patient characteristics.
CONCLUSION
Evidence suggests that remimazolam has a lower hemodynamic effect during general anesthesia and fewer perioperative adverse effects after general anesthesia than propofol; however, which agent is superior regarding quality benefit in postoperative recovery based on the studies included here remains inconclusive. Additional RCTs with updated meta-analyses to enlarge the sample size and properly analyze the benefit-to-risk ratio to patients are needed to determine the evidence for such a relatively new medicine.
Topics: Humans; Propofol; Randomized Controlled Trials as Topic; Anesthesia, General; Benzodiazepines; Hemodynamics
PubMed: 37976477
DOI: No ID Found -
International Journal of Surgery... Dec 2023
Meta-Analysis
Topics: Humans; Propofol; Anesthesia, Intravenous; Benzodiazepines
PubMed: 37816162
DOI: 10.1097/JS9.0000000000000710 -
The International Journal of... Dec 2018We hypothesized that propofol, a unique general anesthetic that engages N-methyl-D-aspartate and gamma-aminobutyric acid receptors, has antidepressant properties. This... (Clinical Trial)
Clinical Trial
BACKGROUND
We hypothesized that propofol, a unique general anesthetic that engages N-methyl-D-aspartate and gamma-aminobutyric acid receptors, has antidepressant properties. This open-label trial was designed to collect preliminary data regarding the feasibility, tolerability, and efficacy of deep propofol anesthesia for treatment-resistant depression.
METHODS
Ten participants with moderate-to-severe medication-resistant depression (age 18-45 years and otherwise healthy) each received a series of 10 propofol infusions. Propofol was dosed to strongly suppress electroencephalographic activity for 15 minutes. The primary depression outcome was the 24-item Hamilton Depression Rating Scale. Self-rated depression scores were compared with a group of 20 patients who received electroconvulsive therapy.
RESULTS
Propofol treatments were well tolerated by all subjects. No serious adverse events occurred. Montreal Cognitive Assessment scores remained stable. Hamilton scores decreased by a mean of 20 points (range 0-45 points), corresponding to a mean 58% improvement from baseline (range 0-100%). Six of the 10 subjects met the criteria for response (>50% improvement). Self-rated depression improved similarly in the propofol group and electroconvulsive therapy group. Five of the 6 propofol responders remained well for at least 3 months. In posthoc analyses, electroencephalographic measures predicted clinical response to propofol.
CONCLUSIONS
These findings demonstrate that high-dose propofol treatment is feasible and well tolerated by individuals with treatment-resistant depression who are otherwise healthy. Propofol may trigger rapid, durable antidepressant effects similar to electroconvulsive therapy but with fewer side effects. Controlled studies are warranted to further evaluate propofol's antidepressant efficacy and mechanisms of action. ClinicalTrials.gov: NCT02935647.
Topics: Adolescent; Adult; Anesthetics, Intravenous; Depressive Disorder, Treatment-Resistant; Electroencephalography; Feasibility Studies; Female; Humans; Male; Middle Aged; Outcome Assessment, Health Care; Pilot Projects; Propofol; Young Adult
PubMed: 30260415
DOI: 10.1093/ijnp/pyy085