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By Richard 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.
A Uruguayan military interrogator made a matter-of-fact statement while discussing “el submarino” (“water-boarding”) during that country’s state of siege in the early 1970s: “There is something more terrifying than pain, and that is the inability to breathe.”1 Particularly unsettling is the fact that practitioners of torture clearly appreciate what often eludes us: Breathing is the primal sensation of postnatal life, the disturbance of which produces the most profound sense of dread.
Compared to pain management, dyspnea and breathlessness in the ICU receive scant attention, as little prospective research informs clinicians and clinical management guidelines are nonexistent.2 Most research on dyspnea and breathlessness occurs outside the ICU in normal subjects or patients with chronic lung disease. Understandably, self-reporting of symptoms is crucial to advancing knowledge. In critical care literature, however, dyspnea has been inferred largely from the results of studies on patient-ventilator asynchrony and work of breathing (WOB). The few studies that have addressed dyspnea during mechanical ventilation (MV) report moderate to severe dyspnea is common (47-62% incidence) and often linked to anxiety.3-6 Moreover, clinicians systematically underestimate the intensity of dyspnea patients experience.4
Dyspnea and breathlessness are distinct phenomena that capture nuanced, overlapping sensations associated with breathing discomfort. Dyspnea and pain are similar in that both sensations possess qualitatively distinct features with varying intensity and cause suffering. In fact, neuroimaging confirms the same primitive brain structures as pain process dyspnea and activate areas associated with emotions.5,6 What are the basic theories regarding the nature of breathing perception and dyspnea and its likely relationship to WOB and asynchrony during MV?
When used as a specific descriptor, dyspnea refers to difficulty in the mechanical act of breathing, or what originally was referred to as length-tension inappropriateness.9 A more comprehensive term (efferent-reafferent dissociation) acknowledges that a complex array of receptors are involved in generating these sensations.10 In essence, dyspnea occurs when an imbalance (or a phase-lag) develops between proprioceptive information regarding tension development in the chest muscles with corresponding proprioceptive signals associated with the magnitude (and/or speed) of displacement of the chest and lungs. When this reaches sufficient intensity, one becomes consciously aware of his or her respiratory drive. Breathlessness, on the other hand, is an unpleasant urge to breathe that can occur regardless of encumbered breathing. It is believed to be the conscious perception of intense neural discharge from the brain stem. Additionally, researchers believe acute hypercapnia, acidosis, hypoxemia, and possibly intense stimulation of irritant receptors in the lung parenchyma clinically trigger the event.
Emotional distress perpetuates and magnifies dyspnea and breathlessness. Factors such as situation, knowledge, and control influence emotional distress. Whereas a healthy person identifies the source of breathlessness and arrests the symptom (i.e., stop exercising or holding breath), patients suffering from cardiopulmonary disease often cannot control their symptoms and may not be able to identify its source, which provokes anxiety. Yet another perplexing aspect of dyspnea is psychogenic hyperventilation syndrome associated with panic disorders.11 Breathlessness and hyperventilation resulting in respiratory alkalosis often accompany anxiety. This, in turn, amplifies breathlessness, further provoking anxiety and increasing the intensity of hyperventilation. This vicious cycle is worse in those whose baseline WOB is elevated due to cardiopulmonary or neuromuscular disease. In patients requiring MV, dyspnea was most strongly associated with anxiety, or was found to coexist with it.3,6 Furthermore, the presence of pain magnifies dyspnea when WOB is abnormal.12 Although the likelihood of identifying patients in the ICU with a documented history of psychogenic hyperventilation disorder is nil, clinicians should suspect it whenever respiratory distress appears enigmatic and disproportionate to the intensity of stimulation (e.g., weaning intolerance despite normal chest mechanics, gas exchange, and low minute ventilation requirements).
In large measure, critically ill patients require MV because pathologic increases in resistance, elastance, and minute ventilation place an unsustainable workload on respiratory muscles. Given the dearth of clinical evidence, clinicians infer the relationship between dyspnea and MV from laboratory studies using respiratory muscle loading either to induce acute fatigue or measure the perceived intensity of inspiratory effort. Not surprisingly, these studies have reported similar results. When inspiratory muscle pressure exceeds ~60% of maximum, acute fatigue eventually develops and occurs more quickly as the duration of inspiratory muscle contraction increases.13,14 Likewise, the perception of effort is linearly related to the fraction of inspiratory muscle pressure/maximal pressure. Dyspnea was rated as “very severe” when inspiratory effort reached 60% of maximum and again was magnified as duration of muscular contraction increased.15
Dyspnea occurring during MV modifies primarily due to three ventilator settings that interact with spontaneous breathing efforts: tidal volume, or VT, (which approximates global inspiratory muscle shortening); peak inspiratory flow rate and flow pattern (which reflects the velocity of muscular contraction); and trigger sensitivity (which represents threshold loading, the phase-lag between the onset of muscular contraction, and onset of gas flow). Seminal research from the 1980s focused practices on adjusting ventilator flow to meet patient demand and minimizing trigger-related work.16,17 With the advent of lung-protective ventilation (LPV), other studies demonstrated that restricting VT increased WOB by imposing resistive work or limiting the power output of the ventilator.18 Moreover, restricting VT below demand interacts with hypercapnia to magnify dyspnea and is particularly relevant when LPV requires permissive hypercapnia.19
There is also a latency period for load detection that is different depending on the nature of inspiratory work (i.e., resistive and threshold loads are detected earlier than elastic loads that are VT-dependent).20 The prolonged detection latency for elastic loading explains a unique form of asynchrony (“reverse triggering”) observed during LPV.18,21 In addition, positive end-expiratory pressure (PEEP), at least in the short term, appears to reduce respiratory drive as evidenced by a decreased respiratory rate that may ameliorate breathlessness in those with moderate to severe acute respiratory distress syndrome; the effect is strongest in those with decreased lung compliance. 22 This suggests PEEP modifies the Hering-Breuer deflation reflex associated with acute volume loss.
Ventilator adjustments often cannot fully alleviate dyspnea. Decreased lung compliance increases threshold loading by blunting negative pressure transmission across edematous lung tissue. Threshold loads are magnified as respiratory drive increases (i.e., greater pressure drop/unit time delay) and also by the presence of intrinsic PEEP. Even mild threshold loads (-2.5 cm H2O) provoke dyspnea and cause hyperpnea.23 Severe acidosis can potentiate asynchrony during LPV because hyperpnea is the compensatory response. The amino alcohol buffer, tromethamine, is a direct respiratory depressant and alleviates severe dyspnea, which at higher doses may be partly due to its ability to directly lower PaCO2.24
What makes the treatment of dyspnea and breathlessness in the ICU perplexing is that adjusting ventilator settings and sedation to minimize symptoms increases morbidity and mortality risks. Alleviating dyspnea ultimately requires substantial off-loading of the respiratory muscles or chemically suppressing respiratory drive. The former strategy often requires a supranormal VT; dyspnea largely drove the practice of using large VT in the 1970s.25 Likewise, high levels of sedation causes delirium, which may exacerbate patient-ventilator asynchrony, and is associated with poorer outcomes. Patient-ventilator asynchrony has been associated with increased mortality risk.26 Whether this merely signifies the presence of more severe disease or plays a contributory role remains unknown.
Balancing these competing problems is vexing but perhaps not hopeless, even if a completely satisfying solution is unrealistic. First, early in the course of severe disease/trauma associated with a hyper-proinflammatory state, give LPV precedence. Treat dyspnea and severe asynchrony with sedation and paralysis. However, excessive sedation stymies the accurate assessment of pain and other potential sources of discomfort that often are the etiologies of apparent anxiety. Prioritizing appropriate pain management may reduce dyspnea and excessive WOB/asynchrony and may result in lower levels of sedation. Thus, treatment of dyspnea becomes a balancing act of harm reduction, in which one must consider multiple variables and options.
During recovery from acute respiratory failure as the proinflammatory state subsides, judicious VT liberalization is often required to promote comfort as clinicians reduce sedation. This should prompt an assessment of weaning readiness. Also, do not overlook minimizing unnecessary ventilatory workloads. High airway resistance associated with prolonged MV often is related to biofilm build-up that can be removed with endotracheal tube cleaners. Patients with large positive fluid balances should undergo aggressive diuresis once hemodynamically stable to reduce elastic workloads and facilitate weaning. These small gestures may have an additive effect that might substantially reduce WOB and if not fully alleviate dyspnea, at least reduce it to discomfort that the patient can tolerate.
Financial Disclosure: Critical Care Alert’s Editor Betty Tran, MD, MSc, Nurse Planner Jane Guttendorf, DNP, RN, CRNP, ACNP-BC, CCRN, Peer Reviewer William Thompson, MD, Executive Editor Leslie Coplin, and Associate Managing Editor Jonathan Springston report no financial relationships relevant to this field of study.