Download Respiratory Muscle Fatigue: A Cause of

Clinical Science and Molecular Medicine (1977) 53,419-422.
Respiratory muscle fatigue: a cause of respiratory failure?
P. T. MACKLEM A N D C. S. ROUSSOS
Meakins-Christie Laboratories, McGill University Clinic, Royal Victoria Hospital,
Montreal, P.Q.,Canada
(Received 26 April 1977; accepted 10 June 1977)
summary
1. The question whether respiratory muscle
fatigue ever causes respiratory failure is over
40 years old, but we still have no definitive
answer to this question. Skeletal muscle fatigue
occurs when the rate of energy consumption of
themu scle is greater than the energy supplied,
so that energy stores are utilized and eventually become depleted.
2. Five factors which are important in the
development of muscle fatigue (a, the tension
developed by the muscle; b, the maximum tension the muscle can develop; c, the enagystored
within the muscle; d, the energy supplied to the
muscle; e, the efficiency of the muscle). These
can be affected in many diseases, so disposing
to fatigue, thus respiratory muscle fatigue is
likely to be a common occurrence.
3. Respiratory muscle fatigue can in principle
easily be diagnosed at the bedside by application
of a simple electromyographictechnique used to
detect fatigue in other skeletal muscles,
Key words : fatigue, muscle, respiratory failure.
Abbreviation: MBC, maximum breathing capacity.
it has been asked time and time again. Skeletal
muscle fatigue is not difficult to quantify and it
is a phenomenon that has been studied intensively. Thus it is astonishing that very few
serious attempts have been made to document
respiratory muscle fatigue in either health or
disease, in either man or experimental animals.
Yet it would appear that we currently have at
our disposal all the technology necessary to
diagnose and document respiratory muscle
fatigue, reliably, non-invasively and before the
muscles actually fail as generators of negative
intrapleural pressures on inspiration.
Skeletal muscle fatigue (as opposed to central
or neuromuscular transmission fatigue) occurs
when the rate of energy consumption by a
muscle is greater than the rate of energy
supplied to the muscle by the blood. That being
the case, muscle draws upon its energy stores
and when they are depleted the muscle has no
further sources of energy and it fails as a
pressure generator. Thus when a muscle becomes
fatigued its total energy consumption (which
equals the total work performed by the muscle
divided by its efficiency) is the sum of the energy
stores plus the total amount of energy extracted
from the blood by the muscle. This can be
expressed by a modification of the equation
developed by Monod & Schemer (1965):
Introduction
D o the respiratory muscles fail in much the
same way as the heart fails? The question is at
least 42 years old (Killick, 1935) and since then
WIE
= a
+ Btllm.
(1)
where W = total external work performed by
the muscle, E = efficiency, u = energy stores,
B = rate of energy supplied to the muscle and
tllm.= endurance time. Solving for tllm.:
Corregpondence: Dr P. T. Macklem, Hopital
Laennec, Clinique de Pneumo-physiologie, 42 rue de
Sevres, Paris 7e, France.
419
420
P. T. Macklem and C. S. Roussos
where @' = muscle power ( = W/tll,,,.).
Eqn. (2)
reveals that when /?E2@, the muscle can
continue to work indefinitely without becoming
fatigued, but that when BE < @, there will be a
finite endurance time, Thus a decrease in either
efficiency or B will predispose to fatigue as will
an increase in muscle power.
In general, skeletal muscle fatigue will occur
when a muscle contracts isometrically and
generates a tension of greater than 15% of its
maximum tension; or when, contracting intermittently with equal contraction and relaxation
times, it develops a tension greater than 40% of
its maximum tension. Thus in terms of the
critical mechanical power a muscle can develop
indefinitely without becoming fatigued, it is
necessary to consider the maximum tension the
muscle can develop, as well as the tension
developed in order to perform the work.
The factors which are important in the development of fatigue are therefore (1) the tension
developed by the muscle; (2) the maximum
tension the muscle can develop; (3) the energy
stored within the muscle; (4) the energy supplied
to the muscle, which is a function of its perfusion, the oxygen content and the concentration of substrates in arterial blood, and the
ability of the muscle to extract these energy
sources; (5) the efficiency of the muscle in
performing external work.
In trying to predict the development of
respiratory muscle fatigue in particular, these
factors must be taken into consideration.
Translated into respiratory physiological terms,
they include the lung volume at which the
muscle is operating. Because the maximum
inspiratory pressures diminish as lung volume
increases (Rahn, Otis, Chadwick & Fern,
1946), one would predict that for any given
power required to breathe, hyperinflation
would predispose to fatigue, as would an
increase in the work of breathing, Other predisposing conditions include conditions leading
to weakness of the inspiratory muscles, hypoxia,
decreased cardiac output, the state of nutrition
of the respiratory muscles and the mechanical
loads against which the muscles must operate,
which are known to alter respiratory muscle
efficiency.
There have been a number of studies designed
to determine the critical minute ventilation that
normal subjects can maintain indefinitely.
Zocche, Fritts & Cournand (1960) found that
normal subjects were capable of maintaining a
ventilatory level of 53% of maximum breathing
capacity (MBC) for 15 min, and Tenney &
Reese (1968) estimated the critical minute
ventilation to be 55% of MBC. On the other
hand, Shephard (1967) and Leith & Bradley
(1976) found that normal subjects could ventilate at 7040% of MBC for 15 min. The reason
for the discrepancy in the various studies is not
clear, but could be related to differences in
respiratory rate and depth in the different
studies. From these studies one could assume
values for resistance and compliance and estimate a critical work load in patients that would
result in fatigue. Such an exercise would probably not be very useful as more information
would be needed about the maximum pressures
the patients could develop, the degree of
hypoxia, etc. Furthermore, McGregor & Becklake (1961) found that respiratory muscle
efficiency decreased markedly as inspiratory
resistance was increased for the same external
power produced by the respiratory muscles.
Sharp, Van Lith, Vej Nuchprayoon, Briney
& Johnson (1968) measured maximum inspiratory mouth pressures in patients with
chronic airways obstruction and calculated
theoretical values based upon the patients' lung
volumes and the normal values of Rahn ei al.
(1946). Their measured values were -1.5-6.0
kPa (-15-60 cm water) [mean, -3.0 kPa
( - 30 cm water)] whereas the calculated values
ranged from zero to - 6.4 kPa ( - 64 cm water)
[mean, -39 kPa (- 39 cm water)]. Our studies
indicate that the critical transdiaphragmatic
pressure above which fatigue occurs is 40% of
maximum (Roussos & Macklem, 1977). For all
the inspiratory muscles acting together we
estimated the critical pressure to be between
50 and 70% of maximum (Roussos, Fixley,
Gross & Macklem, 1976). Combining the two
estimates would indicate that the critical
inspiratory transpulmonary pressure swings in
airways obstruction would be in the order
of 2.0 kPa (20 cm water), a value that is very
likely to be exceeded during exercise in such
patients, and also during a severe attack of
asthma. Sharp et af. (1968) concluded that
' . . ineffectiveness or exhaustion of inspiratory
muscles, working at disadvantageously short
initial lengths . . .' might be a major factor in the
.
Respiratory muscle fatigue
.
development of hypercapnia and that '. .failure
of the inspiratory pump may be an important
contributing factor in their ventilatory failure'.
Although hyperinflation may be beneficial in
opening obstructed airways, and improving
ventilation distribution and gas exchange, it is
hardly beneficial for inspiratory muscle funo
tion.
Our own studies have revealed that when
normal subjects are asked to breathe against
fatiguing loads at the mouth, they alternate
between predominantly using the diaphragm to
develop the necessary pressures and using the
intercostal/accessory muscles. When the diaphragm is the only inspiratory muscle contracting, the abdomen is displaced outward as
the rib cage expands (Goldman & Mead, 1973).
When the intercostallaccessory muscles are the
only muscles contracting and the transdiaphragmatic pressure remains zero, the abdomen
is displaced inwards as the rib cage expands.
Thus by simple bedside observation one may
determine with a fair degree of accuracy which
muscle groups are being used. This may be
important. Ashutosh, Gilbert, Anchincloss &
Peppi (1975) found that asynchronousbreathing
movements in patients with obstructive pulmonary disease were associated with a poorer
prognosis. Although the asynchrony was
complicated, there were inward displacements
of the abdomen during inspiration. Similarly,
Sharp, Goldberg, Druz, Fishman & Danon
(1977) found inward abdominal displacementin
inspiration in five of 20 patients not in respiratory failure, but in eight of ten patients who
were in respiratory failure, and concluded that
there was ' . . growing acceptance of the idea
that faulty co-ordination of overworked and
fatigued respiratory muscles contributes to
dyspnoea and respiratory failure. . .'.
One can easily think of other situations where
inspiratory muscle fatigue is likely to be a cause
of respiratory failure. The devastating effects of
respiratory infections (which increase the load)
in patients with neuromuscular weakness is
a good example. Although the exact physiologicalrole of intra-uterinebreathingmovements
remains obscure, they almost certainly play a
role in training the respiratory muscles for the
day when they must be solely responsible for
the act of breathing. hemature babies are born
with an inadequate training period. If superimposed upon this, they develop an increased load
.
B
421
with the development of the respiratory distress
syndrome of infancy, it would not be surprising
if inspiratory muscle fatigue was responsible for
the hypercapnia that such babies develop.
Weaning problems from respirators are not
uncommon. Our orthopaedic colleagues tell us
that the muscles which atrophy most rapidly
when put to rest are those which normally we
use the most. The skeletal muscles that we use
the most are the respiratory muscles. If they
atrophy during prolonged artificial ventilation,
is it surprising that some patients during the
weaning period can breathe quietly without
distress for a short period, but then become
progressively more dyspnoeic and the arterial
Pcoa starts to climb? In acute pulmonary
oedema, there is a decreased cardiac output and
hypoxaemia, both of which presumably diminish 8, the rate of energy supply to the muscles. In
addition, there is an increase in the work of
breathing. Is the hypercapnia sometimes seen in
acute pulmonary oedema caused by inspiratory
muscle fatigue?
The answer to these questions and the diagnosis of fatigue at the bedside must await the
development of a reliable means to detect
inspiratory muscle fatigue. Such methods are
currently available for other skeletal muscles.
Kogi & Hakamada (1962) and Kaiser &
Petersh (1963) have shown that with the
development of fatigue in a skeletal muscle, the
low-frequency components of the electromyogram increase in amplitude while the highfrequency components decrease, for the same
tension development. Kogi & Hakamada (1962)
showed that the ratio of the two amplitudes
(amplitude <40 Hzlamplitude >40 Hz) was
virtually independent of either muscle strength
or strength of contraction. When the muscle
performed at fatiguing work loads the ratio
increased and the increase was apparent before
any symptoms of fatigue developed. They used a
subjective grading of fatigue. Stage 1 was the
appearance of the sensation of fatigue in the
muscle. Stage 2 was development of local pain;
stage 3 was the desire to relax the contraction
and stage 4 was the incapability to maintain
tension. There was an excellent correlation
between the ratio of the slow- to high-frequency
components of the electromyogram and these
stages. In stage 1 the ratio increased by 20-40%,
in stage 2 by 2040%; stage 3 by 30-100% and
stage 4 by 50-200%. In non-fatiguing loads
422
P. T.Macklem and C. S. Roussos
there was very little change even though the
symptoms of stage 1 were felt.
The important point to emphasize in this landmark study is that the electromyogram signal of
fatigue was easily detectable long before the
muscle actually failed as a pressure generator.
Attempts have now begun to apply this technique to the detection of inspiratory muscle
fatigue. It appears to be suitable in laboratory
circumstances in normal subjects (Gross,
Grassino & Macklem, 1977). This does not
mean that it will be easy to perform in the
hustle and bustle of an intensive care ward.
However, Swedish investigators have developed
this technique to a high degree of sophistication
and it is currently being used to detect muscle
fatigue in industrial workers on site in their
factories (Broman, Magnussum, Peters& &
Ortengren, 1973; Lindstrom, Magnusson &
Peterskn, 1970; Kadeforz, Petersen & Heberts,
1976; Lindstrom, Magnusson & Peters&,
1974; Ortengren, 1975). This suggests that the
application of this technique to the bedside in
hospitals should not be difficult.
We await the results of this development
with interest. It should provide the answer to
the 40-year-old question : is respiratory muscle
fatigue a cause of respiratory failure?
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