Page 666 - Hall et al (2015) Principles of Critical Care-McGraw-Hill

CHAPTER 54: Acute-on-Chronic Respiratory Failure 485

pressure. Patients receiving mechanical ventilation for ACRF in COPD At end expiration, there remains a positive elastic recoil pressure, which
typically have acute-on-chronic hyperinflation due to intrinsic PEEP is called intrinsic positive end-expiratory pressure (PEEPi). Accordingly,
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compounding their pre-intubation lung function impairment. This alveolar pressure remains positive with respect to end-expiratory pres-
hyperexpansion forces the inspiratory muscles to operate in a disadvan- sure at the airway opening, such that a greater effort must be generated
tageous portion of their force-length relationship. by the inspiratory muscles on the subsequent breath. Intrinsic PEEP of
■ RESPIRATORY MUSCLE FATIGUE 5 to 10 cm H O is present in most, if not all, COPD patients with acute
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and PEEPi can be measured in many ambula-
ventilatory failure,
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The role of respiratory muscle fatigue in the pathogenesis of ACRF is tory outpatients as well. This adds a threshold load to spontaneous
inspiration and, in mechanically ventilated patients, makes triggering of
complex. Muscle fatigue is the reversible loss of force generation despite assisted breaths more difficult. Significant additional inspiratory muscle
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adequate neural stimulation. Fatigue is itself a cause of muscle weakness activation is required to reduce pleural pressures below PEEPi before
and can be short lasting (high-frequency fatigue), or long lasting (low- pressure is reduced in the central airway to trigger a mechanical breath.
frequency fatigue), which can persist for days to weeks. In healthy adults, Determinants of the magnitude of PEEPi include the degree of expiratory
experimental induction of low-frequency respiratory muscle fatigue obstruction (including both patient and ventilator), elastic recoil, minute
does not impair maximum ventilatory or exercise performance. ventilation, and expiratory time (therefore, respiratory rate, inspiratory
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However, in ACRF low-frequency fatigue may have significant flow rate, and inspiratory flow profile). As discussed more fully below,
functional consequences. To the extent that fatigue is central to the counterbalancing this PEEPi with external PEEP provides a means by
development of respiratory failure, it may be caused by an inadequate which to lower the work of breathing (or the work of triggering). The
supply of nutrients, excess generation of metabolites such as lactate or impact of PEEPi on the work of breathing is illustrated in Figure 54-1.
hydrogen ion, or depletion of muscle glycogen. Evidence to support the Diaphragm strength (measured by sniff esophageal pressure) in patients
importance of blood supply in the genesis of fatigue comes from studies with severe but stable COPD is only two-thirds that of normal individu-
of respiratory failure in animals with hemorrhagic, cardiogenic, or septic als, virtually all of this ascribable to the diaphragm position rather than to
shock. 44,45 In these animals, fatigue is hastened by circulatory insuf- inherent muscle weakness. Still, patients presenting with ACRF may have
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ficiency. The magnitude of blood flow to the respiratory muscles seems not only worsening hyperinflation but also other conditions (eg, protein-
to be important beyond aerobic needs, as demonstrated in experiments calorie malnutrition, steroid myopathy ) that cause intrinsic muscle
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in which flow was manipulated independently of oxygen delivery. weakness. Even when patients with severe COPD are in a state of compen-
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Hypoperfusion states, hypoxemia, and severe anemia have the potential sation, the increased load and diminished neuromuscular competence are
to contribute to muscle fatigue and thereby to hasten respiratory failure. precariously balanced. Only minor additional decrements in strength or
Notably, moderately severe COPD patients do not develop low- increments in load are sufficient to precipitate inspiratory muscle fatigue
frequency diaphragmatic fatigue after maximal exercise effort when and respiratory failure. It is this incremental deterioration in the balance
measured with nonvolitional magnetic coil–induced twitches. 47,48 of neuromuscular competence and respiratory system load that defines
Consistent with this is that low-frequency diaphragm fatigue has not ACRF. Its many potential contributors are enumerated in Figure 54-2.
been demonstrated in patients receiving mechanical ventilation for
ACRF in AECOPD. This is not surprising given that muscle shorten-
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ing protects against fatigue both in isolated models as well as in vivo ADDITIONAL CAUSES OF DECREASED
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in COPD. In addition intracellular modifications of cell type, con- NEUROMUSCULAR COMPETENCE (SEE FIG. 54-2)
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tractile proteins such as titin, and single-fiber contractile energetics
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would predict that, compared to other muscles, the diaphragm would be ■ FAILED NEUROMUSCULAR TRANSMISSION
fatigue resistant. These cellular changes are discussed below. In order to effect adequate ventilation, the CNS must transmit drive
By contrast, accessory muscles of respiration that are frequently to the working muscles via the spinal cord and peripheral nerves.
recruited for expiration during AECOPD, including abdominal wall Therefore, causes of neuromuscular failure, such as spinal cord lesions,
muscles, are fatigable in COPD patients during loaded exercise. Several primary neurologic diseases, and neuromuscular blocking drugs, may
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experiments in humans indicate that the work intensity required of the produce ACRF. Aminoglycosides and procainamide act as mild
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contracting respiratory muscles, as well as their strength, are crucial neuromuscular blockers, a feature unimportant in the great majority
factors determining fatigue. Additionally myocyte ischemia can result of patients but relevant in those with neuromuscular diseases, such
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from hypotension, reduced cardiac output or “steal” of blood flow by as myasthenia gravis. The clinical setting may be a clue to one of the
other organs. Thus prolonged pathological loading from superimposed unusual causes, such as phrenic nerve injury following cardiopulmonary
infection, heart failure, or other precipitants could result in sarco- bypass. This occult lesion may be induced by direct trauma to the nerve
meric disruption, cellular acidosis, and accessory (expiratory) muscle or, more indirectly, by cold cardioplegia.
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fatigue in the face of increased respiratory system resistance. 59
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Through whatever combination of causes, once respiratory muscle ■ MUSCLE WEAKNESS
force generation fails, neuromuscular competence is unable to sustain the
mechanical load imposed on the respiratory system. The consequence is a The most important causes of decreased neuromuscular competence
rapid-shallow breathing pattern and ultimately failure of alveolar venti- and reduced force generation fall into the category of muscle weakness.
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lation ensues. The intensivist must therefore address both the precipitant In patients with COPD, respiratory muscle changes represent a balance
and resultant respiratory muscle failure for treatment to be successful. between factors capable of impairing respiratory muscle function and
metabolic adaptation of the diaphragm (Table 54-1).
■ AIRFLOW OBSTRUCTION AND DYNAMIC HYPERINFLATION Changes in chest wall geometry and diaphragm position are particu-
(INTRINSIC PEEP) larly important and adversely affect the muscles of inspiration (diaphragm
and intercostal muscles) and expiration (abdominal muscles). The inspi-
Airflow obstruction, compounded by decreased elastic recoil in patients ratory muscles are poorly able to tolerate maximal loading that occurs
with emphysema, leads to prolongation of expiration. When the rate of in emphysema. Hyperexpansion forces them to operate on a disadvanta-
alveolar emptying is slowed, expiration cannot be completed before the geous portion of their force-length curve. The piston-like displacement of
ensuing inspiration. Rather than reaching the normal static equilibrium the diaphragm is compromised and expansion of the lower thoracic cage
of lung and chest wall recoil at functional residual capacity (FRC) at is disturbed. In addition, a flattened diaphragm generates less transmural
the end of each breath, the respiratory system empties incompletely. pressure for a given tension than the normally curved one, as described
Expiration terminates at this higher, dynamically determined FRC. above. Electrolyte disturbances such as hypokalemia, hypophosphatemia,
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