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BMJ Open May 2024Late-life treatment-resistant depression (LL-TRD) is common and increases risk for accelerated ageing and cognitive decline. Impaired sleep is common in LL-TRD and is a...
INTRODUCTION
Late-life treatment-resistant depression (LL-TRD) is common and increases risk for accelerated ageing and cognitive decline. Impaired sleep is common in LL-TRD and is a risk factor for cognitive decline. Slow wave sleep (SWS) has been implicated in key processes including synaptic plasticity and memory. A deficiency in SWS may be a core component of depression pathophysiology. The anaesthetic propofol can induce electroencephalographic (EEG) slow waves that resemble SWS. Propofol may enhance SWS and oral antidepressant therapy, but relationships are unclear. We hypothesise that propofol infusions will enhance SWS and improve depression in older adults with LL-TRD. This hypothesis has been supported by a recent small case series.
METHODS AND ANALYSIS
SWIPED (Slow Wave Induction by Propofol to Eliminate Depression) phase I is an ongoing open-label, single-arm trial that assesses the safety and feasibility of using propofol to enhance SWS in older adults with LL-TRD. The study is enrolling 15 English-speaking adults over age 60 with LL-TRD. Participants will receive two propofol infusions 2-6 days apart. Propofol infusions are individually titrated to maximise the expression of EEG slow waves. Preinfusion and postinfusion sleep architecture are evaluated through at-home overnight EEG recordings acquired using a wireless headband equipped with dry electrodes. Sleep EEG recordings are scored manually. Key EEG measures include sleep slow wave activity, SWS duration and delta sleep ratio. Longitudinal changes in depression, suicidality and anhedonia are assessed. Assessments are performed prior to the first infusion and up to 10 weeks after the second infusion. Cognitive ability is assessed at enrolment and approximately 3 weeks after the second infusion.
ETHICS AND DISSEMINATION
The study was approved by the Washington University Human Research Protection Office. Recruitment began in November 2022. Dissemination plans include presentations at scientific conferences, peer-reviewed publications and mass media. Positive results will lead to a larger phase II randomised placebo-controlled trial.
TRIAL REGISTRATION NUMBER
NCT04680910.
Topics: Humans; Propofol; Cognitive Dysfunction; Aged; Sleep, Slow-Wave; Electroencephalography; Male; Anesthetics, Intravenous; Depressive Disorder, Treatment-Resistant; Female; Middle Aged; Clinical Trials, Phase I as Topic
PubMed: 38816055
DOI: 10.1136/bmjopen-2024-087516 -
Turkish Journal of Medical Sciences 2023Propofol is a positive allosteric modulator of GABAA receptor (GABAAR) and has potent antioxidant activity. The aim of this study was to investigate the effect of...
Propofol mitigates brain injury and oxidative stress, and enhances GABAA receptor α1 subunit expression in a rat model of lithium chloride-pilocarpine induced status epilepticus.
BACKGROUND/AIM
Propofol is a positive allosteric modulator of GABAA receptor (GABAAR) and has potent antioxidant activity. The aim of this study was to investigate the effect of propofol on damage to the cerebral cortex and hippocampus in a lithium chloride (LiCl)-pilocarpine animal model of status epilepticus (SE).
MATERIALS AND METHODS
Adult male Sprague Dawley rats were injected with LiCl-pilocarpine to induce SE. They were then randomized and injected 30 min later with vehicle saline (SE+saline), propofol (SE+PPF, 50 mg/kg), Diazepam (SE+DZP, 10 mg/kg), Scopolamine (SE+SCOP, 10 mg/kg), or MK-801 (SE+MK-801, 2 mg/kg). Another group of rats received saline only and served as the naïve control (BLK). The levels of superoxide dismutase (SOD), glutathione (GSH) and malondialdehyde (MDA) in the serum, cortex and hippocampus were analyzed 2 and 24 h posttreatment. The degree of tissue damage in the cortex and hippocampus of individual rats was assessed 24 h posttreatment, together with expression of the GABAAR α1 subunit.
RESULTS
The propofol group showed reduced levels of tissue damage in the cerebral cortex and hippocampus, decreased levels of MDA, and increased levels of GSH compared to the SE+saline group. No changes in SOD level were observed in serum and tissue samples from the cortex and hippocampus of SE+saline rats. Immunohistochemistry and Western blot assays showed that propofol treatment significantly increased the expression of GABAR α1 subunit in the cortical and hippocampal tissues of SE rats.
CONCLUSION
Propofol treatment protected against SE-induced tissue injury in the cortex and hippocampus of rats. This was due at least in part to its antioxidant activity and to its induction of GABAAR α1 subunit expression in the brain.
Topics: Animals; Propofol; Receptors, GABA-A; Status Epilepticus; Pilocarpine; Male; Rats, Sprague-Dawley; Lithium Chloride; Oxidative Stress; Rats; Disease Models, Animal; Hippocampus; Brain Injuries; Malondialdehyde; Cerebral Cortex
PubMed: 38813010
DOI: 10.55730/1300-0144.5670 -
Turkish Journal of Medical Sciences 2024This study aims to determine the possible embryotoxic effects of propofol on the cerebellum and spinal cord using fertile chicken eggs.
BACKGROUND/AIM
This study aims to determine the possible embryotoxic effects of propofol on the cerebellum and spinal cord using fertile chicken eggs.
MATERIALS AND METHODS
A total of 430 fertile eggs were divided into 5 groups: control, saline, 2.5 mg.kg, 12.5 mg.kg, and 37.5 mg.kg propofol. Injections were made immediately before incubation via the air chamber. On the 15th, 18th, and 21st day of incubation, 6 embryos from each group were evaluated. Serial paraffin sections taken from the cerebellum and spinal cord were stained with hematoxylin-eosin, Kluver-Barrera, toluidine blue, and periodic acid-Schiff's reaction. The outer granular layer and total cortex thickness were measured, and the linear density of the Purkinje cells was determined. The ratios of the substantia grisea surface area to the total surface area of the spinal cord were calculated. The transverse and longitudinal diameters of the canalis centralis were also assessed.
RESULTS
No structural malformation was observed in any embryos examined macroscopically. No significant difference was observed between the groups in terms of development and histologic organization of the cerebellum and spinal cord. However, on the 15th, 18th, and 21st day, the outer granular layer (p < 0.001 for all days) and the total cortex thickness (p < 0.01, p < 0.001, and p < 0.001, respectively) decreased significantly in different propofol dose groups in varying degrees in the cerebellum. Similarly, in the spinal cord, there were significant changes in the ratios of the substantia grisea surface area to the total surface area (p < 0.01 and p < 0.001, respectively).
CONCLUSION
It was concluded that the in-ovo-administered propofol given immediately before incubation has adverse effects on the developing cerebellum and spinal cord. Therefore, it is important for anesthesiologists always to remain vigilant when treating female patients of childbearing age.
Topics: Animals; Propofol; Cerebellum; Spinal Cord; Chick Embryo; Anesthetics, Intravenous
PubMed: 38812654
DOI: 10.55730/1300-0144.5760 -
BMC Anesthesiology May 2024Propofol for anesthesia has become increasingly popular for endoscopic procedures. However, pain on propofol injection (POPI) remains an issue with administration. The...
BACKGROUND
Propofol for anesthesia has become increasingly popular for endoscopic procedures. However, pain on propofol injection (POPI) remains an issue with administration. The primary endpoint of this study was to identify patient characteristics and factors, such as IV site and gauge, that could predict the occurrence of POPI.
METHODS
This was a prospective chart review study of 291 patients undergoing endoscopic procedures. The patient's demographics, intravenous (IV) site, and gauge were extrapolated. POPI was scored 0-3: 0 for no pain, 1 for minimal discomfort or awareness of sensation, 2 for discomfort but manageable/tolerable, and 3 for severe discomfort with writhing.
RESULTS
291 patient charts were reviewed. One patient was excluded for a lower extremity IV site. 225 (77.6%) had no pain, 48 (16.6%) grade 1 pain, 16 (5.5%) grade 2 pain, and 1 (0.3%) grade 3 pain. 137, 13, and 140 patients respectively had antecubital (AC), forearm, and hand IVs. Zero patients with an AC IV experienced a score greater than 1. Compared to AC, forearm IVs with pain of 2-3 had a univariate odds ratio (OR) of 11.3 (0.66,1.92; p-value < 0.001), and hand IVs had a univariate OR of 18.8 (2.46,143.3; p-value < 0.001) with a multivariable OR 15.2 (1.93,118.9; p-value 0.004). Patients with anxiety/depression and pain had a univariate OR 2.31 (1.09, 7.27; p-value 0.031) with a multivariable OR 2.85 (1.06, 7.74; p-value 0.039). SSRI/SNRI use had a univariate OR 1.56 (0.57,4.28; p-value 0.38). Alcohol use had a univariate OR 1.24 (0.39,3.91; p-value 0.71). Narcotic use had a Univariate OR 6.18 (1.49,25.6; p-value 0.012). Diabetic patients had a univariate OR of 1.42 (0.45,4.48; p-value 0.55). Chronic pain had a univariate OR of 3.11 (1.04,9.28; p-value 0.042). Females had a univariate OR 0.98 (0.37,2.63; p-value 0.95).
CONCLUSION
This study identified potential characteristics for having POPI. The incidence of POPI was statistically significant in patients with hand and forearm IVs compared to AC IV sites, larger IV gauges, history of depression/anxiety, history of chronic narcotic use, fibromyalgia, and chronic pain syndromes. This shows the potential of premedicating with analgesics or using AC sites on these select patients to help reduce the risk of POPI.
Topics: Humans; Female; Propofol; Male; Prospective Studies; Middle Aged; Pain; Anesthetics, Intravenous; Adult; Injections, Intravenous; Risk Factors; Aged; Pain Measurement
PubMed: 38807072
DOI: 10.1186/s12871-024-02573-y -
BMC Anesthesiology May 2024Balanced propofol sedation is extensively used in endoscopic retrograde cholangiopancreatography (ERCP), but sedation-related adverse events (SRAEs) are common. In... (Randomized Controlled Trial)
Randomized Controlled Trial Comparative Study
A prospective, randomized, single-blinded study comparing the efficacy and safety of dexmedetomidine and propofol for sedation during endoscopic retrograde cholangiopancreatography.
BACKGROUND
Balanced propofol sedation is extensively used in endoscopic retrograde cholangiopancreatography (ERCP), but sedation-related adverse events (SRAEs) are common. In various clinical settings, the combination of dexmedetomidine with opioids and benzodiazepines has provided effective sedation with increased safety. The aim of this investigation was to compare the efficacy and safety of dexmedetomidine and propofol for sedation during ERCP.
METHODS
Forty-one patients were randomly divided into two groups: the dexmedetomidine (DEX) group and the propofol (PRO) group. Patients in the DEX group received an additional bolus of 0.6 μg kg dexmedetomidine followed by a dexmedetomidine infusion at 1.2 μg kg h, whereas the PRO group received 1-2 mg kg of propofol bolus followed by a propofol infusion at 2-3 mg kg h. During ERCP, the primary outcome was the incidence of hypoxemia (SpO < 90% for > 10 s). Other intraoperative adverse events were also recorded as secondary outcomes, including respiratory depression (respiratory rate of < 10 bpm min), hypotension (MAP < 65 mmHg), and bradycardia (HR < 45 beats min).
RESULTS
The incidence of hypoxemia was significantly reduced in the DEX group compared to the PRO group (0% versus 28.6%, respectively; P = 0.032). Patients in the PRO group exhibited respiratory depression more frequently than patients in the DEX group (35% versus 81%, respectively; P = 0.003). There were no significant differences in terms of hypotension and bradycardia episodes between groups. During the procedures, the satisfaction scores of endoscopists and patients, as well as the pain and procedure memory scores of patients were comparable between groups.
CONCLUSION
In comparison with propofol, dexmedetomidine provided adequate sedation safety with no adverse effects on sedation efficacy during ERCP.
TRIAL REGISTRATION
Chinese Clinical Trial Registry, ChiCTR2200061468, 25/06/2022.
Topics: Humans; Dexmedetomidine; Cholangiopancreatography, Endoscopic Retrograde; Propofol; Male; Female; Hypnotics and Sedatives; Middle Aged; Prospective Studies; Single-Blind Method; Aged; Adult; Hypoxia; Conscious Sedation
PubMed: 38807059
DOI: 10.1186/s12871-024-02572-z -
Drug Design, Development and Therapy 2024Remimazolam tosilate is a novel ultrafast-acting benzodiazepine that has a rapid emergence even after continuous infusion when using flumazenil. So far, relatively few... (Randomized Controlled Trial)
Randomized Controlled Trial Comparative Study Clinical Trial
Comparison of Remimazolam Tosilate and Propofol Sedation on the Early Postoperative Quality of Recovery in Patients Undergoing Day Surgery: A Prospective Randomized Controlled Trial.
PURPOSE
Remimazolam tosilate is a novel ultrafast-acting benzodiazepine that has a rapid emergence even after continuous infusion when using flumazenil. So far, relatively few articles are still focusing on the quality of recovery after general anesthesia with remimazolam, especially in day surgery. This study aimed to compare the early postoperative quality of recovery of remimazolam tosilate with flumazenil and propofol in patients undergoing day surgery.
PATIENTS AND METHODS
137 patients scheduled for day surgery were randomly divided into the remimazolam tosilate or propofol group. The primary endpoint was the incidence of overall recovery assessed with the early postoperative quality of recovery scale (PostopQRS) on postoperative day 1 (POD 1). The Richmond Agitation-Sedation Scale (RASS) scores in the post-anesthesia care unit (PACU), extubation time, postoperative recovery profiles, and perioperative data were documented. Any adverse events were recorded.
RESULTS
The incidence of overall recovery on POD1 was 47.7% in the remimazolam tosilate group and 65.1% in the propofol group (odds ratio, 0.52; 95% confidence interval (CI) 0.26 to 1.06; P = 0.072). In general, the overall recovery of the PostopQRS increased over time, and its interaction between time and group was significant (P = 0.003). Among the five dimensions of PostopQRS, there exist statistical differences between groups including emotional state and cognitive recovery. Upon arrival at the PACU, the remimazolam group was more sedated and took longer to recover to a RASS score similar to propofol. The frequency of application of vasoactive drugs during anesthesia was similar in both groups (P = 0.119). Despite rapid emergence with remimazolam after flumazenil reversal, re-sedation (10.8%) or somnolence (60%) in the PACU was observed, and the length of PACU stay in patients treated with remimazolam tosilate was longer than that of the propofol (35 min vs 30 min, P<0.001).
CONCLUSION
General anesthesia with remimazolam tosilate in conjunction with flumazenil reversal permits rapid recovery of consciousness in day surgery, but there was a notable occurrence of re-sedation or somnolence observed in PACU.
Topics: Humans; Propofol; Female; Male; Prospective Studies; Middle Aged; Benzodiazepines; Hypnotics and Sedatives; Adult; Ambulatory Surgical Procedures; Anesthesia Recovery Period; Aged; Flumazenil
PubMed: 38803562
DOI: 10.2147/DDDT.S456675 -
F1000Research 2022Acute lymphoblastic leukaemia (ALL) is a common type of cancer in children. General anaesthetics are often used on patients undergoing painful procedures during ALL...
BACKGROUND
Acute lymphoblastic leukaemia (ALL) is a common type of cancer in children. General anaesthetics are often used on patients undergoing painful procedures during ALL treatments but their effects on ALL malignancy remain unknown. Herein, we aim to study the effect of propofol and sevoflurane on the migration, homing and chemoresistance of ALL cells.
METHODS
NALM-6 and Reh cells were treated with propofol (5 and 10 μg/ml) or sevoflurane (3.6%) for six hours. Then, cells were harvested for adhesion assay and migration assay . In experiments, GFP-NALM-6 cells were pre-treated with propofol (10 μg/ml) or sevoflurane (3.6%) for six hours. Then, cells were injected intravenously to C57BL/6 female mice followed by intravital microscopy. For chemoresistance study, cells were treated with rising concentrations of Ara-c (0.05-50 nM) plus 10μg/ml of propofol or Ara-C plus 3.6% of sevoflurane for 4 hours, followed by the assessment of cell viability via CCK-8 assay and detection of autophagy via flow cytometry.
RESULTS
Both anaesthetics reduced migration and homing as exemplified by 1) the reduction in the number of cells entering the bone marrow and 2) the disturbance in homing location in relation to endosteal surface. Our results indicated that general anaesthetics reduced the surface CXCR4 expression and the adhesion of leukaemia cells to thrombin cleaved osteopontin (OPN) was reduced. Those changes might result in the alterations in migration and homing. In addition, both anaesthetics sensitised ALL cells to Ara-c possibly through CXCR4 mediated mechanisms. Propofol but not sevoflurane enhanced chemo-related cell death via inducing cytotoxic autophagy.
CONCLUSION
Together, our data suggest that both propofol and sevoflurane could reduce ALL migration, and homing and via CXCR4 and OPN mediated mechanisms. Both anaesthetics could sensitise ALL cells to chemotherapy possibly via CXCR4 mediated mechanisms.
Topics: Animals; Receptors, CXCR4; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Humans; Female; Cell Line, Tumor; Mice; Propofol; Sevoflurane; Osteopontin; Cell Movement; Anesthetics, General; Mice, Inbred C57BL; Drug Resistance, Neoplasm
PubMed: 38798305
DOI: 10.12688/f1000research.125877.2 -
The British Journal of Oral &... Apr 2024The aim of this study was to determine what is considered a long oral surgery and conduct a cost-effective analysis of sedative agents used for intravenous sedation... (Review)
Review
The aim of this study was to determine what is considered a long oral surgery and conduct a cost-effective analysis of sedative agents used for intravenous sedation (IVS) and sedation protocols for such procedures. Pubmed and Google Scholar databases were used to identify human studies employing IVS for extractions and implant-related surgeries, between 2003 and July/2023. Sedation protocols and procedure lengths were documented. Sedative satisfaction, operator satisfaction, and sedation assessment were also recorded. Cost estimation was based on The British National Formulary (BNF). To assess bias, the Cochrane Risk of Bias tools were employed. This review identified 29 randomised control trials (RCT), six cohorts, 14 case-series, and one case-control study. The study defined long procedures with an average duration of 31.33 minutes for extractions and 79.37 minutes for implant-related surgeries. Sedative agents identified were midazolam, dexmedetomidine, propofol, and remimazolam. Cost analysis revealed midazolam as the most cost-effective option (<10 pence per procedure per patient) and propofol the most expensive option (approximately £46.39). Bias analysis indicated varying degrees of bias in the included studies. Due to diverse outcome reporting, a comparative network approach was employed and revealed benefits of using dexmedetomidine, propofol, and remimazolam over midazolam. Midazolam, dexmedetomidine, propofol, and remimazolam demonstrated safety and efficacy as sedative agents for conscious IVS in extended procedures like extractions or implant-related surgeries. While midazolam is the most cost-effective option, dexmedetomidine, propofol, and remimazolam offer subjective and clinical benefits. The relatively higher cost of propofol may impede its widespread use. Dexmedetomidine and remimazolam stand out as closely priced options, necessitating further clinical investigations for comparative efficacy assessment.
PubMed: 38797651
DOI: 10.1016/j.bjoms.2024.04.006 -
JA Clinical Reports May 2024The causes of perioperative hyperlactatemia vary, but they are generally associated with hypoperfusion. Here, we report the case of a pediatric patient who developed...
A case of pediatric Perthes' disease with unexplained hyperlactatemia at the time of initial surgery and anesthetic management with remimazolam for the subsequent surgery.
BACKGROUND
The causes of perioperative hyperlactatemia vary, but they are generally associated with hypoperfusion. Here, we report the case of a pediatric patient who developed unexplained hyperlactatemia during anesthesia with propofol and sevoflurane, which recurred during a second surgery under anesthesia with remimazolam.
CASE PRESENTATION
An 8-year-old boy with Perthes disease and no remarkable past or family history was scheduled for an osteotomy. Anesthesia was induced with propofol and rocuronium and then maintained with sevoflurane and remifentanil. The patient developed lactic acidosis without hemodynamic instability during anesthesia, with a normal lactate/pyruvate ratio after surgery, suggesting a lack of hypoperfusion. We used remimazolam instead of propofol during the second surgery 6 months later, considering the possibility of drug-induced lactic acidosis, including malignant hyperthermia and propofol infusion syndrome, where the unexplained hyperlactatemia recurred.
CONCLUSIONS
Distinguishing the causes of hyperlactatemia, particularly in the absence of other symptoms, is challenging. The lactate/pyruvate ratio during episodes of hyperlactatemia can provide insights into the underlying pathology.
PubMed: 38787500
DOI: 10.1186/s40981-024-00715-2 -
JA Clinical Reports May 2024Post-induction hypotension (PIH) is an independent risk factor for prolonged postoperative stay and hospital death. Patients undergoing transcatheter aortic valve...
PURPOSE
Post-induction hypotension (PIH) is an independent risk factor for prolonged postoperative stay and hospital death. Patients undergoing transcatheter aortic valve implantation (TAVI) are prone to develop PIH. This study aimed to develop a predictive model for PIH in patients undergoing TAVI.
METHODS
This single-center retrospective observational study included 163 patients who underwent TAVI. PIH was defined as at least one measurement of systolic arterial pressure <90 mmHg or at least one incident of norepinephrine infusion at a rate >6 µg/min from anesthetic induction until 20 min post-induction. Multivariate logistic regression analysis was performed to develop a predictive model for PIH in patients undergoing TAVI.
RESULTS
In total, 161 patients were analyzed. The prevalence of PIH was 57.8%. Multivariable logistic regression analysis showed that baseline mean arterial pressure ≥90 mmHg [adjusted odds ratio (aOR): 0.413, 95% confidence interval (95% CI): 0.193-0.887; p=0.023] and higher doses of fentanyl (per 1-µg/kg increase, aOR: 0.619, 95% CI: 0.418-0.915; p=0.016) and ketamine (per 1-mg/kg increase, aOR: 0.163, 95% CI: 0.062-0.430; p=0.002) for induction were significantly associated with lower risk of PIH. A higher dose of propofol (per 1-mg/kg increase, aOR: 3.240, 95% CI: 1.320-7.920; p=0.010) for induction was significantly associated with higher risk of PIH. The area under the curve (AUC) for this model was 0.802.
CONCLUSION
The present study developed predictive models for PIH in patients who underwent TAVI. This model may be helpful for anesthesiologists in preventing PIH in patients undergoing TAVI.
PubMed: 38787499
DOI: 10.1186/s40981-024-00717-0