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Mădălina Duţu, Robert Ivaşcu, Oana Tudorache, Darius Morlova, Alina Stanca, Silvius Negoiţă, Dan Corneci
This review makes an advocacy for neuromuscular blockade monitoring during anaesthesia care, by: (i) describing the fundamental principles of the methods currently available, at the same time emphasizing quantitative recording measurements; (ii) describing the different ways in which muscles respond to the effect of neuromuscular blockade and their use in clinical practice; (iii) presenting results of different studies on timing and agents of neuromuscular block reversal, including a recommendation for sugammadex use and experimental results with calabadion and (iv) in the end emphasizing the need for implementing neuromuscular monitoring as a practice that should be used every time a neuromuscular block is required...
April 2018: Romanian Journal of Anaesthesia and Intensive Care
J M Hunter
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...
December 1, 2017: British Journal of Anaesthesia
Shweta Ganapati, Stephanie D Grabitz, Steven Murkli, Flora Scheffenbichler, Maíra I Rudolph, Peter Y Zavalij, Matthias Eikermann, Lyle Isaacs
We measured the affinity of five molecular container compounds (calabadions 1 and 2, CB[7], sulfocalix[4]arene, and HP-β-CD) toward seven drugs of abuse in homogenous aqueous solution at physiological pH by various methods (1 H NMR, UV/Vis, isothermal titration calorimetry [ITC]) and found binding constants (Ka values) spanning from <102 to >108  m-1 . We also report X-ray crystal structures of CB[7]⋅methamphetamine and 1⋅methamphetamine. We found that 2, but not CB[7], was able to ameliorate the hyperlocomotive activity of rats treated with methamphetamine...
August 17, 2017: Chembiochem: a European Journal of Chemical Biology
N Zoremba, G Schälte, C Bruells, F K Pühringer
Due to the great advantages, it is not possible to imagine current practice in anesthesia without the adminstration of muscle relaxants. For a long time the administration of succinylcholine for rapid sequence induction (RSI) was considered to be the state of the art for patients at risk for aspiration. The favorable characteristics are, however, accompanied by many, sometimes severe side effects. Due to the development of non-depolarizing muscle relaxants, in particular rocuronium in combination with sugammadex, there is the possibility to achieve a profile of action similar to succinylcholine with low side effects...
May 2017: Der Anaesthesist
Daniel Diaz-Gil, Friederike Haerter, Shane Falcinelli, Shweta Ganapati, Gaya K Hettiarachchi, Jeroen C P Simons, Ben Zhang, Stephanie D Grabitz, Ingrid Moreno Duarte, Joseph F Cotten, Katharina Eikermann-Haerter, Hao Deng, Nancy L Chamberlin, Lyle Isaacs, Volker Briken, Matthias Eikermann
BACKGROUND: Calabadion 2 is a new drug-encapsulating agent. In this study, the authors aim to assess its utility as an agent to reverse general anesthesia with etomidate and ketamine and facilitate recovery. METHODS: To evaluate the effect of calabadion 2 on anesthesia recovery, the authors studied the response of rats to calabadion 2 after continuous and bolus intravenous etomidate or ketamine and bolus intramuscular ketamine administration. The authors measured electroencephalographic predictors of depth of anesthesia (burst suppression ratio and total electroencephalographic power), functional mobility impairment, blood pressure, and toxicity...
August 2016: Anesthesiology
Grace Lim, Douglas P Landsittel
No abstract text is available yet for this article.
June 2016: Anesthesiology
Friederike Haerter, Matthias Eikermann
INTRODUCTION: Acetylcholinesterase inhibitors (neostigmine, edrophonium) and encapsulating agents (sugammadex and calabadion) can be used to reverse residual neuromuscular blockade (NMB). AREAS COVERED: This review provides information about efficacy, effectiveness, and side effects of drugs (acetylcholinesterase inhibitors and encapsulating agents) used to reverse neuromuscular blocking agents (NMBAs). EXPERT OPINION: The therapeutic range of acetylcholinesterase-inhibitors is narrow and effectiveness studies demonstrate clinicians don't use these unspecific reversal agents effectively to increase postoperative respiratory safety...
2016: Expert Opinion on Pharmacotherapy
Shweta Ganapati, Peter Y Zavalij, Matthias Eikermann, Lyle Isaacs
An acyclic cucurbit[n]uril (CB[n]) based molecular container (2, a.k.a. Calabadion 2) binds to both amino-steroidal and benzylisoquinolinium type neuromuscular blocking agents (NMBAs) in vitro, and reverses the effect of these drugs in vivo displaying faster recovery times than placebo and the γ-cyclodextrin (CD) based and clinically used reversal agent Sugammadex. In this study we have assessed the potential for other drugs commonly used during and after surgery (e.g. antibiotics, antihistamines, and antiarrhythmics) to interfere with the ability of 2 to bind NMBAs rocuronium and cisatracurium in vitro...
January 28, 2016: Organic & Biomolecular Chemistry
Friederike Haerter, Jeroen Cedric Peter Simons, Urs Foerster, Ingrid Moreno Duarte, Daniel Diaz-Gil, Shweta Ganapati, Katharina Eikermann-Haerter, Cenk Ayata, Ben Zhang, Manfred Blobner, Lyle Isaacs, Matthias Eikermann
BACKGROUND: The authors evaluated the comparative effectiveness of calabadion 2 to reverse non-depolarizing neuromuscular-blocking agents (NMBAs) by binding and inactivation. METHODS: The dose-response relationship of drugs to reverse vecuronium-, rocuronium-, and cisatracurium-induced neuromuscular block (NMB) was evaluated in vitro (competition binding assays and urine analysis), ex vivo (n = 34; phrenic nerve hemidiaphragm preparation), and in vivo (n = 108; quadriceps femoris muscle of the rat)...
December 2015: Anesthesiology
Paul M Heerdt, Hiroshi Sunaga, John J Savarese
PURPOSE OF REVIEW: This review summarizes recent progress in the development of new muscle relaxants that are inactivated by cysteine, and considers the evolving paradigm of selective relaxant binding or degrading agents that can reverse neuromuscular blockade at any time. RECENT FINDINGS: The benzylisoquinoline compound gantacurium is a nondepolarizing muscle relaxant with an ultrashort duration largely determined by the rapid rate at which endogenous L-cysteine binds to, and permanently inactivates, the molecule...
August 2015: Current Opinion in Anaesthesiology
Hassan Farhan, Ingrid Moreno-Duarte, Duncan McLean, Matthias Eikermann
Neuromuscular blocking agents are used to facilitate tracheal intubation in patients undergoing ambulatory surgery. The use of high-dose neuromuscular blocking agents to achieve muscle paralysis throughout the case carries an increased risk of residual post-operative neuromuscular blockade, which is associated with increased respiratory morbidity. Visually monitoring the train-of-four (TOF) fade is not sensitive enough to detect a TOF fade between 0.4 and 0.9. A ratio <0.9 indicates inadequate recovery. Quantitative neuromuscular transmission monitoring (e...
December 2014: Current Anesthesiology Reports
Donal H Macartney
The ideal neuromuscular blocking agent (NMBA) is regarded as being a non-depolarizing equivalent of succinylcholine, having a rapid onset and short duration of action, with minimal side effects. In the absence of a single drug, the administration of an aminosteroid NMBA, such as rocuronium, followed by reversal using an acetylcholinesterase inhibitor, such as neostigmine, is commonly employed. A different and safer approach to rapidly reversing the action of the NMBA, by encapsulating it with a macrocyclic or acyclic host molecule, such as the cyclodextrin sugammadex or more recently, cucurbituril-type hosts such as cyclic cucurbit[7]uril and the acyclic glycoluril tetramer calabadion 1, is described...
November 2013: Future Medicinal Chemistry
Ulrike Hoffmann, Martina Grosse-Sundrup, Katharina Eikermann-Haerter, Sebastina Zaremba, Cenk Ayata, Ben Zhang, Da Ma, Lyle Isaacs, Matthias Eikermann
INTRODUCTION: To evaluate whether calabadion 1, an acyclic member of the Cucurbit[n]uril family of molecular containers, reverses benzylisoquinoline and steroidal neuromuscular-blocking agent effects. METHODS: A total of 60 rats were anesthetized, tracheotomized, and instrumented with IV and arterial catheters. Rocuronium (3.5 mg/kg) or cisatracurium (0.6 mg/kg) was administered and neuromuscular transmission quantified by acceleromyography. Calabadion 1 at 30, 60, and 90 mg/kg (for rocuronium) or 90, 120, and 150 mg/kg (for cisatracurium), or neostigmine/glycopyrrolate at 0...
August 2013: Anesthesiology
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