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doi: 10.1227/NEU.0000000000000256
Research-Human-Clinical Studies

Arterial Blood Pressure Management During Carotid Endarterectomy and Early Cognitive Dysfunction

Heyer, Eric J. MD, PhD*,‡; Mergeche, Joanna L. BA*; Anastasian, Zirka H. MD*; Kim, Minjae MD*; Mallon, Kaitlin A. BA*; Connolly, E. Sander MD‡,§

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*Department of Anesthesiology, Columbia University, New York, New York;

Department of Neurology, Columbia University, New York, New York;

§Department of Neurological Surgery, Columbia University, New York, New York

Correspondence: Eric J. Heyer, MD, PhD, Department of Anesthesiology, Columbia University, 630 W 168th St, P&S Box 46, New York, NY 10032. E-mail: ejh3@cumc.columbia.edu

Received August 27, 2013

Accepted November 14, 2013

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BACKGROUND: A common practice during cross-clamp of carotid endarterectomy (CEA) is to manage mean arterial pressure (MAP) above baseline to optimize the collateral cerebral blood flow and reduce the risk of ischemic stroke.

OBJECTIVE: To determine whether MAP management ≥20% above baseline during cross-clamp is associated with lower risk of early cognitive dysfunction, a subtler form of neurological injury than stroke.

METHODS: One hundred eighty-three patients undergoing CEA were enrolled in this ad hoc study. All patients had radial arterial catheters placed before the induction of general anesthesia. MAP was managed at the discretion of the anesthesiologist. All patients were evaluated with a battery of neuropsychometric tests preoperatively and 24 hours postoperatively.

RESULTS: Overall, 28.4% of CEA patients exhibited early cognitive dysfunction (eCD). Significantly fewer patients with MAP ≥20% above baseline during cross-clamp exhibited eCD than those managed <20% above (11.6% vs 38.6%, P < .001). In a multivariate logistic regression model, MAP ≥20% above baseline during the cross-clamp period was associated with significantly lower risk of eCD (odds ratio [OR], 0.18 [0.07-0.40], P < .001), whereas diabetes mellitus (OR, 2.73 [1.14-6.61], P = .03) and each additional year of education (OR, 1.19 [1.06-1.34], P = .003) were associated with significantly higher risk of eCD.

CONCLUSION: The observations of this study suggest that MAP management ≥20% above baseline during cross-clamp of the carotid artery may be associated with lower risk of eCD after CEA. More prospective work is necessary to determine whether MAP ≥20% above baseline during cross-clamp can improve the safety of this commonly performed procedure.

ABBREVIATIONS: CABG, coronary artery bypass graft

CEA, carotid endarterectomy

eCD, early cognitive dysfunction

EEG, electroencephalography

MAP, mean arterial pressure

MI, myocardial infarction

OR, odds ratio

PVD, peripheral vascular disease

SD, standard deviation

Carotid endarterectomy (CEA) is a surgical treatment performed to reduce the risk of stroke for patients with high-grade carotid artery stenosis.1-3 The neurological risks associated with CEA include perioperative stroke and early cognitive dysfunction (eCD) exhibited 24 hours postoperatively. Perioperative stroke has an incidence of approximately 5%4-6 and is due to either dislodged emboli or ischemia associated with inadequate collateral blood flow during cross-clamping of the carotid artery.4,7 Approximately a quarter of CEA patients demonstrate eCD 24 hours after CEA.8,9 It is a subtler form of neurological injury than stroke and is similar to stroke in its pathophysiology; patients with eCD demonstrate significantly elevated markers of neuronal injury10 as well as asymmetric cerebral blood flow on magnetic resonance perfusion brain scans.11

Although the exact etiology of eCD remains unclear, many studies have investigated a variety of factors that are associated with the incidence of eCD. Those associated with increased risk of eCD include age >75, diabetes mellitus, apolipoprotein-ε4 polymorphism, and a few complement polymorphisms.12-15 Statin use is significantly associated with decreased risk of eCD in the asymptomatic CEA population.16 However, there are no studies that investigate whether eCD is associated with intraoperative mean arterial pressure (MAP) management during the cross-clamp period.

A common practice during the cross-clamp period of CEA is to manage MAP above baseline MAP to optimize collateral cerebral blood flow to reduce the risk of ischemic stroke by adequately perfusing the hemispheres.17-20 As an unpublished rule of thumb, MAP management for CEA is often targeted to be approximately 20% above baseline MAP during the cross-clamp period, but this is not a standardized practice and is at the discretion of the anesthesiologist. During the cross-clamp period, electroencephalography (EEG) monitoring can be used to detect ischemic conditions that lead to stroke. The ischemic threshold for EEG is ∼18 mL·100 g−1·min−1, which is approximately a 60% reduction from normal baseline cerebral blood flow at ∼50 mL·100 g−1·min−1.21 However, subtle neurological injury may occur under mildly ischemic conditions that are undetected by EEG in the range between 18 mL·100 g−1·min−1 and 50 mL·100 g−1·min−1. CEA patients with simultaneous transcranial Doppler and EEG monitoring demonstrate that a mild reduction in blood flow through the middle cerebral artery measured by transcranial Doppler can remain undetected by EEG, but still strongly predict eCD as is shown in a previous study.22 We have demonstrated that a 28% decrease in blood flow velocity through the middle cerebral artery predicts a higher incidence of eCD.23

No previous studies have evaluated MAP management ≥20% above baseline during the cross-clamp period and its association with neurological injury in the context of eCD. We aim to determine if MAP management ≥20% above baseline during the cross-clamp period is associated with a lower risk of eCD.

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Five hundred fifty-one patients were enrolled with written informed consent in an institutional review board-approved observational study at Columbia University Medical Center from 1995 to 2012 (www.ClinicalTrials.gov NCT00597883). Eligible patients were scheduled for elective CEA, were English-speaking, and had no axis-I psychiatric disorders. Exclusion criteria were as follows: 12 experienced a perioperative stroke, 12 were also enrolled in a confounding study, 24 had significant EEG changes during cross-clamp and subsequent shunt placement, 31 withdrew, 32 had postoperative pain exceeding subjective level 5 on a 0 to 10 scale, which has been shown to affect neuropsychometric performance,24 47 did not complete the entire neuropsychometric battery, and 210 did not have cross-clamp times indicated on the anesthesia or EEG records. None of the 183 patients included in this study had significant EEG changes, and, therefore, none had a shunt placed during the cross-clamp period.

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Standard monitors, which included a blood pressure cuff, pulse oximeter, 5-lead electrocardiogram, and esophageal temperature probe, were used for every case. The radial intra-arterial catheter used to measure intraoperative blood pressure was placed before the induction of general anesthesia in every case. All patients received intravenous lines in the operating room. The intravenous fluid goal was 1 L total for each case. The anesthetic technique involved a preinduction dose of midazolam (1-5 mg) and fentanyl (25-250 μg); induction by etomidate (0.15-0.3 mg/kg), propofol (1-2 mg/kg), or thiopental (3-5 mg/kg); and management with 70% nitrous oxide in oxygen and isoflurane (0.3%-0.7%).

MAP changes were achieved by a phenylephrine infusion with the use of a Sigma Spectrum Infusion Pump (Baxter, Deerfield, Illinois), which is used to administer phenylephrine in micrograms per minute, supplemented with boluses. Ephedrine boluses were administered at the discretion of the anesthesiologist if the patient exhibited significant bradycardia in conjunction with hypotension. The administration of drugs, including phenylephrine and ephedrine, were entered manually by the anesthesiologist.

A 16-channel EEG (Xltek, Natus Medical Incorporated, San Carlos, California) was used for 91% of the CEA patients with either an EEG electrode cap (Electro-cap International Inc, Eaton, Ohio) or subdermal needle electrodes according to the 10 to 20 International electrode placement position in a bipolar “double-banana” montage. The remaining 9% of CEA patients had an 8-channel EEG (Neurotrac II; Moberg Medical, Inc, Ambler, Pennsylvania) with the use of a subset of the 10 to 20 International electrode placement in a referential montage referred to the ears. The EEGs were read by either a trained neurosurgical anesthesiologist or a board-certified neurologist. Significant EEG changes at cross-clamping of the carotid artery were defined as either a ≥50% decrease in amplitude in the alpha or beta frequencies and a similar increase in the delta or theta frequencies, or complete loss of all cerebral electrical activity.

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Mean Arterial Pressure

Baseline MAP was recorded in the holding area before surgery via blood pressure cuff, and MAP during the procedure was recorded by using an Anesthesia Information Management System (CompuRecord, Phillips North America, Andover, Massachusetts) via intra-arterial catheter. Cross-clamp time was defined as time during which there was no direct blood flow to the ipsilateral hemisphere; duration of cross-clamp was timed from the moment the clamp was applied to stop flow through the internal artery until the clamp was removed and flow was restored to the ipsilateral hemisphere. The cross-clamp start and end times were identified via the anesthesia and EEG records. The “duration of cross-clamp” was the difference in the minutes between these two time points. Continuous MAP readings with an intra-arterial catheter were recorded at 15 seconds intervals. The cross-clamp MAP value used in this analysis was determined by using an Excel macro (Microsoft Corp, Redmond, Washington). A previously developed algorithm identifies the stable MAP of the cross-clamp period.25

MAP values during the cross-clamp period were extracted and imported into the Excel macro. The average stable MAP during the cross-clamp period was calculated by generating a running MAP standard deviation (SD) curve. A curve is created by calculating the SD of 5 consecutive MAP recordings after the clamp was placed. Once the SD of the running average of MAP was below 5 mm Hg, the subsequent MAP values were averaged until the SD curve exceeded 10 mm Hg, or until the clamp was released. The stable MAP value during the cross-clamp period was then used in all analyses. Again, this technique has been used in previous studies.25

The anesthesiologists managed MAP at their own discretion, because there were no protocols or randomizations in this study. All anesthesiologists were aware that the patient was participating in a research study, but they were not aware that MAP values would be collected or studied. Seven anesthesiologists administered the anesthetics for all patients.

An unpublished rule of thumb for MAP management during CEA is often approximately 20% above baseline during the cross-clamp period. For this reason, we used 20% as the threshold of interest. Change in MAP from baseline to cross-clamp was calculated by subtracting baseline MAP from stable cross-clamp MAP and then dividing by baseline MAP [(MAPcross-clamp − MAPbaseline)/MAPbaseline].

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Cognitive Measures

The outcome of eCD was evaluated by using a battery of neuropsychometric tests preoperatively and 24 hours postoperatively. The outcome of eCD is binary (yes/no). The battery of neuropsychometric tests was developed by an experienced neuropsychologist. The tests used in this study have been well validated and widely used in the field of neuropsychological assessment.26-32 Furthermore, the same and/or similar tests have been used in other studies to determine cognitive dysfunction in CEA patients.8,33,34 The tests evaluate 4 cognitive domains—verbal memory (Hopkins Verbal Learning Test, Controlled Oral Word Association Test, Buschke), visuospatial organization (Rey-Osterrieth Complex Figure Copy and Recall), motor function (Grooved Pegboard and/or Finger Tapping Test), and executive action (Halstead-Reitan Trials A and B). The term “domain” refers to cortical areas that are required to perform a cognitive task in conjunction with each other. For example, the language domain involves neurons in the frontal, parietal, and temporal lobes, specifically the Broca area, the angular gyrus, and Wernicke area. These areas have to be connected and function in an organized sequence for the cognitive task to be completed.

The criteria for eCD are based on difference scores calculated for each test by subtracting the preoperative test performance from the postoperative test performance at 1 day. Similar to previous studies,16,35 a Z score was generated based on a surgical reference group's performance to account for practice effect, general anesthesia, trauma of surgery, and the postoperative experience. The reference group was only used to generate normalized Z scores; they were not included in any other analysis.

The surgical reference group was composed of 156 age- and education-matched patients undergoing lumbar level laminectomy or microdiscectomy ≤2 levels without fusion or blood loss necessitating transfusion. The reference group had an anesthetic similar to the CEA patients, which accounted for any pharmacological influences on eCD in the postoperative period. The mean difference score of the reference group was subtracted from the difference score for the CEA patient and then divided by SD of the reference group ([DifferenceCEA − Mean DifferenceReference]/SDReference). Therefore, each test was evaluated in units of SD of the reference group's change in performance. CEA patient domains were evaluated to account for both focal and global/hemispheric deficits: (1) ≥2 SD worse performance in ≥2 cognitive domains or (2) ≥1.5 SD worse performance in all 4 cognitive domains.

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In an effort to detect potential confounders, we evaluated whether the incidence of eCD was different among a number of variables. For example, we evaluated the surgeons, closure techniques (with a patch or primary closure), durations of surgery, durations of carotid artery cross-clamp, and doses of midazolam (μg/kg) and/or fentanyl (μg/kg). Furthermore, to address whether the 7 anesthesiologists managed patients significantly differently, we evaluated the distribution of MAPs during cross-clamp in increments of 10% (ie, below baseline, ≤10% above baseline, ≤20% above baseline, ≤30% above baseline, <40% above baseline, and ≥40%) above baseline MAP. Another consideration is whether the anesthesiologists altered their anesthetic goals as a function of the patient's cardiac history of myocardial infarction (MI), coronary artery bypass graft (CABG), or the presence of peripheral vascular disease (PVD). We evaluated the incidence of eCD and MAP management for patients with MI, CABG, and PVD.

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Statistical Analysis

Statistical analysis was performed with the use of JMP 10 software (SAS Institute Inc, Cary, North Carolina). For univariate analyses, the Student t test, Wilcoxon rank sum test, Fisher exact test, Pearson χ2 test, and simple logistic regression were used where appropriate. A multiple logistic regression model was constructed to identify independent predictors of eCD. All factors with P < .20 in simple univariate logistic regression with eCD were entered into the final model. Of note, statin use was included, because previous work demonstrates that statins significantly reduce the incidence of eCD.16 P ≤ .05 was considered significant.

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Characteristics of the overall cohort are presented in Table 1. Sixty-nine patients (37.7%) had a MAP managed ≥20% above baseline. Patients managed ≥20% above baseline MAP had significantly lower baseline MAP (109.6 ± 9.8 mm Hg vs 115.5 ± 14.1 mm Hg, P = .002) and higher cross-clamp MAP (141.1 ± 14.8 mm Hg vs 125.2 ± 15.1 mm Hg, P < .001) than patients managed <20%.

Table 1
Table 1
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Overall, 28.4% of CEA patients exhibited eCD. Baseline MAP was similar between patients with and without eCD (112.8 ± 10.1 mm Hg vs 113.5 ± 13.9 mm Hg, P = .75). MAP at cross-clamp was significantly lower in the patients with eCD (124.4 ± 13.4 mm Hg vs 133.9 ± 17.3 mm Hg, P < .001). The incidence of eCD was significantly lower in patients whose MAP was managed ≥20% above baseline compared with those managed <20% above baseline (11.6% vs 38.6%, P < .001).

Seven patients had a MAP below baseline during cross-clamp and exhibited a very high incidence of eCD (85.7%). With each 10% increase above baseline, the incidence of eCD consistently decreased until ≥40% above baseline (Figure). Six patients had a MAP ≥40% above baseline and exhibited a slightly higher incidence of eCD (16.7%); these 6 patients did not differ from the rest of the cohort in patient characteristics, medical histories, medication use, or operative experience.

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FIGURE. Bar graph of...
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Based on simple univariate regression, education, diabetes mellitus, statin use, and MAP ≥20% above baseline during cross-clamp were the only variables included in the final multivariate regression. In the final model, MAP ≥20% above baseline during cross-clamp was associated with significantly lower risk of eCD (odds ratio [OR], 0.18 [0.07-0.40], P < .001), whereas diabetes mellitus (OR, 2.73 [1.14-6.61], P = .03) and each additional year of education (OR, 1.19 [1.06-1.34], P = .003) were associated with significantly higher risk (Table 2).

Table 2
Table 2
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No significant differences in the incidence of eCD were found among the following factors: surgeon (P = .19), closure by the use of a patch or primary closure (P = .74), duration of surgery (P = .77), duration of cross-clamp (P = .88), dose of midazolam (μg/kg) (P = .31), dose of fentanyl (μg/kg) (P = .77). We found no evidence that patients with PVD or previous CABG may have been managed differently, although more patients with previous MI had MAP <20% above baseline during cross-clamp (48.3% vs 64.9%, P = .09). There is no significant evidence that the anesthesiologist altered anesthetic goals as a function of the presence of PVD. There were no differences in the incidence of eCD in patients who had previous CABG (P = .75), PVD (P = .89), or MI (P = .74) in comparison with patients without these conditions. The distribution of MAPs during cross-clamp in increments of 10% was not significantly different among the 7 anesthesiologists (P = .99, χ2 test).

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Neurological risks of CEA include perioperative stroke and eCD exhibited 24 hours postoperatively. MAP managed above baseline during the cross-clamp period optimizes collateral blood flow to adequately perfuse the hemispheres and reduces the risk of ischemia.17-20,36 Although a rule of thumb often used in CEA procedures is to maintain MAP approximately ≥20% above baseline, no studies have investigated MAP ≥20% in the context of neurological outcomes following surgery. This study measured eCD as a function of MAP management. The observations of this study suggest that MAP managed ≥20% above baseline during the cross-clamp period is associated with less risk of eCD and may improve the neurological safety of this commonly performed procedure.

The etiology of eCD is likely associated with mild ischemia, which produces subclinical events during cross-clamp that remain undetected by EEG.22,37 Previous work demonstrates that eCD is not associated with cerebral ischemia severe enough to be measured by magnetic resonance imaging (MRI) with diffusion weighted imaging.37,38 Additionally, scalp EEG electrodes sum large areas of cortical electrical activity that may be up to 45 cm.2,39 Therefore, significant subclinical cortical functional changes likely occur even when not reflected by scalp EEG changes or by MRI with diffusion weighted imaging. However, eCD is reflective of cerebral parenchymal injury as documented by elevations in serum S100B concentrations. S100B is a glial protein associated with the volume of ischemic cerebral tissue.40

We are uncertain whether the mechanism behind the greater incidence of eCD in patients maintained <20% above baseline MAP during cross-clamp is associated with the lack of adequate perfusion of collaterals; patients may have impaired autoregulation and when systemic blood pressure is reduced below the patient's lower limit of autoregulation, cerebral perfusion can be pressure dependent. Furthermore, patients with carotid stenosis are likely to have systemic atherosclerosis and, as such, may have chronic hemispheric ischemia. For example, the stenotic area distal to the carotid occlusion may already be maximally dilated and autoregulation may not be fully intact. This idea was supported by Schoof et al41 in a study of impaired cerebral autoregulation in cardiac surgery as related to carotid stenosis. They similarly reported that increased pressure may be necessary to compensate for “exhausted cerebrovascular reserve,” but remark that increasing pressure can be controversial in terms of stroke risk.41 In summary, there is definite evidence to support reasoning that autoregulation is impaired in CEA patients, making cerebral blood flow pressure dependent. We did not directly evaluate autoregulation as a part of this study, but we found several studies that use transcranial Doppler to confirm this.42-45 Regardless of the etiology in CEA, this study demonstrates that maintaining MAP ≥20% of baseline is significantly associated with lower incidence of eCD.

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We acknowledge the limitations of this study. Although there were a number of potential confounders in this study, we found no evidence that any of the factors were associated with the incidence of eCD or MAP management. This is a single-center observational study; therefore, it does not have strong external validity. The hemodynamic management was neither standardized nor randomized. The hemodynamic intentions of the anesthesiologist were not recorded. More patients with previous MI had MAP <20% above baseline during cross-clamp, and, while not significantly so, this raises a potential confounding variable; patients with previous MI may not only be treated differently hemodynamically, but they may have different cerebrovascular systems. We are uncertain of the influence this has on our findings. Although history of MI was implicated in the maintenance of MAP during cross-clamp, it is important to note that eCD is not associated with previous MI in comparison with patients who had no history of MI (P = .73). Years of education were significantly associated with increased risk of eCD; this finding was unexpected, and, currently, we do not have a plausible suggestion as to why or how this association exists. We can, however, speculate that because patients with increased years of education perform better (on the battery of neuropsychometric tests) at baseline, they subsequently appear to decline more than less educated patients.

It is unclear why 6 patients were managed ≥40% above baseline during cross-clamp and how this influenced their incidence of eCD. We acknowledge that this small subset of patients is not comparable to the greater population; we cannot assert that MAP maintained ≥40% above baseline is always deleterious, but we do believe it is an interesting observation that should be evaluated in future research. We speculate that increasing MAP too high (ie, ≥40% above baseline) could potentially dislodge emboli, hyperperfuse the affected hemisphere, or otherwise result in poor outcomes.46

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Although this is an ad hoc study, we consider it unethical to have performed a prospective study, because lowering the MAP during cross-clamp would be considered a significant deviation from “standard of care.” Further prospective work is necessary to determine whether increasing MAP to ≥20% above baseline is an appropriate and safe threshold for the cross-clamp period of CEA. Future studies also need to consider each patient's comorbidities and determine their influences on safe MAP management. The key observation of this study is that MAP managed ≥20% above baseline may be associated with less risk of eCD and improved neurological safety of CEA. We speculate that this observation is due to optimized collateral blood flow and reduced risk of mildly ischemic conditions. Future studies exploring and confirming these observations can improve the safety of CEA.

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This study suggests MAP management ≥20% above baseline during cross-clamp of the carotid artery may be associated with a significantly lower risk of eCD after CEA. More work is necessary to determine whether MAP ≥20% above baseline during cross-clamp can improve the safety of this commonly performed procedure.

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Drs Heyer and Connolly, Joanna L. Mergeche, and Kaitlin A. Mallon were supported in part by a National Institute on Aging grant (RO1 AG17604-9). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The other authors have no personal, financial, or institutional interest in any of the drugs, materials, or devices described in this article.

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The authors would like to thank Dr Mitchell Berman, Professor of Anesthesiology at Columbia University Medical Center, for his insights and Dr G.T. Yocum, Resident in the Department of Anesthesiology at Columbia University, for his assistance in calculating stable mean arterial pressures.

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44. Reinhard M, Roth M, Müller T, Czosnyka M, Timmer J, Hetzel A. Cerebral autoregulation in carotid artery occlusive disease assessed from spontaneous blood pressure fluctuations by the correlation coefficient index. Stroke. 2003;34(9):2138–2144.

45. Reinhard M, Roth M, Muller T, et al.. Effect of carotid endarterectomy or stenting on impairment of dynamic cerebral autoregulation. Stroke. 2004;35(6):1381–1387.

46. Stoneham MD, Warner O. Blood pressure manipulation during awake carotid surgery to reverse neurological deficit after carotid cross-clamping. Br J Anaesth. 2001;87(4):641–644.

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An interesting hypothesis, elegantly studied in an adequate number of patients who received state of the art surgery that has produced statistically significant validation of an “old saw” surgical teaching. The strengths? Quality surgery, large numbers of patients, intelligent analysis, valid conclusions. The weakness? An unrandomized observational trial with no active control of surgical variables.

Next, the curiosities. None of the 183 patients had EEG changes or needed a shunt. I believe the data, but this is far lower than anyone else reports, myself included,1 for either locoregional or (my choice) general anesthesia. I wonder how many of these patients had contralateral occlusion or other anatomic factors that to most of us might predict a higher likelihood of monitoring change and shunt placement?

I trained (with Drs Correll and Quest) at the institution where this study was performed. In my training, I was taught the practice of universal shunting, but I changed to monitoring-dependent shunting when I evaluated the embolic and dissection risks of a universal-shunting strategy, which have been shown more than once to be unacceptably high. We have all learned that we can “get away” most of the time with unshunted cross-clamping and reliance on collateral flow.

But perhaps Dr Correll's wisdom had a basis in fact, an observation that patients simply did better or “looked brighter” if they had sustained shunt blood flow throughout the cross-clamp period. We cannot ask him, as he has passed away, but the statistically valid evidence presented here supports the idea that things (like borderline blood flow that does not reach an EEG threshold) which we “get away with” may still lead to subtle performance changes in ischemic patients.

I applaud the authors for their methodical and elegant experimental design and data analysis, and I view this as a true contribution.

Christopher M. Loftus

Maywood, Illinois

1. Loftus CM: Carotid Artery Surgery: Principles and Technique. 2nd ed. New York, NY: Informa Publishing; 2006. Cited Here...

The work described in the article has asked the important question of how to manage the arterial blood pressure during the cross-clamp period of carotid endarterectomy.

There are 2 aspects in this question. The first one is the maneuver to maintain an adequate arterial blood pressure. It can be done via intravascular volume expansion (to a limited degree), light anesthesia (patient may move), and vasopressor infusion (most common). The choice of vasopressor is diverse. A previous study showed that, when arterial blood pressure was increased via phenylephrine bolus, both cerebral tissue oxygen saturation measured using near-infrared spectroscopy and cardiac output measured using esophageal Doppler were decreased.1 However, this study was conducted in healthy nonneurosurgical patients. If different vasopressor links to different outcome is not clear. The pharmacological intervention adopted by the study I am commenting on was phenylephrine infusion supplemented with phenylephrine and ephedrine boluses.

The second aspect of this important question is at what level the arterial blood pressure should be maintained. This question is commonly tackled in reference to the baseline pressure. This study showed that maintaining mean arterial blood pressure during cross-clamp at 20% to 40% above baseline had a better outcome in early cognitive function. Whether the same strategy was beneficial in the context of other outcomes was not assessed. In addition, whether tissue of various organs including the brain is better perfused and oxygenated by this strategy was not measured, but it is an intriguing question because optimized tissue perfusion and oxygenation is arguably the physiological end point of arterial blood pressure management.

The physiological ground of why the arterial blood pressure management strategy investigated by this study linked to a better early cognitive outcome is worth further discussion. An increase in arterial blood pressure does not necessarily lead to an increase in flow. In the context of cerebral autoregulation, cerebral blood flow remains stable for a wide range of cerebral perfusion pressure from 60 to 150 mm Hg when other factors such as cerebral metabolic demand and arterial blood carbon dioxide partial pressure remain stable. The arterial blood pressure was within this autoregulatory range in this study. If the autoregulation machinery were intact in those studied patients, different management plans of mean arterial pressure no matter 20% more or less than the baseline would not have affected cerebral blood flow. However, various studies showed that cerebral autoregulation of the hemisphere ipsilateral, not contralateral, to the stenosis is impaired2-5 and the degree of the impairment seems to correlate with the severity of the stenosis.3,4 Therefore, instead of being pressure independent, the flow to the ipsilateral hemisphere is pressure dependent. This offers an explanation of the result of the study: the maintenance of the mean arterial pressure ≥20% above baseline may have compensated the acute flow reduction caused by cross-clamp of the stenotic internal carotid artery via the increase in flow from collateral circulations owing to the increase in perfusion pressure.

In this study, it is not surprising to see that the mean arterial pressure during cross-clamp was less likely to be maintained ≥20% above baseline when the baseline pressure was already higher. This is likely because the anesthesiologist is often concerned when keeping the mean arterial pressure too high while being without knowledge of how various tissues are perfused and if there are potential risks. It is also usually true that the patient with a higher baseline mean arterial pressure has poorer physical condition and more comorbidity. Therefore, the patient whose cross-clamp mean arterial pressure was maintained <20% above baseline may be more comorbidity bound and have more severe carotid stenosis. As a result, those patients may have a higher incidence of postoperative cognitive decline compared with those whose cross-clamp mean arterial pressure was maintained ≥20% above baseline. This can be a significant confounder of this study.

Nonetheless, this study has targeted an important, yet still puzzling, question of how to manage arterial blood pressure during carotid endarterectomy. Although it is a good start, the more definitive answer awaits a randomized and prospective trial.

Lingzhong Meng

San Francisco, California

1. Meng L, Cannesson M, Alexander BS, et al.. Effect of phenylephrine and ephedrine bolus treatment on cerebral oxygenation in anaesthetized patients. Br J Anaesth. 2011;107(2):209–217. View Full Text | PubMed | CrossRef Cited Here... |

2. Jørgensen LG, Schroeder TV. Defective cerebrovascular autoregulation after carotid endarterectomy. Eur J Vasc Surg. 1993;7(4):370–379. PubMed | CrossRef Cited Here... |

3. Reinhard M, Roth M, Müller T, Czosnyka M, Timmer J, Hetzel A. Cerebral autoregulation in carotid artery occlusive disease assessed from spontaneous blood pressure fluctuations by the correlation coefficient index. Stroke. 2003;34(9):2138–2144. View Full Text | PubMed | CrossRef Cited Here... |

4. Gooskens I, Schmidt EA, Czosnyka M, et al.. Pressure-autoregulation, CO2 reactivity and asymmetry of haemodynamic parameters in patients with carotid artery stenotic disease. A clinical appraisal. Acta Neurochir (Wien). 2003;145(7):527–532. Cited Here...

5. Bokkers RP, van Osch MJ, van der Worp HB, de Borst GJ, Mali WP, Hendrikse J. Symptomatic carotid artery stenosis: impairment of cerebral autoregulation measured at the brain tissue level with arterial spin-labeling MR imaging. Radiology. 2010;256(1):201–208. PubMed | CrossRef Cited Here... |

The authors provide an interesting observational study addressing the important question of arterial pressure management during carotid endarterectomy. They make the argument that raising the blood pressure 20% above arterial may be important. They strongly suggest that anesthetic management and blood pressure management remain important during carotid endarterectomy. Their conclusions reinforce many traditional beliefs about carotid endarterectomy, and indeed anesthetic management. Unfortunately, the study does not prove their hypothesis. It is always a concern that, when an article fits your beliefs, that it would be accepted without question. Although it is important that anesthetic management of the entire patient is essential in any case, it must be pointed out that this is an observational, nonrandomized trial that excluded 300 patients to arrive at 183. The primary concern that I have about the article is that blood pressure management was observed but not controlled. A primary result when one looks at the data they present is that it is not clear whether the anesthesiologists were all aiming to achieve a blood pressure 20% above mean arterial. If indeed that was the case, then the results suggest that it is more difficult to obtain if a patient has had a previous myocardial infarction. Therefore, it is not surprising that they could not maintain that blood pressure level, or may have been sicker, and may indeed have had other factors that would preclude an equally good outcome in a group whose blood pressure could be more easily manipulated. Significantly, they exclude people in pain or people who have a stroke, and yet these are probably the most important factors for cognition in the first 24 hours after an endarterectomy. Nevertheless, of the group they studied, 24% did have some cognitive decline 1 day after the procedure, and, as is suggested by the authors, anything that can be done to decrease this number would be important. Because of the nature of the data, one would caution against uncritically accepting their conclusions, some, such as the relationship of education with 24-hour outcome, are inexplicable and further call into question the inclusion/exclusion criteria. The final conclusion is important, however. Cognitive dysfunction early or late after this or any other surgery must be an important parameter. It must be measured. We must make every effort to improve it. Therefore, the major conclusion I take from this article is that careful anesthetic management is an essential component of outcome.

Robert J. Dempsey

Madison, Wisconsin

In this retrospective observational study the authors report a significantly lower risk of early cognitive dysfunction (eCD) for carotid endarterectomy patients when their MAP is maintained 20% above baseline during cross clamping. While it is generally accepted that an increase in MAP during cross clamping provides a theoretical benefit to patients, there have been few studies to define and quantify the magnitude of this effect in a systematic fashion. Although this study is not a prospective randomized trial, it does provide evidence of the effect of hemodynamic management on CEA patients using predetermined outcome measures. Unfortunately there was no uniform anesthesia protocol and the decision of which patients would receive MAP augmentation was not randomized, thereby raising the possibility of confounding. Another important topic that was not explored in this article was the role that shunting plays in this population. At our institution we routinely employ the use of electrophysiological monitoring and shunt patients who display intraoperative EEG changes. It would be interesting to explore the role that shunting has on the prevalence of eCD in patients undergoing CEA. Additionally, it would be interesting to see if there is a correlation between intraoperative EEG changes and early cognitive dysfunction in this population. Nonetheless, this well-written manuscript provides important data that will fuel discussion and further the evolution of one of the most-studied surgical procedures in the history of medicine. We can expect that medical management to reduce the risk of stroke will improve over time. The authors are leading the charge to better understand and improve outcomes from this prophylactic surgical procedure. This is important work if we hope to maintain the advantage of CEA for selected patients shown in earlier trials.

William Humphries

Adam Arthur

Memphis, Tennessee

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CME Questions:

1. What is the incidence of early cognitive dysfunction on neurocognitive test after carotid endarterectomy cross-clamping?

A. 10-20%

B. 20-30%

C. 30-40%

D. 40-50%

E. 50-60%

2. During carotid endarterectomy cross-clamping, which alteration in mean arterial blood pressure (MAP) parameter has been associated with a reduced incidence of early cognitive dysfunction postoperatively?

A. Decrease by > 20%

B. Decrease by 10-20%

C. Less than 10% increase or decrease in MAPs

D. Increase by 10-20%

E. Increase by >20%

3. Of the following, what is the least common complication following carotid endarterectomy?

A. Cranial nerve palsy

B. Stroke

C. Myocardial Infarction

D. Symptomatic Hematoma


Carotid endarterectomy; Cognitive dysfunction; Pressure management

Copyright © by the Congress of Neurological Surgeons


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