Ann Thorac Surg 1995;60:1665-1670
© 1995 The Society of Thoracic Surgeons
Original Articles: Cardiovascular
Influence of Hemodynamics on the Performances of Intravascular Gas Exchangers
Tomislav Mihaljevic, MD,
Ludwig K. von Segesser, MD,
Martin Tönz, MD,
Boris Leskosek, BA,
Marko I. Turina, MD
Clinic for Cardiovascular Surgery and Research Division, Department of Surgery, University Hospital Zurich, Zurich, Switzerland
Accepted for publication July 11, 1995.
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Abstract
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Background. The intravascular gas exchanger is a lung assist device for augmentation of gas exchange in critically ill patients with severe acute respiratory failure. These patients often require inotropic support therapy due to the cardiovascular instability that almost inevitably accompanies severe respiratory failure.
Methods. We investigated the interaction of vasoactive medication (dopamine, nitroglycerin, and noradrenaline) with the gas exchange performances of the intravascular gas exchanger in a bovine experimental model.
Results. Dopamine administration highly increased cardiac output, caval flow rates, and diameter of vena cava inferior. These effects resulted in a significant increase in oxygen transfer (baseline, 35 ± 6 mL/min versus 153 ± 27 mL/min at 20 µg • kg-1 • min-1 of dopamine, p < 0.001) and carbon dioxide elimination (baseline, 35 ± 2 mL/min versus 47 ± 4 mL/min at 20 µg • kg-1 • min-1 of dopamine, p < 0.001). Administration of nitroglycerin did not cause significant changes of the hemodynamic parameters nor did it affect the oxygen transfer or carbon dioxide elimination. Noradrenaline caused a moderate increase in cardiac output and caval flow, but no changes of caval diameter. Hemodynamic changes were accompanied by an increase in oxygen transfer from 38 ± 5 mL/min to 68 ± 7 mL/min (p < 0.01) and carbon dioxide elimination from 33 ± 1 mL/min to 40 ± 1 mL/min (p = 0.03). The multiple regression analysis showed significant influence of changes in cardiac output on oxygen transfer (p < 0.001) and carbon dioxide elimination (p = 0.004). The administration of vasoactive drugs induced slight changes in caval diameter that did not significantly affect the gas transfer.
Conclusions. The results from our study reveal the major influence of cardiac output on efficiency of gas transfer of the intravascular oxygenator.
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Introduction
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The therapy of the severe respiratory failure remains the ultimate challenge for the clinicians in intensive care units. Aggressive ventilatory management with the positive pressure ventilation and the use of high oxygen concentrations may itself cause progressive respiratory injury [1]. Extracorporeal pump oxygenator systems (extracorporeal membrane oxygenation and ECCO2RAu: spell out ECCO2R) can take over complete gas exchange function of the failing lungs [2–4]. However, the use of such devices remains an invasive and complicated procedure requiring the permanent presence of the specialized team.
Recent advances in the membrane oxygenator technology led to the development of new devices for extrapulmonary gas exchange. Intravascular gas exchangers are respiratory assist devices for the therapy of severe, potentially reversible, acute respiratory failure [5, 6]. The device consists of multiple small diameter, siloxane-coated, hollow fibers. It is inserted surgically through the right common femoral or right internal jugular vein into the superior and inferior caval veins, so that venous blood entering the right atrium flows around the crimped fibers of the device. Gas exchange (oxygen to the blood and carbon dioxide from the blood) takes place across the gas permeable surface of the hollow fibers as a result of the differences in partial pressures of blood gases and 100% of oxygen flowing inside the hollow fibers.
The extensive laboratory evaluation of intravascular gas exchangers performances led to their use in clinical trials [7, 8]. Most of the patients included in clinical studies suffered from the adult respiratory distress syndrome often combined with sepsis syndrome-positive inotropic support [9–12]. Changes in hemodynamics due to administration of vasoactive drugs may have an influence on the gas transfer of the intravascular oxygenator.
The purpose of this study was to evaluate the influence of the vasoactive medication on the performance of the intravascular gas exchanger in a laboratory setting.
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Material and Methods
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Animal Instrumentation
The study was performed in 5 calves (mean body weight ± standard error, 76 ± 2 kg). After induction of anesthesia with thiopental sodium, the animals were intubated and placed in the right lateral decubitus position. The anesthesia was maintained using volatile anesthetics. Controlled-volume ventilation (Siemens, Servo 900; Au: city?, Germany) was used in all animals. Ventilatory setting was adjusted to achieve normoventilation (ventilatory frequency, 14 to 20 strokes/min according to body weight with an inspired oxygen fraction of 0.33). Standard monitoring included electrocardiogram, arterial catheter, and central venous catheter. A pulmonary artery catheter for determination of cardiac output and continuous monitoring of mixed venous oxygen saturation (Sat-2 Oximeter/Cardiac Output Computer; Baxter Healthcare Corp, Edwards Critical-Care Division, Irvine, CA) was introduced through the left external jugular vein and floated into position by means of standard clinical procedure. The flow in the caudal portion of the inferior vena cava was measured using an additional pulmonary artery catheter for continuous thermodilution cardiac output determination (8F; IntelliCath, Baxter Healthcare Corp) that was introduced through the femoral vein into the inferior vena cava. After the instrumentation the calf was turned to the left lateral decubitus position. A retroperitoneal approach through the infracostal paravertebral incision was used to expose the inferior vena cava. Two ultrasonic crystals (Triton; Sonomicrometry, San Diego, CA) for the measurement of the diameter of inferior vena cava were placed bilaterally on the anterior and posterior surface of the inferior vena cava at the level of the inferior costal arch margin. A computerized monitoring system (PPG, Hellige GMBH, Freiburg, Germany) enabled the continuous monitoring and recording of changes in hemodynamic parameters and the caval diameter. After systemic heparinization (300 IU/kg body weight; Liquemin, Hoffman-La Roche, Basel, Switzerland) the intravascular oxygenator (38F, size 7; CardioPulmonics Inc, Salt Lake City, UT) was inserted surgically through the right external jugular vein into the superior and inferior caval veins. Each device consisted of 589 fibers with the gas exchange surface area of 0.21 m2. The tip of the intravascular gas exchanger was located a few centimeters above the level of the crystals from the ultrasonic dimension system. The correct position of the device was controlled with portable chest roentgenogram, using lateral supine films. An oxygen source (100% oxygen) was connected to the central gas line of the double lumen gas conduit. Exhaust gas line was connected to a capnograph modified for continuous readout (Accucap; Datascope, Paramus, NJ).
Additional doses of heparin maintained the activated clotting time at approximately 200 seconds throughout the experiment.
Autopsy of the animal and inspection of the device were performed at the end of each experiment.
The study was approved by the Institutional Review Board for the care of animal subjects. All animals were prepared for the experiment by the Department of Animal Care from Central Biological Laboratory of the University Hospital Zurich. The protocol complied with the ``Guide for the Care and Use of Laboratory Animals'' published by the National Institutes of Health (NIH publication 85-23, revised 1985).
Measurements
The measurements in the study included blood gas analysis, measurements of cardiac output and caval flows, concentration of carbon dioxide (CO2) in the effluent limb of the intravascular gas exchanger, as well as changes in the diameter of the inferior vena cava.
The oxygen transfer (in milliliters per minute) was calculated according to following equation: [(O2 content of pulmonary artery blood with the intravascular gas exchanger on - O2 content of pulmonary artery blood with the intravascular gas exchanger off) x cardiac output (L/min) x 10]. The CO2 elimination was calculated by multiplying the percentage of CO2 concentration in the effluent limb of the intravascular gas exchanger gas flow conduit by the gas flow rate through the device.
Measurements were made at the following doses of vasoactive medication: (1) dopamine (Dopamin; Braun Medical AG, Emmenbruecke, Switzerland) 5, 10, and 20 µg • kg-1 • min-1; (2) nitroglycerin (Perlinganit; Schwarz Pharma, Monheim, Germany) 2.5, 5, and 10 µg • kg-1 • min-1; and (3) noradrenaline (Noradrenaline; Sintetica S.A., Mendrisio, Switzerland) 0.05, 0.1, and 0.2 µg • kg-1 • min-1.
All measurements were made with and without gas flow through the device. There was a stabilization interval of 30 to 45 minutes between switching from one drug to another to allow the return of hemodynamic parameters to baseline values.
Statistical Analysis
All values are expressed as mean ± standard error. The analysis of variance of repeated measures test was used to analyze differences between cardiac output, caval flows, diameters of the inferior vena cava, proportion of caval flow versus cardiac output, and gas transfer data. Multiple regression was used to analyze the influence of cardiac output and changes in vascular diameter on the oxygen transfer and CO2 elimination. Differences were considered significant at the probability level of 0.05.
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Results
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Mean blood hemoglobin content was 9.7 ± 1.5 g/dL. Individual values of hemoglobin did not significantly change during the experiment in any of the animals. The mean gas flow through the intravascular gas exchanger was 2,503 ± 63 mL/min (range, 2,460 to 2,640 mL/min).
Dopamine (Fig 1
) caused a significant increase in cardiac output (baseline, 3.6 ± 0.4 L/min versus 13.4 ± 2.6 L/min at 20 µg • kg-1 • min-1 of dopamine, p = 0.03) and caval flow (baseline, 1.2 ± 0.3 L/min versus 4.5 ± 0.6 L/min at 20 µg • kg-1 • min-1 of dopamine, p = 0.002). However, these changes did not affect cardiac output/caval flow ratios (baseline, 32% ± 5% versus 32% ± 4% at 20 µg • kg-1 • min-1 of dopamine, p = 0.46). Continuous measurement of the diameter of the inferior vena cava revealed a slight but highly significant increase in the diameter of the vessel (baseline, 23.1 ± 1.0 mm versus 26.4 ± 1.0 mm at the highest dose of dopamine, p < 0.001). The increasing dosage of dopamine resulted in a fivefold increase of oxygen transfer (baseline, 35 ± 6 mL/min versus 153 ± 27 mL/min at 20 µg • kg-1 • min-1 of dopamine, p < 0.001) (Fig 2). Carbon dioxide elimination shared the same tendency, showing an increase from 35 ± 2 mL/min to 47 ± 4 mL/min (p < 0.001) (Fig 2). The oxygen transfer rate (transfer of oxygen per unit of caval flow rate) remained unchanged (baseline, 30 ± 3 mL/L versus 34 ± 6 mL/L at 20 µg • kg-1 • min-1 of dopamine, p = 0.58); however, the CO2 transfer rate showed a substantial decrease with an increased dosage of dopamine (baseline, 29 ± 3 mL/L versus 11 ± 1 mL/L, p < 0.001). The pulmonary artery oxygen tension rose from 41 ± 1 mm Hg to 54 ± 3 mm Hg (p < 0.05). The mixed venous oxygen saturation showed an significant increase from 67% ± 2% to 77% ± 3% (p = 0.03). The pH of pulmonary artery venous blood did not change significantly (baseline, 7.39 ± 0.03 versus 7.38 ± 0.02 at 20 µg • kg-1 • min-1 of dopamine, p = 0.87).
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Fig 1. . Changes in cardiac output, caval flow, caval flow/cardiac output ratio, and caval diameter caused by administration of dopamine.
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Nitroglycerin (Fig 3) caused no changes of cardiac output (baseline, 5.1 ± 1.2 L/min versus 5.7 ± 1.3 L/min at 10 µg • kg-1 • min-1, p = 0.84), caval flow (baseline, 1.9 ± 0.4 L/min versus 1.8 ± 0.6 L/min at 10 µg • kg-1 • min-1, p = 0.30), or cardiac output/caval flow ratio (baseline, 41% ± 10% versus 30% ± 7% at 10 µg • kg-1 • min-1, p = 0.15). The diameter of the inferior vena cava did not significantly change throughout the treatment with nitroglycerin (baseline, 22.7 ± 1.2 mm versus 22.4 ± 1.2 mm, p = 0.31). The baseline values of oxygen transfer and CO2 elimination were not affected by increasing doses of nitroglycerin (46 ± 7 mL/min versus 48 ± 9 mL/min for oxygen transfer, p = 0.84; 33 ± 2 mL/min versus 34 ± 2 mL/min for CO2 elimination, p = 0.31) (Fig 4). The gas exchange performances of intravascular gas exchanger per unit of caval blood flow remained unchanged (24 ± 2 mL/L versus 26 ± 4 mL/L for oxygen transfer rate, p = 0.76; 17 ± 2 mL/L versus 19 ± 3 mL/L for CO2 transfer rate, p = 0.58). The pulmonary artery oxygen tension showed no significant changes (42 ± 3 mm Hg versus 43 ± 4 mm Hg, p = 0.83). The mixed venous oxygen saturation as well as pH values of pulmonary artery blood remained unaffected by the increasing doses of nitroglycerin (69% ± 3% versus 68% ± 3% for mixed venous oxygen saturation, p = 0.89; 7.38 ± 0.02 versus 7.37 ± 0.02 for pH values, p = 0.22).
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Fig 3. . Changes in cardiac output, caval flow, caval flow/cardiac output ratio, and caval diameter caused by administration of nitroglycerin.
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Fig 4. . Oxygen transfer and carbon dioxide (CO2) elimination during the administration of nitroglycerin.
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Noradrenaline (Fig 5) induced significant increases in cardiac output (baseline, 4.3 ± 0.6 L/min versus 8.8 ± 1.2 L/min at 0.2 µg • kg-1 • min-1, p = 0.04) and caval flow (1.4 ± 0.2 L/min versus 2.8 ± 0.4 L/min, p = 0.03). These changes did not affect the values of cardiac output/caval flow ratio (33% ± 5% versus 32% ± 6%, p = 0.78). Noradrenaline caused no significant changes in caval diameter (baseline, 22.8 ± 1.3 mm versus 22.7 ± 0.9 mm at 0.2 µg • kg-1 • min-1, p = 0.15). Both oxygen transfer and CO2 elimination showed a slight but significant increase (38 ± 5 mL/min to 68 ± 7 mL/min for oxygen transfer, p < 0.01; 33 ± 1 mL/min to 40 ± 1 mL/min for CO2 elimination, p = 0.03) (Fig 6). The increase in oxygen transfer was accompanied with the nonsignificant increase in pulmonary artery oxygen tension values (42 ± 3 mm Hg versus 47 ± 2 mm Hg, p = 0.24) as well as with the significant increase in the mixed venous oxygen saturation (68% ± 1% versus 74% ± 1%, p = 0.04). Oxygen transfer rate remained unchanged (baseline, 27 ± 3 mL/L versus 24 ± 4 mL/L at 0.2 µg • kg-1 • min-1, p = 0.19). The CO2 transfer rate decreased with noradrenaline therapy (baseline, 23 ± 3 mL/L versus 14 ± 2 mL/L at 0.2 µg • kg-1 • min-1, p = 0.03). The pH values of the pulmonary artery blood were not significantly affected by the increasing doses of noradrenaline (baseline, 7.38 ± 0.03 versus 7.36 ± 0.03, p = 0.57).
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Fig 5. . Changes in cardiac output, caval flow, caval flow/cardiac output ratio, and caval diameter caused by administration of noradrenaline.
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Fig 6. . Oxygen transfer and carbon dioxide (CO2) elimination during the administration of noradrenaline.
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Multiple regression analysis revealed statistically significant influence of cardiac output on oxygen transfer (p < 0.001) and CO2 elimination (p = 0.004) (Table 1).
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Table 1. . Multiple Regression Analysis of Influence of Cardiac Output and Diameter of Inferior Vena Cava on Oxygen Transfer and CO2 Elimination Through the Intravascular Gas Exchanger
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Neither oxygen transfer (p = 0.18) nor CO2 elimination (p = 0.63) were influenced through the changes in the diameter of the inferior vena cava (Table 1
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Autopsy revealed no evidence of intravenous thrombosis, vascular injuries, or pulmonary emboli. No clots or deposits were visible at the surface of the explanted devices.
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Comment
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Results of our study demonstrate the major effect of cardiac output in the determination of gas transfer through the intravascular oxygenator. Pharmacologically induced changes of the diameter of the inferior vena cava did not significantly influence the gas transfer.
An intravascular oxygenator serves as a lung support device for critically ill patients with acute, reversible, respiratory failure whose clinical condition progressively deteriorates despite maximal conventional respiratory support. Cardiovascular instability is a common accompanying feature of severe respiratory failure requiring high doses of vasoactive medication. The use of vasoactive medication induces changes in cardiac output and caval diameter, both factors that can affect the gas transfer of the intravascular gas exchanger.
A well-documented correlation between blood flow, oxygen transfer, and CO2 elimination was shown in an experimental study using an ex vivo experimental model [13]. However, the blood flows through the gas exchange chamber used in that study were rather small (1 to 3 L/min). The pharmacologic intervention with dopamine performed in our study provoked a large increase of cardiac output and consequently, significantly higher flow rates through the inferior vena cava. Furthermore, we measured the flow in the caudal portion of the inferior vena cava, which represents only a smaller part of the total caval flow, therefore the actual flow through the inferior vena cava is significantly higher. This difference in blood flow rates, therefore, could explain the discrepancies between previously reported oxygen transfer values and the higher oxygen transfer achieved in our study. We were also able to demonstrate the previously described phenomenon of a decreased CO2 transfer rates (CO2 exchange per unit of caval blood flow) [13].
The position of intravascular oxygenator in the vena cava prefers the gas transfer of the venous blood from lower extremities, pelvic organs, and kidneys because of its longer contact with the large gas exchanging surface of the device. In contrary, the portal and hepatic venous blood flows reach only a small portion of the intravascular gas exchanger surface, which theoretically results in less gas transfer. Any pharmacologically induced change in the proportion of the blood flowing through the hepatic vein or inferior vena cava could affect the performance of the intravascular gas exchanger. Nevertheless, none of the drugs used in our study caused changes in caval flow to cardiac output ratio, indicating the absence of redistribution of venous flow through the vena cava.
The results from experimental studies suggested the possible influence of changes in the vascular diameters on the intravascular gas exchanger gas transfer (von Segesser et al, unpublished data). The use of small diameter gas flow chambers resulted in higher oxygen transfer and CO2 elimination compared with the results obtained with the same device placed in a large diameter gas transfer chamber. These results indicated the importance of a hollow fiber volume to blood space volume ratio in the gas transfer. The slight, but significant, increase in the caval diameter induced with high doses of dopamine is presumably the consequence of a high increase in caval flow rates. Nitroglycerin and noradrenaline induced no significant changes in caval diameter despite strong vasoactive properties of both drugs. Such discrete changes of caval diameter did not affect either oxygen transfer or CO2 elimination.
This in vivo analysis has demonstrated the relationship between cardiac output and caval flow rates in the gas transfer of intravascular oxygenator. Aggressive inotropic and fluid support therapy combined with permissive hypercapnia could optimize the gas transfer of the intravascular gas exchanger and improve the outcome of critically ill patients with acute respiratory failure [14]. Furthermore, the decrease in the cardiac output that occurs after most device implantations should be corrected to optimize the performances of the intravascular gas exchanger [12]. Low output states that do not respond to the inotropic support should be considered as a major contraindication for the insertion of the intravascular oxygenator.
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Footnotes
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Address reprint requests to Dr Mihaljevic, Division of Cardiac Surgery, Brigham and Women's Hospital, 75 Francis St, Boston, MA 02115.
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References
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Abstract
Introduction
