Muscle relaxants are medications used during surgery to facilitate surgical access. The
effect of the muscle relaxant medications is measured by stimulation a motor nerve and
measuring the force of the resultant muscle contraction. Based on the mechanism of action,
two kinds of muscle relaxants are described. First a nondepolarizing muscle relaxant and the
second kind is the depolarizing muscle relaxant. These two kinds of muscle relaxants can be
distinguished by rapidly stimulating the nerve 4 times over 2 seconds (Train of four or
TOF). The nondepolarizing muscle relaxants produce fade ie successive muscle contractions
are less forceful than the preceding ones. Whereas the depolarizing muscle relaxants are
generally believed to produce four contractions of equal strength. However, there is some
indication that this may not be entirely correct. There is evidence that depolarizing muscle
relaxants also may produce fade. The investigators are conducting the following study to
determine if indeed depolarizing muscle relaxants produce fade. The investigators would also
like to characterize the fade ie differences during onset and offset of the block and the
effect of the dose on the degree on the fade.
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
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
The subjects will give an informed consent prior to the participation in the study. All
patients will receive 2 mg of midazolam for premedication. Anesthesia will be induced with
the intravenous administration of fentanyl 5-6 µg/kg and propofol 2-3 mg/kg. Following
tracheal intubation, anesthesia will be maintained with 70% nitrous oxide in oxygen
supplemented with an infusion of propofol (120 -150 µg/kg/min). Ventilation will be
controlled to maintain normocapnia (end-tidal carbon di oxide 35-40 mmHg).
After the commencement of the anesthesia monitoring of neuromuscular transmission will be
commenced. Ulnar nerve at the wrist will be stimulated in a TOF sequence (2 Hz every 12
seconds). The resultant force of contraction of the adductor pollicis will be recorded using
a mechanomyograph. After obtaining a stable muscle contraction, succinylcholine will be
administered. The subjects will be randomly allocated to one of five groups. Group 1 will
receive 0.1 mg/kg, group 2 -0.15 mg/kg, group 3 -0.2 mg/kg, group 4 -0.25 mg/kg, group 5
-0.3 mg/kg. Muscle contraction will be recorded until the force of muscle contraction
returns to baseline (6-8 minutes). At this time the study will be concluded. Further conduct
of the anesthetic will be at the discretion of the subject's primary anesthesiologist.
Data Analysis: We intend to plot the force of all four muscle contractions from immediately
preceding the injection succinylcholine to complete recovery of the muscle contraction. We
would then plot the force of the first twitch (T1) against the ratio of the fourth to the
first twitch (T4/T1 ratio) for each individual subject. This plot will allow us to determine
if there is any difference in fade characteristics between onset and offset of muscle
- ASA PS I or II,
- 18-60 years of age of either sex,
- with a BMI<25Kg/m2
- presence of any disease involving the neuromuscular system.
- Presence of any neurologic illness eg . Paraplegia or hemiplegia, spinal cord
injuries, stroke, multiple sclerosis.
- No liver or kidney disease.
- Known allergy to succinylcholine.
- Family history of malignant hyperthermia.
- Known pseudocholinesterase deficiency.
- Any skin burns within the last 1 year.
We would also exclude subjects with;
- Central core disease,
- duchenne or Becker muscular dystrophy,
- osteogenesis imperfecta,
- Noonan syndrome,
- arthrogryposis multiplex,
- neuroleptic malignant syndrome,
- multiminicore disease,
- King Denborough syndrome,
- Native American myopathy,
- hypokalemic periodic paralysis or
- a history of rhabdomyolysis.
We would also exclude any subject with a history of cardiac arrhythmias.