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BMC Anesthesiology Jun 2022Remimazolam tosilate (HR7056, RT), a novel ultrashort-acting benzodiazepine, can be used for procedural sedation and general anaesthesia. However, few studies have... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Remimazolam tosilate (HR7056, RT), a novel ultrashort-acting benzodiazepine, can be used for procedural sedation and general anaesthesia. However, few studies have focused on the sedative effect of RT during gastrointestinal endoscopy in elderly patients. The purpose of this study is to compare the sedative effect of RT and propofol for gastrointestinal endoscopy in elderly patients.
METHODS
A total of 82 patients aged ≥65 years with an American Society of Anaesthesiologists (ASA) grade I-II and a body mass index (BMI) of 18.0 to 30.0 kg/m who were scheduled for gastrointestinal endoscopy from Jan 2021 to Aug 2021 were selected and randomly divided into a RT group and a propofol group. Alfentanil 5 μg/kg was used for analgesia in both groups. The RT group was given remimazolam tosilate 0.15 mg/kg with supplemental doses of 0.05 mg/kg as need, while the propofol group was given propofol 1.5 mg/kg with supplemental doses of 0.5 mg/kg. The supplemental doses were determined by the modified observational alertness/sedation assessment (MOAA/S) score and the patients' body movements. Sedative effects, such as the time to loss of consciousness (LOC) (MOAA/S score ≤ 1), successful sedation in one dose, number of supplemental doses after successful induction, and recovery time, were evaluated. Sedation-related side effects, such as injection pain, haemodynamic events and respiratory depression, were also noted. Postoperative nausea and vomiting (PONV), visual analogue scale (VAS) scores at rest, remedial analgesics, and dizziness or headache were recorded. In addition, patients' satisfaction and physician's satisfaction of the procedure were compared between the two groups.
RESULTS
Data from 77 patients were analysed. The success rate of sedation in both groups was 100%. The time to LOC (MOAA/S score ≤ 1) in the RT group was longer than that in the propofol group (20.7 ± 6.1s vs. 13.2 ± 5.2s, P < 0.001). There were fewer patients in the RT group reporting injection pain than that in the propofol group (0/39 vs. 5/38, P = 0.025). Haemodynamic events and respiratory depression in the RT group were less frequent than those in the propofol group ((6/39 vs. 17/38, P = 0.005), (2/39 vs. 9/38, P = 0.026), respectively). The number of supplemental doses after successful induction in the RT group was greater than that in the propofol group (4/9/11/13/1/1 vs. 8/4/18/6/2/0 requiring 0, 1, 2, 3, 4 or 5 supplemental doses, P = 0.014). The characteristics of the patients enrolled, postoperative parameters of the patients, and patients' and physician's satisfaction of the procedure were comparable in the two groups.
CONCLUSIONS
Compared with propofol, RT can be safely and effectively used for gastrointestinal endoscopy sedation in elderly patients, and the incidence of sedation-related adverse reactions, especially haemodynamic events and respiratory depression, is lower. When RT is used, the number of supplemental doses after successful induction may increase slightly.
TRIAL REGISTRATION
Chictr.org.cn ChiCTR2000040498. Retrospectively registered (date of registration: December 1, 2020).
Topics: Aged; Benzodiazepines; Endoscopy, Gastrointestinal; Humans; Hypnotics and Sedatives; Pain; Propofol; Prospective Studies; Respiratory Insufficiency
PubMed: 35689208
DOI: 10.1186/s12871-022-01713-6 -
ACS Omega May 2022The ongoing public health emergency of opioid use disorders (OUD) and overdose in the United States is largely driven by fentanyl and its related analogues and has...
The ongoing public health emergency of opioid use disorders (OUD) and overdose in the United States is largely driven by fentanyl and its related analogues and has resulted in over 75 673 deaths in 2021. Immunotherapeutics such as vaccines have been investigated as a potential interventional strategy complementary to current pharmacotherapies to reduce the incidence of OUD and opioid-related overdose. Given the importance of targeting structurally distinct fentanyl analogues, this study compared a previously established lead conjugate vaccine (F-CRM) to a series of novel vaccines incorporating haptens derived from alfentanil and acetylfentanyl (F), and evaluated their efficacy against drug-induced pharmacological effects in rats. While no vaccine tested provided significant protection against alfentanil, lead formulations were effective in reducing antinociception, respiratory depression, and bradycardia elicited by fentanyl, sufentanil, and acetylfentanyl. Compared with control, vaccination with F-CRM also reduced drug levels in the brain of rats challenged with lethal doses of fentanyl. These data further support investigation of F-CRM as a candidate vaccine against fentanyl and selected analogues.
PubMed: 35601290
DOI: 10.1021/acsomega.2c00820 -
Journal of Plastic Surgery and Hand... 2023This study of breast augmentations performed under local anesthesia with intercostal blocks and light sedation describes the outcomes and evaluates benefits and...
INTRODUCTION
This study of breast augmentations performed under local anesthesia with intercostal blocks and light sedation describes the outcomes and evaluates benefits and complications.
METHOD
From December 2005 until August 2019, 335 women consecutively underwent bilateral breast augmentation procedures. The anesthetic protocol consisted of an initial intravenous bolus of 1 mg midazolam and 0.25 mg alfentanil preoperatively. In 2017, this was changed to 2-4 mg midazolam intramuscularly, 1 mg midazolam intravenously, and 2.5 µg sufentanil intravenously. Intercostal blocks were injected at the midaxillary line into the intercostal spaces two to seven. The operating field was infiltrated with tumescent local anesthesia. Retrospective data extraction from patients' medical charts was done, registering demographics, dosage of anesthesia, surgical characteristics, complications, and reoperation rates.
RESULTS
Two hundred and eighty-one women underwent primary augmentation and 54 had implant replacement. The most common complications included suboptimal cosmetic results, asymmetry, and healing-related problems. The overall rate of reoperation was 16.1% within an average follow-up period of 2 years, ranging from 0 to 12.5 years. The majority of the reoperations were due to cosmetic reasons. The change in anesthetic regime was associated with a significantly ( < 0.0001) decreased need for supplementary medication with no increased risk of complications.
CONCLUSION
Breast augmentations in local anesthesia with intercostal blocks and light sedation can be performed safely and can serve as an alternative to procedures in general anesthesia.
Topics: Humans; Female; Anesthesia, Local; Midazolam; Retrospective Studies; Mammaplasty
PubMed: 35510744
DOI: 10.1080/2000656X.2022.2069789 -
Frontiers in Pharmacology 2022Emergence agitation (EA) is a common problem often observed in children after sevoflurane anesthesia, which can be prevented by dexmedetomidine and alfentanil. This...
Emergence agitation (EA) is a common problem often observed in children after sevoflurane anesthesia, which can be prevented by dexmedetomidine and alfentanil. This study aims to compare the effectiveness of dexmedetomidine alone and with different doses of alfentanil in preventing EA in children under sevoflurane anesthesia. In a double-blind trial, 80 children (ASA I or II, 3-7 years old) undergoing tonsillectomy alone and adenotonsillectomy with sevoflurane anesthesia were randomly assigned into four groups: the control group, dexmedetomidine (DEX) group, dexmedetomidine plus 10 μg/kg alfentanil group (DEX + Alf1), and dexmedetomidine plus 20 μg/kg alfentanil group (DEX + ALf2). The incidence of EA was assessed with the Aono's scale, and the severity of EA was evaluated with the Pediatric Anesthesia Emergence Delirium (PAED) scale. The time of tracheal extubation and time of wake were recorded. Postoperative pain and complications such as nausea and vomiting, cough, laryngospasm, and bradycardia were recorded. The incidence of EA was 50% in the control group, 25% in the DEX group, and 5% in the DEX + Alf1 group, and it never happened in the DEX + Alf2 group. The Aono's scale, the PAED scale, and the FLACC scale in the control group and the DEX group were significantly more than those in the DEX + Alf1 group and the DEX + Alf2 group after the tracheal extubation ( < 0.05). The time of tracheal extubation of the control group and the DEX group were significantly shorter than those in the DEX + Alf1 group and the DEX + Alf2 group ( < 0.05). The awakening time of the DEX + Alf2 group is significantly longer than those in other groups ( < 0.05). The case of postoperative nausea and vomiting in the DEX + Alf1 group was fewer than those in the other groups ( < 0.05). And, the cases of cough and laryngospasm and bronchospasm in the DEX + Alf1 group and the DEX + Alf2 group were significantly less than those in the control group and the DEX group after the tracheal extubation ( < 0.05). The combined administration of alfentanil and dexmedetomidine can reduce EA in children undergoing tonsillectomy alone and adenotonsillectomy with sevoflurane anesthesia. Dexmedetomidine plus 10 μg/kg alfentanil seems to be more appropriate than other dose combinations as it reduced EA and postoperative nausea and vomiting but did not prolong the time to awake.
PubMed: 35185554
DOI: 10.3389/fphar.2022.648802 -
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 -
Minerva Surgery Dec 2023
Topics: Humans; Alfentanil; Hemodynamics; Anesthesia, General; Cough
PubMed: 35088992
DOI: 10.23736/S2724-5691.21.09341-2 -
Frontiers in Pharmacology 2021The treatment of most severe COVID-19 patients included the large-scale use of sedatives and analgesics-possibly in higher doses than usual-which was reported in the... (Review)
Review
The treatment of most severe COVID-19 patients included the large-scale use of sedatives and analgesics-possibly in higher doses than usual-which was reported in the literature. The use of drugs that decrease mortality is necessary and opioids are important agents in procedures such as orotracheal intubation. However, these drugs seem to have been overestimated in the COVID-19 pandemic. We performed a review of the PubMed-Medline database to evaluate the use of opioids during this period. The following descriptors were used to enhance the search for papers: "Opioids", "COVID-19," "COVID-19 pandemic," "SARS-CoV-2," "Opioid use disorder," "Opioid dependence" and the names of the drugs used. We also evaluated the distribution of COVID-19 patients in Brazil and the applicability of opioids in our country during the COVID-19 pandemic. Several positive points were found in the use of opioids in the COVID-19 pandemic, for instance, they can be used for analgesia in orotracheal intubation, for chronic pain management, and as coadjutant in the management of acute intensification of pain. However, high doses of opioids might exacerbate the respiratory depression found in COVID-19 patients, their chronic use can trigger opioid tolerance and the higher doses used during the pandemic might result in greater adverse effects. Unfortunately, the pandemic also affected individuals with opioid use disorder, not only those individuals are at higher risk of mortality, hospitalization and need for ventilatory support, but measures taken to decrease the SARS-CoV-2 spread such as social isolation, might negatively affect the treatment for opioid use disorder. In Brazil, only morphine, remifentanil and fentanyl are available in the basic health care system for the treatment of COVID-19 patients. Out of the 5,273,598 opioid units used in this period all over the country, morphine, fentanyl, and remifentanil, accounted for, respectively, 559,270 (10.6%), 4,624,328 (87.6%), and 90,000 (1.8%) units. Many Brazilian regions with high number of confirmed cases of COVID-19 had few units of opioids available, as the Southeast region, with a 0.23 units of opioids per confirmed COVID-19 case, and the South region, with 0.05 units. In the COVID-19 pandemic scenario, positive points related to opioids were mainly the occurrence of analgesia, to facilitate intubation and their use as coadjutants in the management of acute intensification of pain, whereas the negative points were indiscriminate use, the presence of human immunosuppressor response and increased adverse effects due to higher doses of the drug. The importance of rational and individualized use of analgesic hypnotics and sedative anesthetics should be considered at all times, especially in situations of high demand such as the COVID-19 pandemic.
PubMed: 35069193
DOI: 10.3389/fphar.2021.758637 -
Surgical Endoscopy Sep 2022Remifentanil is a rapid onset and rapid recovery opioid. The combination of remifentanil and propofol for deep sedation decreases the incidents of movement, cough, and...
BACKGROUND
Remifentanil is a rapid onset and rapid recovery opioid. The combination of remifentanil and propofol for deep sedation decreases the incidents of movement, cough, and hiccup. We evaluated the efficacy and safety of remifentanil during endoscopic ultrasound-guided tissue acquisition.
METHODS
We retrospectively reviewed patients in whom endoscopic ultrasound-guided tissue acquisition was performed for solid mass lesions of the upper gastrointestinal tract and adjacent organs. All patients were premedicated with midazolam (2 mg), and target-controlled infusion of propofol, opioid, and Bispectral Index (BIS) monitoring were administered as necessary to maintain moderate-to-deep sedation. The opioids used were a bolus of alfentanil or remifentanil infusion. The discharge time, consumption of propofol and opioid, adverse events, diagnostic accuracy, and sensitivity and specificity for malignancy, were compared.
RESULTS
Tissue acquisition was achieved in 123 patients (alfentanil group, n = 64; remifentanil group, n = 59). The discharge time of the remifentanil group (16.5 ± 3.2 min) was significantly shorter than that of the alfentanil group (19.0 ± 4.9 min, P = 0.001). The consumption of propofol, adverse events, diagnostic accuracy, sensitivity, and specificity for malignancy in the alfentanil group were not significantly different from those in the remifentanil group.
CONCLUSIONS
Use of alfentanil or remifentanil for target-controlled infusion of propofol-BIS monitoring can provide good sedative and diagnostic quality for endoscopic ultrasound-guided tissue acquisition. However, remifentanil resulted in faster recovery than alfentanil.
Topics: Alfentanil; Analgesics, Opioid; Anesthetics, Intravenous; Humans; Piperidines; Propofol; Remifentanil; Retrospective Studies; Ultrasonography, Interventional
PubMed: 35041053
DOI: 10.1007/s00464-021-09006-8 -
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 -
Drug Design, Development and Therapy 2021The aim of this work is to identify the most influential initial clinical studies that fomented important developments in anesthesiology over the past 50 years. Studies... (Review)
Review
The aim of this work is to identify the most influential initial clinical studies that fomented important developments in anesthesiology over the past 50 years. Studies fomenting new development can be selected using vastly different approaches and, therefore, might provide diverse outcomes. In the present work, two basic aspects of study assessments - the stage of development (eg, generation of idea, preclinical studies, clinical trials) and the method of selection (eg, committee vote, various types of citation analysis, method of finding the invention disclosure) - were chosen according to the following model. The stage of development: the initial clinical studies demonstrating the basic advantage of an innovation for providing anesthesia. The method: a combination of two factors - the study priority in terms of the time of its publication and the degree of its acknowledgement in the form of citation impact; the time of study publication was regarded as a primary factor, but only if the study's citation count was =/>20. The initial high-impact studies were selected for 16 drug-related topics (ketamine, isoflurane, etomidate, propofol, midazolam in anesthesia, vecuronium, alfentanil, atracurium, sevoflurane, sufentanil, rocuronium, desflurane, ropivacaine, remifentanil, dexmedetomidine in anesthesia, and sugammadex), and 9 technique-related topics (ultrasound-guided peripheral nerve block, capnography in anesthesia, target-controlled intravenous anesthesia, pulse oximetry in anesthesia, total intravenous anesthesia, transesophageal echocardiography in anesthesia, combined spinal-epidural anesthesia, and bispectral index). Twenty-five studies were designated the first high-impact studies (one for each topic); 16 are drug-related and 9 are technique-related. Half of the first high-impact studies had a citation count of =/>100, (range: 100 to 555). The citation count of the other half of high-impact studies did not reach the 100-citation threshold (range: 41 to 97). If a selected first high-impact study had a citation count <100, a next-on-timeline, additional study with citation count =/>100 was also selected; (range: 100 to 344). The present results show that an initial high-impact clinical study on a new development in anesthesiology can be determined and that related citations usually vary from one hundred to five hundred.
Topics: Anesthesia; Anesthesiology; Anesthetics; Animals; Clinical Trials as Topic; Drug Development; History, 20th Century; History, 21st Century; Humans; Publications
PubMed: 34149285
DOI: 10.2147/DDDT.S316636