Effect of Bronchoconstriction-induced Ventilation–Perfusion Mismatch on Uptake and Elimination of Isoflurane and Desflurane

2017 ◽  
Vol 127 (5) ◽  
pp. 800-812 ◽  
Author(s):  
Moritz Kretzschmar ◽  
Alf Kozian ◽  
James E. Baumgardner ◽  
Joao Batista Borges ◽  
Göran Hedenstierna ◽  
...  

Abstract Background Increasing numbers of patients with obstructive lung diseases need anesthesia for surgery. These conditions are associated with pulmonary ventilation/perfusion (VA/Q) mismatch affecting kinetics of volatile anesthetics. Pure shunt might delay uptake of less soluble anesthetic agents but other forms of VA/Q scatter have not yet been examined. Volatile anesthetics with higher blood solubility would be less affected by VA/Q mismatch. We therefore compared uptake and elimination of higher soluble isoflurane and less soluble desflurane in a piglet model. Methods Juvenile piglets (26.7 ± 1.5 kg) received either isoflurane (n = 7) or desflurane (n = 7). Arterial and mixed venous blood samples were obtained during wash-in and wash-out of volatile anesthetics before and during bronchoconstriction by methacholine inhalation (100 μg/ml). Total uptake and elimination were calculated based on partial pressure measurements by micropore membrane inlet mass spectrometry and literature-derived partition coefficients and assumed end-expired to arterial gradients to be negligible. VA/Q distribution was assessed by the multiple inert gas elimination technique. Results Before methacholine inhalation, isoflurane arterial partial pressures reached 90% of final plateau within 16 min and decreased to 10% after 28 min. By methacholine nebulization, arterial uptake and elimination delayed to 35 and 44 min. Desflurane needed 4 min during wash-in and 6 min during wash-out, but with bronchoconstriction 90% of both uptake and elimination was reached within 15 min. Conclusions Inhaled methacholine induced bronchoconstriction and inhomogeneous VA/Q distribution. Solubility of inhalational anesthetics significantly influenced pharmacokinetics: higher soluble isoflurane is less affected than fairly insoluble desflurane, indicating different uptake and elimination during bronchoconstriction.

1981 ◽  
Vol 4 (2) ◽  
pp. 76-81 ◽  
Author(s):  
T. Kolobow ◽  
R.G. Spragg ◽  
J.E. Pierce

We provided total cardiopulmonary support for 1-18 hours in unanesthetized tethered lambs by peripheral vascular cannulation, using a roller pump and the spiral membrane lung. Respirations were allowed to remain spontaneous and unaided. A Swan-Ganz catheter was placed for retrograde pulmonary artery blood flow sampling. Within a few minutes following induced ventricular fibrillation the PCO2 of sampled blood flowing retrograde through the lungs fell below 10 mm Hg, the PO2 rose to near 150 mm Hg, the pH rose to above 7.8, and the glucose level fell to less than 20 mg %. All of these values later gradually shifted, approaching mixed venous blood values within minutes. After 1-18 hrs of perfusion the animals went into shock and were sacrificed. At autopsy, the lungs of animals breathing room air were beefy and hemorrhagic. In lambs that were «breathing» CO2 enriched air the retrograde pulmonary artery blood pH and PCO2 was usually maintained close to the mixed venous blood values. The observed pulmonary changes were considerably less abnormal, and the microscopic abnormalities were at times nonexistent. We believe the integrity of pulmonary blood flow is vital to the survival of the lungs as a functioning organ. Cessation of total forward pulmonary blood flow (unlike partial cardiopulmonary bypass), combined with spontaneous pulmonary ventilation, rapidly leads to massive, pulmonary infactions, shock, and death.


1997 ◽  
Vol 106 (4) ◽  
pp. 314-319 ◽  
Author(s):  
Haya Mover-Lev ◽  
Moshe Harell ◽  
Dalia Levy ◽  
Amos Ar ◽  
Michal Luntz ◽  
...  

The middle ear (ME) steady state gas composition resembles that of mixed venous blood. We changed arterial and venous blood gases by artificially ventilating anesthetized guinea pigs and measured simultaneous ME gas changes during spontaneous breathing, hyperventilation, and hypoventilation. During hyperventilation, PaCO2 and PvCO2 (a = arterial, v = venous) decreased from 46.0 and 53.0 mm Hg to 17.9 and 37.5 mm Hg, respectively, while PaO2 and PvO2 (85.6 and 38.2 mm Hg) did not change. This was accompanied by an ME PCO2 decrease from 70.4 to 58.8 mm Hg and a PO2 decrease from 36.8 to 25.4 mm Hg. During hypoventilation, PaCO2 and PvCO2 increased to 56.8 and 66.4 mm Hg, while PvO2 decreased to 21.8 mm Hg. The ME PCO2 increased simultaneously to 88.8 mm Hg and the ME PO2 decreased to 25.4 mm Hg. The ME PO2 decrease during hyperventilation may be explained by a 33% decrease in ME mucosa perfusion, calculated from the ME ventilation-perfusion ratio. This study shows that ME gas composition follows fluctuations of blood gas levels and thus may affect total ME pressure.


1986 ◽  
Vol 61 (3) ◽  
pp. 1162-1172 ◽  
Author(s):  
H. T. Robertson ◽  
J. Whitehead ◽  
M. P. Hlastala

Partial pressures of intravenously infused acetylene, Freon 22, and isoflurane (gases with similar solubilities in blood but differing molecular weights) were compared in arterial and mixed venous blood and mixed expired gas of 13 anesthetized mongrel dogs to determine whether gas molecular weight influenced gas exchange. Analysis of covariance was used to account for the variables of ventilation-perfusion ratio, partition coefficient, and experimental run before individual gas effects were sought. A gas effect difference was observed such that the arterial fractional retention of isoflurane (mol wt 184.5) would be 12% higher than that of acetylene (mol wt 26) if the two gases had identical partition coefficients. This effect was neither significantly increased by positive end-expiratory pressure nor decreased by high-frequency oscillatory ventilation. To test whether the individual gas effect was greater with gases with disparate erythrocyte and plasma partition coefficients, the exchange of ethyl iodide (erythrocyte-to-plasma solubility ratio 8.1) and diethyl ether (solubility ratio 0.95) was compared in five dogs. A larger difference between the elimination of the two gases was observed than predicted from the differences in molecular weight. The observed individual gas effect appears to be diffusion related, influenced both by the molecular weight of a gas and its erythrocyte-plasma partition coefficient ratio.


1996 ◽  
Vol 81 (2) ◽  
pp. 985-997 ◽  
Author(s):  
C. E. Hahn

A sinusoidal forcing function inert-gas-exchange model (C. E. W. Hahn, A. M. S. Black, S. A. Barton, and I. Scott. J. Appl. Physiol. 75: 1863–1876, 1993) is modified by replacing the inspired inert gas with oxygen, which then behaves mathematically in the gas phase as if it were an inert gas. A simple perturbation theory is developed that relates the ratios of the amplitudes of the inspired, end-expired, and mixed-expired oxygen sine-wave oscillations to the airways' dead space volume and lung alveolar volume. These relationships are independent of oxygen consumption, the gas-exchange ratio, and the mean fractional inspired (FIO2) and expired oxygen partial pressures. The model also predicts that blood flow shunt fraction (Qs/QT) is directly related to the oxygen sine-wave amplitude perturbations transmitted to end-expired air and arterial and mixed-venous blood through two simple equations. When the mean FIO2 is sufficiently high for arterial hemoglobin to be fully saturated, oxygen behaves mathematically in the blood like a low-solubility inert gas, and the amplitudes of the arterial and end-expired sine-wave perturbations are directly related to Qs/QT. This relationship is independent of the mean arterial and mixed-venous oxygen partial pressures and is also free from mixed-venous perturbation effects at high forcing frequencies. When arterial blood is not fully saturated, the theory predicts that QS/QT is directly related to the ratio of the amplitudes of the induced-saturation sinusoids in arterial and mixed-venous blood. The model therefore predicts that 1) on-line calculation of airway dead space and end-expired lung volume can be made by the addition of an oxygen sine-wave perturbation component to the mean FIO2; and (2) QS/QT can be measured from the resultant oxygen perturbation sine-wave amplitudes in the expired gas and in arterial and mixed-venous blood and is independent of the mean blood oxygen partial pressure and oxyhemoglobin saturation values. These calculations can be updated at the sine-wave forcing period, typically 2–4 min.


Oxidative metabolism is essential for our cellular life. Although tissues such as skeletal muscle can operate for short periods anaerobically, human life does not continue for long in the absence of a ready supply of oxygen. Adequate oxygen delivery to tissues is essential for aerobic metabolism and disorders of delivery ultimately become life-threatening. The factors contributing to oxygen delivery are summarised in the oxygen flux equation: OXYGEN FLUX = CARDIAC OUTPUT × ARTERIAL OXYGEN CONTENT The cardiac output is the product of heart rate and stroke volume and amounts to about 5 litres per minute. The arterial oxygen content is the product of the blood’s haemoglobin concentration multiplied by the haemoglobin’s % saturation. The latter is determined by the partial pressure of oxygen in the blood. This is higher in arterial than in venous blood. A small, additional amount of oxygen is carried dissolved in the blood, the amount again determined by the oxygen partial pressure. The five litres of arterial blood delivered to the tissues each minute contain about 1000ml of oxygen. Only a quarter of this (250ml) is needed to support resting metabolism. There is therefore a large safety factor in oxygen delivery. This can be utilized, in concert with adaptive changes to cardiac output, vascular resistance and pulmonary ventilation, in situations such as muscular exercise, where oxygen demand increases dramatically, or at high altitude where inspired oxygen is low. Oxygen delivery depends on the cardiovascular system, respiratory system and the blood. In the lungs, blood in the alveoli is brought into close proximity with alveolar air so that oxygen can diffuse easily into the blood and carbon dioxide, a major waste product of metabolism, can diffuse into the alveolar air. Alveolar air is kept refreshed with atmospheric air by pulmonary ventilation which keeps the partial pressures of oxygen and carbon dioxide in alveolar air and pulmonary capillary blood in a constant equilibrium. This process ensures that pulmonary venous blood and systemic arterial blood have high oxygen and low carbon dioxide partial pressures. Once in the blood, almost all of the oxygen combines with haemoglobin and is transported by the cardiovascular system to the tissues.


1998 ◽  
Vol 84 (2) ◽  
pp. 683-694 ◽  
Author(s):  
Victor Cardenas ◽  
Thomas A. Heming ◽  
Akhil Bidani

Cardenas, Victor, Jr., Thomas A. Heming, and Akhil Bidani.Kinetics of CO2 excretion and intravascular pH disequilibria during carbonic anhydrase inhibition. J. Appl. Physiol. 84(2): 683–694, 1998.—Inhibition of carbonic anhydrase (CA) activity (activity in red blood cells and activity available on capillary endothelium) results in decrements in CO2 excretion (V˙co 2) and plasma-erythrocyte CO2-[Formula: see text]-H+disequilibrium as blood travels around the circulation. To investigate the kinetics of changes in blood [Formula: see text]and pH during progressive CA inhibition, we used our previously detailed mathematical model of capillary gas exchange to analyze experimental data of V˙co 2and blood-gas/pH parameters obtained from anesthetized, paralyzed, and mechanically ventilated dogs after treatment with acetazolamide (Actz, 0–100 mg/kg iv). Arterial and mixed venous blood samples were collected via indwelling femoral and pulmonary arterial catheters, respectively. Cardiac output was measured by thermodilution. End-tidal[Formula: see text], as a measure of alveolar[Formula: see text], was obtained from continuous records of airway [Formula: see text] above the carina. Experimental results were analyzed with the aid of a mathematical model of lung and tissue-gas exchange. Progressive CA inhibition was associated with stepwise increments in the equilibrated mixed venous-alveolar [Formula: see text] gradient (9, 19, and 26 Torr at 5, 20, and 100 mg/kg Actz, respectively). The maximum decrements in V˙co 2were 10, 24, and 26% with 5, 20, and 100 mg/kg Actz, respectively, without full recovery ofV˙co 2 at 1 h postinfusion. Equilibrated arterial [Formula: see text]overestimated alveolar [Formula: see text], and tissue [Formula: see text] was underestimated by the measured equilibrated mixed venous blood[Formula: see text]. Mathematical model computations predicted hysteresis loops of the instantaneous CO2-[Formula: see text]-H+relationship and in vivo blood[Formula: see text]-pH relationship due to the finite reaction times for CO2-[Formula: see text]-H+reactions. The shape of the hysteresis loops was affected by the extent of Actz inhibition of CA in red blood cells and plasma.


2020 ◽  
Vol 133 (3) ◽  
pp. 534-547
Author(s):  
Philip J. Peyton ◽  
Jan Hendrickx ◽  
Rene J. E. Grouls ◽  
Andre Van Zundert ◽  
Andre De Wolf

Background According to the “three-compartment” model of ventilation-perfusion () inequality, increased scatter in the lung under general anesthesia is reflected in increased alveolar deadspace fraction (Vda/Va) customarily measured using end-tidal to arterial (a-a) partial pressure gradients for carbon dioxide. a-a gradients for anesthetic agents such as isoflurane are also significant but have been shown to be inconsistent with those for carbon dioxide under the three-compartment theory. The authors hypothesized that three-compartment Vda/Va calculated using partial pressures of four inhalational agents (Vda/Vag) is different from that calculated using carbon dioxide (Vda/Vaco2) measurements, but similar to predictions from multicompartment models of physiologically realistic “log-normal” distributions. Methods In an observational study, inspired, end-tidal, arterial, and mixed venous partial pressures of halothane, isoflurane, sevoflurane, or desflurane were measured simultaneously with carbon dioxide in 52 cardiac surgery patients at two centers. Vda/Va was calculated from three-compartment model theory and compared for all gases. Ideal alveolar (Pag) and end-capillary partial pressure (Pc’g) of each agent, theoretically identical, were also calculated from end-tidal and arterial partial pressures adjusted for deadspace and venous admixture. Results Calculated Vda/Vag was larger (mean ± SD) for halothane (0.47 ± 0.08), isoflurane (0.55 ± 0.09), sevoflurane (0.61 ± 0.10), and desflurane (0.65 ± 0.07) than Vda/Vaco2 (0.23 ± 0.07 overall), increasing with lower blood solubility (slope [Cis], –0.096 [–0.133 to –0.059], P < 0.001). There was a significant difference between calculated ideal Pag and Pc’g median [interquartile range], Pag 5.1 [3.7, 8.9] versus Pc’g 4.0[2.5, 6.2], P = 0.011, for all agents combined. The slope of the relationship to solubility was predicted by the log-normal lung model, but with a lower magnitude relative to calculated Vda/Vag. Conclusions Alveolar deadspace for anesthetic agents is much larger than for carbon dioxide and related to blood solubility. Unlike the three-compartment model, multicompartment scatter models explain this from physiologically realistic gas uptake distributions, but suggest a residual factor other than solubility, potentially diffusion limitation, contributes to deadspace. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New


1985 ◽  
Vol 50 (8) ◽  
pp. 1642-1647 ◽  
Author(s):  
Štefan Baláž ◽  
Anton Kuchár ◽  
Ernest Šturdík ◽  
Michal Rosenberg ◽  
Ladislav Štibrányi ◽  
...  

The distribution kinetics of 35 2-furylethylene derivatives in two-phase system 1-octanol-water was investigated. The transport rate parameters in direction water-1-octanol (l1) and backwards (l2) are partition coefficient P = l1/l2 dependent according to equations l1 = logP - log(βP + 1) + const., l2 = -log(βP + 1) + const., const. = -5.600, β = 0.261. Importance of this finding for assesment of distribution of compounds under investigation in biosystems and also the suitability of the presented method for determination of partition coefficients are discussed.


2021 ◽  
Vol 11 (3) ◽  
pp. 164
Author(s):  
Mahmoud Al-Obeidallah ◽  
Dagmar Jarkovská ◽  
Lenka Valešová ◽  
Jan Horák ◽  
Jan Jedlička ◽  
...  

Porcine model of peritonitis-induced sepsis is a well-established clinically relevant model of human disease. Interindividual variability of the response often complicates the interpretation of findings. To better understand the biological basis of the disease variability, the progression of the disease was compared between animals with sepsis and septic shock. Peritonitis was induced by inoculation of autologous feces in fifteen anesthetized, mechanically ventilated and surgically instrumented pigs and continued for 24 h. Cardiovascular and biochemical parameters were collected at baseline (just before peritonitis induction), 12 h, 18 h and 24 h (end of the experiment) after induction of peritonitis. Analysis of multiple parameters revealed the earliest significant differences between sepsis and septic shock groups in the sequential organ failure assessment (SOFA) score, systemic vascular resistance, partial pressure of oxygen in mixed venous blood and body temperature. Other significant functional differences developed later in the course of the disease. The data indicate that SOFA score, hemodynamical parameters and body temperature discriminate early between sepsis and septic shock in a clinically relevant porcine model. Early pronounced alterations of these parameters may herald a progression of the disease toward irreversible septic shock.


1979 ◽  
Vol 57 (5) ◽  
pp. 385-388 ◽  
Author(s):  
R. D. Latimer ◽  
G. Laszlo

1. The left lower lobe of the lungs of six anaesthetized dogs were isolated by the introduction of a bronchial cannula at thoracotomy. Catheters were introduced into the main pulmonary artery and a vein draining the isolated lobe. 2. Blood-gas pressures and pH were measured across the isolated lobe and compared with gas pressures in alveolar samples from the lobe. 3. When the isolated lobe was allowed to reach gaseous equilibrium with pulmonary arterial blood for 30 min, there was no significant difference between alveolar and pulmonary venous Pco2. Mean values of whole-blood base excess were similar in pulmonary arterial and pulmonary venous blood. 4. After injection of 20 ml of 8·4% sodium bicarbonate solution into a peripheral vein, Pco2, pH and plasma bicarbonate concentrations rose in the mixed venous blood. There was no change of whole-blood base excess across the lung, indicating that HCO−3, as distinct from dissolved CO2, did not enter lung tissue in measurable amounts. 5. No systematic alveolar—pulmonary venous Pco2 differences were demonstrated in this preparation other than those explicable by maldistribution of lobar blood flow.


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