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Ann Thorac Surg 2002;73:203-208
© 2002 The Society of Thoracic Surgeons
a Division of Cardiothoracic Surgery, Veterans Affairs San Diego Health System, University of California at San Diego, San Diego, California, USA
b Veterans Medical Research Foundation, San Diego, California, USA
c Department of Anesthesia, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA
Accepted for publication August 14, 2001.
* Address reprint requests to Dr Macoviak, Cardiothoracic Surgery, VASDHS/UCSD, 3350 La Jolla Village Dr, MC 112J, San Diego, CA 92161, USA
e-mail: jamacoviak{at}ucsd.edu
| Abstract |
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Methods. A DS catheter inserted into the distal ascending aorta across the arch pumps blood through an upper lumen (maximum 2.25 L/min) directed by a blood-streaming baffle toward the arch vessels. A separate lower lumen pumps blood (maximum 3.75 L/min) into the aorta caudad to the inflated baffle. The baffle is flat and horizontal along the catheter. When the baffle is collapsed the heart or both lumens may perfuse all organs. For 30 minutes 8 randomized CPB pigs had corporeal cooling to 32°C and for 30 minutes had rewarming to 36°C. Eight randomized DS pigs had 25°C upper lumen cooling for 60 minutes. Lower lumen blood flow was streamed at 32°C for 30 minutes, then rewarmed to 36°C for 30 minutes.
Results. The change in relative lower lumen to brain blood flow as determined by brain-counted microspheres (15 µ) injected into the ascending aorta was less for DS brains than controls during full flow (DS 63.4 ± 129.5 versus CPB 2,585.4 ± 250.8, p < 0.001), and when injected into the ejecting-heart left atrium just after weaning off only lower lumen blood flow (DS 250.8 ± 297.3 versus CPB 1,159.1 ± 782.3, p < 0.001). DS brain temperatures were lower at an equal pump-off core temperature of 36°C ± 0.5°C (DS 31.6°C ± 3.2°C versus CPB 36.5°C ± 1.7°C, p < 0.025). Jugular O2 saturations were not different.
Conclusions. DS-CPB prioritizes pump-filtered separate cold blood flow to the brain over a blood-streaming baffle to wash away potentially surgery related air and particulate matter arising from the heart or ascending aorta.
| Introduction |
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The first hypothesis tested was that dual-stream (DS) cardiopulmonary bypass (CPB) can safely and separately perfuse the aortic arch vessels through the upper lumen of an aortic arch dual-stream catheter opening cephalad to a blood-streaming baffle and keeps cardiac and aortic origin emboli below the baffle. The second hypothesis tested was that safe enhanced brain hypothermia can be applied throughout and beyond dual-stream CPB for an extended duration of protection of the brain by hypothermia afforded by cold perfusion of blood through the upper lumen.
Standard single-stream CPB was compared with dual-stream CPB to test these hypotheses.
| Material and methods |
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Dual-stream CPB was implemented by a 24-F outer diameter, dual blood channel aortic arch inserted perfusion catheter (Cardeon Corp, Cupertino, CA) having an inflatable baffle integrally mounted on its exterior (Fig 1). The baffle is designed to assist in streaming extracorporeally pumped, cooled, and oxygenated blood emanating from the upper lumen openings above the baffle to direct flow toward the aortic arch branch blood vessels. Upper lumen arch blood flow is abundant relative to the branch aortic arch vessel runoff. The baffle is designed to allow upper lumen cooler blood to overflow the baffle and to spill into the extracorporeally pumped warmer oxygenated lower lumen corporeal bloodstream.
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When inflated the baffle within the aortic arch is designed to physically divide pumped arterial bloodstreams returned separately through an upper lumen and a lower lumen of the dual-stream catheter. If only the upper lumen is perfused and the baffle is inflated and if the heart is ejecting into the aorta it does so beneath or caudad to the baffle to stream emboli of cardiac and aortic origin into the bloodstream caudad to the baffle causing the emboli to flow downstream and away from the brain. Abundant flow above the runoff of the aortic arch branch vessels and the baffle design creates spillover from the upper lumen flow over the baffle. This design is intended to reduce brain-destined emboli by containing emboli of cardiac and aortic origin to the bloodstream caudad to the baffle causing the emboli to flow downstream and away from the brain.
The upper lumen aortic arch cold blood channel, flow rated at a maximum of 2.25 L/min, opens above the blood-streaming baffle. The lower lumen corporeal channel, flow rated at a maximum of 3.75 L/min, opens caudad to the baffle, downstream at the end of the catheter. The inner DS catheter diameters are sized to maintain this ratio of flow when total pump flow is adjusted upward or downward. No attempt was made to individually externally control flow through either lumen.
Total pump flow index was always kept more than 2 L · min-1 · m-2. Mean arterial pressure was maintained at 30 to 70 mm Hg. This was achieved using nitroprusside or epinephrine for after load control or with crystalloid volume supplementation in all animals. No aortic clamp was used in either group. The heart beat throughout the procedure and was nonejecting during CPB until CPB was weaned off.
Figure 3 shows the dual-stream cardiopulmonary bypass set up. Blood was pumped to the DS catheter through a 3/8-inch line to a Y-connection from a filtered oxygenator-heat exchanger fed by a centrifugal pump head. Blood from the venous reservoir was cooled, pumped and delivered blood at 32.8°C ± 1.7°C to the corporeal or lower blood channel of the dual-stream CPB catheter. From a quarter-inch arm of an in-line Y connector a second heat exchanger was used to deliver cold blood at 25.7°C ± 2.3°C, temperature measured in line, directly to the upper lumen arch channel of the aortic catheter. Another 3/8-inch line from the Y connector was continued to the lower lumen corporeal channel of the dual-stream CPB aortic catheter.
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An indwelling venous access line was placed retrograde into an internal jugular vein for jugular bulb O2 saturation blood gases. Aortic arch mean perfusion pressure and blood gases were monitored in the right brachiocephalic artery. Mean corporeal perfusion pressure was monitored in the midthoracic aorta. Each was measured with a 20-gauge angiocatheter advanced through an aortic arch insertion.
The dual-stream CPB group of 8 pigs randomized from the entire 16-pig group had a catheter-integral baffle inflated to segment the aortic perfusion channels within the aortic arch into upper lumen arch vessel blood flow initially at 25.7°C ± 2.3°C, which then gradually rose when mixed with rewarmed return from the lower body.
The ability to keep the upper lumen blood flow temperature lower than the lower lumen blood flow was dependent upon the resulting mixing of the two returned blood flows in the venous reservoir. This in turn was primarily determined by the temperature goals set for the lower lumen flow to determine targeted corporeal intraperitoneal temperatures.
Upper lumen cooler blood was continually delivered over the baffle at 0.5 L/min until the baffle was deflated 3 minutes after lower lumen blood flow was stopped after the heart began ejecting.
Corporeal blood was initially perfused through the lower lumen at more than 34°C, which was required to keep the core corporeal temperature above 32°C for 30 minutes. This was due to the spillover of cooler upper lumen blood over the baffle.
The lower lumen blood was then rewarmed to attain the core temperature of 35°C to 36°C more than 30 minutes. The heart continued to contract while empty throughout the experiment. The heart was always perfused with warmer blood that back-filled the coronary arteries from the lower lumen corporeal perfusion channel until the lower lumen blood flow was weaned.
For the standard aortic perfusion CPB randomized control group (n = 8), a single blood channel catheter system was used to perfuse the entire animal through a standard 22-F (Research Medical Inc) aortic arch catheter, using a single heat exchanger-oxygenator. The CPB group pigs had systemic cooling to 32°C ± 1.2°C for 30 minutes and then were rewarmed to 36°C for 30 minutes. The heart continued to contract while empty throughout the experiment. Microsphere injection times and locations, measurements, and the rewarming and pump weaning protocols were identical in control CPB pigs to the protocol for the DS group.
Assessments
Thermistors were placed 3 cm deep directly into the superior regions of the right and left halves of the brain through drilled burr holes. Thermistors were placed in the nasopharynx and separately passed across the diaphragm into the peritoneal cavity. In each group arterial, jugular bulb, and pulmonary artery (alpha stat) blood gases were measured at base line; at corporeal temperature 34°C after the onset of rewarming to simulate the time of cross-clamp release; and at approximately 15 minutes after rewarming.
At base line 15 µm red microspheres (106) were injected into the left atrium in 4 animals in each group (DS and CPB) at base line. In 4 separate animals in each group (DS and CPB) were injected with red microspheres into the aortic root with the baffle noninflated. In the same respective 4 animals in each group blue 15 µm microspheres (106) were reinjected with the baffle inflated in the aortic root at 34°C during rewarming at full flow through both catheter lumens to simulate cross-clamp release induced ascending aortic emboli during CPB and during dual-stream CPB. The CPB and the DS left atrium-injected group pigs, now with the baffle inflated, were reinjected with blue microspheres in the same respective 4 animals. This occurred at 0.5 L/min flow through the upper lumen of the catheter, with no pump flow through the lower lumen during full cardiac ejection to simulate cardiogenic air or particulate emboli expelled at the onset of cardiac ejection.
Statistical analyses
For comparison between DS-CPB and control CPB groups, Student t tests for small sample sizes were used to determine the significant differences in brain temperatures, O2 saturation, and microemboli flow counts. Comparisons were done between DS-CPB and control CPB groups within the same time point and across different times observed.
| Results |
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First, as seen in Figure 4, this was observed when the pigs had been rewarmed to 36°C. Then (106) 15 µm blue emboli were injected into the blood-filled left atrium during weaning from extracorporeal support when lower lumen corporeal perfusion was weaned off but with continued perfusion at 0.5 L/min through the upper lumen (DS brains 250.8 ± 297.3 versus CPB brains 1,159.1 ± 782.3, p < 0.001).
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| Comment |
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Differential hypothermic cerebral aortic perfusion was previously studied by us in animals using a dual-balloon/dual-lumen "cardio(neuro)pulmonary bypass" system targeting brain cooling specifically [4, 5]. Secondly studied was a single-lumen "hemi-arch stream wing catheter system" to stream emboli away from the brain and to semiselectively cool the brain during beating heart surgery in animals [6].
Dual-stream cardiopulmonary bypass would be a fundamental change in cardiac surgery extracorporeal perfusion physiology since Gibbon introduced CPB in 1953 [7]. In 1962 Edmunds and colleagues [8] showed that hypothermia in itself is nontoxic to cerebral tissues. This longstanding principle supports the application of deeper degrees of hypothermia to the brain during dual-stream CPB.
Jeopardy for adverse neurologic outcomes in the cardiac surgery patient is highest during and is acutely present throughout and for some time just beyond standard CPB [9, 10].
It is known that hypothermia (34°C to 29°C) profoundly decreases brain infarct size associated with reversible transient ischemic events [11]. Periodic hypotension, hypoxia, or arterial spasm and "reducible emboli" like a bubble, a small clot, or a lipid particle embolus that eventually lyses are in this category. After CPB, transient hypotension and hypoxia may occur for a variety of well-known reasons. Embolic brain injuries may occur in association with the greater numbers of carotid artery Doppler detected emboli at and after cross-clamp release and after the termination of CPB [12, 14].
The spectrum of etiologies of the major physical and more common subtle neuropsychometric deficits in many patients may result from one or more single significant irreversible injuries likely worsened by a "concatenation of brain injuries" superimposed, one on another. Such a chain reaction may be ameliorated or aggravated at several points on the chain. Aggravators along the chain may include additive serials of hypotension, macroembolization and microembolization, brain hyperthermia, anemia, and hypoxemia.
Hypothermia broadly provides neurologic protection throughout the complex pathways of brain ischemia. Firstly, a reduction in metabolic rate and energy depletion occurs. Secondly, decreased excitatory transmitter release occurs. Thirdly, reduced alterations in ion flux occur to prevent sodium and calcium increases that follow the decrease in ATP secondary to ischemia. Fourthly, reduced vascular permeability, reduced edema and reduced blood-brain barrier disruption are seen [11].
Several practitioners have questioned whether hypothermic CPB is truly advantageous with regard to brain protection. Normothermic perfusion has been associated with improved coagulation factors, shorter pump times, and equivalent cardiac outcomes but with a threefold increase in stroke compared with hypothermic CPB in one study [13]. Gaudino and associates [14] report strokes that occur in normothermic perfusion patients are greater in extent than those in hypothermic perfusion patients. Birdi and colleagues [15] noted, "if normothermic CPB proves to be detrimental to brain function, there may be little incentive for its routine use." As it is currently practiced CPB outflow blood temperatures may perilously exceed 41°C and the brain temperature may exceed 39°C [10].
The question becomes then, not whether brain hypothermia can be protective for the brain against transient reversible injuries but rather it is whether brain hypothermia has been optimally applied. Unquestionably the variably published results on studies addressing hypothermic protection of the brain during CPB are valid in their context in which the hypothermia was uniformly applied to the body and brain. In all prior studies brain hypothermia was not applied beginning in approximately the second half of conventional CPB when rewarming was begun [16, 17]. Only if brain hypothermia is present at the time of cross-clamp and partial occlusion clamp removal, and preferably at the time cardiac ejection begins and for some time thereafter, can the truly protective efficacy of brain hypothermia in cardiac surgery be determined [18, 19].
Those who have argued that hypothermia is not additively protective to the brain during CPB were likely correct, "as it has been practiced." None would argue that hypothermia is not protective at the cellular and organ levels as is known in molecular-based experimental studies and for organ transplantation preservation [11, 18, 19].
One question commonly arises: "Is hypothermia toxic in itself to the brain?" This was addressed by Edmunds and coworkers [18] in 1962 and it is generally accepted today that hypothermia in clinical ranges of perfusion blood temperatures more than 12°C and less than 34°C are not toxic to the brain. Those authors concluded, "no cerebral lesions (in canines) were found which could be ascribed to exhaustion of metabolites or to profound hypothermia without circulatory arrest."
A second question arises commonly as well: "Will the device cause more brain injury than it prevents when placed into the aortic arch?" The answer to this question cannot be known fully; however, many standard catheters are advanced into the aortic arch often beyond the left carotid artery and sandblast effects of shorter ones have been questioned. A study of 3,304 nonconsecutive, unselected patients undergoing heart surgery had transesophageal echo [20]. In 268 (8%) of patients aortic arch atheromas of more than 5 mm in diameter or that were mobile were observed. Whether this type of patient group as defined by transesophageal or by epiaortic ultrasound scanning would be at higher or lower risk with a DS catheter or a standard catheter remains to be studied. If one were to exclude use of the DS system in those 8% of cases, based on that study where 15.8% of the 268 patients with these unstable atheromas did experience a stroke, then the remaining 92% of patients may benefit from DS CPB. Because the blood-streaming baffle is designed to be gentle to the intima, and because many catheters used for standard single stream CPB are equally likely to extend into the aortic arch an equal distance, then only clinical usage can determine the true benefit of dual-stream CPB.
In another area of questions to be addressed, despite its modestly greater complexity, dual-stream CPB using existing extracorporeal technology may be more reproducible for cardiac surgery teams on the whole than less controllable beating heart approaches [21].
The primary limitations of this study as they may apply to human conditions include the smaller size of the aortas in the pigs used compared with typical adult human aortas; the model used is an acute nonsurvival model; and the absence of atheroma in the pig aortic arch that may be present in a human.
This study has shown the feasibility and physiologic safety of a new system dual-stream CPB that may improve cardiac surgical related neurologic outcomes. The new capabilities of this system include, firstly, provision of streamed "normothermic or tepid" blood flow to the body excluding the cold-perfused aortic arch vessels. Secondly, pulsatile natural cardiogenic rewarming of the brain is afforded and occurs gradually after CPB. Thirdly, cardiac and ascending aortic origin potentially macroembolic and microembolic laden brain blood flows are directed away from and downstream to the aortic arch vessels which receive luxuriant cold blood flow above the baffle of a dual-stream CPB catheter. Fourthly, a hypothermic brain milieu is attained before, during and following times when transient and reversible embolic or ischemic episodes generally occur at and just after cross-clamp release, partial occlusion clamp release, at the onset of cardiac ejection, and for some time after dual-stream CPB.
Based on this study of dual-stream CPB, a scientifically valid variety of potentially safer cardiac surgery perfusion protocols may necessarily evolve designed by researchers to meet their institutions preference when using dual-stream CPB. Controlled clinical studies of dual-stream CPB are warranted for patients having cardiac surgery who are at risk for brain injury to study its potential to significantly improve neurologic outcomes.
| Acknowledgments |
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| Footnotes |
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| References |
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