-
British Journal of Anaesthesia Mar 2024The phenomena of residual curarisation and recurarisation after the use of long-acting non-depolarising neuromuscular blocking drugs such as tubocurarine and pancuronium...
The phenomena of residual curarisation and recurarisation after the use of long-acting non-depolarising neuromuscular blocking drugs such as tubocurarine and pancuronium were well recognised 60 years ago. But the incidence seemed to decline with the introduction of atracurium and vecuronium. However, recently there have been an increasing number of reports of residual and recurrent neuromuscular block. Some of these reports are a result of inappropriate doses of rocuronium, sugammadex or both, together with inadequate neuromuscular monitoring. We urge clinicians to review their practice to ensure the highest standards of clinical care when using neuromuscular blocking drugs and reversal agents. This includes the use of quantitative neuromuscular monitoring whenever neuromuscular blocking drugs are administered.
Topics: Humans; Neuromuscular Blockade; Neuromuscular Nondepolarizing Agents; Androstanols; Rocuronium; Vecuronium Bromide; Neuromuscular Blocking Agents
PubMed: 38135525
DOI: 10.1016/j.bja.2023.12.001 -
SLAS Discovery : Advancing Life... Dec 2021Butyrylcholinesterase (BChE) is a nonspecific cholinesterase enzyme that hydrolyzes choline-based esters. BChE plays a critical role in maintaining normal cholinergic...
Butyrylcholinesterase (BChE) is a nonspecific cholinesterase enzyme that hydrolyzes choline-based esters. BChE plays a critical role in maintaining normal cholinergic function like acetylcholinesterase (AChE) through hydrolyzing acetylcholine (ACh). Selective BChE inhibition has been regarded as a viable therapeutic approach in Alzheimer's disease. As of now, a limited number of selective BChE inhibitors are available. To identify BChE inhibitors rapidly and efficiently, we have screened 8998 compounds from several annotated libraries against an enzyme-based BChE inhibition assay in a quantitative high-throughput screening (qHTS) format. From the primary screening, we identified a group of 125 compounds that were further confirmed to inhibit BChE activity, including previously reported BChE inhibitors (e.g., bambuterol and rivastigmine) and potential novel BChE inhibitors (e.g., pancuronium bromide and NNC 756), representing diverse structural classes. These BChE inhibitors were also tested for their selectivity by comparing their IC values in BChE and AChE inhibition assays. The binding modes of these compounds were further studied using molecular docking analyses to identify the differences between the interactions of these BChE inhibitors within the active sites of AChE and BChE. Our qHTS approach allowed us to establish a robust and reliable process to screen large compound collections for potential BChE inhibitors.
Topics: Acetylcholinesterase; Alzheimer Disease; Butyrylcholinesterase; Catalytic Domain; Cholinesterase Inhibitors; Humans; Molecular Docking Simulation; Structure-Activity Relationship; Terbutaline
PubMed: 34269114
DOI: 10.1177/24725552211030897 -
Annals of Cardiac Anaesthesia 2023Ivabradine is a specific heart rate (HR)-lowering agent which blocks the cardiac pacemaker I channels. It reduces the HR without causing a negative inotropic or... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Ivabradine is a specific heart rate (HR)-lowering agent which blocks the cardiac pacemaker I channels. It reduces the HR without causing a negative inotropic or lusitropic effect, thus preserving ventricular contractility. The authors hypothesized that its usefulness in lowering HR can be utilized in patients undergoing off-pump coronary artery bypass (OPCAB) surgery.
OBJECTIVE
To study the effects of preoperative ivabradine on hemodynamics (during surgery) in patients undergoing elective OPCAB surgery.
METHODS
Fifty patients, New York Heart Association (NYHA) class I and II, were randomized into group I (control, n = 25) and group II (ivabradine group, n = 25). In group I, patients received the usual anti-anginal medications in the preoperative period, as per the institutional protocol. In group II, patients received ivabradine 5 mg twice daily for 3 days before surgery, in addition to the usual anti-anginal medications. Anesthesia was induced with fentanyl, thiopentone sodium, and pancuronium bromide as a muscle relaxant and maintained with fentanyl, midazolam, pancuronium bromide, and isoflurane. The hemodynamic parameters [HR and mean arterial pressure (MAP)] and pulmonary artery (PA) catheter-derived data were recorded at the baseline (before induction), 3 min after the induction of anesthesia at 1 min and 3 min after intubation and at 5 min and 30 min after protamine administration. Intraoperatively, hemodynamic data (HR and MAP) were recorded every 10 min, except during distal anastomosis of the coronary arteries when it was recorded every 5 min. Post-operatively, at 24 hours, the levels of troponin T and brain natriuretic peptide (BNP) were measured. This trial's CTRI registration number is CTRI/005858.
RESULTS
The HR in group II was lower when compared to group I (range 59.6-72.4 beats/min and 65.8-80.2 beats/min, respectively) throughout the study period. MAP was comparable [range (78.5-87.8 mm Hg) vs. (78.9-88.5 mm Hg) in group II vs. group I, respectively] throughout the study period. Intraoperatively, 5 patients received metoprolol in group I to control the HR, whereas none of the patients in group II required metoprolol. The incidence of preoperative bradycardia (HR <60 beats/min) was higher in group II (20%) vs. group I (8%). There was no difference in both the groups in terms of troponin T and BNP level after 24 hours, time to extubation, requirement of inotropes, incidence of arrhythmias, in-hospital morbidity, and 30-day mortality.
CONCLUSION
Ivabradine can be safely used along with other anti-anginal agents during the preoperative period in patients undergoing OPCAB surgery. It helps to maintain a lower HR during surgery and reduces the need for beta-blockers in the intraoperative period, a desirable and beneficial effect in situations where the use of beta-blockers may be potentially harmful. Further studies are needed to evaluate the beneficial effects of perioperative Ivabradine in patients with moderate-to-severe left ventricular dysfunction.
Topics: Humans; Ivabradine; Metoprolol; Pancuronium; Troponin T; Hemodynamics; Coronary Artery Bypass, Off-Pump; Fentanyl
PubMed: 37470523
DOI: 10.4103/aca.aca_97_22 -
European Journal of Anaesthesiology Oct 2020Drug errors during neuraxial anaesthesia or analgesia are not well known. (Review)
Review
BACKGROUND
Drug errors during neuraxial anaesthesia or analgesia are not well known.
OBJECTIVES
To review the clinical consequences associated with incorrect administration of neuromuscular blocking drugs (NMBDs) during spinal or epidural anaesthesia, and to investigate human factors and strategies available to help prevent such errors.
DESIGN
A review of reports of neuraxial administration of NMBDs in humans.
DATA SOURCES
Published reports of errors involving NMBDs. We searched the period between 1965 and 2019.
ELIGIBILITY CRITERIA
Error reports in any language. Nonneuraxial drug errors were excluded.
RESULTS
We identified 20 reports involving seven different NMBDs inadvertently administered via the epidural or intrathecal routes. All patients developed systemic neuromuscular junction blockade. Fourteen errors occurred while patients were awake. The onset of action was delayed following epidural rocuronium and suxamethonium. The duration of action was prolonged following epidural administration of vecuronium, pancuronium, cisatracrium and suxamethonium. Five patients required emergency airway interventions. Intrethecal gallamine caused convulsions and muscle spasms migrating up the body. Syringe swap was the primary cause for the majority of errors and perceptual errors were the most common. Implementation of recommendations could have prevented the errors.
CONCLUSION
Following the epidural injection of NMBDs the effects are delayed and prolonged. There was no serious morbidity reported following neuraxial administration of the NMBDs used in current practice. Perceptual errors resulting in incorrect syringe choice were the commonest cause. Four measures can be introduced to reduce such errors.
Topics: Humans; Neuromuscular Blockade; Pharmaceutical Preparations; Rocuronium; Succinylcholine; Vecuronium Bromide
PubMed: 32371827
DOI: 10.1097/EJA.0000000000001232 -
Animals : An Open Access Journal From... May 2023(1) Background: Pancuronium bromide is a neuromuscular blocker used for immobilizing crocodiles that can be reversed with neostigmine. A recommended drug dose has only...
(1) Background: Pancuronium bromide is a neuromuscular blocker used for immobilizing crocodiles that can be reversed with neostigmine. A recommended drug dose has only been established for saltwater crocodiles (), mostly based on trials in juveniles and subadults. After trialing a dose recommendation in a small cohort of nine Nile crocodiles (), we developed and applied a new dose recommendation for large adult Nile crocodiles. (2) Methods: we trialed and adapted a pancuronium bromide (Pavulon 4 mg/2 mL) dose in Nile crocodiles originally established for saltwater crocodiles and applied the new dose for the immobilization of 32 Nile crocodiles destined for transport. Reversal was achieved with neostigmine (Stigmine 0.5 mg/mL). (3) Results: Nine crocodiles were included in the trial phase; the induction time was highly variable (average: 70 min; range: 20-143 min), and the recovery time was prolonged (average: 22 h; range: 50 min-5 days), especially in large animals after reversal with neostigmine. Based on these results, we established a dose-independent recommendation (3 mg pancuronium bromide and 2.5 mg neostigmine) for animals weighing ≥ 270 kg (TL ≥ ~3.8 m). When applied to 32 adult male crocodiles (BW range: 270-460 kg; TL range: 3.76-4.48 m), the shortest induction time was ~20 min and the longest ~45 min. (4) Conclusions: Pancuronium bromide and its antidote, neostigmine, are effective for the immobilization and reversal of adult male Nile crocodiles (TL ≥ 3.8 m or BW ≥ 270 kg) when given in a weight-independent fashion.
PubMed: 37238008
DOI: 10.3390/ani13101578 -
The Annals of Pharmacotherapy Sep 2020To review and evaluate neuromuscular blocking agents (NMBAs) in critically ill patients with acute respiratory distress syndrome (ARDS). A literature search utilizing... (Review)
Review
To review and evaluate neuromuscular blocking agents (NMBAs) in critically ill patients with acute respiratory distress syndrome (ARDS). A literature search utilizing PubMed was performed (January 1991 to January 2020) using the following search terms: ( OR OR OR OR OR OR ) AND * OR ). Publications in English were evaluated. Relevant clinical studies in humans were considered. Although NMBAs have been used for decades in the setting of ARDS, questions regarding mortality benefit remain. Early NMBA, within 48 hours of lung injury, have been historically used in critically ill patients with ARDS to aid in increasing alveolar recruitment, improving patient-ventilator synchrony, and promoting oxygenation by the prevention of contraction of respiratory muscles. Until recently, the literature showed an improvement in 90-day adjusted mortality. However, recent literature has demonstrated the lack of a mortality benefit. The continued receipt of NMBAs, with no clear benefit, could potentially lead to increased costs, skin breakdown, corneal abrasions, venous thromboembolisms, intensive care unit acquired weakness, and awareness with inappropriate sedation. This review aims at discussing the preferred NMBA based on mechanism of action and reviews specific clinical trial data for the use of NMBAs in ARDS, clinical implications of these trial data, complications for the use of NMBAs, and needed future directions. The mortality benefit of NMBAs in ARDS has contradicting evidence with potentially serious adverse effects and notable controversies.
Topics: Critical Illness; Humans; Intensive Care Units; Neuromuscular Blockade; Neuromuscular Blocking Agents; Respiratory Distress Syndrome; Severity of Illness Index; Treatment Outcome
PubMed: 32111121
DOI: 10.1177/1060028020910132 -
The Journal of Physiology Dec 2023The role played by the transient receptor potential vanilloid 1 (TRPV1) channel on the thin fibre afferents evoking the exercise pressor reflex is controversial. To shed...
The role played by the transient receptor potential vanilloid 1 (TRPV1) channel on the thin fibre afferents evoking the exercise pressor reflex is controversial. To shed light on this controversy, we compared the exercise pressor reflex between newly developed TRPV1 , TRPV1 and TRPV1 rats. Carotid arterial injection of capsaicin (0.5 μg), evoked significant pressor responses in TRPV1 and TRPV1 rats, but not in TRPV1 rats. In acutely isolated dorsal root ganglion neurons innervating the gastrocnemius muscles, capsaicin evoked inward currents in neurons isolated from TRPV1 and TRPV1 rats but not in neurons isolated from TRPV1 rats. The reflex was evoked by stimulating the tibial nerve in decerebrated rats whose femoral artery was either freely perfused or occluded. We found no difference between the reflex in the three groups of rats regardless of the patency of the femoral artery. For example, the peak pressor responses to contraction in TRPV1 , TRPV1 and TRPV1 rats with patent femoral arteries averaged 17.1 ± 7.2, 18.9 ± 12.4 and 18.4 ± 8.6 mmHg, respectively. Stimulation of the tibial nerve after paralysis with pancuronium had no effect on arterial pressure, findings which indicated that the pressor responses to contraction were not caused by electrical stimulation of afferent tibial nerve axons. We also found that expression levels of acid-sensing ion channel 1 and endoperoxide 4 receptor in the L4 and 5 dorsal root ganglia were not upregulated in the TRPV1 rats. We conclude that TRPV1 is not needed to evoke the exercise pressor reflex in rats whose contracting muscles have either a patent or an occluded arterial blood supply. KEY POINTS: A reflex arising in contracting skeletal muscle contributes to the increases in arterial blood pressure, cardiac output and breathing evoked by exercise. The sensory arm of the reflex comprises both mechanoreceptors and metaboreceptors, of which the latter signals that blood flow to exercising muscle is not meeting its metabolic demand. The nature of the channel on the metaboreceptor sensing a mismatch between supply and demand is controversial; some believe that it is the transient receptor potential vanilloid 1 (TRPV1) channel. Using genetically engineered rats in which the TRPV1 channel is rendered non-functional, we have shown that it is not needed to evoke the metaboreflex.
Topics: Animals; Rats; Blood Pressure; Capsaicin; Femoral Artery; Muscle Contraction; Muscle, Skeletal; Rats, Sprague-Dawley; Reflex; Transient Receptor Potential Channels
PubMed: 37878364
DOI: 10.1113/JP285267