Stimulus-response characteristics of CO2-induced air hunger in normal subjects

doi:10.1016/0034-5687(95)00050-X

Respiration Physiology

Volume 103, Issue 1, January 1996, Pages 19-31

Respiration Physiolo...

https://doi.org/10.1016/0034-5687(95)00050-X Get rights and content

Abstract

Hypercapnia evokes an uncomfortable sensation, termed ‘air hunger’. We examined the relationship between Pet_CO₂ and ratings of air hunger intensity under three conditions in 16 subjects: 1) mechanical ventilation with hyperoxic gas mixtures at fixed frequency and tidal volume (twice resting ventilation), 2) the same mechanical ventilation, but with hypoxic gas mixture, 3) spontaneous breathing with hyperoxic gas mixture. In each case, Pet_CO₂ was varied randomly among several levels, each held for 5 min. During hyperoxic mechanical ventilation, the mean threshold for air hunger sensation was 43 Torr, i.e., 4 Torr above resting Pet_CO₂; intolerable air hunger was evoked by 50 Torr. The threshold and tolerable levels of Pet_CO₂ varied among individuals, but were not well correlated with their ventilatory responses to CO₂. Hypoxia (Pet_O₂ 60–75 Torr) shifted the Pet_CO₂ at both threshold and tolerance down by only 2 Torr. Breathing greatly reduced the air hunger experienced at any given Pet_CO₂ (threshold increased 5 Torr, and sensitivity decreased 50%).

References (24)

R.B. Banzett et al.
‘Air hunger’ arising from increased P_CO₂ in mechanically ventilated quadriplegics
Respir. Physiol.
(1989)
R.B. Banzett et al.
‘Air hunger’ from increased P_CO₂ persists after complete neuromuscular block in humans
Respir. Physiol.
(1990)
P. Flume et al.
The Fowler breathholding study revisited: continuous rating of respiratory sensation
Respir. Physiol.
(1994)
H.L. Manning et al.
Reduced tidal volume increases ‘air hunger’ at fixed P_CO₂ in ventilated quadriplegics
Respir. Physiol.
(1992)
J.E. Remmers et al.
Effect of controlled ventilation on the tolerable limit of hypercapnia
Respir. Physiol.
(1968)
P.M. Simon et al.
Inhibition of respiratory activity during passive ventilation: a role for intercostal afferents?
Respir. Physiol.
(1993)
R. Sternbach
Psychological dimensions and perceptual analyses, including pathologies of pain
L. Adams et al.
Breathlessness during different forms of ventilatory stimulation: a study of mechanisms in normal subjects and respiratory patients
Clin. Sci.
(1985)
D. Bartlett
Effects of Valsalva and Mueller maneuvers on breath-holding time
J. Appl. Physiol.
(1977)
J. Camacho et al.
Inspiratory muscle activity in mechanically ventilated humans
Am. Rev. Respir. Dis.
(1993)

T. Chonan et al.

Effects of changes in level and pattern of breathing on the sensation of dyspnea

J. Appl. Physiol.

(1990)

T. Chonan et al.

Sensation of dyspnea during hypercapnia, exercise, and voluntary hyperventilation

J. Appl. Physiol.

(1990)

Cited by (110)

Dyspnea, Acute Respiratory Failure, Psychological Trauma, and Post-ICU Mental Health: A Caution and a Call for Research
2021, Chest
Dyspnea is an uncomfortable sensation with the potential to cause psychological trauma. Patients presenting with acute respiratory failure, particularly when tidal volume is restricted during mechanical ventilation, may experience the most distressing form of dyspnea known as air hunger. Air hunger activates brain pathways known to be involved in posttraumatic stress disorder (PTSD), anxiety, and depression. These conditions are considered part of the post-intensive care syndrome. These sequelae may be even more prevalent among patients with ARDS. Low tidal volume, a mainstay of modern therapy for ARDS, is difficult to avoid and is likely to cause air hunger despite sedation. Adjunctive neuromuscular blockade does not prevent or relieve air hunger, but it does prevent the patient from communicating discomfort to caregivers. Consequently, paralysis may also contribute to the development of PTSD. Although research has identified post-ARDS PTSD as a cause for concern, and investigators have taken steps to quantify the burden of disease, there is little information to guide mechanical ventilation strategies designed to reduce its occurrence. We suggest such efforts will be more successful if they are directed at the known mechanisms of air hunger. Investigation of the antidyspnea effects of sedative and analgesic drugs commonly used in the ICU and their impact on post-ARDS PTSD symptoms is a logical next step. Although in practice we often accept negative consequences of life-saving therapies as unavoidable, we must understand the negative sequelae of our therapies and work to minimize them under our primary directive to “first, do no harm” to patients.
Dyspnea in Patients Receiving Mechanical Ventilation
2021, Encyclopedia of Respiratory Medicine, Second Edition
In mechanically ventilated patients, dyspnea is one of the most distressing but neglected symptoms. Dyspnea affects half of patients, causes immediate and intense suffering, is strongly associated with fear/anxiety, and associated with delayed weaning from mechanical ventilation and posttraumatic stress disorders. However, one third of critically ill patients are noncommunicative, and therefore at high risk of misdiagnosis. Dyspnea observation scales based on physical and behavioral signs of respiratory discomfort are reliable and promising alternatives to self-report. We sought to summarize current data on the prevalence and prognostic influence of dyspnea in the ICU setting and to provide concise and useful information for dyspnea detection and management.
Aerosol furosemide for dyspnea: High-dose controlled delivery does not improve effectiveness
2018, Respiratory Physiology and Neurobiology
Published studies have shown great variability in response when aerosolized furosemide has been tested as a palliative treatment for dyspnea. We hypothesized that a higher furosemide dose with controlled aerosol administration would produce consistent dyspnea relief. We optimized deposition by controlling inspiratory flow (300–500 mL/s) and tidal volume (15% predicted vital capacity) while delivering 3.4 μm aerosol from either saline or 80 mg of furosemide. We induced dyspnea in healthy subjects by varying inspired PCO₂ while restricting minute ventilation. Subjects rated “Breathing Discomfort” on a Visual Analog Scale (BDVAS, 100% Full Scale ≡ intolerable). At the PET_CO₂ producing 60% BDVAS pre-treatment, furosemide produced a clinically meaningful reduction of BDVAS (i.e., >20% FS) in 5/11 subjects; saline reduced dyspnea in 3/11 subjects; neither treatment worsened dyspnea in any subject. Furosemide and saline treatment effects were not statistically different. There were no significant adverse events. Higher furosemide dose and controlled delivery did not improve consistency of treatment effect compared with prior studies.
Dyspnea
2017, Critical Care Nursing Clinics of North America
Breathlessness and the body: Neuroimaging clues for the inferential leap
2017, Cortex
Breathlessness debilitates millions of people with chronic illness. Mismatch between breathlessness severity and objective disease markers is common and poorly understood. Traditionally, sensory perception was conceptualised as a stimulus-response relationship, although this cannot explain how conditioned symptoms may occur in the absence of physiological signals from the lungs or airways. A Bayesian model is now proposed, in which the brain generates sensations based on expectations learnt from past experiences (priors), which are then checked against incoming afferent signals. In this model, psychological factors may act as moderators. They may alter priors, change the relative attention towards incoming sensory information, or alter comparisons between priors and sensations, leading to more variable interpretation of an equivalent afferent input.
In the present study we conducted a supplementary analysis of previously published data (Hayen et al., 2017). We hypothesised that individual differences in psychological traits (anxiety, depression, anxiety sensitivity) would correlate with the variability of subjective perceptions of equivalent breathlessness challenges. To better understand the resulting inferential leap in the brain, we explored where these behavioural measures correlated with functional brain activity across subjects.
Behaviourally, anxiety sensitivity was found to positively correlate with each subject's variability of intensity and unpleasantness during mild breathlessness, and with variability of unpleasantness during strong breathlessness. In the brain, anxiety sensitivity was found to negatively correlate with precuneus activity during anticipation, positively correlate with anterior insula activity during mild breathlessness, and negatively correlate with parietal sensorimotor areas during strong breathlessness.
Our findings suggest that anxiety sensitivity may reduce the robustness of this Bayesian sensory perception system, increasing the variability of breathlessness perception and possibly susceptibility to symptom misinterpretation. These preliminary findings in healthy individuals demonstrate how differences in psychological function influence the way we experience bodily sensations, which might direct us towards better understanding of symptom mismatch in clinical populations.
On the verge of a respiratory-type panic attack: Selective activations of rostrolateral and caudoventrolateral periaqueductal gray matter following short-lasting escape to a low dose of potassium cyanide
2017, Neuroscience
Intravenous injections of potassium cyanide (KCN) both elicit escape by its own and facilitate escape to electrical stimulation of the periaqueductal gray matter (PAG). Moreover, whereas the KCN-evoked escape is potentiated by CO₂, it is suppressed by both lesions of PAG and clinically effective treatments with panicolytics. These and other data suggest that the PAG harbors a hypoxia-sensitive alarm system the activation of which could both precipitate panic and render the subject hypersensitive to CO₂. Although prior c-Fos immunohistochemistry studies reported widespread activations of PAG following KCN injections, the employment of repeated injections of high doses of KCN (>60 µg) in anesthetized rats compromised both the localization of KCN-responsive areas and their correlation with escape behavior. Accordingly, here we compared the brainstem activations of saline-injected controls (air/saline) with those produced by a single intravenous injection of 40-µg KCN (air/KCN), a 2-min exposure to 13% CO₂ (CO₂/saline), or a combined stimulus (CO₂/KCN). Behavioral effects of KCN microinjections into the PAG were assessed as well. Data showed that whereas the KCN microinjections were ineffective, KCN intravenous injections elicited escape in all tested rats. Moreover, whereas the CO₂ alone was ineffective, it potentiated the KCN-evoked escape. Compared to controls, the nucleus tractus solitarius was significantly activated in both CO₂/saline and CO₂/KCN groups. Additionally, whereas the laterodorsal tegmental nucleus was activated by all treatments, the rostrolateral and caudoventrolateral PAG were activated by air/KCN only. Data suggest that the latter structures are key components of a hypoxia-sensitive suffocation alarm which activation may trigger a panic attack.

View all citing articles on Scopus

View full text

Research articleStimulus-response characteristics of CO2-induced air hunger in normal subjects

Abstract

Respir. Physiol.

Respir. Physiol.

Respir. Physiol.

Respir. Physiol.

Respir. Physiol.

Respir. Physiol.

Breathlessness during different forms of ventilatory stimulation: a study of mechanisms in normal subjects and respiratory patients

Clin. Sci.

Effects of Valsalva and Mueller maneuvers on breath-holding time

J. Appl. Physiol.

Inspiratory muscle activity in mechanically ventilated humans

Am. Rev. Respir. Dis.

Effects of changes in level and pattern of breathing on the sensation of dyspnea

J. Appl. Physiol.

Sensation of dyspnea during hypercapnia, exercise, and voluntary hyperventilation

J. Appl. Physiol.

Research article
Stimulus-response characteristics of CO₂-induced air hunger in normal subjects