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Drug Design, Development and Therapy 2023This study aimed to compare the cardiopulmonary safety of remimazolam and propofol in patients undergoing cervical conization. (Randomized Controlled Trial)
Randomized Controlled Trial Clinical Trial
PURPOSE
This study aimed to compare the cardiopulmonary safety of remimazolam and propofol in patients undergoing cervical conization.
METHODS
This was a single-blind, parallel, randomized controlled study. A total of 204 patients scheduled for day surgery of cold knife cervical conization received either remimazolam-alfentanil anesthesia (remimazolam group) or propofol-alfentanil anesthesia (propofol group). The primary outcome was the incidence of intraoperative cardiopulmonary adverse events (a composite outcome of hypotension, bradycardia and hypoxemia). The occurrence of hypotension, bradycardia, hypoxemia and the degree of body movement were secondary outcomes, as well as the moment at which consciousness was lost, the interval between the end of anesthesia and the operating room's release of the patient, and the overall dosage of alfentanil administered during the procedure.
RESULTS
The incidence of intraoperative cardiopulmonary adverse events was 45 (44.1%) in the remimazolam group and 72 (70.6%) in the propofol group (absolute risk difference [95% CI], -26.47% [-39.55% to -13.39%]; odds ratio (OR) [95% CI], 0.43 [0.28 to 0.65]; < 0.001). The remimazolam group showed lower incidences of hypotension and hypoxemia compared to the propofol group ( = 0.01 for both). No significant differences were observed in the overall alfentanil dosages administered, bradycardia, bodily movement, or time to losing consciousness between the two groups.
CONCLUSION
In patients who underwent cold knife cervical conization, remimazolam-alfentanil anesthesia was associated with a reduced incidence of intraoperative cardiopulmonary adverse events compared with propofol-alfentanil anesthesia.
Topics: Humans; Propofol; Alfentanil; Anesthetics, Intravenous; Conization; Bradycardia; Single-Blind Method; Benzodiazepines; Hypotension; Hypoxia
PubMed: 37125082
DOI: 10.2147/DDDT.S405057 -
Bioengineering (Basel, Switzerland) Apr 2023Supermicrosurgical lymphaticovenous anastomosis (LVA) is a minimally invasive surgical technique that creates bypasses between lymphatic vessels and veins, thereby...
Supermicrosurgical lymphaticovenous anastomosis (LVA) is a minimally invasive surgical technique that creates bypasses between lymphatic vessels and veins, thereby improving lymphatic drainage and reducing lymphedema. This retrospective single-center study included 137 patients who underwent non-intubated LVA in southern Taiwan. A total of 119 patients were enrolled and assigned to two study groups: the geriatric (age ≥ 75 years, = 23) and non-geriatric groups (age < 75 years, = 96). The primary outcome was to investigate and compare the arousal and maintenance of the propofol effect-site concentration (Ce) using an electroencephalographic density spectral array (EEG DSA) in both groups. The results showed that the geriatric group required less propofol (4.05 [3.73-4.77] mg/kg/h vs. 5.01 [4.34-5.92] mg/kg/h, = 0.001) and alfentanil (4.67 [2.53-5.82] μg/kg/h vs. 6.68 [3.85-8.77] μg/kg/h, = 0.047). The median arousal Ce of propofol among the geriatric group (0.6 [0.5-0.7] μg/mL) was significantly lower than that in patients aged ≤ 54 years (1.3 [1.2-1.4] μg/mL, < 0.001), 55-64 years (0.9 [0.8-1.0] μg/mL, < 0.001), and <75 years (0.9 [0.8-1.2] μg/mL, < 0.001). In summary, the combined use of EEG DSA provides the objective and depth of adequate sedation for extensive non-intubated anesthesia in late-elderly patients who undergo LVA without perioperative complications.
PubMed: 37106682
DOI: 10.3390/bioengineering10040494 -
Saudi Journal of Anaesthesia 2023Opsoclonus-myoclonus syndrome (OMS) is a very rare neurological disorder thought to be the result of autoimmune responses in the nervous system. The relationship between...
Opsoclonus-myoclonus syndrome (OMS) is a very rare neurological disorder thought to be the result of autoimmune responses in the nervous system. The relationship between this disorder and anesthesia procedures has not been studied in detail. To our knowledge, there are only 4 case reports, none of them with epidural-general combined anesthesia. We present a 9-year-old female with OMS due to low-grade neuroblastoma, for 7 years, who underwent tumor remotion due to the large size. Intravenous induction was done with alfentanil, lidocaine, propofol and rocuronium and ropivacaine was administered via lumbar epidural catheter. Adding to the sparse anesthetic management information in OMS, we now show one more possible approach, that can be valuable in high-risk cases, where general anesthesia can be involved with higher risk for the patient.
PubMed: 37032696
DOI: 10.4103/sja.sja_558_22 -
BMC Anesthesiology Apr 2023Dexmedetomidine is an alpha-2 agonist with anti-anxiety, sedative, and analgesic effects and causes a lesser degree of respiratory depression. We hypothesized that the...
Opioid-sparing anesthesia with dexmedetomidine provides stable hemodynamic and short hospital stay in non-intubated video-assisted thoracoscopic surgery: a propensity score matching cohort study.
OBJECTIVES
Dexmedetomidine is an alpha-2 agonist with anti-anxiety, sedative, and analgesic effects and causes a lesser degree of respiratory depression. We hypothesized that the use of dexmedetomidine in non-intubated video-assisted thoracic surgery (VATS) may reduce opioid-related complications such as postoperative nausea and vomiting (PONV), dyspnea, constipation, dizziness, skin itching, and cause minimal respiratory depression, and stable hemodynamic status.
METHODS
Patients who underwent non-intubated VATS lung wedge resection with propofol combined with dexmedetomidine (group D) or alfentanil (group O) between December 2016 and May 2022 were enrolled in this retrospective propensity score matching cohort study. Intraoperative vital signs, arterial blood gas data, perioperative results and treatment outcomes were analyzed. Of 100 patients included in the study (group D, 50 and group O, 50 patients), group D had a significantly lower degree of decrement in the heart rate and the blood pressure than group O. Intraoperative one-lung arterial blood gas revealed lower pH and significant ETCO. The common opioid-related side effects, including PONV, dyspnea, constipation, dizziness, and skin itching, all of which occurred more frequently in group O than in group D. Patients in group O had significantly longer postoperative hospital stay and total hospital stay than group D, which might be due to opioid-related side effects postoperatively.
CONCLUSIONS
The application of dexmedetomidine in non-intubated VATS resulted in a significant reduction in perioperative opioid-related complications and maintenance with acceptable hemodynamic performance. These clinical outcomes found in our retrospective study may enhance patient satisfaction and shorten the hospital stay.
Topics: Humans; Thoracic Surgery, Video-Assisted; Analgesics, Opioid; Dexmedetomidine; Retrospective Studies; Cohort Studies; Postoperative Nausea and Vomiting; Length of Stay; Propensity Score; Dizziness; Pain, Postoperative; Hemodynamics; Anesthesia; Respiratory Insufficiency; Dyspnea
PubMed: 37013487
DOI: 10.1186/s12871-023-02032-0 -
British Journal of Pharmacology Sep 2023The illicit use of fentanyl-like drugs (fentanyls), which are μ opioid receptor agonists, and the many overdose deaths that result, has become a major problem....
BACKGROUND AND PURPOSE
The illicit use of fentanyl-like drugs (fentanyls), which are μ opioid receptor agonists, and the many overdose deaths that result, has become a major problem. Fentanyls are very potent in vivo, leading to respiratory depression and death. However, the efficacy and possible signalling bias of different fentanyls is not clearly known. Here, we compared the relative efficacy and bias of a series of fentanyls.
EXPERIMENTAL APPROACH
For agonist signalling bias and efficacy measurements, Bioluminescence Resonance Energy Transfer experiments were undertaken in HEK293T cells transiently transfected with μ opioid receptors, to assess Gi protein activation and β-arrestin 2 recruitment. Agonist-induced cell surface receptor loss was assessed using an enzyme-linked immunosorbent assay, whilst agonist-induced G protein-coupled inwardly rectifying potassium channel current activation was measured electrophysiologically from rat locus coeruleus slices. Ligand poses in the μ opioid receptor were determined in silico using molecular dynamics simulations.
KEY RESULTS
Relative to the reference ligand DAMGO, carfentanil was β-arrestin-biased, whereas fentanyl, sufentanil and alfentanil did not display bias. Carfentanil induced potent and extensive cell surface receptor loss, whilst the marked desensitisation of G protein-coupled inwardly rectifying potassium channel currents in the continued presence of carfentanil in neurones was prevented by a GRK2/3 inhibitor. Molecular dynamics simulations suggested unique interactions of carfentanil with the orthosteric site of the receptor that could underlie the bias.
CONCLUSIONS AND IMPLICATIONS
Carfentanil is a β-arrestin-biased opioid drug at the μ receptor. It is uncertain how such bias influences in vivo effects of carfentanil relative to other fentanyls.
Topics: Rats; Humans; Animals; Receptors, Opioid, mu; beta-Arrestins; Arrestin; Ligands; HEK293 Cells; Fentanyl; Analgesics, Opioid; GTP-Binding Proteins; beta-Arrestin 1; Potassium Channels, Inwardly Rectifying
PubMed: 37005796
DOI: 10.1111/bph.16084 -
Medicine Mar 2023To observe the effect of low-dose propofol combined with dexamethasone on the prevention of postoperative nausea and vomiting (PONV) in gynaecological day surgery under...
Effect of low-dose propofol combined with dexamethasone on the prevention of postoperative nausea and vomiting in gynaecological day surgery under remimazolam-based general anesthesia.
BACKGROUND
To observe the effect of low-dose propofol combined with dexamethasone on the prevention of postoperative nausea and vomiting (PONV) in gynaecological day surgery under remimazolam-based general anesthesia.
METHODS
A total of 120 patients, aged from 18 to 65 years old, American Society of Anesthesiologists grade I or II, were scheduled to undergo hysteroscopy under total intravenous anesthesia. The patients were divided into 3 groups (n = 40 each): dexamethasone plus saline group (DC group), dexamethasone plus droperidol group (DD group) and dexamethasone plus propofol group (DP group). Dexamethasone 5 mg and flurbiprofen axetil 50 mg were given intravenously before induction of general anesthesia. Anesthesia induction: remimazolam 6 mg/kg/hours was continuously pumped until sleep and slow intravenous injection of alfentanil 20 ug/kg and mivacurium chloride 0.2 mg/kg was given. Anesthesia maintenance: remimazolam 1 mg/kg/hour and alfentanil 40 ug/kg/hours were continuously pumped. After the start of surgery, DC group was given 2 mL saline, DD group was given droperidol 1 mg, and DP group was given propofol 20 mg. Primary outcome: incidence of PONV in the postanesthesia care unit (PACU). Secondary outcome: incidence of PONV in patients within 24 hours after surgery, as well as general patient data, duration of anesthesia, the recovery time of patients, dose of remimazolam and alfentanil, etc.
RESULTS
In PACU, patients of group DD and DP showed less PONV than those in group DC (P < .05). Within 24 hours after operation, there was no significant difference in the incidence of PONV among the 3 groups (P > .05), but the incidence of vomiting in DD group and DP group was significantly lower than that in DC group (P < .05). There was no significant difference in general data, anesthesia time, the recovery time of patients and dosage of remimazolam and alfentanil among the 3 groups (P > .05).
CONCLUSION
The effect of low-dose propofol combined with dexamethasone to prevent PONV under remimazolam-based general anesthesia was similar to that of droperidol combined with dexamethasone, both of which significantly reduced the incidence of PONV in the PACU compared to dexamethasone alone. However, low-dose propofol combined with dexamethasone had little effect on the incidence of PONV within 24 hours compared to dexamethasone alone and only reduced the incidence of postoperative vomiting in patients.
Topics: Female; Humans; Adolescent; Young Adult; Adult; Middle Aged; Aged; Postoperative Nausea and Vomiting; Propofol; Droperidol; Antiemetics; Alfentanil; Ambulatory Surgical Procedures; Anesthesia, General; Dexamethasone; Double-Blind Method
PubMed: 36897701
DOI: 10.1097/MD.0000000000033249 -
Pharmaceutics Feb 2023The antifungal ketoconazole, which is mainly used for dermal infections and treatment of Cushing's syndrome, is prone to drug-food interactions (DFIs) and is well known...
The antifungal ketoconazole, which is mainly used for dermal infections and treatment of Cushing's syndrome, is prone to drug-food interactions (DFIs) and is well known for its strong drug-drug interaction (DDI) potential. Some of ketoconazole's potent inhibitory activity can be attributed to its metabolites that predominantly accumulate in the liver. This work aimed to develop a whole-body physiologically based pharmacokinetic (PBPK) model of ketoconazole and its metabolites for fasted and fed states and to investigate the impact of ketoconazole's metabolites on its DDI potential. The parent-metabolites model was developed with PK-Sim and MoBi using 53 plasma concentration-time profiles. With 7 out of 7 (7/7) DFI AUC and DFI C ratios within two-fold of observed ratios, the developed model demonstrated good predictive performance under fasted and fed conditions. DDI scenarios that included either the parent alone or with its metabolites were simulated and evaluated for the victim drugs alfentanil, alprazolam, midazolam, triazolam, and digoxin. DDI scenarios that included all metabolites as reversible inhibitors of CYP3A4 and P-gp performed best: 26/27 of DDI AUC and 21/21 DDI C ratios were within two-fold of observed ratios, while DDI models that simulated only ketoconazole as the perpetrator underperformed: 12/27 DDI AUC and 18/21 DDI C ratios were within the success limits.
PubMed: 36840001
DOI: 10.3390/pharmaceutics15020679 -
Journal of Thoracic Disease Jan 2023
PubMed: 36794143
DOI: 10.21037/jtd-22-1460 -
BMC Pharmacology & Toxicology Jan 2023Regulations have broadened to allow moderate sedation administration for gastrointestinal endoscopy by non-anesthesia personnel. The line between moderate and deep...
PURPOSE
Regulations have broadened to allow moderate sedation administration for gastrointestinal endoscopy by non-anesthesia personnel. The line between moderate and deep sedation is ambiguous. Deep sedation offers patient comfort as well as greater safety concerns. Unintended deep sedation can occur if drug interactions are overlooked. We present a pharmacodynamic model for moderate sedation using midazolam, alfentanil and propofol. The model is suitable for training and devising rationales for appropriate dosing.
METHODS
The study consists of two parts: modeling and validation. In modeling, patients scheduled for esophagogastroduodenoscopy (EGD) or colonoscopy sedation are enrolled. The modified observer's assessment of alertness/sedation (MOAA/S) score < 4 is defined as loss of response to represent moderate sedation. Two patient groups receiving bronchoscopy or endoscopic retrograde cholangiopancreatography (ERCP) are used for validation. Model performance is assessed by receiver operating characteristic (ROC) curves and area under the curve (AUC). Simulations are performed to demonstrate how the model is used to rationally determine drug regimen for moderate sedation.
RESULTS
Interaction between propofol and alfentanil is stronger than the other pairwise combinations. Additional synergy is observed with three drugs. ROC AUC is 0.83 for the modeling group, and 0.96 and 0.93 for ERCP and bronchoscopy groups respectively. Model simulation suggests that 1 mg midazolam, 250 µg alfentanil and propofol maximally benefits from drug interactions and suitable for moderate sedation.
CONCLUSION
We demonstrate the accurate prediction of a three-drug response surface model for moderate sedation and simulation suggests a rational dosing strategy for moderate sedation with midazolam, alfentanil and propofol.
Topics: Humans; Midazolam; Alfentanil; Propofol; Conscious Sedation; Endoscopy, Gastrointestinal
PubMed: 36647160
DOI: 10.1186/s40360-023-00642-5 -
La Tunisie MedicaleCataract is a ubiquitous pathology. Its prevalence increases with age. Nowadays, cataract surgery is increasingly performed on an outpatient basis under locoregional... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
Cataract is a ubiquitous pathology. Its prevalence increases with age. Nowadays, cataract surgery is increasingly performed on an outpatient basis under locoregional anesthesia. In this context, sedation-analgesia is essential but not without risks.
AIM
To evaluate the effectiveness of premedication with melatonin on intraoperative sedation-analgesia.
METHODS
This is a prospective randomized double-blind study including patients proposed for scheduled cataract surgery by phacoemulsification under peribulbar anesthetic block. The participants will be randomized into two groups: group (M) will receive 05 tablets of melatonin (10mg sublingual) and group (P) will receive 05 tablets of Sucralose sublingually. Perioperative sedation-analgesia will be evaluated by the Ramsey score, the bisectral index, the simple verbal scale (EVS) and by the perioperative consumption of midazolam and alfentanyl. Secondary endpoints will be the degree of preoperative anxiety (Amsterdam Preoperative, Anxiety and Information Scale), the perioperative tonus of the eyeball, intraoperative nicardepine consumption and patients and surgeons satisfaction. A value of p <0.05 will be considered statistically significant.
EXPECTED RESULTS
The administration of melatonin as a premedication for scheduled cataract surgery will allow a better quality of intraoperative sedationanalgesia, a reduction in the doses consumed of midazolam and alfentanyl, improves surgical conditions, leads to a decrease in ocular tone, and optimizes surgical safety conditions for the patient.
Topics: Humans; Midazolam; Melatonin; Double-Blind Method; Alfentanil; Prospective Studies; Premedication; Cataract
PubMed: 36571756
DOI: No ID Found