Characterizing Fade Upon Train-of Four Stimulation During Onset and Offset of Neuromuscular Block Produced by Succinlycholine

Muscle relaxants are frequently employed during anesthesia. These medications may be employed to facilitate tracheal intubation, mechanical ventilation or to allow better surgical access. All muscle relaxants act at the neuromuscular junction. Based on the mechanism of action, two kinds of muscle relaxants have been defined1. Nondepolarizing muscle relaxants are competitive antagonists of the neurotransmitter acetylcholine (Ach) at the neuromuscular junction. The second kind of muscle relaxant is the depolarizing muscle relaxant and succinylcholine is the only muscle relaxant in this class that is clinically used. The mechanism of action of succinylcholine is less clear. Succinylcholine appears to mimic the actions of acetylcholine but results in a longer duration of depolarization of the post synaptic membrane1.

The degree of muscle relaxation produced by these muscle relaxants is measured by stimulating a motor nerve and measuring either the force of the muscle contraction produced or its compound muscle action potential (CMAP). As the muscle relaxation increases, the force of muscle contraction or the amplitude of the electromyogram (EMG) is correspondingly reduced.

On occasion, to measure the degree of muscle weakness or paralysis caused by a muscle relaxant, instead of a single stimulus, trains of stimuli are applied2. One method of repetitive stimulation is to apply four stimuli over a two second period. This method of nerve stimulation is called Train-of-Four (TOF). When this form nerve stimulation (TOF) is applied to patients who have been given nondepolarizing muscle relaxants -there is fade. Fade means that the force of successive muscle contractions is less than the preceding contraction3. The second contraction is less than the first, the third less than the second and so on. The degree of fade appears to have some reasonably well defined relationship to the degree of relaxation produced3.

The classic teaching in the anesthetic literature is that depolarizing muscle relaxants do not produce fade upon repetitive stimulation. It means that upon repetitive stimulation, the successive contractions are similar. This is one of the defining features of a depolarizing block and is called a Phase I block. The traditional teaching is that when a depolarizing muscle relaxant is administered in large or repetitive doses, a Phase II block develops. The phase II block has characteristics similar to those of a nondepolarizing muscle relaxant (ie fade on repetitive or TOF stimulation). De Jong and Freund first proposed that this differentiation between deplolarizing and nondepolarizing block based upon fade may not be as clear cut. These investigators demonstrated that succinylcholine caused fade upon repetitive stimulation right from the outset of the neuromuscular block. Other investigators have also demonstrated that succinylcholine causes fade from the initiation of the neuromuscular block. If it can be conclusively demonstrated that succinylcholine causes fade, then fade would be less useful in differentiating a depolarizing from a nondepolarizing block. We have previously investigated and defined the fade caused by nondepolarizing muscle relaxants. Using the experience we have gained in studying fade with nondepolarizing muscle relaxants, we would like to now define the characteristics of fade (if any) caused by succinylcholine.

Method: We intend to enroll fifty healthy adults, 18-60 years of age of either sex who are scheduled to undergo a surgical procedure under general anesthesia. Only subjects with a BMI <25 Kg/m2 will be enrolled. Only subjects free from any hepatic or renal disease will be included. We will exclude any subjects with known allergy to succinylcholine, family history of malignant hyperthermia or any history of skeletal myopathy. We will also exclude subjects that have recently sustained burns, or any illness resulting denervation injury (paraplegia or hemiplegia).