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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

　　Weinvestigated 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 (±g/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.

　　(Anesth Analg 2002;95:1134－41)

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　　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 c ^[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.

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　　Methods

　　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. Onehundred- 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 ±mol/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.

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