Post-COVID changes in lung function 6 months after veno-venous extracorporeal membrane oxygenation: a prospective observational clinical trial.

Background: Severe coronavirus disease 2019 (COVID-19) may require veno-venous extracorporeal membrane oxygenation (V-V ECMO). While V-V ECMO is offered in severe lung injury to COVID-19, long-term respiratory follow-up in these patients is missing. Therefore, we aimed at providing comprehensive data on the long-term respiratory effects of COVID-19 requiring V-V ECMO support during the acute phase of infection. Methods: In prospective observational cohort study design, patients with severe COVID-19 receiving invasive mechanical ventilation and V-V ECMO (COVID group, n = 9) and healthy matched controls (n = 9) were evaluated 6 months after hospital discharge. Respiratory system resistance at 5 and 19 Hz (R5, R19), and the area under the reactance curve (AX5) was evaluated using oscillometry characterizing total and central airway resistances, and tissue elasticity, respectively. R5 and R19 difference (R5-R19) reflecting small airway function was also calculated. Forced expired volume in seconds (FEV1), forced expiratory vital capacity (FVC), functional residual capacity (FRC), carbon monoxide diffusion capacity (DLCO) and transfer coefficient (KCO) were measured. Results: The COVID group had a higher AX5 and R5-R19 than the healthy matched control group. However, there was no significant difference in terms of R5 or R19. The COVID group had a lower FEV1 and FVC on spirometry than the healthy matched control group. Further, the COVID group had a lower FRC on plethysmography than the healthy matched control group. Meanwhile, the COVID group had a lower DLCO than healthy matched control group. Nevertheless, its KCO was within the normal range. Conclusion: Severe acute COVID-19 requiring V-V ECMO persistently impairs small airway function and reduces respiratory tissue elasticity, primarily attributed to lung restriction. These findings also suggest that even severe pulmonary pathologies of acute COVID-19 can manifest in a moderate but still persistent lung function impairment 6 months after hospital discharge. Trial registration: NCT05812196.

Expiratory high-frequency percussive ventilation: a novel concept for improving gas exchange.

BACKGROUND: Although high-frequency percussive ventilation (HFPV) improves gas exchange, concerns remain about tissue overdistension caused by the oscillations and consequent lung damage. We compared a modified percussive ventilation modality created by superimposing high-frequency oscillations to the conventional ventilation waveform during expiration only (eHFPV) with conventional mechanical ventilation (CMV) and standard HFPV. METHODS: Hypoxia and hypercapnia were induced by decreasing the frequency of CMV in New Zealand White rabbits (n = 10). Following steady-state CMV periods, percussive modalities with oscillations randomly introduced to the entire breathing cycle (HFPV) or to the expiratory phase alone (eHFPV) with varying amplitudes (2 or 4 cmH2O) and frequencies were used (5 or 10 Hz). The arterial partial pressures of oxygen (PaO2) and carbon dioxide (PaCO2) were determined. Volumetric capnography was used to evaluate the ventilation dead space fraction, phase 2 slope, and minute elimination of CO2. Respiratory mechanics were characterized by forced oscillations. RESULTS: The use of eHFPV with 5 Hz superimposed oscillation frequency and an amplitude of 4 cmH2O enhanced gas exchange similar to those observed after HFPV. These improvements in PaO2 (47.3 ± 5.5 vs. 58.6 ± 7.2 mmHg) and PaCO2 (54.7 ± 2.3 vs. 50.1 ± 2.9 mmHg) were associated with lower ventilation dead space and capnogram phase 2 slope, as well as enhanced minute CO2 elimination without altering respiratory mechanics. CONCLUSIONS: These findings demonstrated improved gas exchange using eHFPV as a novel mechanical ventilation modality that combines the benefits of conventional and small-amplitude high-frequency oscillatory ventilation, owing to improved longitudinal gas transport rather than increased lung surface area available for gas exchange.

Flow-controlled ventilation maintains gas exchange and lung aeration in a pediatric model of healthy and injured lungs: A randomized cross-over experimental study.

Flow-controlled ventilation (FCV) is characterized by a constant flow to generate active inspiration and expiration. While the benefit of FCV on gas exchange has been demonstrated in preclinical and clinical studies with adults, the value of this modality for a pediatric population remains unknown. Thus, we aimed at observing the effects of FCV as compared to pressure-regulated volume control (PRVC) ventilation on lung mechanics, gas exchange and lung aeration before and after surfactant depletion in a pediatric model. Ten anesthetized piglets (10.4 ± 0.2 kg) were randomly assigned to start 1-h ventilation with FCV or PRVC before switching the ventilation modes for another hour. This sequence was repeated after inducing lung injury by bronchoalveolar lavage and injurious ventilation. The primary outcome was respiratory tissue elastance. Secondary outcomes included oxygenation index (PaO2/FiO2), PaCO2, intrapulmonary shunt (Qs/Qt), airway resistance, respiratory tissue damping, end-expiratory lung volume, lung clearance index and lung aeration by chest electrical impedance tomography. Measurements were performed at the end of each protocol stage. Ventilation modality had no effect on any respiratory mechanical parameter. Adequate gas exchange was provided by FCV, similar to PRVC, with sufficient CO2 elimination both in healthy and surfactant-depleted lungs (39.46 ± 7.2 mmHg and 46.2 ± 11.4 mmHg for FCV; 36.0 ± 4.1 and 39.5 ± 4.9 mmHg, for PRVC, respectively). Somewhat lower PaO2/FiO2 and higher Qs/Qt were observed in healthy and surfactant depleted lungs during FCV compared to PRVC (p < 0.05, for all). Compared to PRVC, lung aeration was significantly elevated, particularly in the ventral dependent zones during FCV (p < 0.05), but this difference was not evidenced in injured lungs. Somewhat lower oxygenation and higher shunt ratio was observed during FCV, nevertheless lung aeration improved and adequate gas exchange was ensured. Therefore, in the absence of major differences in respiratory mechanics and lung volumes, FCV may be considered as an alternative in ventilation therapy of pediatric patients with healthy and injured lungs.

Effect of body position on the redistribution of regional lung aeration during invasive and non-invasive ventilation of COVID-19 patients.

Severe COVID-19-related acute respiratory distress syndrome (C-ARDS) requires mechanical ventilation. While this intervention is often performed in the prone position to improve oxygenation, the underlying mechanisms responsible for the improvement in respiratory function during invasive ventilation and awake prone positioning in C-ARDS have not yet been elucidated. In this prospective observational trial, we evaluated the respiratory function of C-ARDS patients while in the supine and prone positions during invasive (n = 13) or non-invasive ventilation (n = 15). The primary endpoint was the positional change in lung regional aeration, assessed with electrical impedance tomography. Secondary endpoints included parameters of ventilation and oxygenation, volumetric capnography, respiratory system mechanics and intrapulmonary shunt fraction. In comparison to the supine position, the prone position significantly increased ventilation distribution in dorsal lung zones for patients under invasive ventilation (53.3 ± 18.3% vs. 43.8 ± 12.3%, percentage of dorsal lung aeration ± standard deviation in prone and supine positions, respectively; p = 0.014); whereas, regional aeration in both positions did not change during non-invasive ventilation (36.4 ± 11.4% vs. 33.7 ± 10.1%; p = 0.43). Prone positioning significantly improved the oxygenation both during invasive and non-invasive ventilation. For invasively ventilated patients reduced intrapulmonary shunt fraction, ventilation dead space and respiratory resistance were observed in the prone position. Oxygenation is improved during non-invasive and invasive ventilation with prone positioning in patients with C-ARDS. Different mechanisms may underly this benefit during these two ventilation modalities, driven by improved distribution of lung regional aeration, intrapulmonary shunt fraction and ventilation-perfusion matching. However, the differences in the severity of C-ARDS may have biased the sensitivity of electrical impedance tomography when comparing positional changes between the protocol groups.Trial registration: ClinicalTrials.gov (NCT04359407) and Registered 24 April 2020, https://clinicaltrials.gov/ct2/show/NCT04359407 .

Sevoflurane and Hypercapnia Blunt the Physiological Variability of Spontaneous Breathing: A Comparative Interventional Study.

Background: Although spontaneous breathing is known to exhibit substantial physiological fluctuation that contributes to alveolar recruitment, changes in the variability of the respiratory pattern following inhalation of carbon dioxide (CO2) and volatile anesthetics have not been characterized. Therefore, we aimed at comparing the indices of breathing variability under wakefulness, sleep, hypercapnia and sedative and anesthetic concentrations of sevoflurane. Methods: Spontaneous breathing pattern was recorded on two consecutive days in six rabbits using open whole-body plethysmography under wakefulness and spontaneous sleep and following inhalation of 5% CO2, 2% sevoflurane (0.5 MAC) and 4% (1 MAC) sevoflurane. Tidal volume (VT), respiratory rate (RR), minute ventilation (MV), inspiratory time (TI) and mean inspiratory flow (VT/TI) were calculated from the pressure fluctuations in the plethysmograph. Means and coefficients of variation were calculated for each measured variable. Autoregressive model fitting was applied to estimate the relative contributions of random, correlated, and oscillatory behavior to the total variance. Results: Physiological sleep decreased MV by lowering RR without affecting VT. Hypercapnia increased MV by elevating VT. Sedative and anesthetic concentrations of sevoflurane increased VT but decreased MV due to a decrease in RR. Compared to the awake stage, CO2 had no effect on VT/TI while sevoflurane depressed significantly the mean inspiratory flow. Compared to wakefulness, the variability in VT, RR, MV, TI and VT/TI were not affected by sleep but were all significantly decreased by CO2 and sevoflurane. The variance of TI originating from correlated behavior was significantly decreased by both concentrations of sevoflurane compared to the awake and asleep conditions. Conclusions: The variability of spontaneous breathing during physiological sleep and sevoflurane-induced anesthesia differed fundamentally, with the volatile agent diminishing markedly the fluctuations in respiratory volume, inspiratory airflow and breathing frequency. These findings may suggest the increased risk of lung derecruitment during procedures under sevoflurane in which spontaneous breathing is maintained.

Physiologically variable ventilation prevents lung function deterioration in a model of pulmonary fibrosis.

Positive pressure ventilation exerts an increased stress and strain in the presence of pulmonary fibrosis. Thus, ventilation strategies that avoid high pressures while maintaining lung aeration are of paramount importance. Although physiologically variable ventilation (PVV) has proven beneficial in various models of pulmonary disease, its potential advantages in pulmonary fibrosis have not been investigated. Therefore, we assessed the benefit of PVV over conventional pressure-controlled ventilation (PCV) in a model of pulmonary fibrosis. Lung fibrosis was induced with intratracheal bleomycin in rabbits. Fifty days later, the animals were randomized to receive 6 h of either PCV (n = 10) or PVV (n = 11). The PVV pattern was prerecorded in spontaneously breathing, healthy rabbits. Respiratory mechanics and gas exchange were assessed hourly; end-expiratory lung volume and intrapulmonary shunt fraction were measured at hours 0 and 6. Histological and cellular analyses were performed. Fifty days after bleomycin treatment, the rabbits presented elevated specific airway resistance [69 ± 26% (mean ± 95% confidence interval)], specific tissue damping (38 ± 15%), and specific elastance (47 ± 16%) along with histological evidence of fibrosis. Six hours of PCV led to increased respiratory airway resistance (Raw, 111 ± 30%), tissue damping (G, 36 ± 13%) and elastance (H, 58 ± 14%), and decreased end-expiratory lung volume (EELV, -26 ± 7%) and oxygenation ([Formula: see text]/[Formula: see text], -14 ± 5%). The time-matched changes in the PVV group were significantly lower for G (22 ± 9%), H (41 ± 6%), EELV (-13 ± 6%), and [Formula: see text]/[Formula: see text] ratio (-3 ± 5%, P < 0.05 for all). There was no difference in histopathology between the ventilation modes. Thus, prolonged application of PVV prevented the deterioration of gas exchange by reducing atelectasis development in bleomycin-induced lung fibrosis.NEW & NOTEWORTHY The superposition of physiological breathing variability onto a conventional pressure signal during prolonged mechanical ventilation prevents atelectasis development in bleomycin-induced lung fibrosis. This advantage is evidenced by reduced deterioration in tissue mechanics, end-expiratory lung volume, ventilation homogeneity, and gas exchange.

Dopamine Reverses Lung Function Deterioration After Cardiopulmonary Bypass Without Affecting Gas Exchange.

OBJECTIVE: To investigate the effects of dopamine on the adverse pulmonary changes after cardiopulmonary bypass. DESIGN: A prospective, nonrandomized clinical investigation. SETTING: A university hospital. PARTICIPANTS: One hundred fifty-seven patients who underwent elective cardiac surgery that required cardiopulmonary bypass. INTERVENTIONS: Fifty-two patients were administered intravenous infusion of dopamine (3 µg/kg/min) for five minutes after weaning from cardiopulmonary bypass; no intervention was applied in the other 105 patients. MEASUREMENTS AND MAIN RESULTS: Measurements were performed under general anesthesia and mechanical ventilation before cardiopulmonary bypass, after cardiopulmonary bypass, and after the intervention. In each protocol stage, forced oscillatory lung impedance was measured to assess airway and tissue mechanical changes. Mainstream capnography was performed to assess ventilation- and/or perfusion-matching by calculating the normalized phase-3 slopes of the time and volumetric capnograms and the physiologic deadspace. Arterial and central venous blood samples were analyzed to characterize lung oxygenation and intrapulmonary shunt. After cardiopulmonary bypass, dopamineinduced marked improvements in airway resistance and tissue damping, with relatively small decreases in lung tissue elastance. These changes were associated with decreases in the normalized phase-3 slopes of the time and volumetric capnograms. The inotrope had no effect on physiologic deadspace, intrapulmonary shunt, or lung oxygenation. CONCLUSION: Dopamine reversed the complex detrimental lung mechanical changes induced by cardiopulmonary bypass and alleviated ventilation heterogeneities without affecting the physiologic deadspace or intrapulmonary shunt. Therefore, dopamine has a potential benefit on the gas exchange abnormalities after weaning from cardiopulmonary bypass.

Obesity and diabetes: similar respiratory mechanical but different gas exchange defects.

Diabetes mellitus increases smooth muscle tone and causes tissue remodeling, affecting elastin and collagen. Although the lung is dominated by these elements, diabetes is expected to modify the airway function and respiratory tissue mechanics. Therefore, we characterized the respiratory function in patients with diabetes with and without associated obesity. Mechanically ventilated patients with normal body shapes were divided into the control nondiabetic (n = 73) and diabetic (n = 31) groups. The other two groups included obese patients without diabetes (n = 43) or with diabetes (n = 30). The mechanical properties of the respiratory system were determined by forced oscillation technique. Airway resistance (Raw), tissue damping (G), and tissue elastance (H) were assessed by forced oscillation. Capnography was applied to determine phase 3 slopes and dead space indices. The intrapulmonary shunt fraction (Qs/Qt) and the lung oxygenation index (PaO2/FIO2) were estimated from arterial and central venous blood samples. Compared with the corresponding control groups, diabetes alone increased the Raw (7.6 ± 6 cmH2O.s/l vs. 3.1 ± 1.9 cmH2O.s/l), G (11.7 ± 5.5 cmH2O/l vs. 6.5 ± 2.8 cmH2O/l), and H (31.5 ± 11.8 cmH2O/l vs. 24.2 ± 7.2 cmH2O/l (P < 0.001 for all). Diabetes increased the capnographic phase 3 slope, whereas PaO2/FIO2 or Qs/Qt was not affected. Obesity alone caused similar detrimental changes in respiratory mechanics and alveolar heterogeneity, but these alterations also compromised gas exchange. We conclude that diabetes-induced intrinsic mechanical abnormalities are counterbalanced by hypoxic pulmonary vasoconstriction, which maintained intrapulmonary shunt fraction and oxygenation ability of the lungs.

Optimal crystalloid volume ratio for blood replacement for maintaining hemodynamic stability and lung function: an experimental randomized controlled study.

BACKGROUND: Crystalloids are first line in fluid resuscitation therapy, however there is a lack of evidence-based recommendations on the volume to be administered. Therefore, we aimed at comparing the systemic hemodynamic and respiratory effects of volume replacement therapy with a 1:1 ratio to the historical 1:3 ratio. METHODS: Anesthetized, ventilated rats randomly included in 3 groups: blood withdrawal and replacement with crystalloid in 1:1 ratio (Group 1, n = 11), traditional 1:3 ratio (Group 3, n = 12) and a control group with no interventions (Group C, n = 9). Arterial blood of 5% of the total blood volume was withdrawn 7 times, and replaced stepwise with different volume rations of Ringer's acetate, according to group assignments. Airway resistance (Raw), respiratory tissue damping (G) and tissue elastance (H), mean arterial pressure (MAP) and heart rate (HR) were assessed following each step of fluid replacement with a crystalloid (CR1-CR6). Lung edema index was measured from histological samples. RESULTS: Raw decreased in Groups 1 and 3 following CR3 (p < 0.02) without differences between the groups. H elevated in all groups (p < 0.02), with significantly higher changes in Group 3 compared to Groups C and 1 (both p = 0.03). No differences in MAP or HR were present between Groups 1 and 3. Lung edema was noted in Group 3 (p < 0.05). CONCLUSIONS: Fluid resuscitation therapy by administering a 1:1 blood replacement ratio revealed adequate compensation capacity and physiological homeostasis similar with no lung stiffening and pulmonary edema. Therefore, considering this ratio promotes the restrictive fluid administration in the presence of continuous and occult bleeding.

Dopamine ameliorates bronchoconstriction induced by histaminergic and cholinergic pathways in rabbits.

To clarify the potential of dopamine to alter airway tone in the presence of different bronchoconstrictor stimuli, changes in airway function following dopamine administrations were characterized when the bronchial tone was elevated by stimulating the histaminic or cholinergic pathway. Airway resistance, tissue damping and tissue elastance were measured in anesthetized mechanically ventilated rabbits under baseline conditions, during steady-state bronchoconstriction induced by methacholine or histamine, and following intravenous dopamine (5 and 15 µg/kg/min). Bronchoconstriction induced by methacholine and histamine was significantly ameliorated by dopamine (14.8 ± 2.9% and 14.9 ± 2.9%; p < 0.05 for both), with no difference between the mode of stimuli. Dopamine had no effect on the tissue mechanics. These findings indicate that dopamine relaxes the elevated airway smooth muscle tone without affecting the lung periphery, and this effect is independent of the mode of constrictor stimuli. This profile of dopamine suggests its ability to treat effectively cholinergic and histaminergic bronchoconstriction, besides its positive inotropic effects on the myocardial contractility.

Levosimendan prevents bronchoconstriction and adverse respiratory tissue mechanical changes in rabbits.

Levosimendan has a calcium-sensitizing effect in the myocardium and opens ATP-sensitive potassium channels (KATP) in vascular smooth muscle. Because airway smooth muscle also expresses KATP, we characterized the protective potential of levosimendan against increased airway and respiratory tissue resistances. Animals were administered levosimendan alone (group L), levosimendan after pretreatment with a KATP channel blocker (glibenclamide, group LG), glibenclamide only (group G), or solvent alone (dextrose, group C). Airway resistance (Raw), tissue damping, and elastance were determined by forced oscillations under baseline conditions and following provocation tests with intravenous methacholine (MCh). Cardiac output (CO) was assessed by transpulmonary thermodilution. The same sequence of measurements was then repeated during intravenous infusion of levosimendan in groups L and LG or glucose in groups G and C Sham treatments in groups C and G had no effect on lung responsiveness. However, levosimendan treatment in group L elevated CO and inhibited the MCh-induced airway responses [Raw changes of 87.8 ± 83% (SD) vs. 24.4 ± 16% at 4 µg·kg-1·min-1 MCh, P < 0.001], and in G (35.2 ± 12.7 vs. 25.2 ± 12.9%, P < 0.05). The preventive affect of levosimendan against lung constriction vanished in the LG group. Levosimendan exerts a KATP-mediated potential to prevent bronchoconstriction and may prohibit adverse lung peripheral changes both in the small bronchi and the pulmonary parenchyma. The identification of a further pleiotropic property of levosimendan that is related to the pulmonary system is of particular importance for patients with decreased cardiorespiratory reserves for which simultaneous circulatory support is complemented with prevention of adverse respiratory events.

Sevoflurane Relieves Lung Function Deterioration After Cardiopulmonary Bypass.

OBJECTIVE: To investigate sevoflurane's potential to alleviate the detrimental pulmonary changes after cardiopulmonary bypass (CPB). DESIGN: Prospective, randomized clinical investigation. SETTING: University hospital. PARTICIPANTS: One hundred ninety patients undergoing elective cardiac surgery. INTERVENTIONS: Ninety-nine patients under intravenous anesthesia were administered 1 minimal alveolar concentration of sevoflurane for 5 minutes after being weaned from CPB (group SEV); intravenous anesthesia was maintained in the other 91 patients (group CTRL). MEASUREMENTS AND MAIN RESULTS: Measurements were performed with open chest: before CPB, after CPB, and after intervention. The lungs' mechanical impedance and capnogram traces were recorded, arterial and central venous blood samples were analyzed, and lung compliance was documented. Airway resistance, tissue damping, and elastance were obtained from the impedance spectra. The capnogram phase III slope was determined using linear regression. The partial pressure of oxygen in the arterial blood/fraction of inspired oxygen ratio and shunt fraction were calculated from blood gas parameters. After CPB, sevoflurane induced bronchodilation, reflected in marked drops in airway resistance and smaller improvements in lung tissue viscoelasticity indicated by decreases in tissue damping and elastance. These changes were reflected in a decreased capnogram phase III slope and shunt fraction and increased partial pressure of oxygen in the arterial blood/fraction of inspired oxygen ratio and lung compliance. The more severe deteriorations that occurred after CPB, the greater improvements by sevoflurane were observed. CONCLUSIONS: Sevoflurane can alleviate CPB-induced bronchoconstriction, compromised lung tissue mechanics, and enhanced intrapulmonary shunt. This benefit has particular importance in patients with severe CPB-induced lung function deterioration.

Capnographic Parameters in Ventilated Patients: Correspondence with Airway and Lung Tissue Mechanics.

BACKGROUND: Although the mechanical status of the lungs affects the shape of the capnogram, the relations between the capnographic parameters and those reflecting the airway and lung tissue mechanics have not been established in mechanically ventilated patients. We, therefore, set out to characterize how the mechanical properties of the airways and lung tissues modify the indices obtained from the different phases of the time and volumetric capnograms and how the lung mechanical changes are reflected in the altered capnographic parameters after a cardiopulmonary bypass (CPB). METHODS: Anesthetized, mechanically ventilated patients (n = 101) undergoing heart surgery were studied in a prospective consecutive cross-sectional study under the open-chest condition before and 5 minutes after CPB. Forced oscillation technique was applied to measure airway resistance (Raw), tissue damping (G), and elastance (H). Time and volumetric capnography were performed to assess parameters reflecting the phase II (SII) and phase III slopes (SIII), their transition (D2min), the dead-space indices according to Fowler, Bohr, and Enghoff and the intrapulmonary shunt. RESULTS: Before CPB, SII and D2min exhibited the closest (P = 0.006) associations with H (0.65 and -0.57; P < 0.0001, respectively), whereas SIII correlated most strongly (P < 0.0001) with Raw (r = 0.63; P < 0.0001). CPB induced significant elevations in Raw and G and H (P < 0.0001). These adverse mechanical changes were reflected consistently in SII, SIII, and D2min, with weaker correlations with the dead-space indices (P < 0.0001). The intrapulmonary shunt expressed as the difference between the Enghoff and Bohr dead-space parameters was increased after CPB (95% ± 5% [SEM] vs 143% ± 6%; P < 0.001). CONCLUSIONS: In mechanically ventilated patients, the capnographic parameters from the early phase of expiration (SII and D2min) are linked to the pulmonary elastic recoil, whereas the effect of airway patency on SIII dominates over the lung tissue stiffness. However, severe deterioration in lung resistance or elastance affects both capnogram slopes.

Fluid replacement and respiratory function: comparison of whole blood with colloid and crystalloid: A randomised animal study.

BACKGROUND: Fluid replacement with blood products, colloids and crystalloids is associated with morbidity and mortality. Despite this, the consequences of fluid administration on airway and respiratory tissue properties are not fully understood. OBJECTIVE: Comparison of respiratory effects of fluid replacement with autologous blood (Group B), colloid (HES 6% 130/0.4, Group CO) or crystalloid solution (NaCl 0.9%, Group CR) after haemorrhage with separate assessments of airway resistance and respiratory tissue mechanics. DESIGN: A randomised study. SETTING: An experimental model of surgical haemorrhage and fluid replacement in rats. PARTICIPANTS: Anaesthetised, ventilated rats randomly allocated into three groups (Group B: n = 8, Group CO: n = 8, Group CR: n = 9). INTERVENTION: Animals were bled in six sequential steps, each manoeuvre targeting a loss of 5% of total blood volume. The blood loss was then replaced stepwise in a 1 : 1 ratio with one of the three fluids. MAIN OUTCOME MEASURE: After each step, airway resistance (Raw), tissue damping and elastance (H) were determined by forced oscillations. Oedema indices from lung weights and histology were also measured. RESULTS: Raw (mean ±â€ŠSD) decreased in all groups following blood loss (-20.3 ±â€Š9.5% vs. baseline, P < 0.05), and remained low following blood replacement (-21.7 ±â€Š14.5% vs. baseline, P < 0.05), but was normalised by colloid (5.5 ±â€Š10.7%, NS). Crystalloid administration exhibited an intermediate reversal effect (-8.4 ±â€Š14.7%, NS). Tissue viscoelasticity increased following both blood loss and replacement, with no evidence of a significant difference in H between Groups CO and CR. More severe oedema was observed in Groups CR and CO than in Group B (P < 0.05), with no difference between the colloid and crystalloid solutions. CONCLUSION: This model, which mimics surgical haemorrhage, yields no evidence of a difference between colloids and crystalloids with regard to the pulmonary consequences of blood volume restoration. Functional changes in the lung should not be a key concern when choosing fluid replacement therapy with these solutions.

Lung mechanical changes following bronchoaspiration in a porcine model: differentiation of direct and indirect mechanisms.

Bronchoaspiration results in local deterioration of lung function through direct damage and/or indirect systemic effects related to neurohumoral pathways. We distinguished these effects by selectively intubating the two main bronchi in pigs while a PEEP of 4 or 10cm H2O was maintained. Gastric juice was instilled only into the right lung. Lung mechanical and ventilation defects were assessed by measuring unilateral pulmonary input impedance (ZL,s) and the third phase slope of the capnogram (SIII) for each lung side separately before the aspiration and for 120min thereafter. Marked transient elevations in ZL,s parameters and SIII were observed in the affected lung after aspiration. Elevating PEEP did not affect these responses in the ZL,s parameters, whereas it prevented the SIII increases. None of these indices changed in the intact left lung. These findings furnish evidence of the predominance of the local direct damage over the indirect systemic effects in the development of the deterioration of lung function, and demonstrate the benefit of an initially elevated PEEP following aspiration.