Ventilatory muscle support in respiratory failure with nasal positive pressure ventilation.

Long-term intermittent mechanical ventilation results in improvements in ventilatory performance and clinical status between ventilation sessions in patients with chronic respiratory failure. The application of intermittent positive pressure ventilation through a nasal mask (NPPV) is a simple, noninvasive method for the provision of chronic intermittent ventilatory support. We investigated the effects of NPPV on inspiratory muscle activity in three normal subjects and nine patients with acute or chronic ventilatory failure due to restrictive (four subjects) or obstructive (five subjects) respiratory disorders. NPPV resulted in reductions of phasic diaphragm electromyogram amplitude to 6.7 +/- 0.7 percent (mean +/- SEM) of values obtained during spontaneous breathing in the normal subjects, 6.4 +/- 3.2 percent in the restrictive group, and 8.3 +/- 5.1 percent in the obstructive group. Simultaneous decreases in activity of accessory respiratory muscles were observed. The reductions in inspiratory muscle activity were confirmed by the finding of positive intrathoracic pressure swings on inspiration in all subjects. With NPPV, oxygen saturation and PCO2 remained stable or improved as compared with values obtained during spontaneous breathing. These results indicate that NPPV can noninvasively provide ventilatory support while reducing inspiratory muscle energy expenditure in acute and chronic respiratory failure of diverse etiology. Long-term assisted ventilation with NPPV may be useful in improving ventilatory performance by resting the inspiratory muscles.

Respiratory mechanics in status asthmaticus. Effects of inhalational anesthesia.

The incidence and severity of bronchial asthma has increased considerably in recent years. As a result, the number of patients requiring mechanical ventilation and more intensive medical therapy for treatment of refractory asthma has also increased. Despite this, available information concerning the quantitative changes in respiratory mechanics and the response to treatment that occur in such patients is limited. The present study describes the abnormalities in respiratory mechanics and the response to isoflurane anesthesia observed in three adults mechanically ventilated for treatment of status asthmaticus. Airway pressure, flow, and volume were measured during controlled mechanical ventilation in which the airway was periodically occluded in order to determine respiratory system mechanics. In two patients, the volume of hyperinflation and expiratory volume-flow relationship were also obtained. Inspiratory and expiratory indices of respiratory resistance were markedly abnormal. These abnormalities were associated with significant dynamic hyperinflation and high levels of intrinsic PEEP. Expiratory flow limitation was also identified in two patients by failure of low levels of applied positive end-expiratory pressure (PEEP) to alter the expiratory volume-flow relationship. Indices of respiratory resistance as well as the magnitude of dynamic hyperinflation and intrinsic PEEP improved considerably with isoflurane administration, after having been refractory to intensive conventional bronchodilator therapy. In summary, these results demonstrate the severity of abnormalities in respiratory mechanics present in ventilated patients with status asthmaticus and the potential therapeutic efficacy of inhalational anesthesia in this setting.

Pathophysiological findings in a patient with Shy-Drager and alveolar hypoventilation syndromes.

This report describes the clinical, physiologic and pathologic findings in a patient with alveolar hypoventilation, acquired autonomic dysfunction, parkinsonism, and sensorimotor polyneuropathy. While there were pathologic findings in both central and peripheral nervous systems, there were no morphologic changes in the regions of the brainstem considered responsible for respiratory rhythmogenesis. A hypothesis is developed based on the assumption that the abnormalities in respiratory control which led to the patient's death are explained by abnormalities in the feedback control of respiration.

Continuous positive airway pressure facilitates spontaneous breathing in weaning chronic obstructive pulmonary disease patients by improving breathing pattern and gas exchange.

OBJECTIVE: To elucidate the effects of continuous positive airway pressure (CPAP) on breathing pattern, gas exchange and the ability to sustain spontaneous breathing (SB) in chronic obstructive pulmonary disease (COPD) patients with dynamic hyperinflation. DESIGN: Prospective study with two randomised trials of SB without and with CPAP in each patient. SETTING: Medical intensive care units (ICUs) in two university hospitals. PATIENTS: Nine dynamically hyperinflated, intubated COPD patients recuperating from acute exacerbation. INTERVENTIONS: One SB trial with CPAP (5-7.5 cmH2O), one without (control) in each patient. MEASUREMENTS: airway opening pressure, gas flow and thus breathing pattern, oxygen uptake, carbon dioxide excretion, arterial blood gases, dyspnoea and respiratory drive (P100). RESULTS: With CPAP, intrinsic positive end-expiratory pressure (PEEPi) fell from 11.4 to 6.3 cm H2O (p < 0.05). Eight patients sustained SB with CPAP for the maximum time planned (30 min), one failed after 18 min. In contrast, only four patients successfully completed the control trial, the others failing after 5-18 min (p < 0.05). Dyspnoea-gauged on a visual analogue scale by five patients--was less severe or occurred later with CPAP. Breathing with CPAP tended to be slower (18.9 vs 22.2 min(-1), p < 0.05) and deeper (tidal volume 370 vs 323 ml). At the end of the control run, PaCO2 was higher (60 vs 55 mmHg, p < 0.05) and still rising while being stable at the end of the CPAP trial. CONCLUSION: CPAP helps severely ill COPD patients sustain SB. Apparently it does so by promoting slower, deeper breathing and thus facilitating carbon dioxide elimination.

Respiratory compliance and resistance in mechanically ventilated patients with acute respiratory failure.

The purpose of this study was noninvasive assessment of respiratory compliance and resistance in mechanically ventilated patients with acute respiratory failure (ARF). To this end, flow, change in lung volume, and airway pressure were measured at the proximal tip of the endotracheal tubes in twenty nine critically ill unselected patients. Eleven had acute exacerbation of chronic obstructive pulmonary disease (COPD), 8 had adult respiratory distress syndrome (ARDS) and 10 had ARF of various etiologies. Static compliance (Cst,rs), 'intrinsic' PEEP (PEEPi), as well as minimum and maximum resistance (Rrs,min and Rrs,max, respectively) were obtained with end-inspiratory and end-expiratory airway occlusions. We found that: (1) PEEPi was present in all patients with COPD (up to 11.4 cmH2O) and it was not uncommon in patients with ARF without history of chronic airway disease (up to 4.1 cmH2O). (2) Without correction for PEEPi average Cst,rs was not significantly different between ARDS and COPD patients, whereas the average corrected compliance was significantly lower in ARDS patients. (3) Substantial frequency-dependence of resistance was exhibited not only by COPD patients, but also by ARDS patients.

Effect of intestinal afferent stimulation on pattern of respiratory muscle activation.

The purpose of the present study was to examine the reflex effects of mechanical stimulation of intestinal visceral afferents on the pattern of respiratory muscle activation. In 14 dogs anesthetized with pentobarbital sodium, electromyographic activity of the costal and crural diaphragm, parasternal intercostal, and upper airway respiratory muscles was measured during distension of the small intestine. Rib cage and abdominal motion and tidal volume were also recorded. Distension produced an immediate apnea (11.16 +/- 0.80 s). During the first postapneic breath, costal (43 +/- 7% control) and crural (64 +/- 6% control) activity were reduced (P less than 0.001). In contrast, intercostal (137 +/- 11%) and upper airway muscle activity, including alae nasi (157 +/- 16%), genioglossus (170 +/- 15%), and posterior cricoarytenoid muscles (142 +/- 7%) all increased (P less than 0.005). There was greater outward rib cage motion although the abdomen moved paradoxically inward during inspiration, resulting in a reduction in tidal volume (82 +/- 6% control) (P less than 0.005). Postvagotomy distension produced a similar apnea and subsequent reduction in costal and crural activity. However, enhancement of intercostal and upper airway muscle activation was abolished and there was a greater fall in tidal volume (65 +/- 14%). In conclusion, mechanical stimulation of intestinal afferents affects the various inspiratory muscles differently; nonvagal afferents produce an initial apnea and subsequent depression of diaphragm activity whereas vagal pathways mediate selective enhancement of intercostal and upper airway muscle activation.

Effect of CPAP on respiratory effort and dyspnea during exercise in severe COPD.

Recent work has demonstrated the ability of continuous positive airway pressure (CPAP) to relieve dyspnea during exercise in patients with severe chronic obstructive pulmonary disease (COPD). The present study examined the effects of CPAP (7.5-10 cmH2O) on the pattern of respiratory muscle activation and its relationship to dyspnea during constant work load submaximal bicycle exercise [20 +/- 4.8 (SE) W] in eight COPD patients (forced expiratory volume in 1 s = 25 +/- 3% predicted). Tidal volume, respiratory rate, minute ventilation, and end-expiratory lung volume increased with exercise as expected. There was no change in breathing pattern, end-expiratory lung volume, or pulmonary compliance and resistance with the addition of CPAP. CPAP reduced inspiratory muscle effort, as indicated by the pressure-time integral of transdiaphragmatic (integral of Pdi.dt) and esophageal pressure (integral of Pes.dt, P less than 0.01 and P less than 0.05, respectively). In contrast, the pressure-time integral of gastric pressure (integral of Pga.dt), used as an index of abdominal muscle recruitment during expiration, increased (P less than 0.01). Dyspnea improved with CPAP in five of the eight patients. The amelioration of dyspnea was directly related to reductions in integral of Pes.dt (P less than 0.001) but inversely related to increases in integral of Pga.dt (P less than 0.01). In conclusion, CPAP reduces inspiratory muscle effort during exercise in COPD patients. However, the expected improvement in dyspnea is not seen in all patients and may be explained by more marked increases in expiratory muscle effort in some individuals.

Effects of changes in inspiratory muscle strength on the sensation of respiratory force.

The sensation of respiratory muscle force was compared in seven normal subjects before and after inspiratory muscle strength training. Subjects performed 20 sustained maximal inspiratory maneuvers daily for 6-18 wk. Maximal inspiratory pressures (MIP) increased from 124 +/- 10 to 187 +/- 9 (SE) cmH2O (P less than 0.005). Exponents of the power function relationships between mouth pressure (Pm) and the intensity of the sensation of force, corrected for inspiratory duration, during magnitude scaling of resistive and elastic ventilatory loads were the same before and after training (P greater than 0.05). However, absolute sensation intensity (S) during resistive and elastic loading was reduced significantly after strength training but returned toward baseline levels greater than or equal to 8 wk after the cessation of training when the MIP had fallen to 150 +/- 5 cmH2O. The absolute S at a given Pm during ventilatory loading changed inversely with changes in MIP (P less than 0.001). Furthermore the relationship between absolute S and Pm expressed as a proportion of the MIP (Pm/MIP) was constant over testing periods. These results suggest that the sensation of respiratory muscle force reflects the proportion of the maximum force utilized in breathing and may be based on the level of respiratory motor command signals.

Comparison of static and dynamic measurements of intrinsic PEEP in anesthetized cats.

Dynamic measurements of intrinsic positive end-expiratory pressure (PEEPi,dyn) considerably underestimate values obtained under static conditions (PEEPi,stat) in patients with severe airway obstruction. This may be related to regional differences in respiratory system mechanical properties and/or viscoelastic behavior. To evaluate this concept, PEEPi,stat and PEEPi,dyn were compared in six anesthetized paralyzed cats during dynamic hyperinflation produced by inverse ratio ventilation (IRV) and aerosolized methacholine (MCh). PEEPi,stat did not differ between IRV and MCh, averaging 2.70 +/- 0.33 (SE) and 2.70 +/- 0.25 cmH2O, respectively. PEEPi,dyn was significantly less with MCh (0.25 +/- 0.05 cmH2O) than IRV (2.05 +/- 0.28 cmH2O) (P < 0.0001), resulting in a lower PEEPi,dyn/PEEPi,stat ratio for MCh (0.10 +/- 0.02) than for IRV (0.76 +/- 0.03) (P < 0.0001). Compared with control values (33.5 +/- 3.7 cmH2O.l-1.s), maximum resistance (Rmax) was unchanged during IRV (29.1 +/- 2.1 cmH2O.l-1.s) but increased considerably with MCh (288.8 +/- 18.4 cmH2O.l-1.s) (P < 0.0001). Similar changes in minimum resistance (Rmin) and delta R (Rmax-Rmin) were noted. There was a strong inverse relationship between delta P, an index of time constant inequalities and viscoelastic pressure losses and PEEPi,dyn/PEEPi,stat ratio. No correlation was found between this ratio and Rmax, Rmin, delta R, or compliance. In conclusion, PEEPi,dyn considerably underestimates PEEPi,stat in acute nonhomogeneous airway obstruction with MCh in contrast to IRV, where the magnitude and distribution of mechanical properties remain unaltered. These findings support the concept that the difference between PEEPi,dyn and PEEPi,stat is related to regional time constant inequalities and/or increased viscoelastic pressure losses.

A model of the spontaneously breathing patient: applications to intrinsic PEEP and work of breathing.

Intrinsic positive end-expiratory pressure (PEEPi) and inspiratory work of breathing (WI) are important factors in the management of severe obstructive respiratory disease. We used a computer model of spontaneously breathing patients with chronic obstructive pulmonary disease to assess the sensitivity of measurement techniques for dynamic PEEPi (PEEPidyn) and WI to expiratory muscle activity (EMA) and cardiogenic oscillations (CGO) on esophageal pressure. Without EMA and CGO, both PEEPidyn and WI were accurately estimated (r = 0.999 and 0.95, respectively). Addition of moderate EMA caused PEEPidyn and WI to be systematically overestimated by 141 and 52%, respectively. Furthermore, CGO introduced large random errors, obliterating the correlation between the true and estimated values for both PEEPidyn (r = 0.29) and WI (r = 0.38). Thus the accurate estimation of PEEPidyn and WI requires steps to be taken to ameliorate the adverse effects of both EMA and CGO. Taking advantage of our simulations, we also investigated the relationship between PEEPidyn and static PEEPi (PEEPistat). The PEEPidyn/PEEPistat ratio decreased as stress adaptation in the lung was increased, suggesting that heterogeneity of expiratory flow limitation is responsible for the discrepancies between PEEPidyn and PEEPistat that have been reported in patients with severe airway obstruction.

Respiratory responses to ventilatory loading following low cervical spinal cord injury.

This study compared the respiratory responses to ventilatory loading in 8 normal subjects and 11 quadriplegic patients with low cervical spinal cord transection. Progressive hypercapnia was produced by rebreathing. Rebreathing trials were carried out with no added load and with inspiratory resistive loads of 5 and 16 cmH2O. l-1 X s. Measurements were made of ventilation and of diaphragmatic electromyographic activity. Base-line hypercapnic ventilatory responses were significantly lower than normal in the quadriplegic patients, but the effects of resistive loading on the ventilatory responses were comparable in the two groups. The change in peak moving-average diaphragmatic electrical activity (DI peak) for a given change in CO2 partial pressure (PCO2) and DI peak at PCO2 55 Torr increased significantly with resistive loading both in the normal subjects and the quadriplegic patients. In the normal subjects, but not in the quadriplegic patients, inspiratory duration increased progressively with increasing resistance. The increase in DI peak during ventilatory loading in the normal subjects was a consequence of inspiratory prolongation. In contrast, in the quadriplegic patients during breathing against the larger resistive load, there was a significant increase in the average rate of rise (DI peak divided by the time from onset to peak) of diaphragmatic activity. The change in DI rate of rise for a given change in PCO2 increased to 137 +/- 13% (SE), and the DI rate of rise at PCO2 55 Torr increased to 128 +/- 8% (SE) of control values. These results indicate that compensatory increases in diaphragmatic activation during ventilatory loading occur in quadriplegic patients in whom afferent feedback from rib cage receptors is disrupted.

Respiratory mechanics in mechanically ventilated patients with respiratory failure.

In 11 mechanically ventilated patients, respiratory mechanics were measured 1) during constant flow inflation and 2) following end-inflation airway occlusion, as proposed in model analysis (J. Appl. Physiol. 58: 1840-1848, 1985. During the latter part of inflation, the relationship between driving pressure and lung volume change was linear, allowing determination of static respiratory elastance (Ers) and resistance (RT). The latter represents in each patient the maximum resistance value that can obtain with the prevailing time constant inhomogeneity. Following occlusion, Ers and RT were also obtained along with RT (min) which represents a minimum, i.e., resistance value that would obtain in the absence of time constant inhomogeneity. A discrepancy between inflation and occlusion Ers and RT was found only in the three patients without positive end-expiratory pressure, and could be attributed to recruitment of lung units during inflation. In all instances Ers and RT were higher than normal. RT(min) was lower in all patients than the corresponding values of RT, indicating that resistance was frequency dependent due to time constant inequalities. Changes in inflation rate did not affect Ers, while RT increased with increasing flow.

Effects of progressive hypoxia on parasternal, costal, and crural diaphragm activation.

The distribution of motor drive to the costal and crural diaphragm and parasternal intercostal muscles was evaluated during progressive isocapnic hypoxia in anesthetized dogs. Bipolar stainless steel wire electrodes were placed unilaterally into the costal and crural portions of the diaphragm and into the parasternal intercostal muscle in the second or third intercostal space. Both peak and rate of rise of electromyographic activity of each chest wall muscle increased in curvilinear fashion in response to progressive hypoxia. Both crural and parasternal intercostal responses, however, were greater than those of the costal diaphragm. The onset of crural activation preceded that of the costal portion of the diaphragm and parasternal intercostal muscle activation. Despite differences in the degree of activation among the various chest wall muscles, the rate of increase in activation for any given muscle was linearly related to the rate of increases for the other two. This suggests that respiratory drive during progressive hypoxia increases in fixed proportion to the different chest wall inspiratory muscles. Our findings lend further support to the concept that the costal and crural diaphragm are governed by separate neural control mechanisms and, therefore, may be considered separate muscles.

Influence of site of tracheal pressure measurement on in situ estimation of endotracheal tube resistance.

In situ measurement of distal tracheal pressure (Ptr) via an intraluminal side-hole catheter (IC) has been used to determine endotracheal tube (Rett) and intrinsic patient (Rpt) resistances in intubated subjects. Because of differences in cross-sectional area between the endotracheal tube (ETT) and trachea, fluid dynamic principles predict that IC position should critically influence these results. Accordingly, the aim of this study was to determine the effect of IC position on Rett. Ptr was recorded in vitro through an IC from 2 cm inside, at the tip of, or 2 cm outside an ETT (7, 8, and 9 mm ID) situated within an artificial trachea (13, 18, and 22 mm ID). A reference value of Rett was also obtained. Results were unaffected by IC position during inspiration, overestimating Rett by 7.9 +/- 0.7% (SE). In contrast, during expiration, Rett fell as IC position changed from outside to inside the ETT and was underestimated by 41.3 +/- 3.6% with Ptr recorded inside the ETT. Varying ETT or tracheal size had little effect on the relative error in Rett. The IC itself did increase Rett due to a reduction in effective cross-sectional area, the change varying directly with IC size and inversely with ETT caliber. In vivo values in 11 intubated patients were comparable to in vitro results. In summary, IC position and size can have important consequences on in situ measurements of Ptr and should be considered when clinically monitoring Rett or Rpt.

Effect of inspiratory pressure support on the arousal response to CO2 in sleeping dogs.

The aim of the present study was to test the hypothesis that afferent mechanoreceptor stimuli from the respiratory muscles contribute to the arousal response to CO2 from both non-rapid-eye-movement (NREM) and rapid-eye-movement (REM) sleep. We studied three dogs implanted with electromyographic (EMG) electrodes in the costal diaphragm and transversus abdominis muscles. During sleep, the animals were exposed to supplemental CO2 in O2 to maintain a constant level of end-tidal PCO2 (50 Torr for NREM, 56 Torr for REM) and breathed either spontaneously (SB) or with inspiratory pressure support (IPS). The arousal response was quantified as the time from initiation of CO2 administration to arousal. EMG activity of the costal diaphragm on IPS was decreased to approximately 70% (P < 0.01) of that during SB trials for both NREM and REM, whereas EMG activity of the transversus abdominis muscles did not differ between SB and IPS for either sleep state. The mean time to arousal was increased during NREM from 128.3 +/- 24.7 s (SB) to 216.8 +/- 38.7 s (IPS) (P < 0.025) and was increased during REM from 144.9 +/- 26.1 s (SB) to 219.0 +/- 23.8 s (IPS) (P < 0.001). In summary, in support of our hypothesis, we found that suppression of inspiratory muscle activity, without augmented expiratory muscle activity, delayed the arousal response to hypercapnia during both NREM and REM sleep.

Growth hormone does not prevent corticosteroid-induced changes in rat diaphragm structure and function.

The present study tested the hypothesis that growth hormone (GH), an anabolic agent, could prevent the abnormalities of diaphragm structure and function associated with short-term administration of the corticosteroid triamcinolone (TR). During a 10-day period, male rats (n = 33) were assigned to control (CTL), TR (1 mg.kg-1.day-1 im), and TR-GH (2 mg.kg-1.day-1 im) groups. Diaphragm weight was significantly reduced in the TR and TR-GH animals compared with the CTL animals, but there was no difference in the diaphragm-to-body weight ratio. Fiber type (I, IIa, and IIx/b) proportions did not differ among the three groups. However, in TR rats there was a significant reduction in the contribution of type IIx/b fibers to total diaphragm cross-sectional area due to marked atrophy (approximately 42% decrease in mean fiber cross-sectional area). There was no significant reversal of TR-induced type IIx/b fiber atrophy by concomitant GH administration. TR and TR-GH groups both exhibited a left-ward shift of the force-frequency relationship and enhanced in vitro fatigue resistance, whereas maximal specific force was unaltered. We conclude that GH does not prevent corticosteroid-induced effects on the diaphragm under these conditions, possibly as a result of reduced nutritional intake associated with TR administration.

Interrupter technique for measurement of respiratory mechanics in anesthetized humans.

Flow (V), volume (V), and tracheal pressure (Ptr) were measured throughout a series of brief (100 ms) interruptions of expiratory V in six patients during anesthesia (halothane-N2O) and anesthesia-paralysis (succinylcholine). For the latter part of spontaneous expiration and throughout passive deflation during muscle paralysis, a plateau in postinterruption Ptr was observed, indicating respiratory muscle relaxation. Under these conditions, passive elastance of the total respiratory system (Ers) was determined as the plateau in postinterruption Ptr divided by the corresponding V. The pressure-flow relationship of the total system was determined by plotting the plateau in Ptr during interruption against the immediately preceding V. Ers averaged 23.5 +/- 1.9 (SD) cmH2O X l-1 during anesthesia and 25.5 +/- 5.4 cmH2O X l-1 during anesthesia-paralysis. Corresponding values of total respiratory system resistance were 2.0 +/- 0.8 and 1.9 +/- 0.6 cmH2O X l-1 X s, respectively. Respiratory mechanics determined during anesthesia paralysis using the single-breath method (W.A. Zin, L. D. Pengelly, and J. Milic-Emili, J. Appl. Physiol. 52: 1266-1271, 1982) were also similar. Early in spontaneous expiration, however, Ptr increased progressively during the period of interruption, reflecting the presence of gradually decreasing antagonistic (postinspiratory) pressure of the inspiratory muscles. In conclusion, the interrupter technique allows for simultaneous determination of the passive elastic as well as flow-resistive properties of the total respiratory system. The presence of a plateau in postinterruption Ptr may be employed as a useful and simple criterion to confirm the presence of respiratory muscle relaxation.

Respiratory sensation in chronic obstructive pulmonary disease.

Previous work has demonstrated that the perception of added resistive loads is blunted in patients with chronic obstructive pulmonary disease (COPD). It is not clear, however, whether this is due to reduced levels of respiratory muscle force during loaded breathing or to a specific abnormality in respiratory sensation. In the present study, the psychophysical technique of magnitude scaling was used to evaluate the sensation of external resistive and elastic ventilatory loads as well as the perception of inspired volume and inspiratory muscle force in 14 patients with COPD and in 12 normal subjects of similar age. The exponents of the power function relationships between load magnitude and sensation intensity for both resistive and elastic loads were significantly reduced in the patients with COPD compared with those in the normal subjects. While breathing against any given ventilatory load, the peak inspiratory mouth pressure and inspiratory duration were comparable in the 2 groups. Thus, the exponents of the power function relationships between peak inspiratory mouth pressure and sensation intensity were significantly lower in the patients with COPD (0.92 +/- SE 0.17 and 0.96 +/- SE 0.17 for resistive and elastic loads, respectively) compared with those obtained in the normal subjects (1.47 +/- SE 0.12 for resistive loads and 1.52 +/- SE 0.17 for elastic loads) (p less than 0.05). In contrast, the perception of inspired volume and of respiratory muscle force during static inspiratory maneuvers as determined by magnitude estimation and production were no different in either group.(ABSTRACT TRUNCATED AT 250 WORDS)