Respiratory effects of pressure support ventilation in spontaneously breathing patients under anaesthesia: Randomised controlled trial.

BACKGROUND: Lung volume loss is a major risk factor for postoperative respiratory complications after general anaesthesia and mechanical ventilation. We hypothesise that spontaneous breathing without pressure support may enhance the risk for atelectasis development. Therefore, we aimed at characterising whether pressure support prevents changes in lung function in patients breathing spontaneously through laryngeal mask airway. METHODS: In this randomised controlled trial, adult female patients scheduled for elective gynaecological surgery in lithotomy position were randomly assigned to the continuous spontaneous breathing group (CSB, n = 20) or to the pressure support ventilation group (PSV, n = 20) in a tertiary university hospital. Lung function measurements were carried out before anaesthesia and 1 h postoperatively by a researcher blinded to the group allocation. Lung clearance index calculated from end-expiratory lung volume turnovers as primary outcome variable was assessed by the multiple-breath nitrogen washout technique (MBW). Respiratory mechanics were measured by forced oscillations to assess parameters reflecting the small airway function and respiratory tissue stiffness. RESULTS: MBW was successfully completed in 18 patients in both CSB and PSV groups. The decrease in end-expiratory lung volume was more pronounced in the CSB than that in the PSV group (16.6 ± 6.6 [95% CI] % vs. 7.6 ± 11.1%, p = .0259), with no significant difference in the relative changes of the lung clearance index (-0.035 ± 7.1% vs. -0.18 ± 6.6%, p = .963). The postoperative changes in small airway function and respiratory tissue stiffness were significantly lower in the PSV than in the CSB group (p < .05 for both). CONCLUSIONS: These results suggest that pressure support ventilation protects against postoperative lung-volume loss without affecting ventilation inhomogeneity in spontaneously breathing patients with increased risk for atelectasis development. TRIAL REGISTRATION: NCT02986269.

Changes in lung mechanics and ventilation-perfusion match: comparison of pulmonary air- and thromboembolism in rats.

BACKGROUND: Pulmonary air embolism (AE) and thromboembolism lead to severe ventilation-perfusion defects. The spatial distribution of pulmonary perfusion dysfunctions differs substantially in the two pulmonary embolism pathologies, and the effects on respiratory mechanics, gas exchange, and ventilation-perfusion match have not been compared within a study. Therefore, we compared changes in indices reflecting airway and respiratory tissue mechanics, gas exchange, and capnography when pulmonary embolism was induced by venous injection of air as a model of gas embolism or by clamping the main pulmonary artery to mimic severe thromboembolism. METHODS: Anesthetized and mechanically ventilated rats (n = 9) were measured under baseline conditions after inducing pulmonary AE by injecting 0.1 mL air into the femoral vein and after occluding the left pulmonary artery (LPAO). Changes in mechanical parameters were assessed by forced oscillations to measure airway resistance, lung tissue damping, and elastance. The arterial partial pressures of oxygen (PaO2) and carbon dioxide (PaCO2) were determined by blood gas analyses. Gas exchange indices were also assessed by measuring end-tidal CO2 concentration (ETCO2), shape factors, and dead space parameters by volumetric capnography. RESULTS: In the presence of a uniform decrease in ETCO2 in the two embolism models, marked elevations in the bronchial tone and compromised lung tissue mechanics were noted after LPAO, whereas AE did not affect lung mechanics. Conversely, only AE deteriorated PaO2, and PaCO2, while LPAO did not affect these outcomes. Neither AE nor LPAO caused changes in the anatomical or physiological dead space, while both embolism models resulted in elevated alveolar dead space indices incorporating intrapulmonary shunting. CONCLUSIONS: Our findings indicate that severe focal hypocapnia following LPAO triggers bronchoconstriction redirecting airflow to well-perfused lung areas, thereby maintaining normal oxygenation, and the CO2 elimination ability of the lungs. However, hypocapnia in diffuse pulmonary perfusion after AE may not reach the threshold level to induce lung mechanical changes; thus, the compensatory mechanisms to match ventilation to perfusion are activated less effectively.

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.

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.

Invasive and non-invasive assessment of macro- and micro-circulatory effects of vasopressors during sevoflurane anesthesia in a pediatric experimental model: A randomized trial.

BACKGROUND: While non-invasive assessment of macro- and micro-circulation has the promise to optimize anesthesia management, evidence is lacking for the relationship between invasive and non-invasive measurements of cardiac output and microcirculatory indices. AIMS: We aimed to compare the abilities of non-invasive techniques to detect changes in macro- and micro-circulation following deep anesthesia and subsequent restoration of the compromised hemodynamic by routinely used vasopressors in a randomized experimental study. METHODS: A 20%-25% drop in mean arterial pressure was induced by sevoflurane in anesthetized mechanically ventilated just-weaned piglets (n = 12) prior to the administration of vasopressors in random order (dopamine, ephedrine, noradrenaline, and phenylephrine). Simultaneous transpulmonary thermodilution cardiac output assessment with the invasive pulse index continuous contour (PiCCO) method was compared with non-invasive estimates obtained with electrical conductivity (ICON) and echo Doppler (Cardio Q). Changes in microcirculation were characterized by sublingual red blood cell velocity, jugular cerebral venous oxygen saturation, and arterial lactate. MAIN OUTCOME MEASURES: Cardiac output indices obtained by invasive and non-invasive methods. RESULTS: Changes in cardiac output measured invasively and non-invasively correlated significantly after sevoflurane (r = .78, p = .003 and r = .76, p = .006 between PiCCO and ICON or Cardio Q, respectively). Following the administration of vasopressors, invasive and non-invasive cardiac output assessments were unrelated with significant correlations observed only between PiCCO and ICON after dopamine and ephedrine. Sevoflurane-induced hypotension decreased jugular cerebral venous oxygen saturation significantly and was recovered by all vasopressors. Sevoflurane and vasopressors had no effect on red blood cell velocity, which increased only after dopamine. No consistent changes in lactate were observed during the study period. CONCLUSIONS: The results of this study suggest that non-invasive cardiac output measurements may not accurately reflect changes in macrocirculation after hemodynamic optimization by vasopressors. Due to the incoherence between macro- and micro-circulation, monitoring microcirculation is essential to guide patient management.

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.

Lung volume dependence of respiratory function in rodent models of diabetes mellitus.

BACKGROUND: Diabetes mellitus causes the deterioration of smooth muscle cells and interstitial matrix proteins, including collagen. Collagen and smooth muscle cells are abundant in the lungs, but the effect of diabetes on airway function and viscoelastic respiratory tissue mechanics has not been characterized. This study investigated the impact of diabetes on respiratory function, bronchial responsiveness, and gas exchange parameters. METHODS: Rats were allocated randomly to three groups: a model of type 1 diabetes that received a high dose of streptozotocin (DM1, n = 13); a model of type 2 diabetes that received a low dose of streptozotocin with a high-fat diet (DM2, n = 14); and a control group with no treatment (C, n = 14). Forced oscillations were applied to assess airway resistance (Raw), respiratory tissue damping (G), and elastance (H). The arterial partial pressure of oxygen to the inspired oxygen fraction (PaO2/FiO2) and intrapulmonary shunt fraction (Qs/Qt) were determined from blood gas samples at positive end-expiratory pressures (PEEPs) of 0, 3, and 6 cmH2O. Lung responsiveness to methacholine was also assessed. Collagen fibers in lung tissue were quantified by histology. RESULTS: The rats in groups DM1 and DM2 exhibited elevated Raw, G, H, and Qs/Qt, compromised PaO2/FiO2, and diminished airway responsiveness. The severity of adverse tissue mechanical change correlated with excessive lung collagen expression. Increased PEEP normalized the respiratory mechanics, but the gas exchange abnormalities remained. CONCLUSIONS: These findings indicate that diabetes reduces airway and lung tissue viscoelasticity, resulting in alveolar collapsibility that can be compensated by increasing PEEP. Diabetes also induces persistent alveolo-capillary dysfunction and abnormal adaptation ability of the airways to exogenous constrictor stimuli.

Physiologically variable ventilation reduces regional lung inflammation in a pediatric model of acute respiratory distress syndrome.

BACKGROUND: Benefits of variable mechanical ventilation based on the physiological breathing pattern have been observed both in healthy and injured lungs. These benefits have not been characterized in pediatric models and the effect of this ventilation mode on regional distribution of lung inflammation also remains controversial. Here, we compare structural, molecular and functional outcomes reflecting regional inflammation between PVV and conventional pressure-controlled ventilation (PCV) in a pediatric model of healthy lungs and acute respiratory distress syndrome (ARDS). METHODS: New-Zealand White rabbit pups (n = 36, 670 ± 20 g [half-width 95% confidence interval]), with healthy lungs or after induction of ARDS, were randomized to five hours of mechanical ventilation with PCV or PVV. Regional lung aeration, inflammation and perfusion were assessed using x-ray computed tomography, positron-emission tomography and single-photon emission computed tomography, respectively. Ventilation parameters, blood gases and respiratory tissue elastance were recorded hourly. RESULTS: Mechanical ventilation worsened respiratory elastance in healthy and ARDS animals ventilated with PCV (11 ± 8%, 6 ± 3%, p < 0.04), however, this trend was improved by PVV (1 ± 4%, - 6 ± 2%). Animals receiving PVV presented reduced inflammation as assessed by lung normalized [18F]fluorodeoxyglucose uptake in healthy (1.49 ± 0.62 standardized uptake value, SUV) and ARDS animals (1.86 ± 0.47 SUV) compared to PCV (2.33 ± 0.775 and 2.28 ± 0.3 SUV, respectively, p < 0.05), particularly in the well and poorly aerated lung zones. No benefit of PVV could be detected on regional blood perfusion or blood gas parameters. CONCLUSIONS: Variable ventilation based on a physiological respiratory pattern, compared to conventional pressure-controlled ventilation, reduced global and regional inflammation in both healthy and injured lungs of juvenile rabbits.

Physiologically variable ventilation in a rabbit model of asthma exacerbation.

BACKGROUND: Mechanical ventilation during status asthmaticus is challenging and increases the risk of severe complications. We recently reported the value of physiologically variable ventilation (PVV) in healthy and acutely injured lungs. We investigated whether PVV provides benefits compared with pressure-controlled ventilation (PCV) in an experimental model of severe acute asthma. METHODS: Allergen-sensitised rabbits were anaesthetised and randomised to either PCV (n=10) or PVV (n=12) during sustained bronchoconstriction induced by allergen and cholinergic stimuli for 6 h. The PVV pattern was generated from pre-recorded spontaneous breathing. Ventilation parameters, oxygenation index (PaO2/FiO2), and respiratory mechanics were measured hourly. Histological injury and inflammation were quantified after 6 h of ventilation. RESULTS: PVV resulted in lower driving pressures (13.7 cm H2O [12.5-14.9], mean [95% confidence interval]), compared with pressure-controlled ventilation (17.6 cm H2O [15.4-19.8]; P=0.002). PVV improved PaO2/FiO2 (PVV: 55.1 kPa [52-58.2]; PCV: 45.6 kPa [39.3-51.9]; P=0.018) and maintained tissue elastance (PVV: +8.7% [-0.6 to 18]; PCV: -11.2% [-17.3 to -5.1]; P=0.03). PVV resulted in less lung injury as assessed by lower histological injury score (PVV: 0.65 [0.62-0.65]; PCV: 0.71 [0.69-0.73]; P=0.003), cell count (PVV: 247 104 ml-1 [189-305]; PCV: 447 104 ml-1 [324-570]; P=0.005), and protein concentration in bronchoalveolar lavage fluid (PVV: 0.14 µg ml-1 [0.10-0.18]; PCV: 0.21 µg ml-1 [0.15-0.27]; P=0.035). CONCLUSIONS: Applying physiological variable ventilation in a model of asthma exacerbation led to improvements in gas exchange, ventilatory pressures, and respiratory tissue mechanics, and reduced lung injury. A global reduction in lung shear stress and recruitment effects may explain the benefits of PVV in status asthmaticus.

End-expiratory lung volume assessment using helium and carbon dioxide in an experimental model of pediatric capnoperitoneum.

BACKGROUND: Capnoperitoneum during laparoscopy leads to cranial shift of the diaphragm, loss in lung volume, and risk of impaired gas exchange. Infants are susceptible to these changes and bedside assessment of lung volume during laparoscopy might assist with optimizing the ventilation. Thus, the primary aim was to investigate the monitoring value of a continuous end-expiratory lung volume (EELV) assessment method based on CO2 dynamics ( EELV CO 2 ) in a pediatric capnoperitoneum model by evaluating the correlation and trending ability against helium washout (EELVHe ). METHODS: Intra-abdominal pressure (IAP) was randomly varied between 0, 6, and 12 mm Hg with CO2 insufflation, while positive end-expiratory pressure (PEEP) levels of 3, 6, and 9 cm H2 O were randomly applied in eight anesthetized and mechanically ventilated chinchilla rabbits. Concomitant EELV CO 2 and EELVHe and lung clearance index (LCI) were obtained under each experimental condition. RESULTS: Significant correlations were found between EELV CO 2 and EELVHe before capnoperitoneum (r = .85, P < .001), although increased IAP distorted this relationship. The negative influence of IAP was counteracted by the application of PEEP 9, which restored the correlation between EELV CO 2 and EELVHe and resulted in 100% concordance rate between the methods regarding changes in lung volume. EELVHe and LCI showed a curvilinear relationship, and an EELVHe of approximately 20 mL kg-1 , determined with a receiver operating characteristic curve, was associated with near-normal LCI values. CONCLUSION: In this animal model of pediatric capnoperitoneum, reliable assessment of changes in EELV based on EELV CO 2 requires an open lung strategy, defined as EELV above approximately 20 mL kg-1 .

Determination of adequate positive end-expiratory pressure level required for carbon dioxide homeostasis in an animal model of infant laparoscopy.

BACKGROUND: Capnoperitoneum provides a ventilatory challenge due to reduction in end-expiratory lung volume and peritoneal carbon dioxide absorption in both children and adults. The primary aim of this controlled interventional trial was to determine the positive end-expiratory pressure (PEEP) level needed to ensure for adequate carbon dioxide clearance and preservation of carbon dioxide homeostasis in an experimental model of infant laparoscopy. The secondary aim was to evaluate potential effects on cardiac output of PEEP and abdominal pressure level variations in the same setting. METHODS: Eight chinchilla bastard rabbits were anesthetized and mechanically ventilated. Intra-abdominal pressures were randomly set to 0, 6, and 12 mm Hg by carbon dioxide insufflation. Carbon dioxide clearance using volumetric capnography, arterial blood gas data, and cardiac output was recorded, while PEEP 3, 6, and 9 cmH2 O were applied in a random order. RESULTS: A PEEP of 9 cmH2 O showed restoration of carbon dioxide clearance without causing changes in arterial partial pressure of carbon dioxide and bicarbonate and with no associated deterioration in cardiac output. CONCLUSION: The results promote a PEEP level of 9 cmH2 O in this model of infant capnoperitoneum to allow for adequate carbon dioxide removal with subsequent preservation of carbon dioxide homeostasis. The use of high PEEP was not associated with any decrease in cardiac output.

High inspired oxygen fraction impairs lung volume and ventilation heterogeneity in healthy children: a double-blind randomised controlled trial.

BACKGROUND: Although a high inspired oxygen fraction (FiO2) is commonly used in paediatric anaesthesia, the impact on postoperative lung function is unclear. We compared lung volume, ventilation heterogeneity, and respiratory mechanics in anaesthetised children randomised to receive low or high FiO2 intraoperatively. METHODS: In a double-blind randomised controlled trial, children scheduled for elective surgery were randomly assigned FiO2 100% (n=29) or FiO2 80% (n=29) during anaesthesia induction and emergence. During maintenance of anaesthesia, participants assigned FiO2=100% at induction/emergence received FiO2=80% (FiO2>0.8 group); those randomised to FiO2=80% at induction/emergence received FiO2=35% intraoperatively (FiO2 [0.8→0.35 group]). During spontaneous breathing, we measured the (i) functional residual capacity (FRC) and lung clearance index (ventilation inhomogeneity) by multiple-breath nitrogen washout; and (ii) airway resistance and respiratory tissue elastance by forced oscillations, before operation, after discharge from the recovery room, and 24 h after operation. Mean (95% confidence intervals) are reported. RESULTS: Fifty eight children (12.9 [12.3-13.5] yr) were randomised; 22/29 (high group) and 21/29 (low group) children completed serial multiple-breath nitrogen washout measurements. FRC decreased in the FiO2>0.8 group after discharge from recovery (-12.0 [-18.5 to -5.5]%; P=0.01), but normalised 24 h later. Ventilation inhomogeneity increased in both groups after discharge from recovery, but persisted in the FiO2>0.8 group 24 h after surgery (6.1 [2.5-9.8%]%; P=0.02). Airway resistance and respiratory elastance did not differ between the groups at any time point. CONCLUSIONS: FiO2>0.8 decreases lung volume in the immediate postoperative period, accompanied by persistent ventilation inhomogeneity. These data suggest that FiO2>0.8 should be avoided in anaesthetised children with normal lungs. CLINICAL TRIAL REGISTRATION: NCT02384616.

Reversing Cholinergic Bronchoconstriction by Common Inotropic Agents: A Randomized Experimental Trial on Isolated Perfused Rat Lungs.

BACKGROUND: The ability of inotropic agents to alter airway reactivity and lung tissue mechanics has not been compared in a well-controlled experimental model. Therefore, we compared the potential to alter lung tissue viscoelasticity and bronchodilator effects of commonly used inotropic agents in an isolated perfused rat lung model. METHODS: After achieving steady state lung perfusion, sustained bronchoconstriction was induced by acetylcholine (ACh). Isolated rat lungs were then randomly allocated to 6 groups treated with either saline vehicle (n = 8) or incremental concentrations of inotropes (adrenaline, n = 8; dopamine, n = 7; dobutamine, n = 7; milrinone, n = 8; or levosimendan, n = 6) added to the whole-blood perfusate. Airway resistance (Raw), lung tissue damping (G), and elastance were measured under baseline conditions, during steady-state ACh-induced constriction and for each inotrope dose. RESULTS: No change in Raw was observed after addition of the saline vehicle. Raw was significantly lower after addition of dopamine (maximum difference [95% CI] of 29 [12-46]% relative to the saline control, P = .004), levosimendan (58 [39-77]%, P < .001), and adrenaline (37 [21-53]%, P < .001), whereas no significant differences were observed at any dose of milrinone (5 [-12 to 22]%) and dobutamine (4 [-13 to 21]%). Lung tissue damping (G) was lower in animals receiving the highest doses of adrenaline (difference: 22 [7-37]%, P = .015), dobutamine (20 [5-35]%, P = .024), milrinone (20 [6-34]%, P = .026), and levosimendan (36 [19-53]%, P < .001) than in controls. CONCLUSIONS: Although dobutamine and milrinone did not reduce cholinergic bronchoconstriction, they reversed the ACh-induced elevations in lung tissue resistance. In contrast, adrenaline, dopamine, and levosimendan exhibited both potent bronchodilatory action against ACh and diminished lung tissue damping. Further work is needed to determine whether these effects are clinically relevant in humans.

Effect of PEEP and I:E ratio on cerebral oxygenation in ARDS: an experimental study in anesthetized rabbit.

BACKGROUND: Although PEEP and inversed I:E ratio have been shown to improve gas exchange in ARDS, both can adversely affect systemic hemodynamics and cerebral perfusion. The goal of this study was to assess how changes in PEEP and I:E ratio affect systemic and cerebral oxygenation and perfusion in normal and injured lung. METHODS: Eight anesthetized Chinchilla-Bastard rabbits were ventilated at baseline with pressure-regulated volume control mode, VT = 6 ml/kg, PEEP = 6 cmH2O, FIO2 = 0.4; respiratory rate set for ETCO2 = 5.5%, and I:E = 1:2, 1:1 or 2:1 in random order. Ultrasonic carotid artery flow (CF), arterial (PaO2), jugular venous blood gases and near infrared spectroscopic cerebral oxygenation (∆HBO2) were recorded for each experimental condition. After induced lung injury, the animals were ventilated with PEEP = 9 followed by 6 cmH2O. RESULTS: At baseline, inverse-ratio ventilation (IRV) significantly reduced cerebral oxygenation (∆O2HB; - 27 at 1:2; - 15 at 1:1 vs. 0.27 µmol/L at 2:1; p < 0.05), due to a significant reduction in mean arterial pressure and CF without modifying gas exchange. In injured lung, IRV improved gas exchange but decreased cerebral perfusion without affecting brain oxygenation. The higher PEEP level, however, improved PaO2 (67.5 ± 19.3 vs. 42.2 ± 8.4, p < 0.05), resulting in an improved ∆HBO2 (- 13.8 ± 14.7 vs. -43.5 ± 21.3, p < 0.05), despite a drop in CF. CONCLUSIONS: Our data suggest that unlike moderate PEEP, IRV is not effective in improving brain oxygenation in ARDS. In normal lung, IRV had a deleterious effect on brain oxygenation, which is relevant in anesthetized patients.

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.

Cardiorespiratory Alterations Following Acute Normovolemic Hemodilution in a Pediatric and an Adult Porcine Model: A Prospective Interventional Study.

BACKGROUND: Acute normovolemic hemodilution (ANH) is considered as a blood-sparing intervention during the perioperative management. We aimed at comparing the cardiopulmonary consequences of ANH between adult pigs and weaned piglets to establish the effects of lowering hematocrit in these age groups, and thereby testing the hypothesis that difference in the age-related physiological behavior will be reflected in the cardiorespiratory changes following ANH. METHODS: ANH was achieved in anesthetized, mechanically ventilated adult minipigs and 5-week-old weaned piglets by stepwise blood withdrawal (10 mL/kg) with crystalloids replacement. Cardiorespiratory assessments consisted of measuring airway resistance, respiratory tissue elastance, effective lung volume, extravascular lung water, mean arterial pressure, pulmonary blood flow, and cardiac output. Respiratory and hemodynamic measurements were made at control conditions and following each ANH condition obtained with 5 to 7 steps. RESULTS: ANH induced immediate and progressive increases in airway resistance and tissue elastance in both groups, with more pronounced worsening in adults despite the similar decreases in hematocrit. The increases in extravascular lung water were significantly greater in the adult population with the differences in mean (DM) of 25.1% (95% confidence interval [CI], 5.3%-44.9%). Progressive ANH led to significant decreases in the DM of pulmonary blood flow (45.3%; 95% CI, 19.8%-70.8%) and mean arterial pressure (36.3%; 95% CI, 18.7%-53.9%) only in adults, whereas cardiac output increased significantly only in the piglets (DM, 51.6; 95% CI, 14.2%-89.0%). CONCLUSIONS: While ANH led to mild detrimental cardiorespiratory changes in weaned piglets, gradual developments of bronchoconstriction, lung tissue extravasation and stiffening, and deteriorations in systemic and pulmonary hemodynamics were observed in adults. ANH may exert age-dependent cardiorespiratory effect.

Blockade of the cholinergic system during sensitization enhances lung responsiveness to allergen in rats.

Although acute prophylactic administration of atropine modulates airway responsiveness, the role of the parasympathetic nervous system in the pathogenesis of sensitization and in antigen-induced bronchoconstriction remains unclear. The aim of the present study is to determine whether blocking muscarinic receptors during chronic allergen exposure modulates lung responsiveness to the specific allergen. Forty rats were randomly assigned to one of the following five treatment groups: sensitization with saline vehicle, intraperitoneal injection of ovalbumin (1 mg) with or without atropine treatment (10 mg/kg per day) and repeated ovalbumin aerosol (1.25 mg/mL for 20 minutes) either alone or combined with atropine. Lung responsiveness to methacholine (4-16 µg/kg per minute) and intravenous ovalbumin (2 mg) was established before and 21 days after treatment with forced oscillations following bilateral vagotomy. Lung cellularity was determined by analysis of bronchoalveolar lavage fluid (BALF). A lung inflammatory response in all sensitized animals was defined as an increase in the number of inflammatory cells in the BALF. Baseline respiratory mechanics and methacholine responsiveness on Days 0 and 21 were comparable in all groups. However, increases in airway resistance following intravenous allergen challenge were significantly exacerbated in rats that received atropine. Inhibition of the cholinergic nervous system during allergic sensitization potentiates bronchoconstriction following exposure to the specific allergen. These findings highlight the role of the cholinergic neuronal pathway in airway sensitization to a specific allergen.

[Diabetes mellitus: endothelial dysfunction and changes in hemostasis]. / Diabetes mellitus: endotheldiszfunkció és haemostasiselváltozások.

Diabetes mellitus involves a group of chronic metabolic disorders with elevated blood glucose concentrations. Since this disease needs lifelong treatment and care, the medical and social aspects present major public health concerns and pose a global challenge for health care providers. The number of aged patients with degenerative diseases undergoing surgical procedures is continuously increasing, resulting in an overwhelming dominance of diabetes in the perioperative care. There is a particular need for an increased awareness of diabetic patients in cardiovascular units, where the incidence of this disease reaches as high as 30-40%. The main hallmarks of the pathologic metabolic milieu of diabetes are hyperglycaemia, insulin resistance and pathologic lipid metabolism. The biochemical, cellular and organ-level pathophysiological changes lead to endothelial dysfunction including a low-grade prothrombotic balance, inflammatory state and, as a consequence, impaired micro- and macrocirculation. Diabetes is also followed by platelet dysfunction resulting from intracellular hyperglycaemia, because thrombocytes have insulin-independent glucose transporters in their cell membrane. The levels of the coagulation factors of the plasma are increased, and these factors are also modified by oxidation and glycation. Diabetes mellitus is a prothrombotic condition resulting from direct and indirect tendencies of the endothelial platelet and the plasma coagulation factors. The basic "bench to clinical basics" knowledge of the endothelial dysfunction and prothrombotic balance in diabetes may contribute to the better understanding of the clinical focuses in the perioperative care of patients with diabetes mellitus. Orv Hetil. 2018; 159(33): 1335-1345.

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.