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Anaesthesia May 2023Propfol-remifentanil-based total intravenous anaesthesia has dominated recent clinical practice due to its favourable pharmacokinetic profile. Interruption in... (Review)
Review
Propfol-remifentanil-based total intravenous anaesthesia has dominated recent clinical practice due to its favourable pharmacokinetic profile. Interruption in remifentanil supply has presented an opportunity to diversify or even avoid the use of opioids and consider adjuncts to propofol-based total intravenous anaesthesia. Propofol, while a potent hypnotic, is not an effective analgesic. The administration of opioids, along with other adjuncts such as α-2 adrenoceptor agonists, magnesium, lidocaine, ketamine and nitrous oxide provide surgical anaesthesia and avoids large doses of propofol being required. We provide an overview of both target-control and manual infusion regimes for the alternative opioids: alfentanil, sufentanil and fentanyl. The optimal combination of hypnotic-opioid dose, titration sequence and anticipated additional postoperative analgesia required depend on the chosen combination. In addition, we include a brief discussion on the role of non-opioid adjuncts in total intravenous anaesthesia, suggested doses and expected reduction in propofol dose.
Topics: Humans; Remifentanil; Propofol; Anesthesia, Intravenous; Piperidines; Analgesics, Opioid; Anesthesia, General; Hypnotics and Sedatives; Anesthetics, Intravenous
PubMed: 36562193
DOI: 10.1111/anae.15952 -
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 -
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 -
Annals of Palliative Medicine Mar 2020Opioids are complex drugs that produce profit (most importantly analgesia) as well as a myriad of adverse effects including gastrointestinal motility disturbances, abuse... (Review)
Review
Opioids are complex drugs that produce profit (most importantly analgesia) as well as a myriad of adverse effects including gastrointestinal motility disturbances, abuse and addiction, sedation and potentially lethal respiratory depression (RD). Consequently, opioid treatment requires careful evaluation in terms of benefit on the one hand and harm on the other. Considering benefit and harm from an economic perspective, opioid treatment should lead to profit maximization with decision theory defining utility as (profit - loss). We here focus on the most devastating opioid adverse effect, RD and define opioid utility U = P(benefit) - P(harm), where P(benefit) is the probability of opioid-induced analgesia and P(harm) the probability of opioid-induced RD. Other utility functions are also discussed including the utility U = P(benefit AND NOT harm), the most wanted opioid effect, i.e., analgesia without RD, and utility surfaces, which depict the continuum of probabilities of presence or absence of analgesia in combination with the presence or absence of RD. Utility functions are constructed from pharmacokinetic and pharmacodynamic data sets, although pragmatic utility functions may be constructed when pharmacokinetic data are not available. We here discuss utilities of several opioids including the partial mu-opioid-receptor agonist buprenorphine, the full opioid receptor agonists fentanyl and alfentanil, and the bifunctional opioid cebranopadol, which acts at mu-opioid and nociception/orphanin FQ-receptors. We argue that utility functions give clinicians the opportunity to make an informed decision when opioid analgesics are needed for pain relief, in which opioids with a positive utility function are preferred over opioids with negative functions. Furthermore, utility functions of subpopulations will give an extra insight as a utility functions measured in one subgroup (e.g., patients with postoperative pain, good opioid responders) may not be mirrored in other patient subgroups (e.g., neuropathic pain patients, poor opioid responders).
Topics: Analgesics, Opioid; Attitude of Health Personnel; Clinical Decision-Making; Disease Management; Humans; Pain; Pain Management; Pain Measurement
PubMed: 31865743
DOI: 10.21037/apm.2019.10.09 -
Revista de Investigacion Clinica;... 2023Synthetic opioids have played a significant role in the current opioid crisis in the United States (U.S.) and Canada and are a matter of concern worldwide. New... (Review)
Review
Synthetic opioids have played a significant role in the current opioid crisis in the United States (U.S.) and Canada and are a matter of concern worldwide. New psychoactive opioids (NPOs) are classified in the internationally recognized new psychoactive substances (NPSs) category. This group comprises compounds that may have been synthesized decades ago but appeared only recently in the illicit drug market. Such is the case of fentanyl, fentanyl analogs, and non-fentanyl opioids. Most NPOs have effects similar to morphine, including euphoria and analgesia, and can produce fatal respiratory depression. Here, we present an overview of the systemic and molecular effects of main NPOs, their classification, and their pharmacological properties. We first review the fentanyl group of NPOs, including the four compounds of clinical use (fentanyl, alfentanil, sufentanil, and remifentanil) and the veterinary drug carfentanil. We also provide essential information on non-medical fentanyl analogs and other synthetic opioids such as brorphine, etonitazene, and MT-45, used as adulterants in commonly misused drugs. This paper also summarizes the scarce literature on the use of NPOs in Mexico. It concludes with a brief review of the challenges to prevention and treatment posed by NPOs and some recommendations to face them.
Topics: Humans; United States; Analgesics, Opioid; Remifentanil; Canada; Mexico
PubMed: 37441771
DOI: 10.24875/RIC.23000109 -
British Journal of Pharmacology Sep 2023The illicit use of fentanyl-like drugs (fentanyls), which are μ opioid receptor agonists, and the many overdose deaths that result, has become a major problem....
BACKGROUND AND PURPOSE
The illicit use of fentanyl-like drugs (fentanyls), which are μ opioid receptor agonists, and the many overdose deaths that result, has become a major problem. Fentanyls are very potent in vivo, leading to respiratory depression and death. However, the efficacy and possible signalling bias of different fentanyls is not clearly known. Here, we compared the relative efficacy and bias of a series of fentanyls.
EXPERIMENTAL APPROACH
For agonist signalling bias and efficacy measurements, Bioluminescence Resonance Energy Transfer experiments were undertaken in HEK293T cells transiently transfected with μ opioid receptors, to assess Gi protein activation and β-arrestin 2 recruitment. Agonist-induced cell surface receptor loss was assessed using an enzyme-linked immunosorbent assay, whilst agonist-induced G protein-coupled inwardly rectifying potassium channel current activation was measured electrophysiologically from rat locus coeruleus slices. Ligand poses in the μ opioid receptor were determined in silico using molecular dynamics simulations.
KEY RESULTS
Relative to the reference ligand DAMGO, carfentanil was β-arrestin-biased, whereas fentanyl, sufentanil and alfentanil did not display bias. Carfentanil induced potent and extensive cell surface receptor loss, whilst the marked desensitisation of G protein-coupled inwardly rectifying potassium channel currents in the continued presence of carfentanil in neurones was prevented by a GRK2/3 inhibitor. Molecular dynamics simulations suggested unique interactions of carfentanil with the orthosteric site of the receptor that could underlie the bias.
CONCLUSIONS AND IMPLICATIONS
Carfentanil is a β-arrestin-biased opioid drug at the μ receptor. It is uncertain how such bias influences in vivo effects of carfentanil relative to other fentanyls.
Topics: Rats; Humans; Animals; Receptors, Opioid, mu; beta-Arrestins; Arrestin; Ligands; HEK293 Cells; Fentanyl; Analgesics, Opioid; GTP-Binding Proteins; beta-Arrestin 1; Potassium Channels, Inwardly Rectifying
PubMed: 37005796
DOI: 10.1111/bph.16084 -
Pharmacy (Basel, Switzerland) Dec 2020Alfentanil is used for chronic pain relief in palliative care. However, there is a dearth of data on its use. For this reason, a decision was made to review the use of...
Alfentanil is used for chronic pain relief in palliative care. However, there is a dearth of data on its use. For this reason, a decision was made to review the use of alfentanil in palliative care. Retrospective study was carried out in a palliative care service. The files of patients who received alfentanil as an intravenous or subcutaneous continuous infusion for pain relief, between January 2018 and April 2019. In total, 111 patients received alfentanil out of 113 admissions. Of them, 56 were male, and the median age was 70 years. The median number of days on alfentanil was 6 (range 1 to 129). The most frequent primary reasons for switching to alfentanil was uncontrolled pain in 52 (46%) patients and renal impairment in 24 (21%) patients. The median 24-h initial dose of alfentanil was 4 mg (1-20), and the median final 24-h dose of alfentanil was 5 mg (1-60), ( < 0.001). The initial 24-h median number of rescue doses was 2 (0-8), and the final median number of rescue doses was 1 (0 to 8), ( = 0.025). In 56 patients who were on alfentanil for at least 7 days, the dose decreased in 3 (5%), remained stable in 10 (18%) and increased in 43 (77%). The patient on alfentanil for 129 days maintained the same dose throughout that period. Alfentanil can be a useful second-line opioid. The induction of tolerance does not seem to be particularly rapid with alfentanil.
PubMed: 33339325
DOI: 10.3390/pharmacy8040240