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Journal of Perianesthesia Nursing :... Jun 2024Stress response is a common complication during extubation, mainly manifested by dramatic hemodynamic fluctuations. Transcutaneous electrical acupoint stimulation (TEAS)...
Effect of Transcutaneous Electrical Acupoint Stimulation on Extubation-Related Stress Response in Noncardiac Surgery Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
PURPOSE
Stress response is a common complication during extubation, mainly manifested by dramatic hemodynamic fluctuations. Transcutaneous electrical acupoint stimulation (TEAS) is widely applied in the perioperative period. We performed this meta-analysis to evaluate whether the TEAS could relieve the stress response during extubation in noncardiac surgery patients.
DESIGN
A systematic review and meta-analysis of randomized controlled trials.
METHODS
We searched six databases (PubMed, Web of Science, Embase, Cochrane Library, China National Knowledge Infrastructure, CNKI, and Wan Fang) for relevant literature. A risk of bias assessment was executed based on the Cochrane Criteria. We applied RevMan5.4.1 software to analyze data. When the χ test did not show heterogeneity, we adopted the fixed-effect model. Otherwise, the random-effect model was used.
FINDINGS
ln total, 12 randomized controlled trials with 1,347 participants were enrolled in this meta-analysis. Meta-analysis showed the heart rate and mean arterial pressure of the intervention group were significantly lower than the control group at immediately, 5 minutes, and 10 minutes after extubation. The occurrence rate of emergency agitation (RR 0.39, 95% CI [0.26,0.60]) and postoperative delirium (RR 0.40, 95% CI [0.22, 0.72] were also lower in the TEAS group. The consumption of propofol (standardized mean difference (SMD) 0.47, 95% CI [-0.77, -0.18]) and remifentanil (SMD 1.49, 95% CI [-2.01, -0.96]) of the intervention group were also significantly reduced compared with the control group.
CONCLUSIONS
TEAS was beneficial for improving stress response during extubation, emergence agitation, postoperative delirium, and reduced the consumption of intraoperative propofol and remifentanil, but it was necessary to note the limitations of the current evidence.
PubMed: 38904602
DOI: 10.1016/j.jopan.2024.01.015 -
Indian Journal of Anaesthesia Jun 2024Post-discharge nausea and vomiting (PDNV) is a pertinent problem in patients undergoing ambulatory surgery. The objective of this study was to assess the efficacy of the...
Olanzapine versus standard antiemetic prophylaxis for the prevention of post-discharge nausea and vomiting after propofol-based general anaesthesia: A randomised controlled trial.
BACKGROUND AND AIMS
Post-discharge nausea and vomiting (PDNV) is a pertinent problem in patients undergoing ambulatory surgery. The objective of this study was to assess the efficacy of the novel drug olanzapine, which has proved its efficiency in patients undergoing highly emetogenic chemotherapy for PDNV prevention.
METHODS
This randomised controlled trial recruited 106 adult patients (18-65 years) undergoing highly emetogenic daycare surgeries with propofol-based general anaesthesia (GA). Group O received preoperative oral olanzapine 10 mg, and Group C, acting as a control, received 8 mg of intravenous dexamethasone and 4 mg of ondansetron intraoperatively. The primary outcome was nausea (numeric rating scale >3) and/or vomiting 24 h after discharge. Secondary outcomes included nausea and vomiting in the post-anaesthesia care unit (PACU), severe nausea, vomiting and side effects. Normality was assessed using the Shapiro-Wilk test, and the independent samples -test or the Mann-Whitney test was used to compare continuous variables. Fisher's exact test was used to assess any non-random associations between the categorical variables.
RESULTS
The incidence and severity of postoperative nausea and vomiting were similar in both groups within PACU (four patients experienced nausea and vomiting, three had severe symptoms in Group O, = 0.057) and in the post-discharge period (three patients in Group O had nausea and vomiting compared to five patients in Group C, of which four were severe, = 0.484). The side effects (sedation, dizziness, and light-headedness) were comparable between the two groups.
CONCLUSION
A single preoperative oral olanzapine can be an effective alternative to standard antiemetic prophylaxis involving dexamethasone and ondansetron for preventing PDNV in highly emetogenic daycare surgeries with propofol-based GA.
PubMed: 38903258
DOI: 10.4103/ija.ija_1162_23 -
Nature Communications Jun 2024Methaqualone, a quinazolinone marketed commercially as Quaalude, is a central nervous system depressant that was used clinically as a sedative-hypnotic, then became a...
Methaqualone, a quinazolinone marketed commercially as Quaalude, is a central nervous system depressant that was used clinically as a sedative-hypnotic, then became a notorious recreational drug in the 1960s-80s. Due to its high abuse potential, medical use of methaqualone was eventually prohibited, yet it persists as a globally abused substance. Methaqualone principally targets GABA receptors, which are the major inhibitory neurotransmitter-gated ion channels in the brain. The restricted status and limited accessibility of methaqualone have contributed to its pharmacology being understudied. Here, we use cryo-EM to localize the GABA receptor binding sites of methaqualone and its more potent derivative, PPTQ, to the same intersubunit transmembrane sites targeted by the general anesthetics propofol and etomidate. Both methaqualone and PPTQ insert more deeply into subunit interfaces than the previously-characterized modulators. Binding of quinazolinones to this site results in widening of the extracellular half of the ion-conducting pore, following a trend among positive allosteric modulators in destabilizing the hydrophobic activation gate in the pore as a mechanism for receptor potentiation. These insights shed light on the underexplored pharmacology of quinazolinones and further elucidate the molecular mechanisms of allosteric GABA receptor modulation through transmembrane binding sites.
Topics: Receptors, GABA-A; Binding Sites; Cryoelectron Microscopy; Humans; Animals; Etomidate; Propofol; Quinazolinones; Allosteric Regulation; HEK293 Cells; Hypnotics and Sedatives
PubMed: 38898000
DOI: 10.1038/s41467-024-49471-y -
European Journal of Pharmacology Aug 2024Repeated exposure to propofol during early brain development is associated with anxiety disorders in adulthood, yet the mechanisms underlying propofol-induced...
Repeated exposure to propofol during early brain development is associated with anxiety disorders in adulthood, yet the mechanisms underlying propofol-induced susceptibility to anxiety disorders remain elusive. The lateral septum (LS), primarily composed of γ-aminobutyric acidergic (GABAergic) neurons, serves as a key brain region in the regulation of anxiety. However, it remains unclear whether LS GABAergic neurons are implicated in propofol-induced anxiety. Therefore, we conducted c-Fos immunostaining of whole-brain slices from mice exposed to propofol during early life. Our findings indicate that propofol exposure activates GABAergic neurons in the LS. Selective activation of LS GABAergic neurons resulted in increased anxiety-like behavior, while selective inhibition of these neurons reduced such behaviors. These results suggest that the LS is a critical brain region involved in propofol-induced anxiety. Furthermore, we investigated the molecular mechanism of propofol-induced anxiety in the LS. Microglia activation underlies the development of anxiety. Immunofluorescence staining and Western blot analysis of LS revealed activated microglia and significantly elevated levels of phospho-NF-κB p65 protein. Additionally, a decrease in the number of neuronal spines was observed. Our study highlights the crucial role of the LS in the development of anxiety-like behavior in adulthood following childhood propofol exposure, accompanied by the activation of inflammatory pathways.
Topics: Propofol; Animals; Anxiety; Mice; Male; GABAergic Neurons; Behavior, Animal; Microglia; Proto-Oncogene Proteins c-fos; Mice, Inbred C57BL; Transcription Factor RelA; Dendritic Spines
PubMed: 38897021
DOI: 10.1016/j.ejphar.2024.176756 -
Annals of Intensive Care Jun 2024The objective was to compare sevoflurane, a volatile sedation agent with potential bronchodilatory properties, with propofol on respiratory mechanics in critically ill...
BACKGROUND
The objective was to compare sevoflurane, a volatile sedation agent with potential bronchodilatory properties, with propofol on respiratory mechanics in critically ill patients with COPD exacerbation.
METHODS
Prospective study in an ICU enrolling critically ill intubated patients with severe COPD exacerbation and comparing propofol and sevoflurane after 1:1 randomisation. Respiratory system mechanics (airway resistance, PEEPi, trapped volume, ventilatory ratio and respiratory system compliance), gas exchange, vitals, safety and outcome were measured at inclusion and then until H48. Total airway resistance change from baseline to H48 in both sevoflurane and propofol groups was the main endpoint.
RESULTS
Sixteen patients were enrolled and were sedated for 126 h(61-228) in the propofol group and 207 h(171-216) in the sevoflurane group. At baseline, airway resistance was 21.6cmH2O/l/s(19.8-21.6) in the propofol group and 20.4cmH2O/l/s(18.6-26.4) in the sevoflurane group, (p = 0.73); trapped volume was 260 ml(176-290) in the propofol group and 73 ml(35-126) in the sevoflurane group, p = 0.02. Intrinsic PEEP was 1.5cmH2O(1-3) in both groups after external PEEP optimization. There was neither early (H4) or late (H48) significant difference in airway resistance and respiratory mechanics parameters between the two groups.
CONCLUSIONS
In critically ill patients intubated with COPD exacerbation, there was no significant difference in respiratory mechanics between sevoflurane and propofol from inclusion to H4 and H48.
PubMed: 38888818
DOI: 10.1186/s13613-024-01311-4 -
Laryngoscope Investigative... Jun 2024The course of sedation during drug-induced sleep endoscopy (DISE) depends on the application pattern of the sedative drug. The depth of sedation should imitate light and...
OBJECTIVE
The course of sedation during drug-induced sleep endoscopy (DISE) depends on the application pattern of the sedative drug. The depth of sedation should imitate light and deep sleep as well. Moreover, there should be as many breathing cycles as possible available for observation during light and deep sedation. The aim of the study was to evaluate different rates of propofol application with respect to the achieved depth and length of the course of sedation.
METHODS
Sixty-three consecutive patients with obstructive sleep apnea and/or snoring undergoing DISE were randomly sedated by propofol perfusion at seven different application patterns: 14, 16, 18, 19, 20, 22 mg/kg/h (0.233, 0.267, 0.3, 0.317, 0.333, 0.367 mg/kg/min) per perfusor and individual bolus application 10 mg each. Sedation depth was monitored by BiSpectral Index™ (BIS). The influence of baseline parameters and the courses of sedation were analyzed.
RESULTS
The application rate was the only factor that influenced the depth of sedation. Basic parameters (gender, age, body mass index, apnea-hypopnea index) had no influence on the depth of sedation. The sedation depth was dependent on the rate of propofol application. Regimes at 14 and 16 mg/kg/h as well as bolus application did not reach BIS levels below 50 representing deep sleep. Propofol doses of more than 20 mg/kg/h led to rapid decreases of sedation levels below deep sleep niveau. Propofol rates between 18 and 20 mg/kg/h enable BIS levels below 50 representing deep sleep and providing enough breathing cycles for observation.
CONCLUSION
Lower application rates of propofol provide slower courses of sedation and shallower depths of sedation. A rate of 14 mg/kg/h might be appropriate to reach a sedation plateau at light sleep. A rate of 18 mg/kg/h leads to a sedation, corresponding to deep sleep. The combination of both rates might be a suitable pattern for performing sedation-controlled DISE.
LEVEL OF EVIDENCE
2: Randomized trial.
PubMed: 38887705
DOI: 10.1002/lio2.1258 -
Journal of Thoracic Disease May 2024Postoperative pneumonia (POP) is a preventable complication associated with adverse outcomes. The aim of this study is to explore the anesthetic predictor for POP in...
BACKGROUND
Postoperative pneumonia (POP) is a preventable complication associated with adverse outcomes. The aim of this study is to explore the anesthetic predictor for POP in patients with non-small cell lung cancer (NSCLC) after surgery.
METHODS
A total of 306 patients with NSCLC were selected. Multivariable logistic regression analysis model was used to screen the independent predictors for POP. The primary outcome was POP and the secondary outcomes were intensive care unit (ICU) admission rate, reintubation rate and postoperative hospital stay (PHS).
RESULTS
POP occurred in 102 (33.3%) of 306 patients. Multivariable logistic regression analysis showed that perioperative propofol administration >4.42 mg/kg [odds ratio (OR) =0.543, 95% confidence interval (CI): 0.330-0.895, P=0.02] lowered the risk of POP, while duration of surgery >3 h (OR =1.951, 95% CI: 1.189-3.199, P=0.008) and total intraoperative fluid infusion >1,450 mL (OR =2.428, 95% CI: 1.307-4.509, P=0.005) were associated with the increasing risk of POP. There was a higher ICU admission and reintubation rate in the POP group (P<0.05).
CONCLUSIONS
Perioperative propofol administration >4.42 mg/kg may diminish the incidence of POP, while duration of surgery >3 h and intraoperative fluid infusion >1,450 mL increase the development of POP.
PubMed: 38883649
DOI: 10.21037/jtd-24-107 -
Translational Cancer Research May 2024Hepatocellular carcinoma (HCC) is a malignant tumor with high morbidity and mortality. Propofol has been reported to modulate tumorigenesis in HCC; the aim of this study...
BACKGROUND
Hepatocellular carcinoma (HCC) is a malignant tumor with high morbidity and mortality. Propofol has been reported to modulate tumorigenesis in HCC; the aim of this study was to investigate the effect of the interaction of propofol with POLR2L on HCC tumor progression in HCC.
METHODS
The propofol-related GSE101724 dataset was analyzed using weighted gene co-expression network analysis (WGCNA) and differentially expressed genes (DEGs) to identify overlapping genes. Key genes were selected from The Cancer Genome Atlas-liver hepatocellular carcinoma (TCGA-LIHC)-DEGs for prognostic analysis. The impact of POLR2L on LIHC patient survival was assessed, followed by in vitro experiments to validated its effects on HCC cell behavior and signaling pathways.
RESULTS
Fourteen overlapping genes were identified in the turquoise module (highest correlation) of up-regulated DEGs and GSE101724. Further analysis obtained 11 key overlapping genes from 14 overlapping genes and TCGA-LIHC-DEGs, among which HSPE1 and POLR2L showed significant prognostic correlation. Patients with LIHC have a worse chance of surviving when their POLR2L expression is elevated. Knockdown POLR2L significantly inhibited the proliferation, invasion, and migration of HCC cell lines. Downregulation of POLR2L was accompanied by induced apoptosis, cell cycle arrest, and modulation of the expression of apoptosis-related genes. Propofol was found to downregulate POLR2L expression, inhibiting cell proliferation and growth. Further, it was shown that propofol controlled the development of HCC by influencing the POLR2L/TGF-β signaling loop.
CONCLUSIONS
The results validated the predictive relevance of POLR2L in HCC and emphasized that propofol can regulate HCC progression through the POLR2L/TGF-β signaling pathway.
PubMed: 38881942
DOI: 10.21037/tcr-23-2066 -
DEN Open Apr 2025The effectiveness and safety of propofol-based sedation and midazolam sedation in pediatric bidirectional endoscopy were compared.
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, < 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.
PubMed: 38881579
DOI: 10.1002/deo2.391 -
Perioperative Medicine (London, England) Jun 2024Remimazolam is a short-acting benzodiazepine newly approved for the induction and maintenance of general anesthesia. Remimazolam emerges as an ideal drug for the...
BACKGROUND
Remimazolam is a short-acting benzodiazepine newly approved for the induction and maintenance of general anesthesia. Remimazolam emerges as an ideal drug for the neurosurgical population due to its rapid emergence, enabling early neurological assessment, and its ability to maintain perfusion pressure, which is crucial for preventing cerebral ischemia. However, the use of benzodiazepine has been associated with an increased risk of postoperative delirium (POD). There is currently limited evidence about the relationship between remimazolam-based total intravenous anesthesia (TIVA) and POD.
METHODS
In this double-blind, randomized, non-inferiority trial, we plan to include 696 adult patients with American Society of Anesthesiologists physical status class I to III, undergoing elective neurovascular surgery under general anesthesia. After informed consent, the patients will be randomized to receive either remimazolam or propofol-based TIVA with a 1:1 ratio. The primary outcome is the incidence of POD within 5 days after surgery. Secondary outcomes include subtypes, number of positive assessments and severity of POD, emergence agitation, intraoperative awareness and undesirable patient movement, intraoperative hypotension, and postoperative cognitive function. The data will be analyzed in modified intention to treat.
DISCUSSION
This trial will evaluate the effect of remimazolam on the development of POD compared to propofol anesthesia. The results of this trial will provide evidence regarding the choice of optimal anesthetics to minimize the risk of POD in neurosurgical patients.
TRIAL REGISTRATION
The study protocol was prospectively registered at the Clinical trials ( https://clinicaltrials.gov , NCT06115031, principal investigator: Jiseon Jeong; date of first registration: November 2, 2023, before the recruitment of the first participant.
PubMed: 38877533
DOI: 10.1186/s13741-024-00415-6