Neuromuscular monitoring in myasthenic syndrome

We describe the anaesthetic management of a 72-year-old man with myasthenic syndrome. Pre-operatively, he was treated with 3,4-diaminopyridine and showed a strong hand grip. During general anaesthesia with nitrous oxide and sevoflurane in oxygen, a mechanomyograph and two accelerographs were set up for the hands and left foot to monitor neuromuscular function. Insufficient force and acceleration of contraction with 1 Hz stimulation was observed in the hands. In the foot, the twitches produced by 1 Hz and train-of-four stimulation could barely be detected using the accelerograph, and the train-of-four ratio fluctuated between 70 and 100%. No neuromuscular blocking drugs were used during surgery. After discontinuation of sevoflurane, responses to train-of-four stimulation remained small, but a strong response to tetanic stimulation was observed, with post-tetanic facilitation. Extubation was successful, and recovery from anaesthesia was uneventful. Tetanic stimulation and post-tetanic facilitation are important in monitoring neuromuscular function in patients with myasthenic syndrome whose train-of-four responses are insufficient.     

Acidosis and Neuromuscular Blockade

Der Einfluss verschiedener Arten von Azidose auf die Empfindlichkeit für muskelerschlaffende Mittel wurde mit Hilfe von in vivo Experimenten auf den Tibialis-Muskel der Katze und in vitro Experimenten auf das Phrenicus-diaphragma-Präparat der Ratte untersucht.
Die metabole Azidose wurde in vivo durch schwache organische Säure hervorgerufen, welche schnell in die Zelle hineintreten und der metabolen Azidose beim Mensch am nächsten stehen. Respiratorische Azidose wurde durch Inhalation von 10% Kohlensäure im Sauerstoff hervorgerufen.
In den in vitro Experimenten wurde die Azidose durch Titration der Spülflüssigkeit mit den selben Säuren und mit Salzsäure hervorgerufen. Das pH wurde bis gerade oberhalb 7.0 herabgedrückt.
Blanke in vivo Experimente zeigten, dass die metabole Azidose selbst keine signifikante Erniedrigung der indirekten Muskelkontraktion ergibt und respiratorische Azidose nur eine leichte. Auch in den in vitro Experimenten wurde eine leichte Depression durch die metabole Azidose festgestellt.
Die Muskelerlahmung durch Succinylcholine und Decamethonium wurde durch metabole und respiratorische Azidose in vitro und in vivo stärkstens antagonisiert. Muskelerschlaffung durch Pancuronium wurde aber durch metabole und respiratorische Azidose in gleiche Weise in den in vitro und in vivo Experimenten potenziert. Die Änderungen des Ruhepotentials der Zellmembrane werden als verantwortlich für die Empfindlichkeitsveränderungen angesehen.     

Neuromuscular disorders

Neuromuscular diseases form an heterogeneous group of illnesses. These diseases are rare and studies concerning their anaesthetic management are difficult. Patients with neuromuscular disease represent a challenge for the anaesthesiologist because of the frequent perioperative complications. Cardiac and respiratory functions are often involved, and the severity of the lesions are difficult to estimate. The possible interactions of different drugs necessitates a good knowledge of the drugs' actions and pathophysiological mechanisms.     

Neuromuscular disorders and anesthesia

The neuromuscular disorders are associated with diminished cardiopulmonary reserves, deficient airway protection mechanisms, and atypical responses to drugs used during anesthesia. Many of these conditions are uncommon, and methodologically sound evidence to guide clinical practice is limited. The disorders discussed in the present review are the motor neuron diseases, peripheral neuropathies, myasthenic syndromes, and myopathies, including malignant hyperthermia. Recent data on pathogenesis and medical management are outlined, as are studies relating to anesthesia and the perioperative period.     

Neuromuscular function and transmission

Understanding the biological processes and mechanisms underlying neuromuscular function in anaesthetized or sedated patients depends on adequate knowledge of the anatomy, physiology, and pathology of the connections between motor neurons and muscle fibres at neuromuscular junctions. Neuromuscular synaptic integrity depends on: maintenance of Ca²⁺-dependent release of acetylcholine by exocytosis from synaptic vesicles that fuse with active zones in motor nerve terminal membranes; the subsequent depolarizing action of acetylcholine on postsynaptic receptors at motor endplates; and termination of neuromuscular transmission by enzymic action of acetylcholinesterase located in the synaptic basal lamina. Homeostatic mechanisms sustain the magnitude of endplate potentials and the safety factor for neuromuscular transmission; but dysfunction of neuromuscular junctions occurs following administration of neuromuscular blockers or in diseases and other conditions affecting release, action and inactivation of acetylcholine.     

Neuromuscular function and transmission

The neuromuscular junction (NMJ) is a chemical synapse between a motor neurone and a skeletal muscle cell. It has been the most intensively studied synapse in the body owing to its comparatively large size, relative simplicity and accessibility. Commands from the central nervous system are transmitted along motor neurone axons, resulting in the release of the neurotransmitter acetylcholine from axon terminals. The transmitter activates nicotinic cholinergic receptors located on the muscle cell membrane. These receptors are ligand-gated cation channels. Upon binding of acetylcholine, the receptor channel opens to allow mainly Na⁺ ions to enter the muscle cell, causing a partial membrane depolarization. This triggers action potentials in the muscle cell membrane, resulting in Ca²⁺ influx and muscle contraction. The structure and function of the NMJ are such that, even under the extremes of muscular exertion, the operation of the NMJ is highly reliable. This is because a large ‘safety factor’ is intrinsic to NMJ function in the sense that more neurotransmitter is released than is necessary to initiate muscle contraction. However, the normal function of the NMJ can be severely disrupted by drugs, naturally occurring toxins and disease. Myasthenia gravis, for example, is characterized by muscle weakness and easily fatigued muscles. It is an autoimmune disorder in which the body produces antibodies to the muscle nicotinic receptor protein.     

Neuromuscular function and transmission

Neuromuscular transmission occurs across the tiny 50 nm gap between an axon terminal and a skeletal muscle fibre at the end-plate region. An axon with its many terminal branches and connected muscle fibres forms a motor unit. A single axon terminal contains thousands of vesicles of the chemical transmitter acetylcholine. An axonal action potential increases axon terminal permeability to calcium and the resulting increase of free calcium ions above the resting concentration causes about 100 of the vesicles to release their transmitter into the gap. The end-plate region is folded to increase its surface area to about 3000 square micrometres. The acetylcholine released reacts with acetylcholine receptors situated at the crests of these folds. When the receptor has bound two acetylcholine molecules it changes its configuration to form a cation pore that allows sodium and potassium ions to move in and out of the muscle end-plate region. The combined activation of 30,000,000 receptors occurring at one end-plate causes the muscle membrane to depolarize at the muscle junction to about −10 mV, forming a localized end-plate potential. Acetylcholine is rapidly destroyed by the enzyme acetylcholinesterase, which allows the receptors and membrane of the end-plate to recover and respond to further neuronal action potentials. Since the localized end-plate potential is well in excess of the threshold stimulus required to generate a muscle action potential, as long as acetylcholine is being released by presynaptic action potentials, then postsynaptic muscle action potentials will be produced and result in a maintained contraction.     

Neuromuscular monitoring

In patients receiving a neuromuscular blocking agent, quantitative monitoring of neuromuscular function is essential. For this purpose, neuromuscular monitoring devices which provide train-of-four ratio values are necessary In the absence of a quantitative monitoring device, neuromuscular function may be evaluated with the use of a nerve stimulator. Muscle responses can be monitored either using the mechanomyography, electromyography, acceleromyography, or phonomyography. Although, mechanomyography is still considred the gold standard for assessing the neuromuscular function, mechanomyography is not easy to set up and use in a routine clinical setting. At present we have only two commercially available devices which are easy to set up and useful in daily clinical practice. One is M-NMT monitor which comes with Datex AS/3 or S/5 monitor. The other is TOF-Watch acceleromyographic monitor. In clinical anesthesia, sites of monitoring can be any superficially located peripheral nerves and innervated muscles. Since different muscle groups have different sensitivity to neuromuscular blocking agents, results obtained for one muscle cannot be extrapolated to other muscles. Also, results from one monitoring method cannot be extrapolated to other methods. Anesthesiologists should be aware of these differences. In this article, the basics of neuromuscular monitoring are summarized.     

Neuromuscular monitoring

Neuromuscular monitoring is central to the rational use of neuromuscular blocking agents. Stimulation of a peripheral nerve by electrical or magnetic means is followed by contraction of a voluntary muscle. Single impulses may be used but more commonly impulses are given in groups. The train of four, double burst and post-tetanic count are those trains usually employed clinically. Almost any skeletal muscle can be used but those of the hand, face and leg are most commonly employed as they are the easiest to both stimulate and record from. The responses of muscles may be measured by direct visual or tactile means. More accurate methods include mechanomyography, electromyography and accelerometry.     

Neuromuscular monitoring

This review summarizes recent reports on the techniques and the use of methods for monitoring neuromuscular function during anaesthesia. The latest news on the use of acceleromyography in the face and hand, on laryngeal and diaphragmal surface electromyography, on acoustic myography, on evaluation of intense neuromuscular block, and on postoperative residual curarization is presented and discussed. It is concluded that available evidence suggests that more attention should be paid by the anaesthetist to the problems of residual curarization and hence to proper monitoring of neuromuscular function using objective methods.     

Neuromuscular transmission and its blockade

The role of two recently introduced muscle relaxants--atracurium and vecuronium--in contemporary anaesthetic practice is assessed. Recent advances in the physiology of neuromuscular transmission, particularly the roles of calcium and calmodulin, are reviewed, and new ideas concerning the reversal and monitoring of neuromuscular blockade are discussed.