Anesth Analg 2003;97:1657-1660
© 2003 International Anesthesia Research Society
ANESTHETIC PHARMACOLOGY
The Use of Bone Cement Induces an Increase in Serum Astroglial S-100B Protein in Patients Undergoing Total Knee Arthroplasty
Hiroyuki Kinoshita, MD PhD*,
Hiroshi Iranami, MD*,
Keisuke Fujii, MD*,
Akinori Yamazaki, MD*,
Manabu Shimogai, MD*,
Katsutoshi Nakahata, MD*,
Yasuo Hironaka, MD*, and
Yoshio Hatano, MD PhD
*Department of Anesthesia, Japanese Red Cross Society, Wakayama Medical Center, Wakayama, Japan; and
Department of Anesthesiology, Wakayama Medical University, Wakayama, Japan
Address correspondence and reprint requests to Hiroyuki Kinoshita, MD, PhD, Department of Anesthesiology, Wakayama Medical University, 811-1 Kimiidera, Wakayama, Wakayama 641-0012, Japan. Address e-mail to hkinoshi{at}pd5.so-net.ne.jp
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Abstract
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Cerebral microemboli can occur during arthroplasty with the use of bone cement. Astroglial S-100B protein is a sensitive marker of cerebral damage. Therefore, we designed this study to determine the effect of bone cement on the brain by investigating serum levels of S-100B protein in patients undergoing bone surgery with or without bone cement. Fourteen patients undergoing knee arthroplasty (n = 7) or reamed intramedullary nailing for tibial fracture (n = 7) requiring a pneumatic tourniquet were enrolled in this study. Bone cement containing polymethyl methacrylate and methyl methacrylate was used for every patient undergoing knee arthroplasty. Serum samples were obtained from venous blood before the induction of general anesthesia, 15 min after deflation of a pneumatic tourniquet, and 3 days after the operation. The serum level of S-100B protein was significantly increased 15 min after a pneumatic tourniquet deflation in the knee arthroplasty group compared with the tibial fracture group (0.41 and 0.08 ng/mL, respectively; P < 0.05). In all patients studied, no neurological abnormalities were noted in the postoperative period. These results suggest that, in patients undergoing knee arthroplasty, bone cement may transiently induce astroglial injury, although it does not alter neurological outcome.
IMPLICATIONS: Serum S-100B protein was significantly increased 15 min after a pneumatic tourniquet deflation in patients undergoing knee arthroplasty with bone cement, but not in those undergoing reamed intramedullary nailing for tibial fracture without bone cement. These results suggest that bone cement may transiently induce astroglial injury.
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Introduction
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Recent studies have demonstrated acute cerebral emboli during arthroplasty of lower extremities, suggesting that intraoperative cerebral emboli may contribute to brain damage after, as well as during, bone surgeries (1–3). Although bone cement is routinely used to insert and fix joint prostheses during arthroplasty, adverse effects on the brain of bone cementing have not been well studied. S-100B protein forms part of the Ca2+-binding proteins predominantly found in astrocytes and Schwann cells (4). Wunderlich et al. (5) documented that the increase in serum S-100B protein was well correlated with neurological outcome after brain damage. Therefore, this study was designed to determine the effect on the brain of bone cement by investigating serum levels of S-100B protein in patients requiring a pneumatic tourniquet who were undergoing bone surgery with or without bone cement.
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Methods
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The institutional investigation committee approved this study, and written, informed consent was obtained from each patient enrolled. Fourteen patients undergoing knee arthroplasty (n = 7) or reamed intramedullary nailing for tibial fracture (n = 7) requiring a pneumatic tourniquet, without any cerebral or cardiac disturbances, received general anesthesia in combination with epidural anesthesia. There was no premedication. Before the induction of general anesthesia, an epidural catheter was inserted from the L2-3 intervertebral space in all patients. Mepivacaine 2% was administered to the epidural space as needed. Clinical monitoring included a three-lead electrocardiogram, noninvasive measurement of arterial blood pressure, and measurement of pulse oximetric oxygen saturation and end-tidal carbon dioxide tension. General anesthesia was induced with propofol (2 mg/kg), and vecuronium (0.1 mg/kg) was administered to facilitate tracheal intubation. Anesthesia was maintained with 1% to 2% sevoflurane in combination with 50% nitrous oxide. All patients were mechanically ventilated to maintain a constant end-tidal carbon dioxide level. The fractional inspiratory oxygen concentration was increased after surgery for 24 h by insufflating oxygen (3 L/min) through a face mask.
Bone cement containing polymethyl methacrylate and methyl methacrylate (EnduranceTM; DePuy Japan, Tokyo, Japan) was used for every patient undergoing knee arthroplasty. A pneumatic tourniquet was placed around the thigh of the operated limb and inflated (300 mm Hg) after the application of the Esmarch bandage. In all patients, it was inflated at the beginning of the surgery and deflated immediately before skin closure.
Standard neurological assessments—including testing sensory and motor nerve functions and neuropsychological status (by conducting brief calculations and conversation)—were performed for all patients on the day before surgery and the first and third days after the operation. In addition, unconsciousness, delirium, disorientation, paralysis, or memory disturbance was also followed up for 3 days after surgery for each patient.
Serum samples were obtained from venous blood before the induction of anesthesia, 15 min after deflation of a pneumatic tourniquet, and 3 days after the operation. Three milliliters of venous blood was drawn by using plain vacuum tubes, centrifuged, and frozen for batch analysis. S-100B protein was analyzed by chemiluminescent immunoassay (SRL Inc., Tokyo, Japan). This immunoassay has a very small cross-reactivity to other types of S-100 protein (<0.1% and 1.7% for 
and ß protein, respectively), indicating the higher specificity of this assay for S-100B (ßß) protein, especially at the range less than 2 ng/mL (SRL Inc.). The functional detection limit of this assay was 0.05 ng/mL, and, therefore, the value less than this limit was treated as 0 ng/mL of S-100B protein.
Data are shown as mean ± SD. Statistical analysis was performed by using repeated-measures analysis of variance, followed by the Scheffé F test for S-100B protein levels and unpaired Student’s t-tests for demographic data. Differences were considered statistically significant at P < 0.05.
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Results
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There were no differences between the knee arthroplasty (n = 7; all female) and tibial fracture (n = 7; female, n = 4; male, n = 3) groups in age, weight, or duration of tourniquet application (Table 1). Mean serum levels of S-100B protein were significantly increased 15 min after pneumatic tourniquet deflation in the knee arthroplasty group compared with the tibial fracture group (Fig. 1). In contrast, the level of S-100B protein was not increased at 3 days after the operation in either group (Fig. 1). In all patients studied, no neurological abnormalities were noted in the postoperative period.
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Figure 1. Perioperative serum levels of S-100B protein in patients undergoing bone surgery with or without bone cement. Data are shown as means ± SD. *Difference between patients with or without bone cement is statistically significant (P < 0.05).
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Discussion
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This is the first study demonstrating that, in patients undergoing knee arthroplasty, the serum level of S-100B protein is increased immediately after pneumatic tourniquet deflation, suggesting that the use of bone cement may transiently induce brain damage in these patients. S-100B protein is released from glial and Schwann cells after brain damage, and serum concentrations of the protein after stroke and head injury are prognostic for cerebral outcome (4–6). These results suggest that the serum level of this protein is one of the sensitive markers predicting neurological outcome after brain damage. In this study, the mean serum S-100B protein level was significantly increased more than 0.4 ng/mL in patients undergoing knee arthroplasty. One study demonstrated that in patients with unilateral supratentorial infarction, mean serum S-100B protein levels seen at the first and third days of admission were 0.3 or 0.5 ng/mL, respectively, and that, in this case, 65% of the patients exhibited variable degrees of neuropsychological deficits (5). Therefore, these results suggest that the level of S-100B protein obtained in the patients undergoing knee arthroplasty was similar to that reported in patients with unilateral supratentorial cerebral infarction and that this increase may be mediated by certain cerebral damage.
Because previous studies documented that the peak level of S-100B protein was obtained on the third day after stroke, we measured the level at three days after the operation, as well as immediately after the deflation of a pneumatic tourniquet (7,8). However, in the patients undergoing knee arthroplasty, the serum level of S-100B protein was increased immediately after pneumatic tourniquet deflation but not at three days after the operation. A more recent study has demonstrated that S-100B protein levels increase immediately after cardiac arrest and traumatic brain injury and decrease precipitously after 12 hours, indicating that the time course of changes in levels of S-100B protein after these insults is much more consistent with the findings of our study (9). The differential mechanisms of S-100B protein release may contribute to the differential time courses of the increment of this protein among these pathophysiological conditions.
One study demonstrated that in multitrauma patients without head injury, S-100B protein levels increase compared with the levels of healthy control patients, indicating that in the absence of head trauma, serum S-100 B protein may increase in traumatic patients (10). However, in this study, they measured two types of S-100 protein—S-100ß and ßß protein—at the same time, and they treated the sum of these proteins as the S-100B protein value (10). Therefore, it is unclear whether those results were due to increased levels of pure S-100B (ßß) originating from the central nervous system (11). In addition, it is important to note that measurement of pure S-100B (ßß) by using immunoassay has a cross-reactivity to other types of S-100 protein, especially at higher levels of the protein. In this study, the assay we used demonstrated the very high specificity for S-100B (ßß) protein, especially at the range less than 2 ng/mL, and the S-100B protein data obtained in patients enrolled were all less than this limit, suggesting the specific detection of pure S-100B protein in our study.
A pneumatic tourniquet was similarly applied to all patients enrolled in this study, and the duration of tourniquet application did not differ between groups. Therefore, the application of the tourniquet itself probably did not play a role in increased levels of serum S-100B protein, although the prolonged duration of application to a pneumatic tourniquet appeared to augment the number of pulmonary emboli in patients undergoing knee surgeries (12). In addition, all of patients enrolled in this study had reaming of the bone, which has the potential to cause pulmonary embolism during the surgical procedure, supporting the idea that the only difference between groups appeared to be the use of bone cement in patients undergoing arthroplasty (13). It is possible that the bone cement emboli may contribute to the increased S-100B protein in patients undergoing knee arthroplasty, although one study has indicated that during total hip arthroplasty, the venous emboli originated from the reamed bone but not from the bone cement (14). Furthermore, we cannot completely exclude the possibility that the bone cement itself may directly induce neuronal injury that results in S-100B protein release, because polymethyl methacrylate and methyl methacrylate, which are major contents of the bone cement, can induce acute cytotoxicity mediated by the increased chemical mediator release via the activation of leukocytes (15,16). In this study, we did not measure serum levels of these compounds, and, therefore, it is unclear whether increased levels of S-100B protein correlate with serum concentrations of the contents of bone cement.
In this study, no neurological abnormalities were noted in the postoperative period in any patient studied, suggesting that an increase in the serum S-100B protein level of patients undergoing knee arthroplasty was subclinical. Although this may be due to transient cerebral damage induced by bone cement, we do not have a clear explanation for this discrepancy between the increased levels of protein and the clinical symptoms in our patients. In this study, we carefully performed standard neurological assessments for all patients to detect neurological abnormality, but we did not evaluate cognitive dysfunction in detail by using neuropsychological tests with scales (17). Therefore, we cannot completely exclude the possibility that some neuronal abnormalities, which could not be detected by our assessment, might have been missed. However, it is clear that we should carefully interpret the S-100B protein level, depending on the duration after the application of bone cement, when patients undergoing arthroplasty are subjected to clinically significant cerebral ischemia induced by reamed bone emboli, as well as atherosclerotic thrombi.
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Footnotes
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Presented in part at the annual meeting of the American Society of Anesthesiologists, Orlando, FL, October 12–16, 2002.
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References
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- Edmonds CR, Barbut D, Hager D, Sharrock NE. Intraoperative cerebral arterial embolization during total hip arthroplasty. Anesthesiology 2000; 93: 315–8.[ISI][Medline]
- Colonna DM, Kilgus D, Brown W, et al. Acute brain fat embolization occurring after total hip arthroplasty in the absence of a patent foramen ovale. Anesthesiology 2002; 96: 1027–9.[Medline]
- Jenkins K, Chung F, Wennberg R, et al. Fat embolism syndrome and elective knee arthroplasty. Can J Anaesth 2002; 49: 19–24.[Abstract/Free Full Text]
- Shaaban Ali M, Harmer M, Vaughan R. Serum S100 protein as a marker of cerebral damage during cardiac surgery. Br J Anaesth 2000; 85: 287–98.[Abstract/Free Full Text]
- Wunderlich MT, Ebert AD, Kratz T, et al. Early neurobehavioral outcome after stroke is related to release of neurobiochemical markers of brain damage. Stroke 1999; 30: 1190–5.[Abstract/Free Full Text]
- Raabe A, Grolms C, Seifert V. Serum markers of brain damage and outcome prediction in patients after severe head injury. Br J Neurosurg 1999; 13: 56–9.[ISI][Medline]
- Büttener T, Weyers S, Postert T, et al. S100 protein: serum marker of focal brain damage after ischemic territorial MCA infarction. Stroke 1997; 28: 1961–5.[Abstract/Free Full Text]
- Missler U, Wiesmann M, Christine F, Kaps M. S100 protein and neuron-specific enolase concentrations in blood as indicators of infarction volume and prognosis in acute ischemic stroke. Stroke 1997; 28: 1956–60.[Abstract/Free Full Text]
- Mussack T, Biberthaler P, Kanz K-G, et al. Serum S-100B and interleukin-8 as predictive markers for comparative neurologic outcome analysis of patients after cardiac arrest and severe traumatic brain injury. Crit Care Med 2002; 30: 2669–74.[ISI][Medline]
- Anderson RE, Hansson L-O, Nilsson O, et al. High serum S100B levels for trauma patients without head injuries. Neurosurgery 2001; 48: 1255–60.[ISI][Medline]
- Fano G, Biocca S, Fulle S, et al. The S-100: a protein family in search of a function. Prog Neurobiol 1995; 46: 71–82.[ISI][Medline]
- Hirota K, Hashimoto H, Kabara S, et al. The relationship between pneumatic tourniquet time and the amount of pulmonary emboli in patients undergoing knee arthroscopic surgeries. Anesth Analg 2001; 93: 776–80.[Abstract/Free Full Text]
- Robinson CM, Ludlam CA, Ray DC, et al. The coagulative and cardiorespiratory responses to reamed intramedullary nailing of isolated fractures. J Bone Joint Surg Br 2001; 83: 963–73.
- Hayakawa M, Fujioka Y, Morimoto Y, et al. Pathological evaluation of venous emboli during total hip arthroplasty. Anaesthesia 2001; 56: 571–5.[ISI][Medline]
- Dahl OE, Garvik LJ, Lyberg T. Toxic effects of methylmethacrylate monomer on leukocytes and endothelial cells in vitro. Acta Orthop Scand 1994; 65: 147–53.[Medline]
- Horowitz SM, Gautsch TL, Frondoza CG, Riley L Jr. Macrophage exposure to polymethyl methacrylate leads to mediator release and injury. J Orthop Res 1991; 9: 406–13.[Medline]
- Linstedt U, Meyer O, Kropp P, et al. Serum concentration of S-100 protein in assessment of cognitive dysfunction after general anesthesia in different types of surgery. Acta Anaesthesiol Scand 2002; 46: 384–9.[ISI][Medline]
Accepted for publication July 10, 2003.
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Abstract
Introduction
