Ann Thorac Surg 1997;64:100-104
© 1997 The Society of Thoracic Surgeons
Original Articles: Cardiovascular
Cooling Gradients and Formation of Gaseous Microemboli With Cardiopulmonary Bypass: An Echocardiographic Study
Hans J. Geissler, MD,
Steven J. Allen, MD,
Uwe Mehlhorn, MD,
Karen L. Davis, BS,
E. Rainer de Vivie, MD,
Mark Kurusz,
Ccp,
Bruce D. Butler, PhD
Department of Anesthesiology, University of Texas-Houston Medical School, Houston, Texas
Accepted for publication January 14, 1997.
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Abstract
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Background. Previous studies demonstrated gas emboli formation during rewarming from hypothermia on cardiopulmonary bypass when the temperature gradient exceeded a critical threshold. It also has been suggested that formation of arterial gas emboli may occur during cooling on cardiopulmonary bypass when cooled oxygenated blood exiting the heat exchanger is warmed on mixture with the patient's blood. The purpose of this study was to determine under what circumstances gas emboli formation would occur during cooling on cardiopulmonary bypass.
Methods. Eight anesthetized mongrel dogs were placed on cardiopulmonary bypass using a roller pump, membrane oxygenator, and arterial line filter. For emboli detection, we positioned a transesophageal echocardiographic probe at the aortic arch distal to the aortic cannula and Doppler probes at the common carotid artery and the arterial line. Cooling gradients between normothermic blood and cooled arterial perfusate of 5°, 10°, 15°, 20°, and 0°C (isothermal controls) were investigated. In addition to preestablished temperature gradients, we investigated the effect of rapid cooling (maximal flow through the heat exchanger at a water bath temperature of 4°C) after the initiation of normothermic cardiopulmonary bypass.
Results. Minimal gas emboli were detected at the aortic arch at gradients of 10°C or greater. The incidence of emboli was related directly to the magnitude of the temperature gradient (p < 0.01). No emboli were detected at the carotid artery. During rapid cooling, no emboli were observed either at the aorta or at the carotid artery.
Conclusions. Cooling gradients of 10°C or greater may be associated with gas emboli formation, but they may be of limited clinical significance because no emboli were detected distal to the aortic arch. During the application of rapid cooling, no emboli formation was observed.
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Introduction
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The occurrence of gaseous microemboli (GME) during cardiopulmonary bypass (CPB) has been acknowledged as one contributing factor [1, 2] to the varying degrees of cerebral dysfunction observed after cardiac operations [1, 3]. Although numerous sources of GME have been reported with CPB, changes in gas solubility caused by temperature differentials have received little attention with regard to GME formation. Previous studies [4–6] demonstrated gas emboli formation during rewarming from hypothermia on CPB when the temperature gradient exceeded a critical threshold. This observation is due to the increase in gas solubility in cooled solutions, whereas the evolution of gas bubbles occurs as solutions are rewarmed. On the basis of the work of Donald and Fellows [4, 5] almost 40 years ago, it also has been suggested that formation of arterial gas emboli may occur during cooling on CPB, when cooled oxygenated blood exiting from the heat exchanger is warmed on mixture with the patient's blood [2, 7, 8]. Therefore, perfusionists have been instructed to limit the temperature gradient between the heat exchanger and the patient during cooling [2, 7–10], but a particular controversy exists regarding the extent of the cooling gradient that should be observed [11, 12] and the application of rapid cooling, sometimes referred to as "crash cooling" [12–14].
The purpose of this study was to investigate the occurrence of GME during cooling on CPB in an in vivo model and with particular regard to current clinical recommendations. Because of their high sensitivity in the detection of gaseous microemboli, transesophageal and Doppler echocardiography were chosen for the investigation [15].
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Material and Methods
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All procedures were approved by The University of Texas Animal Welfare Committee and were consistent with the National Institutes of Health "Guide for the Care and Use of Laboratory Animals" (NIH publication 85-23, revised 1985)." Eight mongrel dogs (24.8 ± 1.5 kg) of either sex were anesthetized by intravenous administration of thiopental sodium (25 mg/kg body weight), endotracheally intubated, and mechanically ventilated with 50% oxygen using a volume-cycled respirator (Siemens-Elema AB, Sundbyberg, Sweden). Anesthesia was maintained with an intravenous infusion of 1% thiopental sodium in Ringer's solution.
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Surgical Preparation
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Fluid-filled catheters were placed into the left femoral artery and vein for arterial pressure monitoring and blood sampling, and fluid administration, respectively. A 7F thermodilution catheter was placed into the superior vena cava through the right jugular vein for determination of superior vena cava blood temperature. Body core temperature was obtained from an esophageal probe. After a median sternotomy and pericardiotomy, a 16F arterial perfusion cannula was introduced into the ascending aorta and a two-stage venous cannula (36F x 46F) was introduced into the right atrium and inferior vena cava.
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Cardiopulmonary Bypass
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Systemic anticoagulation was achieved by intravenous administration of heparin (300 IU/kg body weight). Additional doses of 150 IU/kg body weight were administered every 60 minutes throughout the experiment. Cardiopulmonary bypass was performed with two roller pumps for extracorporeal circulation and cardiotomy suction (Model 5000; Sarns Inc., Ann Arbor, MI). The extracorporeal circuit and the membrane oxygenator (Affinity venous reservoir bag, cardiotomy reservoir, and hollow-fiber oxygenator, Avecor Cardiovascular, Plymouth, MN; arterial filter H-640 [33 µm], Bard Cardiopulmonary, Tewksbury, MA) were primed with 1,700 mL of Ringer's lactated solution and 1,000 IU of heparin. To allow isolated recirculation of the extracorporeal circuit through the oxygenator-heat exchanger (Dual Cooler/Heater 11160; Sarns Inc.) after weaning from CPB, we inserted a shunt line between the arterial and venous lines (Fig 1
). Arterial perfusate temperature was obtained from a probe at the arterial outlet of the oxygenator. For test injections of air bubbles, a stopcock was placed in the arterial line downstream of the shunt line. Table 1 shows CPB-related data.
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Fig 1. . Cardiopulmonary bypass circuit and placement of echocardiographic and Doppler probes for emboli detection. (A-V = arteriovenous; Echo = echocardiography.)
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Ultrasonic Emboli Detection
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The common carotid artery was exposed for placement of a 10-MHz Doppler probe (Parks Electronics, Beaverton, MA). For direct visualization of emboli in the aorta, we manually positioned a biplane transesophageal echocardiographic probe (Aloka UST-5233, 5 MHz; Corometrics Medical Systems, Wallingfort, CT) at the aortic arch, about 2 cm distal to the arterial cannulation site. In 2 animals, an additional echocardiographic probe (Aloka UST-5233; Corometrics Medical Systems) was placed esophageally to monitor the descending aorta at the mitral valve level. On the extracorporeal circuit, a 5-MHz Doppler probe (Parks Electronics) was attached to the arterial line upstream from the shunt line and distal to the arterial filter. Residual emboli in the extracorporeal circuit were excluded by the absence of a positive Doppler signal during a recirculation period of at least 15 minutes before the initiation of CPB.
No attempt was made to quantify the detected emboli, because of the known technical and physical limitations related to the ultrasonic determination of bubble size and number [16, 17].
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Experimental Protocol
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After the initiation of CPB for about 5 minutes, the animals were weaned from CPB and the arterial and venous lines were clamped. The shunt line was opened and recirculation of the extracorporeal circuit through the heat exchanger was started. We investigated temperature gradients between normothermic superior vena cava blood (range, 35.8° to 37.2°C) and cooled arterial perfusate of 5°, 10°, 15°, and 20°C, as well as 0°C (isothermal controls). As soon as the desired temperature gradient was achieved, CPB was reinstituted by clamping the shunt line and simultaneously releasing the clamps on the arterial and venous lines. Echocardiographic images of the aortic arch, Doppler signals from the right common carotid artery, and, in 2 animals, echocardiographic images of the descending aorta were recorded for emboli detection. Preexisting emboli in the extracorporeal circuit were excluded by the absence of a positive Doppler signal from the arterial line before the reinstitution of CPB. Multiple temperature gradients could be examined in 1 animal after the restoration of baseline conditions. The order of investigated temperature gradients was varied between experiments, and accurate positioning of the Doppler and echocardiographic probes was verified by intermittent test injections of air bubbles into the arterial line. The test bubbles were created by repetitive injection between two 3-mL syringes through a stopcock of about 2 mL of blood and 0.1 mL of air.
In addition to temperature gradients, we investigated in 5 dogs whether emboli formation would occur during rapid cooling. After the initiation of normothermic CPB, rapid cooling of the arterial perfusate was started by maximal flow (setting IV: greater than 16 L/min) through the heat exchanger at a water bath temperature of 4°C. Emboli detection was performed in the same way as described for the temperature gradients.
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Statistics
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Data are presented as percentages or means plus or minus standard errors. Statistical analysis was performed using a paired Wilcoxon rank test. A p value less than 0.05 was considered significant.
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Results
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Temperature Gradients
Gaseous microemboli were detected by echocardiography at the aortic arch at temperature gradients of 10°C or greater (Table 2). The incidence of emboli detection increased significantly with the temperature gradient (p < 0.01). Isothermal controls were constantly negative. Figure 2 shows the influence of the temperature gradient on the incidence of emboli detection at the aortic arch. No emboli were detected distal to the aortic arch, either by Doppler at the site of the common carotid artery or by transesophageal echocardiography at the descending aorta. Although no quantification of detected emboli was performed, we can report the gross observation that in comparison to test injections of 0.1 mL of air dispersed in blood, the number and echogenicity of the emboli we visualized with temperature gradients appeared to be far less (Fig 3). Further, the magnitude of the temperature gradient apparently had no substantial influence on the echogenicity of the detected emboli.
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Table 2. . Cooling on Cardiopulmonary Bypass: Incidence of Emboli Detection at Different Temperature Gradients and During Rapid Coolinga
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Fig 2. . Influence of temperature gradient on incidence of emboli detection. The asterisk indicates p < 0.01 versus 0°C (control). (n.d. = no emboli detected.)
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Fig 3. . Echocardiographic images of gaseous microemboli in the aortic arch. (A) Gaseous microemboli after test injection of 0.1 mL of air dispersed in blood. (B) Minimal gaseous microemboli formation at a cooling gradient of 20°C. The arrow indicates the position of the aortic cannula.
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Rapid Cooling With Normothermic Prime at a Water Bath Temperature of 4°C
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During rapid cooling, no emboli at all were detected, either at the aortic arch or at the carotid artery or descending aorta. Accurate placement of the ultrasonic probes was verified by test injections (see Table 2
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Figure 4 shows the time course of esophageal, superior vena cava blood, arterial perfusate, and water bath temperature during rapid cooling.
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Fig 4. . Time course of esophageal (open squares), venous blood (filled circles), arterial perfusate (filled squares), and water bath (open circles) temperature during rapid cooling (maximal water flow through the cooler greater than 16 L/min at a water bath temperature of 4°C).
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Comment
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The data show that temperature gradients of 10°C or greater between normothermic blood and cooled arterial perfusate had the potential to create gaseous microemboli. The origin of the observed emboli was clearly related to the temperature differential, because the incidence of emboli detection increased significantly with the temperature gradient and isothermal controls were constantly negative.
The theoretic assumption that temperature gradients during cooling on CPB (cooling gradients) may result in the release of gas emboli into the arterial blood when cooled oxygenated blood exiting the heat exchanger is warmed on mixture with the patient's blood [2, 7, 8] is based on the work of Donald and Fellows [4], who reported the release of gas from blood during rewarming in an in vitro model. Thereafter, the significance of temperature gradients during the conduct of CPB has been investigated in various studies [6, 18, 19]. However, the clinical significance of these studies today appears to be limited, because they were conducted more than 30 years ago with the use of bubble [6, 19] or disc [18] oxygenators and in the absence of arterial filters. Because current ultrasonic techniques were not available, demonstration of gas emboli formation was limited to the detection of visible bubbles or pathologic evidence for ischemic brain damage at autopsy. Further, gas release was reported only during rewarming on CPB, and attempts to demonstrate bubble formation during cooling failed [6]. In addition, results of the in vivo experiments were contradictory, showing no evidence of embolic brain damage [5, 19] or demonstrating significant structural changes compatible with brain ischemia [6, 18].
Our investigation demonstrated the formation of GME at the aortic arch when the temperature differential between arterial perfusate and blood exceeded 10°C. However, because no emboli were detected at the site of the common carotid artery or descending aorta, we conclude that these GME were very short-lived or quickly dispersed below detection level. Therefore, their clinical significance as embolic agents may be limited.
The relevance of GME for neurologic outcome after CPB has been questioned [20, 21]. Johnston and colleagues [21] investigated the effect of GME on global and regional cerebral blood flow in an in vivo canine model and found no adverse effect of numerous GME. Left ventricular microbubbles, detected by intraoperative transesophageal echocardiography during cardiac surgery, were not predictive of postoperative neurologic complications [20]. However, it also has been suggested that cerebral injury significant enough to cause mental and behavioral changes can occur at a level that escapes detection with currently available techniques [1]. Determination of regional cerebral blood flow with microspheres cannot exclude microfocal injuries [21]. Psychometric tests for the evaluation of minimal cerebral injury are expensive and have been found to be difficult to standardize and interpret because of the great variation between individuals [1]. Furthermore, GME have the potential to promote the formation of particulate emboli by facilitating leukocyte and platelet aggregation, complement activation, and fibrin deposition [21]. Therefore, it still should be the objective to minimize the occurrence of GME during CPB as much as possible.
No emboli at all were detected during rapid cooling with normothermic prime at a water bath temperature of 4°C, although the gradient between esophageal (core) and water bath temperature exceeded 20°C. However, the determinative temperature gradient for GME formation was the actual gradient in the aortic arch, where the mixing between arterial perfusate and blood took place. Because rapid cooling caused a fast, but steady and continuous, temperature decrease of the arterial perfusate, in distinction to a preestablished gradient, it can be concluded that the resulting temperature differentials at the perfusate–blood interface in the aortic arch were too gradual to allow gaseous emboli formation. Although the technique of rapid cooling (with normothermic or cold prime) has been practiced in various institutions [12], its safety with regard to GME release has been questioned [14]. Our findings suggest that the application of rapid cooling with normothermic prime is not associated with GME formation, whereas a temperature differential between cooled CPB prime and the patient's blood has the potential to create GME when the gradient is 10°C or greater. Although the clinical significance of the demonstrated GME is uncertain, because no emboli could be detected distal to the aortic arch, avoidance of GME formation still appears to be desirable for various reasons [1, 21]. In our experiments, GME formation during cooling on CPB was prevented by minimizing the temperature difference between CPB prime and the animal's blood.
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Acknowledgments
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We thank Mr Ira Lown for his excellent technical assistance and Mr Daniel Allen for the preparation of Figure 1. We express our appreciation to James J. Grady, DrPH, Senior Biostatistician, University of Texas, Medical Branch at Galveston, for his consulting advice on the statistical methods portion of the article.
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Footnotes
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Address reprint requests to Dr Butler, Department of Anesthesiology, University of Texas-Houston Medical School, 6431 Fannin, MSMB 5.020, Houston, TX 77030 (e-mail: bbutler{at}anes1.med.uth.tmc.edu).
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Abstract
Introduction
