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Ann Thorac Surg 2005;80:1371-1374
© 2005 The Society of Thoracic Surgeons

Original article: Cardiovascular

Serum S-100 ß Protein During Coronary Artery Bypass Graft Surgery With or Without Cardiopulmonary Bypass

Kuan-Jen Wang, MD a , Hsiang-Hua Wu, BA a , Shih-Yuan Fang, MD b , Yu-Ren Yang, MD, PhD c , A. Chia-Chih Tseng, MD a , *

a Department of Anesthesiology, Chang Gung Memorial Hospital, Kaohsiung Medical Center, Kaohsiung, Taiwan
b Department of Anesthesiology, Medical Center, National Cheng Kung University, Tainan, Taiwan
c Department of Surgery, Medical Center, National Cheng Kung University, Tainan, Taiwan

Accepted for publication April 5, 2005.

* Address reprint requests to Dr Tseng, Department of Anesthesiology, Chang Gung Memorial Hospital, Kaohsiung Medical Center, 123 Ta Pei Rd, Niao Sung Hsiang, Kaohsiung Hsien 83301, Taiwan (Email: alex1115{at}adm.cgmh.org.tw).


   Abstract
Top
 Abstract
Introduction
 Material and Methods
 Results
 Comment
 References
 
BACKGROUND: Brain damage is a serious complication of cardiac anesthesia. The purpose of this study was to detect brain damage at different surgical stages during coronary artery bypass graft with or without cardiopulmonary bypass.

METHODS: We conducted a prospective, longitudinal study to evaluate serum S-100 ß protein, an early marker of brain injury, in patients electively undergoing off-pump (n = 30) or traditional coronary artery bypass graft (n = 60). Blood was sampled immediately before anesthesia, before and after cardiopulmonary bypass, and on the day after surgery.

RESULTS: Serum S-100 ß protein was lowest immediately before induction of anesthesia and significantly increased before and after cardiopulmonary bypass, then declined by the first postoperative day in both groups. Peak values were highest in the traditional group directly after coronary artery bypass graft. On the day after surgery, S-100 ß protein levels were similar between groups, but were higher than baseline within each group. Significant increase in serum S-100 ß protein was also observed even before cardiopulmonary bypass in cardiopulmonary bypass patients, or before manipulation of the heart and aorta in off-pump patients. These reflect the possibility that brain damage may occur before major manipulation (cardiopulmonary bypass or manipulating heart and aorta). Moreover, S-100 ß levels did not return to normal on the day after the operation.

CONCLUSIONS: This prospective study has shown that serum S-100 ß protein was not only higher than baseline both after cardiopulmonary bypass and on the day after surgery in both groups of patients but it was also significantly increased before cardiopulmonary bypass or manipulation of the heart or aorta. These findings may have implications for anesthesiologic care during the total course of cardiac surgery.


   Introduction
Top
 Abstract
 Introduction
Material and Methods
 Results
 Comment
 References
 
Brain damage is a serious complication of cardiac anesthesia, especially in elderly patients, and cardiopulmonary bypass (CPB) is believed to be one major factor [1–5]. Recently, coronary artery bypass graft (CABG) without CPB, so-called off-pump CABG, has become more common in clinical practice [6, 7]. One potential benefit is lesser risk of brain damage. However, an advantage of off-pump CABG in relation to neurocognitive dysfunction or stroke is not clear [8–11].

Previous studies have monitored the occurrence of stroke, neurocognitive defects, hospital stay, and mortality after cardiac surgery [1–5, 12]. These outcome reports did not indicate in which operative stages the damage occurs. Serum S-100 ß protein has recently been shown to be an early marker of brain injury after cardiac surgery [13–20]. Elevation in the postoperative period has been shown to be related to early and late outcomes and length of hospital stay [13–16]. Moreover, sampling at different stages of surgery has been used to delineate brain damage at different times during surgery [4, 17]. Thus, serum S-100 ß protein can be used as a tool to study the time sequence of brain damage in the perioperative period.

Sequential sampling of serum S-100 ß protein has been used to study brain damage resulting from cardiac surgery [13–15, 18, 19]. However, most of these studies focused on the effects of CPB rather than on the effects of anesthesia from the preoperative to the pre-CPB period [18, 19]. Actually, the neurocognitive dysfunction was found simply after general surgery in aged patients [21, 22]. This means the brain damage may occur in the pre-CPB period, especially in geriatric patients.

The aim of this study was to use a sensitive assay to measure serum S-100 ß protein before major surgery and at different stages during and after surgery in patients undergoing traditional or off-pump CABG.


   Material and Methods
Top
 Abstract
 Introduction
 Material and Methods
Results
 Comment
 References
 
After institutional review board approval and informed consent, 90 patients undergoing elective CABG with CPB (n = 60) and off-pump (n = 30) were entered into this study. The only exclusion was for patients who did not consent. Patients were not randomized.

Anesthesia was induced with propofol (1 to 2 mg/kg) and fentanyl (2 to 3 µg/kg). Rocuronium provided muscle relaxation. Anesthesia was maintained with a combination of the following: fentanyl boluses (1 to 5 µg/kg to a total of less than 10 µg/kg), and isoflurane or desflurane titrated to maintain hemodynamic stability. Patients in the off-pump group had mean arterial blood pressure maintained above 50 mm Hg during the anastomosis stage with vasopressors. If this was not possible, the operation was converted to CPB.

For patients in the CPB group, nonpulsatile CPB, a membrane oxygenator, a 40-µm blood filter (Paul Biomedical, East Hills, NY), and systemic cooling to a rectal temperature of 28° to 30°C with {alpha}-stat pH management were common features of perfusion. A Bio-Medicus centrifugal pump (Medtronic Bio-Medicus, Eden Prairie, MN) was used. Flow rates were set at 1.6 and 2.4 L·min–1 ·m–2 during cooling and warming, respectively. A vaporizer connected to an inlet gas tube to maintain hemodynamic stability in the CPB period was maintained with inhalation anesthetics. Rewarming to a rectal temperature of 36° to 36.5°C was achieved before coming off CPB. The outlet temperature of the pump oxygenator was kept below 38°C, and the rewarming rate was approximately 1°C every 5 minutes. Mean arterial blood pressure on CPB was maintained at approximately 50 mm Hg.

Blood samples (5 mL) were collected from the arterial catheter before induction of anesthesia, before CPB, after CPB, and on the first postoperative day (18 to 24 hours after operation). The pre-CPB sample was taken at 3 minutes after heparin was given, which was the time before manipulation of the heart for distal anastomosis in patients in the off-pump group and before any cannulation in patients in CPB group. The post-CPB sample was taken as the time at which all anastomoses were completed and 3 minutes after protamine for reversal of heparin in both groups. All samples were allowed to clot for 20 minutes at room temperature and then were immediately centrifuged at 1,000 rpm for 10 minutes with a 10°C centrifuge to separate the serum. Serum was then kept at –20°C. Serum S-100 ß protein was measured by a commercially available monoclonal, two-site immunoluminometric assay (Sangtec S-100 ß LIA assay) with a detection limit for serum S-100 ß protein of 0.02 to 20 g/L.

The time to awaken, length of stay in the intensive care unit, and length of hospital stay were collected from the chart after patient discharge. Stays longer than 14 days in the intensive care unit and longer than 60 days in the hospital were set as 14 and 60 days, respectively.

Data are expressed as mean ± standard deviation. Statistical analysis was performed by SPSS (Version 9.0, SPSS Inc, Chicago, IL). One-way analysis of variance was used for numeric data between groups. The nonparametric data were tested with the Kruskal-Wallis test. The paired Student's t test was used to test intragroup numeric changes. A p less than 0.05 was considered statistically significant.


   Results
Top
 Abstract
 Introduction
 Material and Methods
 Results
Comment
 References
 
A total of 90 patients completed the study, of which 60 underwent CPB and 30 did not. Demographic data and preoperative evaluation characteristics were similar between groups (Table 1). The incidence of diabetes mellitus, hypertension, stroke, chronic obstructive pulmonary disease, and end-stage renal disease did not differ. Although mean ejection fraction was 0.75 in CPB patients versus 0.57 in off-pump patients, the difference was not significant.


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  		Table 1. Demographic Data a
 
Serum S-100 ß protein was lowest immediately before induction of anesthesia, significantly increased before CPB, increased further after CPB, then declined to pre- CPB levels by the next day in both groups (Table 2). Serum S-100 ß protein on the day after surgery was higher than at baseline. Peak values were highest after CPB in both groups, but the levels in the traditional group were significantly higher than in off-pump patients. Serum S-100 ß protein levels were the same before induction of anesthesia and before CPB between groups. After CPB, they were significantly higher in the traditional group. On the next day, serum S-100 ß was somewhat lower but not statistically different between groups. There were no significant differences between groups in time to awaken, intensive care unit length of stay, or length of hospital stay (Table 3).


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  		Table 2. Serum S-100 Protein Concentrations a
 

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  		Table 3. Postoperative Clinical Characteristics a
 

   Comment
Top
 Abstract
 Introduction
 Material and Methods
 Results
 Comment
References
 
Serum S-100 ß protein is known to be increased after cardiac operation [13–20]. The rise is most marked immediately after CPB and then decreases slowly in the early postoperative stage [15]. In our data we found the serum S-100 ß protein not only increasing after CPB but also significantly increasing before CPB. Moreover, this increase does not fully return to baseline by the first postoperative day with or without CPB. Blomquist and colleagues [19] found that serum S-100 ß protein did not differ between the preanesthesia and pre-CPB periods. They used a less-sensitive assay than we did (lower limit 0.2 g/L) and had a small number of cases [19]. Lindberg and associates [18] also studied changes in serum S-100 ß protein during cardiac surgery but only in pediatric patients. A major risk for brain damage is age [5], so these results cannot be directly compared with our study.

Ali and coworkers [17] believed that anesthesia itself is not a factor related to serum S-100 ß protein changes. However, silent or minor brain damage may be very common in the early postcardiac operative period, as evidenced by magnetic resonance imaging [12] and tests of neurocognitive dysfunction [2, 8, 9, 16]. Cognitive dysfunction or brain damage may occur in the elderly even after general surgery under general anesthesia [21, 22]. Our data show that serum S-100 ß protein increases during cardiac operation and is not dependent on special procedures exclusive to cardiac surgery, such as CPB or manipulating the heart and aorta. The brain might sustain damage before manipulation of the heart or aorta, suggesting that attention should be paid to hemodynamic stability and anesthesia practice even before CPB.

Increased serum S-100 ß postoperatively is related to neurocognitive dysfunction, severity of brain damage, duration of mechanical ventilation [7, 14, 15], and late mortality [23]. In our study, the mean value of serum S-100 ß protein did not return to baseline on the first day postoperatively in both groups, suggesting that brain damage was present and not significantly affected by the presence or absence of CPB. Brain damage after CPB and off-pump surgery has been studied, but the results are conflicting [8–11]. Ahonen and Salmenpera [4] found that brain damage may occur without use of CPB; off-pump surgery with tangential clamping (proximal graft attachment) can induce disruption of a diseased vessel wall. Our data also showed that the serum S-100 ß protein stopped increasing from before CPB and after CPB in both groups. Although we did not have CPB in off-pump patients, the partially clamped aorta for proximal anastomosis was similar in both groups. We accept the suggestion of Ahonen and Salmenpera [4] that partial clamping may induce damage to the diseased vessel wall that can lead to brain damage even without CPB.

There were some drawbacks to our study. The difference in serum S-100 ß protein between traditional and off-pump groups was significant after CPB only. Serum S-100 protein is usually released after brain damage, but serum S-100 immediately after CPB may not originate from the brain only [24, 25]. Cardiopulmonary bypass or suctioning of blood from the operative wound may contribute to its elevation [24]. The rise in serum S-100 ß may result from different mechanisms, and serum S-100 ß protein levels immediately after CPB must be carefully interpreted. However, we still found serum S-100 ß protein to be increased in post-CPB samples in the off-pump group, which remained elevated until the first postoperative day. This suggests that the brain may be damaged by manipulation of the heart and aorta even without CPB.

We have shown that off-pump CABG is associated with elevation of serum S-100 ß protein. Manipulation of the heart or aorta usually results in unstable hemodynamic status, and a partial aortic clamp is used in proximal anastomosis. These may either decrease brain perfusion or increase the risk of cerebral embolism [26, 27].

Our data did not detect a significant difference between groups, except for significantly higher serum S-100 ß in CPB patients after CPB. However, mean values were not significantly higher in CPB patients in the day after surgery. There were relatively small case numbers, and the effect of age was not evaluated.

In conclusion, serum S-100 ß protein significantly increased from preinduction to before CPB in both groups. Our findings imply that brain damage occurs during cardiac surgery in the absence of CPB, and that brain damage is not completely resolved on the next postoperative day with or without CPB. Close attention to hemodynamic stability from induction of anesthesia is necessary in patients undergoing cardiac surgery. However, only prospective, randomized studies will clarify whether variations in anesthetic treatment affect clinical outcomes.


   References
Top
 Abstract
 Introduction
 Material and Methods
 Results
 Comment
 References
 

  1. Selnes OA, Goldsborough MA, Borowicz LM, McKhann GM. Neurobehavioural sequelae of cardiopulmonary bypass Lancet 1999;353:1601-1606.[Medline]
  2. Borowicz LM, Goldsborough MA, Selnes OA, McKhann GM. Neuropsychologic change following cardiac surgerya critical review. J Cardiothorac Vasc Anesth 1996;10:105-112.[Medline]
  3. Selnes OA, Goldsborough MA, Borowicz Jr LM, Enger C, Quaskey SA, McKhann GM. Determinants of cognitive change after coronary artery bypass surgerya multifactorial problem. Ann Thorac Surg 1999;67:1669-1676.[Abstract/Free Full Text]
  4. Ahonen J, Salmenpera M. Brain injury after adult cardiac surgery Acta Anaesthesiol Scand 2004;48:4-19.[Medline]
  5. Stamous SC, Hill PC, Dangas G, et al. Stroke after coronary artery bypass incidence, predictors, and clinical outcome Stroke 2001;32:1508-1513.[Abstract/Free Full Text]
  6. Cartier R. Current trends and technique in OPCAB surgery J Card Surg 2003;18:32-46.[Medline]
  7. Cartier R, Brann S, Dagenais F, Martineau R, Couturier A. Systematic off-pump coronary artery revascularization in multivessel diseaseexperience of three hundred cases. J Thorac Cardiovasc Surg 2000;119:221-229.[Abstract/Free Full Text]
  8. Lloyd CT, Ascione R, Underwood MJ, Gardner F, Black A, Angelini GD. Serum S-100 protein release and neuropsychologic outcome during coronary revascularization on the beating hearta prospective randomized study. J Thorac Cardiovasc Surg 2000;119:148-154.[Abstract/Free Full Text]
  9. Taggart DP, Browne SM, Halligan PW, Wade DT. Is cardiopulmonary bypass still the cause of cognitive dysfunction after cardiac operations? J Thorac Cardiovasc Surg 1999;118:414-420.[Abstract/Free Full Text]
  10. Anderson RE, Hansson LO, Vaage J. Release of S-100 during coronary artery bypass grafting is reduced by off-pump surgery Ann Thorac Surg 1999;67:1721-1725.[Abstract/Free Full Text]
  11. Wan S, Yim APC. Is off-pump cardiac surgery better for the brain? Chest 2001;119:1-2.[Free Full Text]
  12. Wityk RJ, Goldsborough MA, Hillis A, et al. Diffusion- and perfusion-weighted brain magnetic resonance imaging in patients with neurologic complications after cardiac surgery Arch Neurol 2001;58:571-576.[Abstract/Free Full Text]
  13. Westaby S, Johnsson P, Parry AJ, et al. Serum S-100 proteina potential marker for cerebral events during cardiopulmonary bypass. Ann Thorac Surg 1996;61:88-92.[Abstract/Free Full Text]
  14. Herrmann M, Ebert AD, Galazky I, Wunderlich MT, Kunz WS, Huth C. Neurobehavioral outcome prediction after cardiac surgery role of neurobiochemical markers of damage to neuronal and glial brain tissue Stroke 2000;31:645-650.[Abstract/Free Full Text]
  15. Ueno T, Iguro Y, Yamamoto H, Sakata R, Kakihana Y, Nakamura K. Serial measurement of serum S-100B protein as a marker of cerebral damage after cardiac surgery Ann Thorac Surg 2003;75:1892-1898.[Abstract/Free Full Text]
  16. Farsak B, Gunaydin S, Yorgancioglu C, Zorlutuna Y. Elevated levels of S-100beta correlate with neurocognitive outcome after cardiac surgery J Cardiovasc Surg 2003;44:31-35.[Medline]
  17. Ali MS, Harmer M, Vaughan R. Serum S100 protein as a marker of cerebral damage during cardiac surgery Br J Anaesth 2000;85:287-298.[Abstract/Free Full Text]
  18. Lindberg L, Olsson AK, Anderson K, Jögi P. Serum S100 protein levels after pediatric cardiac operationsa possible new marker for postoperative cerebral injury. J Thorac Cardiovasc Surg 1998;116:281-285.[Abstract/Free Full Text]
  19. Blomquist S, Johnsson P, Luhrs C, et al. The appearance of S-100 protein in serum during and immediately after cardiopulmonary bypass surgerya possible marker for cerebral injury. J Cardiothorac Vasc Anesth 1997;11:699-703.[Medline]
  20. Kumar P, Dhital K, Hossein-Nia M, Patel S, Holt D, Treasure T. S-100 protein release in a range of cardiothoracic surgical procedures J Thorac Cardiovasc Surg 1997;113:953-954.[Free Full Text]
  21. Moller JT, Cluitmans P, Rasmussen LS, et al. Long-term postoperative cognitive dysfunction in the elderlyISPOCD1 study. Lancet 1998;351:857-861.[Medline]
  22. Rasmussen LS, Johnson T, Kuipers HM, et al. Does anaesthesia cause postoperative cognitive dysfunction? A randomised study of regional versus general anaesthesia in 438 elderly patients Acta Anaesth Scand 2003;47:260-266.[Medline]
  23. Johnsson P, Bäckström M, Bergh C, Jonsson H, Luhrs C, Alling C. Increased S100B in blood after cardiac surgery is a powerful predictor of late mortality Ann Thorac Surg 2003;75:162-168.[Abstract/Free Full Text]
  24. Anderson RE, Hansson LO, Liska J, Settergren G, Vaage J. The effect of cardiotomy suction on the brain injury marker S100beta after cardiopulmonary bypass Ann Thorac Surg 2000;69:847-850.[Abstract/Free Full Text]
  25. Anderson R, Hansson L-O, Dijlai-Merzoug R, Settergren G. High serum S100b levels for trauma patients without head injuries Neurosurgery 2001;48:1255-1258.[Medline]
  26. Yao FSF, Tseng CC, Ho CYA, Levin SK, Illner P. Cerebral oxygen desaturation is associated with early postoperative neuropsychological dysfunction in patients undergoing cardiac surgery J Cardiothorac Vasc Anesth 2004;18:552-558.[Medline]
  27. Ura M, Sakata R, Nakayama Y, Goto T. Ultrasonographic demonstration of manipulation-related aortic injuries after cardiac surgery J Am Coll Cardiol 2000;35:1303-1310.[Abstract/Free Full Text]




This Article
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