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Respiratory system mechanics in acute respiratory distress syndrome.

Respiratory mechanics research is important to the advancement of ARDS management. Twenty-eight years ago, research on the effects of PEEP and VT indicated that the lungs of ARDS patients did not behave in a manner consistent with homogenously distributed lung injury. Both Suter and colleagues] and Katz and colleagues reported that oxygenation continued to improve as PEEP increased (suggesting lung recruitment), even though static Crs decreased and dead-space ventilation increased (suggesting concurrent lung overdistension). This research strongly suggested that without VT reduction, the favorable effects of PEEP on lung recruitment are offset by lung overdistension at end-inspiration. The implications of these studies were not fully appreciated at that time, in part because the concept of ventilator-associated lung injury was in its nascent state. Ten years later. Gattinoni and colleagues compared measurements of static pressure-volume curves with FRC and CT scans of the chest in ARDS. They found that although PEEP recruits collapsed (primarily dorsal) lung segments, it simultaneously causes overdistension of non-dependent, inflated lung regions. Furthermore, the specific compliance of the aerated, residually healthy lung tissue is essentially normal. The main implication of these findings is that traditional mechanical ventilation practice was injecting excessive volumes of gas into functionally small lungs. Therefore, the emblematic low static Crs measured in ARDS reflects not only surface tension phenomena and recruitment of collapsed airspaces but also overdistension of the remaining healthy lung. The studies reviewed in this article support the concept that lung injury in ARDS is heterogeneously distributed, with resulting disparate mechanical stresses, and indicate the additional complexity from alterations in chest wall mechanics. Most of these studies, however, were published before lung-protective ventilation. Therefore, further studies are needed to refine the understanding of the mechanical effects of lung-protective ventilation. Although low-VT ventilation is becoming a standard of care for ARDS patients, many issues remain unresolved; among them are the role of PEEP and recruitment maneuvers in either preventing or promoting lung injury and the effects of respiratory rate and graded VT reduction on mechanical stress in the lungs. The authors believe that advances in mechanical ventilation that may further improve patient outcomes are likely to come from more sophisticated monitoring capabilities (ie, the ability to measure P1 or perhaps Cslice) than from the creation of new modes of ventilatory support.

Humans↗

Compliance of the respiratory system in newborn and adult rats after gestation in hypoxia.

We hypothesized that hypoxia during gestation modifies the compliance of the respiratory system of newborn and adult rats. Pregnant rats were placed in a hypobaric chamber at an inspired oxygen pressure of 86 mmHg (equivalent to 12% O2 in normobaria) from day 4 of gestation until day 2 post-partum. Three-day-old rat pups were smaller than controls, with higher hematocrit; the lungs were also small, with less protein and DNA content. The pressure (x-axis)-volume (y-axis) curve of the respiratory system was displaced to the right of the control curve, and the compliance of the respiratory system, measured on the inflation or deflation limb of the pressure-volume curve, was decreased by approximately 20-25%, depending upon the normalization procedure (per body mass or per dry lung weight). In 50-day-old rats exposed to hypoxia during gestation, body weight, hematocrit, lung mass and DNA content were normal; the compliance of the respiratory system, measured at ventilation frequencies between 20 cpm and 100 cpm, was higher than in controls by approximately 20%. It is concluded that the effects of prenatal hypoxia on the compliance of the respiratory system can vary with age. In the rat the process of alveolar formation initiates postnatally. Hence, in the newborn the effects of the prenatal hypoxia on the compliance of the respiratory system are likely to be dominated by the hypoxic pulmonary hypoplasia and hypertension, which decrease the compliance of the respiratory system. In the adult, the effects of the decreased alveolar formation are the prevailing ones, increasing the compliance of the respiratory system.

Age Factors↗

Effect of hypoxia on respiratory system impedance in dogs.

The effects of hypoxia on lung and airway mechanics remain controversial, possibly because of the confounding effects of competing reflexes caused by systemic hypoxemia. We compared the effects of systemic hypoxemia with those of unilateral alveolar hypoxia (with systemic normoxemia) on unilateral respiratory system impedance (Z) in intact, anesthetized dogs. Independent lung ventilation was obtained with a Kottmeier endobronchial tube. Individual left and right respiratory system Z was measured during sinusoidal forcing with 45 ml of volume at frequencies of 0.2-2.1 Hz during control [100% inspired O2 fraction (FIO2)], systemic hypoxemia (10% FIO2), and unilateral alveolar hypoxia (0% FIO2 to left lung, 100% FIO2 to right lung). During systemic hypoxemia, there was a mean Z magnitude increase of 18%. This change was entirely attributable to a decrease in the imaginary component of Z; there was no change in the real component of Z. Administration of atropine (0.2 mg/kg) did not block the increase in Z with systemic hypoxemia. In contrast, there was no change in Z in the lung subjected to unilateral alveolar hypoxia. We conclude that alveolar hypoxia has no direct effect on lung mechanical properties in intact dogs. In contrast, systemic hypoxemia does increase lung impedance, apparently through a noncholinergic mechanism.

Airway Resistance↗

Effect of PEEP on the mechanics of the respiratory system in ARDS patients.

In patients with adult respiratory distress syndrome (ARDS) we studied the effect of positive end-expiratory pressure (PEEP) on respiratory mechanics. We used the technique of rapid airway occlusion during constant flow (V) inflation to partition the total respiratory system resistance (Rrs) into the interrupter resistance (Rint,rs) and the additional resistance (delta Rrs) due to viscoelastic pressure dissipations and time constant inequalities. We also measured static (Est,rs) and dynamic (Edyn,rs) elastance of the respiratory system. The procedure was carried out in nine ARDS patients at different inspiratory V and inflation volumes (delta V) at PEEP of 0, 5, 10, and 15 cmH2O. We found that during baseline ventilation (delta V = 0.7 liter and V = 1 l/s), Est,rs, Edyn,rs, and Rint,rs did not change significantly with PEEP, whereas delta Rrs and Rrs increased significantly only with PEEP of 15 cmH2O. The increase of delta Rrs and Rrs with PEEP was positively correlated with the concomitant changes in end-expiratory lung volume (P < 0.001). At all levels of PEEP, under iso-delta V conditions, delta Rrs decreased with increasing V, whereas at a fixed V, delta Rrs increased with increasing delta V. A four-parameter model of the respiratory system failed to fully describe respiratory dynamics in the ARDS patients, probably due to nonlinearities.

Airway Resistance↗

Effect of two tidal volumes on oxygenation and respiratory system mechanics during the early stage of adult respiratory distress syndrome.

PURPOSE: To study the effect of two tidal volumes on gas exchange, lung mechanics, and hemodynamics in 12 patients with acute respiratory distress syndrome (ARDS) within the first 72 hours of mechanical ventilation. METHODS: Tidal volume (VT) was increased by 40% from the initial value at fixed positive end-expiratory pressure (PEEP) and matched minute ventilation by adjusting the respiratory rate (RR) of the ventilator. Initial VT and RR were 592 +/- 42 mL and 19 +/- 1 min-1, respectively. High VT amounted to 825 +/- 54 mL with a RR of 12 +/- 1 min-1. RESULTS: We found that at high VT (1) the index of oxygenation increased from 0.22 +/- 0.03 to 0.32 +/- 0.04 (P < .001) with a parallel decrease in the right to left venous admixture from 0.26 +/- 0.02 to 0.23 +/- 0.02 (P < .001), and in the ratio of physiological dead space to tidal volume (VDS/VT) from 0.53 +/- 0.05 to 0.46 +/- 0.04 (P < .01), without impairment to hemodynamics and (2) respiratory system compliance improved significantly from 34.8 +/- 2.8 mL/cm H2O to 37.2 +/- 2.9 mL/cm H2O (P < .05). In 4 patients, we performed pressure-volume curves on PEEP with the ventilator finding an upward concavity reflecting progressive alveolar recruitment with increasing inflation volume in 3. CONCLUSIONS: High-tidal ventilation in the early stage of ARDS improved gas exchange, suggesting recruitment during the inspiratory phase. However, the benefit of better oxygenation should be weighed against the potential risk of barotrauma induced at high VT.

Adolescent↗

Respiratory system, lung, and chest wall impedances in anesthetized dogs.

We measured impedances of the respiratory system (Zrs) and lung (ZL) in anesthetized and paralyzed dogs at frequencies between 4 and 64 Hz. Zrs was measured at functional residual capacity (FRC) and with mean transpulmonary pressures (Ptp) of 12 and 30 cmH2O; ZL was measured with the chest wall open at FRC and Ptp = 12 cmH2O. From these data we derived chest wall impedances at FRC and 12 cmH2O. Effective resistances of the respiratory system, lung, and chest wall were all frequency dependent. At frequencies below 22 Hz frequency dependence of respiratory system resistance was due to the frequency dependence of the chest wall, whereas at higher frequencies it was due to frequency dependence of the lung. Analysis of the impedance data between 4 and 32 Hz provided estimates of resistance, inertance, and compliance of the lung, chest wall, and respiratory system. At FRC, 41% of the respiratory system resistance was due to the lung and 59% was associated with the chest wall. Nearly all of the respiratory inertance (98%) was due to the lung. Lung compliance was approximately twice that of the chest wall, the former accounting for approximately one-third of respiratory elasticity. As lung volume was increased, respiratory resistance and compliance decreased; inertance also decreased, although this change was not significant.

Airway Resistance↗

Mechanical respiratory system input impedance during high-frequency oscillatory ventilation in rabbits.

OBJECTIVES: To study the mechanical properties of the rabbit respiratory system during high-frequency oscillatory ventilation by means of mechanical respiratory impedance measurement and to characterize the changes in oscillation mechanics of the respiratory system occurring after bilateral vagotomy. DESIGN: Acute experimental trial. SETTING: Physiology laboratory. SUBJECTS: Ten adult rabbits (mean body weight 3.1 kg). MEASUREMENTS AND MAIN RESULTS: Anesthetized rabbits were exposed to short runs of high-frequency oscillatory ventilation, with stroke volumes of 5.0, 6.6, and 10.0 mL, applied at oscillation frequencies of 10, 15, 20, and 25 Hz before and after vagotomy. Mechanical respiratory input impedance was determined from the pressure and flow signals simultaneously measured at the airway opening and analyzed in terms of its real and imaginary parts. (The real part of respiratory impedance characterizes the resistive property of the lungs and chest wall; the imaginary part of respiratory impedance characterizes the elastic and inertial properties of the lungs and chest wall.) At all stroke volumes and oscillation frequencies studied, vagotomy resulted in a decrease in the real part of respiratory impedance. After vagotomy, the real part of respiratory impedance was stroke volume-independent, and exhibited negative frequency dependency. Vagotomy also led to a decrease in the imaginary part of respiratory impedance, mainly at lower oscillation frequencies, and thus, to a higher resonant frequency of the respiratory system. CONCLUSIONS: Mechanical respiratory impedance measurement proved to be a useful method to study the mechanical properties of the respiratory system during high-frequency oscillatory ventilation. The results suggest that vagally mediated reflex changes in respiratory system mechanics are associated with high-frequency oscillatory ventilation, depending on the ventilatory variables that are used.

Airway Resistance↗

Effects of inhalation of beta 2-sympathicomimetic and anticholinergic agents on the impedance of the respiratory system in normal subjects.

Impedance measurement of the respiratory system by forced oscillations is a sensitive and accurate method to detect mechanical parameters, especially in normal subjects. The effects of inhalation of 0.2 mg of fenoterol and 0.02 mg of ipratropium bromide on the impedance of the respiratory system was studied in 20 healthy subjects in a frequency spectrum between 4 and 52 Hz. Both agents caused a statistically significant decrease in resistance (Rrs). Inhalation of fenoterol and ipratropium bromide caused a significant increase in reactance (Xrs). The decrease in Rrs was greater after inhalation of fenoterol than after ipratropium bromide. Fenoterol and ipratropium bromide caused qualitatively similar changes in Rrs and Xrs of the respiratory system. The changes in Rrs can be explained by dilation of the central airways. The changes in Xrs are supposed to be the result of an increase in the capacitance of the lungs.

Administration, Inhalation↗

Flow and volume dependence of respiratory system flow resistance in patients with adult respiratory distress syndrome.

Using a simple and rapid technique, we studied the flow and volume dependence of the total resistance of the respiratory system (Rrs) in six patients with ARDS. At any given inflation volume, Rrs decreased progressively with increasing flow (V) according to the following hyperbolic function: Rrs = a/V + b, where a and b are constants. At any fixed inflation flow, Rrs increased progressively with increasing inflation volume. The observed flow and volume dependence of Rrs is probably mainly due to the viscoelastic properties of the pulmonary and chest wall tissues. The flow and volume dependence of Rrs found in the patients with ARDS is qualitatively similar to that previously observed in normal anesthetized paralyzed subjects. In ARDS, however, Rrs was considerably greater than in the normal subjects, indicating that besides a low respiratory compliance ARDS is characterized by a high flow resistance. This mainly reflects increased effective flow resistance of the pulmonary and chest wall tissues, although airway resistance is also higher than normal.

Adult↗

Studies on halotolerance in a moderately halophilic bacterium. Effect of growth conditions on salt resistance of the respiratory system.

The effect of sodium chloride on the respiratory activity of a moderately halophilic halotolerant bacterium was studied. Irrespective of growth conditions, resting cells oxidized succinate at a low rate unless sodium chloride was included in the assay mixture, maximum respiratory rates being obtained for sodium chloride concentrations between 0.2m and 0.8m. Neither potassium chloride nor sucrose could replace the sodium salt. The response of the respiratory system to sodium chloride concentration above the optimum depended on growth conditions. Respiration of cells harvested from a low-salt medium was almost inhibited completely by 2.0m-sodium chloride, and that of cells grown and washed in the presence of 2.0m-sodium chloride by 30%. After preincubation with a growth medium containing 2.0m-sodium chloride, even with all multiplication suppressed by chloramphenicol, the resistance of the respiratory system of low-salt-grown organisms to high salt concentrations increased considerably and resembled that of their high-salt-grown counterparts. A similar increase in resistance occurred after preincubation with yeast extract or with choline. With labelled choline, energy-dependent accumulation of labelled material occurred, the conditions required for maximum accumulation and retention being the same as those that increased the salt resistance of the respiratory system. The chromatographic behaviour of the labelled material indicated that the substance was not choline but a derivative, possibly betaine.

Bacteria↗

Surgery of the respiratory system.

Diseases affecting the respiratory tract are common in cattle; however, surgery required for treatment of these diseases is infrequent. Therefore, veterinarians may be reluctant to perform these surgical procedures. Familiarity with the variety and complexity involved in various surgical procedures should reduce this anxiety. When used, surgery of the respiratory tract can offer significant benefit to the patient and profitable returns to the owner.

Animals↗

Endogenous excitatory drive to the respiratory system in rapid eye movement sleep in cats.

A putative endogenous excitatory drive to the respiratory system in rapid eye movement (REM) sleep may explain many characteristics of breathing in that state, e.g. its irregularity and variable ventilatory responses to chemical stimuli. This drive is hypothetical, and determinations of its existence and character are complicated by control of the respiratory system by the oscillator and its feedback mechanisms. In the present study, endogenous drive was studied during apnoea caused by mechanical hyperventilation. We reasoned that if there was a REM-dependent drive to the respiratory system, then respiratory activity should emerge out of the background apnoea as a manifestation of the drive. Diaphragmatic muscle or medullary respiratory neuronal activity was studied in five intact, unanaesthetized adult cats who were either mechanically hyperventilated or breathed spontaneously in more than 100 REM sleep periods. Diaphragmatic activity emerged out of a background apnoea caused by mechanical hyperventilation an average of 34 s after the onset of REM sleep. Emergent activity occurred in 60 % of 10 s epochs in REM sleep and the amount of activity per unit time averaged approximately 40 % of eupnoeic activity. The activity occurred in episodes and was poorly related to pontogeniculo-occipital waves. At low CO2 levels, this activity was non-rhythmic. At higher CO2 levels (less than 0.5 % below eupnoeic end-tidal percentage CO2 levels in non-REM (NREM) sleep), activity became rhythmic. Medullary respiratory neurons were recorded in one of the five animals. Nineteen of twenty-seven medullary respiratory neurons were excited in REM sleep during apnoea. Excited neurons included inspiratory, expiratory and phase-spanning neurons. Excitation began about 43 s after the onset of REM sleep. Activity increased from an average of 6 impulses s-1 in NREM sleep to 15.5 impulses s-1 in REM sleep. Neuronal activity was non-rhythmic at low CO2 levels and became rhythmic when levels were less than 0.5 % below eupnoeic end-tidal levels in NREM sleep. The level of CO2 at which rhythmic neuronal activity developed corresponded to eupnoeic end-tidal CO2 levels in REM sleep. These results demonstrate an endogenous excitatory drive to the respiratory system in REM sleep and account for rapid and irregular breathing and the lower set-point to CO2 in that state.

Animals↗

Comparative mechanics of mammalian respiratory system.

Compliances (C) of lung, thorax and respiratory system as well as resistances (R) of the respiratory system (lower airways + lung + chest wall) and of upper airway (primarily laryngeal and nasal) were measured in 5 species of mammals, spanning a 1000-fold range of body weights (mouse to dog), immediately following sacrifice with an overdose of sodium pentobarbital. The results indicate that compliance is proportional to BW1.0, while respiratory resistance and upper airway resistance have exponents of -0.819 and -0.702, respectively. The reciprocal of the time constant, tau -1 = (RC)-1 is proportional to BW-0.298 for respiratory resistance alone and BW-0.326 when upper airway resistance is included. Since breathing frequency varies as BW-0.28, these results indicate a proportional relationship between breathing frequency and passive emptying time. This suggests that passive respiratory mechanics play a major role in determining TE and therefore TTOT for animals during quiet breathing. Changes in volume history were found not to affect the slope of the relationships between compliance and body weight.

Airway Resistance↗

Computer simulation of the human respiratory system for educational purposes.

The main objective of this study was the development of a computer simulation system for the human respiratory system, in order to educate students of nursing. This approach was based on existing mathematical models and on our own constructed specific functions. For the development of this educational tool the appropriate software packages were used according to the special demands of this process. This system is called ReSim (Respiratory Simulation) and consists of two parts: the first part deals with pulmonary volumes and the second one represents the mechanical behavior of lungs. The target group evaluated ReSim. The outcomes of the evaluation process were positive and helped us realize the system characteristics that needed improvements. Our basic conclusion is that the extended use of such systems supports the educational process and offers new potential for learning.

Anatomy↗