JOURNAL HOME CME HOME THIS MONTH PAST ISSUES ETOC COLLECTIONS AUTHORS REVIEWERS EDITORIAL BOARD FEEDBACK RSS HELP
		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (34) Citing Articles via Google Scholar Google Scholar Articles by Wang, D. Articles by Meng, M. Search for Related Content PubMed PubMed Citation Articles by Wang, D. Articles by Meng, M. Related Collections Cardiovascular Surgery Heart Monitoring (Cardiac)

---

CARDIOVASCULAR ANESTHESIA

The Effect of Lidocaine on Early Postoperative Cognitive Dysfunction After Coronary Artery Bypass Surgery

Dongxin Wang, MD PhD^*, Xinmin Wu, MD^*, Jun Li, MD^*, Feng Xiao, MD, Xiaoying Liu, MD^*, and Meijin Meng, MD^*

Departments of *Anesthesiology and Cardiac Surgery, First Hospital, Peking University, Beijing, China

Address correspondence and reprint requests to Xinmin Wu, MD, Department of Anesthesiology, First Hospital, Peking University, No. 8 Xishiku St., Beijing 100034, China. Address e-mail to wangdongxin{at}hotmail.com

	Abstract

Top Abstract Introduction Methods Results Discussion References

 
We investigated the effect of lidocaine on the incidence of cognitive dysfunction in the early postoperative period after cardiac surgery. One-hundred-eighteen patients undergoing elective coronary artery bypass surgery with cardiopulmonary bypass (CPB) were randomized to receive either lidocaine (1.5 mg/kg bolus followed by a 4 mg/min infusion during operation and 4 mg/kg in the priming solution of CPB) or placebo. A battery of nine neuropsychological tests was administered before and 9 days after surgery. A postoperative deficit in any test was defined as a decline by more than or equal to the preoperative SD of that test in all patients. Any patient showing a deficit in two or more tests was defined as having postoperative cognitive dysfunction. Eighty-eight patients completed pre- and postoperative neuropsychological tests. Plasma lidocaine concentrations (µg/mL) were 4.78 ± 0.52 (mean ± SD), 5.38 ± 0.95, 4.52 ± 0.39, 5.82 ± 0.76, and 7.10 ± 1.09 at 10 min before CPB; 10, 30, and 60 min of CPB; and at the end of operation, respectively. The proportion of patients showing postoperative cognitive dysfunction was significantly reduced in the lidocaine group compared with that in the placebo group (18.6% versus 40.0%; P = 0.028). We conclude that intraoperative administration of lidocaine decreased the occurrence of cognitive dysfunction in the early postoperative period.

IMPLICATIONS: Postoperative cognitive dysfunction is a commonly recognized complication after cardiac surgery. Intraoperative cerebral microembolism and hypoperfusion have been proposed to be the major mechanisms. The results of this study show that intraoperative administration of lidocaine decreased the occurrence of early postoperative cognitive dysfunction, perhaps because of its neuroprotective effects.

	Introduction

Top Abstract Introduction Methods Results Discussion References

 
Cognitive dysfunction has increasingly been recognized as a complication after cardiac surgery. Although technological advances in cardiac surgery, anesthesia, and cardiopulmonary bypass (CPB) have resulted in a steady decrease in the mortality and morbidity associated with these procedures over the past four decades, the incidence of postoperative cognitive decline is still frequent. It is approximately 50% to 80% at discharge, 20% to 50% at 6 wk, and 10% to 30% at 6 mo after operation (1–3). Two major mechanisms have been proposed to explain the occurrence of cognitive dysfunction after cardiac surgery: intraoperative cerebral microembolism and hypoperfusion (1). Considerable evidence suggests that cerebral embolization occurs in all patients subjected to CPB (4). A correlation between intraoperative cerebral microembolic load and postoperative neuropsychological dysfunction has been demonstrated (5). Moreover, low perfusion pressure and rewarming during CPB may cause an imbalance between oxygen supply and extraction (6). In both mechanisms, ischemic injury is the common pathway causing cerebral dysfunction.

Lidocaine, a commonly used local anesthetic and antiarrhythmic drug, has been shown, in vivo, to provide protection to the ischemic brain. It preserved cerebral function after deep hypothermic circulatory arrest in dogs (7); improved cerebral protection provided by retrograde cerebral perfusion in dogs (8,9); and reduced infarct size in a model of transient focal cerebral ischemia in rats (10). Mitchell et al. (11) reported that perioperative infusion of lidocaine in a standard antiarrhythmic dose improved the neuropsychological outcome in patients undergoing left heart valve operations. It is generally believed that neurologic complications occur less frequently in patients undergoing closed-chamber cardiac procedures (i.e., coronary artery bypass surgery) than in those undergoing open-chamber procedures (i.e., valve replacement surgery) (12,13). The purpose of this study was to investigate whether intraoperative administration of lidocaine can reduce the early postoperative occurrences of cognitive dysfunction in patients undergoing coronary artery bypass surgery with CPB.

	Methods

Top Abstract Introduction Methods Results Discussion References

 
Patients
From September 1997 to August 2001, 196 cases of coronary artery bypass surgery were performed using CPB at the First Hospital of Peking University. One-hundred-sixty-five patients met the eligibility criteria, and 118 of these patients gave consent for participation in the study, which received approval from the ethics committee of the hospital. The selection criteria were as follows: elective routine surgery; no other simultaneous surgery (e.g., valvular replacement); no previous cardiac surgery; no history of neurological or psychiatric disorders; no suspected history of adverse reactions to lidocaine; age 70 yr; preoperative left ventricular ejection fraction (LVEF) >35%; no preoperative biochemical evidence of renal dysfunction (indicated by a serum creatinine concentration more than 177 µmol/L [2.0 mg/dl]) or active hepatic disease; and sufficient education to complete preoperative neuropsychological tests. Patients older than 70 yr were excluded from this study because we found that postoperative noncerebral complications occurred more frequently in this age group, which made it difficult to perform postoperative neuropsychological tests and to explain the test results. Moreover, there were only six otherwise eligible patients in this age group.

Neuropsychological Testing
Neuropsychological tests were administered the day before and 9 days after operation. Assessments were performed individually by an experienced psychometrician (JL) who was blinded to treatment group assignments. The test battery, which includes seven tests with nine subscales, was selected on the basis of demonstrated efficiency in similar subject populations (13,14). Specific tests used were as follows: the Mental Control and Digit Span (forward and backward) subtests of the Wechsler Memory Scale (Chinese edition, Hunan Medical University, Hunan, China), measures of attention and concentration, with high scores indicating better function; the Visual Retention and Paired Associate Verbal Learning subtests of the Wechsler Memory Scale (Chinese edition, Hunan Medical University), measures of figural memory and verbal learning/memory, with high scores indicating better function; the Digit Symbol subtest of the Wechsler Adult Intelligence Scale-Revised (Chinese edition, Hunan Medical University), a measure of psychomotor speed, with a high score indicating better function; the Halstead-Reitan Trail Making Test (Part A), a measure of hand-eye coordination, attention, and concentration, with a low score indicating better function; and the Grooved Pegboard Test (favored and unfavored hand), a measure of manual dexterity, with a low score indicating better function. Parallel forms of tests were used in sequential testing in a randomized way when available to minimize any practice effect.

The definition of postoperative cognitive deficit in the field of cardiac surgery proposed by Newman (15) was applied in this study. An SD unit for each test was computed from all the preoperative scores. A deficit in a test was defined as a decline 1 SD in the postoperative score in comparison to the preoperative score. For the deficit to be significant in an individual, it must have occurred in two or more tests. When a test had a number of subtest scores, at least one subtest had to have a significant deterioration for that test to be considered to be in deficit. Subtest scores did not contribute independently to the measure of deficit; thus, when more than one subtest showed a significant deterioration, the neuropsychological test still yielded only one deficit score.

Anesthesia, Operation, and CPB
Patients were premedicated with midazolam (7.5 mg orally, 1.5 h before entering the operating room) and morphine (10 mg IM injection, 0.5 h before entering the operating room). Anesthesia in all patients was based on moderate doses of fentanyl (20 to 30 µg/kg) and midazolam (0.05 to 0.15 mg/kg), supplemented with isoflurane (<1%) when necessary before and after CPB or with propofol (2.5 to 4.0 mg · kg^-1 · h^-1) during CPB. Muscle relaxation was maintained with vecuronium. Standard physiological monitoring—electrocardiogram (ECG), arterial pressure, pulmonary arterial pressure, central venous pressure, nasopharyngeal temperature, arterial oxygen saturation, ETCO₂, airway pressure, and urine output—was used throughout the procedure. Aprotinin (total dose 5,000,000 kallikrein-inhibiting units) was administered in all patients.

Median sternotomy was performed in all patients, and CPB was instituted through cannulation of the ascending aorta and the right atrium. Aortic palpation was used to detect atherosclerosis and, if present, to select an appropriate site for cannulation and clamping. Cold-blood cardioplegia was used for myocardial protection. Distal coronary anastomoses were completed with the proximal aorta cross-clamped and the heart arrested. Proximal aortic anastomoses were made with the aorta partially clamped and the heart beating.

The CPB circuit included a roller pump (Stockert Instrumente, Munich, Germany), a hollow-fiber membrane oxygenator (Medos Medizintechnik AG, Stolberg, Germany), and a 40-µm screen arterial filter (Baxter Healthcare Corp., Irvine, CA). Moderate hypothermia (32°C) was used during CPB. During rewarming, the maximal allowed blood temperature (at heat exchanger) was 37.5°C, and the maximal allowed nasopharyngeal temperature was 37°C. The warming rate was approximately 1°C core temperature increase per 3 min of bypass time. Perfusion was nonpulsatile, with indexed flows set at 2.4 L · m^-2 · min^-1 during cooling and rewarming and 2.0 L · m^-2 · min^-1 during stable CPB. Mean arterial blood pressure was maintained between 60 and 80 mm Hg. -Stat acid-base management was used for all patients.

Patient Grouping
In a prospective, randomized, and double-blinded manner, the patients were divided into two groups (Fig. 1). The medication (2% lidocaine or normal saline) was prepared and coded by an anesthesiologist who did not participate in anesthesia and neuropsychological testing. The administration protocol was designed so that, in the lidocaine group (n = 57), lidocaine was delivered as a bolus of 1.5 mg/kg over 5 min at the opening of the pericardium and was followed by continuous infusion at 4 mg/min until the end of the operation. Another dose of lidocaine (4 mg/kg) was administered to the priming solution of CPB. In the placebo group (n = 61), normal saline was administered in the same volume and rate as that of 2% lidocaine.

View larger version (18K): [in this window] [in a new window]   Figure 1. Flow diagram of the study. CAB = coronary artery bypass.

Statistical Analysis
Comparison of continuous variables within groups was accomplished by using paired two-tailed Student’s t-tests, whereas comparison of these between groups was accomplished with unpaired two-tailed Student’s t-tests or the Mann-Whitney U-test. Comparison of proportions between groups was accomplished with ² or Fisher’s exact tests. Any preoperative or intraoperative factors that differed between the two groups (P < 0.10) were tested together with the treatment factor (the administration of lidocaine or placebo) by multivariate logistic regression analysis against the cognitive outcome of patients, to illustrate their effects on the occurrence of postoperative cognitive deficit. A significant level of P < 0.05 was chosen for all tests. The SPSS 9.0 for Windows (SPSS, Inc., Chicago, IL) software package was used for all statistical analysis.

	Results

Top Abstract Introduction Methods Results Discussion References

 
Thirty of the 118 consenting patients did not enter the review phase of the trial. Eighteen patients refused postoperative testing, although their postoperative recovery was uneventful; of these, 10 (16.4%) were in the placebo group and 8 (14.0%) were in the lidocaine group. Six patients had noncerebral postoperative complications that would have significantly altered neuropsychological performance; of these two (3.3%) were in the placebo group and four (7.0%) were in the lidocaine group. Six patients died in the early postoperative period; of these four (6.6%) were in the placebo group and two (3.5%) were in the lidocaine group. The proportion of patients in either of these conditions did not differ between the two groups (P = 0.722, P = 0.614, and P = 0.738, respectively). The following results are the summary of the remaining 88 patients; of these, 45 were in the placebo group and 43 were in the lidocaine group (Fig. 1). All postoperative tests were completed during the patients’ hospitalization.

The relevant demographic, preoperative, operative, and postoperative data are listed in Tables 1, 2, and 3, respectively. The proportion of patients with preoperative hypertension was smaller in the lidocaine group than in the placebo group (P = 0.049). There were no significant differences in the other aspects between the two groups. Platelet transfusion was not required in either group during the perioperative period.

View larger version (44K): [in this window] [in a new window]   Figure 2. Proportions of patients with no deficit; with deficits in one, two, three, or four tests; and with deficits in two or more tests in the two groups. *P = 0.028 compared with the placebo group.

	Discussion

Top Abstract Introduction Methods Results Discussion References

 
Neurological problems after cardiac procedures, such as delirium, persistent somnolence, cognitive difficulty, seizure, and stroke, were reported more than 40 years ago (16). Neurological complication is an important cause of postoperative morbidity and prolonged hospitalization and is responsible for an increasing proportion of perioperative deaths. Although technological advances over the past decades have greatly improved the safety of cardiac surgery, the incidence of postoperative cognitive dysfunction remains frequent (1–3).

Although it is controversial, evidence suggests that early postoperative cognitive dysfunction after cardiac surgery is perhaps the result of organic cerebral damage. Aberg et al. (17) reported a significant correlation between cerebrospinal fluid concentration of adenylate kinase (a marker of cerebral injury) and performance in postoperative psychometric tests. More recent studies showed that the postoperative serum concentrations and kinetics of S-100B protein and neuron-specific enolase (markers of cerebral injury) have predictive value with respect to the early neuropsychological and neuropsychiatric outcome after cardiac surgery (18,19). Most of the early postoperative cognitive dysfunction is transient. However, a long-term follow-up study by Newman et al. (3) found that cognitive decline immediately after coronary artery bypass surgery was a significant predictor of both the incidence and the severity of cognitive decline five years later. This result further confirmed the importance of assessing the early postoperative cognitive dysfunction.

A strategy to decrease the occurrence of postoperative cognitive dysfunction may require further improvement of techniques in cardiac surgery, perioperative management of patients, and CPB. Another possible treatment that is attracting more attention is pharmacological cerebral protection. At present, however, there is no agreement on the efficiency of prophylactic neuroprotectants in cardiac surgery. Nussmeier et al. (20) reported that thiopental reduced the incidence of early postoperative neuropsychiatric problems, although patients were slower to wake, remained intubated longer, and required more inotropic support than controls. This result was not replicated in subsequent studies, and routine use of thiopental for this purpose is not recommended (21). In a small controlled cardiac surgical trial, nimodipine produced equivocal preservation of memory function six months after operation (22). However, a larger placebo-controlled study of nimodipine in this context was terminated early because of increased rates of death and major bleeding in the treatment group (23). Arrowsmith et al. (24) observed the effect of remacemide, an N-methyl-D-aspartate receptor antagonist. Compared with the placebo group, patients treated with remacemide improved in some variables reflecting neuropsychological performance. However, the proportions of patients showing postoperative cognitive dysfunction did not differ significantly between the groups.

The effects of lidocaine protecting the ischemic brain have been demonstrated by many in vivo studies (7–11). Possible mechanisms for cerebral protection by lidocaine include deceleration of ischemic transmembrane ion shifts (25), reduction in cerebral metabolic rate (26), and reduction of ischemic excitotoxin release (27). Considering its common use in antiarrhythmic treatment, lidocaine may be a suitable cerebral protective drug for clinical purpose.

The optimal dose and treatment duration of lidocaine for cerebral protection during cardiac surgery are not known. In both clinical and animal studies, lidocaine provided cerebral protection at antiarrhythmic doses (10,11). In vitro studies showed that, within a certain range, the protective effect of lidocaine was positively correlated with its concentration (25,27). In this study, the upper limit of the antiarrhythmic dosing regimen was used. The results of plasma lidocaine concentration were at or slightly larger than the upper limit of the antiarrhythmic therapeutic range (28).

Our results further confirmed that there was a frequent incidence of cognitive dysfunction after cardiac surgery and demonstrated for the first time in a clinical trial that intraoperative administration of lidocaine significantly reduced the occurrence of early postoperative cognitive dysfunction after coronary artery bypass surgery. In the study of Mitchell et al. (11), lidocaine was continued for 48 hours. Using a battery of tests consisting of 11 neuropsychological test subscales, they found that the proportions of patients exhibiting decrement in at least one test subscale were significantly less in the lidocaine group than those in the placebo group at 10 days and 10 weeks after operation. However, the proportion of patients exhibiting decrements in at least two test subscales did not differ significantly between the two groups, perhaps because of small group size. A limitation of our study design is that we did not evaluate the postoperative cognitive results at longer intervals, such as 3 months or later. The long-term effect of lidocaine treatment merits further study. No interventional study has shown an outcome difference at long-term intervals after cardiac surgery (20–24).

The definition of cognitive dysfunction in the field of cardiac surgery has been the subject of much discussion. The use of SD values from the preoperative tests as thresholds is a controversial method. One limitation of this method is that the SD value will change according to the number of subjects enrolled in the trial. In addition, we are concerned about changes in an individual, whereas the SD is derived from the entire sample. However, this is a conservative and vigorous method to define deficits. Most neuropsychologic tests repeated on the same individual would be expected to produce some improvement in performance, the so-called "practice effect," and it is against this improvement that any deteriorations are to be considered (15). Because of the practice effect, comparison of the group mean results is not an efficient method of analysis because the results of patients showing deterioration will be counteracted by the results of patients showing learning effects. This is perhaps the reason why a significant difference in the incidence of cognitive dysfunction is not reflected in significant differences in neuropsychological scores between the two groups. However, when compared with preoperative results, four test results decreased significantly in both groups, whereas two test values decreased significantly only in the placebo group, but not in the lidocaine group (Table 5). If we presume that the cognitive function of patients having two, three, or four deficits is worse than of those having no or just one deficit, we come to the conclusion that the severity of postoperative cognitive dysfunction was also less serious in the lidocaine group than in the placebo group (Fig. 2). These results also indicate the beneficial effect of lidocaine treatment.

In our results, the most frequent postoperative neuropsychological performance decline occurred in the test of Paired Associate Verbal Learning, which measured the function of verbal learning and memory. A similar phenomenon has been reported by others (12). A neuropsychological test may assess a particular function or even a specific brain area, so a comprehensive battery of tests will increase the sensitivity to detect cerebral dysfunction. However, some regions of the brain, such as the hippocampus in the temporal lobe, are especially vulnerable to transient hypoxia (29). Tufo et al. (30) showed, in a series of 10 patients who died in the immediate period after cardiac surgery, that anoxic changes in the hippocampal formation were the most common lesion in brain sections. Memory functions depend on the integrity of medial temporal lobe structures. Some authors believe that the neuropsychological dysfunction after cardiac surgery is mainly attributable to temporal lobe dysfunction associated with transient hypoxia (12).

Although patients were randomly divided into two groups in this study, statistical analysis revealed that the proportion of patients with preoperative hypertension was smaller in the lidocaine group than in the placebo group. Although the difference was not significant between the groups, the proportion of patients with preoperative old myocardial infarction was a little less in the lidocaine group. Preoperative hypertension may impair cerebrovascular autoregulation and thus render patients more vulnerable to intraoperative hypotension. Previous myocardial infarction may also reduce cardiac function. However, the mean preoperative LVEF value and the proportion of patients with LVEF <40% did not differ between the groups. Multivariate logistic regression analysis also indicated that there were no significant correlations between preoperative hypertension or/and preoperative old myocardial infarction and the occurrence of postoperative cognitive decline. Intraoperative treatment with lidocaine was the only factor that significantly influenced the incidence of postoperative cognitive dysfunction.

In conclusion, the results of our study further confirmed the frequent incidence of postoperative cognitive dysfunction after cardiac surgery. Intraoperative administration of lidocaine significantly decreased the occurrence of early postoperative cognitive dysfunction. The optimal dosing regimen and long-term results of lidocaine for cerebral protection in cardiac surgery merit further study.

	Acknowledgments

 
Supported by Grant 96-1-264 for scientific research from the Ministry of Public Health of the People’s Republic of China.

We gratefully acknowledge the technical help provided by Drs. Dajian Xie and Xiang Qin and the statistical advice offered by Prof. Yi Zhao.

	Footnotes

 
Presented in part at the International Anesthesia Research Society 76th Clinical and Scientific Congress, San Diego, CA, March 16–20, 2002.

	References

Top Abstract Introduction Methods Results Discussion References

 

1. Selnes OA, Goldsborough MA, Borowicz LM, McKhann GM. Neurobehavioural sequelae of cardiopulmonary bypass. Lancet 1999; 353: 1601–6.[Web of Science][Medline]
2. Sotaniemi KA, Mononen H, Hokkanen TE. Long-term cerebral outcome after open-heart surgery: a five-year neuropsychological follow-up study. Stroke 1986; 17: 410–6.[Abstract/Free Full Text]
3. Newman MF, Kirchner JL, Phillips-Bute B, et al. Longitudinal assessment of neurocognitive function after coronary-artery bypass surgery. N Engl J Med 2001; 344: 395–402.[Abstract/Free Full Text]
4. Moody DM, Bell MA, Challa VR, et al. Brain microemboli during cardiac surgery or aortography. Ann Neurol 1990; 28: 477–86.[Web of Science][Medline]
5. Pugsley W, Klinger L, Paschalis C, et al. The impact of microemboli during cardiopulmonary bypass on neuropsychological functioning. Stroke 1994; 25: 1393–9.[Abstract]
6. Croughwell ND, Frasco P, Blumenthal JA, et al. Warming during cardiopulmonary bypass is associated with jugular bulb desaturation. Ann Thorac Surg 1992; 53: 827–32.[Abstract]
7. Zhou Y, Wang D, Du M, et al. Lidocaine prolongs the safe duration of circulatory arrest during deep hypothermia in dogs. Can J Anaesth 1998; 45: 692–8.[Web of Science][Medline]
8. Wang D, Wu X, Zhou Y, et al. Lidocaine improved the cerebral protection provided by retrograde cerebral perfusion: an experimental study. Chin Med J (Engl) 1998;111:885–90.
9. Wang D, Wu X, Zhong Y, et al. Effect of lidocaine on improving the cerebral protection provided by retrograde cerebral perfusion: a neuropathological study. J Cardiothorac Vasc Anesth 1999; 13: 176–80.[Web of Science][Medline]
10. Lei B, Cottrell JE, Kass IS. Neuroprotective effect of low-dose lidocaine in a rat model of transient focal cerebral ischemia. Anesthesiology 2001; 95: 445–51.[Web of Science][Medline]
11. Mitchell SJ, Pellett O, Gorman DF. Cerebral protection by lidocaine during cardiac operations. Ann Thorac Surg 1999; 67: 1117–24.
12. Ebert AD, Walzer TA, Huth C, Herrmann M. Early neurobehavioral disorders after cardiac surgery: a comparative analysis of coronary artery bypass graft surgery and valve replacement. J Cardiothorac Vasc Anesth 2001; 15: 15–9.[Web of Science][Medline]
13. Murkin JM. Central nervous system dysfunction after cardiopulmonary bypass. In: Kaplan JA, Reich DL, Konstadt SN, eds. Cardiac anesthesia. 4th ed. Philadelphia: WB Saunders, 1999: 1259–79.
14. Murkin JM, Newman SP, Stump DA, Blumenthal JA. Statement of consensus on assessment of neurobehavioral outcomes after cardiac surgery. Ann Thorac Surg 1995; 59: 1289–95.[Free Full Text]
15. Newman SP. Analysis and interpretation of neuropsychologic tests in cardiac surgery. Ann Thorac Surg 1995; 59: 1351–5.[Abstract/Free Full Text]
16. Fox HM, Rizzo ND, Gifford S. Psychological observations of patients undergoing mitral surgery: study of stress. Psychosom Med 1954; 16: 186–208.[Abstract/Free Full Text]
17. Aberg T, Ronquist G, Tyden H, et al. Adverse effects on the brain in cardiac operations as assessed by biochemical, psychometric, and radiologic methods. J Thorac Cardiovasc Surg 1984; 87: 99–105.[Abstract]
18. Kilminster S, Treasure T, McMillan T, Holt DW. Neuropsychological change and S-100 protein release in 130 unselected patients undergoing cardiac surgery. Stroke 1999; 30: 1869–74.[Abstract/Free Full Text]
19. Hermann M, Ebert AD, Galazky I, et al. Neurobehavioral outcome predication after cardiac surgery: role of neurobiochemical markers of damage to neuronal and glial brain tissue. Stroke 2000; 31: 645–50.[Abstract/Free Full Text]
20. Nussmeier NA, Arlund C, Slogoff S. Neuropsychiatric complications after cardiopulmonary bypass: cerebral protection by a barbiturate. Anesthesiology 1986; 64: 165–70.[Web of Science][Medline]
21. Todd M. Barbiturate protection and cardiac surgery: a different result. Anesthesiology 1991; 74: 402–5.[Web of Science][Medline]
22. Forsman M, Olsnes BT, Semb G, Steen PA. Effects of nimodipine on cerebral blood flow and neuropsychological outcome after cardiac surgery. Br J Anaesth 1990; 65: 514–20.[Abstract/Free Full Text]
23. Legault C, Furberg CD, Wagenknecht LE, et al. Nimodipine neuroprotection in cardiac valve replacement: report of an early terminated trail. Stroke 1996; 27: 593–8.[Abstract/Free Full Text]
24. Arrowsmith JE, Harrison MJG, Newman SP, et al. Neuroprotection of the brain during cardiopulmonary bypass: a randomized trail of remacemide during coronary artery bypass in 171 patients. Stroke 1998; 29: 2357–62.[Abstract/Free Full Text]
25. Fried E, Amorim P, Chambers G, et al. The importance of sodium for anoxic transmission damage in rat hippocampal slices: mechanisms of protection by lidocaine. J Physiol (Lond) 1995;489:557–65.
26. Sakabe T, Maekawa T, Ishikawa T, Takeshita H. The effects of lidocaine on canine cerebral metabolism and circulation related to the EEG. Anesthesiology 1974; 40: 433–41.[Web of Science][Medline]
27. Taylor CP, Burke SP, Weber ML. Hippocampal slices: glutamate overflow and cellular damage from ischemia are reduced by sodium-channel blockade. J Neurosci Methods 1995; 59: 121–8.[Web of Science][Medline]
28. Collinsworth KA, Kalman SM, Harrison DC. The clinical pharmacology of lidocaine as an antiarrhythmic drug. Circulation 1974; 50: 1217–30.[Abstract/Free Full Text]
29. Dijkhuizen RM, Knollema S, van der Worp HB, et al. Dynamics of cerebral tissue injury and perfusion after temporary hypoxia-ischemia in the rat: evidence for region-specific sensitivity and delayed damage. Stroke 1998; 29: 695–704.[Abstract/Free Full Text]
30. Tufo HM, Ostfeld AM, Shekelle R. Central nervous system dysfunction following open-heart surgery. JAMA 1970; 212: 1333–40.[Abstract/Free Full Text]

This article has been cited by other articles:

				S. J. Mitchell, A. F. Merry, C. Frampton, E. Davies, D. Grieve, B. P. Mills, C. S. Webster, F. P. Milsom, T. W. Willcox, and D. F. Gorman Cerebral protection by lidocaine during cardiac operations: a follow-up study. Ann. Thorac. Surg., March 1, 2009; 87(3): 820 - 825. [Abstract] [Full Text] [PDF]

				J. P. Mathew, G. B. Mackensen, B. Phillips-Bute, H. P. Grocott, D. D. Glower, D. T. Laskowitz, J. A. Blumenthal, M. F. Newman, and for the Neurologic Outcome Research Group (NORG) o Randomized, Double-Blinded, Placebo Controlled Study of Neuroprotection With Lidocaine in Cardiac Surgery Stroke, March 1, 2009; 40(3): 880 - 887. [Abstract] [Full Text] [PDF]

				Y. Zhang, M. J. Laster, E. I. Eger II, M. Sharma, and J. M. Sonner Lidocaine, MK-801, and MAC Anesth. Analg., May 1, 2007; 104(5): 1098 - 1102. [Abstract] [Full Text] [PDF]

				C. W. Hogue Jr, C. A. Palin, and J. E. Arrowsmith Cardiopulmonary bypass management and neurologic outcomes: an evidence-based appraisal of current practices. Anesth. Analg., July 1, 2006; 103(1): 21 - 37. [Abstract] [Full Text] [PDF]

				G. N. Djaiani Aortic arch atheroma: stroke reduction in cardiac surgical patients. Seminars in Cardiothoracic and Vascular Anesthesia, June 1, 2006; 10(2): 143 - 157. [Abstract] [PDF]

				J. Butterworth, L. E. Wagenknecht, C. Legault, D. J. Zaccaro, N. D. Kon, J. W. Hammon Jr, A. T. Rogers, B. T. Troost, D. A. Stump, C. D. Furberg, et al. Attempted control of hyperglycemia during cardiopulmonary bypass fails to improve neurologic or neurobehavioral outcomes in patients without diabetes mellitus undergoing coronary artery bypass grafting J. Thorac. Cardiovasc. Surg., November 1, 2005; 130(5): 1319 - 1319. [Abstract] [Full Text] [PDF]

				H. Cao, I. S. Kass, J. E. Cottrell, and P. J. Bergold Pre- or Postinsult Administration of Lidocaine or Thiopental Attenuates Cell Death in Rat Hippocampal Slice Cultures Caused by Oxygen-Glucose Deprivation Anesth. Analg., October 1, 2005; 101(4): 1163 - 1169. [Abstract] [Full Text] [PDF]

				W. Nagels, R. Demeyere, J. Van Hemelrijck, E. Vandenbussche, K. Gijbels, and E. Vandermeersch Evaluation of the Neuroprotective Effects of S(+)-Ketamine During Open-Heart Surgery Anesth. Analg., June 1, 2004; 98(6): 1595 - 1603. [Abstract] [Full Text] [PDF]

				J. Butterworth and J. W. Hammon Lidocaine for Neuroprotection: More Evidence of Efficacy Anesth. Analg., November 1, 2002; 95(5): 1131 - 1133. [Full Text] [PDF]

This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (34) Citing Articles via Google Scholar Google Scholar Articles by Wang, D. Articles by Meng, M. Search for Related Content PubMed PubMed Citation Articles by Wang, D. Articles by Meng, M. Related Collections Cardiovascular Surgery Heart Monitoring (Cardiac)

Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999