Effects of Esketamine Combined with Propofol for Hysteroscopy Anesthesia on Patient Hemodynamics and Adverse Reactions.

Objective: To investigate the effect of esketamine combined with propofol on patient hemodynamics and its safety in hysteroscopy anesthesia. Methods: A total of 186 hysteroscopic patients admitted to our hospital from January 2021 to January 2022 were selected, and the patients were divided into group K and Group P according to a completely random number table, with 93 cases each. In short, all patients are uniformly numbered and adequately intermixed, according to the prescribed sampling starting point and order, the sample unit numbers were successively drawn from the random number table, until the extraction to the required sample size. Group K was given esketamine combined with propofol intravenously, and group P was given sufentanil combined with propofol intravenously. The changes in respiratory circulation [heart rate (HR), mean arterial pressure (MAP) and oxygen saturation (SpO2)] at the time of entering the operating room (T0), at the beginning of surgery (T1), 10 minutes after surgery(T2), and 10 minutes after the end of surgery (T3) were compared between the two groups, as well as the total time of surgery, the time to wake up after surgery, the amount of propofol used intraoperatively and the proportion of additional propofol were compared. The numerical rating scale (NRS) was used to assess the pain level of patients in both groups at different times after awakening and the occurrence of intraoperative and postoperative adverse reactions such as body movement, respiratory depression, bradycardia, injection site pain, nausea and vomiting, and dizziness were counted in both groups. Results: There were no significant changes in MAP, HR, and SpO2 in Group K at all moments compared with T0 (P > .05), MAP, HR and SpO2 in Group P at T1 and T2 were lower than those at T0 (P < .05). MAP, HR, and SpO2 were significantly lower in Group P at T1 and T2 moments compared with Group K, suggesting that circulatory depression was more pronounced in Group P at T1 and T2 moments (P < .05) and was not conducive to postoperative recovery. Compared with group P, the postoperative recovery time of group K was significantly shorter, and the dosage of propofol and the proportion of additional propofol were significantly lower (P < .05) which was beneficial to the health of patients. The pain level was significantly lower in Group K at 5, 15, and 30 minutes after awakening than in Group P (P < .05). The incidence of adverse reactions such as intraoperative motion, respiratory depression, bradycardia, injection site pain, and dizziness was significantly lower in group K than in group P (P < .05), and there was no significant difference in the incidence of nausea and vomiting between the two groups (P > .05), and prove that esketamine combined with propofol used for anesthesia which have high safety as well as more effective. Conclusion: The use of esketamine compounded with propofol in hysteroscopy anesthesia has less effect on the patient's circulatory and respiratory systems. This protocol can improve the postoperative analgesic effect of anesthesia in patients, reduce the amount of propofol during surgery, have fewer adverse effects and mild symptoms, is safe and effective, and can be used in clinical practice.

Effects of intravenous administration of magnesium sulfate in propofol-based sedation for ERCP in elderly patients: a randomized, double-blind, placebo-controlled study.

BACKGROUND: Propofol-based sedations are widely used in elderly patients for endoscopic retrograde cholangiopancreatography (ERCP) procedure, but respiratory depression and cardiovascular adverse events commonly occur. Magnesium administered intravenously can alleviate pain and decrease propofol requirements during surgery. We hypothesized that intravenous magnesium was used as adjuvant to propofol might be beneficial in elderly patients undergoing ERCP procedures. METHODS: Eighty patients aged from 65 to 79 years who were scheduled for ERCP were enrolled. All patients were intravenously administered 0.1 µg/kg sufentanil as premedication. The patients were randomized to receive either intravenous magnesium sulfate 40 mg/kg (group M, n = 40) or the same volume of normal saline (group N, n = 40) over 15 min before the start of sedation. Intraoperative sedation was provided by propofol. Total propofol requirement during ERCP was the primary outcome. RESULTS: The total propofol consumption were reduced by 21.4% in the group M compared with the group N (151.2 ± 53.3 mg vs. 192.3 ± 72.1 mg, P = 0.001). The incidences of respiratory depression episodes and involuntary movement were less in the group M than those in the group N (0/40 vs. 6/40, P = 0.011; 4/40 vs. 11/40, P = 0.045; respectively). In the group M, the patients experienced less pain than those in the group N at 30 min after the procedure (1 [0-1] vs. 2 [1-2], P < 0.001). Correspondingly, the patients' satisfaction was clearly higher in the group M (P = 0.005). There was a tendency towards lower intraoperative heart rate and mean arterial pressure in group M. CONCLUSIONS: A single bolus of 40 mg/kg of intravenous magnesium can significantly reduce propofol consumption during ERCP, with higher sedation success and lower adverse events. TRIAL REGISTRATION: ID UMIN000044737. Registered 02/07/2021.

Rapid thalamocortical network switching mediated by cortical synchronization underlies propofol-induced EEG signatures: a biophysical model.

Propofol-mediated unconsciousness elicits strong alpha/low-beta and slow oscillations in the electroencephalogram (EEG) of patients. As anesthetic dose increases, the EEG signal changes in ways that give clues to the level of unconsciousness; the network mechanisms of these changes are only partially understood. Here, we construct a biophysical thalamocortical network involving brain stem influences that reproduces transitions in dynamics seen in the EEG involving the evolution of the power and frequency of alpha/low-beta and slow rhythm, as well as their interactions. Our model suggests that propofol engages thalamic spindle and cortical sleep mechanisms to elicit persistent alpha/low-beta and slow rhythms, respectively. The thalamocortical network fluctuates between two mutually exclusive states on the timescale of seconds. One state is characterized by continuous alpha/low-beta-frequency spiking in thalamus (C-state), whereas in the other, thalamic alpha spiking is interrupted by periods of co-occurring thalamic and cortical silence (I-state). In the I-state, alpha colocalizes to the peak of the slow oscillation; in the C-state, there is a variable relationship between an alpha/beta rhythm and the slow oscillation. The C-state predominates near loss of consciousness; with increasing dose, the proportion of time spent in the I-state increases, recapitulating EEG phenomenology. Cortical synchrony drives the switch to the I-state by changing the nature of the thalamocortical feedback. Brain stem influence on the strength of thalamocortical feedback mediates the amount of cortical synchrony. Our model implicates loss of low-beta, cortical synchrony, and coordinated thalamocortical silent periods as contributing to the unconscious state.NEW & NOTEWORTHY GABAergic anesthetics induce alpha/low-beta and slow oscillations in the EEG, which interact in dose-dependent ways. We constructed a thalamocortical model to investigate how these interdependent oscillations change with propofol dose. We find two dynamic states of thalamocortical coordination, which change on the timescale of seconds and dose-dependently mirror known changes in EEG. Thalamocortical feedback determines the oscillatory coupling and power seen in each state, and this is primarily driven by cortical synchrony and brain stem neuromodulation.

Prevention of pain on injection of propofol using ice gel pack versus pre-treatment with lignocaine: a randomized controlled trial.

PURPOSE: Regardless of the positive attributes of propofol, it is frequently associated with pain on injection. We compared the efficacy of topical cold thermotherapy using an ice gel pack with intravenous lignocaine pre-treatment for reducing pain on propofol injection. METHODS: This single-blinded randomized controlled trial was conducted in 200 American Society of Anesthesiologists physical status I, II, and III patients scheduled for elective/emergency surgery under general anesthesia. The patients were randomized into two groups: the Thermotherapy group- receiving an ice gel pack proximal to the intravenous cannula for 1 min, or the Lignocaine group-receiving 0.5 mg/kg of lignocaine administered intravenously, with occlusion proximal to the site of the intravenous cannula for 30 s. The primary objective was to compare the overall incidence of pain after propofol injection. The secondary objectives included the incidence of discomfort on the application of an ice gel pack, comparison of dose of propofol needed for induction, and hemodynamic changes at induction, between the two groups. RESULTS: Fourteen patients in the lignocaine group and 15 patients in the thermotherapy group reported pain. The incidence of pain and the distribution of pain scores were comparable among groups (p = 1.00). Patients of the lignocaine group required significantly less amount of propofol for induction as compared to the thermotherapy group (p = 0.001). CONCLUSION: Topical thermotherapy using an ice gel pack was not found superior to lignocaine pre-treatment in alleviating pain on injection of propofol injection. However, topical cold therapy using an ice pack remains a non-pharmacological technique that is easily available, reproducible, and cost-effective. Further studies are required to prove its equivalence to lignocaine pre-treatment. TRIAL REGISTRATION: CTRI (CTRI/2021/04/032950).

Use of Remimazolam Combined With Alfentanil for Plastic Surgery Anesthesia Cases: A Clinical Trial.

OBJECTIVE: This study aims to observe the safety and effectiveness of remimazolam benzenesulfonate combined with alfentanil for painless and comfort anesthesia in plastic surgery. METHODS: Two hundred patients with American Society of Anesthesiologists (ASA) I-II for elective facial autologous lipofilling + autologous liposuction (thigh or abdomen) plastic surgery in our hospital were selected. One hundred patients received comfort anesthesia (observation group) on odd-numbered day of surgery, and other 100 patients received painless anesthesia (control group) on even-numbered day. Patients in both groups were given slow injection of remimazolam benzenesulfonate 0.1 mg/kg and alfentanil 5 µg/kg to induce sleep before local anesthesia. Depending on body action reaction to surgical stimulation, patients in the observation group were received with remimazolam 0.05 mg/kg and alfentanil 2.5 µg/kg for maintenance until the end of surgery after local anesthesia, and patients in the control group received with remimazolam 0.25 to 0.5 mg/kg/h and alfentanil 25 to 50 µg/kg/h in continuous pumps. Time to fall asleep, sedation score, time to end of medication, time to open eyes, recovery score, and the presence of body movement, glossoptosis, arousal or jaw support during hypoxia, hypotension, bradycardia, operation time, total amount of remimazolam and alfentanil used, and the presence of postoperative complications such as pruritus, dizziness, nausea, and vomiting were recorded in both 2 groups. RESULTS: There were no significant differences in the preoperative vital sign parameters as mean arterial pressure, heart rate, and oxygen saturation between 2 groups ( P > 0.05). Intraoperative mean arterial pressure and heart rate were significantly lower in both groups compared with preoperative ( P < 0.05), but there was no statistically significant between the 2 groups ( P > 0.05). There was no significant decrease in oxygen saturation in both groups under the condition of intraoperative oxygen inhalation ( P > 0.05). There was no significant difference between the 2 groups in the incidence of adverse reactions, such as intraoperative body movement induced by skin cutting, glossoptosis requiring jaw thrust, postoperative pruritus, dizziness, nausea, and vomiting ( P > 0.05). There was no statistically significant difference in time to fall asleep, sedation score during local anesthesia, time to open eyes after stopping anesthetics, and recovery score between the 2 groups ( P > 0.05). Meanwhile, the total amount of remimazolam and alfentanil use was significantly reduced in patients in the observation group compared with the control group ( P < 0.05). CONCLUSIONS: Remimazolam benzenesulfonate combined with alfentanil can be used as a comfort anesthesia and painless anesthesia protocol in plastic surgery, which has the advantages of rapid onset of action, safety and comfort for patients, rapid recovery, and good cooperation. Furthermore, the protocol of remimazolam benzenesulfonate combined with alfentanil used in the observation group can significantly reduce the total amount of remimazolam and alfentanil used.

Paraventricular thalamus controls consciousness transitions during propofol anaesthesia in mice.

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

Clinical Study on Anesthesia with Remifentanil and Propofol in Patients with High Hemodynamics.

Objective: To study the effect of remifentanil and propofol as an anesthesia regimen in patients with high hemodynamics. Methods: From January 2019 to October 2020, 200 patients with high hemodynamics undergoing surgery at the First Affiliated Hospital of Nanchang University in China were selected as study participants, including 100 patients anesthetized with remifentanil and propofol (research group), and 100 patients anesthetized with fentanyl and propofol (control group). Vital signs, hemodynamic changes and recovery time after anesthesia were compared in the 2 groups and any adverse events while under anesthesia were recorded. Results: Both groups had significant fluctuations in vital signs and hemodynamics during anesthesia (P > .05), but the research group showed smaller changes with more stable vital signs and hemodynamics (P < .05). In addition, postoperative recovery time from anesthesia was shorter and the incidence of adverse events was lower in the research group than in the control group (P < .05). Conclusion: Remifentanil-propofol anesthesia is simple, convenient, safe and reliable in patients with high hemodynamics, and can integrate narcotic drugs with blood pressure control.

Does propofol ameliorate occurrence of postoperative cognitive dysfunction after general anaesthesia? A protocol of systematic review.

BACKGROUND: Postoperative cognitive dysfunction (POCD) is a common condition after general anesthesia (GA). Previous studies have reported that propofol can ameliorate the occurrence of such disorder. However, its results are still inconsistent. Therefore, this systematic review will assess the efficacy and safety of propofol on POCD after GA. METHODS: Literature sources will be sought from inception to the present in Cochrane Library, MEDLINE, EMBASE, PsycINFO, Web of Science, Scopus, Allied and Complementary Medicine Database, Chinese Biomedical Literature Database, and China National Knowledge Infrastructure for randomized controlled trials (RCTs) assessing the administration of propofol on POCD after GA. All searches will be carried out without limitations to language and publication status. Outcomes comprise of cognitive impairments changes, impairments in short-term memory, concentration, language comprehension, social integration, quality of life, and adverse events. Cochrane risk of bias tool will be utilized to assess study quality. We will evaluate the quality of evidence for each outcome using Grading of Recommendations Assessment, Development and Evaluation approach. A narrative synthesis or a meta-analysis will be undertaken as appropriate. DISCUSSION: This study will systematically and comprehensively search literature and integrate evidence on the efficacy and safety of propofol on POCD after GA. Our findings will be of interest to clinicians and health-related policy makers. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020164096.

Anesthetic efficacy of propofol combined butorphanol in laparoscopic surgery for ectopic pregnancy: A protocol of systematic review and meta-analysis.

BACKGROUND: Recent studies have suggested that propofol combined butorphanol (PB) has anesthetic effect in laparoscopic surgery (LS) for ectopic pregnancy (EP). But investigations of its potential effects are inconsistent. We will explore the current literature examining PB in LS for EP. METHODS: We will perform a comprehensive search from MEDLINE, Embase, Cochrane Library, PsycINFO, Global Health, Web of Science, Allied and Complementary Medicine Database, and China National Knowledge Infrastructure from inception to the present. Other literatures, such as conference abstracts, references to the relevant reviews will also be checked. Two authors will check the titles, abstracts, and full texts independently. They will also independently carry out data collection and study quality assessment. We will conduct statistical analysis using RevMan 5.3 software. RESULTS: This study will provide accurate results on the anesthetic effect and safety of PB in LS for EP. CONCLUSION: This study will establish high-quality evidence of the anesthetic effect and safety of PB in LS for EP to facilitate the clinical practice and guideline development. STUDY REGISTRATION NUMBER: INPLASY202040044.

Propofol use in children with allergies to egg, peanut, soybean or other legumes.

Propofol is the most commonly administered intravenous agent for anaesthesia in children. However, there are concerns that the emulsified preparation may not be safe in children with an allergy to egg, peanut, soybean or other legumes. We conducted a retrospective study of children with immunologically confirmed egg, peanut, soybean or legume allergy and who underwent general anaesthesia at Princess Margaret Hospital for Children between 2005 and 2015. We extracted details regarding allergy diagnosis, each anaesthetic administered and any adverse events or signs of an allergic reaction in the peri-operative period. A convenience sample of patients without any known food allergies was identified from our prospective anaesthesia research database and acted as a control group. We identified 304 food-allergic children and 649 procedures where propofol was administered. Of these, 201 (66%) had an egg allergy, 226 (74%) had a peanut allergy, 28 (9%) had a soybean allergy and 12 (4%) had a legume allergy. These were compared with 892 allergy-free patients who were exposed to propofol. In 10 (3%) allergy patients and 124 (14%) allergy-free patients, criteria for a possible allergic reaction were met. In nine of the food-allergic children and in all the controls valid non-allergic explanations for the clinical symptoms were found. One likely mild allergic reaction was experienced by a child with a previous history of intralipid allergy. We conclude that genuine serious allergic reaction to propofol is rare and is not reliably predicted by a history of food allergy.

Drug-Induced Loss of Preexcitation in Pediatric Patients with WPW Pattern During Electrophysiologic Study.

Ablation of accessory pathways (AP) is one of the most often performed procedures in pediatric electrophysiology. In pediatric patients these procedures are mostly performed in anaesthesia or sedation. In some of these patients who are referred for electrophysiologic (EP) study, we could observe disappearance of the preexcitation, i.e. antegrade conduction of an AP during introduction of sedation. As a suppression of AP conduction capacities has been reported as negative side effect of propofol and other anaesthetics, the aim of this study was to evaluate risk factors for drug-induced suppression of AP conduction properties. Consecutive, pediatric patients with Wolff-Parkinson-White (WPW) pattern referred for EP study in the period of 2016-2017 were reviewed in retrospect. Patients with complex congenital heart disease were excluded. An entire chart review including ECG, bicycle stress testing, and periprocedural data was performed. In 4 of 37 patients included into the study, loss of preexcitation could be observed during sedation. Data analysis showed weaker conduction capacities of the AP as a risk factor (p = 0.009). Interestingly, absolute (p = 0.11) or adjusted to body weight (p = 0.92) drug doses were not a relevant risk factor. Patients with WPW and weaker conduction capacities of the AP, as implied by an early disappearance of preexcitation during exercise stress testing, seem to be more prone to drug-induced suppression of an AP.

Propofol-induced unresponsiveness is associated with impaired feedforward connectivity in cortical hierarchy.

BACKGROUND: Impaired consciousness has been associated with impaired cortical signal propagation after transcranial magnetic stimulation (TMS). We hypothesised that the reduced current propagation under propofol-induced unresponsiveness is associated with changes in both feedforward and feedback connectivity across the cortical hierarchy. METHODS: Eight subjects underwent left occipital TMS coupled with high-density EEG recordings during wakefulness and propofol-induced unconsciousness. Spectral analysis was applied to responses recorded from sensors overlying six hierarchical cortical sources involved in visual processing. Dynamic causal modelling (DCM) of induced time-frequency responses and evoked response potentials were used to investigate propofol's effects on connectivity between regions. RESULTS: Sensor space analysis demonstrated that propofol reduced both induced and evoked power after TMS in occipital, parietal, and frontal electrodes. Bayesian model selection supported a DCM with hierarchical feedforward and feedback connections. DCM of induced EEG responses revealed that the primary effect of propofol was impaired feedforward responses in cross-frequency theta/alpha-gamma coupling and within frequency theta coupling (F contrast, family-wise error corrected P<0.05). An exploratory analysis (thresholded at uncorrected P<0.001) also suggested that propofol impaired feedforward and feedback beta band coupling. Post hoc analyses showed impairments in all feedforward connections and one feedback connection from parietal to occipital cortex. DCM of the evoked response potential showed impaired feedforward connectivity between left-sided occipital and parietal cortex (T contrast P=0.004, Bonferroni corrected). CONCLUSIONS: Propofol-induced loss of consciousness is associated with impaired hierarchical feedforward connectivity assessed by EEG after occipital TMS.

Postoperative nausea and vomiting (PONV) in outpatient repair of inguinal hernia.

PURPOSE: Nausea and vomiting are among the most frequent complications following anesthesia and surgery. Due to anesthesia seems to be primarily responsible for post operative nausea and vomiting (PONV) in Day Surgery facilities, the aim of the study is to evaluate how different methods of anesthesia could modify the onset of postoperative nausea and vomiting in a population of patients undergoing inguinal hernia repair. METHODS: Ninehundredten patients, aged between 18 and 87 years, underwent open inguinal hernia repair. The PONV risk has been assessed according to Apfel Score. Local anesthetic infiltration, performed by the surgeon in any cases, has been supported by and analgo-sedation with Remifentanil in 740 patients; Fentanyl was used in 96 cases and the last 74 underwent deep sedation with Propofol . RESULTS: Among the 910 patients who underwent inguinal hernia repair, PONV occurred in 68 patients (7.5%). Among patients presenting PONV, 29 received Remifentanil, whereas 39 received Fentanyl. In the group of patients receiving Propofol, no one presented PONV. This difference is statistically significant (p < .01). Moreover, only 50 patients of the total sample received antiemetic prophylaxis, and amongst these, PONV occurred in 3 subjects. CONCLUSIONS: Compared to Remifentanil, Fentanyl has a major influence in causing PONV. Nonetheless, an appropriate antiemetic prophylaxis can significantly reduce this undesirable complication. Key words: Day Surgery, Fentanyl, Inguinal, Hernia repair, Nausea, Vomiting.

Judicial Precedent-Based Clinical Practice Guidelines of Propofol in Sedative Esthetic Surgery.

BACKGROUND: Propofol is has been widely used for sedation in the field of esthetic surgery because of its favorable pharmacokinetic profile. Propofol sedation-induced side effects are rare. However, when present, they can be serious. The number of malpractice claims associated with propofol sedation has increased in recent years. This study aims to show which procedures lead to the most claims in the field of esthetic surgery through a review of Korean precedents. METHODS: Thirteen precedent cases of propofol sedation in the field of esthetic surgery were collected between 2000 and 2016. We analyzed the type of procedure, administration route, anesthesia provider, complications, timing of damaging events, average indemnification, plaintiff's (patients) winning rate, ratio and the reason of limitation of liability and the key factors affecting the judgement in these cases. RESULTS: Most plaintiffs were women, and in most cases (11/13, 73.3%), the times of the damaging events were in maintenance and the anesthesia provider was the surgeon. The most common complication related to propofol sedation was hypoxic brain damage. Among the 13 cases, 12 were won by the plaintiff. The mean claim settlement was 339,455,814 KRW (USD 301,792.15). The key factors affecting the judgement were administration method and staff, monitoring method, preparation of emergency kit, response to emergencies, transfer to a higher-level hospital, detailed medical recording about event and informed consent. CONCLUSION: The number of claims owing to propofol sedation after esthetic surgery is increasing. Close monitoring during the operation, immediate reaction to an event and thorough medical records were main key factors that influenced the judgement. Preoperative explanation about the possibility of complications was important. The findings will help surgeons achieve high patient satisfaction and reduce liability concerns. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Propofol exposure during early gestation impairs learning and memory in rat offspring by inhibiting the acetylation of histone.

Propofol is widely used in clinical practice, including non-obstetric surgery in pregnant women. Previously, we found that propofol anaesthesia in maternal rats during the third trimester (E18) caused learning and memory impairment to the offspring rats, but how about the exposure during early pregnancy and the underlying mechanisms? Histone acetylation plays an important role in synaptic plasticity. In this study, propofol was administered to the pregnant rats in the early pregnancy (E7). The learning and memory function of the offspring were tested by Morris water maze (MWM) test on post-natal day 30. Two hours before each MWM trial, histone deacetylase 2 (HDAC2) inhibitor, suberoylanilide hydroxamic acid (SAHA), Senegenin (SEN, traditional Chinese medicine), hippyragranin (HGN) antisense oligonucleotide (HGNA) or vehicle were given to the offspring. The protein levels of HDAC2, acetylated histone 3 (H3) and 4 (H4), cyclic adenosine monophosphate (cAMP) response element-binding protein (CREB), N-methyl-D-aspartate receptor (NMDAR) 2 subunit B (NR2B), HGN and synaptophysin in offspring's hippocampus were determined by Western blot or immunofluorescence test. It was discovered that infusion with propofol in maternal rats on E7 leads to impairment of learning and memory in offspring, increased the protein levels of HDAC2 and HGN, decreased the levels of acetylated H3 and H4 and phosphorylated CREB, NR2B and synaptophysin. HDAC2 inhibitor SAHA, Senegenin or HGN antisense oligonucleotide reversed all the changes. Thus, present results indicate exposure to propofol during the early gestation impairs offspring's learning and memory via inhibiting histone acetylation. SAHA, Senegenin and HGN antisense oligonucleotide might have therapeutic value for the adverse effect of propofol.

Angiotensin converting enzyme inhibitors enhance the hypotensive effects of propofol by increasing nitric oxide production.

Propofol anesthesia is usually accompanied by hypotension. Studies have shown that the hypotensive effects of propofol increase in patients treated with angiotensin-converting enzyme inhibitors (ACEi). Given that both propofol and ACEi affect nitric oxide (NO) signaling, the present study tested the hypothesis that ACEi treatment induces pronounced hypotensive responses to propofol by increasing NO bioavailability. In this study we evaluated 65 patients, divided into three groups: hypertensive patients chronically treated with ACEi (HT-ACEi; n = 21), hypertensive patients treated with other antihypertensive drugs instead of ACEi, such as angiotensin II receptor blockers, ß-blockers or diuretics (HT; n = 21) and healthy normotensive subjects (NT; n = 23). Venous blood samples were collected at baseline and after 10min of anesthesia with propofol 2mg/kg administrated intravenously by bolus injection. Hemodynamic parameters were recorded at each blood sample collection. Nitrite levels were determined by using an ozone-based chemiluminescence assay, while NOx (nitrites+nitrates) levels were measured by using the Griess reaction. Additionally, experimental approaches were used to validate our clinical findings. Higher decreases in blood pressure after propofol anesthesia were observed in HT-ACEi group as compared with those found in NT and HT groups. Consistently, rats treated with the ACEi enalapril showed more intense hypotensive responses to propofol. The hypotensive effects of propofol were associated with increased NO production in both clinical and experimental approaches. Enhanced increases in nitrite levels after propofol anesthesia were observed in HT-ACEi patients compared with NT and HT groups. Accordingly, rats treated with enalapril showed increased vascular NO formation after propofol anesthesia compared with rats receiving vehicle. Our data show that ACEi enhance the hypotensive responses to propofol anesthesia and increase nitrite concentrations. These findings suggest that increased NO bioavailability may account for the enhanced hypotensive effects of propofol in ACEi-treated patients.

Effects of Propofol on Cellular Bioenergetics in Human Skeletal Muscle Cells.

OBJECTIVES: Propofol may adversely affect the function of mitochondria and the clinical features of propofol infusion syndrome suggest that this may be linked to propofol-related bioenergetic failure. We aimed to assess the effect of therapeutic propofol concentrations on energy metabolism in human skeletal muscle cells. DESIGN: In vitro study on human skeletal muscle cells. SETTINGS: University research laboratories. SUBJECTS: Patients undergoing hip surgery and healthy volunteers. INTERVENTIONS: Vastus lateralis biopsies were processed to obtain cultured myotubes, which were exposed to a range of 1-10 µg/mL propofol for 96 hours. MEASUREMENTS AND MAIN RESULTS: Extracellular flux analysis was used to measure global mitochondrial functional indices, glycolysis, fatty acid oxidation, and the functional capacities of individual complexes of electron transfer chain. In addition, we used [1-C]palmitate to measure fatty acid oxidation and spectrophotometry to assess activities of individual electron transfer chain complexes II-IV. Although cell survival and basal oxygen consumption rate were only affected by 10 µg/mL of propofol, concentrations as low as 1 µg/mL reduced spare electron transfer chain capacity. Uncoupling effects of propofol were mild, and not dependent on concentration. There was no inhibition of any respiratory complexes with low dose propofol, but we found a profound inhibition of fatty acid oxidation. Addition of extra fatty acids into the media counteracted the propofol effects on electron transfer chain, suggesting inhibition of fatty acid oxidation as the causative mechanism of reduced spare electron transfer chain capacity. Whether these metabolic in vitro changes are observable in other organs and at the whole-body level remains to be investigated. CONCLUSIONS: Concentrations of propofol seen in plasma of sedated patients in ICU cause a significant inhibition of fatty acid oxidation in human skeletal muscle cells and reduce spare capacity of electron transfer chain in mitochondria.

Incidence of anaphylactic reactions after propofol administration in dogs.

Propofol is an anesthetic agent suspended in an emulsion system that includes egg yolk lecithin and soybean oil, because of which, there is concern about the use of propofol in patients allergic to these substances. We examined the association between propofol administration and incidence of adverse events in dogs with allergy to egg yolk lecithin and soybean oil. On the basis of the findings of an allergen-specific immunoglobulin E (IgE) test, 14 dogs with high levels (high-IgE group) and 7 dogs with low levels (normal-IgE group) of IgE were selected. Following intravenous administration of propofol, the incidence of anaphylactic reactions and plasma histamine concentrations under general anesthesia maintained with isoflurane throughout surgery were compared between the two groups. The frequency of anaphylactic reactions and plasma histamine concentrations were compared by the chi-square test and Student t-test, respectively. The statistical significance for both tests was set at P<0.05. In the high- and normal-IgE groups, the average frequencies of anaphylactic reactions after propofol administration were 21.4 and 14.3%, and the mean plasma histamine concentrations were 167.9 ± 94.5 nM and 65.7 ± 40.3 nM, respectively. Animals of neither groups experienced shock-like symptoms. These results revealed that propofol might be relatively safe, although careful perioperative anesthesia monitoring and standby protocols are required when using propofol in dogs with a history of allergic diseases or high chicken- or soybean-specific IgE levels.

Electroacupuncture Ameliorates Propofol-Induced Cognitive Impairment via an Opioid Receptor-Independent Mechanism.

While general anesthesia is known to induce cognitive deficits in elderly and pediatric patients, its influence on adults is less well-characterized. The present study was designed to evaluate the influence of propofol on the learning and memory of young adult rats, as well as the potential neuroprotective role of electroacupuncture (EA) in propofol-induced cognitive impairment. Intravenous anesthesia with propofol was administered to young adult male Sprague-Dawley (SD) rats for 6 h, and EA was administered three times before and after anesthesia. The Morris Water Maze (MWM) test was conducted to determine the rat's cognitive performance following the anesthesia treatment. Our results showed that propofol induced obvious cognitive impairment in young adult rats, which could be ameliorated by multiple EA treatments. Moreover, the decreased level of phosphorylated glycogen synthase kinase 3 ß (pGSK-3ß) in the CA1 region of the hippocampus accompanying the cognitive impairment was also reversed by EA treatment. Further experiments demonstrated that neither 2 nor 10 mg/kg (I.P.) naloxone blocked the effect of EA, indicating that the neuroprotective effect of EA on propofol-induced cognitive impairment was not mediated via the opioid receptors. The present study suggests that EA could ameliorate the cognitive impairment induced by prolonged anesthesia with propofol in young adult rats, which is likely associated with pGSK-3ß levels in the CA1 independently of opioid receptors. These findings imply that EA may be used as a potential neuroprotective therapy for post-operative cognitive dysfunction (POCD).