Anesth Analg 2002;94:1107-1112
© 2002 International Anesthesia Research Society
CARDIOVASCULAR ANESTHESIA
Pulmonary Gas Exchange in Coronary Artery Surgery Patients During Sevoflurane and Isoflurane Anesthesia
Alexander Loeckinger, MD,
Christian Keller, MD,
Karl H. Lindner, MD, and
Axel Kleinsasser, MD
Department of Anesthesiology, Critical Care and Emergency Medicine, The Leopold-Franzens University Innsbruck, Innsbruck, Austria
Address correspondence and reprint requests to Alexander Loeckinger, MD, Department of Anesthesiology, Critical Care and Emergency Medicine, The Leopold-Franzens University Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria. Address e-mail to alex.loeckinger{at}uibk.ac.at
 |
Abstract
|
|---|
As the surgical population ages, the number of patients presenting with coronary artery disease and age-related loss of pulmonary recoil will increase. Although their influence on gas exchange in this population remains unknown, sevoflurane and isoflurane are used for an increasing variety of surgical procedures. We examined pulmonary gas exchange (multiple inert gas elimination technique) in 30 patients presenting for coronary artery bypass grafting. After a baseline measurement taken during midazolam anesthesia, patients were continued on sevoflurane (n = 10), isoflurane (n = 10), or midazolam (n = 10) for 20 min, then a second measurement was taken. During sevoflurane and isoflurane anesthesia, blood flow to lung areas with a low ventilation/perfusion ratio (
a/
) was significantly increased in comparison with control. During sevoflurane anesthesia, blood flow to lung areas with a normal a/ ratio (76 ± 12 versus control: 89 ± 5, mean ± SD) and PaO2 (138 ± 31 versus control: 156 ± 35 mm Hg, mean ± SD) were depressed, whereas an increase in a/-dispersion (log SDQ) was observed during isoflurane anesthesia. We conclude that both sevoflurane and isoflurane alter the distribution of perfusion in the lung, but only sevoflurane significantly depresses PaO2.
IMPLICATIONS: Both sevoflurane and isoflurane modified pulmonary blood flow in patients with coronary artery disease, but only sevoflurane depresses arterial oxygenation in this population.
|
Introduction
|
|---|
Many studies performed in vitrohave shown that halogenated volatile anesthetics depress the arterial partial pressure of oxygen (PaO2) by attenuation of hypoxic pulmonary vasoconstriction (HPV) (1). In vivo studies regarding HPV and volatile anesthetics, however, have been less consistent (1). The central function of HPV is to limit the amount of intrapulmonary right-to-left shunt and subsequently to confine the depression of PaO2 (2). This is accomplished by increasing the blood flow to better aerated lung areas, which leads to improved conditions for the use of alveolar air (2). If this regional response to alveolar hypoxia is impaired by volatile anesthetics, the affected lung areas fail to achieve an adequate end-capillary PaO2 during anesthesia (3–5), and intrapulmonary shunt (QS/QT) increases. Whereas the use of classic vapor halothane declines, sevoflurane and isoflurane are used for an increasing variety of surgical procedures. Furthermore, there is a progressive aging of the population of surgical patients, and the percentage of those presenting with coronary artery disease (CAD) and age-related loss of pulmonary recoil will increase. The effects of newer volatile anesthetics on pulmonary gas exchange in this population, however, remain unclear. Our aim was to examine the influence of sevoflurane and isoflurane on pulmonary gas exchange in patients presenting for coronary artery bypass grafting (CABG). For a precise evaluation of the expected gas exchange alterations during volatile anesthesia, the multiple inert gas elimination technique (MIGET) was used. We hypothesized that volatile anesthesia changes ventilation/perfusion relationships and PaO2 significantly more in comparison with anesthesia with midazolam.
|
Methods
|
|---|
This study was approved by the institutional ethics committee, and written informed consent was obtained from all patients. Inclusion criteria consisted of the following: patients scheduled for CABG, CAD with 2 to 4 vessel disease, body mass index between 20 and 25, and age older than 60 years. Patients presenting with obesity, premedication with nitrates, pulmonary hypertension, a history of obstructive lung disease, or valvular cardiac disease were excluded.
After preoxygenation for at least 3 min, anesthesia was induced by using midazolam 0.07–0.14 mg/kg, fentanyl 7 µg/kg, and rocuronium 0.6 mg/kg. This was followed by manual ventilation at a fraction of inspired oxygen (FIO2) of 1.0 for 60 s and subsequent tracheal intubation. Lungs were ventilated by using 7 mL/kg tidal volume at a respiratory rate of 15 breaths/min (SA 2, semi-open circle; Dräger, Lübeck, Germany). After intubation, FIO2 was immediately set to 0.4. Positive end-expiratory pressure was set to 5 cm H2O during the period of observation in all patients. During insertion of catheters, anesthesia was maintained by a constant infusion of fentanyl and midazolam as required. An arterial catheter (radial artery, nondominant hand), a central venous catheter (left subclavian vein), and a 7.5F pulmonary artery catheter (right internal jugular vein) were inserted. Patients were then randomly assigned to receive isoflurane (n = 10) or sevoflurane (n = 10) anesthesia, or to be continued on midazolam. After completed induction of anesthesia, intubation, and insertion of catheters, a baseline measurement including blood gas, inert gas, respiratory, and hemodynamic variables was taken. Anesthesia was then continued with sevoflurane at 2.0 vol% end-tidal concentration, isoflurane at 1.1 vol% end-tidal concentration, or with midazolam IV at a continuous infusion of 2–3 µg · kg-1 · min-1. In all patients, fentanyl was continued at 0.3–0.4 µg · kg-1 · min-1. Twenty minutes was then allowed for equilibration, before the second measurement was taken. Twenty minutes was chosen because it is a sufficiently long period for achieving steady-state conditions with both vapors and it also keeps the interval of anesthesia without surgery as brief as practically feasible. During this period, no surgery was performed and no other drugs except the anesthetics described were administered. After completion of the second measurement, anesthesia was continued according to the needs of the patient.
Distributions of ventilation and perfusion were determined by using the MIGET in a standard manner (6–9). The main goals of the MIGET are precise calculations of the amounts of blood flow or ventilation to lung areas with zero ventilation (shunt, ventilation/perfusion ratio [a/] < 0.005), limited ventilation (low a/, a/ > 0.005 through 0.1), and normal ventilation (normal a/, a/ > 0.1 through 10). Ventilation of unperfused lung areas (alveolar dead space, a/ > 100) may also be calculated. The MIGET is based on the assumptions that ventilation and blood flow were continuous, not tidal or pulsatile, respectively, and that all calculated lung units were in a steady state. To perform the MIGET, a mixture of 6 inert gases, including sulfur hexafluoride, ethane, cyclopropane, halothane, diethyl ether, and acetone, was dissolved in saline and infused via a peripheral vein at a rate of 3 mL/min. These substances have different blood gas solubilities and accordingly a different retention excretion behavior on the passage through the lung. The infusion was started at least 30 min ahead of the first set of measurements. Ten-milliliter blood samples were collected in heparinized glass syringes from the pulmonary and the radial artery. Thirty-milliliter mixed expired gas samples were obtained from a heated mixing chamber into warmed gas-tight glass syringes. All samples were kept at a temperature of 38°C and immediately prepared for analysis. Inert gas extraction was performed as described by Wagner et al. (6,7). Concentrations of inert gases were measured by using gas chromatography. The gas chromatograph was equipped with packed columns, a flame ionization detector, and an electron capture detector. The device was exclusively set up and used for the technique and was calibrated before each set of measurements. Ventilation/perfusion distributions were then computed from inert gas data by using the 50-compartment model of Evans and Wagner (8). The basis of this calculation is comparison of the ratios of retention and excretion of the individual gases in mixed venous and arterial blood and in mixed expired air. Other factors are incorporated in this calculation, including cardiac output, respiratory minute volume, temperature, and barometric pressure. Because the tracer gas halothane cannot be chromatographically measured during application of sevoflurane or isoflurane at anesthetic concentrations (peak overlapping), distributions of ventilation and perfusion were calculated from five inert gases at the second measurement in all groups.
For examining the irreducible variability (noise) in the data, the residual sum of squares (RSS) was calculated and used as an indicator of fit of the experimental data in this model (9). Mean arterial, central venous, pulmonary arterial, and pulmonary arterial occlusion pressure were measured by using an anesthesia monitor (AS-3; Datex, Helsinki, Finland) and standard pressure transducers, which had been zeroed to the level of the right atrium. Hemodynamic measurements were taken immediately before each collection of blood and expired samples for inert gas determination. Arterial and mixed venous samples of 2 mL each were collected and instantly analyzed for the partial pressures of oxygen (PO2), carbon dioxide (PCO2), and pH by using a blood gas analyzer (Ciba Corning 806; Ciba-Geigy, Basel, Switzerland). Values were corrected to body temperature.
Statistical analysis of hemodynamic, blood gas, and inert gas variables was done by using an analysis of variance for repeated measurements. A two-sided test was used. Significant differences were further post hoc examined by using the Newman-Keuls test. Data were also tested for normal distribution. All values were presented as mean ± SD. A P value < 0.05 was considered significant.
|
Results
|
|---|
Demographic data are presented in Table 1. All variables listed were comparable among the groups. Furthermore, no intergroup differences were found at the baseline measurement. Inert gas variables are presented in Table 2 and Figure 1. Both sevoflurane and isoflurane anesthesia resulted in increased blood flow to lung areas with a low a/ ratio. Isoflurane, but not sevoflurane, increased the second moment of the distribution of perfusion (log SDQ). Mean of , reflecting the height of the perfusion curve, and log SDQ, reflecting the width of the perfusion curve, are shown in Figure 1. Typical distributions of ventilation and perfusion are shown in Figure 2. Curves were unimodal before and after administrations of the vapors. An indication of acceptable quality of the a/ distribution is an RSS of 
5.3 in half of the experimental runs (50th percentile) or 10.6 in 90% of the experimental runs (90th percentile) (9). In the present study, 90% of the RSS were <5.3 and 95% were <10.6. At the measurement/calculation using 5 inert gases, 93.3% of the RSS were <5.3 and 96.6% were <10.6.
View larger version (16K):
[in this window]
[in a new window]
|
Figure 1. The first moment (mean of ) and second moment (log SDQ) of the distribution of perfusion as a box-and-whiskers plot displaying the values for minimum, maximum, median, 25th percentile, and 75th percentile. Mean of represents the height of the distribution of perfusion, whereas log SDQ represents the width of the perfusion curve. In both graphs, the left triplet reflects the values at the baseline measurement during midazolam anesthesia, whereas the right triplet reflects the values after 20 min of midazolam (cont), isoflurane (isof), or sevoflurane (sevo) anesthesia. The boxes in the box-and-whisker plots consist of 25th and 75th percentiles, median and SD as the whiskers, respectively resulting in an asymmetrical presentation. *P < 0.05 compared with midazolam-control.
|
|
View larger version (34K):
[in this window]
[in a new window]
|
Figure 2. Distributions of ventilation and perfusion before and during vapor exposure and midazolam control on a log scale.
|
|
Measured and calculated blood gas and oxygen transport variables are shown in Table 3. Compared with control, sevoflurane significantly depressed PaO2, whereas other blood gas variables including pHa and PaCO2 remained stable.
Hemodynamic data are presented in Table 3. Compared with control, sevoflurane depressed cardiac index.
In patients treated with midazolam, total doses applied during the period of observation were 1.3 ± 0.2 mg fentanyl and 15 ± 0.4 mg midazolam (induction boluses included).
|
Discussion
|
|---|
In the present study, sevoflurane and isoflurane anesthesia resulted in modified inert gas exchange variables compared with midazolam-control when applied in patients scheduled for CABG. During sevoflurane anesthesia, the additive effect of an insignificantly increased blood flow to lung areas with a zero a/ ratio (shunt) and an increased blood flow to lung areas with a low a/ ratio resulted in a decreased PaO2. Isoflurane, however, increased low a/ perfusion without depressing normal a/ perfusion or PaO2. Furthermore, during isoflurane anesthesia, the second moment (9) of the distribution of perfusion (log SDQ) was increased, indicating a/ inhomogeneity.
Whether the observed differences are based on alterations in the HPV cannot be determined from our data, because a difference in pulmonary vascular resistance index between groups suggesting a modification in HPV was not observed. One plausible explanation is that vasodilation in basal, poorly aerated lung areas resulted in less blood passing through ventral, independent, and better-aerated lung areas. Sevoflurane induced a redistribution of pulmonary blood flow as shown with the MIGET obviously without changing the overall precapillary diameter of the lung. Also the fact that, in well-aerated ventral lung areas, alveolar pressure is (with rare exceptions) higher than the intravascular pressure (West-zone I condition) possibly supported this redistribution. The development of such alveolar pressures was also aided by continuous (positive end-expiratory pressure 5 cm H2O) positive pressure ventilation (10) used in our study.
The question arises at which site in the lung volatile anesthetics caused the detected redistribution of blood flow. Whereas HPV is predominantly caused by a local hypoxic alveolar gas composition and less by arterial hypoxia (1), opposing factors may apply to the inhibition of HPV via volatile anesthetics. A volatile anesthetic mediating a vasodilator action in poorly aerated lung areas reaches the site of action primarily through the pulmonary circulation. In other words, an anesthetic vapor taken up in lung units with a balanced a/ may, when reappearing in the lung with the pulmonary blood flow, cause the identical lung unit to shift to a lower a/.
Furthermore, circulatory factors possibly contributed to our results. At lower cardiac output values, however, increased oxygen uptake in the tissues occurs, resulting in a decreased mixed venous PO2. The degree to which mixed venous blood is loaded in the pulmonary capillary depends on the a/ ratio of the lung unit. If a certain degree of a/ mismatch is present and decreased cardiac output is superimposed, then arterial desaturation must result.
The choice of the population included in our study may have influenced our results. None of the examined patients presented with a history of chronic obstructive pulmonary disease because this was an exclusion criterion. Nevertheless, a certain degree of a/ inequality has to be presumed at the age of our patients (Table 1). In obstructive lung disease, the ventilation to units with a high a/ and dead space are particularly increased, whereas higher values of shunt are less common (11). When patients with chronic obstructive pulmonary disease, especially with bronchial asthma, are given a ß-adrenergic-based bronchodilator, a slight decrease in PaO2 can be observed (12). Because of the vasodilator action of ß-adrenergic drugs, a subsequent redistribution of pulmonary blood flow toward lung areas with a lower a/ ratio is induced. Our results during volatile anesthesia are comparable with these findings, because a shift to lung units with a low a/ was found during both isoflurane and sevoflurane anesthesia. Both vapors examined also had comparable effects on the bronchomotor tone in a canine model of bronchoconstriction associated to anaphylaxis (13).
Some limitations of this study should be noted. First, the application of the MIGET during volatile anesthesia poses a methodological problem. One of the tracer gases used in the MIGET is halothane, and during chromatographic measurements, halothane’s chromatographic peak is superposed by the volatile anesthetic applied. This is especially relevant for sevoflurane because its chromatographic peak has an extremely wide basis. Accordingly, halothane could not be measured during volatile anesthesia, and MIGET calculations were performed using five inert gases instead of six at the second measurement. The inert gas infusion always was prepared the classic way including halothane. Because halothane represents one point in the linear section of the retention/excretion relationship, differences compared with the six-gas analysis are negligible. Also the RSS (9) calculated from the five-gas analysis at the second measurement indicated adequate quality of our data.
We conclude that both sevoflurane and isoflurane modify pulmonary blood flow in patients with CAD and that sevoflurane anesthesia depresses PaO2 in this population.
|
Acknowledgments
|
|---|
This study was supported by the Department of Anesthesiology, Critical Care and Emergency Medicine, The Leopold-Franzens University Innsbruck, Innsbruck, Austria.
|
References
|
|---|
-
Eisenkraft JB. Effects of anaesthetics on the pulmonary circulation. Br J Anaesth 1990; 65: 63–78.[Free Full Text]
-
Von Euler US, Liljestrand G. Observations on the pulmonary arterial blood pressure in the cat. Acta Physiol Scand 1946; 12: 301–20.
-
Bjertnaes LJ. Hypoxia induced pulmonary vasoconstriction in man: inhibition due to di-ethyl ether and halothane anesthesia. Acta Anaesth Scand 1978; 22: 133–47.
-
Marshall BE, Cohen PJ, Klingenmaier CH, Aukberg S. Pulmonary venous admixture before, during and after halothane: oxygen anesthesia in man. J Appl Physiol 1969; 27: 653–7.[Free Full Text]
-
Marshall BE. Anesthesia for one-lung ventilation. Anesthesiology 1988; 69: 630–1.[ISI][Medline]
-
Wagner PD, Naumann PF, Laravuso RB. Simultaneous measurement by eight foreign gases in blood using gas chromatography. J Appl Physiol 1974; 36: 600–5.[Free Full Text]
-
Wagner PD, Saltzman JA, West JB. Measurement of continuous distributions of ventilation-perfusion ratios: theory. J Appl Physiol 1974; 36: 588–99.[Free Full Text]
-
Evans JW, Wagner PD. Limits on a/ distributions from analysis of experimental inert gas elimination. J Appl Physiol 1977; 42: 889–98.[Abstract/Free Full Text]
-
Roca J, Wagner PD. Principles and information content of the multiple inert gas elimination technique. Thorax 1993; 49: 815–24.[Abstract/Free Full Text]
-
Nunn JF. Pulmonary vascular resistance. In: Nunn JF, ed. Nunn’s applied respiratory physiology. 4th ed. Oxford: Butterworth-Heinemann, 1997: 141–2.
-
Wagner PD, Danzker DR, Dueck DR, et al. Ventilation-perfusion inequality in chronic obstructive pulmonary disease. J Clin Invest 1977; 59: 203–6.
-
West JB. Pulmonary pathophysiology: the essentials. 4th ed. Baltimore: Williams & Wilkins, 1992: 83–6.
-
Mitsuhata H, Saitoh J, Shimizu R, et al. Sevoflurane and isoflurane protect against bronchospasm in dogs. Anesthesiology 1994; 81: 1230–4.[ISI][Medline]
Accepted for publication December 11, 2001.
This article has been cited by other articles:
|
|
|
|
 
J. S. Savino and A. T. Cheung
Cardiac Anesthesia
Card. Surg. Adult,
January 1, 2008;
3(2008):
281 - 314.
[Full Text]
|
|
|
|
|
|
|
C. Praetel, M. J. Banner, T. Monk, and A. Gabrielli
Isoflurane Inhalation Enhances Increased Physiologic Deadspace Volume Associated with Positive Pressure Ventilation and Compromises Arterial Oxygenation
Anesth. Analg.,
October 1, 2004;
99(4):
1107 - 1113.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. S. Savino, T. F. Floyd, and A. T. Cheung
Cardiac Anesthesia
Card. Surg. Adult,
January 1, 2003;
2(2003):
249 - 281.
[Full Text]
|
|
|
Top
Abstract
Introduction
