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Pharmaceuticals (Basel, Switzerland) Aug 2022Intraocular pressure (IOP) is crucial to the well-being of eyes. During anesthesia, the administration of succinylcholine and endotracheal intubation are associated with... (Review)
Review
Intraocular pressure (IOP) is crucial to the well-being of eyes. During anesthesia, the administration of succinylcholine and endotracheal intubation are associated with an increase in IOP, which may be attenuated by short-acting opioids. However, the drug of choice among the commonly used short-acting opioids is unclear. This study aimed to evaluate the effects of fentanyl, sufentanil, alfentanil, and remifentanil on IOP measured after the administration of succinylcholine and after endotracheal intubation in patients undergoing general anesthesia. Five databases were searched. Randomized controlled trials (RCTs) that compared short-acting opioids and reported at least one of the clinical outcomes of interest were included. Nine RCTs with 357 patients were included. Remifentanil (1 μg kg) more effectively alleviated the increase in IOP than the placebo after the administration of succinylcholine [mean difference (MD) of IOP, -3.64; confidence interval (CI), -5.47 to -1.81 and after endotracheal intubation (MD, -9.71; CI, -11.91 to -7.51). Remifentanil (1 μg kg) ranked the best in terms of both attenuating the increase in IOP after the administration of succinylcholine [surface under the cumulative ranking curve (SUCRA), 0.91; normalized entropy (NE), 0.47; and after endotracheal intubation (SUCRA, 0.89; NE, 0.54) among all of the treatments. Remifentanil (1 μg kg) should be considered the drug of choice in the circumstances where increased IOP is a great concern.
PubMed: 36015137
DOI: 10.3390/ph15080989 -
BMC Anesthesiology Aug 2022Remimazolam is a newer benzodiazepine with properties of rapid onset, short duration of action, and fast recovery. Our study was to evaluate the effects of different... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Remimazolam is a newer benzodiazepine with properties of rapid onset, short duration of action, and fast recovery. Our study was to evaluate the effects of different doses of remimazolam combined with alfentanil in colonoscopic polypectomy.
METHODS
One hundred twenty patients were randomly divided into four groups: alfentanil and propofol (AP) group, alfentanil and remimazolam 0.1 mg/kg (AR1 group), 0.15 mg/kg (AR2 group), or 0.2 mg/kg (AR3 group). Patients in the four groups received alfentanil 10 μg/kg, followed by propofol 2 mg/kg and three dosages of remimazolam. Modified Observer's Assessment of Alertness and Sedation (MOAA/S) scale, heart rate (HR), oxygen saturation (SpO), respiratory rate (RR), bispectral index (BIS) values and mean arterial pressure (MAP) were collected at intervals of 5 min and analyzed at different time points: before anesthesia (T0), 5 min (T1), 10 min (T2), 15 min after anesthesia (T3) and at the end of surgery (T4). The average MAP was calculated utilizing the average of all MAP values. The primary outcome was the success rate of sedation. Secondary outcomes included time to full alert and adverse events.
RESULTS
The success rate of sedation was 100% among the four groups. The incidence of hypotension was significantly decreased (all P < 0.05) and the average MAP was higher in AR1-AR3 groups than AP group (all P < 0.001). None of the patients developed bradycardia or hypertension during surgery in all study groups. BIS values were higher (all P < 0.001) and the time to full alert was statistically shorter in AR1-AR3 groups (all P < 0.05) compared with the AP group. The MOAA/S score in AR1 was higher than AR2 (P < 0.05) and the AR3 group (P < 0.05) at T1 and BIS values in the AR1 group were significantly higher than AR3 group (P < 0.05) at T4.
CONCLUSIONS
Remimazolam combined with alfentanil have a non-inferior sedative effect than propofol during the colonoscopic polypectomy. Moreover, this combination of two short-acting drugs might be a safer alternative.
TRIAL REGISTRATION
The clinical trial was registered on (16/05/2021, ChiCTR2100046492).
Topics: Alfentanil; Benzodiazepines; Humans; Hypnotics and Sedatives; Propofol; Prospective Studies
PubMed: 35974309
DOI: 10.1186/s12871-022-01805-3 -
Medicine Aug 2022The efficacy of alfentanil supplementation for the sedation of bronchoscopy remains controversial. We conduct a systematic review and meta-analysis to explore the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The efficacy of alfentanil supplementation for the sedation of bronchoscopy remains controversial. We conduct a systematic review and meta-analysis to explore the influence of alfentanil supplementation on the sedation during bronchoscopy.
METHODS
We search PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases through December 2019 for randomized controlled trials (RCTs) assessing the effect of alfentanil supplementation versus placebo for the sedation during bronchoscopy. This meta-analysis is performed using the random-effect model.
RESULTS
Five RCTs are included in the meta-analysis. Overall, compared with control group for bronchoscopy, alfentanyl supplementation is associated with significantly reduced coughing scores (Std. MD = -0.55; 95% CI = -0.96 to -0.14; P = 0.009) and dose of propofol (Std. MD = -0.34; 95% CI = -0.64 to -0.04; P = 0.03), but reveals the increase in hypoxemia (RR = 1.56; 95% CI = 1.17 to 2.08; P = 0.002).
CONCLUSIONS
Alfentanyl supplementation benefits to reduce coughing scores and dose of propofol for bronchoscopy, but increases the incidence of hypoxemia. The use of alfentanyl supplementation for bronchoscopy should be with caution.
Topics: Humans; Alfentanil; Bronchoscopy; Cough; Dietary Supplements; Hypoxia; Propofol; Randomized Controlled Trials as Topic
PubMed: 35945737
DOI: 10.1097/MD.0000000000027401 -
Anaesthesia Feb 2023
Topics: Humans; Alfentanil; Remifentanil; Anesthetics, Intravenous; Propofol; Double-Blind Method
PubMed: 35921080
DOI: 10.1111/anae.15837 -
Anesthesiology Oct 2022Animal data suggest that the antidepressant and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor modulator tianeptine is able to prevent opioid-induced... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Animal data suggest that the antidepressant and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor modulator tianeptine is able to prevent opioid-induced respiratory depression. The hypothesis was that oral or intravenous tianeptine can effectively prevent or counteract opioid-induced respiratory depression in humans.
METHODS
Healthy male and female volunteers participated in two studies that had a randomized, double blind, placebo-controlled, crossover design. First, oral tianeptine (37.5-, 50-, and 100-mg doses with 8 subjects) pretreatment followed by induction of alfentanil-induced respiratory depression (alfentanil target concentration, 100 ng/ml) was tested. Primary endpoint was ventilation at an extrapolated end-tidal carbon dioxide concentration of 55 mmHg (V̇E55). Next, the ability of four subsequent and increasing infusions of intravenous tianeptine (target tianeptine plasma concentrations 400, 1,000, 1,500, and 2,000 ng/ml, each given over 15 min) to counteract remifentanil-induced respiratory depression was determined in 15 volunteers. Ventilation was measured at isohypercpania (baseline ventilation 20 ± 2 l/min). The primary endpoint was minute ventilation during the 60 min of tianeptine versus placebo infusion.
RESULTS
Alfentanil reduced V̇E55 to 13.7 (95% CI, 8.6 to 18.8) l/min after placebo pretreatment and to 17.9 (10.2 to 25.7) l/min after 50-mg tianeptine pretreatment (mean difference between treatments 4.2 (-11.5 to 3.0) l/min, P = 0.070). Intravenous tianeptine in the measured concentration range of 500 to 2,000 ng/ml did not stimulate ventilation but instead worsened remifentanil-induced respiratory depression: tianeptine, 9.6 ± 0.8 l/min versus placebo 15.0 ± 0.9 l/min; mean difference, 5.3 l/min; 95% CI, 2.5 to 8.2 l/min; P = 0.001, after 1 h of treatment.
CONCLUSIONS
Neither oral nor intravenous tianeptine were respiratory stimulants. Intravenous tianeptine over the concentration range of 500 to 2000 ng/ml worsened respiratory depression induced by remifentanil.
Topics: Alfentanil; Analgesics, Opioid; Antidepressive Agents, Tricyclic; Carbon Dioxide; Double-Blind Method; Female; Humans; Male; Remifentanil; Respiratory Insufficiency; Respiratory System Agents; Thiazepines; alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
PubMed: 35867853
DOI: 10.1097/ALN.0000000000004324 -
British Journal of Anaesthesia Dec 2022A fundamental concept in pharmacology is that increasing dose increases drug effect. This is the basis of anaesthetic titration: the dose is increased when increased...
BACKGROUND
A fundamental concept in pharmacology is that increasing dose increases drug effect. This is the basis of anaesthetic titration: the dose is increased when increased drug effect is desired and decreased when reduced drug effect is desired. In the setting of titration, the correlation of doses and observed drug effects can be negative, for example increasing dose reduces drug effect. We have termed this the drug titration paradox. We hypothesised that this could be explained, at least in part, by intrasubject variability. If the drug titration paradox is simply an artifact of pooling population data, then a mixed-effects analysis that accounts for interindividual variability in drug sensitivity should 'flip' the observed correlation, such that increasing dose increases drug effect.
METHODS
We tested whether a mixed-effects analysis could correctly reveal the underlying pharmacology using previously published data obtained during automatic feedback control of mean arterial pressure (MAP) with alfentanil (effect site concentration, Ce) during surgery. The relationship between MAP and Ce was explored with linear regression and a linear mixed-effects model.
RESULTS
A linear mixed-effects model did not identify the correct underlying pharmacology because of the presence of the titration paradox in the individual data.
CONCLUSIONS
The relationship between drug dose and drug effect must be determined under carefully controlled experimental conditions. In routine care, where the effect is profoundly influenced by varying clinical conditions and drugs are titrated to achieve the desired effect, it is nearly impossible to draw meaningful conclusions about the relationship between dose and effect.
Topics: Humans; Alfentanil; Anesthetics; Dose-Response Relationship, Drug
PubMed: 35863951
DOI: 10.1016/j.bja.2022.05.036 -
Paediatric Anaesthesia Oct 2022The protease inhibitor, ritonavir, is a strong inhibitor of CYP 3A. The drug is used for management of the human immunovirus and is currently part of an oral antiviral... (Review)
Review
The protease inhibitor, ritonavir, is a strong inhibitor of CYP 3A. The drug is used for management of the human immunovirus and is currently part of an oral antiviral drug combination (nirmatrelvir-ritonavir) for the early treatment of SARS-2 COVID-19-positive patients aged 12 years and over who have recognized comorbidities. The CYP 3A enzyme system is responsible for clearance of numerous drugs used in anesthesia (e.g., alfentanil, fentanyl, methadone, rocuronium, bupivacaine, midazolam, ketamine). Ritonavir will have an impact on drug clearances that are dependent on ritonavir concentration, anesthesia drug intrinsic hepatic clearance, metabolic pathways, concentration-response relationship, and route of administration. Drugs with a steep concentration-response relationship (ketamine, midazolam, rocuronium) are mostly affected because small changes in concentration have major changes in effect response. An increase in midazolam concentration is observed after oral administration because CYP 3A in the gastrointestinal wall is inhibited, causing a large increase in relative bioavailability. Fentanyl infusion may be associated with a modest increase in plasma concentration and effect, but the large between subject variability of pharmacokinetic and pharmacodynamic concentration changes suggests it will have little impact on an individual patient, especially when used with adverse effect monitoring. It has been proposed that drugs that have no or only a small metabolic pathway involving the CYP 3A enzyme be used during anesthesia, for example, propofol, atracurium, remifentanil, and the volatile agents. That anesthesia approach denies children of drugs with considerable value. It is better that the inhibitory changes in clearance of these drugs are understood so that rational drug choices can be made to tailor drug use to the individual patient. Altered drug dose, anticipation of duration of effect, timing of administration, use of reversal agents and perioperative monitoring would better behoove children undergoing anesthesia.
Topics: Alfentanil; Anesthesia; Antiviral Agents; Child; Cytochrome P-450 CYP3A; Drug Interactions; Enzyme Inhibitors; Humans; Ketamine; Midazolam; Protease Inhibitors; Ritonavir; Rocuronium; COVID-19 Drug Treatment
PubMed: 35842922
DOI: 10.1111/pan.14529 -
Spinal Cord Series and Cases Jul 2022Systematic review.
STUDY DESIGN
Systematic review.
OBJECTIVES
This systematic review evaluates all randomized clinical trials (RCTs) conducted on assessing the efficacy and safety of pharmacologic therapies for the treatment of Spinal Cord Injury (SCI)-associated pain.
METHODS
The PubMed/Medline, EMBASE, and Cochrane library online databases were searched from 1946 to May 2019 using specific search terms for SCI, pain, and RCTs meeting predetermined inclusion criteria. The efficacy outcome of interest was pain reduction, discontinuations, and adverse events (AEs).
RESULTS
Of 2746 records identified through database searching, 703 duplicates were deleted. 1814 were excluded, the full text of the remaining 230 articles was reviewed, and finally, 28 papers were selected for drafting. The most studied medications were pregabalin, gabapentin, amitriptyline, and ketamine. Pregabalin, gabapentin, and amitriptyline reduced VAS by more than 30%, and ketamine reduced VAS by 40%. Oxcarbazepine, lamotrigine, alfentanil, tramadol, and morphine added to clonidine, baclofen, and botulinum toxin type A (BTA) significantly reduced pain compared with placebo. On the other hand, valproate, levetiracetam, trazodone, and duloxetine did not significantly alleviate SCI-associated pain compared to placebo. The risks of AEs and discontinuations in anticonvulsants were the least, while it was highest in analgesics.
CONCLUSIONS
Studies of SCI-associated pain were few, small, heterogenic in measures and values, and did not allow quantitative comparisons of efficacy. However, available data suggested pregabalin and gabapentin led to a more marked reduction in SCI-associated pain with fewer AEs. Additional clinical studies are needed to assess the effect of established and novel management options.
Topics: Amitriptyline; Anticonvulsants; Gabapentin; Humans; Ketamine; Pain; Pregabalin; Spinal Cord Injuries
PubMed: 35788127
DOI: 10.1038/s41394-022-00529-3 -
Paediatric Drugs Jul 2022Emergence delirium can occur after general anesthesia in children. An intravenous infusion of alfentanil may reduce the incidence or severity of emergence delirium after... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Emergence delirium can occur after general anesthesia in children. An intravenous infusion of alfentanil may reduce the incidence or severity of emergence delirium after sevoflurane anesthesia.
OBJECTIVE
The study aimed to investigate the effects of alfentanil intravenous infusion on emergence delirium and other perioperative complications.
METHOD
This was a single-center, randomized, placebo-controlled, double-blind clinical trial. A total of 172 children undergoing ambulatory dental treatment were randomized into three groups. Alfentanil group Alf2 received 0.2 μg/kg/min of alfentanil for continuous infusion, alfentanil group Alf4 received 0.4 μg/kg/min alfentanil, and the saline group (group Sal) received a continuous infusion of normal saline, with the same volume as the two other groups, as a placebo. The incidence of emergence delirium (assessed by the Paediatric Anaesthesia Emergence Delirium [PAED] scale), hemodynamic parameters, and recovery characteristics were recorded during the recovery period. The Aono scale was also used to assess for emergence delirium. A WeChat applet was designed to facilitate a caregiver teleconsultation and to provide feedback on postoperative nausea and vomiting and any other complications after discharge.
RESULTS
The incidence of emergence delirium in group Alf2 (22.9%) and group Alf4 (21.1%) was significantly lower than that observed in the Sal group (48.3%). The PAED scores in group Alf2 (6.4 ± 3.5) and group Alf4 (5.8 ± 3.8) were significantly lower than those for group Sal (9.6 ± 5.1) (p < 0.01). Ten children in the Alf4 group needed manual ventilatory assistance to maintain end-tidal carbon dioxide (ETCO) < 55 mm; children in group Alf2 did not. There was no significant difference between the discharge time of groups Alf2 and Sal (31.2 ± 4.64 vs 30.5 ± 2.82 min; 0.659 [95% confidence interval {CI} -1.052 to 2.369], p = 0.643); the time to discharge of group Alf4 (35.16 ± 3.97 min) was significantly longer than that of groups Alf2 and Sal (p < 0.01). The incidence of nausea and vomiting was similar in the three groups. No other clinically relevant adverse events were observed.
CONCLUSIONS
Intravenous infusion of 0.2 μg/kg/min and 0.4 μg/kg/min alfentanil decreased the incidence of emergence delirium in the post-anesthesia care unit. The 0.2 μg/kg/min dose of alfentanil resulted in less respiratory depression and discharge delay than the 0.4 μg/kg/min alfentanil dose.
TRIAL REGISTRATION
Chinese Clinical Trial Registry (ChiCTR2100043320).
Topics: Alfentanil; Anesthesia Recovery Period; Anesthesia, General; Anesthetics, Inhalation; Child; Double-Blind Method; Emergence Delirium; Humans; Methyl Ethers
PubMed: 35698001
DOI: 10.1007/s40272-022-00510-5 -
Journal of Thoracic Disease May 2022In practice, the optimal dose of alfentanil that should be used when painless bronchoscopy is performed is unknown. The purpose of this study was to investigate the...
Estimation of the median effective dose and the 95% effective dose of alfentanil required to inhibit the bronchoscopy reaction during painless bronchoscopy with i-gel supraglottic airway device: an Up-and-Down Sequential Allocation Trial.
BACKGROUND
In practice, the optimal dose of alfentanil that should be used when painless bronchoscopy is performed is unknown. The purpose of this study was to investigate the effective dose of alfentanil in suppressing bronchoscopy responses to painless bronchoscopy with an i-gel supraglottic airway device.
METHODS
Patients aged 18-70 years, with American Society of Anesthesiologists (ASA) physical status I-II, who planned to undergo painless bronchoscopy were recruited for this study. Alfentanil was administered intravenously 2 minutes before propofol administration. The response to bronchoscopy was measured, including oxygen saturation (SPO) and changes in respiratory rhythm. The median effective dose of alfentanil (ED) required to alleviate responses to the bronchoscopy was calculated using Dixon's up-and-down method in the female and male groups. Probit analysis was used to generate a dose-response curve in each group.
RESULTS
A total of 48 patients were recruited for the study including 25 females and 23 males. The ED of alfentanil for suppressing responses to painless bronchoscopy in females and males was 13.68±4.75 and 17.96±3.45 µg/kg, respectively. The difference was not statistically significant between the two groups (P=0.078). Probit analysis showed the ED of alfentanil in female bronchoscopy was 12.4 µg/kg [95% confidence interval (CI): 4.5 to 17 µg/kg]. In men, the ED of alfentanil was 16.4 µg/kg (95% CI: 12.1 to 20.1 µg/kg). According to the probit analysis, the 95% effective dose (ED) of alfentanil was 22.4 µg/kg (95% CI: 17.5 to 67.3 µg/kg) in female bronchoscopy. In men, the ED of alfentanil was 23.3 µg/kg (95% CI: 19.8 to 46.2 µg/kg).
CONCLUSIONS
Our data suggest that there were no obvious differences between men and women in the effective dose of alfentanil in painless bronchoscopy.
PubMed: 35693612
DOI: 10.21037/jtd-22-412