Raising end-expiratory volume relieves air hunger in mechanically ventilated healthy adults.

Air hunger is an unpleasant urge to breathe and a distressing respiratory symptom of cardiopulmonary patients. An increase in tidal volume relieves air hunger, possibly by increasing pulmonary stretch receptor cycle amplitude. The purpose of this study was to determine whether increasing end-expiratory volume (EEV) also relieves air hunger. Six healthy volunteers (3 women, 31 +/- 4 yr old) were mechanically ventilated via a mouthpiece (12 breaths/min, constant end-tidal Pco(2)) at high minute ventilation (Ve; 12 +/- 2 l/min, control) and low Ve (6 +/- 1 l/min, air hunger). EEV was raised to approximately 150, 400, 725, and 1,000 ml by increasing positive end-expiratory pressure (PEEP) to 2, 4, 6, and 8 cmH(2)O, respectively, for 1 min during high and low Ve. The protocol was repeated with the subjects in the seated and supine positions to test for the effect of shifting baseline EEV. Air hunger intensity was rated at the end of each breath on a visual analog scale. The increase in EEV was the same in the seated and supine positions; however, air hunger was reduced to a greater extent in the seated position (13, 30, 31, and 44% seated vs. 3, 9, 23, and 27% supine at 2, 4, 6, and 8 cmH(2)O PEEP, respectively, P < 0.05). Removing PEEP produced a slight increase in air hunger that was greater than pre-PEEP levels (P < 0.05). Air hunger is relieved by increases in EEV and tidal volume (presumably via an increase in mean pulmonary stretch receptor activity and cycle amplitude, respectively).

Mechanical chest-wall vibration does not relieve air hunger.

Mechanical vibration of the chest wall can reduce dyspnea. It is unclear which sensations of respiratory discomfort are modulated by vibration (work/effort, air hunger, tightness). We performed two experiments to test whether vibration modifies air hunger: Experiment 1-eight adults performed six breath holds and rated their uncomfortable 'urge to breathe.' Vibration was applied separately at four chest-wall and two control sites, using two amplitudes. Breath-hold duration and ratings were unchanged by vibration at any site or amplitude. Experiment 2-nine adults were mechanically ventilated (mean 8.73 L/min) at constant hypercapnia (mean 48 mmHg) to produce mild to moderate ratings of air hunger (mean 37% of scale) with minimal respiratory muscle work. Vibration at 2nd or 3rd intercostal spaces during either inspiration or expiration did not change air hunger compared to triceps vibration. These experiments demonstrated that vibration does not relieve air hunger; we postulate that the effect of vibration is specific to the form of dyspnea.

Hypoxic and hypercapnic drives to breathe generate equivalent levels of air hunger in humans.

Anecdotal observations suggest that hypoxia does not elicit dyspnea. An opposing view is that any stimulus to medullary respiratory centers generates dyspnea via "corollary discharge" to higher centers; absence of dyspnea during low inspired Po(2) may result from increased ventilation and hypocapnia. We hypothesized that, with fixed ventilation, hypoxia and hypercapnia generate equal dyspnea when matched by ventilatory drive. Steady-state levels of hypoxic normocapnia (end-tidal Po(2) = 60-40 Torr) and hypercapnic hyperoxia (end-tidal Pco(2) = 40-50 Torr) were induced in naive subjects when they were free breathing and during fixed mechanical ventilation. In a separate experiment, normocapnic hypoxia and normoxic hypercapnia, "matched" by ventilation in free-breathing trials, were presented to experienced subjects breathing with constrained rate and tidal volume. "Air hunger" was rated every 30 s on a visual analog scale. Air hunger-Pet(O(2)) curves rose sharply at Pet(O(2)) <50 Torr. Air hunger was not different between matched stimuli (P > 0.05). Hypercapnia had unpleasant nonrespiratory effects but was otherwise perceptually indistinguishable from hypoxia. We conclude that hypoxia and hypercapnia have equal potency for air hunger when matched by ventilatory drive. Air hunger may, therefore, arise via brain stem respiratory drive.

High strength stimulation of the vagus nerve in awake humans: a lack of cardiorespiratory effects.

UNLABELLED: Vagus nerve stimulation is used to reduce the frequency and intensity of seizures in patients with epilepsy. In the present study four such patients were studied while awake. We analyzed the physiological responses to vagus nerve stimulation over a broad range of tolerable stimulus parameters to identify vagal A-fiber threshold and to induce respiratory responses typical of C-fiber activation. A-fiber threshold was determined by increasing stimulation current until laryngeal motor A-fibers were excited (frequency=30 Hz). With A-fiber threshold established, C-fiber excitation was attempted with physiologically appropriate stimulus parameters (low frequency and high amplitude). RESULTS: A-fiber thresholds were established in all patients, threshold currents ranged between 0.5 and 1.5 mA. Stimulation at lower frequency (2-10 Hz) and higher amplitudes (2.75-3.75 mA) did not produce cardiorespiratory effects consistent with C-fiber activation. It is possible that such effects were not observed because vagal C-fibers were not excited, because C-fiber effects were masked by the 'wakeful drive' to breathe, or because epilepsy or the associated therapy had altered central processing of the vagal afferent inputs.

Oscillation of the lung by chest-wall vibration.

Vibration of the thoracic surface has been shown to modify the drive to breathe and the sensation of dyspnea. It has been suggested that respiratory muscle afferents generate these effects. The possibility that the consequences of chest-wall vibration also involve intra-pulmonary afferents led us to investigate whether such vibration reaches the airways. Two vibratory stimuli were independently applied to four chest-wall sites and two control sites on eight healthy subjects. During separate breath holds, the vibrator was held on each site while subjects periodically opened and closed the pharynx. Airway pressure (P(AW)) was measured at the mouth. Spectral analysis of P(AW) showed pressure oscillations occurred at the same frequency as that of the vibrators when the pharynx was open; oscillation amplitude was vastly reduced when the pharynx was closed. Oscillation amplitude was also significantly larger during vibration at greater amplitude. These data demonstrate that vibration over the chest-wall vibrates the lung and could potentially excite intrapulmonary receptors.