Respiration Physiology, 90 (1992) 19-30 © 1992 Elsevier Science Publishers B,V. All fights reserved. 0034-5687/92/$05.00
19
RESP 01950
Reduced tidal volume increases 'air hunger' at fixed Pco in ventilated quadriplegics Harold L. Manning a'~, Steven A. Sheab, Richard M. Schwartzstein a Robert W. Lansing b, Robert Brown c and Robert B. Banzett b ' Department of Medicine, Beth Israel Hospital. and Harvard Medical School. Boston. MA, USA. bDepartment of Environmental Science and Physiology. Harvard School of Public Health. Boston. MA. USA and ~ West Roxbury VA Medical Center. Boston. MA. USA (Accepted 1 June 1992)
Abstract. The act of breathing diminishes the discomfort associated with hypercapnia and breath-holding. To investigate the mechanisms involved in this effect, we studied the effect of tidal volume (VT) on CO2evoked air hunger in 5 high-level quadriplegic subjects whose ventilatory capacity was negligible, and who lacked sensory information from the chest wall. Subjects were ventilated at constant frequency with a hyperoxic gas mixture, and end-tidal Pco, was maintained at a constant but elevated level. VT was varied between the subjects' normal VT and a smaller VT. Subjects used a category scale to rate their respiratory discomfort or 'air hunger' at 30-40 sec intervals, in 4 of 5 subjects there was a strong inverse relationship between breath size and air hunger ratings. The quality of the sensation associated with reduced VT was nearly identical to that previously experienced with CO2 alone. We conclude that afferent information from the lungs and upper airways is sufficient to modify the sensation of air hunger.
Bl0athlessness, CO,, tidal volume (quadriplegics); Control of breathing, respiratory sensation; Dyspnea, CO,, tidal volume (quadriplegics); Mammals, humans
When end-tidal Pco, (PETco.~) is raised by addition of CO2 to inspired gas, subjects report a sensation of urgency to breathe, or 'air hunger' (e.g., Adams et al., 1985; Banzett et al., 1989, 1990). Subjects liken this sensation to that experienced during breath-holding (Banzett et ai., 1989, 1990). It is likely that studies measuring tolerance for breath-holding or for suppressed ventilation combined with hypercapnia are indirectly measuring air hunger. The air hunger at the end of a long breath-hold can be temporarily relieved by rebreathing a gas nfixture that provides no improvement in blood gases (Hill and Flack, 1908; Fowler, 1954). Similarly, prior studies have shown that during hypercapnia, a decrease in ventilation increases respiratory discomfort even when PETco2 is held constant (Chonan et al., 1987; Schwartzstein et al., 1989). What mechanisms might be proposed to explain this effect of breathing upon the intensity of air hunger? An increase in breathing implies both an increase in respiratory motor 1Correspondence to: Present address: H.L. Manning, Pulmonary Division, Dartmouth-Hitchcock Medical Center, Lebanon, NH 03756, USA.
H.L. MANNING et al.
20
output and an increase in afferent signals from mechanoreceptors in the lungs, chest wall, and upper airways. Either motor output or afferent feedback might diminish air hunger during increased breathing; conversely, the willful effort to suppress breathing might intensify air hunger. To determine whether afferent signals arising from the passive motion of the respiratory system are sufficient to modify air hunger, we examined whether changes in tidal volume (VT) were accompanied by changes in the intensity of air hunger in ventilatordependent CI-C3 quadriplegics. In these subjects ventilatory capacity was negligible, thus obviating the need for them to suppress spontaneous ventilation in order to achieve completely passive ventilation. The use of high-level quadriplegic subjects also helps to define the afferent pathway involved, since afferent information from the chest wall is absent or markedly diminished in these individuals. We reasoned that if an inverse relationship between air hunger and breath size existed in this group of subjects, it would provide evidence that the intact afferent information from the lungs and airways is sufficient to modify the sensation of air hunger. The experiment was done in two parts: the first to determine the relationship of air hunger intensity to PETco2 at fixed tidal volume, the second to determine the relationship of air hunger intensity to tidal volume at fixed PETco,. The quality of air hunger sensation was examined after each part.
Methods Subjects
We studied 5 high cervical quadriplegics whose characteristics are summarized in Table 1. Subject 2 was studied on two occasions because the initial study was limited by time constraints; the second study included only part 2 of the protocol (see Protocol, below). The study was approved by the institutional review boards, and informed consent was obtained from each subject. None of the subjects was aware of the purTABLE 1 Subject characteristics and baseline ventilation parameters Subject
Age/sex Levelof injury
Tracheostomy
Ventilation
VT (ml)
f (min-t)
VC (ml)
MIP (cmH20)
1 2 5 6 8
35/F 40/M 41/M 29/M 53/M
Cuffed Uncuffed Uncurled Cuffed Untufted
IPPV IPPV PPM PPM IPPV
1000 1565 890 833 1200
10 10 12 8 10
80 0 0 30 NM
NM 0 0 NM NM
C, C~ C2 C2=3 C2
Abbreviations: IPPV, intermittent positive pressure ventilation; PPM, phrenic pacemaker; VT, baseline ventilator tidal volume; f, baseline ventilator frequency; VC, vital capacity; MIP, maximal inspiratory pre~sure; NM, not measured.
2!
EFFECT OF TIDAL VOLUME ON AIR HUNGER
pose of the study. Subjects 1, 2, 5, and 6 had participated in previous studies of respiratory sensation and are described in detail in previous publications using corresponding numbers (Banzett et al., 1987, 1989). Subject 8 was a 53-year-old man who suffered a traumatic spinal cord injury 13 years prior to the study. He had no sensation below the level of C2. He retained some movement in his sternocleidomastoid and trapezius muscles, and could sustain spontaneous ventilation for approximately 5 min. All of the subjects required chronic ventilatory support, achieved via a tracheostomy by either intermittent positive pressure ventilation (IPPV) or phrenic pacing. The baseline ventilator settings were those selected by the clinicians caring for the subjects. As is common in ventilator-dependent individuals, all of our subjects were normally mainrained on relatively large tidal volumes, which seemed to provide them with greater breathing comfort. Accordingly, all of the subjects were chronically hypocapnic (Table 2). The ventilator settings for all subjects had been stable for months or years prior to this study. In 2 of the subjects, the tracheostomy tube was cuffed; the remaining 3 subjects were unable to tolerate a cuffed tube, but maintained a closed glottis to prevent air leaks. All studies were performed with the subject positioned almost fully reclined in his or her wheel chair. Throughout the experiment, white noise was played to the subject via headphones in order to mask the noise from the ventilator, thereby avoiding auditory cues to changes in tidal volume. Ventilation
Baseline ventilator settings and PETco, were recorded for each subject upon their arrival in the laboratory (Table 1). During the study, subjects were supported by a volume-cycled ventilator (Siemens 900C). The standard ventilator circuit was modified TABLE 2 Results of part 1: relationship between air hunger and CO2 Subject
Baseline
PETco2/ Slight AH (mmHg)
PETco2/ Extreme AH (mmHg)
Air hunger/PETco~
(mmHg)
PETco2/ No AH (mmHg)
Rho
P value
13 16 25 31 25
22 26 30 32 27
25 31 33 36 31
33 45 39 44 42
0.87 0.57 0.74 0.61 0.54
19
RESP 01950
Reduced tidal volume increases 'air hunger' at fixed Pco in ventilated quadriplegics Harold L. Manning a'~, Steven A. Sheab, Richard M. Schwartzstein a Robert W. Lansing b, Robert Brown c and Robert B. Banzett b ' Department of Medicine, Beth Israel Hospital. and Harvard Medical School. Boston. MA, USA. bDepartment of Environmental Science and Physiology. Harvard School of Public Health. Boston. MA. USA and ~ West Roxbury VA Medical Center. Boston. MA. USA (Accepted 1 June 1992)
Abstract. The act of breathing diminishes the discomfort associated with hypercapnia and breath-holding. To investigate the mechanisms involved in this effect, we studied the effect of tidal volume (VT) on CO2evoked air hunger in 5 high-level quadriplegic subjects whose ventilatory capacity was negligible, and who lacked sensory information from the chest wall. Subjects were ventilated at constant frequency with a hyperoxic gas mixture, and end-tidal Pco, was maintained at a constant but elevated level. VT was varied between the subjects' normal VT and a smaller VT. Subjects used a category scale to rate their respiratory discomfort or 'air hunger' at 30-40 sec intervals, in 4 of 5 subjects there was a strong inverse relationship between breath size and air hunger ratings. The quality of the sensation associated with reduced VT was nearly identical to that previously experienced with CO2 alone. We conclude that afferent information from the lungs and upper airways is sufficient to modify the sensation of air hunger.
Bl0athlessness, CO,, tidal volume (quadriplegics); Control of breathing, respiratory sensation; Dyspnea, CO,, tidal volume (quadriplegics); Mammals, humans
When end-tidal Pco, (PETco.~) is raised by addition of CO2 to inspired gas, subjects report a sensation of urgency to breathe, or 'air hunger' (e.g., Adams et al., 1985; Banzett et al., 1989, 1990). Subjects liken this sensation to that experienced during breath-holding (Banzett et ai., 1989, 1990). It is likely that studies measuring tolerance for breath-holding or for suppressed ventilation combined with hypercapnia are indirectly measuring air hunger. The air hunger at the end of a long breath-hold can be temporarily relieved by rebreathing a gas nfixture that provides no improvement in blood gases (Hill and Flack, 1908; Fowler, 1954). Similarly, prior studies have shown that during hypercapnia, a decrease in ventilation increases respiratory discomfort even when PETco2 is held constant (Chonan et al., 1987; Schwartzstein et al., 1989). What mechanisms might be proposed to explain this effect of breathing upon the intensity of air hunger? An increase in breathing implies both an increase in respiratory motor 1Correspondence to: Present address: H.L. Manning, Pulmonary Division, Dartmouth-Hitchcock Medical Center, Lebanon, NH 03756, USA.
H.L. MANNING et al.
20
output and an increase in afferent signals from mechanoreceptors in the lungs, chest wall, and upper airways. Either motor output or afferent feedback might diminish air hunger during increased breathing; conversely, the willful effort to suppress breathing might intensify air hunger. To determine whether afferent signals arising from the passive motion of the respiratory system are sufficient to modify air hunger, we examined whether changes in tidal volume (VT) were accompanied by changes in the intensity of air hunger in ventilatordependent CI-C3 quadriplegics. In these subjects ventilatory capacity was negligible, thus obviating the need for them to suppress spontaneous ventilation in order to achieve completely passive ventilation. The use of high-level quadriplegic subjects also helps to define the afferent pathway involved, since afferent information from the chest wall is absent or markedly diminished in these individuals. We reasoned that if an inverse relationship between air hunger and breath size existed in this group of subjects, it would provide evidence that the intact afferent information from the lungs and airways is sufficient to modify the sensation of air hunger. The experiment was done in two parts: the first to determine the relationship of air hunger intensity to PETco2 at fixed tidal volume, the second to determine the relationship of air hunger intensity to tidal volume at fixed PETco,. The quality of air hunger sensation was examined after each part.
Methods Subjects
We studied 5 high cervical quadriplegics whose characteristics are summarized in Table 1. Subject 2 was studied on two occasions because the initial study was limited by time constraints; the second study included only part 2 of the protocol (see Protocol, below). The study was approved by the institutional review boards, and informed consent was obtained from each subject. None of the subjects was aware of the purTABLE 1 Subject characteristics and baseline ventilation parameters Subject
Age/sex Levelof injury
Tracheostomy
Ventilation
VT (ml)
f (min-t)
VC (ml)
MIP (cmH20)
1 2 5 6 8
35/F 40/M 41/M 29/M 53/M
Cuffed Uncuffed Uncurled Cuffed Untufted
IPPV IPPV PPM PPM IPPV
1000 1565 890 833 1200
10 10 12 8 10
80 0 0 30 NM
NM 0 0 NM NM
C, C~ C2 C2=3 C2
Abbreviations: IPPV, intermittent positive pressure ventilation; PPM, phrenic pacemaker; VT, baseline ventilator tidal volume; f, baseline ventilator frequency; VC, vital capacity; MIP, maximal inspiratory pre~sure; NM, not measured.
2!
EFFECT OF TIDAL VOLUME ON AIR HUNGER
pose of the study. Subjects 1, 2, 5, and 6 had participated in previous studies of respiratory sensation and are described in detail in previous publications using corresponding numbers (Banzett et al., 1987, 1989). Subject 8 was a 53-year-old man who suffered a traumatic spinal cord injury 13 years prior to the study. He had no sensation below the level of C2. He retained some movement in his sternocleidomastoid and trapezius muscles, and could sustain spontaneous ventilation for approximately 5 min. All of the subjects required chronic ventilatory support, achieved via a tracheostomy by either intermittent positive pressure ventilation (IPPV) or phrenic pacing. The baseline ventilator settings were those selected by the clinicians caring for the subjects. As is common in ventilator-dependent individuals, all of our subjects were normally mainrained on relatively large tidal volumes, which seemed to provide them with greater breathing comfort. Accordingly, all of the subjects were chronically hypocapnic (Table 2). The ventilator settings for all subjects had been stable for months or years prior to this study. In 2 of the subjects, the tracheostomy tube was cuffed; the remaining 3 subjects were unable to tolerate a cuffed tube, but maintained a closed glottis to prevent air leaks. All studies were performed with the subject positioned almost fully reclined in his or her wheel chair. Throughout the experiment, white noise was played to the subject via headphones in order to mask the noise from the ventilator, thereby avoiding auditory cues to changes in tidal volume. Ventilation
Baseline ventilator settings and PETco, were recorded for each subject upon their arrival in the laboratory (Table 1). During the study, subjects were supported by a volume-cycled ventilator (Siemens 900C). The standard ventilator circuit was modified TABLE 2 Results of part 1: relationship between air hunger and CO2 Subject
Baseline
PETco2/ Slight AH (mmHg)
PETco2/ Extreme AH (mmHg)
Air hunger/PETco~
(mmHg)
PETco2/ No AH (mmHg)
Rho
P value
13 16 25 31 25
22 26 30 32 27
25 31 33 36 31
33 45 39 44 42
0.87 0.57 0.74 0.61 0.54
