Tidal Volume Lowering by Instrumental Dead Space Reduction in Brain-Injured ARDS Patients: Effects on Respiratory Mechanics, Gas Exchange, and Cerebral Hemodynamics.

BACKGROUND: Limiting tidal volume (VT), plateau pressure, and driving pressure is essential during the acute respiratory distress syndrome (ARDS), but may be challenging when brain injury coexists due to the risk of hypercapnia. Because lowering dead space enhances CO2 clearance, we conducted a study to determine whether and to what extent replacing heat and moisture exchangers (HME) with heated humidifiers (HH) facilitate safe VT lowering in brain-injured patients with ARDS. METHODS: Brain-injured patients (head trauma or spontaneous cerebral hemorrhage with Glasgow Coma Scale at admission < 9) with mild and moderate ARDS received three ventilatory strategies in a sequential order during continuous paralysis: (1) HME with VT to obtain a PaCO2 within 30-35 mmHg (HME1); (2) HH with VT titrated to obtain the same PaCO2 (HH); and (3) HME1 settings resumed (HME2). Arterial blood gases, static and quasi-static respiratory mechanics, alveolar recruitment by multiple pressure-volume curves, intracranial pressure, cerebral perfusion pressure, mean arterial pressure, and mean flow velocity in the middle cerebral artery by transcranial Doppler were recorded. Dead space was measured and partitioned by volumetric capnography. RESULTS: Eighteen brain-injured patients were studied: 7 (39%) had mild and 11 (61%) had moderate ARDS. At inclusion, median [interquartile range] PaO2/FiO2 was 173 [146-213] and median PEEP was 8 cmH2O [5-9]. HH allowed to reduce VT by 120 ml [95% CI: 98-144], VT/kg predicted body weight by 1.8 ml/kg [95% CI: 1.5-2.1], plateau pressure and driving pressure by 3.7 cmH2O [2.9-4.3], without affecting PaCO2, alveolar recruitment, and oxygenation. This was permitted by lower airway (- 84 ml [95% CI: - 79 to - 89]) and total dead space (- 86 ml [95% CI: - 73 to - 98]). Sixteen patients (89%) showed driving pressure equal or lower than 14 cmH2O while on HH, as compared to 7 (39%) and 8 (44%) during HME1 and HME2 (p < 0.001). No changes in mean arterial pressure, cerebral perfusion pressure, intracranial pressure, and middle cerebral artery mean flow velocity were documented during HH. CONCLUSION: The dead space reduction provided by HH allows to safely reduce VT without modifying PaCO2 nor cerebral perfusion. This permits to provide a wider proportion of brain-injured ARDS patients with less injurious ventilation.

EANM guideline for ventilation/perfusion single-photon emission computed tomography (SPECT) for diagnosis of pulmonary embolism and beyond.

These guidelines update the previous EANM 2009 guidelines on the diagnosis of pulmonary embolism (PE). Relevant new aspects are related to (a) quantification of PE and other ventilation/perfusion defects; (b) follow-up of patients with PE; (c) chronic PE; and (d) description of additional pulmonary physiological changes leading to diagnoses of left ventricular heart failure (HF), chronic obstructive pulmonary disease (COPD) and pneumonia. The diagnosis of PE should be reported when a mismatch of one segment or two subsegments is found. For ventilation, Technegas or krypton gas is preferred over diethylene triamine pentaacetic acid (DTPA) in patients with COPD. Tomographic imaging with V/PSPECT has higher sensitivity and specificity for PE compared with planar imaging. Absence of contraindications makes V/PSPECT an essential method for the diagnosis of PE. When V/PSPECT is combined with a low-dose CT, the specificity of the test can be further improved, especially in patients with other lung diseases. Pitfalls in V/PSPECT interpretation are discussed. In conclusion, V/PSPECT is strongly recommended as it accurately establishes the diagnosis of PE even in the presence of diseases like COPD, HF and pneumonia and has no contraindications.

Apparent dead space with the anesthetic conserving device, AnaConDa®: a clinical and laboratory investigation.

BACKGROUND: The anesthetic conserving device (ACD) reduces consumption of volatile anesthetic drug by a conserving medium adsorbing exhaled drug during expiration and releasing it during inspiration. Elevated arterial CO2 tension (PaCO2) has been observed in patients using the ACD, despite tidal volume increase to compensate for larger apparatus dead space. In a test lung using room temperature dry gas, this was shown to be due to adsorption of CO2 in the ACD during expiration and release of CO2 during the following inspiration. The effect in the test lung was higher than in patients. We tested the hypothesis that a lesser dead space effect in patients is due to higher temperature and/or moisture attenuating rebreathing of CO2. METHODS: The lungs of 6 postoperative cardiac surgery patients were ventilated using a conventional heat and moisture exchanger (HME) or an ACD. The ACD was studied with a test lung at varying temperatures and moistures. Infrared spectrometry was used to measure apparent dead space by the single-breath test for CO2 as well as rebreathing of CO2. RESULTS: In patients, the median apparent dead space was 136 mL (95% confidence interval [CI,] 120-167) larger using the ACD compared with an HME (after correction for difference in internal volume 100 and 50 mL, respectively). Median rebreathing of CO2 using the ACD was 53% (range 48-58) of exhaled CO2 compared with 29% (range 27-32) with an HME. The median difference in CO2 rebreathing was 23% (95% CI, 18-27). In the test lung apparent dead space using ACD was unaffected by body temperature but decreased from 360 to 260 mL when moisture was added. This decreased rebreathing of CO2 from 62% to 48%. CONCLUSIONS: The use of an ACD increases apparent dead space to a greater extent than can be explained by its internal volume. This is caused by adsorption of CO2 in the ACD during expiration and release of CO2 during inspiration. Rebreathing of CO2 was attenuated by moisture. The dead space effect of the ACD could be clinically relevant in acute respiratory distress syndrome and other diseases associated with ventilation difficulties, but investigations with larger sample sizes would be needed to determine the clinical importance.

Dead space and CO2 elimination related to pattern of inspiratory gas delivery in ARDS patients.

INTRODUCTION: The inspiratory flow pattern influences CO2 elimination by affecting the time the tidal volume remains resident in alveoli. This time is expressed in terms of mean distribution time (MDT), which is the time available for distribution and diffusion of inspired tidal gas within resident alveolar gas. In healthy and sick pigs, abrupt cessation of inspiratory flow (that is, high end-inspiratory flow (EIF)), enhances CO2 elimination. The objective was to test the hypothesis that effects of inspiratory gas delivery pattern on CO2 exchange can be comprehensively described from the effects of MDT and EIF in patients with acute respiratory distress syndrome (ARDS). METHODS: In a medical intensive care unit of a university hospital, ARDS patients were studied during sequences of breaths with varying inspiratory flow patterns. Patients were ventilated with a computer-controlled ventilator allowing single breaths to be modified with respect to durations of inspiratory flow and postinspiratory pause (TP), as well as the shape of the inspiratory flow wave. From the single-breath test for CO2, the volume of CO2 eliminated by each tidal breath was derived. RESULTS: A long MDT, caused primarily by a long TP, led to importantly enhanced CO2 elimination. So did a high EIF. Effects of MDT and EIF were comprehensively described with a simple equation. Typically, an efficient and a less-efficient pattern of inspiration could result in ± 10% variation of CO2 elimination, and in individuals, up to 35%. CONCLUSIONS: In ARDS, CO2 elimination is importantly enhanced by an inspiratory flow pattern with long MDT and high EIF. An optimal inspiratory pattern allows a reduction of tidal volume and may be part of lung-protective ventilation.

Ventilation/perfusion SPECT in chronic obstructive pulmonary disease: an evaluation by reference to symptoms, spirometric lung function and emphysema, as assessed with HRCT.

PURPOSE: Chronic obstructive pulmonary disease (COPD) is characterized by airflow limitation which is not fully reversible. Despite the heterogeneity of COPD, its diagnosis and staging is currently based solely on forced expiratory volume in 1 s (FEV(1)). FEV(1) does not explain the underlying pathophysiology of airflow limitation. The relationship between FEV(1), symptoms and emphysema extent is weak. Better diagnostic tools are needed to define COPD. Tomographic lung scintigraphy [ventilation/perfusion single photon emission tomography (V/P SPECT)] visualizes regional V and P. In COPD, relations between V/P SPECT, spirometry, high-resolution computed tomography (HRCT) and symptoms have been insufficiently studied. The aim of this study was to investigate how lung function imaging and obstructive disease grading undertaken using V/P SPECT correlate with symptoms, spirometric lung function and degree of emphysema assessed with HRCT in patients with COPD. METHODS: Thirty patients with stable COPD were evaluated with the Medical Research Council dyspnoea questionnaire (MRC) and the clinical COPD questionnaire (CCQ). Spirometry was performed. The extent of emphysema was assessed using HRCT. V/P SPECT was used to assess V/P patterns, total reduction in lung function and degree of obstructive disease. RESULTS: The total reduction in lung function and degree of obstructive disease, assessed with V/P SPECT, significantly correlated with emphysema extent (r = 0.66-0.69, p < 0.0001) and spirometric lung function (r = 0.62-0.74, p < 0.0005). The correlation between emphysema extent and spirometric lung function was weaker. No correlation between MRC, CCQ and objective measurements was found. CONCLUSION: V/P SPECT is sensitive to early changes in COPD. V/P SPECT also has the possibility to identify comorbid disease. V/P SPECT findings show a significant correlation with emphysema extent and spirometric lung function. We therefore recommend that scintigraphic signs of COPD, whenever found, should be reported. V/P SPECT can also be used to categorize the severity of functional changes in COPD as mild, moderate or severe.

Revised rates for the stellar triple-alpha process from measurement of 12C nuclear resonances.

In the centres of stars where the temperature is high enough, three alpha-particles (helium nuclei) are able to combine to form 12C because of a resonant reaction leading to a nuclear excited state. (Stars with masses greater than approximately 0.5 times that of the Sun will at some point in their lives have a central temperature high enough for this reaction to proceed.) Although the reaction rate is of critical significance for determining elemental abundances in the Universe, and for determining the size of the iron core of a star just before it goes supernova, it has hitherto been insufficiently determined. Here we report a measurement of the inverse process, where a 12C nucleus decays to three alpha-particles. We find a dominant resonance at an energy of approximately 11 MeV, but do not confirm the presence of a resonance at 9.1 MeV (ref. 3). We show that interference between two resonances has important effects on our measured spectrum. Using these data, we calculate the triple-alpha rate for temperatures from 10(7) K to 10(10) K and find significant deviations from the standard rates. Our rate below approximately 5 x 10(7) K is higher than the previous standard, implying that the critical amounts of carbon that catalysed hydrogen burning in the first stars are produced twice as fast as previously believed. At temperatures above 10(9) K, our rate is much less, which modifies predicted nucleosynthesis in supernovae.

Re-inspiration of CO(2) from ventilator circuit: effects of circuit flushing and aspiration of dead space up to high respiratory rate.

INTRODUCTION: Dead space negatively influences carbon dioxide (CO(2)) elimination, particularly at high respiratory rates (RR) used at low tidal volume ventilation in acute respiratory distress syndrome (ARDS). Aspiration of dead space (ASPIDS), a known method for dead space reduction, comprises two mechanisms activated during late expiration: aspiration of gas from the tip of the tracheal tube and gas injection through the inspiratory line - circuit flushing. The objective was to study the efficiency of circuit flushing alone and of ASPIDS at wide combinations of RR and tidal volume (V(T)) in anaesthetized pigs. The hypothesis was tested that circuit flushing and ASPIDS are particularly efficient at high RR. METHODS: In Part 1 of the study, RR and V(T) were, with a computer-controlled ventilator, modified for one breath at a time without changing minute ventilation. Proximal dead space in a y-piece and ventilator tubing (VD(aw, prox)) was measured. In part two, changes in CO(2) partial pressure (PaCO(2)) during prolonged periods of circuit flushing and ASPIDS were studied at RR 20, 40 and 60 minutes(-1). RESULTS: In Part 1, VDaw, prox was 7.6 +/- 0.5% of V(T) at RR 10 minutes(-1) and 16 +/- 2.5% at RR 60 minutes(-1). In Part 2, circuit flushing reduced PaCO(2) by 20% at RR 40 minutes(-1) and by 26% at RR 60 minutes(-1). ASPIDS reduced PaCO(2) by 33% at RR 40 minutes(-1) and by 41% at RR 60 minutes(-1). CONCLUSIONS: At high RR, re-breathing of CO(2) from the y-piece and tubing becomes important. Circuit flushing and ASPIDS, which significantly reduce tubing dead space and PaCO2, merit further clinical studies.

Pattern of inspiratory gas delivery affects CO2 elimination in health and after acute lung injury.

OBJECTIVE: To avoid ventilator induced lung injury, tidal volume should be low in acute lung injury (ALI). Reducing dead space may be useful, for example by using a pattern of inspiration that prolongs the time available for gas distribution and diffusion within the respiratory zone, the mean distribution time (MDT). A study was conducted to investigate how MDT affects CO2 elimination in pigs at health and after ALI. DESIGN AND SETTING: Randomised crossover study in the animal laboratory of Lund University Biomedical Center. SUBJECTS AND INTERVENTION: Healthy pigs and pigs with ALI, caused by surfactant perturbation and lung-damaging ventilation were ventilated with a computer-controlled ventilator. With this device each breath could be tailored with respect to insufflation time and pause time (TI and TP) as well as flow shape (square, increasing or decreasing flow). MEASUREMENTS AND RESULTS: The single-breath test for CO2 allowed analysis of the volume of expired CO2 and the volume of CO2 re-inspired from Y-piece and tubes. With a long MDT caused by long TI or TP, the expired volume of CO2 increased markedly in accordance with the MDT concept in both healthy and ALI pigs. High initial inspiratory flow caused by a short TI or decreasing flow increased the re-inspired volume of CO2. Arterial CO2 increased during a longer period of short MDT and decreased again when MDT was prolonged. CONCLUSIONS: CO2 elimination can be enhanced by a pattern of ventilation that prolongs MDT. Positive effects of prolonged MDT caused by short TI and decreasing flow were attenuated by high initial inspiratory flow.

Effects of inspiratory pause on CO2 elimination and arterial PCO2 in acute lung injury.

A high respiratory rate associated with the use of small tidal volumes, recommended for acute lung injury (ALI), shortens time for gas diffusion in the alveoli. This may decrease CO(2) elimination. We hypothesized that a postinspiratory pause could enhance CO(2) elimination and reduce Pa(CO(2)) by reducing dead space in ALI. In 15 mechanically ventilated patients with ALI and hypercapnia, a 20% postinspiratory pause (Tp20) was applied during a period of 30 min between two ventilation periods without postinspiratory pause (Tp0). Other parameters were kept unchanged. The single breath test for CO(2) was recorded every 5 min to measure tidal CO(2) elimination (VtCO(2)), airway dead space (V(Daw)), and slope of the alveolar plateau. Pa(O(2)), Pa(CO(2)), and physiological and alveolar dead space (V(Dphys), V(Dalv)) were determined at the end of each 30-min period. The postinspiratory pause, 0.7 +/- 0.2 s, induced on average <0.5 cmH(2)O of intrinsic positive end-expiratory pressure (PEEP). During Tp20, VtCO(2) increased immediately by 28 +/- 10% (14 +/- 5 ml per breath compared with 11 +/- 4 for Tp0) and then decreased without reaching the initial value within 30 min. The addition of a postinspiratory pause significantly decreased V(Daw) by 14% and V(Dphys) by 11% with no change in V(Dalv). During Tp20, the slope of the alveolar plateau initially fell to 65 +/- 10% of baseline value and continued to decrease. Tp20 induced a 10 +/- 3% decrease in Pa(CO(2)) at 30 min (from 55 +/- 10 to 49 +/- 9 mmHg, P < 0.001) with no significant variation in Pa(O(2)). Postinspiratory pause has a significant influence on CO(2) elimination when small tidal volumes are used during mechanical ventilation for ALI.

The influence of venous admixture on alveolar dead space and carbon dioxide exchange in acute respiratory distress syndrome: computer modelling.

INTRODUCTION: Alveolar dead space reflects phenomena that render arterial partial pressure of carbon dioxide higher than that of mixed alveolar gas, disturbing carbon dioxide exchange. Right-to-left shunt fraction (Qs/Qt) leads to an alveolar dead space fraction (VdAS/VtA; where VtA is alveolar tidal volume). In acute respiratory distress syndrome, ancillary physiological disturbances may include low cardiac output, high metabolic rate, anaemia and acid-base instability. The purpose of the present study was to analyze the extent to which shunt contributes to alveolar dead space and perturbs carbon dioxide exchange in ancillary physiological disturbances. METHODS: A comprehensive model of pulmonary gas exchange was based upon known equations and iterative mathematics. RESULTS: The alveolar dead space fraction caused by shunt increased nonlinearly with Qs/Qt and, under 'basal conditions', reached 0.21 at a Qs/Qt of 0.6. At a Qs/Qt of 0.4, reduction in cardiac output from 5 l/minute to 3 l/minute increased VdAS/VtA from 0.11 to 0.16. Metabolic acidosis further augmented the effects of shunt on VdAS/VtA, particularly with hyperventilation. A Qs/Qt of 0.5 may increase arterial carbon dioxide tension by about 15% to 30% if ventilation is not increased. CONCLUSION: In acute respiratory distress syndrome, perturbation of carbon dioxide exchange caused by shunt is enhanced by ancillary disturbances such as low cardiac output, anaemia, metabolic acidosis and hyperventilation. Maintained homeostasis mitigates the effects of shunt.

Heart failure diagnostics based on ventilation/perfusion single photon emission computed tomography pattern and quantitative perfusion gradients.

OBJECTIVE: Left heart failure (LHF) is a common and frequently overlooked condition owing to insufficient diagnostic methods. This can potentially delay onset of treatment. Our clinical experience with ventilation/perfusion single photon emission computed tomography (V/P SPECT) indicates that perfusion shows an antigravitational distribution pattern in LHF. The aim of the study was to test the hypothesis that LHF diagnosis can be made on the basis of V/P SPECT, and to develop and perform a first evaluation of objective parameters for LHF diagnostics in terms of perfusion gradients. METHODS: This retrospective study included 247 consecutive patients with clinical suspicion of pulmonary embolism (PE), who were examined with V/P SPECT. Perfusion gradients were developed and quantified in dorso-ventral and cranio-caudal directions. Quantitative results were compared with visual interpretation of patients with normal and heart failure patterns. Patients with LHF pattern were retrospectively followed up by review of medical records to confirm or discard heart failure diagnosis at the time of V/P SPECT examination. RESULTS: LHF pattern on V/P SPECT was identified in 36 patients (15%), normal ventilation/perfusion pattern was found in 67 patients (27%), and PE in 62 patients (25%). The follow-up confirmed heart failure diagnosis in 32 of the 36 cases with LHF pattern, leading to a positive predictive value of 88% for LHF diagnosis based on V/P SPECT. Dorso-ventral perfusion gradients discriminated normal from LHF patients. CONCLUSION: In patients with suspected PE, LHF is common. Appropriate V/P SPECT pattern recognition, supported by objectively determined dorso-ventral perfusion gradients, allows the diagnosis of LHF. A positive perfusion gradient in the dorso-ventral direction should lead to consideration of heart failure as a possible explanation for the symptoms in these patients.

The Efficiency Index (EFFi), based on volumetric capnography, may allow for simple diagnosis and grading of COPD.

Background: Spirometry, the main tool for diagnosis and follow-up of COPD, incompletely describes the disease. Based on volumetric capnography (VCap), an index was developed for the diagnosis and grading of COPD, aimed as a complement or alternative to spirometry. Methods: Nine non-smokers, 10 smokers/former smokers without COPD and 54 smokers/former smokers with COPD were included in the study. Multiple breath washout of N2 and VCap were studied with Exhalyzer D during tidal breathing. VCap was based on signals for flow rate and CO2 and was recorded during one breath preceding N2 washout. Efficiency Index (EFFi) is the quotient between exhaled CO2 volume and the hypothetical CO2 volume exhaled from a completely homogeneous lung over a volume interval equal to 15% of predicted total lung capacity. Results: EFFi increased with increased Global initiative for chronic Obstructive Lung Disease (GOLD) stage and the majority of subjects in GOLD 2 and all subjects in GOLD 3 and 4 could be diagnosed as having COPD using the lower 95% confidence interval of the healthy group. EFFi also correlated with N2 washout (r=-0.73; p<0.001), forced expiratory volume in 1 second (r=0.70; p<0.001) and diffusion capacity for carbon oxide (r=0.69; p<0.001). Conclusion: EFFi measures efficiency of tidal CO2 elimination that is limited by inhomogeneity of peripheral lung function. EFFi allows diagnosis and grading of COPD and, together with FEV1, may explain limitation of physical performance. EFFi offers a simple, effortless and cost-effective complement to spirometry and might serve as an alternative in certain situations.

Computer simulation allows goal-oriented mechanical ventilation in acute respiratory distress syndrome.

INTRODUCTION: To prevent further lung damage in patients with acute respiratory distress syndrome (ARDS), it is important to avoid overdistension and cyclic opening and closing of atelectatic alveoli. Previous studies have demonstrated protective effects of using low tidal volume (VT), moderate positive end-expiratory pressure and low airway pressure. Aspiration of dead space (ASPIDS) allows a reduction in VT by eliminating dead space in the tracheal tube and tubing. We hypothesized that, by applying goal-orientated ventilation based on iterative computer simulation, VT can be reduced at high respiratory rate and much further reduced during ASPIDS without compromising gas exchange or causing high airway pressure. METHODS: ARDS was induced in eight pigs by surfactant perturbation and ventilator-induced lung injury. Ventilator resetting guided by computer simulation was then performed, aiming at minimal VT, plateau pressure 30 cmH2O and isocapnia, first by only increasing respiratory rate and then by using ASPIDS as well. RESULTS: VT decreased from 7.2 +/- 0.5 ml/kg to 6.6 +/- 0.5 ml/kg as respiratory rate increased from 40 to 64 +/- 6 breaths/min, and to 4.0 +/- 0.4 ml/kg when ASPIDS was used at 80 +/- 6 breaths/min. Measured values of arterial carbon dioxide tension were close to predicted values. Without ASPIDS, total positive end-expiratory pressure and plateau pressure were slightly higher than predicted, and with ASPIDS they were lower than predicted. CONCLUSION: In principle, computer simulation may be used in goal-oriented ventilation in ARDS. Further studies are needed to investigate potential benefits and limitations over extended study periods.

Effect of inspired oxygen fraction on alveolar derecruitment in acute respiratory distress syndrome.

OBJECTIVE: High fractions of inspired oxygen (FIO(2)) used in acute lung injury (ALI) may promote resorption atelectasis. The impact of derecruitment related to high FIO(2) in ALI is debated. We evaluated derecruitment with 100% vs. 60% FIO(2) at two levels of positive end-expiratory pressure (PEEP). PATIENTS: Fourteen consecutive patients with ALI were studied. INTERVENTIONS: Recruited volume at two PEEP levels was computed from two pressure-volume curves, recorded from PEEP and from zero end-expiratory pressure, using the sinusoidal flow modulation method. PEEP-induced recruitment was measured during prolonged expiration as the difference between the two curves at a given pressure. PaO(2)/FIO(2) was also measured. PEEP was 5 +/- 1 or 14 +/- 3 cmH(2)O and FIO(2) was 60% or 100%, yielding four combinations. We looked for differences between the beginning and end of a 30-min period with each combination. MEASUREMENT AND RESULTS: With low PEEP and 100% FIO(2), recruited volume decreased significantly from 68 +/- 53 to 39 +/- 43 ml and PaO(2)/FIO(2) from 196 +/- 104 to 153 +/- 83 mmHg. With the three other combinations (low PEEP and 60% FIO(2) or high PEEP and 60% or 100% FIO(2)) none of the parameters decreased significantly. CONCLUSION: In mechanically ventilated patients with ALI the breathing of pure oxygen leads to derecruitment, which is prevented by high PEEP.

Relationship between pressure-volume curve and markers for collagen turn-over in early acute respiratory distress syndrome.

OBJECTIVE: In acute respiratory distress syndrome, the relationships between changes in the elastic behavior of the respiratory system and biological markers of extra-cellular matrix or surfactant turn-over could give some insights into its pathophysiological determinants. DESIGN AND MEASUREMENTS: In 17 patients with acute respiratory distress syndrome, we assessed the relationship between chord compliance measured on pressure-volume curves obtained at two levels of positive end-expiratory pressure (0 and 10[Symbol: see text]cm[Symbol: see text]H(2)O) and biological markers of collagen turn-over or surfactant degradation in bronchoalveolar lavage fluid obtained simultaneously in the early phase of the disease (first 4 days). MAIN RESULTS: The compliance of the respiratory system obtained from the pressure-volume curves was significantly correlated with markers for collagen turn-over (type III procollagen peptide and matrix metalloproteinase 2) and with markers of surfactant degradation (type-IIA secretory phospholipase A2). The correlations were stronger when the curve was traced from positive end-expiratory pressure, suggesting that this condition may improve the assessment of tissue mechanics. A logarithmic relationship best described the correlation between compliance and type III procollagen peptide, in agreement with a collagen-dependent model of maximal distension. The marker for surfactant degradation was associated with ongoing alveolar inflammation (cellularity of bronchoalveolar lavage fluid and tumor necrosis factor-alpha concentration). Interleukin-10, an anti-inflammatory mediator, showed no correlation with compliance. CONCLUSION: These preliminary data suggest that a severe reduction in compliance in the early phase of acute respiratory distress syndrome is associated with both collagen deposition and surfactant degradation.

Effects of vertical positioning on gas exchange and lung volumes in acute respiratory distress syndrome.

OBJECTIVE: Supine position may contribute to the loss of aerated lung volume in patients with acute respiratory distress syndrome (ARDS). We hypothesized that verticalization increases lung volume and improves gas exchange by reducing the pressure surrounding lung bases. DESIGN AND SETTING: Prospective observational physiological study in a medical ICU. SUBJECTS AND INTERVENTION: In 16 patients with ARDS we measured arterial blood gases, pressure-volume curves of the respiratory system recorded from positive-end expiratory pressure (PEEP), and changes in lung volume in supine and vertical positions (trunk elevated at 45 degrees and legs down at 45 degrees ). MEASUREMENTS AND RESULTS: Vertical positioning increased PaO(2) significantly from 94+/-33 to 142+/-49 mmHg, with an increase higher than 40% in 11 responders. The volume at 20 cmH(2)O measured on the PV curve from PEEP increased using the vertical position only in responders (233+/-146 vs. -8+/-9 1ml in nonresponders); this change was correlated to oxygenation change (rho=0.55). End-expiratory lung volume variation from supine to vertical and 1 h later back to supine, measured in 12 patients showed a significant increase during the 1-h upright period in responders (n=7) but not in nonresponders (n=5; 215+/-220 vs. 10+/-22 ml), suggesting a time-dependent recruitment. CONCLUSIONS: Vertical positioning is a simple technique that may improve oxygenation and lung recruitment in ARDS patients.

Pressure-volume curves with and without muscle paralysis in acute respiratory distress syndrome.

OBJECTIVE: Pressure-volume (PV) curves are recorded after induction of complete muscle paralysis, which may limit their clinical use. The feasibility of recording PV curves without paralysis has not been tested. In 19 patients with acute respiratory distress syndrome (ARDS) and no hemodynamic instability we prospectively evaluated whether PV curves can be safely and reliably recorded under deep sedation without neuromuscular blockade. METHODS: After standardized sedation (continuous infusion of midazolam and fentanyl) PV curves were recorded during apneic sedation, defined as absence of respiratory effort during a 6-s expiratory pause and during paralysis induced by cis-atracurium. MEASUREMENTS AND RESULTS: Agreement between PV curve parameters in the two conditions was evaluated. Curves were obtained from 10 cmH2O and from zero end-expiratory pressure in all patients under apneic sedation. In five patients propofol was given in addition to midazolam and fentanyl, and in two of them fluid resuscitation was needed. A strong agreement was found for respiratory system compliance and the lower inflection point and for chest wall compliance in the five patients whose esophageal pressure was measured. The variability of the measurements, however, should be taken into account in clinical practice. CONCLUSION: Neuromuscular blockade can be dispensed with when recording PV curves in many ARDS patients. Reliable PV curves can be obtained under anesthesia alone, with no serious adverse effects.