Electrical activity of the diaphragm during pressure support ventilation in acute respiratory failure.

We compared crural diaphragm electrical activity (EAdi) with transdiaphragmatic pressure (Pdi) during varying levels of pressure support ventilation (PS) in 13 intubated patients. With changing PS, we found no evidence for changes in neuromechanical coupling of the diaphragm. From lowest to highest PS (2 cm H(2)O +/- 4 to 20 cm H(2)O +/- 7), tidal volume increased from 430 ml +/- 180 to 527 ml +/- 180 (p < 0.001). The inspiratory volume calculated during the period when EAdi increased to its peak did not change from 276 +/- 147 to 277 +/- 162 ml, p = 0.976. Respiratory rate decreased from 23.9 (+/- 7) to 21.3 (+/- 7) breaths/min (p = 0.015). EAdi and Pdi decreased proportionally by adding PS (r = 0.84 and r = 0.90, for mean and peak values, respectively). Mean and peak EAdi decreased (p < 0.001) by 33 +/- 21% (mean +/- SD) and 37 +/- 23% with the addition of 10 cm H(2)O of PS, similar to the decrease in the mean and peak Pdi (p < 0.001) observed (34 +/- 36 and 35 +/- 23%). We also found that ventilator assist continued during the diaphragm deactivation period, a phenomenon that was further exaggerated at higher PS levels. We conclude that EAdi is a valid measurement of neural drive to the diaphragm in acute respiratory failure.

Proportional assist ventilation may improve exercise performance in severe chronic obstructive pulmonary disease.

PURPOSE: Exercise tolerance is impaired in chronic obstructive pulmonary disease (COPD), in part because of a reduction in ventilatory capacity and excessive dyspnea experienced. The authors reasoned that proportional assist ventilation (PAV), a ventilator mode in which the level of support varies proportionately with patient effort, could be used during exercise to assist ventilation. The purpose of this study was to evaluate the efficacy of PAV to improve exercise endurance and related physiologic parameters in COPD. METHODS: In 8 patients (age = 62.8 years mean, +/- 6.9 standard deviation) with severe COPD (forced expiratory volume in 1 second = 0.70 +/- 0.21 L) flow, volume, dyspnea, leg fatigue, arterial blood gases, and gas exchange were measured during constant workrate exercise (37 +/- 18 watts; i.e., 80% previously determined maximum oxygen consumption). Crossover exercise trials were performed in random order: while spontaneously breathing through the experimental circuit without assistance (control trial) and with PAV (using 9.8 +/- 2.1 cm H2O/L and 3.3 +/- 1.0 cm H2O/L/sec of volume assist and flow assist, respectively). RESULTS: The application of PAV during exercise was well tolerated by each subject. Compared with the control measurement at equivalent time during exercise, PAV improved breathing pattern and arterial blood gases while dyspnea was reduced. Consequently, there was a significant increase in exercise duration with PAV (323 +/- 245 seconds during the control trial compared with 507 +/- 334 seconds with PAV, P = 0.02). CONCLUSIONS: Proportional assist ventilation can improve performance during constant workrate exercise in severe COPD.

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.

Diaphragm sarcolemmal injury is induced by sepsis and alleviated by nitric oxide synthase inhibition.

Endotoxemia is associated with impaired diaphragm contractility, and increased nitric oxide (NO) production has recently been implicated in this phenomenon. However, the precise nature of sepsis-related alterations in diaphragm myofiber function remains unclear. We tested the hypothesis that enhanced NO synthesis during sepsis produces diaphragm sarcolemmal injury with attendant abnormalities of myofiber membrane electrophysiology. Two different rat sepsis models were employed: acute (4 h) intraarterial endotoxin (LPS; 20 mg/kg) and subacute (24 h) peritonitis induced by cecal ligation and perforation (CLP). Diaphragm damage occurred after both LPS and CLP, as indicated by hyperpermeability of myofibers to a low molecular weight tracer dye, which is normally unable to penetrate the sarcolemma. Sarcolemmal injury was significantly correlated with reductions in the resting membrane potential (Em) of single diaphragm myofibers. Western analysis revealed increased diaphragmatic expression of the inducible isoform of NO synthase (iNOS) after LPS and CLP. An inhibitor of NOS activity, LNMMA, significantly decreased morphologic as well as electrophysiologic signs of myofiber membrane injury and dysfunction. Therefore, we conclude that both acute endotoxemia and subacute peritonitis models of sepsis lead to significant sarcolemmal damage and altered Em in diaphragm myofibers. These changes appear to be mediated, at least in part, through the pathway of increased nitric oxide production.

Regulation of myosin heavy chain gene expression after short-term diaphragm inactivation.

Although prolonged diaphragm denervation (DNV) produces myofiber atrophy and a loss of type I myosin heavy chain (MHC) expression, short-term DNV leads to significant diaphragm hypertrophy. The purpose of this study was to explore the regulation of MHC isoform expression and muscle remodeling during DNV hypertrophy of the diaphragm. Both unilateral and bilateral DNV led to similar changes, with a significant increase in total RNA content and muscle mass but no change in dry-to-wet weight ratio. Sarcomere number was also increased in diaphragm myofibers after DNV ( approximately 20%), suggesting an adaptive response to muscle stretch. There was hypertrophy of type I myofibers and increased coexpression of type I and type II MHCs within single myofibers by immunocytochemistry as well as increased type I MHC (25-46%) and decreased type IIb MHC (14-39%) by SDS-PAGE. Contractility parameters were also consistent with a type II-to-type I MHC phenotype transformation. Importantly, DNV-induced modulation of MHC isoform mRNA transcript levels did not correspond to changes in their cognate proteins, suggesting a major degree of posttranscriptional control. We conclude that DNV hypertrophy of the diaphragm is associated with reciprocal changes in type I and type II MHC isoforms that are directly opposed to the type I-to-type II MHC phenotype transformation reported in the diaphragm DNV atrophy model. Furthermore, in contradistinction to most hypertrophy models, control of MHC gene expression and myofibrillar remodeling after short-term DNV appears to entail major involvement of posttranscriptional regulatory mechanisms.

An adaptive filter to reduce cardiogenic oscillations on esophageal pressure signals.

Measurements of pressure swings in the esophagus (Pes) can be used to estimate variables of clinical importance, e.g., intrinsic positive end-expiratory pressure (PEEPi). Unfortunately, cardiogenic oscillations frequently corrupt Pes and complicate further analysis. Due to significant band overlap with the respiratory component of Pes, cardiogenic oscillations cannot be suppressed adequately using standard filtering techniques. In this article, we present an adaptive filter that employs the electrocardiogram to identify and suppress the cardiogenic oscillations. This filter was tested using simulated data, where the variance accounted for relative to the simulated respiratory pressure swings increased from as low as 55% for the unfiltered Pes signal to over 95% when the adaptive filter was used. In patient data, the adaptive filter reduced the apparent cardiogenic oscillations without noticeably distorting the sharp deflections in Pes due to respiration. Furthermore, the filter suppressed peaks in the Fourier transform of Pes at integer multiples of the heart rate, while the remaining frequencies remained largely unchanged. During stable breathing, the standard deviation of PEEPi was reduced by between 44% and 71% in these four patients when the filter was used. We conclude that our filter removes a significant fraction of the cardiogenic oscillations that corrupt records of Pes.

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.

Proportional assist ventilation in acute respiratory failure: effects on breathing pattern and inspiratory effort.

Proportional assist ventilation (PAV) is a new mode of assisted ventilation which, by applying pressure in proportion to volume (volume assist, VA) and flow (flow assist, FA), should specifically reduce the inspiratory effort needed to overcome respiratory system elastance (Ers) and resistance (Rrs), respectively. The aims of this study were to determine (1) the effects of varying the level of VA on breathing pattern, inspiratory effort, and work of breathing, and (2) the interaction between VA and FA. In eight intubated patients with acute respiratory failure, four levels of VA (20 to 80% Ers) with and without a fixed amount of FA (approximately 50% Rrs) were evaluated. Compared with spontaneous breathing, VA increased tidal volume (VT) while respiratory rate (RR) was unchanged or fell slightly. The increase in minute ventilation (VE) was small and not significant. The addition of FA further increased VT while RR was significantly reduced so that VE remained unchanged. Increasing VA produced a graded reduction in inspiratory effort, reflected by decreases in the pressure-time integral of the diaphragm and the inspiratory muscles. These were further reduced when FA was added. VA decreased the elastic work of breathing (Wel) whereas resistive work (Wres) tended to increase so that the fall in total work (W/tot) was less than expected. At each VA setting, the addition of FA significantly reduced Wres and, as a result, Wtot. These results demonstrate that PAV can improve breathing pattern while reducing inspiratory effort by specifically decreasing Wel and Wres, and that VA and FA should be used together to optimize reductions in Wtot and the efficacy of assistance provided.

Efficacy of noninvasive CPAP in COPD with acute respiratory failure.

Dynamic hyperinflation and the development of intrinsic positive end-expiratory pressure (PEEPi) are commonly observed in patients with severe chronic obstructive pulmonary disease (COPD) in acute respiratory failure. Previous studies have shown that externally applied PEEP reduces PEEPi and its adverse effects in mechanically-ventilated COPD patients. The purpose of this study was to determine the effects of graded amounts of continuous positive airway pressure (CPAP) on the degree of inspiratory effort, pattern of breathing, gas exchange, and level of dyspnoea in a group of spontaneously breathing, nonintubated COPD patients in acute hypercapnic respiratory failure. Ten COPD patients admitted to the intensive care unit in acute hypercapnic respiratory failure were studied. Inspiratory effort was measured by the tidal excursions of oesophageal (Poes) and transdiaphragmatic (Pdi) pressure. Inspiratory effort and both the pressure-time product for the diaphragm (integral of Pdi-dt) and for the inspiratory muscles (integral of Poes.dt) were measured during the application of 5, 7.5, and 10 cmH2O of CPAP. Dyspnoea, gas exchange and pattern of breathing were also assessed. Inspiratory effort and the pressure-time product both for the diaphragm and the inspiratory muscles fell significantly with CPAP in a dose-dependent fashion. Both the pattern of breathing and level of dyspnoea improved with CPAP. End-expiratory lung volume remained stable at the lower levels of CPAP, with only modest increases at the higher levels. Arterial oxygen tension (Pa,O2) and arterial carbon dioxide tension (Pa,CO2) either improved or remained stable with CPAP. We conclude that the noninvasive application of CPAP to spontaneously breathing patients with severe COPD in acute respiratory failure decreases inspiratory effort and dyspnoea whilst improving breathing pattern. It is conceivable that the early institution of CPAP in this setting may obviate the need for intubation and conventional mechanical ventilation.

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.

Pressure support reduces inspiratory effort and dyspnea during exercise in chronic airflow obstruction.

Exercise training has been of limited success in patients with severe chronic airflow obstruction (CAO), in part because of the reduced ventilatory capacity and excessive dyspnea experienced. Pressure support (PS) is a new form of mechanical ventilation which can effectively assist ventilation when applied noninvasively to patients in acute respiratory failure. It was hypothesized that PS might also be used to improve exercise performance, and ultimately physical conditioning, in ambulatory patients with CAO undergoing exercise training. To begin to address this concept, the objectives of the present study were (1) to examine the feasibility of providing PS to exercising patients with CAO and (2) to determine its effects on breathing pattern, inspiratory effort, and dyspnea. Flow and volume, mouth, esophageal, and gastric pressure were measured in seven patients with severe CAO (mean FEV1 = 0.75 +/- SEM 0.09 L) performing constant workload bicycle exercise (33 +/- 6 watts) during control conditions and with the application of PS (approximately 10 cm H2O). PS increased minute ventilation as a result of changes in both tidal volume and respiratory rate. This occurred despite marked reductions in inspiratory effort, as indicated by the pressure-time integrals of esophageal (68 +/- 5% control, p < 0.0005) and transdiaphragmatic pressure (52 +/- 8% control, p < 0.0005). Using a 5-point bidirectional scale to assess changes in dyspnea, breathlessness improved significantly with the addition of PS (2.3 +/- 0.6, p < 0.05) and worsened to a similar degree when it was removed (2.1 +/- 0.5, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

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.

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.

Comparison of static and dynamic measurements of intrinsic PEEP in mechanically ventilated patients.

Intrinsic positive end-expiratory pressure (PEEPi) is routinely determined under static conditions by occluding the airway at end-expiration (PEEPi,stat), the resulting plateau pressure representing the average PEEPi present within a nonhomogeneous lung. In contrast, PEEPi can also be evaluated dynamically (PEEPi,dyn) by recording the change in pressure required to initiate lung inflation. It has been suggested that PEEPi,dyn reflects the lowest regional PEEPi, and therefore underestimates PEEPi,stat in the presence of heterogenous mechanical properties. The purposes of this study were (1) to compare PEEPi obtained with these two methods in mechanically ventilated patients with significant airway obstruction (AWO) and those without (non-AWO), and (2) to relate any discrepancies observed with other indices of respiratory mechanics. PEEPi,stat, PEEPi,dyn, and respiratory mechanics were measured during controlled mechanical ventilation in 22 sedated, paralyzed patients. PEEPi,dyn was significantly less than PEEPi,stat in AWO, averaging 3.0 +/- 0.5 (SEM) and 9.3 +/- 1.1 (SEM) cm H2O, respectively (p < 0.0001). In contrast, these values were more comparable in non-AWO, averaging 4.6 +/- 0.8 and 5.4 +/- 1.0 cm H2O (p > 0.05). As a result, the ratio of PEEPi,dyn to PEEPi,stat amounted to 0.36 +/- 0.06 for AWO compared with 0.87 +/- 0.05 in non-AWO (p < 0.005). Maximal (Rmax) and minimal (Rmin) respiratory resistance were greater in AWO whereas respiratory compliance (Crs) was no different between groups. PEEPi,dyn/PEEPi,stat was inversely related to delta P, the pressure losses attributable to time constant inequalities and viscoelastic tissue properties (r = 0.64, p < 0.005). No correlation was found between this ratio and Rmax, Rmin, or Crs.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

Mechanisms of apnea termination in obstructive sleep apnea. Role of chemoreceptor and mechanoreceptor stimuli.

Previous work from our laboratory has indicated that mechanoreceptor feedback from the respiratory muscles may play an important role in arousal and apnea termination in obstructive sleep apnea (OSA). Other studies have pointed to a prominent role for chemoreceptor stimuli. We postulated that mechanoreceptor stimuli from the respiratory system are the primary determinant of apnea termination, and that chemoreceptor stimuli exert their effect indirectly through stimulation of ventilation and thus proprioceptive feedback. To test this, we measured the diaphragmatic tension-time index (TTdi) during obstructive sleep apneas in seven male subjects with severe untreated OSA. We compared the maximal TTdi values at end-apnea during administration of air, O2, and CO2. We reasoned that if mechanoreceptor stimuli mediate apnea termination, changing the degree of chemoreceptor stimulation during apneas should not alter the level of respiratory effort at end-apnea. O2 administration produced a significant increase in end-apneic arterial oxygen saturation (SaO2) and increased apnea duration. CO2 administration led to an increase in pre- and postapneic end-tidal carbon dioxide pressure (PETCO2), and tended to shorten apneas. However, the mean value for maximal end-apneic TTdi was 0.12 +/- 0.01 (SEM) during room air breathing and was unaltered by O2 (0.12 +/- 0.01) or CO2 (0.11 +/- 0.01) administration. The consistency of end-apneic TTdi values despite the varying chemical drive supports the hypothesis that apnea termination in OSA is mediated by mechanoreceptor feedback from the respiratory system, most likely from the respiratory muscles. The influence of chemoreceptor information may be mediated indirectly through an effect on ventilatory effort.

Physiologic effects of positive end-expiratory pressure in patients with chronic obstructive pulmonary disease during acute ventilatory failure and controlled mechanical ventilation.

Dynamic hyperinflation and intrinsic positive end-expiratory pressure (PEEPi) are observed in patients with chronic obstructive pulmonary disease (COPD) and flow limitation. Several reports suggest that PEEP levels approaching PEEPi reduce inspiratory load due to PEEPi, without further hyperinflation. Hence PEEP should not increase intrathoracic pressure or affect hemodynamics and gas exchange. To verify this hypothesis, the effects of PEEP (0 to 15 cm H2O) on respiratory mechanics, hemodynamics, and gas exchange were studied in nine COPD patients during controlled mechanical ventilation. PEEP levels approaching PEEPi (9.8 +/- 0.5 cm H2O) did not affect the expiratory flow/volume relationship, confirming the presence of flow limitation. PEEP levels of 5 and 10 cm H2O did not change lung volume and PEEPi in the respiratory system (PEEPtot,rs) and chest wall (PEEPtot,cw) or affect hemodynamics and gas exchange. When applied PEEP overcame PEEPi, changes in lung volume and the expiratory flow/volume relationship were observed. PEEPtot,rs and PEEPtot,cw also increased. Under these circumstances, PEEP increased static elastance in both the respiratory system and the chest wall, reducing cardiac index and affecting hemodynamics and gas exchange. Our data show that in mechanically ventilated COPD patients with PEEPi due to flow limitation, PEEP levels exceeding the 85% of PEEPi (Pcrit) caused further hyperinflation and compromised hemodynamics and gas exchange.

A simple method for the measurement of intrinsic positive end-expiratory pressure during controlled and assisted modes of mechanical ventilation.

OBJECTIVE: To evaluate a new and simple method for the measurement of intrinsic positive end-expiratory pressure during controlled and assisted modes of mechanical ventilation. DESIGN: Prospective study. SETTING: Three university hospital medical ICUs. PATIENTS: A total of 13 intubated, mechanically ventilated patients with severe airway obstruction. INTERVENTIONS: Airway occlusions reproducibly timed to occur coincidently with end-expiration were obtained by: a) manipulation of a three-way manual valve placed in the inspiratory limb of the external ventilator circuit (manual valve method) and b) activation of the expiratory pause hold function of the mechanical ventilator (Siemens 900C). MEASUREMENTS AND MAIN RESULTS: Airway pressure, flow, and volume were recorded during controlled and assisted modes of mechanical ventilation. Intrinsic positive end-expiratory pressure was determined from the plateau in airway pressure, which was developed during end-expiratory occlusions. For controlled mechanical ventilation, intrinsic positive end-expiratory pressure averaged 11.42 +/- 0.77 (SEM) cm H2O with the manual valve method, compared with 11.38 +/- 0.70 cm H2O, using the ventilator expiratory pause hold function. There was close correlation between results over the wide range of intrinsic positive end-expiratory pressure observed, which varied from approximately 5 to 22 cm H2O (y = 1.08x - 0.92; r2 = .99). Values of intrinsic positive end-expiratory pressure were comparable for the two methods during assist-control ventilation, pressure support ventilation, and spontaneous breathing through the ventilator circuit. The manual valve method was also effective when tested with different mechanical ventilators using a mechanical lung model. CONCLUSIONS: The manual valve method can be used to determine intrinsic positive end-expiratory pressure during controlled and assisted modes of ventilatory support with current ventilators. The availability of such an approach should facilitate the routine monitoring of intrinsic positive end-expiratory pressure in mechanically ventilated patients, thereby aiding clinical decision-making and management in these critically ill individuals.