Respiratory mechanics in mechanically ventilated patients with respiratory failure

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

Proteoglycan fragmentation and respiratory mechanics in mechanically ventilated healthy rats.

This research investigated whether stretching of lung tissue due to increased positive alveolar pressure swings during mechanical ventilation (MV) at various tidal volumes (V(T)) might affect the composition and/or structure of the glycosaminoglycan (GAG) components of pulmonary extracellular proteoglycans. Experiments were performed in 30 healthy rats: 1) anesthetized and immediately killed (controls, C-0); 2) anesthetized and spontaneously breathing for 4 h (C-4h); and 3) anesthetized, paralyzed, and mechanically ventilated for 4 h with air at 0-cmH(2)O end-expiratory pressure and V(T) of 8 ml/kg (MV-1), 16 ml/kg (MV-2), 24 ml/kg (MV-3), or 32 ml/kg (MV-4), adjusting respiratory rates at a minute ventilation of 270 ml/min. Compared with C-0 and C-4h, a significant reduction of dynamic and static compliance of the respiratory system and of the lung was observed only in MV-4, while extravascular lung water significantly increased in MV-3 and MV-4, but not in MV-1 and MV-2. However, even in MV-1, MV induced a significant fragmentation of pulmonary GAGs. Extraction of covalently bound GAGs and wash out of loosely bound or fragmented GAGs progressively increased with increasing V(T) and was associated with increased expression of local (matrix metalloproteinase-2) and systemic (matrix metalloproteinase-9) activated metalloproteases. We conclude that 1) MV, even at "physiological" low V(T), severely affects the pulmonary extracellular architecture, exposing the lung parenchyma to development of ventilator-induced lung injury; and 2) respiratory mechanics is not a reliable clinical tool for early detection of lung injury.     

Cardiac output estimation using pulmonary mechanics in mechanically ventilated patients

The application of positive end expiratory pressure (PEEP) in mechanically ventilated (MV) patients with acute respiratory distress syndrome (ARDS) decreases cardiac output (CO). Accurate measurement of CO is highly invasive and is not ideal for all MV critically ill patients. However, the link between the PEEP used in MV, and CO provides an opportunity to assess CO via MV therapy and other existing measurements, creating a CO measure without further invasiveness.     

Prognosis of mechanically ventilated patients.

In this Department of Veterans Affairs cooperative study, we examined predictors of in-hospital and 1-year mortality of 612 mechanically ventilated patients from 6 medical intensive care units in a retrospective cohort design. The outcome variable was vital status at hospital discharge and after 1 year. The results showed that 97% of patients were men, the mean age was 63 +/- 11 years (SD), and hospital mortality was 64% (95% confidence interval, 60% to 68%). Within the next year, an additional 38% of hospital survivors died, for a total 1-year mortality of 77% (95% confidence interval, 73% to 80%). Hospital and 1-year mortality, respectively, for patients older than 70 years was 76% and 94%, for those with serum albumin levels below 20 grams per liter it was 92% and 96%, for those with an Acute Physiology and Chronic Health Evaluation II (APACHE II) score greater than 35 it was 91% and 98%, and for patients who were being mechanically ventilated after cardiopulmonary resuscitation it was 86% and 90%. The mortality ratio (actual mortality versus APACHE II-predicted mortality) was 1.15. Conclusions are that patient age, APACHE II score, serum albumin levels, or the use of cardiopulmonary resuscitation may identify a subset of mechanically ventilated veterans for whom mechanical ventilation provides little or no benefit.     

Partitioning of respiratory mechanics in halothane-anesthetized humans

In five spontaneously breathing anesthetized subjects [halothane approximately 1 minimal alveolar concentration (MAC), 70% N2O, 30% O2], flow, changes in lung volume, and esophageal and airway opening pressure were measured in order to partition the elastance (Ers) and flow resistance (Rrs) of the total respiratory system into the lung and chest wall components. Ers averaged (+/- SD) 23.0 +/- 4.9 cmH2O X l-1, while the corresponding values of pulmonary (EL) and chest wall (EW) elastance were 14.3 +/- 3.2 and 8.7 +/- 3.0 cmH2O X l-1, respectively. Intrinsic Rrs (upper airways excluded) averaged 2.3 +/- 0.2 cmH2O X l-1 X s, the corresponding values for pulmonary (RL) and chest wall (RW) flow resistance amounting to 0.8 +/- 0.4 and 1.5 +/- 0.5 cmH2O X l-1 X s, respectively. Ers increased relative to normal values in awake state, mainly reflecting increased EL. Rw was higher than previous estimates on awake seated subjects (approximately 1.0 cmH2O X l-1 X s). RL was relatively low, reflecting the fact that the subjects had received atropine (0.3-0.6 mg) and were breathing N2O. This is the first study in which both respiratory elastic and flow-resistive properties have been partitioned into lung and chest wall components in anesthetized humans.     

Breathing cardiovascular variability and baroreflex in mechanically ventilated patients

Heart rate and blood pressure variations during spontaneous ventilation are related to the negative airway pressure during inspiration. Inspiratory airway pressure is positive during mechanical ventilation, suggesting that reversal of the normal baroreflex-mediated pattern of variability may occur. We investigated heart rate and blood pressure variability and baroreflex sensitivity in 17 mechanically ventilated patients. ECG (RR intervals), invasive systolic blood pressure (SBP), and respiratory flow signals were recorded. High-frequency (HF) amplitude of RR and SBP time series and HF phase differences between RR, SBP, and ventilatory signals were continuously computed by Complex DeModulation (CDM). Cross-spectral analysis was used to assess the coherence and the gain functions between RR and SBP, yielding baroreflex sensitivity indices. The HF phase difference between SBP and ventilatory signals was nearly constant in all patients with inversion of SBP variability during the ventilator cycle compared with cycling with negative inspiratory pressure to replicate spontaneous breathing. In 12 patients (group 1), the phase difference between RR and ventilatory signals changed over time and the HF-RR amplitude varied. In the remaining five patients (group 2), RR-ventilatory signal phase and HF-RR amplitude showed little change; however, only one of these patients exhibited a RR-ventilatory signal phase difference mimicking the normal pattern of respiratory sinus arrhythmia. Spectral coherence between RR and SBP was lower in the group with phase difference changes. Positive pressure ventilation exerts mainly a mechanical effect on SBP, whereas its influence on HR variability seems more complex, suggesting a role for neural influences.     

Locally measured shear moduli of pulmonary tissue and global lung mechanics in mechanically ventilated rats

This study was aimed at measuring shear moduli in vivo in mechanically ventilated rats and comparing them to global lung mechanics. Wistar rats (n = 28) were anesthetized, tracheally intubated, and mechanically ventilated in supine position. The animals were randomly assigned to the healthy control or the lung injury group where lung injury was induced by bronchoalveolar lavage. The respiratory system elastance E(rs) was analyzed based on the single compartment resistance/elastance lung model using multiple linear regression analysis. The shear modulus (G) of alveolar parenchyma was studied using a newly developed endoscopic system with adjustable pressure at the tip that was designed to induce local mechanostimulation. The data analysis was then carried out with an inverse finite element method. G was determined at continuous positive airway pressure (CPAP) levels of 15, 17, 20, and 30 mbar. The resulting shear moduli of lungs in healthy animals increased from 3.3 ± 1.4 kPa at 15 mbar CPAP to 5.8 ± 2.4 kPa at 30 mbar CPAP (P = 0.012), whereas G was ~2.5 kPa at all CPAP levels for the lung-injured animals. Regression analysis showed a negative correlation between G and relative E(rs) in the control group (r = -0.73, P = 0.008 at CPAP = 20 mbar) and no significant correlation in the lung injury group. These results suggest that the locally measured G were inversely associated with the elastance of the respiratory system. Rejecting the study hypothesis the researchers concluded that low global respiratory system elastance is related to high local resistance against tissue deformation.     

CO(2)-controlled sampling of alveolar gas in mechanically ventilated patients.

A newly designed gas-sampling device using end-tidal CO(2) to separate dead space gas from alveolar gas was evaluated in 12 mechanically ventilated patients. For that purpose, CO(2)-controlled sampling was compared with mixed expiratory sampling. Alveolar sampling valves were easily controlled via CO(2) concentration. Concentrations of four volatile substances were determined in the expired and inspired gas. Isoflurane and isoprene, which did not occur in the inspired air, had ratios of end-tidal to mixed expired concentrations of 1.75 and 1.81, respectively. Acetone and pentane, found in both the inspired and expired air, showed ratios of 0.96 and 1.0, respectively. Precision of concentration measurements was between 2.4% (isoprene) and 11.2% (isoflurane); reproducibility (as coefficient of variation) was 5%. Because the only possible source of isoflurane and isoprene in this setting was patients' blood, selective enrichment of alveolar gas was demonstrated. By using the new sampling technique, sensitivity of breath analysis was nearly doubled.     

Impact of inspired substance concentrations on the results of breath analysis in mechanically ventilated patients.

A well-defined relationship has to exist between substance concentrations in blood and in breath if blood-borne volatile organic compounds (VOCs) are to be used as breath markers of disease or health. In this study, the impact of inspired substances on this relationship was investigated systematically. VOCs were determined in inspired and expired air and in arterial and mixed venous blood of 46 mechanically ventilated patients by means of SPME, GC/MS. Mean inspired concentrations were 25% of expired concentrations for pentane, 7.5% for acetone, 0.7% for isoprene and 0.4% for isoflurane. Only if inspired concentrations were <5% did substance disappearance rates from blood and exhalation rates correlate well. Exhaled substance concentrations depended on venous and inspired concentrations. Patients with sepsis had higher n-pentane and lower acetone concentrations in mixed venous blood than patients without sepsis (2.27 (0.37-8.70) versus 0.65 (0.33-1.48) nmol L-1 and 69 (22-99) versus 18 (6.7-56) micromol L-1). n-Pentane and acetone concentrations in breath showed no differences between the patient groups, regardless whether or not expired concentrations were corrected for inspired concentrations. In mechanically ventilated patients, concentration profiles of volatile substances in breath may considerably deviate from profiles in blood depending on the relative amount of inspired concentrations. A simple correction for inspired substance concentrations was not possible. Hence, substances having inspired concentrations>5% of expired concentrations should not be used as breath markers in these patients without knowledge of concentrations in blood and breath.     

Model-based optimal PEEP in mechanically ventilated ARDS patients in the Intensive Care Unit

Background

Swallowing accelerometry has been suggested as a potential non-invasive tool for bedside dysphagia screening. Various vibratory signal features and complementary measurement modalities have been put forth in the literature for the potential discrimination between safe and unsafe swallowing. To date, automatic classification of swallowing accelerometry has exclusively involved a single-axis of vibration although a second axis is known to contain additional information about the nature of the swallow. Furthermore, the only published attempt at automatic classification in adult patients has been based on a small sample of swallowing vibrations.

Methods

In this paper, a large corpus of dual-axis accelerometric signals were collected from 30 older adults (aged 65.47 ± 13.4 years, 15 male) referred to videofluoroscopic examination on the suspicion of dysphagia. We invoked a reputation-based classifier combination to automatically categorize the dual-axis accelerometric signals into safe and unsafe swallows, as labeled via videofluoroscopic review. From these participants, a total of 224 swallowing samples were obtained, 164 of which were labeled as unsafe swallows (swallows where the bolus entered the airway) and 60 as safe swallows. Three separate support vector machine (SVM) classifiers and eight different features were selected for classification.

Results

With selected time, frequency and information theoretic features, the reputation-based algorithm distinguished between safe and unsafe swallowing with promising accuracy (80.48 ± 5.0%), high sensitivity (97.1 ± 2%) and modest specificity (64 ± 8.8%). Interpretation of the most discriminatory features revealed that in general, unsafe swallows had lower mean vibration amplitude and faster autocorrelation decay, suggestive of decreased hyoid excursion and compromised coordination, respectively. Further, owing to its performance-based weighting of component classifiers, the static reputation-based algorithm outperformed the democratic majority voting algorithm on this clinical data set.

Conclusion

Given its computational efficiency and high sensitivity, reputation-based classification of dual-axis accelerometry ought to be considered in future developments of a point-of-care swallow assessment where clinical informatics are desired.     

Effects of endotoxic shock on diaphragmatic function in mechanically ventilated rats.

Diaphragmatic function was investigated in mechanically ventilated rats during endotoxic shock (group E, n = 18) and after saline solution injection (group C, n = 8). Endotoxic shock was produced by a 1-min injection of Escherichia coli endotoxin (10 mg/kg iv) suspended in saline. Diaphragmatic strength was assessed before (T0) and 15 (T15) and 60 (T60) min after injection by measuring transdiaphragmatic pressure (Pdi) generated during bilateral phrenic stimulation at 0.5, 10, 20, 30, 50, and 100 Hz. Diaphragmatic neuromuscular transmission was assessed by measuring the integrated electrical activity of the diaphragm. Diaphragmatic endurance was assessed 75 min after injection from the rate of Pdi decline after a 30-s continuous 10-Hz phrenic stimulation. In 16 additional animals, diaphragmatic glycogen content was determined 60 min after inoculation with endotoxin (n = 8) or 0.9% sodium chloride solution (n = 8). Diaphragmatic resting membrane potential (Em) was measured in 16 additional animals 60 min after endotoxin (n = 8) or saline injection (n = 8). Mean blood pressure decreased from 74 +/- 3 to 53 +/- 6 mmHg at T60 in group E, whereas it was maintained in group C. At T60 Pdi was decreased in group E for frequencies of 50 and 100 Hz and was associated with a decreased diaphragmatic electromyographic activity of 25.3 +/- 2.5 and 26.5 +/- 5.2% for 50- and 100-Hz stimulations, respectively, in comparison with T0 values.(ABSTRACT TRUNCATED AT 250 WORDS)     

Functional residual capacity and ventilation homogeneity in mechanically ventilated small neonates.

A modification of a computerized tracer gas (SF6) washout method was designed for serial measurements of functional residual capacity (FRC) and ventilation homogeneity in mechanically ventilated very-low-birth-weight infants with tidal volumes down to 4 ml. The method, which can be used regardless of the inspired O2 concentration, gave accurate and reproducible results in a lung model and good agreement compared with He dilution in rabbits. FRC was measured during 2-4 cmH2O of positive end-expiratory pressure (PEEP) in 15 neonates (700-1,950 g), most of them with mild-to-moderate respiratory distress syndrome. FRC increased with body weight and decreased (P less than 0.05) with increasing O2 requirement. Change to zero end-expiratory pressure caused an immediate decrease in FRC by 29% (P less than 0.01) and gave FRC (ml) = -1.4 + 17 x weight (kg) (r = 0.83). Five minutes after PEEP was discontinued (n = 12), FRC had decreased by a further 16% (P less than 0.01). The washout curves indicated a near-normal ventilation homogeneity not related to changes in PEEP. This was interpreted as evidence against the presence of large volumes of trapped alveolar gas.     

Raising end-expiratory volume relieves air hunger in mechanically ventilated healthy adults.

Air hunger is an unpleasant urge to breathe and a distressing respiratory symptom of cardiopulmonary patients. An increase in tidal volume relieves air hunger, possibly by increasing pulmonary stretch receptor cycle amplitude. The purpose of this study was to determine whether increasing end-expiratory volume (EEV) also relieves air hunger. Six healthy volunteers (3 women, 31 +/- 4 yr old) were mechanically ventilated via a mouthpiece (12 breaths/min, constant end-tidal Pco(2)) at high minute ventilation (Ve; 12 +/- 2 l/min, control) and low Ve (6 +/- 1 l/min, air hunger). EEV was raised to approximately 150, 400, 725, and 1,000 ml by increasing positive end-expiratory pressure (PEEP) to 2, 4, 6, and 8 cmH(2)O, respectively, for 1 min during high and low Ve. The protocol was repeated with the subjects in the seated and supine positions to test for the effect of shifting baseline EEV. Air hunger intensity was rated at the end of each breath on a visual analog scale. The increase in EEV was the same in the seated and supine positions; however, air hunger was reduced to a greater extent in the seated position (13, 30, 31, and 44% seated vs. 3, 9, 23, and 27% supine at 2, 4, 6, and 8 cmH(2)O PEEP, respectively, P < 0.05). Removing PEEP produced a slight increase in air hunger that was greater than pre-PEEP levels (P < 0.05). Air hunger is relieved by increases in EEV and tidal volume (presumably via an increase in mean pulmonary stretch receptor activity and cycle amplitude, respectively).