Alleviating Dyspnea and Possible Biologic Mechanisms

To the Editor:

Dr Hallenbeck explained the pathophysiology of dyspnea and the neural and humoral regulation of the respiratory drive. ¹ Dyspnea means “when there is either some perceived imbalance between the ability to ventilate adequately for a given demand or when there is a perception that the balance between demand and the respiratory response is unsustainable.” ¹ We outline additional mechanisms that can prevent the onset and/or attenuate the severity of dyspnea by balancing ventilatory demand and capacity and augmenting the “sustainability” of ventilation.

First, the cardiovascular and respiratory systems respond physiologically to changing metabolic demands. Proportional changing of cardiac output (CO) predominantly regulates oxygen delivery (DO₂) and oxygen consumption (VO₂) to varying metabolic requirements. ² Cardiovascular response can decrease the ventilatory demand necessary for an increased VO₂:

a. The increase in CO (and DO₂) and whole body extraction of oxygen stored in venous blood hemoglobin can prevent an early onset of anaerobic metabolism. The threshold for anaerobic metabolism and lactic acid production is reached when mixed venous oxyhemoglobin falls from the normal level of 75% to less than 50%.

b. The increase in CO and CO₂ production is associated with an increase of total pulmonary blood and alveolar perfusion and a simultaneous reduction of the dead space to tidal volume ratio. The reduction in the dead space to tidal volume ratio augments the alveolar ventilation and CO₂ elimination via the lungs without causing a disproportionate increase of the respiratory rate.

Second, the downregulation of resting and peak VO₂ (similar to biologic metabolic hibernation) is another mechanism that may decrease ventilatory demand in the terminally ill and advanced chronic illnesses.^3–5

Third, the mechanical capacity and efficiency of respiratory muscles (the diaphragm and intercostal muscles) may be diminished in cachectic patients. However, the concomitant global reduction of total body muscle mass in cachectic patients facilitates the redistribution of a higher fraction of the CO and DO₂ to the respiratory muscles than in healthy individuals. This preferential redistribution of CO and DO₂ enhances the aerobic capacity of the respiratory muscles to cope with the mechanical load of breathing. This can diminish the fatigability of respiratory muscles.

Fourth, altering blood and tissue gases and acid-base concentrations can stimulate central and peripheral chemoreceptors and neural reflexes regulating respiratory centers. ¹ Resetting of the setpoint and altering of the sensitivity of the neural reflexes under different conditions of ventilatory demand can reestablish new steady-state blood concentrations of gases and acid-base without exhausting native ventilatory capacity. Therefore, dynamic modulation of the neural reflexes can ameliorate dyspnea associated with hypoxia, hypercarbia, and metabolic acidosis.

Finally, Dr Hallenbeck described the cognitive and affective processing of dyspnea. ¹ This has profound implications on terminal withdrawal of mechanical ventilation and extubation in the intensive care unit. Patients with severe pulmonary dysfunction and/or respiratory muscle weakness can develop work-of-breathing dyspnea upon terminal withdrawal of mechanical ventilation. When patients with absent or diminished airway reflexes are terminally extubated, they can develop airway obstruction and suffocation dyspnea. The clinical efficacy of analgesics and sedatives in alleviating the distress of dyspnea after terminal withdrawal of mechanical ventilation and extubation is unknown. ⁶ This distress can be difficult to assess and treat optimally. Perhaps from pathophysiologic inference, abandoning the practice of terminally extubating and withdrawing positive pressure ventilation is the most appropriate way of avoiding distress in patients who are prone to dyspnea. Delivering high-quality palliative care is feasible without removing endotracheal tubes and/or positive pressure ventilation that provides symptomatic relief from suffocation and/or work-of-breathing dyspnea. The avoidance of dyspnea before death and continuation of palliative care for a longer time could outweigh the perceived benefit of treatment withdrawal to shorten the dying process and therefore the suffering.

We agree with Dr Hallenbeck that contemporary understanding of the pathophysiology and biologic mechanisms alleviating dyspnea is deficient. Better scientific characterization of these mechanisms and the cognitive-affective processing of dyspnea are essential for an optimal end-of-life care and good ethical decision making.