Approaches to reduce neurologic complications during cardiac surgery.

As outcome measures of cardiac surgery are carefully analyzed, neurologic outcomes are a prominent determinant of overall outcome. Sensitive measures of pre- and postoperative neuropsychologic performance and intraoperative emboli reveal a risk group of patients at an advanced age, with severe generalized atherosclerosis who require cardiac surgery. By using the results of observational studies, we have developed a protocol that uses innovative intraoperative techniques to minimize injury and thus improve outcome.

Reduced regional and global cerebral blood flow during fenoldopam-induced hypotension in volunteers.

UNLABELLED: Dopamine has a wide spectrum of receptor and pharmacologic actions that may affect cerebral blood flow (CBF). A new, selective dopamine-1 agonist, fenoldopam, is a potent systemic vasodilator with moderate alpha(2)-receptor affinity. However, the effects of fenoldopam on the cerebral circulation are undefined. We therefore hypothesized that infusion of fenoldopam would decrease mean arterial blood pressure (MAP) and might concurrently decrease CBF via vascular alpha(2)-adrenoreceptor activation in awake volunteers. We studied nine healthy normotensive subjects, using positron emission tomography to measure CBF in multiple cortical and subcortical regions of interest. In addition, bioimpedance cardiac output and middle cerebral artery blood flow velocity were determined during fenoldopam-induced hypotension. Three men and four women, aged 25-43 yr, completed the study. Fenoldopam infused at 1.3 +/- 0.4 microg. kg(-1). min(-1) (mean +/- SD) reduced MAP 16% from baseline: from 94 (89-100) mm Hg (mean [95% confidence interval]) to 79 [74-85] mm Hg (P < 0.0001). During the fenoldopam infusion, both cardiac output (+39%), and heart rate (+45%) increased significantly, whereas global CBF decreased from baseline, 45.6 [35.6-58.5] mL. 100 g(-1). min(-1), to 37.7 [33.9-42.0] mL. 100 g(-1). min(-1) (P < 0.0001). Despite restoration of baseline MAP with a concurrent infusion of phenylephrine, global CBF remained decreased relative to baseline values at 37.9 [34.0-42.3] mL. 100 gm(-1). min(-1) (P < 0.0001). Changes in middle cerebral artery velocity did not correlate with positron emission tomography-measured changes of CBF induced by fenoldopam, with or without concurrent phenylephrine. IMPLICATIONS: In awake volunteers with (presumably) intact cerebral autoregulation,fenoldopam-induced hypotension significantly decreased global cerebral bloodflow (CBF). Clinicians should be aware of these pharmacodynamic effects when choosing a vasodilator to control blood pressure, especially in situations where control of CBF, cerebral blood volume, and intracranial pressure are therapeutic priorities.

Similar neurobehavioral outcome after valve or coronary artery operations despite differing carotid embolic counts.

OBJECTIVES: The interrelationships among coronary and valvular operations, microemboli, and neurobehavioral outcome are unclear. We hypothesized that adult patients undergoing cardiac valve operations would have more total emboli delivered to the brain than patients undergoing coronary artery bypass grafting and that this would associate with worse neurobehavioral outcomes. METHODS: One hundred ninety-three patients undergoing coronary artery bypass grafting and 73 patients undergoing cardiac valve operations were compared. Patients received neurologic, neuro-ophthalmologic, and 11 standardized neurobehavioral tests preoperatively and 5 to 7 days, 1 month, and 6 months postoperatively. Left common carotid Doppler ultrasonographic embolus detection was performed intraoperatively. Repeated measures and logistic regression analyses of outcome were performed. RESULTS: Patients undergoing either coronary or valve operations were well matched by age (61 +/- 10 and 59 +/- 12 years, respectively), but a significantly greater fraction of patients undergoing valve operations were female, diabetic, or had undergone previous cardiac operations. Neurobehavioral scores of patients undergoing either coronary artery bypass grafting or cardiac valve operations did not differ significantly at any time. Total embolus counts differed significantly: the median was 105 during coronary artery bypass grafting and 479 during cardiac valve operations (geometric means of 104 and 412, respectively; P =.0001). Significantly more emboli were detected in the patients undergoing cardiac valve operations after removal of the left ventricular vent and after separation from cardiopulmonary bypass, but comparable numbers of emboli were seen in the 2 groups before cardiopulmonary bypass. In both groups decreased neurobehavioral performance was apparent at 5 to 7 days, with improvement at 1 and 6 months. Increasing numbers of carotid emboli significantly associated with worse performance on the letter cancellation test. There were no significant differences between patients undergoing valve and coronary operations in neurobehavioral outcomes, strokes, transient ischemic attacks, or deaths. CONCLUSIONS: The significantly greater number of emboli in the group of patients undergoing cardiac valve operations is likely the result of the entrainment of intracardiac air. The greater numbers of emboli during cardiac valve operations do not appear associated with a commensurately greater risk of adverse neurologic or neurobehavioral outcome.

Processing scavenged blood with a cell saver reduces cerebral lipid microembolization.

BACKGROUND: Microembolization during cardiopulmonary bypass (CPB) can be detected in the brain as lipid deposits that create small capillary and arteriolar dilations (SCADs) with ischemic injury and neuronal dysfunction. SCAD density is increased with the use of cardiotomy suction to scavenge shed blood. Our purpose was to determine whether various methods of processing shed blood during CPB decrease cerebral lipid microembolic burden. METHODS: After hypothermic CPB (70 minutes), brain tissue from two groups of mongrel dogs (28 to 35 kg) was examined for the presence of SCADs. In the arterial filter (AF) group (n = 12), shed blood was collected in a cardiotomy suction reservoir and reinfused through the arterial circuit. Three different arterial line filters (Pall LeukoGuard, Pall StatPrime, Bentley Duraflo) were used alone and in various combinations. In the cell saver (CS) group (n = 12), shed blood was collected in a cell saver with intermittent preocessing (Medtronic autoLog model) or a continuous-action cell saver (Fresenius Continuous Auto Transfusion System) and reinfused with and without leukocyte filtration through the CPB circuit. RESULTS: Mean SCAD density (SCAD/cm2) in the CS group was less than the AF group (11 +/- 3 vs 24 +/- 5, p = 0.02). There were no significant differences in SCAD density with leukocyte filtration or with the various arterial line filters. Mean SCAD density for the continuous-action cell saver was 8 +/- 2 versus 13 +/- 5 for the intermittent-action device. CONCLUSIONS: Use of a cell saver to scavenge shed blood during CPB decreases cerebral lipid microembolization.

Age and other risk factors for neuropsychologic decline in patients undergoing coronary artery bypass graft surgery.

OBJECTIVE: To evaluate if increasing age is a major determinant of long-term neuropsychologic (NP) dysfunction in patients undergoing coronary artery bypass graft (CABG) surgery. DESIGN: Prospective cohort study. SETTING: A single university hospital. PARTICIPANTS: Three hundred eighty-one patients undergoing elective CABG surgery. INTERVENTIONS: Baseline preoperative and intraoperative characteristics were assessed for all patients. A comprehensive NP test battery was conducted preoperatively and at 1 month postoperatively. MEASUREMENTS AND MAIN RESULTS: Of the initial 381 patients, 319 (84%) returned for the 1-month visit. The overall incidence of an NP deficit was 21.6%. There was no significant difference seen with increasing age, although a trend was observed with highest NP deficit rate in the older than 65 age group. Other preoperative risk factors, including gender, education level, and preexisting diseases, were nonsignificant. Intraoperative variables were evaluated and revealed no significant differences across the age groups. CONCLUSIONS: This cohort study did not find an increased incidence of NP deficits in elderly patients after CABG surgery. It has addressed the limitations of other studies, however, with (1) a comprehensive NP test battery, (2) longer-term follow-up, and (3) adequate sample size.

Longer duration of cardiopulmonary bypass is associated with greater numbers of cerebral microemboli.

BACKGROUND AND PURPOSE: Many patients who undergo cardiac surgery assisted with cardiopulmonary bypass (CPB) experience cerebral injury, and microemboli are thought to play a role. Because an increased duration of CPB is associated with an increased risk of subsequent cerebral dysfunction, we investigated whether cerebral microemboli were also more numerous with a longer duration of CPB. METHODS: Brain specimens were obtained from 36 patients who died within 3 weeks after CPB. Specimens were embedded in celloidin, sectioned 100 microm thick, and stained for endogenous alkaline phosphatase, which outlines arterioles and capillaries. In such preparations, emboli can be seen as swellings in the vessels. Cerebral microemboli were counted in equal areas and scored as small, medium, or large to estimate the embolic load (volume of emboli). RESULTS: With increasing survival time after CPB, the embolic load declined (P<0.0001). (Lipid emboli are known to pump slowly through the brain.) Also with increasing time after CPB, the percentage of large and medium emboli became lower (P=0.0034). This decline is consistent with the concept that the emboli break into smaller globules as they pass through the capillary network. A longer duration of CPB was associated with increased embolic load (P=0. 0026). For each 1-hour increase in the duration of CPB, the embolic load increased by 90.5%. CONCLUSIONS: Thousands of microemboli were found in the brains of patients soon after CPB, and an increasing duration of CPB was associated with an increasing embolic load.

Neurophysiologic monitoring and outcomes in cardiovascular surgery.

The first step to make in improving neurologic outcome is to recognize and accept neurologic injury occurs in all patient groups undergoing CPB. Fortunately, that stage has now been passed. Accurate detection and documentation of the incidence of brain injury is the next progression. At the same time, the cause of the injury needs to be established. Since the introduction of CPB, numerous improvements and refinements have been achieved, making it the acceptable, everyday clinical tool that has enabled the development of cardiac surgery. Despite these improvements, CPB-related morbidity persists. The advent of new technologic advances drives the quest for new techniques. New protective strategies for many end organs, including the heart, kidney, and brain, are evolving. No organ system should be viewed in isolation; otherwise, organ-specific protective strategies may arise in conflict. A strategy that confers absolute myocardial protection would be ideal, but at what cost to the protection of the kidneys, intestines, and brain? A neuroprotective strategy would ideally eliminate brain injury and be beneficial for all organs. The only way to continue to make progress is by the scientific evaluation of new techniques. The use of appropriate monitoring and outcome measures is fundamental to this process.

A randomized, blinded trial of the antioxidant pegorgotein: no reduction in neuropsychological deficits, inotropic drug support, or myocardial ischemia after coronary artery bypass surgery.

OBJECTIVE: To determine whether patients receiving pegorgotein preoperatively would be less likely than patients receiving placebo to demonstrate postoperative cerebral or myocardial dysfunction and thus would be less likely to (1) demonstrate a decline in neuropsychologic testing after cardiopulmonary bypass, (2) receive inotropic drug support, or (3) demonstrate electrocardiographic signs of ischemia or infarction. DESIGN: Prospective, randomized, blinded clinical trial. SETTING: University teaching hospital and clinics. PARTICIPANTS: Sixty-seven patients with normal left ventricular function undergoing elective, primary coronary artery bypass surgery. INTERVENTIONS: Six to 18 hours before aortic cross-clamping, patients received a single dose of placebo (n = 22); pegorgotein, 2,000 IU/kg intravenously (n = 23); or pegorgotein, 5,000 IU/kg intravenously (n = 22). MEASUREMENTS AND MAIN RESULTS: Patients in the three groups were similar; the mean ages were 65, 66, and 67 years, and there were seven, eight, and seven women in the placebo; pegorgotein, 2,000 IU/kg; and pegorgotein, 5,000 IU/kg groups. Fifty-one of 67 patients demonstrated neuropsychologic deficit 5 to 7 days postoperatively (n = 17, 19, and 15 for placebo, 2,000 IU/kg, and 5,000 IU/kg; p = NS). Median duration of cardiopulmonary bypass was longer in patients with two or more deficits at 4 to 6 weeks than in those with fewer than two deficits (121 v. 98 minutes; p = 0.04). No patient demonstrated a perioperative stroke. Twenty-seven patients required inotropic drug support after cardiopulmonary bypass (n = 8, 11, and 8 for placebo, 2,000 IU/kg, and 5,000 IU/kg; p = NS). Inotropic drug support was associated with history of angina (p = 0.01) and increasing weight (p = 0.03). Nine patients demonstrated early postoperative ischemia or infarction (n = 1, 7, and 1 for placebo, 2,000 IU/kg, and 5,000 IU/kg; p = 0.07). CONCLUSIONS: This study showed no positive influence of pegorgotein on the incidence of any of the findings and showed a trend toward an increased incidence of myocardial ischemia or infarction.

Cardiotomy suction: a major source of brain lipid emboli during cardiopulmonary bypass.

BACKGROUND: Brain injury remains a significant problem in patients undergoing cardiac surgery assisted by cardiopulmonary bypass (CPB). Autopsy brain specimens of patients after cardiac operations with CPB reveal numerous acellular lipid deposits (10 to 70 microm) in the microvasculature. We hypothesize that these small capillary and arterial dilatations result from a diffuse inflammatory response to CPB or from emboli delivered by the bypass circuit. This study was undertaken to determine which aspect of CPB is most clearly associated with these dilatations. METHODS: Thirteen dogs were studied in four groups: group I (n = 3), right-heart CPB; group II (n = 2), lower-extremity CPB; group III (n = 3), hypothermic CPB; and group IV (n = 5), hypothermic CPB with cardiotomy suction. All dogs in all groups were maintained on CPB for 60 minutes and then euthanized. Brain specimens were harvested, fixed in ethanol, embedded in celloidin, and stained with the alkaline phosphate histochemical technique so that dilatations could be counted. RESULTS: All dogs completed the protocol. The mean density of dilatations per square centimeter for each group was as follows: group I, 1.77 +/- 0.77; group II, 4.17 +/- 1.65; group III, 4.54 +/- 1.69; and group IV, 46.5 +/- 14.5. In group IV (cardiotomy suction), dilatation density was significantly higher than in group III (hypothermic cardiopulmonary bypass) (p = 0.04) and all other groups (p = 0.04). CONCLUSIONS: Blood aspirated from the surgical field and subsequently reinfused into dogs undergoing CPB produces a greater density of small capillary and arterial dilatations than CPB without cardiotomy suction, presumably because of lipid microembolization.

Cerebral emboli during cardiac surgery in children.

BACKGROUND: Microemboli occur commonly during cardiac surgery in adults, and, when present, increase the risk of neuropsychological deficits. Their incidence and significance during correction of congenital heart disease is unknown. The authors hypothesized that microemboli would occur before bypass with right-to-left cardiac shunts and would also occur in large numbers when the aortic crossclamp was released in children during repair of congenital heart defects. METHODS: In 25 children studied with carotid artery Doppler, embolic signals were counted and timed in relation to 13 intraoperative events. Patients were classified as either at high risk (obligate right-to-left shunt or uncorrected transposition of the great arteries) or at low risk (net left-to-right shunt or simple obstructive lesions) for paradoxical (venous to arterial) emboli. RESULTS: The median number of emboli detected was 122 (range, 2-2,664). Forty-two percent of all emboli were detected within 3 min of release of the aortic crossclamp. The high-risk group had significantly more emboli (median, 66; range, 0-116) during the time interval before cardiopulmonary bypass than did the low-risk group (median, 8; range, 0-73), with P < 0.01. There was no significant difference between the high- and low-risk groups in the total number of emboli detected. There was no apparent association between number of emboli and gross neurologic deficits. CONCLUSIONS: Microemboli can be detected in the carotid arteries of children undergoing repair of congenital heart disease and are especially prevalent immediately after release of the aortic crossclamp. The role of emboli in causing neurologic injury in children undergoing repair of congenital heart disease remains to be determined.

Risk factors and solutions for the development of neurobehavioral changes after coronary artery bypass grafting.

BACKGROUND: As operative mortality for coronary artery bypass grafting has decreased, greater attention has focused on neurobehavioral complications of coronary artery bypass grafting and cardiopulmonary bypass. METHODS: To assess risk factors and to evaluate changes in surgical technique, between 1991 and 1994 we evaluated 395 patients undergoing coronary artery bypass grafting with an 11-part neurobehavioral battery administered preoperatively and at 1 and 6 weeks postoperatively. Patients were instrumented with 5-MHz focused continuous-wave carotid Doppler transducers intraoperatively to estimate cerebral microembolism as an instantaneous perturbation of the velocity signal. Microembolism data were quantitated and compared with surgical technical maneuvers during operation and with neurobehavioral deficit (> or = 20% decline from preoperative performance on two or more neurobehavioral tests) postoperatively. These data and patient demographics were statistically analyzed (chi2, t test) and the results at 2 years (1991 and 1992; group A) were used to influence surgical technique in 1993 and 1994 (group B). RESULTS: Significantly associated with new neurobehavioral deficits were increasing patient age (p < 0.05), more than 100 emboli per case (p < 0.04), and palpable aortic plaque (p < 0.02). Group B patients had a significant decline in the neurobehavioral event rate (group A, 69%, 140/203; versus group B, 60%, 115/192; p < 0.05) of postoperative neurobehavioral deficits at 1 week and at 1 month (group A, 29%, 52/180; versus group B, 18%, 35/198; p < 0.01). The stroke rate was less than 2% in both groups (p = not significant). Modifications of surgical technique used in group B patients included increased use of single cross-clamp technique, increased venting of the left ventricle, and application of transesophageal and epiaortic ultrasound scanning to locate and avoid trauma to aortic atherosclerotic plaques. CONCLUSIONS: Neurobehavioral changes after coronary artery bypass grafting are common and associated with cerebral microembolization. Surgical technical maneuvers designed to reduce emboli production may improve neurobehavioral outcome.

Nimodipine neuroprotection in cardiac valve replacement: report of an early terminated trial.

BACKGROUND: We conducted a double-blind, randomized clinical trial in patients undergoing cardiac valve replacement to determine whether nimodipine, a dihydropyridine calcium antagonist, reduced the risk of new neurological, neuro-ophthalmologic, or neuropsychological deficits-common complications associated with cardiac surgery-1 week after surgery. METHODS AND RESULTS: Enrollment for a total of 400 patients started in May 1992 and was stopped in September 1994, with 150 patients randomized to the study. Nimodipine was given to the patients during the perioperative period. Patients underwent examinations before surgery and at approximately 1 week, 1 month, and 6 months after surgery. Major adverse events, including deaths and strokes, were monitored monthly. The trial was terminated early because of both an unexpected disparity in death rates between groups and a lack of evidence of a beneficial effect of nimodipine. New deficits were observed in 72% of the placebo group versus 77% of the nimodipine group (p=.55). In the 6-month follow-up period, 8 deaths (10.7%) occurred in the nimodipine group (n=75) compared with 1 death (1.3) in the placebo group (n=74) (p=.02). Major bleeding occurred in 10 patients in the nimodipine group versus 3 in the placebo group (13.3% versus 4.1%; P=.04). Six (46.2%) of the 13 patients with major bleeding died compared with 3 deaths (2.2%) among the 136 patients without major bleeding. CONCLUSIONS: Our findings add to the growing evidence that calcium antagonists have a prohemorrhagic effect in some patients and suggest that nimodipine use should be restricted perioperatively in patients scheduled for cardiac valve replacement.

Cerebral emboli and cognitive outcome after cardiac surgery.

There have been major advancements in cardiac surgery over the past two decades, with a concomitant decrease in mortality and major morbidity. However, several recent studies have demonstrated that cardiac surgery poses significant risk for negative neurologic and neuropsychologic outcome. Although very few patients die as a result of cardiac surgery, more than two thirds of the patients demonstrate evidence of neuropsychologic dysfunction postoperatively. The mechanisms contributing to post-cardiopulmonary bypass neuropsychologic deficits are uncertain. However, two major interrelated etiologic factors, hypoperfusion and emboli, are suggested as probable culprits. It is important to define the relationship between these two putative mechanisms and postoperative neuropsychologic outcome in order to either prevent the problem or treat the effects of emboli or hypoperfusion. For example, if embolism is the cause of the deficits, increasing cerebral perfusion would deliver more emboli and increase the amount of severity of injury. Conversely, if hypoperfusion is the cause of the injury, then decreasing brain blood flow would increase the likelihood of injury. If both are important, their relative significance must be established, then one prevented and the effects of the other treated. This report discusses the methodology for detecting cerebral emboli during cardiac surgery. The incidence and severity of neuropsychologic deficits after cardiac surgery are discussed, as well as emboli in relation to composition and time of occurrence and their effect on neuropsychologic outcome.

Dog model for cerebrovascular studies of the proximal-to-distal distribution of sequentially injected emboli.

This study was undertaken to determine whether microemboli injected in a predetermined sequence would maintain that sequence once they came to rest in brain microvessels. If so, the injection of different-colored microspheres at different times could be used to bracket-in-time emboli that are known to be released into the circulation during cardiopulmonary bypass. We injected different-colored microspheres into the arterial circulation of anesthetized dogs before and after the injection of fat emboli and before and after cardiopulmonary bypass. Coronal slices of the dog brains were embedded in celloidin, sectioned at 100 microns, and stained for alkaline phosphatase. The afferent cerebrovasculature stained dark brown against a light background, and the proximal/distal orientation of many of the arterioles could be determined by following their course within the thick sections. When different types of emboli were found in a single arteriole, they appeared in the order injected or the order of occurrence in the bypass protocol in 99.3% of the 867 such arterioles counted. Therefore, the microemboli maintained their ordered sequence with only a very small degree of mixing. Once they came to rest, there was not sufficient collateral blood flow in the brain microvessels to move them into disordered positions. This dog model should facilitate studies of the time of release of microemboli within narrower windows of time during cardiopulmonary bypass.