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Respiratory muscle function in the critically ill 

Respiratory muscle function in the critically ill
Chapter:
Respiratory muscle function in the critically ill
Author(s):

Theodoros Vassilakopoulos

and Charis Roussos

DOI:
10.1093/med/9780199600830.003.0077
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date: 29 November 2020

Key points

  • The main inspiratory muscle is the diaphragm.

  • Hyperinflation places the diaphragm at a great mechanical disadvantage, decreasing its force generating capacity.

  • The ability to take one breath depends on the balance between the load faced by the inspiratory muscles and their neuromuscular competence, whereas the ability to breathe over time (endurance) depends on the balance between energy supplies to the inspiratory muscles and their energy demands.

  • In response to acute increases in load, the inspiratory muscles develop fatigue, inflammation, and injury. In response to unloading by the use of mechanical ventilation they develop atrophy and dysfunction.

  • Respiratory muscle function can be tested using the maximum static inspiratory and expiratory mouth pressures, and sniff pressure. Diaphragm function can be tested by measuring the transdiaphragmatic pressures, and the twitch pressures developed upon electrical or magnetic stimulation of the phrenic nerve.

Functional anatomy

The intercostal muscles

The intercostal muscles are two thin layers of muscle fibres occupying each of the intercostal spaces, the external being superficial to the internal [1]‌. The muscle fibres of the two layers run approximately at right angles to each other: The external intercostals extend from the tubercles of the ribs dorsally to the costochondral junctions ventrally, and their fibres are orientated obliquely, downward and forward, from the rib above to the rib below [1]. The internal intercostals begin posteriorly, as the posterior intercostal membrane on the inner aspect of the external intercostal muscles. From approximately the angle of the rib, the internal intercostal muscles run obliquely, upward and forward from the superior border of the rib and costal cartilage below to the floor of the subcostal groove of the rib and the edge of the costal cartilage above, ending at the sternocostal junctions [1]. All the intercostal muscles are innervated by the intercostal nerve [1].

The external intercostal muscles have an inspiratory action on the rib cage, whereas the internal intercostal muscles are expiratory, with the exemption of the parasternal intercostals, which are inspiratory [1]‌.

The diaphragm

The floor of the thoracic cavity is closed by a thin musculotendinous sheet, the diaphragm, the most important inspiratory muscle, accounting for approximately 70% of minute ventilation in normal subjects [1]‌. The diaphragmatic fibres radiate from the central tendon to insert peripherally into skeletal structures. The diaphragm has two main components based on its point of origin—the crural (vertebral) part and the costal (sternocostal) part. The crural part arises from the crura (strong, tapering tendons attached vertically to the anterolateral aspects of the bodies, and intervertebral disks of the first three lumbar vertebrae on the right and two on the left) and the three aponeurotic arcuate ligaments. The costal part of the diaphragm arises from the xiphoid process, and the lower end of the sternum and the costal cartilages of the lower six ribs. These costal fibres run cranially so that they are directly apposed to the inner aspect of lower rib cage, creating a zone of apposition [1].

The shape of the relaxed diaphragm at the end of a normal expiration is that of two domes joined by a saddle that runs from the sternum to the anterior surface of the spinal column. The motor and proprioceptive innervation of the diaphragm is from the phrenic nerves. When tension develops within the diaphragmatic muscle fibres, a caudally-orientated force is applied on the central tendon and the dome of the diaphragm descends; this descent has two effects. First, it expands the thoracic cavity along its craniocaudal axis and, consequently, the pleural pressure falls. Secondly, it produces a caudal displacement of the abdominal visceral contents and an increase in the abdominal pressure that in turn results in an outward motion of the ventral abdominal wall. Moreover, when the diaphragm contracts, a cranially-orientated force is applied by the costal diaphragmatic fibres to the upper margins of the lower six ribs that has the effect of lifting and rotating them outward (insertional force) [1]‌. The actions mediated by the changes in pleural and abdominal pressures are more complex. If the diaphragm was the only muscle acting on the rib cage, it would have two opposing effects when it contracts [1]. On the upper rib cage, it causes a decrease in the anteroposterior diameter, and this expiratory action is primarily because of the fall in pleural pressure. On the lower rib cage, it causes an expansion. This inspiratory action on the lower rib cage is caused by the concomitant action of two different forces, the ‘insertional’ force already described and the ‘appositional’ force, whereby the increase in abdominal pressure expands the lower rib cage at the zone of apposition.

The abdominal muscles

The abdominal expiratory muscles constitute the ventrolateral wall of the abdomen (i.e. the rectus abdominis ventrally, and the external oblique, internal oblique, and transverses abdominis laterally). They are innervated by the lower six thoracic nerves and the first lumbar nerve [1]‌. As they contract, they pull the abdominal wall inward, thus increasing the intra-abdominal pressure. This causes the relaxed diaphragm to move cranially into the thoracic cavity, increasing the pleural pressure and decreasing lung volume. Expiration is usually passive, but can become active when minute ventilation has to be increased (e.g. during exercise) or during respiratory distress. Expiratory muscle action is also essential during cough.

Physiology: the ability to breathe—the load/capacity balance

For a human to take a spontaneous breath, the inspiratory muscles must generate sufficient force to overcome the elastance of the lungs and chest wall (lung and chest wall elastic loads), as well as the airway and tissue resistance (resistive load). This requires an adequate output of the centres controlling the muscles, anatomic and functional nerve integrity, unimpaired neuromuscular transmission, an intact chest wall, and adequate muscle strength [2,3]. This can be schematically represented by considering the ability to take a breath as a balance between inspiratory load and neuromuscular competence (Fig. 77.1a). Under normal conditions, this system is polarized in favour of neuromuscular competence (i.e. there are reserves that permit considerable increases in load). However, for a human to breathe spontaneously, the inspiratory muscles should be able to sustain the aforementioned load over time, as well as adjust the minute ventilation in such a way that there is adequate gas exchange. The ability of the respiratory muscles to sustain this load without the appearance of fatigue is called endurance, and is determined by the balance between energy supplies and energy demands (Fig. 77.1b).

Fig. 77.1a Balance between inspiratory load and neuromuscular competence. The ability to take a spontaneous breath is determined by the balance between the load imposed on the respiratory system (pressure developed by the inspiratory muscles; PI) and the neuromuscular competence of the ventilatory pump (maximum inspiratory pressure; PI, max). Normally, this balance weighs in favour of competence, permitting significant increases in load. However, if the competence is, for whatever reason, reduced below a critical point (e.g. drug overdose, myasthenia gravis), the balance may then weigh in favour of load, rendering the ventilatory pump insufficient to inflate the lungs and chest wall.

Fig. 77.1a Balance between inspiratory load and neuromuscular competence. The ability to take a spontaneous breath is determined by the balance between the load imposed on the respiratory system (pressure developed by the inspiratory muscles; PI) and the neuromuscular competence of the ventilatory pump (maximum inspiratory pressure; PI, max). Normally, this balance weighs in favour of competence, permitting significant increases in load. However, if the competence is, for whatever reason, reduced below a critical point (e.g. drug overdose, myasthenia gravis), the balance may then weigh in favour of load, rendering the ventilatory pump insufficient to inflate the lungs and chest wall.

Reproduced with permission of the European Respiratory Society ©. Eur Respir J November 1, 1996 9, 2383–400; doi: 10.1183/09031936.96.09112383.

Fig. 77.1b Balance between energy supplies and energy demands. Respiratory muscle endurance is determined by the balance between energy supplies and demands. Normally, the supplies meet the demands, and a large reserve exists. Whenever this balance weighs in favour of demands, the respiratory muscles ultimately become fatigued, leading to inability to sustain spontaneous breathing. VT/TI, Mean inspiratory flow (tidal volume/inspiratory time); TI/TTOT, duty cycle (fraction of inspiration to total breathing cycle duration); PI/PI,max, inspiratory pressure/maximum inspiratory pressure ratio; VʹE, minute ventilation.

Fig. 77.1b Balance between energy supplies and energy demands. Respiratory muscle endurance is determined by the balance between energy supplies and demands. Normally, the supplies meet the demands, and a large reserve exists. Whenever this balance weighs in favour of demands, the respiratory muscles ultimately become fatigued, leading to inability to sustain spontaneous breathing. VT/TI, Mean inspiratory flow (tidal volume/inspiratory time); TI/TTOT, duty cycle (fraction of inspiration to total breathing cycle duration); PI/PI,max, inspiratory pressure/maximum inspiratory pressure ratio; VʹE, minute ventilation.

Reproduced with permission of the European Respiratory Society ©. Eur Respir J November 1, 1996 9, 2383–400; doi: 10.1183/09031936.96.09112383.

Energy supplies depend on the inspiratory muscle blood flow, the blood substrate (fuel) concentration, and arterial oxygen content, the muscle’s ability to extract and use energy sources, and the muscle’s energy stores [2,3]. Under normal circumstances, energy supplies are adequate to meet the demand, and a large recruitable reserve exists (see Fig. 77.1b). Energy demands increase proportionally with the mean pressure developed by the inspiratory muscles per breath (PI) expressed as a fraction of maximum pressure that the respiratory muscles can voluntarily develop (PI/PI,max), the minute ventilation (VE), the inspiratory duty cycle (TI/TTOT), and the mean inspiratory flow rate (VT/TI) and are inversely related to the efficiency of the muscles [2,3]. Fatigue develops when the mean rate of energy demands exceeds the mean rate of energy supply (i.e. when the balance is polarized in favour of demands) [2,3].

The product of TI/TTOT and the mean transdiaphragmatic pressure expressed as a fraction of maximal (Pdi/Pdi,max) defines a useful ‘tension-time index’ (TTIdi) that is related to the endurance time (i.e. the time that the diaphragm can sustain the load imposed on it). Whenever TTIdi is smaller than the critical value of 0.15, the load can be sustained indefinitely; but when TTIdi exceeds the critical zone of 0.15–0.18, the load can be sustained only for a limited time period—in other words, the endurance time. This was found to be inversely related to TTIdi [2,3]. The TTI concept is assumed to be applicable not only to the diaphragm, but also to the respiratory muscles as a whole:

TTI = P I / P I , max × T I / T TOT
[eqn 1]

Because endurance is determined by the balance between energy supply and demand, TTI of the inspiratory muscles has to be in accordance with the energy balance view [2,3]. In fact, as Fig. 77.1b demonstrates, PI/PI,max and TI/TTOT, which constitute the TTI, are among the determinants of energy demands. An increase in either that will increase the TTI value, will also increase the demands, but what determines the ratio PI/PI,max? The numerator, the mean inspiratory pressure developed per breath, is determined by the elastic and resistive loads imposed on the inspiratory muscles. The denominator, the maximum inspiratory pressure, is determined by the neuromuscular competence (i.e. the maximum inspiratory muscle activation that can be voluntarily achieved). It follows, then, that the value of PI/PI,max is determined by the balance between load and competence (see Fig. 77.1a). However, PI /PI,max is also one of the determinants of energy demands (see Fig. 77.1b; therefore, the two balances (i.e. between load and competence, and energy supply and demand) are in essence linked, creating a system (Fig. 77.1c). Schematically, when the central hinge of the system moves upward, or is at least at the horizontal level, spontaneous ventilation can be sustained indefinitely. The ability of a subject to breathe spontaneously depends on the fine interplay of many different factors. Normally, this interplay moves the central hinge far upward and creates a great ventilatory reserve for the healthy individual. When the central hinge of the system, for whatever reason, moves downward, spontaneous ventilation cannot be sustained, and ventilatory failure ensues [2,3].

Fig. 77.1c System of two balances—load and competence, energy supplies and demands. The system of two balances, incorporating the various determinants of load, competence, energy supplies, and demands is represented schematically. The PI/PI,max, one of the determinants of energy demands (see Fig. 77.1a) is replaced by its equivalent—the balance between load and neuromuscular competence (see Fig. 77.1b). In fact, this is the reason the two balances are linked. When the central hinge of the system moves upward or is at least at the horizontal level, a balance exists between ventilatory needs and neurorespiratory capacity, and spontaneous ventilation can be sustained. In healthy persons, the hinge moves far upward, creating a large reserve.

Fig. 77.1c System of two balances—load and competence, energy supplies and demands. The system of two balances, incorporating the various determinants of load, competence, energy supplies, and demands is represented schematically. The PI/PI,max, one of the determinants of energy demands (see Fig. 77.1a) is replaced by its equivalent—the balance between load and neuromuscular competence (see Fig. 77.1b). In fact, this is the reason the two balances are linked. When the central hinge of the system moves upward or is at least at the horizontal level, a balance exists between ventilatory needs and neurorespiratory capacity, and spontaneous ventilation can be sustained. In healthy persons, the hinge moves far upward, creating a large reserve.

Reproduced with permission of the European Respiratory Society ©. Eur Respir J November 1, 1996 9, 2383–400; doi: 10.1183/09031936.96.09112383.

Hyperinflation

Hyperinflation (frequently observed in obstructive airway diseases) compromises the force-generating capacity of the diaphragm for a variety of reasons [2]‌: First, the respiratory muscles, like other skeletal muscles, obey the length–tension relationship. At any given level of activation, changes in muscle fibre length alter tension development. This is because the force-tension developed by a muscle depends on the interaction between actin and myosin fibrils (i.e. the number of myosin heads attaching and thus pulling the actin fibrils closer within each sarcomere). The optimal fibre length (Lo) where tension is maximal, is the length at which all myosin heads attach and pull the actin fibrils. Below this length (as with hyperinflation, which shortens the diaphragm), actin-myosin interaction becomes suboptimal, and tension development declines. Second, as lung volume increases, the zone of apposition of the diaphragm decreases in size, and a larger fraction of the rib cage becomes exposed to pleural pressure. Hence, the diaphragm’s inspiratory action on the rib cage diminishes. Third, the resultant flattening of the diaphragm increases its radius of curvature (Rdi) and, according to Laplace’s law, Pdi = 2Tdi/Rdi, diminishes its pressure-generating capacity (Pdi) for the same tension development (Tdi).

Respiratory muscle responses to changes in load

Acute responses to increased load

Respiratory muscle fatigue

Fatigue is defined as the loss of capacity to develop force and/or velocity in response to a load that is reversible by rest [4,5]. Fatigue should be distinguished from weakness, in which reduced force generation is fixed and not reversed by rest. Theoretically, the site of fatigue may be located anywhere in the long chain of events involved in voluntary muscle contraction leading from the brain to the contractile machinery. A widely-used convention is to classify fatigue as central, peripheral high-frequency, or peripheral low-frequency.

Central fatigue is present when a maximal voluntary contraction generates less force than does maximal electrical stimulation [4,5].

Peripheral fatigue refers to failure at the neuromuscular junction or distal to this structure and is present when muscle force output falls in response to direct electrical stimulation [4,5]. This type of fatigue may occur because of failure of impulse propagation across the neuromuscular junction, the sarcolemma, or the T-tubules (transmission fatigue), impaired excitation–contraction coupling, or failure of the contractile apparatus of the muscle fibres. Peripheral fatigue can be further classified into high-frequency and low-frequency, on the basis of the shape of the muscle force-frequency curve. High-frequency fatigue results in depression of the forces generated by a muscle in response to high-frequency electrical stimulation (50–100 Hz), whereas low-frequency fatigue results in depression of force generation in response to low-frequency stimuli (1–20 Hz) [4,5]. High-frequency fatigue is attributed to transmission fatigue. Normal subjects breathing against high-intensity inspiratory resistive loads develop high-frequency fatigue, which resolves very quickly after cessation of the strenuous diaphragmatic contractions.

When the loss of force is not accompanied by a parallel decline in the electrical activity impaired excitation-contraction coupling is thought to be responsible. This type of fatigue is characterized by a selective loss of force at low frequencies of stimulation (low-frequency fatigue) and is long-lasting, taking several hours to recover [4,5].

Inflammation and injury

Strenuous diaphragmatic contractions (induced by resistive breathing, which accompanies many disease states such as chronic obstructive pulmonary disease (COPD) and asthma) initiate an up-regulation of cytokines within the diaphragm [6]‌. Prolonged, strenuous resistive breathing results in diaphragmatic ultrastructural injury (such as sarcomere disruption, necrotic fibres, flocculent degeneration, and influx of inflammatory cells) in both animals and humans. The mechanisms involved are not definitely established, but may involve intradiaphragmatic cytokine induction, adhesion molecule up-regulation, calpain activation, and reactive oxygen species formation [6].

Respiratory muscle response to inactivity and unloading

Respiratory muscles also adapt when they become inactive, as happens during denervation or when a mechanical ventilator undertakes their role as force generator to create the driving pressure permitting airflow into the lungs. Inactivity and unloading of the diaphragm caused by mechanical ventilation is harmful, resulting in decreased diaphragmatic force-generating capacity, diaphragmatic atrophy, and diaphragmatic injury, which are described by the term ventilator-induced diaphragmatic dysfunction (VIDD) [7]‌. The mechanisms are not fully explained, but muscle atrophy, oxidative stress, and structural injury contribute to various extents in the development of VIDD [7].

Testing respiratory muscle function

Maximal static mouth pressures

Measurement of the maximum static inspiratory (PI,max) or expiratory (PE,max) pressure that a subject can generate at the mouth is a simple way to estimate inspiratory and expiratory muscle strength [3,5]. These are measured at the side port of a mouthpiece that is occluded at the distal end. A small leak is incorporated to prevent glottic closure and buccal muscle use during inspiratory or expiratory manoeuvres [5]‌. The pressure must be maintained for at least 1.5 seconds, so that the maximum pressure sustained for 1 second can be recorded [5]. The pressure measured during these manoeuvres (Pmo) reflects the pressure developed by the respiratory muscles (Pmus), plus the passive elastic recoil pressure of the respiratory system including the lung and chest wall (Prs). At functional residual capacity, Prs is 0 so that Pmo represents Pmus. Normal values are available for adults, children, and the elderly. The tests are easy to perform, yet exhibit significant between- and within-subject variability, as well as learning effect. Nervertheless, a PI,max of –80 cmH2O usually excludes clinically important inspiratory muscle weakness. In critically ill patients who cannot cooperate PI,max can be measured as the airway pressure developed after a prolonged (20 seconds) occlusion of the airway

Transdiaphragmatic pressure

When inspiratory muscle weakness is confirmed, the next diagnostic step is to unravel whether this is due to diaphragmatic weakness. This is accomplished by the measurement of maximum transdiaphragmatic pressure (Pdi,max) [3,5]. Pdi,max is the difference between gastric pressure (reflecting abdominal pressure) and oesophageal pressure (reflecting intrapleural pressure) on a maximum inspiratory effort after the insertion of appropriate balloon catheters in the oesophagus and the stomach, respectively.

Sniff pressure

A sniff is a short, sharp voluntary inspiratory manoeuvre performed through one or both unoccluded nostrils [5]‌. It achieves rapid, fully coordinated recruitment of the diaphragm and other inspiratory muscles. The nose acts as a Starling resistor, so that nasal flow is low and largely independent of the driving pressure that is the oesophageal pressure. Pdi measured during a sniff (Pdi,sn,max) reflects diaphragm strength, and Pes reflects the integrated pressure of the inspiratory muscles on the lungs. Pressures measured in the mouth, nasopharynx, or one nostril give a clinically useful approximation to oesophageal pressure during sniffs without the need to insert oesophageal balloons, especially in the absence of significant obstructive airway disease. There is a wide range of normal values, reflecting the wide range of normal muscle strength in different individuals. In clinical practice, Pdi,sn,max values greater than 100 cmH2O in males and 80 cmH2O in females are unlikely to be associated with clinically significant diaphragm weakness. Values of maximal sniff oesophageal or nasal pressure numerically greater than 70 cmH2O (males) or 60 cmH2O (females) are also unlikely to be associated with significant inspiratory muscle weakness.

Electrophysiological testing

Electrophysiological testing helps determining whether weakness is due to muscle, nerve, or neuromuscular transmission impairment. This requires the measurement of Pdi in response to bilateral supramaximal phrenic nerve electrical or magnetic stimulation, with concurrent recording of the elicited electromyogram of the diaphragm with either surface or oesophageal electrodes [3,5].

References

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2. Vassilakopoulos T, Zakynthinos S, and Roussos C. (1996). Respiratory muscles and weaning failure. European Respiratory Journal, 9, 2383–400.Find this resource:

3. Vassilakopoulos T and Roussos C. (2006). Neuromuscular respiratory failure. In: Albert R, Slutsky A, Ranieri M, Takala J, and Torres A. (eds) Clinical Critical Care Medicine, pp. 275–82. St. Louis, MO: Mosby.Find this resource:

4. Roussos C and Zakynthinos S. (1996). Fatigue of the respiratory muscles. Intensive Care Medicine, 22, 134–55.Find this resource:

5. ATS/ERS (2002). Statement on respiratory muscle testing. American Journal of Respiratory and Critical Care Medicine, 166, 518–624.Find this resource:

6. Vassilakopoulos T, Roussos C, and Zakynthinos S. (2004). The immune response to resistive breathing. European Respiratory Journal, 24, 1033–43.Find this resource:

7. Vassilakopoulos T. (2008). Ventilator-induced diaphragmatic dysfunction: the clinical relevance of animal models. Intensive Care Medicine, 34, 7–16.Find this resource: