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September 2002
Volume 66 |
Number 9
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Monitoring of Neuromuscular
Function: Past, Present and Future
John J. Savarese, M.D
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From the introduction of d-tubocurarine into clinical practice
in 1942 until the early 1980s, all neuromuscular blocking drugs
were long-acting because they were not metabolized and were excreted
very slowly by the kidney. Recovery from paralysis was so slow
and gradual that it was difficult to decide at which point clinical
function had returned to normal in a patient who was still unresponsive.
Consequently, this poorly definable and lengthy period of paralysis
required a conservative approach to dosing and reversal, and the
importance of testing neuromuscular function evolved out of clinical
necessity. Guidelines for clinical practice were badly needed
to help ensure safety, particularly during recovery and emergence
from anesthesia.
At the time when d-tubocurarine (1942), alcuronium (1964) and
pancuronium (1967) were the staple relaxants, Christie and Churchill-Davidson1
and Katz1A first popularized the
use of peripheral nerve stimulation in the mid-1960s (the "Block-AidŽ
Monitor") to evaluate neuromuscular function. This device
applied a twitch (every four seconds) or tetanic stimulation (30
Hz on demand). These investigators popularized the observation
and recording of adductor responses from the thumb, elicited via
the ulnar nerve at the wrist.1A Shortly
thereafter, Ali and others (1971)2
introduced train-of-four (TOF) stimulation, and Lee (1975)3
further popularized this technique by quantifying and correlating
depth of blockade (percent twitch inhibition) according to the
TOF count. The TOF technique has remained the most useful method
of evaluation of neuromuscular function in the clinic for more
than 30 years because of its simplicity and ease of evaluation
and because the stimulus pattern creates its own internal standard
each time the response is evaluated; that is, the strength of
the fourth response is simply compared with that of the first
without the need for establishment of a baseline prior to the
administration of neuromuscular blocking drugs.
The trouble is, the TOF response/evaluation needs updating to
properly link new relaxants and new techniques to the more stringent
safety requirements of today's anesthetic practice. The introduction
of double-burst stimulation (DBS),4
which enables the practitioner to estimate a depth of paralysis
corresponding with a TOF value of about 60 percent, was an advance
in this direction. DBS, in turn, usually suggests that the patient
will be able to perform clinical tests such as head lift. This
test is not discriminating enough, however, to ensure normal function
of airway and swallowing reflexes.
Several recent studies 5-7 have called
for the adoption of a TOF value of 0.90 as an indicator of the
ability to protect the airway and to swallow (or vomit) normally.
At present, we have no test or response that we can elicit via
a nerve stimulator in order to infer a level of neuromuscular
function compatible with a TOF value of 0.90. This level of function
can presently be measured only by accelerometry, electromyography
or mechanomyography and not by any easily observed clinical test
that can be performed or without a sophisticated measuring device.
So a test is needed that will tell the clinician that the patient's
level of paralysis is compatible with the maintenance of his or
her airway, the ability to swallow and with a TOF value of at
least 0.90. In addition, the test should be applicable using only
a nerve stimulator without the aid of an expensive device to measure
the response. What exactly is needed is a new stimulus pattern,
more "sensitive" than DBS, to elicit a response that
can be seen or felt and is compatible with or indicates a TOF
value of 0.90 and the level of neuromuscular function appropriate
to that indicator.
"There
are at least two new developments in testing that
will change neuromuscular monitoring significantly
and dramatically and will thereby alter clinical practice
very much in the direction of added patient safety."
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The above commentary would be completely pertinent if we continue
to practice with current relaxants (intermediate and long-acting
nondepolarizers) and antagonists (anticholinesterase agents).
What about the future? There are at least two new developments
in testing that will change neuromuscular monitoring significantly
and dramatically and will thereby alter clinical practice very
much in the direction of added patient safety. These drugs and
techniques might conceivably render "routine" neuromuscular
monitoring unnecessary or at least superfluous in nearly all cases.
The first is a new antagonist, most specific for rocuronium but
which may also be given to remove residual paralysis due to other
steroidal relaxants such as vecuronium or pancuronium.8
This compound is a doughnut-shaped polysaccharide (cyclodextrin)
that is negatively charged and, as a result, is able to chelate
the steroidal relaxants and thereby prevent their ability to block
nicotinic receptors. The "reversal" is rapid and complete,
according to early reports, and the chelating agent has minimal
side effects. This may allow the cancellation of relatively deep
paralysis without the need for some evidence of beginning recovery
such as the reappearance of one or two twitches on TOF stimulation.
The second is the new ultra short-acting nondepolarizing relaxant
GW280430A (430A).9-10 This nondepolarizer
has all the kinetic characteristics in humans of succinylcholine
(onset, duration and recovery), is destroyed chemically with a
probable half-life of one to two minutes and is noncumulative
with minimal side effects. It appears to be the first true candidate
to actually replace succinylcholine. If administered by infusion,
it can be predicted that patients will recover spontaneously to
TOF values of greater than 0.90 within six to seven minutes after
stopping the infusion, and this speed of recovery can be expected
even if double the dose required to maintain a 95-percent blockade
were infused. Since the destruction of GW280430A in the body is
entirely a chemical reaction, most likely there will not be any
rare exceptions to its normal kinetics. In other words, pseudocholinesterase
problems are rare because the drug is destroyed in a chemical
reaction requiring no enzymatic catalyst. With this kind of speed
of spontaneous recovery, will antagonism of residual blockade
ever be necessary?
Will neuromuscular monitoring disappear from clinical practice?
Not entirely, I think. Most likely we will be influenced to monitor
more for documentation and safety purposes and less for precise
control of depth of relaxation. How about the following fantasies?
If spontaneous recovery from paralysis occurs in everybody within
six to seven minutes without reversal following 430A, and if the
compound always "reverses" block by steroidal relaxants
within five to 10 minutes, why bother to monitor at all?
References:
1. Christie TH, Churchill-Davidson HC. The St.
Thomas's Hospital nerve stimulator in the diagnosis of prolonged
apnoea. Lancet. 1958; 1:776.
1A. Katz RL. A nerve stimulator for the continuous
monitoring of muscle relaxant action. Anesthesiology. 1965; 26:832.
2. Ali HH, Utting JE, Gray C. Quantitative assessment
of residual antidepolarizing block (part II). Br J Anaesth. 1971;
43:478.
3. Lee CM. Train-of-4 quantitation of competitive
neuromuscular block. Anesth Analg. 1975; 54:649.
4. Engbaek J, Ostergaard D, Viby-Mogensen J. Double-burst
stimulation (DBS): A new pattern of nerve stimulation to identify
residual curarization. Br J Anaesth. 1989; 62:274.
5. Erikson LI, Sundman E, Olsson R, et al. Functional
assessment of the pharynx at rest and during swallowing in partially
paralyzed humans. Anesthesiology. 1997; 87:1035.
6. Kopman AF, Yee PS, Neuman GG. Relationship
of train-of-four fade to clinical signs and symptoms of residual
paralysis in awake volunteers. Anesthesiology. 1997; 85:765.
7. Viby Mogensen J, Chraemmer Jorgensen B, Berg
H, et al. Residual neuromuscular block is a risk factor for postoperative
pulmonary complications. A prospective, randomized and blended
study of postoperative pulmonary complications after atracurium,
vecuronium and pancuronium. Acta Anaesthesiol Scand. 1997; 41:1095.
8. Bom A, Cameron K, Clark JK, et al. Chemical
chelation as a novel method of NMB reversal discovery of ORG 25969.
Eur J Anesthesiology. 2002 (in press).
9. Belmont MR, Lien CA, Savarese JJ, et al. Neuromuscular
blocking effects of GW280430A at the adductor pollicis and larynx
in human volunteers. Br J Anaesth. 1999; 82 (suppl):A419.
10. Belmont MR, Lien CA, Savarese JJ, et al.
Dose-response relations of GW280430A in the adductor pollicis
under propofol, nitrous oxide, opioid anesthesia. Anesthesiology.
1999; 91:A1014.
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John
J. Savarese, M.D., is Professor and Chair, Cornell-Weill Medical
Center, Cornell University, New York, New York. |
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