Elevation of monocyte chemoattractant protein-1 in patients experiencing neurocognitive decline following carotid endarterectomy.

BACKGROUND: Previous studies have demonstrated that elevated pre-operative monocyte count is an independent predictor of acute neurocognitive decline following carotid endarterectomy (CEA). Monocyte chemoattractant protein-1 (MCP-1), secreted by human endothelial and monocyte-like cells, is a potent mediator of inflammation and mononuclear cell trafficking. This study examines the relationship between peri-operative serum MCP-1 elevation and post-operative neurocognitive injury following CEA. METHODS: Fifty-two patients undergoing CEA and 67 lumbar laminectomy (LL) controls were administered a battery of five neuropsychological tests pre-operatively and on post-operative day 1 (POD 1). Change in individual test scores from baseline to POD 1 were converted into Z-score and used to develop a point system quantifying the degree of neurocognitive dysfunction relative to change within the LL group. Neurocognitive injury following CEA was defined as a score greater than 2 standard deviations above mean total deficit scores of LL controls. Serum MCP-1 levels were measured pre-operatively and on POD 1 by enzyme-linked immunosorbent assay. FINDINGS: Mean percent MCP-1 elevation was higher for the 13 injured CEA patients (147.7 +/- 32.4%) in our cohort compared to 39 age- and sex-matched uninjured CEA patients (76.0 +/- 16.5%). In unconditional multivariate logistic regression analysis, percent elevation in serum MCP-1 level was associated with neurocognitive injury one day after CEA (OR = 2.19, 95% CI = 1.13-4.26, P = 0.021, for a 100% elevation from pre-operative levels). CONCLUSIONS: Peri-operative elevations in serum MCP-1 levels correlate with acute neurocognitive dysfunction following CEA. These data implicate an inflammatory mechanism in the pathogenesis of Ischaemic neurocognitive decline.

APOE-epsilon4 predisposes to cognitive dysfunction following uncomplicated carotid endarterectomy.

BACKGROUND: Between 9% and 23% of patients undergoing otherwise uncomplicated carotid endarterectomy (CEA) develop subtle cognitive decline 1 month postoperatively. The APOE-epsilon4 allele has been associated with worse outcome following stroke. OBJECTIVE: To investigate the ability of APOE-epsilon4 to predict post-CEA neurocognitive dysfunction. METHODS: Seventy-five patients with CEA undergoing elective CEA were prospectively recruited in this nested cohort study and demographic variables were recorded. Patients were evaluated before and 1 month after surgery with a standard battery of five neuropsychological tests. APOE genotyping was performed by restriction fragment length polymorphism analysis in all patients. Neuropsychological deficits were identified by comparing changes (before to 1 month post-operation) in individual performance on the test battery. Logistic regression was performed for APOE-epsilon4 and previously identified risk factors. RESULTS: Twelve of 75 (16%) CEA patients possessed the APOE-epsilon4 allele. Eight of 75 (11%) patients experienced neurocognitive dysfunction on postoperative day 30. One month post-CEA, APOE-epsilon4-positive patients were more likely to be cognitively injured (42%) than APOE-epsilon4-negative patients (5%) (p = 0.002). In multivariate analysis, the presence of the APOE-epsilon4 allele increased the risk of neurocognitive dysfunction at 1 month 62-fold (62.28, 3.15 to 1229, p = 0.007). Diabetes (51.42, 1.94 to 1363, p = 0.02), and obesity (24.43, 1.41 to 422.9, p = 0.03) also predisposed to injury. CONCLUSION: The APOE-epsilon4 allele is a robust independent predictor of neurocognitive decline 1 month following CEA.

Sex-based differences in serum cardiac troponin I, a specific marker for myocardial injury, after cardiac surgery.

BACKGROUND: Prevalence and causes of sex-based differences in morbidity and mortality secondary to cardiovascular disease remain controversial. Cardiac troponin I (cTnI) is a sensitive and specific marker for myocardial injury. Serial cTnI measurements have been used to identify perioperative myocardial cell injury. OBJECTIVE: To determine whether sex influences the extent of myocardial injury during cardiac surgery, we measured perioperative cTnI in male and female patients. DESIGN: A total of 17 male and 17 female patients were prospectively studied in an age- and case-matched manner. Arterial cTnI were obtained preinduction, 30 mins after the application of the aortic cross-clamp, at arrival to the intensive care unit, and on postoperative day 1. SETTING: Tertiary cardiac surgery center at a major teaching hospital. RESULTS: There was no difference between men and women in body mass index (kg/m2), duration of cardiopulmonary bypass, and aortic cross-clamp times. Preoperative cTnI measurements were similar in men (0.24 +/- 0.15 ng/mL) and women (0.25 +/- 0.13 ng/mL, mean +/- sem). The maximum serum cTnI occurred on postoperative day 1 in all patients, and it was 3-fold higher in men (18.5 +/- 5.7 ng/mL) compared with women (6.4 +/- 1.0 ng/mL). CONCLUSIONS: Men had markedly higher serum cTnI compared with women, although they were case matched with respect to age and cardiac risk factors. Our results may suggest there may be sex-related differences in the myocardial response to ischemia and reperfusion injury or intrinsic differences between the male and female myocardium.

Cardiac surgical patients exposed to heparin-bonded circuits develop less postoperative cerebral dysfunction than patients exposed to non-heparin-bonded circuits.

A prospective randomized trial was used to study the incidence of cerebral dysfunction in patients undergoing cardiopulmonary bypass (CPB) with heparin-bonded vs non-heparin-bonded circuits. Although the etiology of postoperative cerebral dysfunction is controversial, activation of the systemic inflammatory response may play a role. After institutional approval and informed written consent, 39 elective coronary artery bypass (CABG) patients were studied. A battery of neuropsychometric tests (NPMTs) was performed preoperatively, and 5 days and 6 weeks postoperatively. Significant change in NPMT performance was defined as a 25% or greater decrease in postoperative performance, compared to baseline. The number of abnormal tests per patient was calculated. Analysis using the Mann-Whitney rank test was performed for the first follow-up. Patients randomized to heparin-bonded circuits had fewer abnormal NPMTs (>1 abnormal test) on postoperative day 5 (58 vs 70%, n=19 and 20) than patients randomized to non-heparin-bonded circuits. Patients exposed to heparin-bonded circuits had fewer abnormal tests (>1 abnormal test) at 6 weeks (36 vs 63%, n=14 and 16). Results suggested that the attenuation of systemic inflammation by heparin-bonded CPB circuits may lower the incidence of cerebral injury in cardiac surgical patients.

Serum S100B protein levels are correlated with subclinical neurocognitive declines after carotid endarterectomy.

OBJECTIVE: Carotid endarterectomy (CEA) is an effective means of stroke prevention among appropriately selected patients; however, neuropsychometric testing has revealed subtle cognitive injuries in the early postoperative period. The purpose of this study was to establish whether serum levels of two biochemical markers of cerebral injury were correlated with postoperative declines in neuropsychometric test performance after CEA. METHODS: Fifty-five consecutive patients underwent a battery of neuropsychometric tests 24 hours before and 24 hours after elective CEA. Two patients were excluded because of postoperative strokes. The pre- and postoperative serum levels of S100B protein and neuron-specific enolase for injured patients, defined as those who exhibited significant declines in neuropsychometric test performance (n = 12), were compared with the levels for uninjured patients (n = 41). RESULTS: There were no significant differences in the baseline S100B levels for the two groups. Injured patients exhibited significantly higher S100B levels, compared with uninjured patients, at 24, 48, and 72 hours after surgery (P < 0.05). There were no significant differences in neuron-specific enolase levels for injured and uninjured patients at any time point. CONCLUSION: These data suggest that subtle cerebral injuries after CEA, even in the absence of overt strokes, are associated with significant increases in serum S100B but not neuron-specific enolase levels. Analyses of earlier time points in future studies of subtle cognitive injuries and biochemical markers of cerebral injury after CEA may be revealing.

Severe pain confounds neuropsychological test performance.

There is little information on the effect of pain on neuropsychological test performance. We have undertaken this study to explore which tests are affected by pain, the magnitude of these changes, and other confounders of neuropsychological performance in a population of patients having spine surgery. Twenty-four elderly English speaking Caucasian patients (age > 60 years) were enrolled pre-operatively in this Institutional Review Board approved study. Pain scores using an 11-point Numeric Pain Intensity scale and performance on a neuropsychological battery (Controlled Oral Word Association, Rey Complex Figure, Trails A and B) were assessed at two times, before and one day after surgery. Scores were calculated using the standard algorithms and change scores were calculated by subtracting the baseline from follow-up scores. After surgery, performance on the Rey Complex Figure ( r = -0.577, p = 0.004) and Trails Part A (r = 0.527, p = 0.01) declined with increasing post-operative pain scores. Women reported higher pain scores post-operatively than men (p = 0.046), and performed worse than men for change in performance on Trails Part A (p = 0.027). These data suggest that pain can influence performance on certain cognitive tests, and that some gender differences in these effects may occur. Interpretation of performance measures should take into account possible effects of pain, although our understanding of pain effects and ability to predict them in individual people, currently are quite limited.

Transcranial Doppler monitoring during carotid endarterectomy: a technical case report.

We report a case involving a patient undergoing carotid endarterectomy in whom transcranial doppler monitoring demonstrated impaired cerebral blood flow during the initial dissection of the carotid artery, during cross-clamping of the carotid artery, and after the shunt was kinked inadvertently. Only when the carotid artery was cross-clamped were these ischemic changes also seen by electroencephalography. During the other episodes, the electroencephalography tracings demonstrated no detectable changes. This case illustrates the importance of using multiple modalities to determine the adequacy of cerebral blood flow and neuronal integrity.

Droperidol suppresses spontaneous electrical activity in neurons cultured from ventral midbrain. Implications for neuroleptanesthesia.

Droperidol is used in anesthesia as an antiemetic and as a component in neuroleptanalgesia. Its mechanism of action is thought to involve dopamine receptor blockade in the brain. The electrophysiological consequences associated with this action however, have not been elucidated. In this study we demonstrate a dose-dependent electrophysiological response to droperidol in central nervous system (CNS) neurons that express dopamine receptors that is absent in CNS neurons that do not express dopamine receptors. Primary dissociated cell (PDC) cultures were prepared from embryonal tissue dissected from ventral mesencephalon (VM) and spinal cord (SC). VM neurons were used to investigate the electrophysiological action of droperidol, a dopamine receptor antagonist, since these cultures contain neurons having dopamine receptors on their surface. SC neurons were used as a control as they do not express dopamine receptors. Some dopamine receptors are on dopaminergic neurons and therefore are called autoreceptors, while others are on nondopaminergic neurons, such as GABA producing (GABAergic) neurons. All neurons in both PDC cultures were spontaneously active. The percentage of neurons which spontaneously generated action potentials was reduced in a dose-dependent manner by droperidol (1 nM-10 microM) only in PDC cultures of VM. Exposure to droperidol had no effect on neurons from PDC cultures of SC which lack dopamine receptors. Our results suggest that droperidol modulates the electrophysiological properties of VM neurons with dopamine receptors possibly through facilitation of inhibitory interneurons. The reduced activity of VM neurons might contribute to the antiemetic and/or anesthetic activity of droperidol, since the concentrations of droperidol used in this study are at clinically relevant concentrations.

Incidence of atrial fibrillation after mild or moderate hypothermic cardiopulmonary bypass.

OBJECTIVES: Atrial fibrillation remains a significant source of morbidity after coronary artery bypass grafting (CABG). Whether cardiopulmonary bypass (CPB) temperature influences the occurrence of postoperative atrial fibrillation in CABG patients has not been specifically examined. In the present study, we reviewed postoperative data from patients who were prospectively randomized to mild or moderate hypothermic CPB for elective CABG to determine the incidence of postoperative atrial fibrillation. DESIGN: Randomized, single center, observational study. SETTING: Tertiary university medical center. PATIENTS: Adults undergoing elective CABG surgery. INTERVENTIONS: Enrolled patients were prospectively randomized to mild (34 degrees C [93.2 degrees F]) or moderate (28 degrees C [82.4 degrees F]) hypothermic CPB. MEASUREMENTS AND MAIN RESULTS: The incidence of postoperative atrial fibrillation was determined by review of ICU and hospital records. There was a significantly higher incidence of atrial fibrillation in the moderate compared with the mild hypothermic CPB group. Patients who had postoperative atrial fibrillation were significantly older than those without atrial fibrillation. Furthermore, a significant increase in the relative risk of developing postoperative atrial fibrillation was found for both age and CPB temperature. CONCLUSIONS: Our results indicate that the temperature of systemic cooling during CPB is an important factor in the development of atrial fibrillation after CABG surgery. In addition, this study confirms that increasing age is a significant determinant of postoperative atrial fibrillation.

Significant reductions in length of stay after carotid endarterectomy can be safely accomplished without modifying either anesthetic technique or postoperative ICU monitoring.

BACKGROUND AND PURPOSE: We sought to determine whether postoperative length of stay (LOS) and resource utilization could be safely reduced without changing our uniform protocol of performing carotid endarterectomy (CEA) under general anesthesia with postoperative intensive care unit monitoring. METHODS: We retrospectively reviewed the hospital records of 421 consecutive CEA operations performed during a 3-year period of transition in discharge policy to determine LOS, complications, and resource utilization. We divided operated patients into 3 cohorts: cohort I patients were operated on before a stay reduction policy was instituted (1995, n=171); cohort II patients were operated on after the institution of a single-day-stay policy for selected patients (January to August 1996, n=95); and cohort III patients were operated on after the institution of a universal single-day-stay policy (September 1996 to December 1997, n=155). RESULTS: While significant in-hospital complications leading to increased LOS remained essentially unchanged over time (cohort I: 4.0%; II: 6.3%; III: 3.9%; P=NS), the mean postoperative LOS decreased from 2.6+/-0.3 days in cohort I to 1.6+/-0.1 days in cohort III (P<0.0001). The median postoperative LOS also decreased from 2 days to 1 day from cohort I to III, with 70% of patients discharged after 1 day in cohort III compared with only 32% for cohort I (P<0.0001). In addition, the total number of laboratory studies ordered decreased from 8.0+/-0.8 per patient in cohort I to 6.4+/-0.5 in cohort III (P<0.01). CONCLUSIONS: A uniform policy of discharge home from the intensive care unit on postoperative day 1 following CEA under general anesthesia can reduce LOS and decrease resource utilization without compromising care.

Safety and efficacy of fixed-dose heparin in carotid endarterectomy.

OBJECTIVE: Although fixed dosage of heparin is frequently used during vascular surgery, there are very few studies that document the appropriateness of this type of dosing. We have undertaken a prospective study to determine the physiological response to a fixed dose of heparin, using a conventional measure of anticoagulation, and have correlated this measure with complications. METHODS: We studied 140 consecutive patients undergoing elective carotid endarterectomy. Serial activated clotting times (ACT values) were obtained in duplicate before administration of heparin, 15 minutes after application of a carotid artery cross-clamp, and 1 hour after administration of 5000 U of heparin by intravenous bolus. Postoperatively, patients were assessed for new neurological deficits (transient ischemic attack and stroke) and neck hematomas. A battery of neuropsychometric tests was performed in 49 patients at baseline and on the day after carotid endarterectomy to identify subtle new neurological deficits. RESULTS: ACT values were found to be highly reproducible, with less than a 1.5% difference between duplicate baseline samples. Although all patients received 5000 U of heparin, the dose received per kilogram of body weight varied considerably (44-116 U/kg), as did ACT values at both 15 minutes (178-423 s) and 1 hour (173-390 s). Nevertheless, there was a significant correlation between heparin dose per kilogram and ACT values at 15 minutes (r = 0.45) and at 1 hour (r = 0.38) postinfusion, as well as ACT ratios (final ACT/initial ACT) at 15 minutes (r = 0.43) and at 1 hour (r = 0.34) after heparin bolus. Eight patients (5.7%) developed postoperative wound hematomas, one of which (0.7%) required reoperation. No patient had a stroke, but one patient had a transient ischemic attack, and 19 (39%) of 49 patients demonstrated significant early postoperative neuropsychometric deficits. Although the incidence of neck hematoma was not influenced by the heparin dose (P = 0.23), the ACT value at 15 minutes (P = 0.71) or 1 hour (P = 0.61), or the ACT ratio (P = 0.68), the only severe hematoma requiring reoperation occurred when the maximal ACT value was more than 400 seconds. Although performance on neuropsychometric tests did not appear to be statistically influenced by heparin dosing, the ACT value, or the degree of ACT elevation, there was a trend for deficits to be associated with lower heparin doses. CONCLUSION: Fixed heparin dosing achieves safe and efficacious anticoagulation in the great majority of patients having carotid endarterectomy, with 5000 U expected to result in 15-minute and 1-hour ACT values of 175 to 425 seconds and 170 to 390 seconds, respectively. Although weight-based heparin dosing may reduce the incidence of subtle complications (hematoma formation or decline on neuropsychometric tests) and may result in more predictable 15-minute and 1-hour ACT values (85 U/kg; 225-375 and 200-340 s, respectively), no statistically compelling clinical advantage could be demonstrated. Therefore, either weight-based or fixed dosing is acceptable, with both obviating the need for routine pre-clamp ACT confirmation, thereby saving operative time and expense.

Neuropsychometric changes in patients after carotid endarterectomy.

BACKGROUND AND PURPOSE: One hundred twelve patients undergoing elective carotid endarterectomy for symptomatic and asymptomatic carotid artery stenosis were enrolled in a prospective study to evaluate the incidence of change in postoperative cerebral function. METHODS: Patients were evaluated preoperatively and postoperatively before hospital discharge and at follow-up 1 and 5 months later with a battery of neuropsychometric tests. The results were analyzed by both event-rate and group-rate analyses. For event-rate analysis, change was defined as either a decline or improvement in postoperative neuropsychometric performance by 25% or more compared with a preoperative baseline. RESULTS: Approximately 80% of patients showed decline in one or more test scores, and 60% had one or more improved test scores at the first follow-up examination. The percentage of declined test scores decreased and the percentage of improved test scores increased with subsequent follow-up examinations. Group-rate analysis was similar for group performance on individual tests. However, a decline in performance was seen most commonly on verbal memory tests, and improved performance was seen most commonly on executive and motor tests. CONCLUSIONS: Neuropsychometric evaluation of patients undergoing carotid endarterectomy for significant carotid artery stenosis demonstrates both declines and improvements in neuropsychometric performance. The test changes that showed decreased performance may be associated with ischemia from global hypoperfusion or embolic phenomena, and the improvement seen may be related to increased cerebral blood flow from removal of stenosis.

Sympathetic response during cardiopulmonary bypass: mild versus moderate hypothermia.

OBJECTIVE: To determine the sympathetic response during cardiopulmonary bypass at mild (34 degrees C) and moderate (28 degrees C) hypothermia. DESIGN: A randomized study. SETTING: Tertiary university hospital. PATIENTS: Adults undergoing elective coronary artery bypass graft surgery. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Plasma norepinephrine, epinephrine, and neuropeptide Y concentrations were measured. Moderate, but not mild, hypothermic cardiopulmonary bypass evoked a significant sympathetic response with increases in plasma norepinephrine and neuropeptide Y concentrations. A significantly higher incidence of postoperative atrial fibrillation was also observed in the moderate hypothermic compared with the mild hypothermic group. CONCLUSIONS: Our results indicate that the degree of hypothermia significantly influences the sympathetic response during cardiopulmonary bypass. The higher incidence of postoperative atrial fibrillation in the moderate hypothermic group suggests that the enhanced sympathetic response might be one contributing factor in the development of atrial fibrillation.

Cerebral dysfunction after coronary artery bypass grafting done with mild or moderate hypothermia.

OBJECTIVE: Ninety-nine patients undergoing elective coronary artery bypass grafting were enrolled in a prospective, randomized study to evaluate the incidence of cerebral dysfunction after "mild" or "moderate" hypothermia during cardiopulmonary bypass. METHODS: Patients were evaluated before and after operation before hospital discharge and in some cases at follow-up at least 6 weeks later with a complete neurologic examination (85 patients) and a battery of standard neuropsychometric tests (86 patients). RESULTS: Postoperative changes detected by neurologic examination consisted of the appearance of new primitive reflexes in both groups. No statistically significant differences in incidence were found. The neuropsychometric performances of the two groups were statistically similar by either event-rate or group-rate analysis. CONCLUSIONS: There is no detectable difference in postoperative cerebral dysfunction in patients undergoing coronary artery bypass grafting who are supported by cardiopulmonary bypass with either mild or moderate hypothermia.

Intraoperative monitoring of motor evoked potentials: a review of 116 cases.

We reviewed the results of motor evoked potential (MEP) and somatosensory evoked potential (SEP) monitoring during 116 operations on the spine or spinal cord. We monitored MEPs by electrically stimulating the spinal cord and recording compound muscle action potentials from lower extremity muscles and monitored SEPs by stimulating posterior tibial or peroneal nerves and recording both cortical and subcortical evoked potentials. We maintained anesthesia with an N2O/O2/opioid technique supplemented with a halogenated inhalational agent and maintained partial neuromuscular blockade using a vecuronium infusion. Both MEPs and SEPs could be recorded in 99 cases (85%). Neither MEPs nor SEPs were recorded in eight patients, all of whom had preexisting severe myelopathies. Only SEPs could be recorded in two patients, and only MEPs were obtained in seven cases. Deterioration of evoked potentials occurred during nine operations (8%). In eight cases, both SEPs and MEPs deteriorated; in one case, only MEPs deteriorated. In four cases, the changes in the monitored signals led to major alterations in the surgery. We believe that optimal monitoring during spinal surgery requires recording both SEPs and MEPs. This provides independent verification of spinal cord integrity using two parallel but independent systems, and also allows detection of the occasional insults that selectively affect either motor or sensory systems.

Jugular venous bulb oxyhemoglobin saturation during cardiac surgery: accuracy and reliability using a continuous monitor.

Previous studies have demonstrated the feasibility of continuously monitoring jugular venous oxygen saturation (SjO2) with a fiberoptic catheter during hypothermic cardiopulmonary bypass (CPB). In the present study, with patients maintained at either moderate (28 degrees C) or mild (32-34 degrees C) hypothermia during CPB, SjO2 values obtained from a fiberoptic catheter were compared to intermittent samples analyzed by a co-oximeter. Twenty patients scheduled for elective coronary artery or valvular surgery had a 5.5 Fr Opticath catheter inserted into the left internal jugular bulb after induction of general anesthesia. The catheter was calibrated in vitro and in vivo according to the manufacturer's specifications. Catheter and co-oximetry SjO2 values obtained at four time points--1) pre-CPB, 2) target CPB temperature, 3) mid-rewarming, and 4) post-CPB--were compared using linear regression, Bland-Altman analysis, and Shrout-Fleiss interclass correlation coefficient analysis. These statistical methods revealed poor correlation between the catheter and co-oximetry SjO2 values: r = 0.44 by linear regression and 0.32 by interclass correlation coefficient analysis, and was unacceptably discrepant by Bland-Altman analysis. Oxyhemoglobin saturation values obtained continuously from a jugular venous bulb fiberoptic catheter during CPB may not accurately reflect true oxyhemoglobin saturation, and caution is warranted when interpreting SjO2 values obtained from a fiberoptic catheter during CPB.