-
Clinical Pharmacokinetics Feb 2018Fentanyl and its derivatives sufentanil, alfentanil, and remifentanil are potent opioids. A comprehensive review of the use of fentanyl and its derivatives in the... (Review)
Review
Fentanyl and its derivatives sufentanil, alfentanil, and remifentanil are potent opioids. A comprehensive review of the use of fentanyl and its derivatives in the pediatric population was performed using the National Library of Medicine PubMed. Studies were included if they contained original pharmacokinetic parameters or models using established routes of administration in patients younger than 18 years of age. Of 372 retrieved articles, 44 eligible pharmacokinetic studies contained data of 821 patients younger than 18 years of age, including more than 46 preterm infants, 64 full-term neonates, 115 infants/toddlers, 188 children, and 28 adolescents. Underlying diagnoses included congenital heart and pulmonary disease and abdominal disorders. Routes of drug administration were intravenous, epidural, oral-transmucosal, intranasal, and transdermal. Despite extensive use in daily clinical practice, few studies have been performed. Preterm and term infants have lower clearance and protein binding. Pharmacokinetics was not altered by chronic renal or hepatic disease. Analyses of the pooled individual patients' data revealed that clearance maturation relating to body weight could be best described by the Hill function for sufentanil (R = 0.71, B 876 mL/min, K 16.3 kg) and alfentanil (R = 0.70, B 420 mL/min, K 28 kg). The allometric exponent for estimation of clearance of sufentanil was 0.99 and 0.75 for alfentanil clearance. Maturation of remifentanil clearance was described by linear regression to bodyweight (R = 0.69). The allometric exponent for estimation of remifentanil clearance was 0.76. For fentanyl, linear regression showed only a weak correlation between clearance and bodyweight in preterm and term neonates (R = 0.22) owing to a lack of data in older age groups. A large heterogeneity regarding study design, clinical setting, drug administration, laboratory assays, and pharmacokinetic estimation was observed between studies introducing bias into the analyses performed in this review. A limitation of this review is that pharmacokinetic data, based on different modes of administration, dosing schemes, and parameter estimation methods, were combined.
Topics: Adolescent; Alfentanil; Analgesics, Opioid; Body Weight; Child; Child, Preschool; Fentanyl; Humans; Infant; Infant, Newborn; Linear Models; Models, Biological; Remifentanil; Sufentanil
PubMed: 28688027
DOI: 10.1007/s40262-017-0569-6 -
Current Clinical Pharmacology 2019Opioid analgesics are commonly used along with propofol during general anesthesia. Due to the dearth of data on the quality of anesthesia achieved with this combination,... (Comparative Study)
Comparative Study Meta-Analysis
Comparison of Fentanyl, Remifentanil, Sufentanil and Alfentanil in Combination with Propofol for General Anesthesia: A Systematic Review and Meta-analysis of Randomized Controlled Trials.
BACKGROUND
Opioid analgesics are commonly used along with propofol during general anesthesia. Due to the dearth of data on the quality of anesthesia achieved with this combination, the present meta-analysis was carried out.
METHODS
Electronic databases were searched for appropriate studies using a suitable search strategy. Randomized clinical trials comparing the combination of remifentanil/sufentanil/alfentanil with propofol with fentanyl and propofol, were included. The outcome measures were as follows: total propofol dose to achieve the desired general anesthesia; time of onset and duration of general anesthesia; depth of general anesthesia; and recovery time (time for eye-opening and time taken for extubation). Risk of bias was assessed and Forest plots were generated for eligible outcomes. The weighted mean difference [95% confidence intervals] was used as the effect estimate.
RESULTS
Fourteen studies were included in the systematic review and 13 were included in the metaanalysis. Statistically significant differences were observed for remifentanil in comparison to fentanyl when combined with propofol: Propofol dose (in mg) -76.18 [-94.72, -57.64]; time of onset of anesthesia (min) -0.44 [-0.74, -0.15]; time taken for eye-opening (min) -3.95 [-4.8, -3.1]; and time for extubation (min) -3.53 [-4.37, -2.7]. No significant differences were observed for either sufentanil or alfentanil about the dose of propofol required and due to scanty data, pooling of the data could not be attempted for other outcome measures for either sufentanil or alfentanil.
CONCLUSION
To conclude, we found that remifentanil has a statistically significant anesthetic profile than fentanyl when combined with propofol. Scanty evidence for both alfentanil and sufentanil precludes any such confirmation.
Topics: Alfentanil; Anesthesia, General; Anesthesia, Intravenous; Anesthetics, Intravenous; Fentanyl; Humans; Propofol; Randomized Controlled Trials as Topic; Remifentanil; Sufentanil
PubMed: 30868958
DOI: 10.2174/1567201816666190313160438 -
CPT: Pharmacometrics & Systems... Oct 2018According to current US Food and Drug Administration (FDA) and European Medicines Agency (EMA) guidance documents, physiologically based pharmacokinetic (PBPK) modeling...
According to current US Food and Drug Administration (FDA) and European Medicines Agency (EMA) guidance documents, physiologically based pharmacokinetic (PBPK) modeling is a powerful tool to explore and quantitatively predict drug-drug interactions (DDIs) and may offer an alternative to dedicated clinical trials. This study provides whole-body PBPK models of rifampicin, itraconazole, clarithromycin, midazolam, alfentanil, and digoxin within the Open Systems Pharmacology (OSP) Suite. All models were built independently, coupled using reported interaction parameters, and mutually evaluated to verify their predictive performance by simulating published clinical DDI studies. In total, 112 studies were used for model development and 57 studies for DDI prediction. 93% of the predicted area under the plasma concentration-time curve (AUC) ratios and 94% of the peak plasma concentration (C ) ratios are within twofold of the observed values. This study lays a cornerstone for the qualification of the OSP platform with regard to reliable PBPK predictions of enzyme-mediated and transporter-mediated DDIs during model-informed drug development. All presented models are provided open-source and transparently documented.
Topics: ATP Binding Cassette Transporter, Subfamily B, Member 1; Alfentanil; Clarithromycin; Cytochrome P-450 CYP3A; Digoxin; Drug Interactions; Humans; Itraconazole; Midazolam; Models, Biological; Rifampin
PubMed: 30091221
DOI: 10.1002/psp4.12343 -
British Journal of Anaesthesia Nov 2022Rapid elimination of remifentanil facilitates application of intense opioid effect during general anaesthesia whilst maintaining prompt emergence. Interruptions in...
Rapid elimination of remifentanil facilitates application of intense opioid effect during general anaesthesia whilst maintaining prompt emergence. Interruptions in remifentanil supply mean clinicians must relearn titration of pharmacokinetically longer-acting opioids to achieve appropriate levels of opioid effect whilst maintaining acceptable recovery times. Opioid-free anaesthesia is achievable for many minor and intermediate surgical procedures for which remifentanil might have been used previously.
Topics: Humans; Remifentanil; Anesthetics, Intravenous; Alfentanil; Propofol; Piperidines; Analgesics, Opioid; Anesthesia, General
PubMed: 36057481
DOI: 10.1016/j.bja.2022.08.001 -
Contrast Media & Molecular Imaging 2022The efficacy and adverse reactions of remimazolam besylate (RB) in combination with alfentanil in patients with painless gastroscopy remain unclear. (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
The efficacy and adverse reactions of remimazolam besylate (RB) in combination with alfentanil in patients with painless gastroscopy remain unclear.
OBJECTIVE
The aim of the study is to observe the efficacy and adverse reactions of RB in combination with alfentanil in patients with painless gastroscopy RB.
METHODS
All patients were randomly divided into two groups: RB combined with the alfentanil group (research group) and propofol combined with the alfentanil group (control group). After full oxygen inhalation and electrocardiographic monitoring, the research group was given 10 g/Kg alfentanil + RB 0.2 mg/kg intravenously, and the control group was given 10 g/Kg alfentanil + propofol 1.5 mg/kg. If there is a clinical need, the research group was given 2.5 mg/additional RB, whereas the control group was treated with an additional 0.5 mg/kg propofol. Main outcome measures were as follows: The vital endpoints including diachronic changes in heart rate (HR), blood pressure (BP), respiratory rate (RR), blood oxygen saturation (SPO), end-expiratory carbon dioxide (etCO), IPI, modified observer's assessment of alert/sedation (MOAA/S), time-related endpoints, perioperative adverse events, endoscopy, and anesthesiologist satisfaction, and 24-hour follow-up of adverse reactions, IPI scores, and satisfaction were recorded.
RESULTS
The HR and BP of the patients in the research group and the control group decreased, with a greater decrease in the control group, and the difference was statistically significant ( < 0.05). The values of RR, PETCO, and IPI in the research group and the control group decreased to the lowest at 2-3 min but the decrease in the control group was more significant. Furthermore, there was no significant difference in the time from the completion of administration to 4 minutes of IPI and the total examination time, but the awakening time in the research group was slightly longer than that in the control group, and the difference was statistically significant ( < 0.05). The incidences of respiratory depression and hypotension during the operation were shown to be markedly smaller in the investigation relative to the control team, and the difference was statistically significant ( < 0.05), whereas the occurrence of cough, movements, and singultus was more common in the investigations, and the difference was statistically significant ( < 0.05). The results of the 24-hour follow-up showed that the adverse reactions such as nausea, dizziness, fatigue, abdominal pain, and abdominal distension were much less frequent in the study team, and the difference was statistically significant ( < 0.05), and the patient satisfaction was higher than in the control group, and the difference was statistically significant ( < 0.05). The regression results showed that age, sedative, and total dose of analgesia had significant effects on the results, and the covariance coefficient of sedative was 1.57 of IPI score in the research group higher than that of the control group.
CONCLUSIONS
RB combined with alfentanil can provide safe and effective sedation for patients undergoing painless gastroscopy. Compared with propofol, RB and alfentanil for injection can avoid large hemodynamic fluctuations and deep sedation, and have fewer adverse reactions. However, the cases involved in this study are all from a single-center data, which requires further multicenter research and conformation.
Topics: Humans; Alfentanil; Propofol; Single-Blind Method; Gastroscopy; Carbon Dioxide; Conscious Sedation; Hypnotics and Sedatives; Oxygen
PubMed: 36263002
DOI: 10.1155/2022/7102293 -
BMC Anesthesiology Feb 2022We aimed to determine the time interval between alfentanil and rocuronium administration, at a 50% probability of preventing pain-induced withdrawal movement from...
BACKGROUND
We aimed to determine the time interval between alfentanil and rocuronium administration, at a 50% probability of preventing pain-induced withdrawal movement from rocuronium injection (Time50).
METHODS
A total of 64 patients scheduled for general anesthesia were enrolled in this study (33 men and 31 women). Anesthesia was induced with target-controlled infusion of propofol, at an effect-site target concentration of 3 μg/mL. Then, alfentanil 15 μg/kg was injected for 30 s. After 60 s, rocuronium 0.6 mg/kg was administered to the first patient. The Dixon's up-and-down method was used to determine the time interval for each subsequent patient (interval of 5 s). Mean arterial pressure (MAP) and heart rate (HR) were recorded at three time points: T0, pre-induction; T1, before rocuronium injection; and T2, 1 min after rocuronium injection.
RESULTS
The Time50 ± standard deviation (SD) was 5.6 ± 3.7 s and 21.9 ± 5.6 s in the male and female patients, respectively. Based on the probit regression, the Time50 was 4.7 s (95% confidence interval [CI], 1.2-7.6 s) and 20.3 s (95% CI, 7.7-26.1 s) in the male and female patients, respectively. The Time95 was 10.6 s (95% CI, 7.7-25.3 s) and 35.0 s (95% CI, 28.1-95.5 s) in the male and female patients, respectively, with significantly higher values in females than in males (P < 0.001). Compared with the T0, MAP and HR decreased significantly at T1 and T2 in both groups.
CONCLUSION
The Time50 required for preventing rocuronium-induced withdrawal movement were 4.7 s and 20.3 s in male and female patients, respectively.
TRIAL REGISTRATION
This study was registered with the Chinese Clinical Trials Registry on April 7, 2021 (URL: http://www.chictr.org.cn . Registry number: ChiCTR2100045137 ) .
Topics: Adult; Alfentanil; Analgesics, Opioid; Arterial Pressure; Double-Blind Method; Female; Heart Rate; Humans; Male; Movement; Neuromuscular Nondepolarizing Agents; Pain; Prospective Studies; Rocuronium; Sex Factors; Time
PubMed: 35105302
DOI: 10.1186/s12871-022-01580-1 -
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 -
European Journal of Medical Research Jan 2021Intravenous opioids are administered for the management of visceral pain after laparoscopic surgery. Whether oxycodone has advantages over other opioids in the treatment... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Intravenous opioids are administered for the management of visceral pain after laparoscopic surgery. Whether oxycodone has advantages over other opioids in the treatment of visceral pain is not yet clear.
METHODS
In this study, the analgesic efficiency and adverse events of oxycodone and other opioids, including alfentanil, sufentanil, fentanyl, and morphine, in treating post-laparoscopic surgery visceral pain were evaluated. This review was conducted according to the methodological standards described in the Cochrane Handbook for Systematic Reviews of Interventions and the Preferred Reporting Items for Systematic Reviews and Meta-analysis statement. The PubMed, Embase, and Cochrane databases were searched in December 2019.
RESULTS
Ten studies were included in this review. The sample size was 695 participants. The results showed that compared with morphine and fentanyl, oxycodone had a more potent analgesic efficacy on the first day after laparoscopic surgery, especially during the first 0.5 h. There was no significant difference in sedation between the two groups. Compared to morphine and fentanyl, oxycodone was more likely to lead to dizziness and drowsiness. Overall, patient satisfaction did not differ significantly between oxycodone and other opioids.
CONCLUSIONS
Oxycodone is superior to other analgesics within 24 h after laparoscopic surgery, but its adverse effects should be carefully considered.
Topics: Alfentanil; Analgesics, Opioid; Fentanyl; Humans; Laparoscopy; Morphine; Oxycodone; Pain; Pain Management; Sufentanil
PubMed: 33422129
DOI: 10.1186/s40001-020-00463-w -
BMC Anesthesiology Jun 2023Although the operation time of hysteroscopy is short, the incidence of postoperative nausea and vomiting is high. The aim of this study was to compare the incidence of... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Although the operation time of hysteroscopy is short, the incidence of postoperative nausea and vomiting is high. The aim of this study was to compare the incidence of postoperative nausea and vomiting in hysteroscopy when remimazolam is combined with remifentanil or alfentanil.
METHODS
We conducted a randomized, controlled, double-blind trial. Patients undergoing hysteroscopy were recruited and randomly assigned to either the remimazolam-remifentanil (Group RR) or the remimazolam-alfentanil group (Group RA). All patients in the two groups were started with an induction dose of remimazolam besylate 0.2 mg/kg and then maintained with a dosage of 1.0 mg/kg/h. After induction with remimazolam besylate, in Group RR, remifentanil was infused using a target-controlled infusion system with a target concentration of 1.5 ng/ml and titrated throughout the procedure. In Group RA, infusion of alfentanil was started with an initial bolus dose of 20 µg/kg over 30 s and then maintained at an initial rate of 0.16 µg/kg/min. The primary observation outcome was the incidence rate of postoperative nausea and vomiting. The secondary observation outcomes were the time to awakening, the length of stay in the PACU, the total remimazolam dose and adverse effects, such as low SpO, bradycardia, hypotension and body movement.
RESULTS
A total of 204 patients were successfully included in this study. The incidence of postoperative nausea and vomiting in Group RR (2/102, 2.0%) was significantly lower than that in Group RA (12/102, 11.8%) (p < 0.05). There was no significant difference in the incidence of adverse events, such as low SpO, bradycardia, hypotension and body movement, between Groups RR and RA (p > 0.05).
CONCLUSIONS
Remimazolam-remifentanil causes less postoperative nausea and vomiting than remimazolam-alfentanil in hysteroscopy.
TRIAL REGISTRATION
Clinical trial registration number: ChiCTR2100044177. Full date of the first registration: 12/03/2021.
Topics: Humans; Female; Pregnancy; Postoperative Nausea and Vomiting; Alfentanil; Remifentanil; Bradycardia; Hysteroscopy; Hypotension
PubMed: 37308843
DOI: 10.1186/s12871-023-02164-3 -
Techniques in Coloproctology Aug 2012Colonoscopy is a proven method for bowel cancer screening and is often experienced as a painful procedure. Today, there are two main strategies to facilitate... (Review)
Review
Colonoscopy is a proven method for bowel cancer screening and is often experienced as a painful procedure. Today, there are two main strategies to facilitate colonoscopy. First, deep sedation results in satisfied patients but increases sedation-associated risks and raises costs for healthcare providers. Second, there is the advocacy for colonoscopies without any form of sedation. This might be an option for a special group of patients, but does not hold true for everybody. Following Moerman's hypothesis: "If pain is the crucial point, why do we need sedation?" this review shows the analgesic options for a painless procedure, increasing success rates without increasing risk of sedation. There are two agents, with the potential to be a nearly ideal analgesic agent for colonoscopy: alfentanil and nitrous oxide (N(2)O). Administration of either substance causes the patient to be comfortable yet alert and facilitates a short turnover. Advantages of these drugs include rapid onset and offset of action, analgesic and anxiolytic effects, ease of titration to desired level, rapid recovery, and an excellent safety profile.
Topics: Alfentanil; Analgesia; Analgesics, Non-Narcotic; Analgesics, Opioid; Colonoscopy; Humans; Nitrous Oxide; Pain; Pain Management
PubMed: 22669482
DOI: 10.1007/s10151-012-0834-5