Jörg Haberstroh

The Effects of Increasing Concentrations of Desflurane on Systemic Oxygenation During One-lung Ventilation in Pigs

UNLABELLED During one-lung ventilation (OLV), hypoxic pulmonary vasoconstriction reduces venous admixture and attenuates the decrease in arterial O2 tension by diverting blood from the nonventilated to the ventilated lung. In vitro, increasing concentrations of desflurane depresses hypoxic pulmonary vasoconstriction in a dose-dependent manner. Accordingly, we investigated the effects of increasing concentrations of desflurane on oxygenation during OLV in vivo. Thirteen pigs (25-30 kg) were anesthetized (induction: propofol 2-3 mg/kg IV; maintenance: N2O/O2 50%/50%, desflurane 3%, propofol 50 microg x kg(-1) min(-1), and vecuronium 0.2 mg x kg(-1) x h(-1) IV), orotracheally intubated, and mechanically ventilated. After placement of femoral arterial and thermodilution pulmonary artery catheters, a leftsided, 28F, double-lumen tube was placed via tracheotomy. After double-lumen tube placement, N2O and desflurane were discontinued, propofol was increased to 200 microg x kg(-1) x min(-1), and the fraction of inspired oxygen was adjusted at 0.8. Anesthesia was then continued in random order with desflurane 5%, 10%, or 15% end-tidal concentrations while propofol was discontinued. Whereas mixed venous PO2, mean arterial pressure, cardiac output, and shunt fraction decreased in a dose-dependent manner, PaO2 remained unchanged with increasing concentrations of desflurane during OLV. These findings indicate that, in vivo, increasing concentrations of desflurane do not necessarily worsen oxygenation during OLV. IMPLICATIONS Oxygenation during one-lung ventilation depends on reflex vasoconstriction in the nonventilated lung. In vitro, desflurane inhibits this reflex dose-dependently. Our results indicate that, in vivo, this does not necessarily translate to dose-dependent decreases in oxygenation during one-lung ventilation.

Effects of intra-abdominal pressure on respiratory system mechanics in mechanically ventilated rats.

We investigated the effects of intra-abdominal pressure on respiratory system compliance at different PEEP levels. 20 ventilated rats underwent four pressure levels (7, 9, 11, 13 mm Hg) of helium pneumoperitoneum and were allocated to one of the four PEEP groups (0, 3, 6 and 9 cm H(2)O). From the expiratory pressure-volume curve the mathematical inflection point (MIP) was calculated. Volume-dependent compliance was analyzed using the SLICE-method. MIP-pressure correlated to the intra-abdominal pressure (r(2)=0.94, p<0.001). Peak inspiratory pressure increased with intra-abdominal pressure, and was lower after recruitment-maneuvers (p<0.001). The compliance gain following recruitment-maneuvers depended on PEEP, intra-abdominal pressure and intratidal volume (all p<0.001). Mean arterial pressure was independent of PEEP (p=0.068) and intra-abdominal pressure (p=0.293). Volume-dependent compliance courses varied according to PEEP and intra-abdominal pressure. The level of intra-abdominal pressure alters respiratory system mechanics in healthy lungs. Intratidal compliance can be used to guide the PEEP adjustment in intra-abdominal hypertension. If counterbalanced by PEEP, elevated intra-abdominal pressure has no negative effects on oxygenation or hemodynamics.

Rapid increase in inspired desflurane concentration does not elicit a hyperdynamic circulatory response in the pig

The effects of a rapid increase in inspired desflurane concentration on systemic haemodynamics and plasma catecholamines were studied in seven pigs (22-30 kg). Following premedication (flunitrazepam 0.4 mg/kg i.m.), anaesthesia was induced (propofol 2.5 mg/kg i.v., vecuronium 0.2 mg/kg i.v.), the trachea orally intubated, and ventilation controlled. Anaesthesia was maintained with N2O/O2 (70%/30%), propofol (50 μg/kg/min), desflurane 12% end-tidal concentration), and vecuronium (0.3 mg/kg/h). After cannulation of both femoral arteries for subsequent simultaneous systemic pressure measurements and blood sampling for determination of epinephrine (E) and norepinephrine (NE) plasma levels, N2O and propofol were discontinued, and FiO2 and end-tidal concentration of desflurane increased to >0.9 and 3%, respectively. Forty minutes later, the inspired concentration of desflurane was abruptly increased to 15%. Mean arterial pressure (MAP), heart rate (HR), and plasma concentrations of E and NE were determined before and 1, 2, 4, 8, 16, and 32 min after increasing the desflurane concentration. Plasma concentrations of E and NE were determined by high performance liquid chromatography (HPLC) with electrochemical detection. Data were analysed by repeated measures ANOVA (significance level P<0.05). The abrupt increase in inspired desflurane concentration caused an insignificant increase (11%) in HR at 1, 2 and 4 min. There was an immediate decrease in MAP. Plasma levels of E and NE remained unchanged throughout. In conclusion, in contrast to findings in humans, a rapid increase in inspired desflurane concentration does not cause a hyperdynamic circulatory response in the pig.

Endoscopic Imaging to Assess Alveolar Mechanics During Quasi-static and Dynamic Ventilatory Conditions in Rats With Noninjured and Injured Lungs.

Objectives:Although global respiratory mechanics are usually used to determine the settings of mechanical ventilation, this approach does not adequately take into account alveolar mechanics. However, it should be expected that the ventilatory condition (quasi-static vs. dynamic) and lung condition (noninjured vs. injured) affect alveolar mechanics in a clinically relevant way. Accordingly, the aim of this study was to investigate alveolar mechanics during quasi-static and dynamic ventilatory maneuvers in noninjured and injured lungs. We hypothesized that alveolar mechanics vary with ventilatory and lung conditions. Design:Prospective animal study. Setting:Animal research laboratory. Subjects:Male Wistar rats. Interventions:Alveolar mechanics (derived from alveolar size and airway pressure) were determined in noninjured (n = 9) and in lungs lavaged with saline (n = 8) at quasi-static (low flow at a peak pressure of 40 cm H2O) and dynamic ventilatory maneuvers (increase and decrease in positive end-expiratory pressure from 0 to 15 and back to 0 cm H2O in steps of 3 cm H2O). Alveoli were recorded endoscopically and alveolar mechanics were extracted using automated tracking of alveolar contours. Measurements and Main Results:The increase in alveolar size during quasi-static maneuvers was significantly greater than during dynamic maneuvers in noninjured (mean difference 18%, p < 0.001) but not in injured lungs (mean difference 3%, p = 0.293). During dynamic maneuvers, slope of the intratidal alveolar pressure/area curve (reflecting distensibility) decreased with increasing positive end-expiratory pressure (p = 0.001) independent of lung condition (noninjured and injured lungs). In contrast, independent of positive end-expiratory pressure but dependent on lung condition, the maximal tidal change in alveolar size was greater by an average of 40% in injured compared with noninjured lungs (p = 0.028). Conclusions:Alveolar mechanics during mechanical ventilation differed between quasi-static and dynamic conditions and varied with lung condition. Our data thus confirm that analysis of respiratory system mechanics under dynamic conditions is preferable to analysis during static conditions.

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

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

Endomicroscopic analysis of time- and pressure-dependent area of subpleural alveoli in mechanically ventilated rats

We investigated the effects of recruitment maneuvers on subpleural alveolar area in healthy rats. 36 mechanically ventilated rats were allocated to either ZEEP-group or PEEP - 5cmH2O - group. The subpleural alveoli were observed using a transthoracal endoscopic imaging technique. Two consecutive low-flow maneuvers up to 30cmH2O peak pressure each were performed, interrupted by 5s plateau phases at four different pressure levels. Alveolar area change at maneuver peak pressures and during the plateau phases was calculated and respiratory system compliance before and after the maneuvers was analyzed. In both groups alveolar area at the second peak of the maneuver did not differ significantly compared to the first peak. During the plateau phases there was a slight increase in alveolar area. After the maneuvers, compliance increased by 30% in ZEEP group and 20% in PEEP group. We conclude that the volume insufflated by the low-flow recruitment maneuver is distributed to deeper but not to subpleural lung regions.

The Equilibration of PCO2 in Pigs Is Independent of Lung Injury and Hemodynamics.

Objectives: In mechanical ventilation, normoventilation in terms of PCO2 can be achieved by titration of the respiratory rate and/or tidal volume. Although a linear relationship has been found between changes in respiratory rate and resulting changes in end-tidal cO2 (△PetCO2) as well as between changes in respiratory rate and equilibration time (t eq) for mechanically ventilated patients without lung injury, it is unclear whether a similar relationship holds for acute lung injury or altered hemodynamics. Design: We performed a prospective randomized controlled animal study of the change in PetCO2 with changes in respiratory rate in a lung-healthy, lung-injury, lung-healthy + altered hemodynamics, and lung-injury + altered hemodynamics pig model. Setting: University research laboratory. Subjects: Twenty mechanically ventilated pigs. Interventions: Moderate lung injury was induced by injection of oleic acid in 10 randomly assigned pigs, and after the first round of measurements, cardiac output was increased by approximately 30% by constant administration of noradrenalin in both groups. Measurements and Main Results: We systematically increased and decreased changes in respiratory rate according to a set protocol: +2, -4, +6, -8, +10, -12, +14 breaths/min and awaited equilibration of Petco2. We found a linear relationship between changes in respiratory rate and △PetCO2 as well as between changes in respiratory rate and t eq. A two-sample t test resulted in no significant differences between the lung injury and healthy control group before or after hemodynamic intervention. Furthermore, exponential extrapolation allowed prediction of the new PetCO2 equilibrium and t eq after 5.7 ± 5.6 min. Conclusions: The transition between PetCO2 equilibria after changes in respiratory rate might not be dependent on moderate lung injury or cardiac output but on the metabolic production or capacity of cO2 stores. Linear relationships previously found for lung-healthy patients and early prediction of PetCO2 equilibration could therefore also be used for the titration of respiratory rate on the PetCO2 for a wider range of pathologies by the physician or an automated ventilation system.

Investigation of alveolar stability in the rat lung using transthoracic endoscopy.

Transthoracic endoscopy was used to investigate mechanical stability of subpleural alveoli during repeated recruitment manoeuvres and at different plateau pressures between these manoeuvres in healthy rats ventilated at ZEEP. Images of subpleural alveoli were continuously recorded and alveolar size was measured frame by frame. Preliminary results show that the size of subpleural alveoli is constant over a wide pressure range and that repeated recruitment manoeuvres do not lead to further enlargement of alveoli. Higher plateau pressures lead to slight enlargement of subpleural alveoli.

Response of the Committee for Anaesthesia, Analgesia and Pain Prophylaxis of the Society for Laboratory Animal Science to ‘Temporary inhalation anaesthesia in experimental pigs’

In Sasaki et al.’s article, Letter to the Editor: Temporary inhalation anaesthesia in experimental pigs (Lab Anim 2010;44:69–70), a device for short-term inhalation anaesthesia with sevoflurane in ketamine/metedomidine-sedated mini-pigs was presented. The device consists of a 500 mL beaker (standard laboratory glassware), three pieces of gauze (30 30 cm) and a cut-off surgical glove. The pieces of gauze were soaked with 5 mL of sevoflurane. The device covered the pig’s maxilla, nose and mandible. The device was fitted closely to the animal’s nose by means of the surgical glove to prevent leakage of sevoflurane. The animals were removed from the device when the respiratory rate decreased and palpebral reflex disappeared. The Committee for Anaesthesia, Analgesia and Pain Prophylaxis of the Society for Laboratory Animal Science comments on this publication as follows: The anaesthesia procedure using this device appears easy to perform, cheap and practical but in our opinion it is potentially harmful to both animals and man for the reasons detailed below.