HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Lars G. Svensson Ali Husain David M. Shahian Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Svensson, L. G. Articles by Shahian, D. M. Search for Related Content PubMed PubMed Citation Articles by Svensson, L. G. Articles by Shahian, D. M.

J Thorac Cardiovasc Surg 2000;119:163-167
© 2000 Mosby, Inc.

BRIEF COMMUNICATIONS

A PROSPECTIVE RANDOMIZED STUDY OF NEUROCOGNITIVE FUNCTION AND S-100 PROTEIN AFTER ANTEGRADE OR RETROGRADE BRAIN PERFUSION WITH HYPOTHERMIC ARREST FOR AORTIC SURGERY

From the Lahey Clinic Medical Center, Burlington, Mass.

Address for reprints: Lars G. Svensson, MD, PhD, Department of Thoracic and Cardiovascular Surgery, Lahey Hitchcock Clinic, 41 Mall Rd, Burlington, MA 01805.

Several studies in patients undergoing coronary artery bypass (CAB) surgery have shown evidence of postoperative neurocognitive dysfunction or increased levels of the serum brain injury protein S-100. ^1,2 S-100 protein is a calcium-binding dimer found in glial and Schwann cells, and postoperative levels above 0.5 to 1.3 µg/L may be associated with mild neurologic injury. ² However, the large series on hypothermic arrest for aortic surgery have not examined these parameters nor compared outcomes according to whether patients had deep hypothermic circulatory arrest alone (DHCA), antegrade brain perfusion (ANTE), or retrograde brain perfusion (RBP). ^(1-5) Thus, to determine the incidence and prognosis (temporary or permanent) of brain injury, we compared these parameters in a prospective randomized study.

Methods.

Institutional review board approval was obtained for block randomizing a series of 15 patients into 3 equal groups undergoing DHCA, ANTE, and RBP by folded cards in an opaque envelope. In addition, 5 patients undergoing CAB served as controls. Patients who were either undergoing emergency surgery or were older than 75 years were excluded from the study. Patients were operated on between November 1996 and November 1997. DHCA was performed as described previously, ³ as was RBP (300-500 mL/min via the occluded superior vena cava to maintain a pressure of 25-35 mm Hg). ^2,3 ANTE was performed by cannulating the right subclavian artery, occluding the innominate artery origin with a balloon catheter, and perfusing the common carotid artery with a balloon catheter while maintaining pressures at 40 to 60 mm Hg. Electroencephalograms were preformed during the operation and the morning after the operation in all patients. A battery of 14 neurocognitive test types (Tables I-IV) were performed before the operation, 4 to 6 days after the operation, 2 to 3 weeks after the operation, and 6 months after the operation. Serum S-100 protein levels were measured with S-100 immunoradiometric reagents from Sangtec, Bromma, Sweden, before cardiopulmonary bypass (CPB), while CPB was being started, after cooling, after circulatory arrest, after rewarming, at the conclusion of CPB, on leaving the operating room, and at 6, 12, 18, 24, and 48 hours after the operation. Limits of detection were 0.2 µg/L S-100, and normal is less than 0.2 µg/L. Statistical analysis was done with the paired Student t test for time-related data and comparison between the groups. Regression analysis was performed by means of simple linear regression.

All patients survived the operation, awoke the following morning, and showed no electroencephalographic evidence of seizures or localized deficits. None had a stroke. Hemi-arch replacements required substantially shorter arrest times than did total arch replacements: 21.0 minutes (standard deviation [SD] 12.7 minutes) versus 49.3 minutes (SD 10.3 minutes) (P = .0003) (total arch = 6, including 3 elephant trunk procedures). The respective circulatory arrest times for DHCA, ANTE, and RBP were 24.2 (SD 22.7), 39.8 (SD 19.1), and 37.3 (SD 15.0) minutes (P value indicated no significant difference); however, ANTE hemi-arch repairs required longer circulatory arrest times (31 minutes [SD 9.5] vs 10 minutes [SD 3.5] for DHCA/RBP, P = .004).

There were no differences in the preoperative neurocognitive tests among the groups (Tables I-IV). Of the preoperative tests, Logical Memory II (Wechsler Memory Scale–Revised, WMS-R) correlated with age (P = .02, r2 = 0.3), as did Reaction Time (P = .03, r2 = 0.3). Postoperatively, however, 5 tests (including subtests) showed a decline in neurocognitive function (P < .05) 4 to 6 days after hypothermic arrest(Table II). Later, neurocognitive tests at 2 to 3 weeks showed no significant difference compared with preoperative values. In comparisons among the groups, at 4 to 6 days after the operation(Tables III andIV), the following were significantly different (P < .05): Beck Depression Inventory (RBP patients scored the highest level of depression and physical concerns); Shipley Vocabulary Raw and Age Scores (DHCA scored the highest and ANTE the lowest of the hypothermic arrest patients); Shipley Abstraction Raw and Age Scores (RBP scored the highest and ANTE the lowest); Shipley Total Mental Age (RBP scored the highest and ANTE the lowest); and Shipley Estimated Wechsler Adult Intelligence Score (WAIS) IQ (DHCA scored the highest and ANTE the lowest) despite estimated intellectual function being equal before the operation. RBP and DHCA Shipley scores were similar to CAB scores (no significant difference), except that depression (Beck Depression Inventory) was higher in the RBP group. The Shipley scores of ANTE patients were significantly worse than those of CAB patients. Nevertheless, 2 to 3 weeks after discharge from the hospital, there were no significant differences between the groups (including CAB), nor was there a significant difference at 6 months. The in-hospital neurocognitive tests before discharge showed a correlation between age and Wechsler Adult Intelligence Scale—Revisited (WAIS-R):Logical Memory I (P = .03, r2 = 0.3), Trail Making Test B (P = .03, r2 = 0.3), and Symbol Digit Test (P = .04, r2 = 0.3). However, 2 to 3 weeks after the operation, this correlation no longer existed except for the Symbol Digit Test, and 6 months after the operation this was also no longer significant. The S-100 levels significantly increased transiently after circulatory arrest compared with both baseline and CAB, as shown inFig 1.

View larger version (27K): [in this window] [in a new window]   Fig. 1. Mean S-100 serum protein values (µg/L). CA, Combined mean of circulatory arrest groups (DHCA, ANTE, RBP); CPB, cardiopulmonary bypass; OR, operation.

In this small preliminary study, by 2 to 3 weeks after the operation, patients had recovered to their original preoperative levels of neurocognitive function. This study does not take into account the practice effect of learning how to do the tests. Furthermore, we were unable to show any significant difference in brain protection 2 to 3 weeks or 6 months after the operation between the DHCA alone versus ANTE and RBP groups or in comparison between the patients who had DHCA arrest versus CAB. In addition, we also evaluated the patients on the basis of other criteria proposed in the literature. ⁵ These criteria for neurocognitive defects include more than 1 SD decrease in individual neurocognitive tests, or more than a 20% decline in individual tests with more than 20% of individual tests showing a decline. On the basis of these 2 criteria, none of the patients had a significant neurocognitive deficit.

For hemi-arch repairs, the circulatory arrest time is considerably longer with ANTE because of the additional time required for insertion of the innominate and carotid artery catheters for antegrade brain perfusion and later removal of the catheters. However, for longer circulatory arrest times, particularly for total aortic arch replacements, ANTE and RBP may be shown to be beneficial. S-100 levels increased transiently after termination of CPB, indicating some possible brain injury, although these levels returned to normal and undetectable levels within 24 hours and there was no significant difference between the circulatory arrest study groups(Fig 1). This study suggests that brain injury is transient for patients undergoing a relatively brief period of DHCA for aortic arch repairs. We are continuing the study to obtain greater statistical power to better define the incidence of neurologic injury, correlation between neurocognitive function and S-100 protein release, and superiority of any method of brain protection.

References

1. Blumenthal JA, Mahanna EP, Madden DJ, White WD, Croughwell ND, Newman MF. Methodological issues in the assessment of neuropsychologic function after cardiac surgery. Ann Thorac Surg 1995;59:1345-50.[Abstract/Free Full Text]
   
2. Johnsson P, Lundqvist C, Lindgren A, Ferencz I, Alling C, Stahl E. Cerebral complications after cardiac surgery assessed by S-100 and NSE levels in blood. J Cardiothorac Vasc Anesth 1995;9:694-9.[Medline]
   
3. Svensson LG, Crawford ES, Hess KR, Coselli JS, Raskin S, Shenaq SA, et al. Deep hypothermia with circulatory arrest: determinants of stroke and early mortality in 656 patients. J Thorac Cardiovasc Surg 1993;106:19-31.[Abstract]
   
4. Ergin MA, Galla JD, Lansman SL, Quintana C, Bodian C, Griepp RB. Hypothermic circulatory arrest in operations on the thoracic aorta: determinants of operative mortality and neurologic outcome. J Thorac Cardiovasc Surg 1994;107:788-99.[Abstract/Free Full Text]
   
5. Lytle BW, McCarthy PM, Meaney KM, Stewart RW, Cosgrove DM III. Cardiopulmonary bypass, myocardial management, and support techniques. J Thorac Cardiovasc Surg 1995;109:738-43.[Abstract/Free Full Text]
   

This article has been cited by other articles:

				T. Kunihara, D. Tscholl, F. Langer, G. Heinz, F. Sata, and H.-J. Schafers Cognitive brain function after hypothermic circulatory arrest assessed by cognitive P300 evoked potentials Eur. J. Cardiothorac. Surg., September 1, 2007; 32(3): 507 - 513. [Abstract] [Full Text] [PDF]

				I. Dorotta, P. Kimball-Jones, and R. Applegate II Deep hypothermia and circulatory arrest in adults. Seminars in Cardiothoracic and Vascular Anesthesia, March 1, 2007; 11(1): 66 - 76. [Abstract] [PDF]

				R.S. Bonser and D.K. Harrington Editorial comment Eur. J. Cardiothorac. Surg., July 1, 2005; 28(1): 102 - 103. [Full Text] [PDF]

				L. G. Svensson, E. H. Blackstone, J. Rajeswaran, J. F. Sabik III, B. W. Lytle, G. Gonzalez-Stawinski, P. Varvitsiotis, M. K. Banbury, P. M. McCarthy, G. B. Pettersson, et al. Does the Arterial Cannulation Site for Circulatory Arrest Influence Stroke Risk? Ann. Thorac. Surg., October 1, 2004; 78(4): 1274 - 1284. [Abstract] [Full Text] [PDF]

				D.K. Harrington, A.S. Walker, H. Kaukuntla, R.M. Bracewell, T.H. Clutton-Brock, M. Faroqui, D. Pagano, and R.S. Bonser Selective Antegrade Cerebral Perfusion Attenuates Brain Metabolic Deficit in Aortic Arch Surgery: A Prospective Randomized Trial Circulation, September 14, 2004; 110(11_suppl_1): II-231 - II-236. [Abstract] [Full Text] [PDF]

				L. G. Svensson, E. M. Nadolny, and W. A. Kimmel Multimodal protocol influence on stroke and neurocognitive deficit prevention after ascending/arch aortic operations Ann. Thorac. Surg., December 1, 2002; 74(6): 2040 - 2046. [Abstract] [Full Text] [PDF]

				L. G. Svensson Antegrade perfusion during suspended animation? J. Thorac. Cardiovasc. Surg., December 1, 2002; 124(6): 1068 - 1070. [Full Text]

				D. Harrington, C. H. Wong, and R. S. Bonser Neurological Complications of Aortic Surgery Seminars in Cardiothoracic and Vascular Anesthesia, March 1, 2002; 6(1): 7 - 16. [Abstract] [PDF]

				D. L. Reich, S. Uysal, M. A. Ergin, and R. B. Griepp Retrograde cerebral perfusion as a method of neuroprotection during thoracic aortic surgery Ann. Thorac. Surg., November 1, 2001; 72(5): 1774 - 1782. [Abstract] [Full Text] [PDF]

				L. G. Svensson Reply to Zamvar et al. Eur. J. Cardiothorac. Surg., October 1, 2001; 20(4): 890 - 890. [Full Text] [PDF]

				L. G. Svensson, E. M. Nadolny, D. L. Penney, J. Jacobson, W. A. Kimmel, M. H. Entrup, and R. S. D'Agostino Prospective randomized neurocognitive and S-100 study of hypothermic circulatory arrest, retrograde brain perfusion, and antegrade brain perfusion for aortic arch operations Ann. Thorac. Surg., June 1, 2001; 71(6): 1905 - 1912. [Abstract] [Full Text] [PDF]

				S. A. LeMaire, J. K. Bhama, Z. C. Schmittling, P. J. Oberwalder, C. Koksoy, S. A. Raskin, P. E. Curling, and J. S. Coselli S100{beta} correlates with neurologic complications after aortic operation using circulatory arrest Ann. Thorac. Surg., June 1, 2001; 71(6): 1913 - 1919. [Abstract] [Full Text] [PDF]

				E. M. Nadolny and L. G. Svensson Hypothermic arrest for descending aortic rupture in reoperative patients Ann. Thorac. Surg., June 1, 2001; 71(6): 2027 - 2030. [Abstract] [Full Text] [PDF]

				J. Rimpilainen, M. Pokela, K. Kiviluoma, V. Anttila, V. Vainionpaa, J. Hirvonen, P. Ohtonen, A. Mennander, E. Remes, and T. Juvonen Leukocyte filtration improves brain protection after a prolonged period of hypothermic circulatory arrest: A study in a chronic porcine model J. Thorac. Cardiovasc. Surg., December 1, 2000; 120(6): 1131 - 1140. [Abstract] [Full Text] [PDF]

				L. G. Svensson, J. Longoria, W. A. Kimmel, and E. Nadolny Management of aortic valve disease during aortic surgery Ann. Thorac. Surg., March 1, 2000; 69(3): 778 - 783. [Abstract] [Full Text] [PDF]

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Lars G. Svensson Ali Husain David M. Shahian Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Svensson, L. G. Articles by Shahian, D. M. Search for Related Content PubMed PubMed Citation Articles by Svensson, L. G. Articles by Shahian, D. M.