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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 -
Anaesthesia, Critical Care & Pain... Jun 2023Intraoperative monitoring of nociception has made great progress in adult anesthesia. However, pediatric data are scarce. The Nociception Level (NOL) is one of the most... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
Intraoperative monitoring of nociception has made great progress in adult anesthesia. However, pediatric data are scarce. The Nociception Level (NOL) is one of the most recent indexes of nociception. Its originality is that it provides a multiparametric assessment of nociception. In adults, NOL monitoring allowed lower perioperative opioid requirements, hemodynamic stability, and qualitative postoperative analgesia. So far, the NOL has never been used in children. Our objective was to validate the ability of NOL to provide a quantitative assessment of nociception in anesthetized children.
METHODS
In 5-12 years old children anesthetized with sevoflurane and alfentanil (10 µg kg), before surgical incision, we performed three standardized tetanic stimulations (5 s, 100 Hz) of different intensities (10-30-60 mA) in a randomized order. NOL, heart rate, blood pressure and Analgesia-Nociception Index variations were assessed after each stimulation.
RESULTS
Thirty children were included. Data were analyzed with a covariance pattern linear mixed regression model. NOL increased after the stimulations (p < 0.05 at each intensity). NOL response was influenced by stimulation intensity (p < 0.001). Heart rate and blood pressure were barely modified by the stimulations. Analgesia-Nociception Index decreased after the stimulations (p < 0.001 at each intensity). Analgesia-Nociception index response was not influenced by stimulation intensity (p = 0.064). NOL and Analgesia-Nociception Index responses were significantly correlated (Pearson r = 0.47; p < 0.001).
CONCLUSIONS
NOL allows a quantitative assessment of nociception under anesthesia in 5-12 years-old children. This study provides a solid basis for all future investigations on NOL monitoring in pediatric anesthesia.
REGISTRATION
NCT05233449.
Topics: Adult; Child; Child, Preschool; Humans; Analgesics, Opioid; Anesthesia; Heart Rate; Monitoring, Intraoperative; Nociception; Pain
PubMed: 36863410
DOI: 10.1016/j.accpm.2023.101207 -
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 -
Applied Spectroscopy May 2023Raman cross sections and spectra were measured for five synthetic opioid fentanyl analogs: fentanyl citrate, sufentanil citrate, alfentanil HCl, carfentanil oxalate, and...
Raman cross sections and spectra were measured for five synthetic opioid fentanyl analogs: fentanyl citrate, sufentanil citrate, alfentanil HCl, carfentanil oxalate, and remifentanil HCl. The measurements were performed with excitation wavelengths in the visible (532 nm) and near infrared (785 nm). In addition, density functional theory (DFT) calculations were employed to generate simulated spectra of the compounds and aid in identification of the observed spectral modes. These cross-section measurements and calculations were also used to assess results from a series of measurements of fentanyls cut with other powdered materials. These measurements are valuable for assessment of field-deployable Raman chemical sensors for detection of fentanyl and fentanyl analogs, including when mixed with other materials.
PubMed: 36792941
DOI: 10.1177/00037028231160565 -
Journal of Clinical Anesthesia Jun 2023In many countries, the combination of propofol and opioid is used as the preferred sedative regime during ERCP. However, the most serious risks of propofol sedation are... (Randomized Controlled Trial)
Randomized Controlled Trial
STUDY OBJECTIVE
In many countries, the combination of propofol and opioid is used as the preferred sedative regime during ERCP. However, the most serious risks of propofol sedation are oxygen deficiency and hypotension. Compared to midazolam, remimazolam has a faster onset and offset of hypnotic effect, as well as cardiorespiratory stability, and to achieve widespread acceptance for procedural sedation, remimazolam must replace propofol which is the most commonly used for procedural sedation. The objective of this study was to compare the safety and efficacy profiles of the remimazolam and propofol when combined with alfentanil for sedation during ERCP procedures.
DESIGN
A randomized, controlled, single-center trial.
SETTING
The Endoscopic Centre of Tianjin Nankai Hospital, China.
PATIENTS
518 patients undergoing elective ERCP under deep sedation.
INTERVENTIONS
Patients scheduled for ERCP were randomly assigned to be sedated with either a combination of remimazolam-alfentanil or propofol-alfentanil.
MEASUREMENTS
The primary outcome was the prevalence of hypoxia, which was defined as SpO < 90% for >10 s. Other outcomes were the need for airway maneuver, procedure, and sedation-related outcomes and side effects (e.g., nausea, vomiting, and cardiovascular adverse events).
MAIN RESULTS
A total of 518 patients underwent randomization. Of these, 250 were assigned to the remimazolam group and 255 to the propofol group. During ERCP, 9.6% of patients in the remimazolam group showed hypoxia, while in the propofol group, 15.7% showed hypoxia (p = 0.04). The need for airway maneuvering due to hypoxia was significantly greater in the propofol group (p = 0.04). Furthermore, patients sedated with remimazolam had a lower percentage of hypotension than patients sedated with propofol (p < 0.001). Patients receiving remimazolam sedation expressed higher satisfaction scores and were recommended the same sedation for the next ERCP. The procedure time in the remimazolam group was much longer than in the propofol group due to the complexity of the patient's disease, which resulted in a longer sedation time.
CONCLUSION
During elective ERCP, patients administered with remimazolam showed fewer respiratory depression events under deep sedation with hemodynamic advantages over propofol when administered in combination with alfentanil.
Topics: Humans; Propofol; Alfentanil; Cholangiopancreatography, Endoscopic Retrograde; Hypnotics and Sedatives; Hypoxia; Hypotension; Conscious Sedation
PubMed: 36764022
DOI: 10.1016/j.jclinane.2023.111077 -
Clinical Therapeutics Nov 2022Propofol infusion is a popular single drug of choice for sedation in the gastrointestinal endoscopy suite. Drug combinations are more beneficial than single-drug... (Randomized Controlled Trial)
Randomized Controlled Trial
PURPOSE
Propofol infusion is a popular single drug of choice for sedation in the gastrointestinal endoscopy suite. Drug combinations are more beneficial than single-drug regimens in gastroscopy sedation. However, the cardiopulmonary complications of propofol sedation raise concern. Remimazolam is a novel, ultra-short-acting benzodiazepine sedative, and alfentanil is a weak opioid. During endoscopic procedures, remimazolam is an effective and safe sedative procedure. No synergistic effect has been reported when remimazolam was combined with alfentanil in gastroscopy sedation. Here, we evaluated the effective dose, sedative efficacy, and safety of the remimazolam-alfentanil combination in gastroscopy sedation and compared the results with those of the propofol-alfentanil combination.
METHODS
This study was conducted in two parts. In Part 1, Dixon's up-and-down method (sequential distribution) was adopted for determining the 95% effective dose (ED95) (95% CI) and 95% CI of remimazolam combined with 5 µg/kg alfentanil. In Part 2, after obtaining the predictive remimazolam ED95, 161 patients were randomized into the remimazolam group (remimazolam-alfentanil) and the propofol group (propofol-alfentanil). The effectiveness of the drug combinations was measured according to successful sedation parameters. Changes in vital signs and the appearance of adverse events were used to assess the safety of drug combinations. Evaluation of patient and physician satisfaction was included as quality indicators of treatment.
RESULTS
Baseline demographic and clinical characteristics were comparable between the 2 parts of the study. The ED95 of remimazolam in inhibiting a positive response to gastroscopy placement into the pharyngeal cavity was 0.33 mg/kg (95% CI, 0.289 to 1.023). The procedure success rate was 97.53% in the remimazolam group and 97.50% in the propofol group. The difference in the success rate of the procedure between the remimazolam and propofol groups was 0.03% (95% CI, -2.5 to 2.4). However, the incidence of injection pain, hypotension, respiratory depression, and dizziness was lower in the remimazolam group compared with the propofol group (P < 0.05). Furthermore, patients from the propofol group were more likely to be drowsy, and their work efficiency was reduced the day after leaving the hospital, whereas patients in the remimazolam group were less affected (P < 0.05).
IMPLICATIONS
The ED95 of remimazolam was 0.33 mg/kg when it was combined with alfentanil (5 µg/kg) for gastroscopy sedation. The sedation strategy of remimazolam-alfentanil has noninferior efficacy, fewer adverse effects, and a better postoperative recovery process than propofol-alfentanil for patients undergoing gastroscopy. Chinese Clinical Trials Registry identifier: ChiCTR2100051565.
Topics: Humans; Alfentanil; Propofol; Gastroscopy; Benzodiazepines; Hypnotics and Sedatives; Double-Blind Method; Drug Combinations; Conscious Sedation
PubMed: 36763995
DOI: 10.1016/j.clinthera.2022.09.014