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Ann Thorac Surg 2000;70:1577-1579
© 2000 The Society of Thoracic Surgeons

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Original articles: cardiovascular

Off-pump coronary bypass operations significantly reduce S100 release: an indicator for less cerebral damage?

^a Department of Cardiothoracic Surgery, General Hospital Klagenfurt, Klagenfurt, Austria
^b Department of Anesthesiology, General Hospital Klagenfurt, Klagenfurt, Austria
^c Institute for Laboratory Medicine, General Hospital Klagenfurt, Klagenfurt, Austria

Address reprint requests to Dr Wandschneider, Department of Cardiothoracic Surgery, General Hospital Klagenfurt, St. Veiter Strasse 47, A-9020 Klagenfurt, Austria
e-mail: wwand{at}netway.at

	Abstract

Top Abstract Introduction Material and methods Results Comment Acknowledgments References

 
Background. Cardiac operations using extracorporeal circulation bear a risk of cerebral complications. The aim of our study was to investigate if off-pump operations without heart-lung machines can reduce cerebral injury.

Methods. S100, a protein specific for cerebral tissue, was used as a marker for cerebral impairment in 108 randomized patients undergoing coronary bypass operation: 67 patients (group A) were operated on with extracorporeal circulation and cardioplegic cardiac arrest, and 41 patients (group B) underwent off-pump beating heart revascularization. Both groups were similar regarding age, sex, ejection fraction, and number of anastomoses. S100 levels were measured from induction of anesthesia until 24 hours after the operation.

Results. Data collection was 100% complete. There was no in-hospital death. Nonfatal myocardial infarctions occurred in 2 patients in group A, and 1 patient in group B required resternotomy for bleeding. There was no neurologic deficit in either group. S100 levels increased only slightly in the off-pump patients (group B), whereas in group A there was a sharp rise in S100 concentration during extracorporeal circulation, only returning to baseline 6 hours after the end of the operation. Peak S100 levels were four times higher in group A than in group B (2.1 µg/L versus 0.5 µg/L; p < 001).

Conclusions. The results of our study suggest that perioperative cerebral impairment is reduced in cardiac operations without the use of extracorporeal circulation. Further large-scale studies are needed to show whether this result is reflected by fewer neurologic deficits.

	Introduction

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Despite improvements in extracorporeal perfusion there is still a significant risk of postoperative neurologic deficits and cognitive dysfunction for patients undergoing cardiac operations with the use of the heart-lung machine [1–5]. During the last few years "off-pump" or "beating heart" techniques were introduced to avoid these adverse side effects. Although this less invasive kind of operation has met widespread interest, there are to our knowledge no prospective randomized trials proving a significant reduction in cerebral damage in off-pump coronary operations. We therefore conducted a prospective randomized study in 108 patients undergoing coronary bypass operation with and without extracorporeal circulation, using S100 protein as a marker for intraoperative cerebral damage. If off-pump operations were more physiologic or less invasive, there should be less or no S100 release in this group of patients.

S100 is a calcium binding protein present in astroglial and microglial cells and is highly specific for the brain [6]. As it does not normally pass the blood-brain barrier its appearance in the serum is an indicator for cerebral damage [7, 8]. By means of a specific immunoassay (Sangtec 100, Byk-Sangtec Diagnostica, Dietzenbach, Germany) it is possible to measure serum levels of the isoenzyme S100b.

	Material and methods

Top Abstract Introduction Material and methods Results Comment Acknowledgments References

 
After written informed consent 108 consecutive patients undergoing cardiac operation for coronary heart disease were randomly assigned to two groups.

Group A (67 patients) underwent classic coronary bypass grafting using extracorporeal circulation and cardioplegic cardiac arrest. Heart-lung machine consisted of a roller pump and a CML Duo (Cobe Cardiovascular Inc, Arvada, CO) membrane oxygenator. We used cold (8°C) blood cardioplegia administered antegrade into the aortic root and retrograde into the coronary sinus. Patients were not actively cooled, but "drifted" to a mean rectal temperature of 33.4°C and rewarmed to at least 37°C before coming off bypass.

Group B (41 patients) underwent operation on the beating heart without extracorporeal circulation. For anastomoses we used the CTS Retractor (Cardio Thoracic Systems Inc, Cupertino, CA) or the Medtronic Octopus II Retractor (Medtronic, DLP, Grand Rapids, MI).

Demographic variables and surgical details are listed in Table 1. All patients were extubated in the intensive care unit (ICU) only after being sufficiently awake, adequately warm, and in stable circulatory condition.

S100 probes were taken as listed in Table 2. All samples were immediately centrifuged and the sera deep frozen. The samples were then analyzed collectively after patient recruitment was finished.

	Results

Top Abstract Introduction Material and methods Results Comment Acknowledgments References

 
Data collection was 100% in all 108 patients. No patient died, and there was no transient or permanent neurologic deficit in either group. No cognitive or psychometric test was used.

Surgical complications consisted of two nonfatal myocardial infarctions in group A, one wound infection in group A, and one postoperative bleeding in group B requiring resternotomy. No patient needed an intraaortic balloon pump or other mechanical assist in either group. There was no autotransfusion of shed blood after the end of the operation.

S100 levels (Fig 1) were nearly identical in both groups at the beginning of the operation (no. 1). In off-pump patients (group B), S100 concentration increased slightly with a flat "peak" at the time of ICU admission (no. 4) and then quickly dropped to preoperative levels.

View larger version (15K): [in this window] [in a new window]   Fig 1. S100b serum levels (µg/L) with and without heart-lung machine. During extracorporeal circulation (EC), S100 levels rise sharply (test point no. 2) and only return to preoperative levels after 6 hours postoperation. In off-pump procedures, S100 levels remain within normal range throughout the operation.

	Comment

Top Abstract Introduction Material and methods Results Comment Acknowledgments References

 
Since Benetti and colleagues [9] and Buffolo and associates [10] introduced the "off-pump" coronary operation as a less invasive technique, coronary bypass grafting without the use of extracorporeal circulation has been accepted as an alternative technique in many centers. Although on theoretical grounds this new method should be a more physiologic one, avoiding all of the long-known disadvantages of the heart-lung machine, its technical feasibility and various means of stabilizing the anastomotic field have met with more interest in the literature than its possible advantage for neurologic or respiratory function.

As the incidence of stroke is low in coronary bypass operations, even when using extracorporeal circulation [1, 3, 11], large cohorts of patients would be necessary to prove any statistical difference between on-pump and off-pump techniques. Neurocognitive deficits are even harder to evaluate and results differ widely [3, 5] according to patient numbers and test methods.

Since the discovery of S100 protein as a marker for cerebral damage it has been used in neurologic and trauma patients [7] to prove organic cerebral damage. A number of studies have shown elevated S100 levels also in patients undergoing cardiac operations using extracorporeal circulation [8, 12–15]. Other investigators, such as Kumar and coworkers [16] and Taggart and colleagues [17], have also described S100 release during and after extracorporeal circulation in neurologic asymptomatic patients. These findings suggest impairment of the blood-brain barrier and cerebral cell injury even in the absence of neurologic symptoms. Our own data confirm the adverse side effects of extracorporeal circulation, showing a fourfold increase of serum S100 levels immediately after the onset of cardiopulmonary bypass and a return to baseline levels only 6 hours after decannulation. In the off-pump group, however, S100 levels remained nearly normal, suggesting a more physiologic course of the operation, at least where the brain is concerned.

As the incidence of manifest neurologic deficits or severe psychologic deterioration is rare in routine coronary bypass operations, we are not sure whether these results will have any clinical impact. In our trial there was no neurologic deficit in either group. Further studies, including large cohorts of patients, are necessary to answer this question. Considering increasing age and comorbidity of cardiac patients, we think that less invasive techniques will be of utmost importance in the future.

	Acknowledgments

Top Abstract Introduction Material and methods Results Comment Acknowledgments References

 
We thank Mr Norbert Haberfellner for data collection and retrieval, Prof Heinz Stettner (Institute for Biometrics at the University of Klagenfurt) for the statistical analysis, and the entire cardioanesthetic team for their collaboration.

	References

Top Abstract Introduction Material and methods Results Comment Acknowledgments References

 

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