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Biomedical subjects

J Milic-Emili

Publications and source records attributed to J Milic-Emili.

At least 109 records · Page 6Linked to original sources

A single-compartment model cannot describe passive expiration in intubated, paralysed humans.

The time-course of thoracic volume changes (respiratory inductive plethysmograph) during relaxed expiration was studied in 11 intubated, paralysed, mechanically ventilated subjects. The semilog volume-time curves show that expiration is governed by two apparently separate mechanisms: one causes emptying of most of the expired volume (approximately 80%) with a time constant of 0.50 +/- 0.22 s for a baseline tidal volume of 0.44 +/- 0.12 l (mean +/- SD) and 0.37 +/- 0.14 s when the tidal volume is reduced (VTP); the other contributes a relatively small amount to the expired volume over a significantly longer time, the time constant amounting to 3.27 +/- 1.54 s for baseline VT and 2.95 +/- 1.65 s for VTp. The first mechanism probably reflects the standard elastic and flow resistive properties of the respiratory system, while the second, slower compartment, is probably an expression of the viscoelastic properties of the pulmonary and chest wall tissues.

Adult↗

Effect of serotonin on expiratory pulmonary resistance in cats.

In five anesthetized paralyzed cats, mechanically ventilated with tidal volumes of 36-48 ml, the isovolume pressure-flow (IVPF) relationships of the lung were studied under control conditions and during serotonin-induced bronchoconstriction. At the end of a tidal inspiration, airway opening pressure was set between +3 and -15 cmH2O for single tidal expirations. After control measurements, animals were treated with progressively increasing doses of intravenous serotonin (10, 20, 50, and 100 micrograms.kg-1.min-1) and all measurements were repeated at each dose. No animal became flow limited during passive expiration against atmospheric pressure. Disregarding flow-limited segments, IVPF plots for three lung volumes showed that the resistive pressure-flow relationships were curvilinear under all conditions, thus fitting Rohrer's equation. Under control conditions and during the lowest dose of serotonin, the volume dependence of pulmonary resistance (RL) tended to balance its flow dependence so that during lung deflation against atmospheric pressure RL remained nearly constant. However, as bronchoconstriction became more pronounced, RL often increased disproportionately at the lower lung volumes. Changes in expiratory RL with serotonin relative to control values varied according to the flow rates used to make comparisons. The technique used to determine RL will partly determine the results obtained.

Airway Resistance↗

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↗

Intrinsic PEEP and arterial PCO2 in stable patients with chronic obstructive pulmonary disease.

Dynamic pulmonary hyperinflation and intrinsic PEEP (PEEPi) are known to play an important role in causing acute respiratory failure in COPD patients. In the present study, we have explored (1) the prevalence and magnitude of PEEPi in stable COPD patients, and (2) the correlation of PEEPi with respiratory mechanics and PaCO2. In 96 stable COPD patients with varying degrees of airway obstruction, we measured pulmonary flow resistance (RL), dynamic lung compliance (CLdyn), breathing pattern, arterial blood gases, and dynamic PEEPi. Dynamic PEEPi was determined as a negative deflection in esophageal pressure from the start of inspiratory effort to the onset of inspiratory flow. A significant correlation was found between dynamic PEEPi and FEVi (% predicted; r = -0.56, p less than 0.001), between PEEPi and RL (r = 0.69, p less than 0.001), and between PaCO2 and PEEPi (r = 0.6, p less than 0.001). These results indicate that increased severity of airway obstruction promotes PEEPi and concomitant dynamic hyperinflation. This implies increased inspiratory work in the face of decreased effectiveness of the inspiratory muscles as pressure generators. The present results suggest that dynamic hyperinflation may play a role in causing chronic hypoventilation in COPD patients.

Aged↗

Endogenous opioids modulate the increase in ventilatory output and dyspnea during severe acute bronchoconstriction.

The aim of this study was to evaluate whether endogenous opioids are involved in the regulation of breathing pattern and respiratory drive during bronchoconstriction induced by methacholine (MCh). We studied six male asymptomatic asthmatics 18 to 35 yr of age. In a preliminary study we determined the concentration of MCh causing a 60% fall in FEV1 (PC60 FEV1). On two subsequent days, we measured breathing pattern, dyspnea sensation (Borg scale), mouth occlusion pressure (P0.1), and FEV1 before and 10 min after an intravenous injection of either naloxone (0.1 mg/kg) or saline according to a randomized double-blind crossover design. A MCh concentration equal to the PC60 FEV1 was then inhaled, and measurements were repeated 5 min later. Neither placebo nor naloxone affected baseline breathing pattern, P0.1, and FEV1. Naloxone pretreatment did not influence airway response to MCh; the mean percent fall in FEV1 was 65.9 +/- 1.3 and 64.7 +/- 1.2% (mean +/- 1 SE) on the placebo day and the naloxone day, respectively. After MCh inhalation no significant changes in VE, VT, and breathing frequency occurred when patients received placebo. However, P0.1 increased from 1.48 +/- 0.17 to 3.43 +/- 0.70 cm H2O (p less than 0.05), and VT/TI fell from 0.66 +/- 0.08 to 0.52 +/- 0.04 L/s (p less than 0.05). Naloxone pretreatment resulted in an increase in breathing frequency (from 18.2 +/- 1.7 to 22.8 +/- 2.6 breaths/min; p less than 0.05) and VT/TI (from 0.58 +/- 0.06 to 0.74 +/- 0.05 L/s; p less than 0.05) after MCh.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

Dynamic pulmonary hyperinflation and intrinsic PEEP: consequences and management in patients with chronic obstructive pulmonary disease.

The presence of dynamic hyperinflation and intrinsic PEEP is a common and yet too often unrecognized occurrence in patients with airway obstruction both in stable state and during acute exacerbations. Intrinsic PEEP may represent an important load on the inspiratory muscles which are operating at a mechanical disadvantage due to hyperinflation. This may contribute significantly to ventilatory failure. The presence of intrinsic PEEP also has other important clinical ramifications. Prompt recognition of intrinsic PEEP will allow for proper measurement and interpretation of a variety of cardiopulmonary parameters and improved clinical decision making and management of these critically ill patients.

Acute Disease↗

The role of PEEP in patients with chronic obstructive pulmonary disease during assisted ventilation.

In patients with acute respiratory failure (ARF) due to acute exacerbation of chronic obstructive pulmonary disease (COPD), the intrinsic positive end-expiratory pressure (PEEPi) can significantly increase workload for ventilation. It has been suggested that, in the presence of expiratory flow limitation, application of low levels of PEEP by the ventilator can be used to reduce PEEPi and therefore the magnitude of the inspiratory effort during assisted mechanical ventilation (or pressure support) and weaning. Clearly, pulmonary hyperinflation should not be further enhanced in order not to counteract the beneficial effect of removing PEEPi by decreasing respiratory muscle length and force. This use of PEEP in COPD patients is supported not only by theory, but also by recent experimental work, although sufficient clinical information is not yet available to provide a guideline for titration of the PEEP level. Therefore, application of PEEP in COPD patients requires close monitoring of the end-expiratory lung volume. This can be accomplished, among other noninvasive ways (e.g. the inductive plethysmography), by inspection of flow/volume curves during application of increasing levels of PEEP. The shape of the expiratory limb of the flow/volume curve can also suggest the presence of dynamic hyperinflation and expiratory flow limitation.

Humans↗

The pattern of resting breathing in patients with upper airway obstruction.

The flow-time curve of resting breathing was recorded in 14 patients (aged 36 +/- 16 yrs) with mild to moderate symptoms of upper airway obstruction (UawO) and compared to that of 28 matched, healthy controls (HC) in order to characterize the breathing pattern of such patients. The inspiratory time over total time (TI/Ttot) was higher in the patients (0.42; SD 0.04) than in HC (0.37; SD 0.04) (p less than 0.001), and tidal volume (VT) over TI was lower in patients (0.37; SD 0.07 l.s-1) than in HC (0.43; SD 0.09 l.s-1) (p less than 0.01). Inspiratory and expiratory peak flows at rest were also lower in the patients (p less than 0.001). In these, the mean to peak flow ratio of inspiration (0.74; SD 0.07) was higher than in HC (0.66; SD 0.04) (p less than 0.0005). This indicates a more rectangular wave of inspiration in the patients. All of these changes may be due to the increased inspiratory load. However, since the patients were breathing at rest with VT and flows far below their values on the maximal flow volume loop, the changes can also be interpreted as adaptive rather than imposed by absolute mechanical limitations.

Adult↗

[Evaluation of mechanic characteristics of the respiratory system in artificial ventilation].

Measuring respiratory mechanics is reputed to be difficult and therefore is seldom done in intensive care units although simple techniques are available. Air flow interruption after constant rate inflation enables the total respiratory system resistance (Rrs) to be divided into airway resistance (Raw) and additional resistance (delta R), the latter being associated with the viscosity and elasticity of the respiratory system and with the inhomogeneity of the lung. Thus, in patients with chronic obstructive lung disease this end-inspiratory air flow interruption provides physiopathological data (increase of Rrs to the detriment of Raw and delta R, due to major disparities of time constants in the lung) and therapeutic data (optimum ventilation mode reducing the patient's breathing work during assisted ventilation). Air flow interruption at the end of expiration measures the intrinsic positive end-expiratory pressure which indicates hyperinflation with damaging effects on cardiac performance and respiratory muscle function and constitutes a major factor of weaning failure. Combining the end-inspiratory and end-expiratory techniques enables a realistic and complete pressure-volume curve to be drawn easily. It is therefore possible during mechanical ventilation to evaluate the characteristics of respiratory mechanics very precisely and very simply. This should improve both our understanding of some diseases and our management of ventilated patients.

Humans↗

Evaluation of the flow-volume loop as an intra-operative monitor of respiratory mechanics in infants.

Airway pressure is currently the primary indicator of respiratory mechanics used by the anesthetist in the operating room. This quantity can signal that the mechanical properties of the respiratory system have changed. However, there is a need for more sophisticated monitors of mechanics, capable of indicating the nature of the change. We have investigated the use of the tidal flow-volume loop in differentiating between an obstruction of the endotracheal tube and changes in the distribution of regional ventilation, using a computer model. Endotracheal obstruction caused the descending limb of flow-volume loop to become convex to the volume axis, whereas ventilation inhomogeneity caused the curve to become concave to the volume axis. In contrast, examination of peak airway pressure did not allow differentiation between the two conditions. We conclude that, while the peak airway pressure is useful in signaling a change in a patient's condition, the combination of airway pressure and the flow-volume loop serves as a more comprehensive monitor of respiratory mechanics.

Computer Simulation↗

Airway pressures during crying in healthy infants.

Maximal inspiratory and expiratory airway pressures (PI max and PE max) were measured in 100 healthy infants (51 males, 49 females; age range, 0.06-3.76 years) by occluding the airway with a suitable face mask during a crying effort. Mean values +/- SD for PI max and PE max were 118 +/- 21 cm H2O and 125 +/- 35 cm H2O, respectively. Maximal inspiratory pressure was independent of age, sex, and anthropometrics, while maximal expiratory pressure showed a low but statistically significant positive correlation with body weight (P less than 0.001).

Age Factors↗

Pulmonary flow resistance.

In the past it has been generally assumed that pulmonary flow resistance (RL) increases with increasing flow and decreases with increasing lung volume. Recent work indicates that RL decreases with increasing flow, at least up to flow rates 3-4 times greater than those at rest, and increases progressively with increasing lung volume. This behaviour results mainly from dynamic pressure dissipations within the pulmonary tissues due to viscoelastic phenomena. In fact, during resting breathing the contribution of the latter to RL is more important than that of airway resistance.

Airway Resistance↗

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↗

Respiratory mechanics determined by flow interruption during passive expiration in cats.

We used the interrupter technique to measure the resistance Rinit (equal to the initial change delta Pinit in tracheal pressure divided by flow at interruption) during expiration in six normal anaesthetized-paralyzed cats. By performing interruptions at different points in expiration we found Rinit in each cat to be linearly dependent on flow. By allowing the cats to expire through two different resistances we were also able to demonstrate a volume dependence of Rinit in four of the cats. In addition, we obtained a secondary pressure change delta Pdif in each cat, as the magnitude of the slow change in tracheal pressure in the 2 sec following interruption of flow. delta Pdif was approximately constant over most of the expired volume range, and represented the difference between the static elastic recoil pressure of the respiratory system and the pressure driving flow at any volume during a passive expiration. delta Pdif became larger than delta Pinit towards the end of expiration. Since previously used methods for measuring respiratory system resistance have employed varying combinations of delta Pinit and delta Pdif as the resistive pressure drop, it is clear that measurements of resistance must be made with standard techniques under standard conditions if they are to be compared.

Airway Resistance↗

Early detection of pulmonary congestion and edema in dogs by using lung sounds.

Five mongrel dogs (2 interstitial and 3 alveolar edema) were studied. Lung mechanics were measured by recording the flow, volume, and esophageal pressure according to the standard technique. Edema was produced by infusion of Ringer lactate solution. Lung sounds were recorded on tape from the dependent part of the chest wall. Lung sound signals were high-pass filtered at 100 Hz and subjected to fast Fourier transform. Samples of lung sounds were analyzed before (control) and at 5, 10, 20, 30, and 40 min after the infusion. The mean, median, and mode frequencies of sound power spectra at the control time were, respectively, 169.6 +/- 29.19, 129.6 +/- 29.81, and 136.0 +/- 29.87 (SD) Hz. These values increased significantly at 5 min after infusion to 194.0 +/- 26.08 (P less than 0.0037), 150.2 +/- 23.48 (P less than 0.0085), and 164.6 +/- 28.74 Hz (P less than 0.02), respectively. These values stayed significantly elevated at 10, 20, 30, and 40 min. The pulmonary wedge pressure, lung dynamic compliance, and pulmonary resistance were measured also at the same times. The mean, median, and mode frequencies correlated with pulmonary wedge pressure (P less than 0.00001, P less than 0.0001, P less than 0.0001), lung dynamic compliance (P less than 0.001, P less than 0.0001, P less than 0.0001), and pulmonary resistance (P less than 0.00001, P less than 0.00001, P less than 0.0001), respectively. There were no significant adventitious sounds up to 40 and 50 min after infusion. We concluded that pulmonary congestion and early edema alter the frequency characteristics of lung sounds early, before the occurrence of adventitious sounds. These altered lung sounds may be used as an index of pulmonary congestion and impending edema.

Animals↗