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Dyspnoea in the critically ill 

Dyspnoea in the critically ill
Dyspnoea in the critically ill

Paolo Tarsia

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date: 06 July 2022

Key points

  • Dyspnoea is a common clinical finding in patients with respiratory, cardiovascular, neuromuscular, and neoplastic diseases. It may also be present in healthy obese and/or deconditioned subjects.

  • Dyspnoea is thought to derive from the conscious awareness of a mismatch between outgoing motor command to the respiratory system and afferent information on the ventilatory response to the command.

  • At least three qualitatively distinct sensations of breathing discomfort have been recognized—air hunger, effort of breathing, and chest tightness.

  • Dyspnoea quantification measures should be employed to better assess dyspnoea and evaluate response to treatment.

  • Both pharmacological and non-pharmacological treatment options are available for dyspnoea relief. In refractory dyspnoea, interventions aimed at reducing the affective component of breathlessness that do not necessarily modulate symptom intensity may be of use.


In healthy conditions, the human respiratory system is built in such a way that, lungs, airways, and respiratory muscles adequately satisfy the ventilatory demands imposed by the entire organism, even during vigorous exercise conditions. However, a number of common clinical conditions are associated with dyspnoea. Dyspnoea may be defined as a subjective experience of discomfort associated with breathing. An American Thoracic Society Statement on dyspnoea recognizes that ‘the experience derives from interactions among multiple physiological, psychological, social, and environmental factors, and may induce secondary physiological and behavioural responses’ [1]‌. Being a subjective experience, each individual perceives, interprets, and reacts differently to the sensation of dyspnoea depending on circumstances, previous experiences, values, and beliefs. Dyspnoea and pain share both neurological pathways and perceptive behaviours. Both consist of sensory (intensity) and affective (unpleasantness) dimensions. The sensation of dyspnoea is not unique to respiratory diseases, but may be also be experienced in cardiovascular, neuromuscular, and malignant diseases. Furthermore, dyspnoea may be present in healthy individuals who are obese and/or deconditioned.

Dyspnoea is common in the acute setting, affecting up to 50% of patients requiring hospital admission or 25% of patients seeking ambulatory assistance [2]‌. Chronic shortness of breath is reported in over 90% of advanced chronic obstructive pulmonary disease (COPD) patients and > 60% of patients with advanced heart disease [3]. Among the general population mild-to-moderate dyspnoea may be observed in roughly 15% of adults aged over 40 years, and roughly 30% of adults aged over 70 years [4].


Breathing discomfort arises as a result of complex interactions between signals relayed from the upper airways, the chest wall, the lungs, and the central nervous system. Integration of this information with higher brain centres provides further processing. The final aspects of the sensation of dyspnoea are influenced by contextual, environmental, behavioural, and cognitive factors.


Blood variations in pH, PaCO2 and PaO2 are sensed by central chemoreceptors in the medulla and peripheral chemoreceptors in the carotid and aortic bodies. The effect of PaCO2 is primarily mediated through chemoreceptor changes in hydrogen ion (and thus pH). Increased chemoreceptor activation results in afferent information reaching respiratory motor centres, triggering their activity. In healthy subjects, hypercapnia and severe hypoxaemia cause breathlessness. Studies in quadriplegics with spinal cord transaction indicate that hypercapnia elicits a reflex increase of respiratory centre motor output. Resulting dyspnoea is therefore an expression of involuntary reflex respiratory activity, rather than increased voluntary respiratory muscle activity [5]‌. Patients with congenital central hypoventilation syndrome lack a ventilator response to CO2. These subjects do not feel breathless during CO2 rebreathing or protracted breath hold.

Chest wall receptors

Mechanoreceptors in the joints, tendons, and muscle spindles of the chest sense muscle tension and contraction, and send afferent signals to the somatosensory cortex in the brain. This information contributes to proprioception and kinaesthesia. The central areas receiving information from chest wall afferents may have a role in gating the intensity of the dyspnoea sensation. Vibrations of the chest wall in phase with respiration (vibration of inspiratory muscles during inspiration and expiratory muscles during expiration) attenuate breathlessness, whereas out-of-phase vibrations worsen dyspnoea [6]‌. Thus, chest wall mechanoreceptors may have an important modifying effect on dyspnoea, rather than playing an essential role in generating the perception of dyspnoea per se.

Airway vagal receptors

Receptors present in the airways and the lung relay afferent information via vagus nerve fibres. These include cold receptors, slow-adapting stretch receptors (SARs) and rapidly-adapting stretch receptors (RARs), and C-fibre receptors. Stimulation of cold receptors in the upper airways relieves dyspnoea, as evidenced by sources of cool air directed onto the face [7]‌. SARs are present in the smooth muscle cells of the large airways. Stimulation of these receptors is also associated with reduced sensation of dyspnoea. RARs react rapidly to sustained inflation or deflation of the lungs, and may be associated with dyspnoea sensation in conditions such as pneumothorax and asthma. Stretch receptors are mainly involved in pulmonary stretch and cough reflexes, modulating airway calibre and ventilator pattern. Their activation permits awareness of the level of ventilation and dilation of the lungs, thus contributing to the overall sensation of dyspnoea. Juxta-pulmonary capillary receptors (J receptors) are localized close to alveolar capillaries and respond to increases in interstitial fluid. Pulmonary C-fibres are located in the lung parenchyma, whereas bronchial C-fibre receptors are located in the airways. Stimulation of these receptors with a number of agents (e.g. capsaicin) induces respiratory sensations such as cough, but not breathlessness in humans. In contrast, adenosine activation of C-fibre receptors is dyspnogenic [8].

Central processing of dyspnoea

Afferent information from chemoreceptors, airway and chest sensors reach the nucleus tractus solitarius (NTS) in the medulla. The NTS is a key site where all peripheral afferent signals are processed prior to presentation to higher centres. Information from the NTS is first projected to the thalamus. The thalamus relays information to areas of the limbic system, such as the insula, the amygdala, and the anterior and posterior insular cortex. These cortical structures are also involved in the perception of other sensations, such as pain, nausea, hunger, and thirst. It is possible that common areas of the brain process the unpleasant perception of different sensations. The anterior insular cortex is thought to play a central role in the conscious awareness of dyspnoea, rather than just processing information. Patients with lesions of the insular cortex present reduced perception of dyspnoea and pain [9]‌.

Corollary discharge

When the brainstem and the motor cortex send outgoing efferent commands to the ventilator muscles, a neurological copy of this information is sent to the sensory cortex. This exchange between the motor and sensory cortex is known as corollary discharge. Corollary discharge is thought to be the mechanism through which conscious awareness of the effort of breathing occurs.

Therefore, afferent information from chemoreceptor and peripheral receptors shapes the motor neural output to the respiratory system. A copy of this information is relayed to the sensory cortex. If afferent feedback to the sensory cortex indicates that the neural motor output does not produce the expected results in terms of airflow or ventilation, a sensation of dyspnoea is generated [10]. It is assumed that the cortical centres possess a pre-existing memory of expected respiratory response to given intensity of motor commands, and that a mismatch between afferent/efferent information and pre-existing memory determines the intensity of dyspnoea. Respiratory disruption leads to distressing emotions, thus eliciting behavioural adaptations.

Qualitatively distinct sensations of dyspnoea

Dyspnoea is not a single sensation. Using patient questionnaires, at least three qualitatively distinct sensations have been employed to describe discomfort in breathing. These are:

  • Air hunger.

  • Increased effort or work of breathing.

  • Chest tightness.

These different sensations are, at least in part, associated with diverse pathophysiological mechanisms.

The sensation termed as ‘air hunger’ may be defined by patients as unsatisfied inspiration, needing more air, not getting enough air, an unpleasant urge to breath, etc. Air hunger has been shown to be associated with the stimulation of chemoreceptors, such as by hypoxia, hypercapnia, or acidosis, which results in increased spontaneous respiratory drive. Information regarding this increased spontaneous respiratory motor drive activity of the brainstem is conveyed to the cerebral cortex as corollary discharge. When this is not matched by an adequate ventilator response, individuals perceive air hunger. This seldom happens in healthy individuals, except at strenuous exercise levels. Conversely, in cardiac or respiratory conditions, the capacity to provide the additional ventilation required by the increased motor drive activity is limited. This creates an imbalance between the motor drive to breathe, as sensed by corollary discharge, and afferent feedback from mechanoreceptors on the ventilatory response of the respiratory system. The intensity of the sensation of air hunger may be regulated by inhibitory activity from mechanoreceptors. In fact, pulmonary stretch receptor and chest wall afferent information is capable of relieving the sensation of air hunger through signalling the level of current ventilation. Therefore, the perceived severity of the sensation of air hunger is the result of a balance between medullary respiratory motor discharge and simultaneous mechanosensor feedback. Air hunger is not specific to any particular disease or stimulus.

A sense of increased effort of breathing has also been termed as ‘difficult breathing’, ‘breathing takes a lot of work’, or ‘breathing takes effort’. Chest wall volume variations during breathing activate respiratory muscle afferent information that projects to the cerebral cortex. During normal breathing or exercise in healthy subjects, unless physiological capacity to match ventilation to metabolic demand is surpassed, afferent mechanoreceptor feedback signals that breathing is appropriate to the prevailing respiratory drive. In clinical conditions that impair respiratory muscle performance through abnormal mechanical loads (COPD, asthma, or interstitial lung disease) or when respiratory muscles are weakened (neuromuscular diseases), increased work of breathing generates greater muscle afferent cortical projections that induce motor cortical increase in voluntary breathing drive. Corollary discharge from cortical motor centres to cortical sensory centres increases awareness of cortical motor command and thus contributes to generating the work/effort dyspnoea sensation. Therefore, whereas air hunger is the result of perceived increased spontaneous brainstem ventilatory drive through chemoreceptor stimulation, work/effort is the result or perceived increased voluntary cortical motor centre activity associated with increased work of breathing.

A sensation of ‘chest tightness’ is often experienced by asthmatic patients during episodes of acute bronchoconstriction and may alternatively be described as ‘chest is constricted’ or ‘chest is tight’. This sensation may be prevalent during the early phases of an asthma attack. With increasing severity of bronchoconstriction, hyperinflation may ensue, giving rise to a work/effort sensation. In fact, patients describe that the feeling of chest tightness rapidly responds to albuterol administration [11], whereas the work/effort sensation is best alleviated by mechanical ventilation. It has been suggested that chest tightness develops through stimulation from pulmonary receptor afferents, such as C-fibres or RARs, which respond to bronchoconstriction. Blocking such afferent information relieves the sensation of tightness.

Quantification of dyspnoea

Measurement of dyspnoea is essential in order to assess it adequately and monitor response to treatment. Dyspnoea assessment may be carried out thorough different scales, questionnaires or exercise tests. It must be recognized that different tools measure different aspects of breathlessness. For example, some tools address the intensity of dyspnoea, others the unpleasantness associated with breathlessness, whereas others investigate the impact on dyspnoea on performing tasks or on quality of life. It is important to understand whether a patient is reporting ‘how much’ or ‘how bad’ the symptom is. Rating may be influenced by the condition giving rise to the dyspnoeic symptom: healthy adults under laboratory conditions are more prone to report dyspnoea intensity, whereas a COPD patient may give ratings dominated by unpleasantness.

Measures of intensity include the Borg scale, and the visual analogue scale. So far, measures of the affective component have been relatively little used in the context of dyspnoea compared with other sensations such as pain. However, there is evidence that intensity and affective dimensions of breathlessness can meaningfully be distinguished during laboratory challenges [12], and may be thus usefully employed in clinical practice.

Measures of the impact of dyspnoea on functional ability or quality of life encompass both one- and multidimensional rating scales. Examples of the former include the Medical Research Council (MRC) five-point scale that asks the patient to indicate the level of activity that evokes dyspnoea, ranging from strenuous exercise to resting conditions. Multidimensional ratings include the Saint George Respiratory Questionnaire (SGRQ), a 76-item questionnaire involving three areas—symptoms, activity, and impact on daily life.

Dyspnoea management

Management of both acute and chronic forms of dyspnoea should be targeted to optimizing medical treatment of the underlying condition. However, in many cases, maximal medical treatment is ineffective in controlling breathlessness and the symptom persists. This requires the adoption of measures that impact on the symptom per se. Strategies in controlling dyspnoea should not focus uniquely on decreasing dyspnoea intensity. Patients may favourably profit from interventions that decrease the unpleasantness associated with breathlessness without necessarily affecting the intensity component of the symptom. Consequently, both pharmacological and non-pharmacological coping strategies may be of use in bedside clinical management.


Administration of opioids relieves dyspnoea in a number of different clinical conditions such as COPD, interstitial lung diseases, cancer, and heart failure. Opioids may attenuate breathlessness via different mechanisms. On the one hand, opioids are respiratory depressants that blunt the central processing of neural signalling related to breathing status and result in decreased motor respiratory command and ventilatory drive. On the other hand, these drugs also alter perceptual sensitivity, thus decreasing patient perception of breathlessness. Therefore, these agents affect both the ‘intensity’, and the ‘unpleasantness’ associated with dyspnoea. The side effects of opioids include altered mental status, hypercapnic respiratory failure, constipation, nausea, and vomiting. Opioid administration is still underused in conditions such as COPD, possibly due to clinician fear of precipitating respiratory acidosis. Nonetheless, a systematic review [13] indicated that opioids are associated with a significant 16% improvement in dyspnoea intensity, and a randomized control trial supports the notion that opioids are both effective and safe in patients with refractory dyspnoea [14]. Although opioid receptors are present on sensory nerves in the airways, current evidence does not support the use of nebulized morphine in relieving dyspnoea [13].

Anxiolytic agents

Similarly to opioids, anxiolytic agents may exert a two-fold positive effect in breathless patients by depressing hypoxic—or hypercapnic-induced increases in respiratory drive and dampening emotional responses to dyspnoea. Nonetheless, clinical trials have failed to indicate consistent superiority over placebo for various benzodiazepine derivatives [15], indicating that these drugs should not be routinely employed in the management of dyspnoea. Their use may be considered in individual patients, particularly when anxiety components are critical symptom determinants.

Oxygen therapy

In hypoxic patients, oxygen administration decreases peripheral chemoreceptor activity, thereby causing a reduction in hypoxic ventilatory drive, and thus relieving dyspnoea. Conversely, oxygen use in non-hypoxaemic advanced-stage respiratory and cardiac patients has not been convincingly demonstrated to be of benefit as a symptom reliever, and should not be routinely employed.

Other pharmacological approaches

Novel treatment approaches are currently being evaluated in the management of dyspnoea. Nebulized furosemide decreases breathlessness in healthy volunteers, possibly through the mediation of vagal efferents [16]. Retrosternal block with injection of 35–50 mL of lidocaine 1% attenuates dyspnoea, either through changes in afferent information from chest wall and respiratory muscles, or by direct inhibitory effects on cholinergic airway pathways [17].

Non-pharmacological approaches

Pulmonary rehabilitation in patients with chronic lung diseases is associated with reduced exertional dyspnoea and improves exercise tolerance. The benefit likely derives from multiple mechanisms, including improved physical conditioning, pacing of activities, and desensitization to respiratory distress. Chest wall vibration in COPD patients relieves dyspnoea at rest, but not during exercise [6]‌, probably through the activation of muscle spindles in the intercostals muscles causing modified respiratory sensations. Dyspnoeic patients report that movement of cool air through a fan is associated with symptom relief. Cold air on the face attenuates dyspnoea in healthy individuals [7], and preliminary data indicate some activity in clinical practice [18]. Neuromuscular electrical muscle stimulation over 4–6 weeks attenuates dyspnoea in COPD patients, and may be of particular use in patients who are unable to exercise [19]. A number of additional techniques have been insufficiently tested as dyspnoea-relief modalities, such as acupuncture, yoga, or relaxation, self-efficacy dyspnoea management, cognitive-behavioural psychotherapy, and educational counselling, and are currently not recommended for routine use [20].


1. American Thoracic Society. (1999). Dyspnea: mechanism, assessment, and management. A consensus statement. American Journal of Respiratory and Critical Care Medicine, 159, 321–40.Find this resource:

2. Kroenke K, Arrington ME, and Mangelsdorff AD. (1990). The prevalence of symptoms in medical outpatients and the adequacy of therapy. Archives of Internal Medicine, 150, 1685–9.Find this resource:

3. Bausewein C, Farquhar M, Booth S, Gysels M, and Higginson IJ. (2007). Measurement of breathlessness in advanced disease: a systematic review. Respiratory Medicine, 101, 399–410.Find this resource:

4. Bowden J, To T, Abermethy A, and Currow D. (2011). Predictors of chronic breathlessness: a large population study. BMC Public Health, 11, 33.Find this resource:

5. Banzett RB, Lansing RW, Reid MB, Adams L, and Brown R. (1989). ‘Air hunger’ arising from increased PCO2 in mechanically ventilated quadriplegics. Respiratory Physiology, 76, 53–67.Find this resource:

6. Sibuya M, Yamada M, Kanamaru A, et al. (1994) Effect of chest wall vibration on dyspnea in patients with chronic respiratory disease. American Journal of Respiratory and Critical Care Medicine, 149, 1235–40.Find this resource:

7. Schwartzstein R, Lahive MK, Pope A, Weinberger SE, and Weiss JW. (1987). Cold facial stimulation reduces breathlessness induced in normal subjects. American Review of Respiratory Disease, 136, 58–61.Find this resource:

8. Burki NK, Dale WJ, and Lee L-Y. (2005). Intravenous adenosine and dyspnea in humans. Journal of Applied Physiology, 98, 180–5.Find this resource:

9. Schon D, Rosenkranz M, Regelsberg J, et al. (2008). Reduced perception of dyspnea and pain after right insular cortex lesions. American Journal of Respiratory and Critical Care Medicine, 178, 1173–9.Find this resource:

10. Burki NK and Lee L-Y. (2010). Mechanisms of dyspnea. Chest, 138, 1196–201.Find this resource:

11. Moy ML, Lantin ML, Harver A, and Schwartzstein RM. (1998). Language of dyspnea in assessment of patients with acute asthma treated with nebulized albuterol. American Journal of Respiratory and Critical Care Medicine, 158,749–53.Find this resource:

12. Wan L, Van Diest I, De Peuter S, et al. (2009). Repeated breathlessness experiences induced by hypercapnia: differential effects on intensity and unpleasantness. Chest, 135, 455–61.Find this resource:

13. Jennings AL, Davies AN, Higgins JP, Gibbs JS, and Broadley KE. (2002). A systematic review of the use of opioids in the management of dyspnea. Thorax, 57, 939–44.Find this resource:

14. Abernethy AP, Currow DC, Frith P, Fazekas BS, Mc Hugh A, and Bui C. (2003). Randomised, double blind, placebo controlled crossover trial of sustained release morphine for the management of refractory dyspnea. British Medical Journal, 327, 523–8.Find this resource:

15. Man GC, Hsu K, and Sproule BJ. (1986). Effect of alprazolam on exercise and dyspnea in patients with chronic obstructive pulmonary disease. Chest, 90, 832–6.Find this resource:

16. Moosavi SH, Binks AP, Lansing RW, Topulos GP, Banzett RB, and Schwartzstein RM. (2007). Effect of inhaled furosemide on air hunger induced in healthy humans. Respiratory Physiology and Neurobiology, 156, 1–8.Find this resource:

17. Barak M, Isserles S, and Katz Y. (2005). Retrosternal block use in the treatment of dyspnoea. Anaesthesia and Intensive Care, 33, 531–3.Find this resource:

18. Galbraith S, Fagan P, Perkins P, Lynch A, and Booth S. (2010). Does the use of a handheld fan improve chronic dyspnea? A randomized, controlled, crossover trial. Journal of Pain Symptom Management, 39, 831–8.Find this resource:

19. Vivodtzev I, Pepin JL, Voltero G, et al. (2006). Improvement in quadriceps strength and dyspnea in severely deconditioned and malnourished COPD. Chest, 129, 1540–9.Find this resource:

20. Marciniuk DD, Goodridge D, Hernandez P, et al. (2011). Canadian Thoracic Society COPD Committee Dyspnea Expert Working Group. Managing dyspnea in patients with advanced chronic obstructive pulmonary disease: a Canadian Thoracic Society clinical practice guideline. Canadian Respiratory Journal, 18(2), 69–78.Find this resource: