Does Hypoxia cause Dyspnoea?

Dyspnoea or breathlessness is a very common and significant presentation. Breathlessness is the primary reason 3.5% of people present to emergency department in the United States. Of these, approximately 51% are admitted to hospital and 13% are dead within a year. Some studies have suggested that up to 27% of people suffer from dyspnoea, while in dying patients 75% will experience it. It has been shown that presence of dyspnoea in patients with Diabetes and Cardiovascular disease has 60% mortality in 10 years. Dyspnoea was a stronger predictor of mortality than gastrointestinal symptoms in oesophageal and gastric cancer in studies. Self -reported dyspnoea severity has been shown as a much stronger predictor of 5-year mortality than FEV1 (in COPD).

It is a common misconception that dyspnoea occurs due to hypoxia. In reality, many patients with dyspnoea are not hypoxic, and some patients with hypoxia do not have dyspnoea. In fact, even in cardiopulmonary disease hypoxia plays a limited role in breathlessness and when hypoxia is corrected only slight improvement occurs in symptoms. In normal people, rate and severity of ventilation does not increase unless pO2 is reduced significantly (below 60mmHg). In comparison pCO2 plays a very significant role in hyperventilation and dyspnoea. Researcher showed on ventilated patients under controlled conditions that only few mmHg of pCO2 rise caused air hunger and breathlessness. Fig. 1 shows effect of minimal pCO2 rise causes significant increase of ventilation but only minimal rise of ventilation occurs with hypoxia.

Fig. 1: Effects of pO2 and pCO2 rise on ventilation

American Thoracic Society defines dyspnoea as "a subjective experience of breathing discomfort that consists of qualitatively distinct sensations that vary in intensity," Like pain, it is also a subjective feeling of discomfort or distress. In fact recent sophisticated imaging managed to reveal activation of a key region in anterior insula in the brain by both pain and dyspnoea. Dyspnoea results from a disassociation or a mismatch between central respiratory motor activity and incoming afferent information from receptors in the airways, lungs, and chest wall structures.

Patient self-reporting is the best guide for assessing severity of dyspnoea. No objective measure of the disorder is available. Measurement of respiratory rate, oxygen saturation and arterial blood gas do not correlate with and do not measure dyspnoea. Attempts have been made to standardise symptoms reporting. Some scales are developed for clinical settings which include Visual Analogue Scale, Modified Borg Scale and MRC scale; of them last two are widely used.

To identify specific nature of the disorder causing dyspnoea, clinician has to elaborate history and examination and organise appropriate laboratory investigations .The primary cause is usually heart, lung, or neuromuscular abnormalities. A staggering 497 distinct causes of dyspnoea were listed by ‘DiagnosisPro’, an online medical expert system which shows the extensive nature of the underlying causes. Once an underlying pathology is detected, management should be directed accordingly.

However, in many cases a cause cannot be found. This is a common problem in advanced cancer patients and palliative patients. Frequency of dyspnoea in cancer patients varies from 21% to 90%, depending on the stage of cancer. The National Hospice Study found that 24% of patients with dyspnoea had no known cardiopulmonary pathology. In those situations best management is directed to alleviate symptom. Different measures e.g. bronchodilation, oxygen therapy, exercise training etc. have been tried with marginal effects in studies. A Meta-analysis of studies on Oxygen therapy did not show significant benefit. Among medications, Opioids are the most effective in these patients. Variable doses of opioids of different forms (Codeine, morphine, hydro morphine etc.) are recommended for different severity of dyspnoea. Dose of opioids needs to be titrated according to the response of the patient.

In conclusion, dyspnoea is described as a "synthetic sensation, like thirst or hunger” which is the result of a complex interaction of signals from automatic centres in the brain stem and from motor cortex, and from a variety of receptors in the upper airway, lungs, and chest wall. Our capacity to alleviate the symptom of dyspnoea largely depends on our ability to define the complex mechanisms which determine its quality and intensity in our patients.

Bibliography:

1. Dyspnoea: Mechanisms, Assessment, and Management: A Consensus Statement by American Thoracic Society, Am J Respir Crit Care Med Vol 159. pp 321–340, 199

2. Pathophysiology of Dyspnoea, Harold L. Manning, Richard M. Schwartzstein, Nejm, Vol. 333:1547-1553 December 7, 1995 Number 23.

3. Determinants of Dyspnoea in Patients with Different Grades of Stable Asthma, Dra.Eva Martínez-Moragón at el,Journal of Asthma 2003 40:4 , 375-382 3. Determinants of Dyspnoea in Patients with Different Grades of Stable Asthma, Dra.Eva Martínez-Moragón at el,Journal of Asthma 2003 40:4 , 375-382 3.