Gergely H. Fodor

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 ± SD) decreased in all groups following blood loss (−20.3 ± 9.5% vs. baseline, P < 0.05), and remained low following blood replacement (−21.7 ± 14.5% vs. baseline, P < 0.05), but was normalised by colloid (5.5 ± 10.7%, NS). Crystalloid administration exhibited an intermediate reversal effect (−8.4 ± 14.7%, 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.

Airway mechanics and lung tissue viscoelasticity: effects of altered blood hematocrit in the pulmonary circulation

The contribution of the hematocrit (Hct) of the blood in the pulmonary vasculature to the overall lung mechanics has not been characterized. We therefore set out to establish how changes of the Hct level in the pulmonary circulation affect the airway and lung tissue viscoelastic properties. The Hct level of the blood in an isolated perfused rat lung model was randomly altered. Intermediate (26.5%), followed by low (6.6%) or normal (43.7%), Hct was set in two consecutive sequences. The pulmonary capillary pressure was maintained constant throughout the experiment, and the pulmonary hemodynamic parameters were monitored continuously. The airway resistance (Raw), the viscous (G) and elastic (H) parameters, and the hysteresivity (η = G/H) of the lung tissues were obtained from measurements of forced oscillatory input impedance data. Raw was not affected by the alterations of the Hct levels. As concerns the lung tissues, the decrease of Hct to intermediate or low levels resulted in close to proportional decreases in the viscoelastic parameters G [16.5 ± 7.7% (SD), 12.1 ± 9.5%, P < 0.005] and H (13.2 ± 8.6%, 10.8 ± 4.7%, P < 0.001). No significant changes in η were detected in a wide range of Hct, which indicates that coupled processes cause alterations in the resistive and elastic properties of the lungs following Hct changes in the pulmonary circulation. The diminishment of the viscous and elastic parameters of the pulmonary parenchyma following a reduction of blood Hct demonstrates the significant contribution of the red blood cells to the overall lung viscoelasticity.

Capnogram slope and ventilation dead space parameters: comparison of mainstream and sidestream techniques.

BACKGROUND Capnography may provide useful non-invasive bedside information concerning heterogeneity in lung ventilation, ventilation-perfusion mismatching and metabolic status. Although the capnogram may be recorded by mainstream and sidestream techniques, the capnogram indices furnished by these approaches have not previously been compared systematically. METHODS Simultaneous mainstream and sidestream time and volumetric capnography was performed in anaesthetized, mechanically ventilated patients undergoing elective heart surgery. Time capnography was used to assess the phase II (SII,T) and III slopes (SIII,T). The volumetric method was applied to estimate phase II (SII,V) and III slopes (SIII,V), together with the dead space values according to the Fowler (VDF), Bohr (VDB), and Enghoff (VDE) methods and the volume of CO2 eliminated per breath ([Formula: see text]). The partial pressure of end-tidal CO2 ([Formula: see text]) was registered. RESULTS Excellent correlation and good agreement were observed in SIII,T measured by the mainstream and sidestream techniques [ratio=1.05 (sem 0.16), R(2)=0.92, P<0.0001]. Although the sidestream technique significantly underestimated [Formula: see text] and overestimated SIII,V [1.32 (0.28), R(2)=0.93, P<0.0001], VDF, VDB, and VDE, the agreement between the mainstream and sidestream techniques in the difference between VDE and VDB, reflecting the intrapulmonary shunt, was excellent [0.97 (0.004), R(2)=0.92, P<0.0001]. The [Formula: see text] exhibited good correlation and mild differences between the mainstream and sidestream approaches [0.025 (0.005) kPa]. CONCLUSIONS Sidestream capnography provides adequate quantitative bedside information about uneven alveolar emptying and ventilation-perfusion mismatching, because it allows reliable assessments of the phase III slope, [Formula: see text] and intrapulmonary shunt. Reliable measurement of volumetric parameters (phase II slope, dead spaces, and eliminated CO2 volumes) requires the application of a mainstream device.

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.

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.

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.