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Drug Metabolism and Disposition: the... Nov 2021Fentanyl is an opioid analgesic used to treat obstetrical pain in parturient women through epidural or intravenous route, and unfortunately can also be abused by...
Fentanyl is an opioid analgesic used to treat obstetrical pain in parturient women through epidural or intravenous route, and unfortunately can also be abused by pregnant women. Fentanyl is known to cross the placental barrier, but how the route of administration and time after dosing affects maternal-fetal disposition kinetics at different stages of pregnancy is not well characterized. To address this knowledge gap, we developed a maternal-fetal physiologically based pharmacokinetic (mf-PBPK) model for fentanyl to evaluate the feasibility to predict the maternal and fetal plasma concentration-time profiles of fentanyl after various dosing regimens. As fentanyl is typically given via the epidural route to control labor pain, an epidural dosing site was developed using alfentanil as a reference drug and extrapolated to fentanyl. Fetal hepatic clearance of fentanyl was predicted from CYP3A7-mediated norfentanyl formation in fetal liver microsomes (intrinsic clearance = 0.20 ± 0.05 µl/min/mg protein). The developed mf-PBPK model successfully captured fentanyl maternal and umbilical cord concentrations after epidural dosing and was used to simulate the concentrations after intravenous dosing (in a drug abuse situation). The distribution kinetics of fentanyl were found to have a considerable impact on the time course of maternal:umbilical cord concentration ratio and on interpretation of observed data. The data show that mf-PBPK modeling can be used successfully to predict maternal disposition, transplacental distribution, and fetal exposure to fentanyl. SIGNIFICANCE STATEMENT: This study establishes the modeling framework for predicting the time course of maternal and fetal exposures of fentanyl opioids from mf-PBPK modeling. The model was validated based on fentanyl exposure data collected during labor and delivery after intravenous or epidural dosing. The results show that mf-PBPK modeling is a useful predictive tool for assessing fetal exposures to fentanyl opioid therapeutic regimens and potentially can be extended to other drugs of abuse.
Topics: Administration, Intravenous; Adult; Analgesia, Epidural; Analgesics, Opioid; Anesthesia, Epidural; Anesthesia, Obstetrical; Aryl Hydrocarbon Hydroxylases; Cytochrome P450 Family 2; Female; Fentanyl; Fetus; Humans; Infant, Newborn; Injections, Epidural; Liver; Maternal-Fetal Exchange; Microsomes, Liver; Models, Statistical; Predictive Value of Tests; Pregnancy; Tissue Distribution; Umbilical Cord
PubMed: 34407992
DOI: 10.1124/dmd.121.000612 -
Frontiers in Psychiatry 2023Postictal agitation (PIA) after electroconvulsive therapy (ECT) is a serious clinical problem estimated to occur in 7-36% of patients and recur in 19-54% of patients....
BACKGROUND
Postictal agitation (PIA) after electroconvulsive therapy (ECT) is a serious clinical problem estimated to occur in 7-36% of patients and recur in 19-54% of patients. PIA has the potential to cause dangerous situations for the patient and staff members aside from the financial impact. To date, it is unclear which pharmacological interventions should be used in the management of PIA. This study aimed to systematically review the (preventative) pharmacological treatment options for PIA after ECT.
METHOD
A systematic search was done in PubMed, EMBASE, PsycINFO, and Web of Science from inception until 10 November 2022. We included randomized trials with any pharmacological intervention or comparison and a predefined outcome measure on PIA. Studies that solely included patients with neurodegenerative disorders or stroke were excluded. Data quality was assessed with the RoB2 and GRADE. Meta-analysis was performed if possible. This study was registered on PROSPERO under CRD42021262323.
RESULTS
We screened 2,204 articles and included 14 studies. Dexmedetomidine was investigated in 10 studies. Alfentanil, lignocaine, esmolol, midazolam, propofol, ketamine, haloperidol, and diazepam were each studied in only one study. Meta-analysis revealed an OR of 0.45 (0.32-0.63), a moderate effect size, in favor of dexmedetomidine than placebo to prevent PIA with very low heterogeneity (I = 0%). The certainty of the evidence was moderate. The other interventions studied were all found to have low certainty of evidence.
CONCLUSION
For clinical practice, we believe that our results indicate that dexmedetomidine should be considered for the prevention of PIA in patients that have previously experienced PIA.
PubMed: 37151968
DOI: 10.3389/fpsyt.2023.1170931 -
European Review For Medical and... Jan 2024This study aimed at determining the optimal dose combination of alfentanil and propofol for outpatient abortion anesthesia. (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
This study aimed at determining the optimal dose combination of alfentanil and propofol for outpatient abortion anesthesia.
PATIENTS AND METHODS
The study was separated into two parts. In the first part, patients were to determine the median effective dose (ED50) and the 95% effective dose (ED95) of alfentanil in combination with 2.5 mg·kg-1 propofol to inhibit body movements during the abortion using the Dixon up-and-down sequential allocation method. In the second part, 170 patients were randomly divided into group C (2.0 mg·kg-1 propofol with alfentanil 12.16 μg·kg-1) and group E (2.5 mg·kg-1 propofol with its ED95) to compare the anesthetic effect. The primary outcome was the sedation level during general anesthesia. The secondary outcomes were circulation, respiratory complications, and postoperative recovery quality.
RESULTS
The ED50 and the ED95 values of alfentanil were 3.37 μg·kg-1 (95% CI: 2.58-3.97 μg·kg-1) and 4.68 μg·kg-1 (95% CI: 4.04-9.32 μg·kg-1). The frequency of deep sedation in group E was significantly higher than in group C (76.5% vs. 60%). Patients in group C showed more wakefulness even during the surgery (14.3% vs. 4.4%). The results of our exploratory analyses did not reveal differences in respiratory depression, circulatory depression, postoperative side effects, or recovery outcomes.
CONCLUSIONS
The combination of 2.5 mg·kg-1 propofol and 4.68 μg·kg-1 alfentanil produces a better sedative effect than the combination of 2.0 mg·kg-1 propofol and 12.16 μg·kg-1 alfentanil without increasing additional risks associated with anesthesia.
Topics: Pregnancy; Female; Humans; Propofol; Alfentanil; Outpatients; Prospective Studies; Double-Blind Method
PubMed: 38235864
DOI: 10.26355/eurrev_202401_34898 -
Minerva Surgery Dec 2023
Topics: Humans; Alfentanil; Hemodynamics; Anesthesia, General; Cough
PubMed: 35088992
DOI: 10.23736/S2724-5691.21.09341-2 -
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 -
Anaesthesia Feb 2023
Topics: Humans; Alfentanil; Remifentanil; Anesthetics, Intravenous; Propofol; Double-Blind Method
PubMed: 35921080
DOI: 10.1111/anae.15837 -
Drug Design, Development and Therapy 2024Remimazolam besylate is a novel ultra-short-acting benzodiazepine that is rapidly hydrolyzed to zolpidem propionic acid by tissue lipases. We designed this study to... (Randomized Controlled Trial)
Randomized Controlled Trial Comparative Study
Comparison of the Safety and Efficacy of Remimazolam Besylate versus Dexmedetomidine for Patients Undergoing Fiberoptic Bronchoscopy: A Prospective, Randomized Controlled Trial.
OBJECTIVE
Remimazolam besylate is a novel ultra-short-acting benzodiazepine that is rapidly hydrolyzed to zolpidem propionic acid by tissue lipases. We designed this study to compare the safety and efficacy of remimazolam besylate alfentanil versus dexmedetomidine-alfentanil for fiberoptic bronchoscopy (FB).
METHODS
One hundred and twenty patients undergoing FB into this prospective randomized controlled trial were divided into two groups. The anesthesia induction consisted of 6 mg/kg/h of remimazolam besylate in the RA group and 0.5 μg/kg of dexmedetomidine in the DA group. 1-2 mg/kg/h of remimazolam besylate or 0.2-0.7 µg/kg/h of dexmedetomidine were administered to maintain during FB. The lowest oxygen saturation, success rate of FB, hemodynamics, time metrics, bronchoscopy feasibility, drug dose requirements, patient and bronchoscopist satisfaction scores, occurrence of intraoperative awareness, number of patients willing to repeat FB with the same sedation regimen, and occurrence and severity of adverse events.
RESULTS
The lowest oxygen saturation during the FB was significantly higher in the RA group ( = 0.001). Compared with the variables in the DA group, peripheral oxygen saturation, systolic blood pressure, and diastolic blood pressure were significantly lower at T2 and T3 in the RA group ( < 0.05). Heart rates were significantly higher from T2 to T4 in the DA group ( < 0.05). More patients experienced bradycardia in the DA group ( = 0.041). Compared with time metrics in the DA group, the induction time, fully-alert time, and recovery room-leaving time were all significantly shorter in the RA group ( < 0.05). The bronchoscopy feasibility scores in the RA group were significantly lower at T2, whereas they were lower at T3 in the DA group ( < 0.05).
CONCLUSION
Remimazolam besylate is superior to dexmedetomidine when combined with alfentanil during FB, promoting faster patients' recovery, better operative conditions and respiratory stability with similar rates of occurrence and severity of adverse events.
Topics: Humans; Dexmedetomidine; Bronchoscopy; Prospective Studies; Male; Female; Middle Aged; Adult; Benzodiazepines; Hypnotics and Sedatives; Aged
PubMed: 38915861
DOI: 10.2147/DDDT.S460949 -
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 -
Journal of Anesthesia Jun 2024More literature studies have reported that alfentanil is safe and effective for labor analgesia. However, there is no unified consensus on the optimal dosage of... (Randomized Controlled Trial)
Randomized Controlled Trial
The 90% effective concentration of alfentanil combined with 0.075% ropivacaine for epidural labor analgesia: a single-center, prospective, double-blind sequential allocation biased-coin design.
PURPOSE
More literature studies have reported that alfentanil is safe and effective for labor analgesia. However, there is no unified consensus on the optimal dosage of alfentanil used for epidural analgesia. This study explored the concentration at 90% of minimum effective concentration (EC90) of alfentanil combined with 0.075% ropivacaine in patients undergoing epidural labor analgesia to infer reasonable drug compatibility and provide guidance for clinical practice.
METHODS
In this prospective, single-center, double-blind study, a total of 45 singleton term primiparas with vaginal delivery who volunteered for epidural labor analgesia were recruited. The first maternal was administered with 3 μg/mL alfentanil combined with 0.075% ropivacaine with the infusion of 10 mL of the mixture every 50 min at a background dose of 3 mL/h. In the absence of PCEA, a total of 15 mL of the mixture is injected per hour. The subsequent alfentanil concentration was determined on the block efficacy of the previous case, using an up-down sequential allocation with a bias-coin design. 30 min after epidural labor analgesia, the block of patient failed with visual analog score (VAS) > 3, the alfentanil concentration was increased in a 0.5 μg/mL gradient for the next patient, while the block was successful with VAS ≤ 3, the alfentanil concentration was remained or decreased in a gradient according to a randomized response list for the next patient. EC90 and 95% confidence interval were calculated by linear interpolation and prediction model with R statistical software.
RESULTS
In this study, the estimated EC90 of alfentanil was 3.85 μg/mL (95% confidence interval, 3.64-4.28 μg/mL).
CONCLUSION
When combined with ropivacaine 0.075%, the EC90 of alfentanil for epidural labor analgesia is 3.85 μg/mL in patients undergoing labor analgesia.
Topics: Humans; Ropivacaine; Female; Double-Blind Method; Alfentanil; Pregnancy; Analgesia, Epidural; Prospective Studies; Adult; Anesthetics, Local; Analgesia, Obstetrical; Analgesics, Opioid; Dose-Response Relationship, Drug; Pain Measurement
PubMed: 38441686
DOI: 10.1007/s00540-024-03322-8 -
Journal of Pain Research 2021After knee surgery, analgesia should be effective for mobilization and discharge. (Clinical Trial)
Clinical Trial
BACKGROUND
After knee surgery, analgesia should be effective for mobilization and discharge.
AIM OF THE STUDY
The primary objective of this study was to achieve the lowest effective analgesic concentration (MEC50 and MEC90) of ropivacaine for saphenous nerve block in arthroscopic meniscectomy. The secondary objective was to determine whether the block causes muscle weakness in the postoperative period.
METHODS
The study was randomized, comparative, and double-blind. Fifty-one patients between 18 and 65 years old of both sexes, ASA I or II, who underwent knee arthroscopic meniscectomy at São Domingos Hospital were included. Patients underwent saphenous nerve block with 10 mL of ropivacaine administered by using the up-and-down method. The ropivacaine concentration was determined based on the previous patient's response (a biased-coin up-down design sequential method). If a patient had a negative response, the concentration of ropivacaine was increased by 0.05% in the next patient; if the response was positive, the next patient was randomized to be administered the same concentration of ropivacaine or a 0.05% lower concentration. Successful block was defined as pain <4 during 6 h. Patients underwent general anesthesia with 30 µg/kg alfentanil and propofol and maintenance with propofol, and, if necessary, remifentanil was administered. Postoperative analgesia was complemented with dipyrone, and if necessary, tramadol (100 mg) could be used. The following parameters were assessed: the success of the block; pain intensity after 2, 4, and 6 h; the consumption of remifentanil; time to the first analgesic supplementation; percent of patients who needed analgesics during 6h; and muscle strength.
RESULTS
The MEC50 of ropivacaine was 0.36%, and the MEC90 was 0.477%. The block was successful in 45 patients.
CONCLUSION
Saphenous block with 10 mL of 0.36% ropivacaine provides adequate analgesia for outpatient meniscectomy.
PubMed: 33469356
DOI: 10.2147/JPR.S282286