Changes In Minute Ventilation Research Articles

Effect of lumbar epidural anesthesia on ventilatory response to hypercapnia in young and elderly patients

Study Objective: To examine the influence of age on resting ventilation, arterial blood gas tensions, and the ventilatory response to hypercapnia in lumbar epidural anesthesia. Design: Clinical study using groups of young and elderly patients. Setting: Surgical operation center of a university hospital. Patients: Seven young (average age 39 years) and seven elderly (average age, 69 years) unpremeditated patients undergoing lower abdominal surgery. Interventions: Patients were administered lumbar epidural anesthesia with 10 ml of 2% lidocaine. Measurements and Main Results: Resting ventilation, arterial blood gas tensions, and ventilatory response to hypercapnia were measured before and 20 minutes after the block. Regarding the ventilatory response to hypercapnia, the mean slope of the hypercapnic response curve (change in minute ventilation (V̇E) divided by change in end-tidal partial pressure of carbon dioxide (P ET CO 2)] increased significantly following the epidural block, by 16% in the young patients. and by 23% in the elderly patients, and the mean V̇E at a P ET CO 2 of 55 mmHg (V̇E 55) also increased significantly,, by 16% in the young subjects and by 26% in the older subjects. These changes in ΔV̇E/ΔP ET CO 2 and V̇E 55 were statistically equivalent between the two age-groups. Conclusions: The effects of lumbar epidural anesthesia on resting ventilation, arterial blood gas tensions, and ventilatory response to hypercapnia were not affected by age.

Fresh gas flow changes during controlled mechanical ventilation with the circle breathing system have significantly greater effects on the ventilatory parameters of toddlers compared with children

Summary Fresh gas flow into a circle system can affect the delivered minute ventilation because fresh gas flow augments the flow delivered by the ventilator bellows during inspiration. After establishing a stable ventilatory pattern with 3.0 l·min-1 fresh gas flow into a circle system, changes in peak inflation pressure, minute ventilation and end-tidal carbon dioxide were measured at 1.5 l·min-1 and 6.0 l·min-1 in 10 toddlers (10–20 kg) and 10 children (30–60 kg). Changes in all variables were observed but these changes were greater in toddlers compared with children (P < 0.001). Some toddlers were noted to have as much as a 37% change in ventilatory parameters when fresh gas flow was altered between 1.5 and 6.0 l·min-1. Whenever changes are made in fresh gas flow, compensatory changes in minute ventilation should be considered to avoid unintended hyperventilation or hypoventilation. This is especially important during anaesthesia for toddlers.

Expiratory muscle activity in the awake and sleeping human during lung inflation and hypercapnia.

Expiratory muscle activity has been shown to occur in awake humans during lung inflation; however, whether this activity is dependent on consciousness is unclear. Therefore we measured abdominal muscle electromyograms (intramuscular electrodes) in 13 subjects studied in the supine position during wakefulness and non-rapid-eye-movement sleep. Lung inflation was produced by nasal continuous positive airway pressure (CPAP). CPAP at 10-15 cmH2O produced phasic expiratory activity in two subjects during wakefulness but produced no activity in any subject during sleep. During sleep, CPAP to 15 cmH2O increased lung volume by 1,260 +/- 215 (SE) ml, but there was no change in minute ventilation. The ventilatory threshold at which phasic abdominal muscle activity was first recorded during hypercapnia was 10.3 +/- 1.1 l/min while awake and 13.8 +/- 1 l/min while asleep (P less than 0.05). Higher lung volumes reduced the threshold for abdominal muscle recruitment during hypercapnia. We conclude that lung inflation alone over the range that we studied does not alter ventilation or produce recruitment of the abdominal muscles in sleeping humans. The internal oblique and transversus abdominis are activated at a lower ventilatory threshold during hypercapnia, and this activation is influenced by state and lung volume.

The effect of auto-positive end-expiratory pressure on the arterial-end-tidal carbon dioxide pressure gradient and expired carbon dioxide slope in critically ill patients during total ventilatory support

To examine the effect of auto-positive end-expiratory pressure (autoPEEP) on the estimation of arterial carbon dioxide pressure (PaCO 2) from end-tidal carbon dioxide pressure (PetCO 2) during changes in minute ventilation (MV), we studied 24 consecutive sedated and paralyzed patients under controlled mechanical ventilation for acute respiratory failure. The patients were grouped according to whether they had autoPEEP: group I (n = 11) comprised non-autoPEEP patients and group II (n = 13) comprised autoPEEP patients. Patients were randomly ventilated at three different levels of MV: normal MV (basal tidal volume), high MV (tidal volume 2.5 mL/kg above basal), and low MV (tidal volume 2.5 mL/ kg below basal). Respiratory rate and inspiration to expiration ratio were kept constant during the study. In each condition, we measured arterial blood gases, expiratory capnograms, airway pressure, and autoPEEP. We determined PaCO 2-PetCO 2 gradient, predicted PaCo 2 (Pa'CO 2) [Pa'CO 2 = PetCO 2 for each condition + (PaCO 2 PetCO 2 gradient at normal MV)], and expired CO 2 slope. The PaCO 2-PetCO 2 gradient only remained stable in group I (mean values for low, normal, and high MV were 3.3, 3.3, and 3.5 mm Hg, respectively), while group II showed a significant difference during low MV (12.2 mm Hg) when compared with normal MV (8.4 mm Hg; P < .01) and high MV (8.9 mm Hg; P < .05). PaCO 2 and PetCO 2 showed significant correlations in both groups ( r = .92 in group I and .79 in group II). However, Pa'CO 2 could only be safely estimated in patients without autoPEEP when the difference between PaCO 2 and Pa'CO 2, ranged between 1.6 and −1.9 mm Hg. Slopes of expired CO 2 greater than 3 mm Hg/s identified patients with autoPEEP of 89% sensitivity, 93% specificity, 94% positive predictive power, and 95% accuracy. A significant correlation was found between autoPEEP and expired CO 2 slope ( r = .70; P < .001), between autoPEEP and PaCO 2-PetCO 2 gradient ( r = .46; P < .001), and between CO 2 expired slope and PaCO 2 PetCO 2 gradient ( r = .74; P < .001). These results indicate that in patients with acute respiratory failure under controlled mechanical ventilation, the presence of autoPEEP is associated with inaccuracy in the calculation of predicted PacoZ from PetcoZ after changes in MV at fixed respiratory rates.

Oxygen-induced Hypercarbia in Obstructive Pulmonary Disease

We investigated the mechanisms responsible for oxygen-induced hypercarbia in ventilator-dependent patients with advanced chronic obstructive pulmonary disease (COPD). To quantitate the effects of oxygen (O2) on respiratory drive, we determined the CO2 recruitment threshold (PCO2 RT) in 10 mechanically ventilated patients under normoxic (PaO2 = 67 +/- 7 mm Hg) and hyperoxic (PaO2 = 370 +/- 67 mm Hg) conditions. PCO2 RT is a measure of the CO2 responsiveness of the mechanically unloaded respiratory system and, as such, is independent of mechanical impedance and respiratory muscle strength. After O2 supplementation, PCO2 RT increased from 42 +/- 6 to 45 +/- 6 mm Hg (p less than or equal to 0.05), indicating a suppression of so-called hypoxic respiratory drive. The effect of hyperoxia on the dead space to tidal volume ratio (VD/VT) and CO2 elimination (VCO2) was studied in 6 patients. Measurements were made at identical ventilator settings, thus eliminating breathing pattern- and respiratory work-related effects on these variables. VD/VT rose from 0.49 +/- 0.09 to 0.55 +/- 0.06 (p less than or equal to 0.05), but VCO2 remained constant at 0.21 L/min. We discuss why measuring O2-induced changes in minute ventilation, VCO2, PaO2, and VD/VT in spontaneously breathing patients is insufficient to distinguish between gas exchange- and respiratory drive-related mechanisms for hypercarbia. Based on the O2-induced increase in PCO2 RT, we conclude that so-called suppression of hypoxic drive plays an important role in the pathogenesis of this disorder.

Effect of chest wall vibration on breathlessness in normal subjects

This study evaluated the effect of chest wall vibration (115 Hz) on breathlessness. Breathlessness was induced in normal subjects by a combination of hypercapnia and an inspiratory resistive load; both minute ventilation and end-tidal CO2 were kept constant. Cross-modality matching was used to rate breathlessness. Ratings during intercostal vibration were expressed as a percentage of ratings during the control condition (either deltoid vibration or no vibration). To evaluate their potential contribution to any changes in breathlessness, we assessed several aspects of ventilation, including chest wall configuration, functional residual capacity (FRC), and the ventilatory response to steady-state hypercapnia. Intercostal vibration reduced breathlessness ratings by 6.5 +/- 5.7% compared with deltoid vibration (P less than 0.05) and by 7.0 +/- 8.3% compared with no vibration (P less than 0.05). The reduction in breathlessness was accompanied by either no change or negligible change in minute ventilation, tidal volume, frequency, duty cycle, compartmental ventilation, FRC, and the steady-state hypercapnic response. We conclude that chest wall vibration reduces breathlessness and speculate that it may do so through stimulation of receptors in the chest wall.

Breathing During Sleep in Normal Middle-Aged Subjects

Although ventilation during sleep has been studied in normal young and elderly subjects, little data are available concerning possible quantitative changes in ventilatory parameters in normal middle-aged subjects. We studied the occurrence of respiratory events and the changes in minute ventilation, tidal volume, and respiratory rate during rapid-eye-movement (REM) and non-REM (NREM) sleep in 40 normal (20 men and 20 women) middle-aged subjects, using polysomnography with pneumotachography and oximetry. Apnea indices greater than 5, with apneas predominantly of the obstructive type, were found in 17.5% of the subjects (30% of the men and 5% of the women). These "apneic" subjects differed from the "nonapneic" subjects only in that they had a higher body mass index. Minute ventilation decreased from wakefulness to sleep by 14% to 19%, owing to a decrease in tidal volume without a significant change in respiratory rate. This decrease was not greater in slow wave (stage 3-4 NREM) or in REM sleep than in stage 2 NREM sleep, nor was it greater in men than in women. It correlated with the minute ventilation during wakefulness: the higher the minute ventilation during wakefulness, the greater the decrease during sleep. The occurrence of respiratory events was not related to the degree of the decrease in minute ventilation from wakefulness to apnea-free sleep.

End-tidal Carbon Dioxide in Critically ill Patients during Changes in Mechanical Ventilation

Values of end-tidal CO2 (PETCO2) approximate PaCO2 in spontaneous breathing normal subjects and in stable patients receiving mechanical ventilatory support (MVS). Because marked inequality of ventilation/perfusion ratios in critically ill patients might affect this correlation, we assessed changes of PETCO2 in predicting changes in PaCO2 (delta PaCO2) and changes in minute ventilation (delta Ve) in this patient population. Twenty consecutive intubated patients 38 to 89 yr of age (mean, 70 yr) with respiratory failure while receiving MVS with indwelling arterial lines were studied. Settings on the mechanical ventilator were varied for frequency and tidal volume, and after a minimum of 5 to 10 min equilibration, PaCO2 and PETCO2 were measured. Vt and Ve were recorded from the digital indicator of the pneumotachygraph within the mechanical ventilator and corrected for compression volume in the respirator circuit. A total of 116 simultaneous measurements were performed. PETCO2 correlated well with PaCO2 (r = 0.78, p less than 0.001). The 95% confidence interval for the mean difference in PaCO2-PETCO2 was 4.0 +/- 0.97 mm Hg. However, delta PETCO2 (measured from baseline) did not correlate as well with delta PaCO2 (r = 0.58, p = less than 0.001). In four patients, the trend in their PETCO2 during changes in mechanical ventilation were in the opposite direction from the trend in their PaCO2. Thus, many critically ill patients, who cannto be preidentified, have an inconstant PaCO2-PETCO2 gradient with changes of ventilation. Utilization of PETCO2 as a noninvasive monitoring substitute for trends in PaCO2 in critically ill patients may be misleading despite establishing an initial PaCO2-PETCO2 relationship.

Energy Expenditure Associated with CPAP and T-Piece Spontaneous Ventilatory Trials: Changes Following Prolonged Mechanical Ventilation

The use of portable metabolic carts to assess energy expenditure (EE) by measuring oxygen consumption (VO2) and carbon dioxide production (VCO2) has recently been applied to patients undergoing weaning from mechanical ventilation. The VO2 and EE can be used to estimate changes in the work of breathing (WOB) associated with different weaning strategies. The purpose of this study was to use VO2 and EE to assess changes in the WOB when assisted mechanical ventilation (AMV) was replaced with two spontaneous ventilatory trial (SVT) techniques: continuous positive airway pressure (CPAP) and T-piece. Nine difficult-to-wean patients were studied during the initial weaning period following 26 +/- 18 days (mean +/- SD) of mechanical ventilatory support. The VO2 and EE during all AMV were 296 +/- 75 ml/min and 2069 +/- 519 kcal/day, respectively. Compared to the baseline AMV levels, during CPAP overall VO2 and EE increased 14 percent and 13 percent, respectively, and during T-piece overall VO2 and EE increased 20 percent and 19 percent, respectively. Respiration rate (f) increased and tidal volume (VT) decreased during both SVTs compared to AMV although no significant change in minute ventilation was seen. The WOB, as judged from changes in VO2, was only 5 percent higher during T-piece compared to CPAP; however, patients tolerated an average of only 141 +/- 45 min on T-piece vs 165 +/- 29 minutes on CPAP. We conclude that during the initial weaning stages in patients who have received prolonged mechanical ventilatory support, the WOB associated with SVTs is increased compared to AMV but that the WOB associated with T-piece is not significantly greater than that for CPAP.

Effects of unilateral nasal occlusion on ventilation and pulmonary resistance in infants.

Because neonates are vulnerable to spontaneous nasal obstruction, this study was designed to evaluate the ventilatory consequences of obstructing a single nasal passage in preterm infants. We employed a nasal pneumotachograph that separately quantified airflow between the two nasal passages and permitted unilateral nasal mask occlusions. Changes in minute ventilation (VI) and total (RT) and inspiratory pulmonary resistance (RI) were measured in response to 30-s unilateral occlusions during quiet and active sleep in 11 subjects. Unilateral nasal obstruction caused VI to fall significantly in both sleep states, because of a fall in both tidal volume and respiratory rate, without alteration in transcutaneous blood gases. RT and RI increased by 27 and 24 cmH2O.1-1.s, respectively, during unilateral nasal occlusion; this increase was greater than would be expected solely from elimination of one nasal passage. In 7 of the 11 infants a single dominant side could be identified as contributing 56-67% to tidal volume. The effect of occlusion on VI, RT, or RI did not differ whether the dominant or nondominant side was occluded. We conclude that unilateral nasal mask occlusion increases RT and RI and decreases VI in preterm infants. The larger than expected increase in resistance suggests that unilateral nasal loading predisposes to narrowing of the extrathoracic airway, and this may explain the comparable ventilatory responses to occluding the dominant and nondominant nasal passage.

Response of normal subjects to inspiratory resistive unloading.

The purpose of this study was to examine the role of the normal inspiratory resistive load in the regulation of respiratory motor output in resting conscious humans. We used a recently described device (J. Appl. Physiol. 62: 2491-2499, 1987) to make mouth pressure during inspiration positive and proportional to inspiratory flow, thus causing inspiratory resistive unloading (IRUL); the magnitude of IRUL (delta R = -3.0 cmH2O.1(-1).s) was set so as to unload most (approximately 86% of the normal inspiratory resistance. Six conscious normal humans were studied. Driving pressure (DP) was calculated according to the method of Younes et al. (J. Appl. Physiol. 51: 963-1001, 1981), which provides the equivalent of occlusion pressure at functional residual capacity throughout the breath. IRUL resulted in small but significant changes in minute ventilation (0.6 1/min) and in end-tidal CO2 concentration (-0.11%) with no significant change in tidal volume or respiratory frequency. There was a significant shortening of the duration (neural inspiratory time) of the rising phase of the DP waveform and the shape of the rising phase became more convex to the time axis. There was no change in the average rate of rise of DP or in the duration or shape of the declining phase. We conclude that 1) the normal inspiratory resistance is an important determinant of the duration and shape of the rising phase of DP and 2) the neural responses elicited by the normal inspiratory resistance are similar to those observed with added inspiratory resistive loads.

Attenuation of hypoxic ventilation by hyperbaric O2: effects of pressure and exposure time.

Hyperoxia affects O2 chemoreception in the highly perfused carotid bodies and causes a reduction of the ventilatory hypoxic drive (HD) as was shown for anesthetized cats and awake rats. We looked for a quantitative description of such an effect on HD as a function of both O2 pressure and exposure duration. Ventilation of rats was measured using the barometric method before and after hyperbaric O2 (HBO) exposure, at either air, 80% O2, or 4% O2. We used three exposure durations: 180, 550 and 900 min. The O2 pressure ranged between 1.2 and 3.0 ATA. At each time duration we used four to five groups of rats at a range of O2 pressures that yielded the full scale of effect on HD but avoided obvious lasting difficulties in breathing. HBO caused a reduction of breathing frequency and elevation of tidal volume in both air and 80% O2 but almost no change in minute ventilation. Hypoxic minute ventilation (4% O2) decreased after HBO, mainly through reduced frequency. HD was described by a power function of O2 pressure for each HBO duration. HD did not decline below 20% of the full control response. Ventilatory HD diminution is pictured as a function of both O2 pressure and HBO duration. The dependency of HD on exposure time and on pressure is similar to other known toxic effects of HBO.

The effect of metabolic acid-base changes on the ventilatory changes at the end of heavy exercise

The purpose of this study was to determine the effect of altered metabolic acid-base status on the changes in ventilation in the transition from heavy exercise above anaerobic threshold to rest. Seven subjects ingested, in a randomized and blind manner, either NaHCO3 or CaCO3 (placebo) at a dose of 300 mg.kg-1 body mass and ran on a treadmill for five minutes (90% VO2max and above anaerobic threshold) on ten different occasions. Changes in minute ventilation in the exercise transitions were studied by starting and stopping the treadmill abruptly with a remote switch. The fast increase in ventilation at the start of exercise was not accompanied by a corresponding fast drop in ventilation at the end of exercise (P less than or equal to 0.001) and the effects of chemicals on these changes were not significantly different (P greater than 0.05). A single-component exponential model, without a time delay, was used to determine the time constants of off-transitional decay in ventilation for the two chemicals in each subject. Parametric and non-parametric statistical tests revealed that the time constants were not as significantly different as the venous pH measurements which were significantly higher with NaHCO3 (P less than or equal to 0.001). The results indicate that the absence of fast change in ventilation at the end of heavy exercise is not due to lactic acidosis and the consequent slow ventilatory changes in the off-transition of heavy exercise are at least partly mediated by non-humoral factors such as a central neural reverberatory mechanism.

Rate Responsive Pacing Using a Minute Ventilation Sensor

Minute ventilation, the product of respiratory rate and tidal volume, correlates directly with oxygen consumption, cardiac output, and heart rate. An implantable pacemaker has been developed which allows variation in pacing rate in response to measured changes in minute ventilation. This single chamber system measures transthoracic impedance between the tip electrode of a standard bipolar lead and the pulse generator case. Low amplitude current pulses (1 mA for 15 microseconds) are generated each 50 msec between the the ring electrode and the case. In the adaptive mode, the pulse generator calculates a rate response factor or slope after maximal exercise. This slope, which describes the relationship between pacing rate and minute ventilation together with the pacing rate limits are the only programmable rate responsive features. Minute ventilation rate responsive systems have been implanted in 12 patients (8 females, 4 males), of mean age 63 years. Indications were His bundle ablation (6), acquired complete heart block (4), and sick sinus syndrome (2). At post-implant exercise testing, pacing rate rose within the first minute. Peak rate and time to upper rate were dependent on workload. After exercise, pacing rate remained at peak for up to 2 minutes before a gradual fall to resting rate. Comparative studies of the minute ventilation and the activity sensor pacing systems in the same patients confirmed that the minute ventilation system more closely parallels normal sinus response to activity. The minute ventilation rate responsive pacing system is simple to programme, no special lead is required and the system is highly physiologic.

Changes in respiration in the transition from heavy exercise to rest.

Transitions from rest to exercise and vice versa are reported to be associated with instantaneous changes in minute ventilation and the changes in the off-transitions are thought to be the reverses of those in the on-transitions. Such changes have been observed mainly in mild-moderate exercise and their extrapolation to heavy exercise above anaerobic threshold is unwarranted. Hence, the purpose of this study was to determine the changes in ventilation in the transition from heavy exercise above anaerobic threshold to rest. Five healthy volunteers ran on a motor-driven treadmill at a constant work-load corresponding to 80% VO2max and above anaerobic threshold. Changes in minute ventilation and end-tidal PCO2 in the on- and off-transitions were determined breath by breath by starting and stopping the treadmill abruptly. The results indicate that, contrary to what is reported for mild-moderate exercise, an instantaneous drop in ventilation is absent in the off-transition of heavy exercise above anaerobic threshold. The gradual decline in minute ventilation may be due to a sustained respiratory drive from a central neural reverberatory mechanism, blood-borne respiratory stimuli and/or a peripheral neurogenic drive originating in the so-called metaboloreceptors.

Low dose aminophylline selectively increases upper airway motor activity in normals

Because certain pharmacologic agents differentially influence upper airway and diaphragm motor activity, we postulated that the adenosine antagonist theophylline might preferentially increase alae nasi activity in human subjects. Using a double-blinded, randomized, placebo controlled design, we studied the effect of low dose aminophyline (1–2 mg/kg) on alae nasi and diapragm surface electromyographic (EMG) activity. Seven healthy volunteers served as subjects for two trials on separate days. Subjects breathed from a closed circuit while end tidal P CO 2 was held constant in the eucapnic range. During each trial we recorded EMG signals from the alae nasi and diaphragm before and after intravenous infusion of either aminophylline or placebo. After the administration of aminophylline, the mean alae nasi EMG signal increased 87 ± 31 (SD)% ( P<0.005) while the mean diaphragmatic EMG signal did not change. There was no significant change in either the alae nasi or diaphragmatic EMG signal after placebo. There was no change in minute ventilation, tidal volume, or respiratory frequency after either aminophylline or placebo. We speculate that low dose aminophylline produced a selective increase in upper airway muscle activity through stimulation of the reticular activating system.

Influence of dopamine and norepinephrine on the central ventilatory response to hypoxia in conscious cats

The effects of intravenous administration of agonists and antagonists of dopamine (DA) and norepinephrine (NE) on the central ventilatory response to hypoxia were studied in unanesthetized cats. The experiments were performed in intact animals exposed to CO-hypoxia and in carotid-body denervated animals breathing a hypoxic mixture. The DA agonist, apomorphine (APO) significantly decreased minute ventilation in response to central hypoxia, whereas the opposite effect occurred with the DA antagonist, haloperidol (HAL). Indeed, the characteristic tachypnea elicited by CO or hypoxia was inhibited by APO as the respiratory frequency markedly decreased while tidal volume concomitantly increased. Conversely, HAL administration enhanced the tachypnea during milder hypoxia or reversed the inhibitory action of APO. In contrast, the NE agonist, clonidine (CLO) and antagonists propranolol (PRO) and phenoxybenzamine (PHE) did not cause significant changes in minute ventilation and breathing pattern although CLO tended to attenuate the hypoxic tachypnea. This study confirms, therefore, that catecholamines are involved in the central ventilatory responses to hypoxia and suggests that the brain dopaminergic system plays a major role in the CO of hypoxic tachypnea.

DIDS decreases CSF HCO3- and increases breathing in response to CO2 in awake rabbits.

An inhibitor of the HCO3-/Cl- exchange carrier protein, 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) or vehicle was infused in mock cerebrospinal fluid (CSF) via the cisterna magna in conscious rabbits at 10 mumol/l for 40 min at 10 microliter/min. Neither treatment had any effect over 2-5 h on the non-CO2-stimulated CSF ion values or blood gases. With CO2 stimulation such that arterial PCO2 (PaCO2) was increased 25 Torr over 3 h, DIDS treatment significantly decreased the stoichiometrically opposite changes in CSF [HCO3-] and [Cl-] that normally accompany hypercapnia and reflect ionic mechanisms of CSF pH regulation. Expressed as delta CSF [HCO3-]/delta PaCO2, DIDS treatment decreased the CSF ionic response by 35%. In a separate paired study design DIDS administration via the same protocol had no effect on resting ventilation but significantly increased the ventilation and tidal volume responses to a 28-Torr increase in PaCO2. Expressed as change in minute ventilation divided by delta PaCO2, DIDS treatment produced a 39.6% increase. The results support the concept of a DIDS-inhibitable anion exchange carrier being involved in CSF pH regulation in hypercapnia and suggest a DIDS-related effect on the ventilatory response to CO2.

Hyperventilation occurs during lactate-induced panic

Previous work has indicated hyperventilation to be an important concomitant of laboratory provoked anxiety in patients with panic disorder and of anxiety disorder in general. This has led to considerable speculation about the role of hyperventilation in the pathogenesis of panic attacks. We studied minute ventilation changes in 32 patients with panic disorder and 9 normal controls during sodium lactate infusion. The group of patients who had acute panic attacks during the infusion had greater increase in minute ventilation over baseline than patients or controls who did not experience panic attacks. This provides further confirmation that hyperventilation occurs during panic attacks.

Long-term effects of hydralazine on ventilation and blood gas values in patients with chronic obstructive pulmonary disease and pulmonary hypertension

Hydralazine has been shown to increase minute ventilation, alveolar ventilation, and arterial partial pressure of oxygen (PaO 2) after short-term administration in patients with chronic obstructive pulmonary disease and pulmonary hypertension. The effects of orally administered hydralazine on ventilation and blood gas values were evaluated after six to 18 months of treatment in 10 male patients who had demonstrated an increase in minute ventilation after 24 hours of treatment. Hydralazine was administered at a dose of 200 mg per day during the initial 24 hours and in doses ranging from 40 mg per day to 200 mg per day during long-term therapy. Following 24 hours of treatment, a statistically significant increase in minute ventilation, alveolar ventilation, and PaO 2, and reduction in arterial partial pressure of carbon dixoide (PaCO 2) were seen both at rest and during exercise. After six to 18 months of hydralazine therapy, the increase in minute ventilation at rest persisted when compared with the pre-hydralazine value (15.3 ± 1.3 liters/minute versus 13.1 ± 1.1 liters/minute; p <0.05). The improvement in PaO 2 at rest continued relative to the prehydralazine value (70.9 ± 3.2 mm Hg versus 65.1 ± 3.0 mm Hg, p <0.05) as did the PaO 2 during exercise (60.3 ± 3.5 mm Hg versus 53.3 ± 2.0 mm Hg; p <0.05). The reduction in PaCO 2 at rest persisted compared with the pre-hydralazine value (41.2 ± 2.4 mm Hg versus 47.0 ± 3.0 mm Hg; p <0.05) as did the PaCO 2 during exercise (44.0 ± 2.8 mm Hg versus 48.0 ± 2.8 mm Hg; p <0.05). No significant changes in minute ventilation, PaO 2, or PaCO 2 were seen at rest or during exercise, when re-measured after six to 18 months in an age-and sex-matched control group of 10 patients who did not receive hydralazine. These results demonstrate that the short-term effects of hydralazine on ventilation and blood gas values persisted after six to 18 months of treatment in this sample of patients, some of whom received doses less than 200 mg per day.