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Ann Thorac Surg 2000;69:1346-1350
© 2000 The Society of Thoracic Surgeons

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Original articles: Cardiovascular

Differential perfusion: a new technique for isolated brain cooling during cardiopulmonary bypass

^a Divisions of Division of Cardiothoracic Surgery, Mayo Foundation and Mayo Clinic, Rochester, Minnesota, USA
^b Division of Cardiothoracic Anesthesiology, Mayo Foundation and Mayo Clinic, Rochester, Minnesota, USA

Address reprint requests to Dr Cook, Mayo Foundation, 200 First St SW, Rochester, MN 55905
e-mail: cook.david{at}mayo.edu

	Abstract

Top Abstract Introduction Material and methods Results Comment References

 
Background. The purpose of this study was to determine the feasibility of differential perfusion of the aortic arch and descending aorta during cardiopulmonary bypass using a cannula designed for aortic segmentation.

Methods. Pigs weighing 57 kg (n = 8), underwent cardiopulmonary bypass using the dual lumen aortic cannula. An inflatable balloon separated proximal (aortic arch) and distal (descending aorta) ports. During differential perfusion, the aorta was segmented and the arch and descending aorta perfused differentially using parallel heat exchangers. Ability to independently control brain and body temperature, cardiopulmonary bypass flow rate and mean arterial blood pressure was determined.

Results. During differential perfusion cerebral hypothermia (27°C) with systemic normothermia (38°C) was established in 23 minutes. Independent control of arch and descending aortic flow and mean arterial blood pressure was possible. Analysis of internal jugular venous O₂ saturation data indicated an increase in the ratio of cerebral O₂ supply to demand during differential perfusion.

Conclusions. A cannulation system segmenting the aorta allows independent control of cerebral and systemic perfusion. This device could provide significant cerebral protection while maintaining the advantages of warm systemic cardiopulmonary bypass temperatures.

	Introduction

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Since the development of cardiopulmonary bypass (CPB) as a technique to facilitate cardiac surgery, management of temperature during CPB has been evolving [1]. For many years moderate hypothermia was standard for most cardiac operations, but since the introduction of warm heart surgery in 1991 many institutions have shifted to higher CPB temperatures [2]. A variety of advantages of warmer bypass temperatures are demonstrated or suggested in the literature. These include hemodynamic benefits resulting from the combination of better rhythm [1–5] and lower systemic vascular resistance in the period after CPB [3, 5, 6]. Furthermore, because of the elimination of the need for cooling and rewarming, the warm technique is also typically associated with shorter CPB times [7–9]. Postoperatively, a variety of studies have suggested that bleeding may be reduced with the warm technique [10, 11] and postoperative temperature "afterdrop" [12, 13] is probably reduced. Finally, the postoperative respiratory demands may be less with the warm technique and this has been shown by some investigators to be associated with shorter times to extubation [6, 14].

In spite of this experience with warmer CPB temperatures, there have been concerns over the neurologic effects of this technique. Hypothermia was introduced to increase flexibility in perfusion practice and because it offers important organ protection from ischemia [3]. A variety of reports have been published regarding the neurologic effects of warm CPB, citing both significantly increased neurologic morbidity with the technique [8, 15, 16], as well as no difference relative to patients undergoing hypothermic CPB [17–19]. In spite of advances in surgical technique and perfusion, neurologic morbidity is a primary reason why reservations persist over the use of warm CPB.

In addition to systemic hypothermia, a variety of techniques have been applied experimentally and clinically to provide more selective hypothermic cerebral protection. These include topical cooling as well as antegrade and retrograde cerebral perfusion [20, 21]. Another alternative, which may provide marked cerebral hypothermic protection, while maintaining warm body temperatures during CPB, would be segmentation of the aorta and differential perfusion of the arch and descending aorta.

The purpose of this study was to determine, in a swine model, the feasibility of differential perfusion of the arch and descending aorta with an aortic cannula (CNPB System, Cardeon Inc, Cupertino, CA) designed for aortic segmentation.

	Material and methods

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After review and approval by the Institutional Animal Care and Use Committee fasting pigs (n = 8) weighing 55 to 60 kg were studied. Pigs were premedicated with Telazol (Fort Dodge Labs, Fort Dodge, IA) (4 mg/kg) and xylazine (2 mg/kg) intramuscularly. General anesthesia was induced (halothane, 2% by mask) and the trachea was intubated. Peripheral intravenous access was secured and muscle relaxation obtained with pancuronium (0.1 mg/kg). Ventilation was controlled to maintain an arterial carbon dioxide tension at 35 to 40 mm Hg and an arterial oxygen tension at more than 150 mm Hg. Anesthesia was maintained with 0.5% to 1% halothane and a continuous intravenous infusion of fentanyl (0.7 µg · kg^-1 · min^-1) and ketamine (28 µg · kg^-1 · min^-1). A pancuronium infusion (0.3 µg · kg^-1 · min^-1) was administered to provide continuous muscle relaxation.

Ten-centimeter 18-gauge catheters were surgically inserted into right femoral and left axillary arteries for blood sampling and mean arterial blood pressure monitoring of the corporeal and arch circulations, respectively. Catheters were also placed into the left internal jugular vein (threaded cephalad to the base of the skull) and into the inferior vena cava (IVC) from the right femoral vein.

A wire thermocouple was advanced 20 cm into the IVC through a right femoral vein catheter. Brain temperature was monitored with a needle thermocouple placed 2 cm into the brain through a parietal skull burr hole. Thermocouples were also placed into the septum of the heart, nasopharynx, and rectum. Temperatures were recorded every minute with a multichannel recording system by a single microprocessor (TM-12, Physitemp Instruments Inc, Clifton, NJ) and downloaded to a laptop and stored on a floppy disk.

Blood gases and O₂ saturation (IL-BGE Analyzer and IL 482 Co-oximeter, Instrumentation Laboratories, Inc, Boston, MA) from the femoral artery, IVC, and internal jugular veins were obtained every 15 minutes during all phases of CPB. In addition, blood gas data were continuously monitored by a CPB in-line analyzer (CDI 400, Cardiovascular devices, Inc, Tustin, CA). The CPB flows and mean arterial blood pressure in the arch and corporeal circulation were recorded at 5-minute intervals throughout the experiment.

Cannulation and cardiopulmonary bypass
The heart was approached through a left thoracotomy and the pericardium reflected. A dual lumen 24F cannula (CNPB System), with an inflatable aortic balloon separating proximal and distal outflow ports, was inserted through a standard ascending aortotomy (Fig 1). The cannula was advanced such that the balloon was positioned distal to the origin of the left brachiocephalic artery. Cannula position was confirmed by one or more of the following techniques: transesophageal echocardiographic imaging of the proximal descending aorta, palpation of the inflated balloon distal to the left brachiocephalic artery, and observation of the left axillary waveform and loss of femoral arterial waveforms from aortic segmentation with balloon inflation. Venous drainage to the extracorporeal circuit was with a two-stage 46F cannula placed in the right atrium through the atrial appendage.

View larger version (17K): [in this window] [in a new window]   Fig 1. Schematic of the differential perfusion cannulation system. Cannula is positioned with balloon distal to the left brachiocephalic artery. Cannula balloon inflated for differential perfusion of the aortic arch and descending aorta. Blood flow through the cannula is coaxial.

The CPB was initiated and blood gases, total CPB flow (3.0 to 4.0 L/min or 2.0 to 2.7 L · min^-1 · m^-2), mean arterial blood pressure (60 to 70 mm Hg), and temperature (38°C to 39°C) were stabilized for at least 15 minutes before the aorta was segmented by balloon inflation. Differential perfusion (DP) was initiated and flows to both the arch and descending aorta were measured by ultrasonic flowmeters (Delphin II, Sarns 3M) placed on the two limbs of the circuit.

Cardiopulmonary bypass was divided into three phases: (1) CPB before DP, (2) DP, and (3) after DP. Differential perfusion was initiated after inflation of the cannula balloon with agitated saline or ultrasound contrast. The balloon was only filled to the extent required to eliminate the pulse pressure tracing observed in the femoral artery. With inflation of the balloon, cooling of the arch heat exchanger was initiated and arch flow was maintained at 1.0 to 1.5 L/min and descending aortic flow at 2.0 to 3.0 L/min. Alpha-stat management was used at all times when the perfusate of the arch was less than 37°C. Cooling continued until a 10°C difference between the cerebral and IVC temperatures was achieved. Differential perfusion was then maintained for 60 minutes. At the end of that time, the balloon was deflated, cooling of the arch heat exchanger was stopped, and the arch circulation was allowed to warm.

After completion of the experiment, the heart was fibrillated and CPB terminated. The heart and aorta (to the distal thoracic segment) were excised en bloc. The aorta was opened in a longitudinal fashion to verify cannula position. The aortic specimen was visually inspected for damage at the site of insertion and balloon inflation.

Data analysis
We determined the cooling time required to achieve a cerebral tissue temperature 10°C less than IVC temperature while maintaining corporeal normothermia (> 38°C). We also determined the duration of time that a 10°C temperature differential between brain and IVC was maintained. Duration and percentage of time after DP that cerebral temperature remained lower than 35°C was also determined. Changes in physiologic variables during the three study periods were assessed using one-way analysis of variance followed by Student-Newman-Keuls test when indicated. Differences in physiologic variables between the arch and descending aortic circulations during DP were tested using the Student’s t test. Data are expressed as mean ± standard error of the mean.

	Results

Top Abstract Introduction Material and methods Results Comment References

 
The mean animal weight was 57 ± 1.7 kg and mean body surface area, 1.5 ± 0.03 m². Placement of the dual lumen aortic cannula did not result in bleeding from the aortotomy site and in all 8 animals the balloon was positioned distal to the left brachiocephalic artery without difficulty.

Physiologic data before and during the three phases of bypass (pre-DP, DP, and post-DP) are provided in Table 1. Cardiopulmonary bypass was initiated (pre-DP phase) and the total CPB flow before the initiation of DP was 2.6 ± 0.1 L · min^-1 · m^-2. During this period axillary and femoral artery mean arterial blood pressures did not differ significantly. Furthermore, they did not differ from their respective values before bypass (Table 1). In addition, brain and IVC (corporeal) temperatures were unchanged. However, corporeal temperature was slightly greater than that of the brain. During this period (pre-DP) the internal jugular and IVC venous O₂ saturations were reduced relative to their pre-CPB values, but did not differ from each other (Fig 2). During bypass the hemoglobin concentration was reduced relative to the period before bypass.

View larger version (29K): [in this window] [in a new window]   Fig 2. Internal jugular (IJ) versus inferior vena cava (IVC) oxygen saturation before cardiopulmonary bypass (pre-CPB) and during the three phases of cardiopulmonary bypass. (Pre-DP = predifferential perfusion; DP = differential perfusion; Post-DP = postdifferential perfusion.) *Internal jugular venous oxygen saturation versus inferior vena cava oxygen saturation during differential perfusion (p < 0.0001) and after differential perfusion phases (p < 0.05). Values are mean ± standard error of the mean (n = 8).

Changes in brain and IVC temperatures during CPB are illustrated in Figure 3. At the time DP was initiated, the mean brain and IVC (corporeal) temperatures were 38.7 ± 0.2°C and 39.4 ± 0.3°C, respectively. The mean time to reach a 10°C differential between the two circulations was 23 ± 7 minutes. During this period the brain underwent an 11.6°C temperature decrease, whereas the IVC (corporeal) temperature decreased 1.9°C. The DP was maintained for 60 ± 2 minutes after the 10°C differential was established. During this time the mean brain and corporeal temperatures were 27.1 ± 0.4°C and 37.5 ± 0.3°C, respectively.

View larger version (14K): [in this window] [in a new window]   Fig 3. Temperature changes over the three phases of cardiopulmonary bypass. At time = 0 differential perfusion initiated. Error given as standard error of the mean at 10-minute intervals (n = 8).

At the end of 60 minutes of DP, the balloon was deflated and cooling of the arch flow was stopped. Rewarming of the brain after DP to a mean temperature of 37.7°C ± 0.3°C occurred during 29.6 ± 1.1 minutes and cerebral hyperthermia was not observed in any animal. In the post-DP phase, brain temperature remained less than 35°C for 57% ± 5% of the post-DP period. In addition, the internal jugular venous O₂ saturation remained higher than in the pre-DP phase (p = 0.007), but not different from the phase before CBP (Fig 2). The internal jugular venous O₂ saturation also remained higher than that of the IVC (81% ± 3% versus 43% ± 5%, p < 0.05) (Fig 2). Among the three CPB phases, there was no difference in the venous O₂ saturation of the IVC(p > 0.05).

Temperature monitored in the myocardium and nasopharynx underwent changes similar to those of the brain, whereas the rectal temperature changes were not significantly different from the IVC (corporeal) temperature (data not shown).

Finally, visual inspection of the aorta showed no evidence of either dissection from placement of the differential perfusion cannula or aortic disruption from inflation of the segmenting aortic balloon.

	Comment

Top Abstract Introduction Material and methods Results Comment References

 
In this study we show that DP of the arch and descending aorta with a cannula capable of segmenting the aorta allows for independent temperature control of these two circulations. Independent control of mean arterial pressure and CPB flow is also possible; selective delivery of therapeutic agents might also be devised.

The CPB circuit requires little modification to achieve DP. A cardioplegia heat exchanger was used to control arch temperature and a second pump head was used to control arch flow. However, the system might also be used with a single pump head design. Cerebral hypothermia was rapidly established, and easily maintained. In this study mild cerebral hypothermia and high internal jugular venous O₂ saturation persisted after deflation of the balloon; however, even greater cerebral benefit might result from hypothermic perfusion of the arch until closer to the termination of CPB.

This study has several limitations. We measured venous O₂ saturation of the internal jugular vein and cerebral temperature as indicators of cerebral protection during DP. It would be more desirable to have made direct measurements of cerebral blood flow and O₂ consumption, as well as to conduct a neurologic or pathologic outcome assessment in a survival study. However, in this first report of feasibility, those end points are beyond the scope of the investigation. Nonetheless, the degree of cerebral hypothermia we achieved and maintained has been associated with marked cerebral protection in ischemia models.

Another practical question raised by our study was how much flow should be directed to the arch and descending aortic circulations during DP. Cerebral blood flow measurements would also help with that determination. We chose to use a high total bypass flow in the pre-DP period (2.7 L · min^-1 · m^-2) and maintain that total body flow during DP. The venous O₂ saturation and mean arterial blood pressure data suggest that during differential perfusion our arch flow may have been higher than required and the descending aortic flows lower than desirable.

Our surgical approach also deserves comment. We approached the heart from a left lateral thoracotomy to allow for palpation of the aortic balloon in the proximal descending aorta. However, we expect that clinical placement of the segmenting aortic cannula would be as simple when approached through a median sternotomy. Furthermore, balloon placement is easily confirmed by either transesophageal echocardiography or observation of the arterial pressure tracing in the left upper extremity so palpation is not required.

Finally, the potential risk for aortic injury with a balloon cannula must be considered. In this series there was no visible evidence of aortic injury at the site of balloon inflation. The balloon integrated into the CNPB cannula requires small volumes and does not require high pressures on the aorta to achieve segmentation. Furthermore, if excess fluid is added, the balloon tends to elongate rather than expand radially. More important, if the balloon is temporarily inflated before cardioplegic arrest then aortic injury should be avoided by inflating the balloon to the minimum volume required to eliminate the arterial pulse pressure monitored in a lower extremity. Alternatively, DP might be achieved with incomplete aortic occlusion. Although we did not conduct our testing with incomplete aortic occlusion, we anticipate that cerebral hypothermia would be equally easy to obtain and that systemic temperature would decrease no more than 2°C to 4°C.

In addition to being able to achieve cerebral hypothermia with systemic normothermia, differential perfusion might be used where profound cerebral hypothermia is indicated, but where the surgeon would like to avoid the disadvantages of profound systemic hypothermia. The range of applications for aortic segmentation and DP will need to be evaluated but could expand beyond the conditions tested here.

	Footnotes

 
Funding for this study was provided by Cardeon Inc. Doctors Christopher G.A. McGregor, John A. Macoviak, and David J. Cook, are Scientific Advisory Board members of Cardeon Inc.

	References

Top Abstract Introduction Material and methods Results Comment References

 

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