Expiratory muscle dysfunction in critically ill patients: towards improved understanding
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This narrative review summarizes current knowledge on the physiology and pathophysiology of expiratory muscle function in ICU patients, as shared by academic professionals from multidisciplinary, multinational backgrounds, who include clinicians, clinical physiologists and basic physiologists.
The expiratory muscles, which include the abdominal wall muscles and some of the rib cage muscles, are an important component of the respiratory muscle pump and are recruited in the presence of high respiratory load or low inspiratory muscle capacity. Recruitment of the expiratory muscles may have beneficial effects, including reduction in end-expiratory lung volume, reduction in transpulmonary pressure and increased inspiratory muscle capacity. However, severe weakness of the expiratory muscles may develop in ICU patients and is associated with worse outcomes, including difficult ventilator weaning and impaired airway clearance. Several techniques are available to assess expiratory muscle function in the critically ill patient, including gastric pressure and ultrasound.
The expiratory muscles are the "neglected component" of the respiratory muscle pump. Expiratory muscles are frequently recruited in critically ill ventilated patients, but a fundamental understanding of expiratory muscle function is still lacking in these patients.
KeywordsExpiratory muscles Acute respiratory failure Mechanical ventilation Respiratory muscle weakness Respiratory muscle monitoring
Take home message
The expiratory muscles are the “neglected component” of the respiratory muscle pump. This narrative review summarizes the physiology and pathophysiology of expiratory muscles in critically ill ventilated patients. Techniques to monitor expiratory muscle function in these patients are also discussed.
The respiratory muscle pump drives alveolar ventilation and is therefore of vital importance. The diaphragm, rib cage muscles and abdominal wall muscles are the most important components of the respiratory muscle pump . Recruitment of each muscle depends on the (relative) load imposed on the respiratory system, lung volume, and the phase of the respiratory cycle. An acute imbalance between respiratory muscle load and capacity will result in respiratory failure and, ultimately, the need for mechanical ventilation. Many studies and reviews have focused on diaphragm structure and function in patients with acute respiratory failure, including critically ill patients [2, 3, 4, 5, 6, 7, 8, 9, 10, 11]. However, the role of expiratory muscles in the physiology of breathing in acute respiratory failure is largely neglected in the literature. This is surprising, given the important role of these muscles in respiration, especially in patients with impending respiratory failure.
The aim of the current paper is to discuss the role of the expiratory muscles in respiration, in particular in critically ill patients in whom respiratory muscle weakness develops rapidly, and may thus have a large clinical impact. We will also describe techniques used to evaluate expiratory muscle function in intensive care unit (ICU) patients. We will not focus in detail on the role of the expiratory muscles in coughing or maintaining body position.
Physiology of expiratory muscle recruitment
It should be recognized that isolated contraction of the abdominal expiratory muscles causing an increase in abdominal pressure and pleural pressure would result in chest wall distortion, in particular expansion of the lower rib cage. This would likely increase the elastic inspiratory work of breathing and flatten the diaphragm. To limit distortion of the lower rib cage during active expiration, the internal intercostal muscles are recruited to stabilize the rib cage .
Another fundamental role of the expiratory muscles is to develop effective cough pressure to facilitate airway clearance . Contraction of the expiratory muscles against a closed airway may increase the intrathoracic pressure may increase to as high as 300 mmHg within 0.2 s. Once the glottis is open, a very high expiratory flow (up to 720 L/min) can be generated [33, 34]. Expiratory muscle weakness reduces cough strength and peak flow velocity, predisposing patients to pneumonia and atelectasis [33, 35, 36].
Undesirable effects of expiratory muscle recruitment
Clinical impact of expiratory muscle dysfunction
Expiratory muscles-related mechanisms
Weaning failure/extubation failure
Increased respiratory energy consumption, ineffective cough, inability to improve diaphragm efficiency
Small airway and alveolar injury
Negative expiratory transpulmonary pressure resulting in alveolar collapse and/or airway closure
Inability to increase expiratory flow
First, in patients with acute respiratory distress syndrome (ARDS) or atelectasis, increased pleural pressure during expiration resulting from expiratory muscle recruitment may result in negative transpulmonary pressure during expiration, leading to cyclic alveolar collapse or airway closure and thereby facilitating small airway and alveolar injury [37, 38, 39, 40]. Consistent with this reasoning, a recent study in ARDS patients demonstrated a higher expiratory transpulmonary pressure in patients receiving neuromuscular blockers compared with control patients (1.4 ± 2.7 cmH2O versus − 1.8 ± 3.5 cmH2O, respectively, p = 0.02) . Interestingly, neuromuscular blockers also abolish expiratory activity of the diaphragm (if present)  which is expected to decrease expiratory transpulmonary pressure. However, the pressure generated by the diaphragm in the expiratory phase is relatively low compared with that generated by the expiratory muscles. Therefore, the effects of neuromuscular blockers on expiratory transpulmonary pressure largely depend on the relaxation of the expiratory muscles.
Third, in patients weaning from mechanical ventilation, expiratory muscle recruitment is expected when an imbalance exists between the respiratory load and inspiratory muscle capacity. Indeed, activation of the expiratory muscles has been demonstrated during ventilator weaning, especially in patients failing a weaning trial [22, 23, 24]. We recently found that expiratory muscle effort progressively increased throughout the trial in such patients . The neuromuscular efficiency of the diaphragm was lower in weaning failure patients compared with weaning success patients, which challenges the concept that expiratory muscle activation improves diaphragm contractile efficiency , although this requires further evaluation. Nevertheless, recruitment of the expiratory muscles during a weaning trial appears to be a strong marker of weaning failure.
Technically, expiratory muscle activity interferes with the assessment of PEEPi.
PEEPi can be measured using different techniques. In patients with expiratory muscle activity, an end-expiratory occlusion will be highly influenced and exaggerated by the contraction of the expiratory muscles . Similarly, the relaxation of the expiratory muscles at the beginning of the effort explains part of the initial drop in esophageal pressure, which is not entirely explained by so-called dynamic PEEPi. Either the drop in gastric pressure (Pga) or the rise in Pga during expiration must be subtracted from the esophageal drop in order to measure a reliable PEEPi .
Expiratory muscle strength in critically ill patients
Several studies have demonstrated the development of expiratory muscle weakness in critically ill patients [48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 64]. Most studies used the maximum expiratory pressure (MEP) as a marker of expiratory muscle strength [48, 49, 50, 51, 52, 53, 54, 55, 56, 57]. Despite the heterogeneity of the studies in terms of populations and measurement techniques, the MEP was lower than the reference values  in all studies that obtained MEP at the time of ventilator weaning [48, 49, 50, 51, 52, 53, 54, 55, 64]. Patients failing extubation exhibit a lower MEP (mean decrease varying from 9 to 31 cmH2O) compared with extubation success patients [48, 49, 50, 51, 52, 53, 54, 55, 64]. This indicates that expiratory muscle weakness is a potential predictor of weaning outcome. How expiratory muscle weakness affects weaning and extubation outcome is largely unknown. Potential explanations include inadequate secretion clearance and insufficient cough capacity resulting in atelectasis, reduced contractile efficiency of the diaphragm, or inadequate reduction of PEEPi.
Remarkably, no studies have investigated the association between diaphragm weakness and expiratory muscle weakness.
Risk factors for expiratory muscle weakness in critically ill patients
Risk factors for the development of ICU-acquired weakness of the peripheral muscles and diaphragm have been discussed recently [2, 4, 57, 65]. Whether these risk factors also have an impact on the expiratory muscles is largely unknown. We briefly discuss risk factors that may contribute to the development of expiratory muscle weakness.
Sepsis and systematic inflammation have been linked to the development of muscle weakness, including weakness of the expiratory muscles [2, 61, 65]. Sepsis induces a severe and persistent increase in protein catabolism, resulting in muscle wasting and muscle weakness [59, 60]. Compared with non-septic surgical patients, the rectus abdominis muscle from surgical patients with sepsis showed significantly lower in vitro contractility . In addition, the reduced MEP (≤ 30 cmH2O) found at the time patients regained normal consciousness showed an independent association with septic shock .
Mechanical ventilation plays an important role in the development of diaphragmatic dysfunction in critically ill patients [2, 9, 10, 66]. Potential mechanisms include disuse atrophy due to ventilator over-assist, or load-induced injury as a result of ventilator under-assist. The impact of mechanical ventilation on expiratory muscles has not been systematically investigated. However, as mentioned earlier, ventilator settings including PEEP and the level of inspiratory assist may have an impact on the activity of the expiratory muscles (Fig. 3) [46, 67], although the ultimate impact of mechanical ventilation on expiratory muscle strength is largely unknown and should be further investigated.
Other risk factors
Co-morbidities, such as COPD and myopathies, or complications such as intra-abdominal hypertension, may put patients at increased risk of ICU-associated expiratory muscle weakness [68, 69]. Drugs such as sedatives, neuromuscular blockers and corticosteroids have been shown to affect peripheral muscle function and diaphragm muscle function in ICU patients [2, 65, 70]. The effects of these drugs on expiratory muscle function have not been systematically studied.
Strategies to maintain or improve expiratory muscle strength
Quantification of expiratory muscle effort in critically ill patients
While visual inspection of the trunk and palpation of the abdominal wall may reveal activation of the expiratory muscles, they do not allow quantification of effort. In this section, we summarize the main clinical techniques that can be used to quantify expiratory muscle effort in ICU patients.
Activation of the abdominal wall muscles increases abdominal pressure. Changes in Pga during expiration reflect changes in abdominal pressure and can thus be used to quantify expiratory muscle effort [22, 24, 39, 63, 73]. Pga is measured using an air-filled balloon catheter inserted into the stomach. Bladder pressure has also been proposed as a means of quantifying intra-abdominal pressure [74, 75], and showed an acceptable correlation with Pga in supine position (bias = 0.5 mmHg, and precision = 3.7 mmHg (limits of agreement, − 6.8 to 7.5 mmHg)) . To quantify the effort of expiratory muscles, Pga amplitude and the Pga pressure–time product (PTP) during expiration can be calculated (Fig. 3).
Amplitude of gastric pressure
Both the rise in Pga over the course of expiration  and the drop in Pga at the onset of the next inspiration  have been used to quantify the activity of the expiratory muscles. However, only the expiratory increase in Pga showed a good correlation with the electromyographic amplitude of the transverse abdominis muscle (correlation coefficient ranging from 0.70 to 0.95) .
The PTP of the expiratory muscles has been quantified using the area enclosed by the esophageal pressure curve and the static chest-wall recoil pressure curve during expiration . The PTP accounts for the energy expenditure during both the isometric and dynamic phases of expiration (independently of volume displacement). However, expiratory esophageal pressure only represents the pressure generated by the abdominal wall muscles when the diaphragm is completely relaxed [39, 79]. As diaphragm activity has been demonstrated during expiration [42, 67], abdominal wall muscle effort cannot be reliably quantified using the expiratory esophageal PTP alone. Therefore, it is recommended to use the expiratory Pga in order to calculate the PTP of the expiratory muscles [80, 81, 82, 83]. The gastric PTP can be obtained from the area under the expiratory Pga curve, in which the baseline is defined as the resting end-expiratory Pga from the preceding breath [24, 80, 81].
Work of breathing
Traditionally, the Campbell diagram is used to quantify the inspiratory work of breathing , but it allows estimation of the expiratory work as well. The area of the esophageal pressure–volume loop at the right side of the chest wall relaxation curve represents expiratory muscle effort [85, 86]. By definition, work is performed only when there is volume displacement (work = pressure × volume). However, as explained above, during dynamic airway collapse part of the pressure generated by the expiratory muscles does not result in lung volume displacement, and therefore the Campbell diagram underestimates the total effort of the expiratory muscles [44, 87]. Under these circumstances, the PTP may better reflect expiratory muscle effort.
Volitional tests of expiratory muscle strength
The MEP is the most widely used measure of expiratory muscle strength . Standard procedures for non-intubated subjects have been established . For intubated patients, the MEP can be measured using a unidirectional valve that allows inspiration but prevents expiration [48, 51, 88]. Some investigators coached subjects to perform an expiratory effort against an occluded airway for 25 to 30 s, and then recorded the most positive pressure developed [48, 51, 88]. Calculating the ratio of maximum inspiratory pressure to MEP is a simple way to assess the relative impairment of the inspiratory muscles versus the expiratory muscles . As MEP measurement requires a voluntary patient effort, this might not be feasible in a proportion of ICU patients. As an alternative to MEP, cough pressure can be assessed to quantify expiratory muscle strength [33, 63, 73].
The cough test is a relatively easy-to-perform, complementary test for the diagnosis of expiratory muscle weakness. Both cough pressure measured via air-filled balloons in the stomach or esophagus, and cough peak expiratory flow measured at the opening of an endotracheal tube or using the ventilator flow sensor , are feasible in ICU patients. In patients unable to cooperate, a cough may be induced either by instilling physiological saline  or by advancing a suctioning catheter through the patient’s tube .
Abdominal wall muscle ultrasound
Other diagnostic tests
Electrical and magnetic stimulation of the abdominal wall muscles are other methods used to quantify the strength of these muscles [25, 79, 81]. As these techniques are cumbersome and uncomfortable, they are rarely used either in clinical practice or for research purposes.
Electromyography of the expiratory muscles has been used in research settings to study the timing of expiratory muscle recruitment during respiration [17, 77], but has not reached clinical implementation. Therefore, these techniques are beyond the scope of this review.
The expiratory muscles are the “neglected component” of the respiratory muscle pump. Rather as the heart does not comprise only a left ventricle, but also a right one, the respiratory muscle pump is much more than just the diaphragm. In this paper, we have summarized the physiology and pathophysiology of expiratory muscles, with a special focus on critically ill patients. Expiratory muscles are frequently recruited in critically ill ventilated patients, but a fundamental understanding of expiratory muscle function is still lacking in these patients. Gastric pressure monitoring provides multiple bedside parameters for analysis of expiratory muscle effort, but their clinical implications need to be established.
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