100 Hz-5 s tetanic stimulation to illustrate the presence of "residual paralysis" co-existing with accelerometric 0.90 train-of-four ratio-A proof-of-concept study.

BACKGROUND: An acceleromyographic train-of-four (TOF) ratio of 0.90 at extubation does not prevent postoperative pulmonary complications in surgical patients receiving non-depolarising muscle relaxants. This recent observation suggests that a more selective neuromuscular transmission monitoring parameter is mandatory to detect more precisely any remaining residual paralysis. The aim of our proof-of-concept study was to evaluate, in patients receiving rocuronium, the degree of 100-Hz, 5-s tetanic fade present when the acceleromyographic TOF ratio has recovered to 0.90. METHODS: Twenty adult patients scheduled for surgery under general anaesthesia were included. Before anaesthesia induction, a TOF-Watch SX™ and a VISUAL-ITF© (a prototype monitor for recording isometric force) were positioned on both hands. After induction but before rocuronium injection, a 100-Hz, 5-s tetanus (TET0) was delivered to both ulnar nerves. Thereafter, TOF stimulations every 15 s were delivered to both arms until a TOF ratio > 0.90 was recorded; then, a 100-Hz, 5-s tetanus (TET1) was recorded on the VISUAL-ITF© monitor. The values of the tetanic parameters (force) recorded at TET0 and TET1 were compared using a Wilcoxon rank sum test. RESULTS: Compared to TET0, tetanic parameters of TET1 were significantly lower (median [range]): maximal force 36.4 [19.2-82.6] vs. 25.5 [5.0-42.4] Newton (p < 0.005); residual force 36.2 [18.2-82.0] vs. 5.5 [0.20-38.3] Newton (p < 0.0001) and residual force/maximal force ratio 0.98 [0.89-0.99] vs. 0.17 [0.03-0.90] (p < 0.0001). CONCLUSION: Our results confirm that even when the acceleromyographic TOF ratios have recovered to above 0.90, the contralateral 100-Hz, 5-s tetanic stimulus may show tetanic fade characteristic of residual neuromuscular block, and may help improve the safety of tracheal extubation.

Tetanic Facilitation of Neuromuscular Transmission by Adenosine A2A and Muscarinic M1 Receptors is Dependent on the Uptake of Choline via High-Affinity Transporters.

BACKGROUND/AIMS: In this study, we evaluated the functional impact of facilitatory presynaptic adenosine A2A and muscarinic M1 receptors in the recovery of neuromuscular tetanic depression caused by the blockage of high-affinity choline transporter (HChT) by hemicholinium-3 (HC-3), a condition that mimics a myasthenia-like condition. METHODS: Rat diaphragm preparations were indirectly stimulated via the phrenic nerve trunk with 50-Hz frequency trains, each consisting of 500-750 supramaximal intensity pulses. The tension at the beginning (A) and at the end (B) of the tetanus was recorded and the ratio (R) B/A calculated. RESULTS: Activation of A2A and M1 receptors with CGS21680 (CGS; 2 nmol/L) and McN-A-343c (McN; 3 µmol/L) increased R values. Similar facilitatory effects were obtained with forskolin (FSK; 3 µmol/L) and phorbol 12-myristate 13-acetate (PMA; 10 µmol/L), which activate adenylate cyclase and protein kinase C respectively. HC-3 (4 µmol/L) decreased transmitter exocytosis measured by real-time videomicroscopy with the FM4-64 fluorescent dye and prevented the facilitation of neuromuscular transmission caused by CGS, McN, and FSK, with a minor effect on PMA. The acetylcholinesterase inhibitor, neostigmine (NEO; 0.5 µmol/L), also decreased transmitter exocytosis. The paradoxical neuromuscular tetanic fade caused by NEO (0.5 µmol/L) was also prevented by HC-3 (4 µmol/L) and might result from the rundown of the positive feedback mechanism operated by neuronal nicotinic receptors (blocked by hexamethonium, 120 µmol/L). CONCLUSION: Data suggest that the recovery of tetanic neuromuscular facilitation by adenosine A2A and M1 receptors is highly dependent on HChT activity and may be weakened in myasthenic patients when HChT is inoperative.

Atropine is more efficient than ZM241385 to reduce a drastic level of fade caused by cisatracurium at 50 Hz / Atropina é mais eficiente que ZM241385 para reduzir o intenso nível de fadiga causada por cisatracurium a 50 Hz

The effects of atropine (non selective muscarinic antagonist) and ZM241385 (A2A receptors antagonist) in the cisatracurium-induced drastic (100%) level of fade at 50 Hz (10 s) (100% Fade) were compared in the phrenic nerve-diaphragm muscle preparations of rats indirectly stimulated at a physiological tetanic frequency (50 Hz). The lowest dose and the instant cisatracurium caused 100% Fade were investigated. Cisatracurium induced 100% Fade 15 min after being administered. Atropine reduced the cisatracurium-induced 100% Fade, but the administration of ZM241385 separately, or combined with atropine, did not cause any effect in the cisatracurium-induced 100% Fade. Data indicate that the simultaneous blockage of M1 and M2 muscarinic receptors on motor nerve terminal by atropine is more efficient than the blockage of presynaptic A2A receptors for a safer recovery of patients from neuromuscular blockade caused by cisatracurium.

Os efeitos de atropina e ZM241385 (antagonistas de receptores A2A) no drástico (100%) nível de fadiga (100% Fadiga) produzido pelo cisatracúrio a 50 Hz (10 s) foram comparativamente investigados em preparações nervo frênico músculo diafragma isolado de ratos indiretamente estimuladas com a frequência fisiológica tetanizante de 50 Hz. A menor dose e o instante no qual cisatracúrio causou 100% Fadiga foram pesquisados. O cisatracúrio induziu 100% Fadiga 15 min depois de ser administrado. A atropina reduziu a fadiga de 100% causada pelo cisatracúrio, mas ZM241385, ou a administração combinada de atropina com ZM241385, não causou qualquer efeito na 100% Fadiga produzida pelo cisatracúrio. Os dados indicam que o bloqueio simultâneo dos receptores muscarínicos M1 e M2 no terminal nervoso motor pela atropina é mais eficiente do que o bloqueio dos receptores pré-sinápticos A2A no auxilio da recuperação mais segura do bloqueio da transmissão neuromuscular causada por cisatracúrio.

Succinylcholine-induced phase II block and pharmacodynamics in rat diaphragm

BACKGROUND: Succinylcholine causes phase II block by a large dose or a prolonged exposure. There are rare data in a pharmacodynamics of phase II block. The purpose of this study was to investigate a concentration-response relationship, the occurrence and recovery of phase II block, and to clarify whether pretreatment of succinylcholine potentiates muscle relaxation caused by rocuronium. METHODS: Hemidiaphragm-phrenic nerve preparations were dissected from male Sprague-Dawley rats (150-250 g). Preparations were bathed in Krebs' solution, then maintained at 32oC, and saturated with a mixture of 95% O2 and 5% CO2. Isometric forces made with supramaximal stimulations (0.1 Hz, and 50 Hz for 1.9 s) to the phrenic nerve, were measured with a force transducer, before and after each treatment. Succinylcholine, 10, 20, 40, 60 and 80microM were cumulatively added to the bath. Succinylcholine 80microM (for 100 min) or succinylcholine 300microM (for 20 min) was washed out. After succinylcholine 300microM (for 20 min), or 0microM as pretreatment was washed out, rocuronium, 2, 4, 8, 12, 16, 20microM were cumulatively added to the bath. RESULTS: The potencies of single twitch, peak tetanic tension and tetanic fade for succinylcholine were 36.1, 26.0, 20.7microM. Irrespective of dose or exposure duration, the recovery of muscle relaxation caused by succinylcholine was almost complete around 20 min after succinylcholine was washed out. CONCLUSIONS: Tetanic fade occurred at a lower concentration of succinylcholine than single twitch. The recovery from phase II block was relatively rapid if the concentration of succinylcholine is sufficiently low.

Prejunctional Phenomenon during Succinylcholine Onset in Cats / 대한마취과학회지

BACKGROUND: Succinylcholine (Sch) has been generally reported not to produce tetanic stimulation fade on train of four in phase I block, except phase II block. But, the prejunctional phenomenon of Sch during onset is rarely reported these days, and so we investigated whether the prejunctional phenomenon of Sch during onset exists in cats. METHODS: We checked train of four ratios (TOF-R) and tetanic fade ratios (TF-R) by using a nerve stimulator before and after 50microgram/kg of Sch less than ED95 was administered, and during recovery in anesthetized cats. We analyzed TOF-R and TF-R before drug administration as a control and during onset and recovery time in order to estimate the statistic significance of fade. RESULTS: TOF fade and tetanic stimulation during the onset of Sch appeared like those in the partial block of nondepolarizing neuromuscular blockades TOF-R and TF-R during Sch onset compared with those in control and recovery time of Sch had statistical significance (P <0.05). CONCLUSIONS: The prejunctional phenomenon appeared only during Sch onset in cats and then disappeared during recovery to the control level.