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Intrinsic PEEP and unilateral lung hyperinflation. Pathophysiology and clinical significance.

Over a 14-month period, three patients developed unilateral lung hyperinflation during mechanical ventilation as a manifestation of intrinsic PEEP. These patients all had a history of CAO and an inflammatory or fibrotic disease process involving the contralateral lung. Physicians caring for patients with CAO need to be familiar with this presentation of intrinsic PEEP due to the associated barotrauma and cardiac dysfunction which can result from it.

Aged↗

Factors limiting exercise performance in lung disease. Ventilatory insufficiency.

Because of the additive effects of impaired ventilatory muscle function on the one hand and the increased ventilatory load on the other, increasing attention is now directed at therapies to improve ventilatory muscle function. Three main approaches are being used: (1) reduction in load; (2) increase in intrinsic ventilatory muscle function; and (3) reduction in dyspnea perception. While promising results have been achieved, additional investigative work is required to resolve outstanding questions.

Dyspnea↗

Maneuver-free determination of compliance and resistance in ventilated ARDS patients.

At present, most methods of lung mechanics analysis do not take nonlinearities of compliance and resistance into account. Nevertheless, nonlinearity of compliance is an inherent property of the respiratory system in ARDS and nonlinearity of resistance is an inherent property of the endotracheal tube. Herein we describe a computer-assisted multipoint method (LOOP) for breath-by-breath calculation of total respiratory system compliance (Ctrs) and total respiratory system resistance (Rtrs). Unlike our previously published method, LOOP excludes nonlinearities of compliance and resistance by confining the data used from the P/V/V loop to sequences with constant flow in inspiration and with steadily decreasing flow in expiration. LOOP was applied to five patients ventilated after open heart surgery (HEART group) and 12 patients ventilated for ARDS (ARDS group). The compliance results from LOOP were compared with the semistatic reference values corrected for intrinsic PEEP (CsST,IP). In the ARDS patients the compliance values from LOOP (46 ml/mbar) corresponded well with the semistatic compliance (CsST,IP = 42 ml/mbar). Despite the fact that there is no reference method for resistance known to date, we also determined the semistatic resistance (RsST) at end-inspiratory pause. The resistance values determined with LOOP were 8.5 mbar/L/s (RsST = 7.3 mbar/L/s) in the HEART group and 11.1 mbar/L/s (RsST = 8.6 mbar/L/s) in the ARDS group. LOOP gives a good correspondence between the linear RC model and the measured data in ARDS patients. In conclusion, LOOP requires neither an end-inspiratory pause (EIP) nor additional determination of intrinsic PEEP and gives Ctrs, automatically corrected for IPEEP, as well as Rtrs breath by breath at the bedside.

Adult↗

Lung tissue behavior during methacholine challenge in rabbits in vivo.

Previous studies have shown that lung challenge with smooth muscle agonists increases tissue viscance (Vti), which is the pressure drop between the alveolus and the pleura divided by the flow. Passive inflation also increases Vti. The purpose of the present study was to measure the changes in Vti during positive end-expiratory pressure- (PEEP) induced changes in lung volume and with a concentration-response curve to methacholine (MCh) in rabbits and to compare the effects of induced constriction vs. passive lung inflation on tissue mechanics. Measurements were made in 10 anesthetized open-chest mechanically ventilated New Zealand male rabbits exposed first to increasing levels of PEEP (3-12 cmH2O) and then to increasing concentrations of MCh aerosol (0.5-128 mg/ml). Lung elastance (EL), lung resistance (RL), and Vti were determined by adjusting the equation of motion to tracheal and alveolar pressures during tidal ventilation. Our results show that under baseline conditions, Vti accounted for a major proportion of RL; during both passive lung inflation and MCh challenge this proportion increased progressively. For the same level of change in EL, however, the increase in Vti was larger during MCh challenge than during passive inflation; i.e., the relationship between energy storage and energy dissipation or hysteresivity was dramatically altered. These results are consistent with a MCh-induced change in the intrinsic rheological properties of lung tissues unrelated to lung volume change per se. Lung tissue constriction is one possible explanation.

Administration, Inhalation↗

Passive expiration as a test of lung function.

Twenty-five normal subjects, 14 non-smokers and 11 smokers, passively expired into a spirometer after a maximal active inspiration, and after a passive inflation of the chest by a pressure cycled intermittent positive-pressure breathing (IPPB) machine. Acceptable passive expirations could be performed by all subjects after a passive inspiration but by only 12 after an active inspiration. Expired volume was found to change exponentially with time (r greater than 0.98), and the time constant of passive expiration (Tp) was obtained. There was no significant difference between the smokers and non-smokers in age, sex, forced vital capacity, FEV1 FEV1/FVC%, maximum mid-expiratory flow rate, maximum expiratory flow at 50% and 25% of the vital capacity, or the magnitude of the fall in the dynamic compliance with increasing frequency of breathing (Cdyn/f). Tp in smokers (1.06 +/- 0.47 SD) was significantly longer than in the non-smokers (0.65 +/- 0.25 SD P less than 0.02). Tp had a significant correlation with Cdyn/f(Tp = 0.6 + 161.81 Cdyn/f +/- 0.38 SE, r = 0.49, P less than 0.02). We conclude that satisfactory passive expiratory spirograms can be easily obtained after a mechanically assisted passive inspiration. Tp thus obtained is determined by the intrinsic properties of the respiratory system (lung plus thorax), and is significantly prolonged in smokers compared with non-smokers when other studies of pulmonary function including frequency dependence of compliance are unchanged.

Adult↗

"Intrinsic" positive end-expiratory pressure in stable patients with chronic obstructive pulmonary disease.

We have assessed "intrinsic" positive end-expiratory pressure (PEEPi), during quiet breathing in 18 patients with chronic obstructive pulmonary disease (COPD) in stable condition. Ventilatory flow, lung volume, oesophageal (Poes), gastric (Pga), and transdiaphragmatic pressure (Pdi) were measured. PEEPi was measured as the pressure difference (delta Poes) between the onset of the inspiratory effort, indicated by the start of the Pdi swing, and the point corresponding to zero flow. PEEPi was present in all of the 18 COPD patients, and averaged 2.4 +/- 1.6 cmH2O. The maximum transdiaphragmatic pressure (Pdi,max) was also measured and averaged 81.5 +/- 17.4 cmH2O. Following a randomized sequence, ten patients then inhaled an adrenergic agonist (fenoterol 1.6 mg), and eight patients the corresponding placebo. Fenoterol, but not placebo, caused a significant increase in forced expiratory volume in one second (FEV1) (+34%, on average), associated with a significant decrease in PEEPi (-63%, on average) and a significant improvement in Pdi,max (+19%, on average). We conclude that: 1) intrinsic PEEP can be present in stable COPD patients due to increased airflow resistance; 2) fenoterol improved diaphragmatic strength (Pdi,max) in our COPD patients, possibly due to a decrease in lung volume.

Aged↗

Effect of nasal-CPAP on patients with chronic obstructive pulmonary disease.

Patients with chronic obstructive pulmonary disease [COPD] breath at large lung volumes because of dynamic hyperinflation. Their end-tidal lung volumes will then be much above the equilibrium position of the respiratory system and the elastic recoil pressure would be above zero at end-tidal exhalation. This auto or intrinsic positive end-expiratory pressure [auto-PEEP] contributes to the elastic work of inspiration and the sensation of dyspnoea. The purpose of this study was to offset the auto-PEEP in patients with exacerbated chronic airflow obstruction by applying continuous positive airway pressure via the nose [nasal-CPAP]. Nine out of 14 patients experienced alleviation of dyspnoea while on nasal-CPAP [4 to 8 cmH2O]. These 9 patients had significantly more severe hyperinflation than the 5 patients who did not respond positively to nasal-CPAP. While there is a complex relationship between intrinsic and extrinsically applied PEEP in patients with COPD, the result of this study is consistent with the notion that CPAP may alleviate dyspnoea by reducing auto-PEEP, improving lung mechanics and unloading the inspiratory muscles. Nasal-CPAP may have a potential therapeutic role in exacerbations of COPD.

Dyspnea↗

Measurement of effective elastance of the total respiratory system in ventilated patients by a computed method. Comparison with the static method.

We have studied 28 patients mechanically ventilated for acute respiratory failure at different levels of externally applied positive end-expiratory pressure (PEEPe). We describe and compare a computed method of measuring "effective" elastance of the total respiratory system (Ers,eff) with the static values of elastance of the total respiratory system (Ers,st), obtained with the end-inflation occlusion technique. Ers,eff was computed by an original device (Heres, R.P.A., Belgium), also the effective resistance of the total respiratory system was calculated. At zero end-expiratory pressure set by the ventilator (ZEEP). Ers,eff averaged 29.5 +/- 13.5 cm H2O x L-1 while Ers,st non-corrected for intrinsic PEEP (PEEPi) averaged 36.4 +/- 15.1 cm H2O x L-1 and Ers,st corrected for PEEPi averaged 28.2 +/- 13.4 cm H2O x L-1. The small difference between Ers,eff and Ers,st corrected for PEEPi was statistically significant and these two values were highly correlated (r = 0.98). This significant difference disappeared rapidly with PEEPe and probably reflects a frequency-dependance due to pendelluft. We also observed that PEEPi was present in 21 of 27 patients at ZEEP. Our results also indicate that low levels of PEEP may improve Ers in hyperinflated COPD patients, without inducing further hyperinflation. In conclusion, values of Ers,eff are very similar to static values corrected for PEEPi and permit an accurate and rapid approach to the management of ventilated patients.

Adult↗

Inspiratory pressure support compensates for the additional work of breathing caused by the endotracheal tube.

Breathing through an endotracheal tube and a demand valve may increase the work performed by the respiratory muscles. Inspiratory pressure support (PS) is known to reduce this work and might therefore compensate for this increased requirement. To test this hypothesis, we measured the work of breathing (WOB) in 11 patients whose tracheas were intubated. Five had no intrinsic lung disease, but six had chronic obstructive lung disease. We compared WOB measurements taken under several sets of conditions: during assisted breathing at four levels of PS, during unassisted breathing and connection to a T-piece, and after extubation of the trachea. During unassisted breathing via the ventilator circuit (PS set at 0 cmH20), the WOB per minute was greater than that after extubation, with a mean increase (+/- standard deviation) of 68 +/- 38% (10.3 +/- 5.1 vs. 6.5 +/- 3.7 J.min-1, P less than 0.01). While breathing through the T-piece, the WOB was 27 +/- 18% greater than after tracheal extubation (8.2 +/- 5.1 vs. 6.5 +/- 3.7 J.min-1, P less than 0.05). The principal reason why inspiratory work decreased after extubation was that the ventilatory requirement decreased. For each patient, we determined retrospectively, after extubation, the level of PS that had reduced WOB to its postextubation value and obtained levels ranging from 3.4 to 14.4 cmH2O. The PS level at which additional WOB was compensated for, was greater in patients with chronic lung disease than in those free of lung disease (12.0 +/- 1.9 vs. 5.7 +/- 1.5 cm H2O, P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Respiratory mechanics in mechanically ventilated newborns: a comparison between passive inflation and occlusion methods.

A passive inflation method was described for measuring total respiratory elastance and resistance during mechanical ventilation in adult patients (Rossi et al., J Appl Physiol 58:1849, 1985). We applied this method to preterm and full-term mechanically ventilated newborn infants and we compared the results with those obtained by the occlusion method. We performed 37 tests in 16 newborn infants (B.W. 880-4,500 g; G.A. 28-42 weeks), between 1 and 45 days of postnatal age, ventilated with a Servo Ventilator 900C, set in controlled-volume mode. Flow was measured through a pneumotachograph inserted between the endotracheal tube (ETT) and the breathing circuit, tidal volume by integration of flow and airway pressure directly at the airway opening. Flow, volume, and pressure were recorded on an X/Y plotter to obtain pressure-volume (P/V), flow-volume (V/V) loops, and pressure-time curves. Occlusion was performed by using the end-inspiratory and the end-expiratory pause buttons of the ventilator. Analysis of P/V and V/V loops provided respiratory system compliance (Crs, infl.), resistance (Rrs, infl.), and "intrinsic positive end-expiratory pressure" (PEEPi, infl.). These values were compared with Crs, occl., Rrs, occl., and PEEPi, occl. measured by the occlusion method. The measurements were well correlated (Crs, infl./Crs, occl.: r = 0.90; Rrs, infl./Rrs, occl.: r = 0.91; PEEPi, infl./PEEPi, occl.: r = 0.91). Rrs, infl./Rrs, occl. and PEEPi, infl./PEEPi, occl. did not differ significantly. However, Crs, occl. was 15% higher than Crs, infl. (P less than 0.01). The passive inflation method is simple to use and well tolerated in preterm and full-term ventilated newborn infants, it provides accurate results, and can be a good alternative to occlusion methods. It requires, however, a constant inflation flow and adaptation to the ventilator.

Airway Resistance↗

Intrinsic PEEP on static pressure-volume curves.

The static pressure volume (PV) curve of the total respiratory system is a well established method to assess pulmonary mechanics during respiratory failure. We have tested the impact of auto-PEEP on the PV curve determination in 16 COPD patients. An isovolumic pressure increment (IPI) was found at the beginning of the curve and a close correlation between IPI and auto-PEEP level (r = 0.962) p less than 0.001) was observed. The regression equation was not significantly different from the identity line. We conclude that the appearance of IPI in PV curves is largely determined by auto-PEEP and it is a good estimate of the existing auto PEEP level.

Aged↗

Assessment of induced bronchoconstriction in anesthetized cats by the end-inflation occlusion method.

Airway occlusion during constant flow inflation allows rapid determination of frequency-dependence of pulmonary resistance by estimating its extreme values: RL,max (zero frequency) and RL,min (high frequency). RL,max represents the maximum resistance value that can be obtained with the prevailing time constant inequalities and stress relaxation, while RL,min represents the resistance that would be obtained in the absence of time constant inequalities and stress relaxation. In 5 anesthetized, tracheostomized, paralyzed, and artificially ventilated cats, RL,min, RL,max, and static pulmonary elastance (EL,st) have been measured following airway occlusion at the end of constant flow tidal inflations. Measurements were made before and during continuous infusion of increasing doses of serotonin (10-100 micrograms/kg/min IV). The development of intrinsic positive end-expiratory pressure (PEEPi) was also assessed. Cats varied greatly in their responsiveness to serotonin, but RL,min, RL,max, and EL,st increased and PEEPi developed in all cats. Increases in RL,max did not always parallel increases in RL,min but were similar to those in EL,st, suggesting that altered viscoelastic properties of the lung contributed to the increases in RL,max. We conclude that time-constant inequalities, changes in the lung periphery, and hyperinflation probably all contribute to the observed increases in RL,max and will influence conventional methods of measuring RL. Measuring RL,min potentially provides a better method for assessing the reduction in caliber of the conducting airways in isolation.

Airway Obstruction↗

Therapeutic use of intrinsic positive end-expiratory pressure.

A patient with acute hypoxemic respiratory failure undergoing mechanical ventilation with PEEP developed significant obstructive airway disease. We found that intrinsic PEEP, substituted for externally applied PEEP, could maintain oxygenation. The increased inspiratory/expiratory time ratio, which resulted in the development of intrinsic PEEP, beneficially reduced airway pressures.

Airway Obstruction↗

Partitioning of respiratory mechanics in mechanically ventilated patients.

In ten mechanically ventilated patients, six with chronic obstructive pulmonary disease (COPD) and four with pulmonary edema, we have partitioned the total respiratory system mechanics into the lung (l) and chest wall (w) mechanics using the esophageal balloon technique together with the airway occlusion technique during constant-flow inflation (J. Appl. Physiol. 58: 1840-1848, 1985). Intrinsic positive end-expiratory pressure (PEEPi) was present in eight patients (range 1.1-9.8 cmH2O) and was due mainly to PEEPi,L (80%), with a minor contribution from PEEPi,w (20%), on the average. The increase in respiratory elastance and resistance was determined mainly by abnormalities in lung elastance and resistance. Chest wall elastance was slightly abnormal (7.3 +/- 2.2 cmH2O/l), and chest wall resistance contributed only 10%, on the average, to the total. The work performed by the ventilator to inflate the lung (WL) averaged 2.04 +/- 0.59 and 1.25 +/- 0.21 J/l in COPD and pulmonary edema patients, respectively, whereas Ww was approximately 0.4 J/l in both groups, i.e., close to normal values. We conclude that, in mechanically ventilated patients, abnormalities in total respiratory system mechanics essentially reflect alterations in lung mechanics. However, abnormalities in chest wall mechanics can be relevant in some COPD patients with a high degree of pulmonary hyperinflation.

Aged↗

Intrinsic PEEP monitored in the ventilated ARDS patient with a mathematical method.

Under mechanical volume-controlled ventilation, the intensive care patient can develop intrinsic positive end-expiratory pressure (iPEEP); that is, the passive expiration is terminated by the following inspiration before the alveolar pressure comes to its physical equilibrium value. We present a mathematical method to estimate this alveolar dynamic iPEEP breath by breath, without the need of a maneuver. We tested it in paralyzed patients ventilated for adult respiratory distress syndrome after multiple trauma and/or sepsis, and we compared the results obtained with the new mathematical method with those from the occlusion method introduced by Pepe and Marini. The results agreed well (median difference of 0.8 mbar in 201 investigations in 12 patients). However, the mathematically determined values, representing dynamic iPEEP, are systematically slightly smaller than those measured by the occlusion maneuver. A variation of expiratory time suggests that this difference might be due to mechanical time-constant inhomogeneity, viscoelastic processes, or other mechanisms showing time dependence.

Adult↗

Inspiratory pressure support prevents diaphragmatic fatigue during weaning from mechanical ventilation.

Persistent inability to tolerate discontinuation from mechanical ventilation is frequently encountered in patients recovering from acute respiratory failure. We studied the ability of inspiratory pressure support, a new mode of ventilatory assistance, to promote a nonfatiguing respiratory muscle activity in eight patients unsuccessful at weaning from mechanical ventilation. During spontaneous breathing, seven of the eight patients demonstrated electromyographic signs of incipient diaphragmatic fatigue. During ventilation with pressure support at increasing levels, the work of breathing gradually decreased (p less than 0.02) as well as the oxygen consumption of the respiratory muscles (p less than 0.01), and electrical signs suggestive of diaphragmatic fatigue were no longer present. In addition, intrinsic positive end-expiratory pressure was progressively reduced. For each patient an optimal level of pressure support was found (as much as 20 cm H2O), identified as the lowest level maintaining diaphragmatic activity without fatigue. Above this level, diaphragmatic activity was further reduced and untoward effects such as hyperinflation and apnea occurred. When electrical diaphragmatic fatigue occurred, the activity of the sternocleidomastoid muscle was markedly increased, whereas it was minimal when the optimal level was reached. We conclude that in patients demonstrating difficulties in weaning from the ventilator: (1) pressure support ventilation can assist spontaneous breathing and avoid diaphragmatic fatigue (pressure support allows adjustment of the work of each breath to provide an optimal muscle load); (2) clinical monitoring of sternocleidomastoid muscle activity allows the required level of pressure support to be determined to prevent fatigue.

Acute Disease↗

Continuous positive airway pressure reduces work of breathing and dyspnea during weaning from mechanical ventilation in severe chronic obstructive pulmonary disease.

Dynamic hyperinflation and the development of intrinsic positive end-expiratory pressure (PEEPi) are commonly observed in patients with severe chronic obstructive pulmonary disease (COPD) and acute respiratory failure. The presence of intrinsic PEEP acts as an inspiratory threshold load, and contributes significantly to the observed increase in work and oxygen cost of breathing. The present study examined the effects of continuous positive airway pressure (CPAP) (at 5, 10, and 15 cm H2O) and its ability to reduce the mechanical load imposed by PEEPi on breathing pattern, work of breathing, and dyspnea in seven patients with severe COPD during weaning from mechanical ventilation. Tidal volume remained stable at all levels of applied pressure. Breathing frequency was also stable except for a small (12%) decrease during CPAP of 15 cm H2O. Inspiratory pulmonary resistance and elastance were unaltered by the application of CPAP. There were progressive reductions in the inspiratory work of breathing as the level of CPAP increased. At the highest level of CPAP, the amount of inspiratory work performed per minute and per liter of ventilation decreased by 49.8 and 41.8%, respectively. Similar progressive reductions were also obtained in the pressure-time product for the inspiratory muscles and the diaphragm, which amounted to decreases of 42.9 and 42.2%, respectively, at the highest level of CPAP. End-expiratory lung volume remained stable at the lowest level of CPAP, with only modest increases occurring at the higher levels. In addition, all patients reported a reduction in dyspnea during the administration of CPAP.(ABSTRACT TRUNCATED AT 250 WORDS)

Dyspnea↗