How Should the Respiratory Muscles be Managed During Critical Illness?
February 1, 2014
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SPECIAL FEATURE
How Should the Respiratory Muscles be Managed During Critical Illness?
By Richard H. Kallet, MS, RRT, FAARC, FCCM
Director of Quality Assurance, Respiratory Care Services, San Francisco General Hospital
Mr. Kallet reports no financial relationships relevant to this field of study.
Mechanical ventilation (MV) increases the cost and duration of critical care by an average of 240% and 170%, respectively.1 Although the average duration of MV in critically ill patients is approximately 6 days, it occurs with a wide dispersion.2 Approximately 40% of time spent on MV is devoted to weaning,3 and a sizable minority of patients (perhaps 25%) are considered difficult to wean.4 This implies that respiratory muscle dysfunction is a significant factor. Despite intense research on respiratory muscle physiology and patient-ventilator interfacing, this knowledge has not been integrated into a comprehensive approach toward managing the respiratory muscles in critical illness. This special feature describes the complex array of issues complicating such an endeavor.
EFFECTS OF MECHANICAL VENTILATION ON THE RESPIRATORY MUSCLES
The art and science of MV are inextricably bound to its own history. In a 25-year span beginning in the late 1960s, several technological advancements occurred, including patient-triggered ("assisted") volume ventilation, intermittent mandatory ventilation, pressure control/pressure support ventilation, airway pressure-release ventilation, and dual mode control. Yet, introduction of these purported advancements invariably preceded both clinical and laboratory studies assessing their impact on respiratory muscle function. Also, the general success of critical care in rescuing catastrophically ill/injured patients often resulted in pronounced respiratory muscle weakness as a sequela. Theories developed in the early 1970s to explain this phenomenon (along with its implications for MV strategies) occurred under a "veil of ignorance."
Research on respiratory muscle physiology did not begin in earnest until the mid 1970s. And studies of the impact of MV on respiratory muscle function began only in the mid-1980s with the seminal work of Marini5 and others. From these studies, several crucial facts have emerged: 1) the respiratory muscles continue to perform considerable work during assisted mechanical breaths; 2) the off-switch for patient effort during assisted MV is based on a neural-targeted tidal volume approximating the patient's spontaneous tidal volume;6 3) ventilators actually impose resistive, elastic, and threshold loads in addition to intrinsic loads caused by disease; and 4) settings for trigger sensitivity, inspiratory flow rate, flow pattern, and tidal volume significantly impact both the magnitude of imposed work as well as modifying the intrinsic workload.
Recent evidence has introduced several more vexing problems. Generous tidal volumes off-load the respiratory muscles and ameliorate dyspnea, but have a profound negative impact on morbidity and mortality. High doses of sedatives effectively suppress tidal volume demand and promote synchrony, but are associated with delirium, prolonged MV, and other sequelae. Likewise, prolonged use of neuromuscular blocking agents also can cause profound respiratory muscle weakness. Yet, restricting tidal volume below patient demand increases work of breathing.7
Allowing sustained high-level work can cause acute inflammation and structural damage to the respiratory muscles,8 as well as fatigue. Similarly, complete respiratory muscle inactivity causes inflammation and muscle damage that also results in weakness.9 Moreover, patients with sepsis and organ dysfunction have pronounced respiratory muscle weakness at the onset of MV.10 This finding is consistent with preclinical evidence that the diaphragm appears particularly vulnerable to inflammation and structural damage from severe gram-negative bacterial infections.11,12 Paradoxically, passive MV may protect the respiratory muscles during sepsis.13 Thus, from the standpoint of both physics and pathophysiology, there are important but contradictory goals of care during MV. These require a careful balancing of competing issues at different time points in the course of critical illness and are discussed below.
VENTILATOR-INDUCED DIAPHRAGMATIC DYSFUNCTION
Like all skeletal muscles, the respiratory muscles are prone to disuse atrophy, which develops within days of controlled ventilation. However, disuse atrophy requires prolonged, passive MV and seemingly has little relevance when patient-triggered ("assisted") MV is used.14 Studies of assisted MV consistently demonstrate that patient work of breathing is elevated above normal limits. Therefore, minimizing the risk of disuse atrophy requires that sedation and mandatory ventilator frequencies be titrated to achieve consistent patient triggering. Passive ventilation should be restricted to situations characterized by some combination of pronounced gas exchange dysfunction, profound abnormalities in chest mechanics, hemodynamic instability, severe intracranial hypertension, or ensuring the stability of large surgical wounds.
FATIGUE, WEAKNESS, AND USE ATROPHY
Muscle fatigue is the inability to generate a targeted force because of activity under loaded conditions and is reversible by rest, whereas weakness is the inability to develop a targeted force in a rested muscle. Acute fatigue occurs when inspiratory muscle pressures reach 50-70% of maximum capability. The time to actual fatigue onset in normal muscles is not immediate but decreases based on both the degree of loading and the inspiratory time percentage ("duty-cycle"). During critical illness, the duty cycle often reaches 50% when the muscles are stressed.15 In addition, weakened muscles are more susceptible to fatigue precisely because of their diminished force-producing capacity.
In general, fatigue is categorized into high- or low-frequency forms according to the muscle fibers most affected. Type 2 fibers have enhanced power output but are readily susceptible to fatigue (high frequency), whereas Type 1 fibers have high endurance but limited power-generating capacity (low frequency). High-frequency fatigue occurs first during weaning failure, when the Type 2 fibers deplete their energy stores and begin to fail as pressure generators. This typically coincides with overt signs of distress, so that quickly unloading the muscles often results in functional recovery within a matter of hours. However, prolonged exposure to fatiguing loads likely induces tension-related muscle injury8 and complete recovery may require between 24-48 hours of rest.16 Moreover, preclinical evidence now suggests that, like other skeletal muscle, even brief periods (e.g., 1.5 hours) of high fatigue-inducing loads are associated with secondary diaphragmatic injury detected several days later.17 Although the damage appears limited in scope, this raises the possibility that chronically exposing the respiratory muscles to excessive workloads might perpetuate muscle damage and prolong ventilator dependence in some patients.
REST vs EXERCISE
That the respiratory muscles must reach at least 50% of their maximal force capacity during tidal breathing to induce fatigue contradicts the notion that work of breathing must be normalized or minimized during MV. Given this physiologic reserve, and in the absence of fatigue, malnutrition, or hemodynamic/gas exchange instability, the majority of patients can likely tolerate sustained increases in work of breathing of at least twice normal (e.g., ~1 joule/L) without difficulty. The likely exception is when acute respiratory failure occurs under conditions of either prolonged respiratory distress prior to instituting MV (e.g., COPD exacerbation) or severe gram-negative infection. These patients may require careful reintroduction of respiratory muscle activity after a reasonable period of complete rest (e.g., 24 hours). However, the rate and magnitude by which respiratory muscle work is reintroduced should be tested empirically. In other words, this process should not be assumed problematic until patients "declare" themselves so. In contrast, many patients with acute respiratory failure have normal respiratory muscle function, and likely have MV initiated prior to the development of low frequency fatigue and muscle damage. These patients should be managed initially with assisted ventilation and quickly challenged with a spontaneous breathing trial once the underlying cause of respiratory failure has subsided.
In this regard, spontaneous breathing trials are concordant with the principles of muscle training, and should be used (at least initially) in all patients. Discrete periods of intense activity stimulate muscle growth and strength.18 However, to be effective, strenuous activity must be interspersed with periods of relative rest. In patients requiring prolonged weaning, pressure support levels should be titrated toward usual weaning parameters for tidal volume (e.g., ≥ 5 mL/kg) and respiratory frequency (25-35 breaths/minute) to ensure that the respiratory muscles are sufficiently challenged. When pain, discomfort, or anxiety have been ruled out, overt distress and pronounced accessory muscle use likely indicate the onset of high-frequency fatigue. Therefore, these signs should be used to discontinue discrete weaning trials and provide at least several hours of rest. Although patient work of breathing cannot be measured without esophageal manometry, it can be reasonably inferred by evaluating changes in the breathing pattern, accessory muscle use, vital signs, and ventilator waveform graphics in response to changes in the level of MV support.
THE CARDIOPULMONARY IMPACT OF STRENUOUS INSPIRATORY EFFORTS
In the presence of either altered pulmonary capillary permeability or hypervolemia, the repetitive generation of large negative intrathoracic pressure increases the transcapillary hydrostatic pressure and promotes pulmonary edema.19 In addition, cardiac afterload is increased, which may have a significant negative impact on patients with depressed myocardial contractility. Finally, when respiratory muscle work is highly elevated, expiration becomes active. This, in part, is a compensatory response to increased resting diaphragmatic length and enhances inspiratory muscle performance. Under conditions of alveolar instability (e.g., ARDS), active expiration promotes de-recruitment and thus counteracts the effects of PEEP. Thus, pronounced patient-ventilator asynchrony and labored breathing in severe respiratory failure are clear justifications for rapid institution of passive ventilation until the patient can be stabilized.
In summary, respiratory muscle dysfunction is common in critical illness but has multiple causes, not all of which are fully understood or whose treatment approach has been clearly demonstrated. One of the primary goals of mechanical ventilation is to assume all or some of the work of breathing. Unfortunately, achieving this end often is at odds with other equally important goals, such as the prevention of ventilator-induced lung injury and avoiding the use of both paralytics and high amounts of sedatives that also can increase the duration of MV. A comprehensive strategy for managing respiratory muscle function requires the clear delineation of when competing goals take precedence over one another. When the respiratory muscles should be rested or stressed should be based on the best clinical and preclinical evidence available, in concert with the particular circumstances of individual patients and how they respond empirically to adjustments in MV.
REFERENCES
- Dasta JF, et al. Daily cost of an intensive care unit stay: The contribution of mechanical ventilation. Crit Care Med 2005;33: 1266-1271.
- Esteban A. Characteristics and outcomes in adult patients receiving mechanical ventilation. JAMA 2002;287:345-355.
- The ACCP, AARC, ACCCM Taskforce. Evidence-based guidelines for weaning and discontinuing ventilatory support. Chest 2001;120:375S-395S.
- Caroleo S, et al. Weaning from mechanical ventilation: An open issue. Minerva Anesthesiol 2007;73:417-427.
- Marini JJ, et al. The inspiratory workload of patient-initiated mechanical ventilation. Am Rev Respir Dis 1986;134:902-909.
- Flick GR, et al. Diaphragmatic contraction during assisted mechanical ventilation. Chest 1989;96:130-135.
- Kallet RH, et al. The effects of tidal volume demand on work of breathing during lung-protective ventilation in patients with acute lung injury and acute respiratory distress syndrome. Crit Care Med 2006;34:8-14.
- Zhu E, et al. Diaphragm muscle fiber injury after inspiratory resistive breathing. Am J Respir Crit Care Med 1997;155:1110-1116.
- Jaber S, et al. Rapidly progressive diaphragmatic weakness and injury during mechanical ventilation in humans. Am J Respir Crit Care Med 2011;183:364-371.
- Demoule A, et al. Diaphragm dysfunction on admission to the intensive care unit. Am J Respir Crit Care Med 2013;188:213-219.
- Demoule A, et al. Endotoxin triggers nuclear factor-kB-dependent up-regulation of multiple proinflammatory genes in the diaphragm. Am J Respir Crit Care Med 2006;174:646-653.
- Divangahi M, et al. Preferential diaphragmatic weakness during sustained pseudomonas aeruginosa lung infection. Am J Respir Crit Care Med 2004;169:679-686.
- Ebihara S, et al. Mechanical ventilation protects against diaphragm injury in sepsis. Am J Respir Crit Care Med 2002;165: 221-228.
- Sassoon CSH. Assist-control mechanical ventilation attenuates ventilator-induced diaphragmatic dysfunction. Am J Respir Crit Care Dis 2004;626-632.
- Kallet RH. Patient-ventilator interaction during acute lung injury and the role of spontaneous breathing (Part 1): Respiratory muscle function during critical illness. Respir Care 2011;56:190-206.
- Laghi F, et al. Pattern of recovery from diaphragmatic fatigue over 24 hours. J Appl Physiol 1995;79:539-546.
- Jiang TX, et al. Load dependence of secondary diaphragm inflammation and injury after acute inspiratory loading. Am J Respir Crit Care Med 1998;157:230-236.
- Fluck M. Functional, structural and molecular plasticity of mammalian skeletal muscle in response to exercise stimuli. J Experimental Biol 2006;209:2239-2248.
- Kallet RH, et al. Exacerbation of acute pulmonary edema during assisted mechanical ventilation using a low tidal-volume, lung-protective ventilator strategy. Chest 1999;116:1826-1832.
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