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J Thorac Cardiovasc Surg 2003;125:378-384
© 2003 The American Association for Thoracic Surgery

Evolving Technology (ET)

Effectiveness of the Cobra aortic catheter for dual-temperature management during adult cardiac surgery

D. J. Cook, MD, T. A. Orszulak, MD, K. J. Zehr, MD, N. A. Nussmeier, MD, J. J. Livesay, MD, J. W. Hammon, MD, X. Chen, PhD

From the Departments of Anesthesiology and Divisions of Cardiothoracic Surgery, Mayo Clinic and Foundation, Rochester, Minn; Texas Heart Institute at St Luke's Episcopal Hospital, Houston, Tex; Wake Forest University School of Medicine, Winston-Salem, NC; and the Harvard Clinical Research Institute, Boston, Mass.

Received for publication March 15, 2002. Revisions requested May 24, 2002; revisions received June 26, 2002. Accepted for publication Aug 6, 2002. Address for reprints: David J. Cook, MD, Mayo Clinic, 200 First St SW, Rochester, MN 55905 (E-mail: cook.david{at}mayo.edu).


   Abstract
Top
 Abstract
Introduction
 Methods
 Results
 Discussion
 Appendix 1
 Appendix 2
 References
 
Objectives: In animals the Cardeon Cobra catheter (Cardeon Corp, Cupertino, Calif) allows independent control of aortic arch and descending aortic temperatures and profoundly reduces cerebral embolization during bypass. This investigation describes the first clinical use of the device during adult cardiac surgery. The purpose of the study was to confirm that the Cobra catheter delivers adequate cerebral and systemic perfusion while providing simultaneous cerebral hypothermia and systemic normothermia during cardiopulmonary bypass.
Methods: In a prospective multicenter study the Cobra aortic catheter was placed in 20 adults undergoing cardiopulmonary bypass. Arch and corporeal temperatures, bypass flows, and arterial blood pressures were recorded intraoperatively. Jugular bulb and mixed venous oxygen saturation was used to assess the adequacy of cerebral and systemic perfusion.
Results: Surgeons at 3 institutions placed the Cobra catheter in patients undergoing coronary artery bypass grafting (n = 13), valve (n = 3), and combined valve-bypass (n = 4) operations. Mean total bypass flows of 2.1 ± 0.2 L · min-1 · -2 maintained mean arterial pressures in arch and descending aortic circulations of greater than 55 mm Hg. A mean differential of 4.3°C between arch and descending aortic temperatures was established before crossclamp application, and a mean maximum temperature differential of 7°C was established during bypass. A 2.4°C temperature differential was maintained at crossclamp removal. Cerebral and systemic venous oxygen saturation remained greater than 65% during bypass.
Conclusions: The Cobra device met all expectations for an arterial cannula with adequate perfusion to the arch and corporeal circulations. Dual perfusion with the Cobra catheter allows for independent temperature control during cardiopulmonary bypass with simultaneous cerebral hypothermia and systemic normothermia.


   Introduction
Top
 Abstract
 Introduction
Methods
 Results
 Discussion
 Appendix 1
 Appendix 2
 References
 
Neurologic complications of cardiac surgery are serious, frequent, and costly. Depending on the patient population, stroke might occur in 1% to 10% of patients,Go Go 1-3 with higher percentages experiencing encephalopathy or cognitive deficits. Sixty percent of patients undergoing coronary artery bypass grafting (CABG) might show cognitive deficits before hospital discharge. At 1-month follow-up, greater than 20% of these patients might remain unimproved.Go Go 4,5

The ideal temperature for cardiopulmonary bypass (CPB) is a subject of debate. A body of evidence indicates that warm bypass can improve cardiac, pulmonary, and bleeding outcomes,Go Go 6-9 but concerns about warm bypass persistGo Go 10,11 because hypothermia is the most effective intervention for brain protection when ischemia occurs.Go Go 12,13

An optimal temperature-management strategy might combine cerebral hypothermia simultaneously with a warm body during CPB. A variety of interventions, including topical cooling and selective retrograde or antegrade perfusion, have been tried to provide more selective brain cooling during bypass.Go Go 14,15 However, these techniques have not been embraced because they can be technically cumbersome. More recently, dual-temperature control through a single aortic catheter has been described.Go Go 16,17

In large-animal bypass studies the Cobra catheter (Cardeon Corp, Cupertino, Calif) has been shown to allow independent control of arch and descending aortic temperature.Go 17 Additionally, it has been demonstrated to profoundly reduce brain and ocular embolization.Go 18 These 2 features, intended to improve patient outcomes by regionalizing perfusion, have been termed targeted circulatory management. The aim of this investigation was to determine whether the Cobra catheter delivers adequate perfusion while providing cerebral hypothermia and relatively normothermic systemic temperature in adults undergoing CPB.


   Methods
Top
 Abstract
 Introduction
 Methods
Results
 Discussion
 Appendix 1
 Appendix 2
 References
 
Patients from a general cardiac surgery population undergoing first-time elective surgery with CPB through a sternotomy were eligible for participation. Enrollees were between 21 and 75 years of age, had a body surface area of 2.4 m2 or less, and had both an ejection fraction and hematocrit level of greater than 30%. Patient exclusion criteria are provided in Appendix 1.

After institutional review board approval and written informed consent, final eligibility was determined with the intraoperative determination of aortic dimensions and severity of atherosclerosis. Grade IV atherosclerosisGo Go 19,20 (severe; atheroma >5 mm in addition to >=1 of the following: mobile or ulcerating lesions, extensive calcification, large protruding atheromatous debris or thrombus, or porcelain aorta) or an ascending aortic diameter of less than 19 mm or greater than 35 mm excluded patients intraoperatively before catheter placement.

The anesthetic management was according to the discretion of the attending anesthesiologist at each of the participating institutions. However, protocol required radial and femoral arterial lines, as well as a central venous pressure catheter or pulmonary artery catheter and transesophageal or epiaortic echocardiography for all patients. All patients had a No. 16 catheter placed retrograde into the jugular bulb through the internal jugular vein for intermittent sampling of cerebral venous oxygen saturation (SjVO2). Patients had body temperature measured at both the bladder (descending aortic circulation) and the nasopharynx (n = 18), jugular bulb (n = 19), or both (arch circulation).

The CPB circuit selection was determined by the participating institutions; however, the circuit modification required for dual-temperature control was standardized. The primary heat exchanger was, as usual, incorporated into the hollow-fiber oxygenator. Distal to the oxygenator, a bifurcation in the tubing allowed the warm oxygenated blood to be delivered either to the catheter port supplying the distal lumen (descending aorta) of the Cobra catheter (Figure 1) or to a second heat exchanger (BIOtherm; Medtronic, Minneapolis, Minn) used to cool the aortic arch perfusate. The hypothermic aortic arch perfusate was delivered to the proximal (arch) ports of the aortic catheter. An arterial filter (Affinity 351, Medtronic) was placed in both limbs of the aortic inflow line.



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  		Fig. 1. Schematic of the Cobra cannula demonstrating the baffle or wing (1), the arch perfusion ports (2), the descending aortic perfusion port (3), the sewing ring (4), 2 proximal connection ports (5 and 6), and the pilot balloon (7) for baffle inflation.

 
The Cobra catheter (Figure 1Go) is a 24F catheter and comes in 2 wing sizes (28 and 36 mm wing width). Catheter size selection and wing inflation volume were determined on the basis of descending aortic size. An aortic diameter of greater than 25 mm (measured echocardiographically 1-2 cm distal to the origin of the left subclavian artery) was the indication for the 36-mm wing. Wing inflation volume was determined with a nomogram on the basis of wing size and descending aortic diameter (Appendix 2).

After sternotomy and anticoagulation, the Cobra catheter was placed through a standard purse-string suture in the ascending aorta. Positioning was confirmed echocardiographically, and the 2 ports on the catheter were connected to the respective 1/4-inch (arch) and 3/8-inch (descending aortic) inflow lines. Venous cannulation was then completed, and CPB was initiated.

When CPB was established, the Cobra baffle or wing was inflated with saline, and cooling of the arch perfusate was initiated. An efficacy end point was to achieve 3°C of arch cooling measured at the nasopharynx or jugular bulb before placement of the aortic crossclamp. After crossclamp placement, the target temperature for the arch circulation was 28°C to 31°C. For the descending aortic circulation, the target temperature was 35°C to 37°C. The goal was to establish a minimum of a 5°C temperature gradient between the 2 circulations.

Temperatures, flows, and mean arterial pressures in arch (radial arterial line) and descending aortic circulations (femoral arterial line) were measured continuously, while venous blood samples from the jugular bulb and bypass venous return line were drawn intermittently. The Cobra device used was rated for maximum flow rates of 2.75 L/min for the arch lumen and 3.25 L/min for the corporeal lumen, with a maximum pressure decrease of 200 mm Hg.

Patients were statistically characterized by using tables, figures, and descriptive statistics for demographic and baseline clinical variables. All statistical summaries and analyses were provided for the intent-to-treat population, which was defined as all consenting subjects who met the selection criteria. The one patient enrolled who did not undergo targeted circulatory management is included in the analysis of all data.

The analysis of variance technique was used to analyze the continuous variables, such as temperature, over time. A {chi}2 test was used to analyze discrete variables, such as sex. Paired t tests were used to compare physiologic variables, such as venous oxygen saturation and temperature, in arch and descending aortic circulations.

Unless otherwise indicated, all comparisons of the treatment effect were performed with a 1-sided test at a less than .05 level of significance.


   Results
Top
 Abstract
 Introduction
 Methods
 Results
Discussion
 Appendix 1
 Appendix 2
 References
 
Twenty patients at 3 institutions were enrolled between November 2000 and February 2001. The mean patient age was 62 ± 9 years. The mean weight and body surface area were 95 ± 16 kg and 2.1 ± 0.2 m2, respectively. The mean preoperative ejection fraction was 57% ± 10%. Patients underwent isolated CABG (n = 13), valve (n = 3), and combined valve-CABG (n = 4) surgery with CPB by using the Cobra aortic catheter.

In 19 of the 20 patients, the Cobra catheter was successfully placed, requiring no repositioning. In one instance, after initial placement, initiation of cooling resulted in decreasing bladder temperature and a stable nasopharyngeal temperature. This temperature pattern did not change after rotation of the catheter by the attending surgeon, and therefore bypass proceeded with the use of the Cobra device as a standard aortic cannula (a single temperature was delivered through both perfusion lumens). In the remaining patients the Cobra catheter allowed for the rapid establishment of cerebral hypothermia relative to systemic normothermia.

Before bypass, mean arch (n = 20) and bladder (n = 19) temperatures were 35.9°C ± 0.5°C and 36.1°C ± 0.3°C, respectively. With the onset of wing inflation and cooling, the arch perfusate temperature was initially set at a mean of 24.9°C, with the descending aortic perfusate temperature set at a mean of 35.3°C. The crossclamp was applied a mean of 3.4 minutes later, by which time a mean temperature differential between bladder and arch circulation of 4.3°C was established. The mean temperatures at this time were 30.5°C ± 2.1°C at the nasopharynx or jugular bulb and 34.8°C ± 1.7°C at the bladder.

In the 19 patients undergoing differential temperature management, the targeted maximum differential was 6.7°C ± 0.8°C. A mean maximum temperature gradient of 7°C ± 1.2°C was established at 22.0 ± 18 minutes of cooling time (Figure 2). At that time, mean arch and bladder temperatures were 28.2°C ± 2.2°C and 34.6°C ± 1.7°C, respectively. Gradual rewarming of the arch circulation was initiated at the discretion of the surgeon, such that a modest temperature differential and mild cerebral hypothermia remained at the time of crossclamp removal. At crossclamp removal, temperatures in the arch and descending aortic circulations were 32.9°C ± 1.7°C and 35.3°C ± 0.8°C, respectively. At that time, active rewarming of the arch circulation was stopped. During bypass with the Cobra device, all measured arch temperatures were lower than bladder temperatures, with a P value of less than .000 by using the paired t test. After weaning from bypass, the mean arch and bladder temperatures were 36.1°C ± 1.2°C and 36.5°C ± 0.8°C (Figure 2Go).



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  		Fig. 2. Bladder and arch (jugular bulb-nasopharyngeal) circulation temperatures during 5 study time points. Values shown are means ± SD. **P < .001 between 2 sites by paired t test (n = 20). X-clamp, Crossclamp; TCM, targeted circulatory management.

 
The mean duration of CPB and crossclamp time were 73 ± 21 and 49 ± 13 minutes, respectively. Mean total bypass flow with the Cobra device was 4.4 ± 0.5 L/min (2.1 ± 0.2 L · min-1 · -2), with mean flows to the aortic arch and descending aorta of 2.0 ± 0.4 and 2.5 ± 0.5 L/min, (0.9 ± 0.2 and 1.2 ± 0.2 L · min-1 · -2), respectively. These flows maintained mean arterial pressures in both circulations within the desired range (mean >55 mm Hg).

The adequacy of cerebral and systemic perfusion was assessed on the basis of measurements of mixed systemic venous oxygen saturation (SVO2) and SjVO2. Figure 3 shows the values for SVO2 and SjVO2 in the prebypass period during stable targeted circulatory management with the Cobra device and in the postbypass period. During stable CPB, the SVO2 and SjVO2 ranged from 71% to 87% and 68% to 98%, respectively. Before and after bypass, the SjVO2 was lower than the SVO2 (P = .004 and .003, respectively, paired t test), whereas during bypass, the 2 saturations did not differ.



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  		Fig. 3. Jugular bulb (SjVO2) and systemic mixed (SVO2) venous oxygen saturations during 3 study time periods. Values shown are means ± SD. *P < .01 between the 2 circulations by paired t test (n = 20). TCM, Targeted circulatory management.

 

   Discussion
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
Appendix 1
 Appendix 2
 References
 
In the last 10 years, 2 practice issues receiving considerable attention in the cardiac surgical literature have been temperature management and cerebral embolization during CPB. With regard to temperature in cardiac surgical patients, there appear to be clear cardiopulmonary advantages to warm bypass. At the same time, the experimental literature indicates that hypothermia is the single best means to minimize the effects of cerebral ischemia. The last decade has also brought appropriate emphasis to the problem of cerebral embolization as a primary cause of brain injury during cardiac surgery. The Cobra aortic catheter, clinically described for the first time here, has been developed as the direct result of both of these discussions.

The Cobra device is unique in several ways. It is a dual-lumen aortic catheter intended as a substitute for a traditional aortic cannula and is capable of establishing and maintaining cerebral hypothermia with simultaneous warm bypass to the rest of the body.Go 17 By means of a second heat exchanger, we show that it is possible to establish greater than 3°C of cerebral hypothermia before crossclamp application and maintain cerebral hypothermia (32.9°C ± 1.7°C) late in bypass at the time of crossclamp removal. This is important because aortic manipulation with the crossclamp is probably the most important cause of brain embolization in cardiac surgery.Go Go 21-25

In addition to providing brain cooling at the time of crossclamp placement and removal, a greater degrees of cerebral hypothermia can be achieved and maintained through the bulk of the surgical procedure when using the Cobra catheter. In this study of 20 patients at 3 institutions, we achieved a maximum mean gradient of 7°C with a mean brain temperature of 28.2°C when the mean bladder temperature was 34.6°C. Greater degrees of cerebral hypothermia could be established in cases of longer duration without the requirement to cool the body to the same degree. Although not the design of this study, a brain temperature of 17°C to 20°C and a body temperature of 25°C to 27°C might be practical for such cases, reducing cooling, rewarming, and bypass time and potentially reducing the bleeding associated with profound whole-body hypothermia.

The other unique feature related to temperature management with the Cobra device is elimination of most of the need for rewarming. When this catheter is used, the bulk of body mass stays relatively normothermic. The requirement to replace the thermal debt is minimal, and therefore little energy needs to be applied to reach target temperature before weaning. This eliminates the overheating of the brain and cerebral oxygenation stress that can frequently occur when rewarming the body from hypothermic bypass.Go Go 26,27 With the Cobra device, a low level of selective cerebral cooling can be maintained through the last part of bypass, or the temperature of the arch circulation can be gradually equilibrated with body temperature. Because high brain temperatures and low oxygen saturations during late bypass are associated with worsened neurologic outcome,Go 28 managing temperature in this fashion probably has cerebral advantages.

Although dual-temperature control expands what is possible during bypass and would be predicted to offer both neurologic and cardiac advantages, the Cobra catheter has a more unique feature that might prove more valuable than dual-temperature bypass.

A novel design feature of the Cobra catheter is a deployable wing that facilitates aortic arch flow segmentation and dual-temperature management. However, a more unique feature of this wing design is its ability to protect the cerebral circulation from embolization originating in the heart or aortic root.Go 18 The catheter has a perfusion lumen on the cephalad surface of the cannula, as well as a distal port that perfuses the descending aorta. The catheter is nonocclusive proximally, and the intrinsic resistance of the device results in a flow to the arch lumen that is high relative to the body surface area perfused. This results in continuous overflow around the proximal edge of the wing. This proximal overflow continually irrigates the aortic root and directs the blood in the root around the lesser curvature of the arch and down the descending aorta. In large-animal bypass studies the Cobra wing reduced embolization to the brain by approximately 90%.Go 18 This dramatic result was achieved in the absence of any cerebral hypothermia. If cerebral cooling was added, we would predict that the reduction in brain embolization with the Cobra device would be even greater.

The Cobra device is easy to use and is equivalent in function to traditional arterial cannula with or without the use of the wing. The wing is prepared and deployed by using standard techniques (ie, fluid inflation with syringe). The catheter is placed through a standard ascending aortic aortotomy and is sized and shaped so that it sits in the middle of the flow stream in the transverse aortic arch. Its positioning is easily confirmed by imaging the distal portion of the cannula with transesophageal echocardiography. Perfusion with the device at conventional flow rates (2-2.4 L · min-1 · -2) results in mean arterial pressures above the autoregulatory threshold. The adequacy of cerebral perfusion and systemic perfusion is evidenced in this clinical trial by SjVO2 and SVO2 values equal to or greater than those seen under nonbypass conditions (Figure 3Go).

In one patient in this trial, use of the catheter resulted in temperature changes opposite those expected. Body temperature cooled, while the nasopharyngeal temperature remained warm. Rotation of the device did not change this situation, and therefore the surgeon elected to use the catheter as a conventional device. In retrospect, it is not possible to definitively determine the cause of the difficulty in this early case experience. It is possible that the catheter was rotated on insertion, such that the arch ports faced the lesser curvature of the aorta; however, rotation did not change the temperature control. It is more likely, however, that either the water lines to the arch and body heat exchangers or the connections for the 2 temperature probes were reversed. It should also be noted that this case was the first use of the Cobra device at that hospital. In greater than 130 subsequent clinical placements of the Cobra catheter at 15 institutions, this experience has not been repeated.

An experimental large-animal study has indicated that the Cobra device can dramatically reduce brain embolization by shunting those emboli down the descending aorta.Go 18 It must therefore be asked whether use of this device would adversely affect organs supplied by the descending aorta. Although this trial is not designed to answer that question, we would speculate that this effect should be quite small. Both experimentalGo 18 and clinicalGo 22 studies found that the mean percentage of the aortic embolic load entering the cerebral circulation was approximately 7% to 8%.Go Go 18,22 As such, redirecting 90% of that 8% would have a small effect on the total embolization down the descending aorta. Furthermore, that additional fraction of emboli would be distributed to a much larger mass of body, and therefore the concentration effect of the redirected emboli should be very small. Additionally, those redirected emboli would be delivered to organs with much lower metabolic demands and better collateralization than the brain. Nevertheless, the randomized clinical outcome trial for the Cobra catheter will need to assess renal and visceral organ outcomes, as well as its neurologic effect.

In this investigation we demonstrate that the Cobra device meets the standards of adequacy of perfusion during bypass, as well as its ability to provide targeted dual-temperature control. Although this catheter is designed to provide neuroprotection by means of cerebral hypothermia and emboli reduction, it was not the purpose of this investigation to determine whether this device could improve neurologic outcome. Although 19 of the 20 patients in this trial underwent National Institutes of Health Stroke Scale assessment within 36 hours of operation and no patient demonstrated stroke or focal neurologic event, the study is not powered to provide neurologic outcomes. In contrast to this small prospective study, a neuroprotection trial must be randomized and appropriately powered for low-incidence events. A randomized, prospective, multicenter trial examining neurologic, cognitive, cardiac, pulmonary, and renal outcomes with the Cobra catheter has been initiated.


   Appendix 1
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 Appendix 1
Appendix 2
 References
 
Patient exclusion criteria

  1. Patient with a myocardial infarction (<1 week)
  2. Patient requires inotropic agents (eg, vasoconstrictive-vasodilatory) or mechanical support (eg, intra-aortic balloon pump)
  3. Positive pregnancy test result
  4. Patient is currently in atrial fibrillation
  5. Patient has a history of severe chronic obstructive pulmonary disease, chronic bronchitis, and emphysema; is extubated; has uncontrolled asthma or forced expiratory volume in 1 second value of less than 70% of predicted value or documented pneumonia; or has other severe pulmonary disease within the month of admission
  6. Patient has a history of severe hypotension (systolic blood pressure < 70 mm Hg within 1 week of surgical intervention)
  7. Patient has a history of cerebrovascular disease (cerebrovascular accident-stroke, reversible ischemic neurologic deficit, or transient ischemic attack); previous carotid artery intervention or significant (>50%) carotid stenosis, as determined by means of ultrasonic Duplex scanning; symptomatic head trauma; seizures; or other neurologic disorder
  8. Patient's left radial artery is being harvested for CABG
  9. Patient has a history of severe peripheral vascular disease (history of diminished or absent femoral pulses, hip claudication, deep venous thrombosis, systolic blood pressure difference of > 15 mm Hg between the left and right arms)
  10. Patient has a history of hepatic disease (aspartate aminotransferase level >= 50 U/mL, bilirubin level > 1.5 mg/dL, or increased prothrombin time of > 5 seconds above control values), bleeding disorder, or coagulopathy
  11. Patient has received short-acting IIbIIIa medications (eg, eptifibatide [Integrelin]) in the last 8 hours or long-acting IIbIIIa medications (eg, abciximab [ReoPro]) in the past 24 hours
  12. Patient has renal insufficiency during this hospitalization (creatinine level > 2.5 mg/dL and blood urea nitrogen level > 50 mg/dL)
  13. Patient has severe systemic disease (eg, lupus, heart failure, cold agglutinin syndrome, terminal cancer, pancreatic biliary disease, and/or uncontrolled diabetes)
  14. Patient has calcification of aorta on routine preoperative angiography, if available, or aortic aneurysm
  15. Patient has uncontrolled hypertension (blood pressure > 185/95 mm Hg on antihypertensive medications)
  16. Patient has score of less than 20 on Folstein Mini Status Examination
  17. Patient is currently participating in another device-drug trial
  18. Patient has any other significant medical factor that in the judgment of the physician would exclude the patient from participating


   Appendix 2
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 Appendix 1
 Appendix 2
References
 


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  		Wing size and inflation volumes on the basis of aortic diameter
 


   Footnotes
 
The Mayo Foundation, Drs Cook, Orszulak, and Zehr have a licensure agreement with Cordeon, Inc, for the Cobra catheter. Back


   References
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 Appendix 1
 Appendix 2
 References
 

  1. Roach GW, Kanchuger M, Mangano CM, Newman M, Nussmeier N, Wolman R, et al. Adverse cerebral outcomes after coronary bypass surgery. Multicenter Study of Perioperative Ischemia Research Group and the Ischemia Research and Education Foundation Investigators. N Engl J Med. 1996;335:1857-63.[Abstract/Free Full Text]
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  17. Slater JM, Orszulak TA, Zehr KJ, Cook DJ. Use of the Cobra catheter for targeted temperature management during cardiopulmonary bypass in swine. J Thorac Cardiovasc Surg. 2002;123:936-42.[Abstract/Free Full Text]
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D. J. Cook, J. Huston III, M. R. Trenerry, R. D. Brown Jr, K. J. Zehr, and T. M. Sundt III
Postcardiac Surgical Cognitive Impairment in the Aged Using Diffusion-Weighted Magnetic Resonance Imaging
Ann. Thorac. Surg., April 1, 2007; 83(4): 1389 - 1395.
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 J. Thorac. Cardiovasc. Surg.Home page
T.M. Sundt, K.J. Zehr, J.A. Dearani, R.C. Daly, C.J. Mullany, C.G.A. McGregor, F.J. Puga, T.A. Orszulak, and H.V. Schaff
Is early anticoagulation with warfarin necessary after bioprosthetic aortic valve replacement?
J. Thorac. Cardiovasc. Surg., May 1, 2005; 129(5): 1024 - 1031.
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 Eur. J. Cardiothorac. Surg.Home page
H. Kaukuntla, A. Walker, D. Harrington, T. Jones, and R. S. Bonser
Differential brain and body temperature during cardiopulmonary bypass--a randomised clinical study
Eur. J. Cardiothorac. Surg., September 1, 2004; 26(3): 571 - 579.
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