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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 -
Prehospital Emergency Care Jun 2024Pain is a common symptom in prehospital emergency care and pain treatment in this context can be challenging. While previous research has assessed the use of morphine...
OBJECTIVES
Pain is a common symptom in prehospital emergency care and pain treatment in this context can be challenging. While previous research has assessed the use of morphine and other synthetic opioids for pain management in this setting, the evaluation of alfentanil is limited. The objective of this study was to evaluate the safety and effect of intravenous alfentanil when administered by ambulance nurses in prehospital emergency care.
METHODS
This retrospective observational study consecutively included patients suffering from pain, treated with alfentanil in a Swedish EMS service from September 2011 to 31 September 2022. Data regarding occurrence of adverse events (AE), serious adverse events (SAE) - were used for safety evaluation and pain scores with a visual analogue scale (VAS) before and after treatment were used for evaluation of pain treatment. These data were extracted from the electronic patients' medical records database for analysis. Univariate logistic regression analysis was used to identify significant predictors of AE following injection of alfentanil by nurses in prehospital emergency care.
RESULTS
During the evaluation period 17,796 patients received pain relief with alfentanil. Adverse events affected 2.5% of the patients, while serious adverse events were identified in 25 cases (0.01%). Out of the 5970 patients with a complete VAS score for pain, the median VAS score was 8 (IQR 3) before treatment and 4 (IQR 3) after treatment. The mean reduction in pain measured by VAS was -4.1 ± 2.6 from the time before, to the evaluation after alfentanil administration. The administration frequency increased during the first year up to a steady level during the later part of the evaluation period.
CONCLUSIONS
This study proposes that alfentanil represents a safe and efficacious alternative for addressing urgent pain relief within the prehospital emergency context. Alfentanil demonstrates efficacy in alleviating pain across various conditions, with a relatively low risk of adverse events or serious adverse events when administered cautiously.
PubMed: 38830199
DOI: 10.1080/10903127.2024.2363509 -
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... 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.
Topics: Humans; Alfentanil; Prospective Studies; Female; Male; Gastroscopy; Adult; Middle Aged; Benzodiazepines; Dose-Response Relationship, Drug; Hypnotics and Sedatives; Aged; Analgesics, Opioid; Young Adult
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
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: Adult; Female; Humans; Male; Middle Aged; Alfentanil; Analgesics, Opioid; Anesthesia, General; Cough; Dose-Response Relationship, Drug; Double-Blind Method; Prospective Studies; Sufentanil
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 -
Journal of Clinical Pharmacology May 2024The rapid growth in the use of pediatric physiologically based pharmacokinetic (PBPK) models, particularly for regulatory applications, has focused emphasis on model...
Prediction of Pediatric Pharmacokinetics for CYP3A4 Metabolized Drugs: Comparison of the Performance of Two Hepatic Ontogeny Within a Physiologically Based Pharmacokinetic Model.
The rapid growth in the use of pediatric physiologically based pharmacokinetic (PBPK) models, particularly for regulatory applications, has focused emphasis on model verification and ensuring system parameters are robust, including how these change with age. Uncertainty remains regarding the ontogeny of some enzymes and transporters, in this study 2 published ontogeny profiles for hepatic CYP3A4 were compared. Clinical pharmacokinetic data on 4 intravenously administered CYP3A4 substrates (alfentanil, fentanyl, midazolam, and sildenafil) used across the pediatric age range was collected from the literature. The PBPK models were verified in the adult population and then used to compare the Salem and a modified Upreti ontogeny profiles for CYP3A4 in terms of parent drug clearance and area under the curve from birth onward. Overall, the modified Upreti ontogeny profile resulted in 15 out of 17 age-related predictions within 2-fold and 12 out of 17 predictions within 1.5-fold ranges of observed values, for the Salem ontogeny these values were 12 out of 17 and 8 out of 17, respectively. The Upreti ontogeny profile performed better than Salem, average fold error and absolute average fold error were 1.14 and 1.35 compared to 1.56 and 1.90, respectively. Identifying the optimal CYP3A4 ontogeny is important for regulatory use of PBPK especially given the number of drugs cleared by this enzyme. This study broadens the evidence from previous studies that Upreti is more favorable than Salem, but further work is needed especially in the neonatal and early infant age range.
PubMed: 38696325
DOI: 10.1002/jcph.2452 -
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