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Pharmaceuticals (Basel, Switzerland) May 2024Several commonly used opioid analgesics, such as fentanyl, sufentanil, alfentanil, and hydrocodone, are by report primarily metabolized by the CYP3A4 enzyme. The...
Several commonly used opioid analgesics, such as fentanyl, sufentanil, alfentanil, and hydrocodone, are by report primarily metabolized by the CYP3A4 enzyme. The concurrent use of ritonavir, a potent CYP3A4 inhibitor, can lead to significant drug interactions. Using physiologically based pharmacokinetic (PBPK) modeling and simulation, this study examines the effects of different dosing regimens of ritonavir on the pharmacokinetics of these opioids. The findings reveal that co-administration of ritonavir significantly increases the exposure of fentanyl analogs, with over a 10-fold increase in the exposure of alfentanil and sufentanil when given with ritonavir. Conversely, the effect of ritonavir on fentanyl exposure is modest, likely due to additional metabolism pathways. Additionally, the study demonstrates that the steady-state exposure of hydrocodone and its active metabolite hydromorphone can be increased by up to 87% and 95%, respectively, with concurrent use of ritonavir. The extended-release formulation of hydrocodone is particularly affected. These insights from PBPK modeling provide valuable guidance for optimizing opioid dosing and minimizing the risk of toxicity when used in combination with ritonavir-containing prescriptions.
PubMed: 38794210
DOI: 10.3390/ph17050640 -
Brazilian Journal of Anesthesiology... May 2024To explore the median effective dose (ED50) and 95% effective dose (ED95) of remimazolam besylate combined with alfentanil for adult gastroscopy.
BACKGROUND
To explore the median effective dose (ED50) and 95% effective dose (ED95) of remimazolam besylate combined with alfentanil for adult gastroscopy.
METHODS
This prospective studyenrolled 31 patients scheduled to painless gastroscopy at Anhui No. 2 Provincial People's Hospital between April and May, 2022. 5 µg.kg of alfentanil hydrochloride was used for pre-analgesia. The initial single loading dose of remimazolam besylate was 0.12 mg.kg, increased or reduced by 0.01 mg.kg for the next patient with modified Dixon sequential method. The modified Observer's Assessment of Alertness/Sedation Scale (MOAA/S) was used to assess sedation.
RESULTS
Combined with alfentanil, the ED50 of remimazolam besylate was 0.147 mg.kg (95% CI: 0.138-0.160 mg.kg) and ED95 0.171 mg.kg (95% CI: 0.159-0.245 mg.kg). The induction time after injection of remimazolam besylate was 70 ± 25 s, with the anesthesia recovery time and the observation time in resuscitation room 5.13 ± 2.13 min and 2.32 ± 1.6 min, respectively. Twenty nine patients' vital signs were within acceptable limits during gastroscopy.
CONCLUSIONS
The ED50 of remimazolam besylate combined with alfentanil for painless gastroscopy was 0.147 mg.kg, and the ED95 was 0.171 mg.kg.
PubMed: 38789004
DOI: 10.1016/j.bjane.2024.844518 -
Drug Design, Development and Therapy 2024Cough is one of the most common complications following intravenous administration of sufentanil during anesthesia induction. The study aimed to investigate the... (Randomized Controlled Trial)
Randomized Controlled Trial Clinical Trial
BACKGROUND
Cough is one of the most common complications following intravenous administration of sufentanil during anesthesia induction. The study aimed to investigate the protective effect of alfentanil, afentanyl derivative with short onset time and short duration, in reducing sufentanil-induced cough.
PATIENTS AND METHODS
Eighty patients that scheduled for thyroid surgery under general anesthesia were randomly divided into the alfentanil group and normal saline group, with 40 cases per group. Patients in the alfentanil group received intravenous administration of 2 μg/kg alfentanil prior to sufentanil injection during general anesthesia induction, while the same dose of normal saline was administered in the normal saline group. The outcomes measures included the incidence and severity of cough and common side effects of opioids following the administration of sufentanil during the induction of general anesthesia, intraoperative hemodynamics parameters and major adverse events during anesthesia recovery period.
RESULTS
The incidence of cough within one minute after the injection of sufentanil during anesthesia induction was 40% in the normal saline group, and the pretreatment of alfentanil significantly reduced the incidence of sufentanil-induced cough to 5% (p < 0.05). Correspondingly, the patients in the alfentanil group had decreased severity of sufentanil-induced cough compared with the normal saline group (p < 0.05). No significant differences in the incidences of common side effects of opioids (dizziness, nausea and vomiting, chest tightness and respiratory depression) within one minute after sufentanil injection were found (p > 0.05). Furthermore, there were no significant differences between the two groups in intraoperative hemodynamic parameters, extubation time, or the incidences of emergence agitation, respiratory depression, delayed recovery from anesthesia and postoperative nausea and vomiting during Postanesthesia Care Unit stay (p > 0.05).
CONCLUSION
Pretreatment with low-dose alfentanil (2 μg/kg) effectively and safely reduced both the incidence and severity of sufentanil-induced cough during anesthesia induction.
CLINICAL TRIAL REGISTRATION NUMBER
Chinese Clinical Trial Registry (identifier: ChiCTR2300069286).
Topics: Alfentanil; Humans; Sufentanil; Cough; Male; Double-Blind Method; Female; Adult; Prospective Studies; Middle Aged; Dose-Response Relationship, Drug; Analgesics, Opioid; Anesthesia, General
PubMed: 38774482
DOI: 10.2147/DDDT.S464823 -
BMC Anesthesiology May 2024Compared to midazolam, remimazolam has a faster onset and offset of hypnotic effect, as well as cardiorespiratory stability, this study aims to determine the 90%... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Compared to midazolam, remimazolam has a faster onset and offset of hypnotic effect, as well as cardiorespiratory stability, this study aims to determine the 90% effective dose (ED90) of remimazolam to inhibit responses to insertion of a duodenoscope during endoscopic retrograde cholangiopancreatography (ERCP).
METHODS
A dose-response study was carried out undergoing ERCP who received remimazolam-alfentanil anesthesia using 10 µg/kg of alfentanil between September 2021 and November 2021. The initial dose of remimazolam was 0.2 mg/kg. The dose was then decided based on the responses of earlier patients by exploiting the sequential ascend and descend according to a 9: 1 biased coin design. Upon failure, the dose of remimazolam was increased by 0.025 mg/kg in the next patient. When the insertion was successful, the succeeding patient was randomized to an identical dose or a dose that was lower by 0.025 mg/kg.The ED90 of remimazolam for inhibiting responses to the insertion of a duodenoscope during ERCP was calculated. Adverse events and complications of remimazolam were recorded.
RESULTS
A total of 55 elderly patients (age > 65) were included in the study. 45 successfully anesthetized patients, and 10 unsuccessfully. The ED90 of remimazolam was 0.300 mg/kg (95% CI = 0.287-0.320). ED95 was 0.315 (95% CI = 0.312-0.323) and ED99 was 0.323 (95% CI = 0.323-0.325). Among the patients, 9 patients developed hypotension, 2 patients developed bradycardia and 1 patient developed tachycardia, and hypoxia occurred in 2 patients.
CONCLUSIONS
A loading dose of 0.300 mg / kg of remimazolam for elderly patients undergoing ERCP can safely, effectively, and quickly induce patients to fall asleep and inhibit responses to the insertion of a duodenoscope.
TRIAL REGISTRATION
The study protocol was registered at the website ClinicalTrials.gov on 22/09/2021(NCT05053763).
Topics: Humans; Cholangiopancreatography, Endoscopic Retrograde; Male; Female; Hypnotics and Sedatives; Duodenoscopes; Dose-Response Relationship, Drug; Aged; Alfentanil; Middle Aged; Benzodiazepines
PubMed: 38745175
DOI: 10.1186/s12871-024-02554-1 -
Medicine Apr 2024Remimazolam is a novel, ultrashort-acting benzodiazepine. This study aimed to compare the efficacy and safety of remimazolam and propofol for hysteroscopic examination,... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Remimazolam is a novel, ultrashort-acting benzodiazepine. This study aimed to compare the efficacy and safety of remimazolam and propofol for hysteroscopic examination, to determine the optimal dose of remimazolam combined with alfentanil for painless hysteroscopy, and to calculate its median effective dose (ED50).
METHODS
Step 1: A total of 208 patients undergoing hysteroscopic examination were prospectively included in this study. Patients were randomized into 4 groups: 0.2 mg/kg remimazolam (group A), 0.25 mg/kg remimazolam besylate (group B), 0.3 mg/kg remimazolam (group C), and 2 mg/kg propofol (group D), with 52 patients in each group. One minute after losing consciousness, patients received an intravenous injection of alfentanil at 5 µg/kg, followed by a continuous infusion of alfentanil at 0.5 µg/kg/min. If patients showed frowning, movement, or MOAA/S > 1, sedatives were added: 0.05 mg/kg/dose of remimazolam for groups A, B, and C, and 0.5 mg/kg/dose of propofol for group D. Step 2: Dixon's up-and-down method was used to calculate the ED50 of remimazolam combined with alfentanil during hysteroscopic examination.
MAIN RESULTS
The sedation success rates of the remimazolam groups were 88.46%, 94.23%, and 98.08%, respectively, compared to 96.15% in the propofol group, with no significant difference (P = .175). MAP in groups A and B was higher than in group D (P < .05), and significantly higher in group C than in group D (P = .0016). SpO2 values in groups A, B, and C were higher than in group D at T2 to T3 (P < .001). HR in groups A, B, and C was significantly higher than in group D (P < .001). The ED50 of remimazolam combined with alfentanil in hysteroscopy was 0.244 mg/kg, 95%CI (0.195-0.22) and ED95 was 0.282 mg/kg, 95%CI (0.261-1.619).
CONCLUSION
In hysteroscopy, the sedative effect of remimazolam is like that of propofol, with 0.25 mg/kg remimazolam showing better safety and efficacy, and less impact on the respiratory and circulatory systems. Additionally, under the influence of alfentanil, the ED50 of remimazolam in hysteroscopy is 0.244 mg/kg, with no severe adverse reactions observed.
Topics: Humans; Alfentanil; Propofol; Prospective Studies; Single-Blind Method; Benzodiazepines; Hypnotics and Sedatives
PubMed: 38608088
DOI: 10.1097/MD.0000000000037627 -
BMC Gastroenterology Apr 2024Proper sedation of patients, particularly elderly individuals, who are more susceptible to sedation-related complications, is of significant importance in endoscopic...
BACKGROUND
Proper sedation of patients, particularly elderly individuals, who are more susceptible to sedation-related complications, is of significant importance in endoscopic retrograde cholangiopancreatography (ERCP). This study aims to assess the safety and efficacy of a low-dose combination of midazolam, alfentanil, and propofol for deep sedation in elderly patients undergoing ERCP, compared to a group of middle-aged patients.
METHODS
The medical records of 610 patients with common bile duct stones who underwent elective ERCP under deep sedation with a three-drug regimen, including midazolam, alfentanil, and propofol at Shandong Provincial Third Hospital from January 2023 to September 2023 were retrospectively reviewed in this study. Patients were categorized into three groups: middle-aged (50-64 years, n = 202), elderly (65-79 years, n = 216), and very elderly (≥ 80 years, n = 192). Intraoperative vital signs and complications were compared among these groups.
RESULTS
The three groups showed no significant difference in terms of intraoperative variation of systolic blood pressure (P = 0.291), diastolic blood pressure (P = 0.737), heart rate (P = 0.107), peripheral oxygen saturation (P = 0.188), bispectral index (P = 0.158), and the occurrence of sedation-related adverse events including hypotension (P = 0.170) and hypoxemia (P = 0.423).
CONCLUSION
The results suggest that a low-dose three-drug regimen consisting of midazolam, alfentanil, and propofol seems safe and effective for deep sedation of elderly and very elderly patients undergoing ERCP procedures. However, further studies are required to verify these findings and clarify the benefits and risks of this method.
Topics: Aged; Middle Aged; Humans; Propofol; Midazolam; Alfentanil; Cholangiopancreatography, Endoscopic Retrograde; Hypnotics and Sedatives; Deep Sedation; Retrospective Studies; Conscious Sedation
PubMed: 38566038
DOI: 10.1186/s12876-024-03197-9 -
Medicine Mar 2024To date, there is no standardized practice for the use of pharmacological sedatives during flexible bronchoscopy, particularly for elderly patients. This exploratory... (Randomized Controlled Trial)
Randomized Controlled Trial
Bolus administration of remimazolam was superior to midazolam for deep sedation in elderly patients undergoing diagnostic bronchoscopy: A randomized, double-blind, controlled trial.
BACKGROUND
To date, there is no standardized practice for the use of pharmacological sedatives during flexible bronchoscopy, particularly for elderly patients. This exploratory study aimed to assess the efficacy and safety of remimazolam at a single induced dose for deep sedation in elderly patients undergoing diagnostic flexible bronchoscopy (DFB), and compare with midazolam, a commonly used sedative.
METHODS
A total of 100 elderly patients (age range 65-80 yr; American Society of Anesthesiologists Physical Status I-III) undergoing DFB were randomly allocated into 2 groups according to the sedatives used for induction: the remimazolam group and the midazolam group. Sedation induction was initiated by an intravenous bolus of remimazolam (0.135 mg/kg) or midazolam (0.045 mg/kg), respectively, both groups were combined with a high-dose of alfentanil (18 µg/kg), and supplemented with high-flow nasal cannula (HFNC) oxygen supply at a flow rate of 45 L/min. If the target depth of sedation was not achieved, propofol would be titrated as a rescue. The primary outcome was the success rate of sedation at a single induced dose to achieve target depth (Ramsay sedation score [RSS] = 4) during induction, intraoperative changes in vital signs, postoperative follow-up situation and incidence of post-bronchoscopy adverse events were evaluated as secondary outcomes.
RESULTS
The success rate of sedation in the remimazolam group was significantly higher than that in the midazolam group (65.2% vs 39.6%, P = .013), while the incidence of extra sleep within 6 hours after procedure was lower in the remimazolam group as compared to the midazolam group (10.9% vs 31.3%, P = .016). No statistically significant differences were observed between the 2 groups regarding hemodynamic fluctuations, incidence of hypoxemia, and cough response during the procedure, as well as postoperative recall, willingness to undergo reexamination, and other post-bronchoscopy adverse events.
CONCLUSIONS
Bolus administration of remimazolam offers advantages over midazolam for deep sedation in elderly patients undergoing DFB, in terms of a higher success rate of sedation and a lower incidence of extra sleep within 6 hours after procedure, though the safety profiles of both groups were favorable.
Topics: Humans; Aged; Aged, 80 and over; Midazolam; Bronchoscopy; Deep Sedation; Benzodiazepines; Hypnotics and Sedatives; Propofol; Double-Blind Method
PubMed: 38518001
DOI: 10.1097/MD.0000000000037215 -
Drug Design, Development and Therapy 2024To evaluate the effect of flumazenil antagonizing remimazolam on postoperative nausea and vomiting (PONV) after gynecologic day surgery. (Randomized Controlled Trial)
Randomized Controlled Trial
PURPOSE
To evaluate the effect of flumazenil antagonizing remimazolam on postoperative nausea and vomiting (PONV) after gynecologic day surgery.
PATIENTS AND METHODS
141 cases of gynaecological daycase surgery patients in Weifang People's Hospital were selected, randomized into group F (flumazenil group, 71 cases) and group C (control group, 70 cases). Dexamethasone 5 mg, flurbiprofen axetil 50 mg, and droperidol 1 mg were given intravenously before induction of anesthesia in both groups. Anesthesia induction: Remimazolam 0.25mg / kg was injected within 1 minute. After the patient fell asleep, mivacurium chloride 0.2mg / kg was injected for 30 seconds and alfentanil 20ug / kg was injected for 30 seconds. Anesthesia maintenance: Remimazolam 1mg/kg/h and alfentanil 40ug/kg/h were continuously pumped by micro pump. Stopping the injection of remimazolam and alfentanil at the end of the operation. Flumazenil 0.2 mg was given to antagonize remimazolam in group F after 1 minute. Group C was given an equal volume of saline. The incidence of PONV in the postoperative PACU and over a 24-hour period, patient awakening time, and general patient information were recorded.
RESULTS
The incidence of PONV in both groups within 24 hours was 50.70% in group F was significantly higher than 32.86% in group C. The difference was statistically significant (P < 0.05). The incidence of PONV in the PACU was 5.6% in group F and 8.6% in group C. The difference was not statistically significant (p > 0.05).
CONCLUSION
Flumazenil antagonism of remimazolam increases the incidence of PONV within 24 hours in gynecologic day surgery patients and has no significant effect on the incidence of PONV in the PACU.
Topics: Female; Humans; Alfentanil; Ambulatory Surgical Procedures; Antiemetics; Benzodiazepines; Flumazenil; Gynecologic Surgical Procedures; Postoperative Nausea and Vomiting
PubMed: 38465267
DOI: 10.2147/DDDT.S444313 -
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 -
Pharmacogenomics and Personalized... 2024The polymorphism of the gene coding mu-opioid receptor () is one of the factors contributing to the variability in the response to opioid analgesics in children. The...
INTRODUCTION
The polymorphism of the gene coding mu-opioid receptor () is one of the factors contributing to the variability in the response to opioid analgesics in children. The goal of this study is to investigate its role in association with postoperative acute pain in children of various ages.
METHODS
This prospective study analyzed 110 pediatric patients, after plastic or orthopedic surgery, who were genotyped and randomly assigned to receive fentanyl or alfentanil. Postoperative pain was rated using Numerical Rating Scale (0-10). All the patients were genotyped for () gene polymorphism.
RESULTS
School children under the age of 11 with the genotype were shown to have a higher BMI (p<0.05). Children over the age of 12 carrying G allele , had increased postoperative pain sensitivity and intensity (3.28±1.95 vs 4.91±2.17; p<0.05), as compared to allele carriers.
DISCUSSION
polymorphism may explain the variation in the perception of postoperative pain in children over the age of 12 and may be a useful predictor for adjusting the dose of analgesics, but the dose is relative to the patient's needs regardless of his genetic characteristics. In younger children, carriers of polymorphic allele may be protected from obesity, due to diminished expression.
PubMed: 38313794
DOI: 10.2147/PGPM.S443035