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Romanian Journal of Anaesthesia and... Oct 2018Patients with pre-excitation abnormalities are at a high risk for life-threatening perioperative arrhythmias. In Wolff-Parkinson-White syndrome, the anaesthetics used... (Review)
Review
Patients with pre-excitation abnormalities are at a high risk for life-threatening perioperative arrhythmias. In Wolff-Parkinson-White syndrome, the anaesthetics used for invasive diagnostic testing/ablation, should not affect cardiac electrophysiology; propofol, sevoflurane, fentanyl, sufentanil, alfentanil are suitable. In non-ablative surgery, propofol, sevoflurane, isoflurane, fentanyl, alfentanil, sufentanil have been used safely. Among neuromuscular blockers, cis-atracurium, rocuronium and vecuronium are good choices. Ketamine, pancuronium and pethidine should be avoided because of their sympathomimetic actions. Anticholinergic/ anticholinesterase combinations for neuromuscular block reversal should preferably be omitted, while sugammadex seems more attractive. In regional anaesthesia, addition of epinephrine and high sympathetic blocks should be avoided. Hypotension should be treated with pure alpha-adrenergic agonists. Other pre-excitation abnormalities associated with different accessory pathways are the Mahaim Fiber and Lown-Ganong-Levine syndrome. Sympathetic activation should be avoided. Total intravenous anaesthesia with propofol probably represents the safest option. A careful anaesthetic plan and close cooperation with cardiologists are mandatory for successful management.
PubMed: 30393770
DOI: 10.21454/rjaic.7518.252.stk -
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 -
Acta Cirurgica Brasileira Jul 2016To evaluate the effects of levobupivacaine on neuromuscular transmission and neuromuscular blockade produced by pancuronium in vitro.
PURPOSE
To evaluate the effects of levobupivacaine on neuromuscular transmission and neuromuscular blockade produced by pancuronium in vitro.
METHODS
Thirty rats were distributed into groups (n = 5) according to the drug used alone or in combination: Group I - levobupivacaine (5 µg.mL-1); Group II - pancuronium (2 µg.mL-1); Group III - pancuronium (2 µg.mL-1) + levobupivacaine (5µg.mL-1). The following parameters were evaluated: 1) amplitude of diaphragmatic response to indirect stimulation, before and 60 minutes after the addition of levobupivacaine and pancuronium alone, and after the addition of levobupivacaine combined with pancuronium; 2) membrane potentials (MP) and miniature endplate potentials (MEPP).
RESULTS
Levobupivacaine alone did not alter the amplitude of muscle response and MP. In preparations previoulsy exposed to levobupivacaine, the block with pancuronium was significantly denser (90.2 ± 15.2%), showing a significant difference (p=0.031) in comparison to the block produced by pancuronium alone (48.9% ± 9.8%). There was a decrease in the frequency and amplitude of MEPPs.
CONCLUSION
Levobupivacaine potentiated the neuromuscular blockade produced by pancuronium, confirming a presynaptic action by a decrease in miniature endplate potentials.
Topics: Anesthetics, Local; Animals; Bupivacaine; Diaphragm; Drug Therapy, Combination; Electric Stimulation; Levobupivacaine; Male; Membrane Potentials; Models, Animal; Neuromuscular Blockade; Neuromuscular Junction; Neuromuscular Nondepolarizing Agents; Pancuronium; Rats, Wistar; Synaptic Transmission
PubMed: 27487284
DOI: 10.1590/S0102-865020160070000009 -
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 -
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 -
The Journal of Pharmacology and... May 2019Platelets are key mediators of thrombosis. Many agonists of platelet activation are known, but fewer endogenous inhibitors of platelets, such as prostacyclin and nitric...
Platelets are key mediators of thrombosis. Many agonists of platelet activation are known, but fewer endogenous inhibitors of platelets, such as prostacyclin and nitric oxide (NO), have been identified. Acetylcholinesterase inhibitors, such as donepezil, can cause bleeding in patients, but the underlying mechanisms are not well understood. We hypothesized that acetylcholine is an endogenous inhibitor of platelets. We measured the effect of acetylcholine or analogs of acetylcholine on human platelet activation ex vivo. Acetylcholine and analogs of acetylcholine inhibited platelet activation, as measured by P-selectin translocation and glycoprotein IIb IIIa conformational changes. Conversely, we found that antagonists of the acetylcholine receptor, such as pancuronium, enhance platelet activation. Furthermore, drugs inhibiting acetylcholinesterase, such as donepezil, also inhibit platelet activation, suggesting that platelets release acetylcholine. We found that NO mediates acetylcholine inhibition of platelets. Our data suggest that acetylcholine is an endogenous inhibitor of platelet activation. The cholinergic system may be a novel target for antithrombotic therapies.
Topics: Acetylcholine; Blood Platelets; Humans; Nitric Oxide; Platelet Activation; Receptors, Cholinergic
PubMed: 30765424
DOI: 10.1124/jpet.118.253583 -
British Journal of Anaesthesia Dec 2017The use of anticholinesterases to reverse residual neuromuscular block at the end of surgery became routine practice in the 1950s. These drugs could only be used when... (Review)
Review
The use of anticholinesterases to reverse residual neuromuscular block at the end of surgery became routine practice in the 1950s. These drugs could only be used when recovery from block was established [two twitches of the train-of-four (TOF) count detectable] and concern was expressed about their cholinergic side-effects. By the 1990s, it was recognized that failure to reverse residual block adequately to a TOF ratio (TOFR) >0.7 was associated with increased risk of postoperative pulmonary complications (POPCs) following the long-acting non-depolarizing neuromuscular blocking drug (NDNMBD) pancuronium. By 2003, and the introduction of acceleromyography, a TOFR ≥0.9 was considered necessary to protect the airway from aspiration before tracheal extubation. It was also considered that four, not two, twitches of the TOF should be detectable before neostigmine was given. Use of any NDNMBD was subsequently shown to be associated with increased risk of POPCs, but it was thought that neostigmine reduced that risk. Recently, there has been conflicting evidence that use of neostigmine might increase the incidence of POPCs. Although sugammadex has been shown to rapidly reverse profound neuromuscular block from aminosteroidal agents, there is currently no evidence that sugammadex is superior to neostigmine in its effect on POPCs. Other new antagonists, including cysteine to degrade CW002 and calabadion 1 and 2 to antagonize aminosteroidal and benzylisoquinolium NDNMBDs, are being studied in preclinical and clinical trials. Quantitative neuromuscular monitoring is essential whenever a NDNMBD is used to ensure full recovery from neuromuscular block.
Topics: Anesthesia Recovery Period; Delayed Emergence from Anesthesia; Humans; Muscle Relaxation; Neuromuscular Blockade; Neuromuscular Monitoring; Neuromuscular Nondepolarizing Agents; Perioperative Care
PubMed: 29161387
DOI: 10.1093/bja/aex318