John W. Hammon

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 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.

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.

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.

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.

The effects of airway pressure on cardiac function in intact dogs and man.

Ventilation with positive end-expiratory pressure (PEEP) is associated with reduced cardiac output, but the mechanisms involved are controversial. Possible explanations include increased intrathoracic pressure, reflex changes in myocardial inotropism, pulmonary vascular obstruction and abnormal ventricular interaction. Three types of conscious canine preparations were developed to examine simultaneously each of these factors during ventilation with PEEP. In addition, similar measurements were obtained in patients after cardiac surgical procedures and compared with the results of animal experiments. The primary cause of reduced cardiac output during PEEP appeared to be a diminished end-diastolic volume of the left ventricle, and this appeared to be the result of elevated intrathoracic pressure and increased impedance to blood flow through the lungs. Abnormal interventricular septal shifting and reflex autonomic alterations did not appear to be significant in the normal cardiovascular system. These data provide insight into the cardiac effects of PEEP and emphasize the importance of simultaneous quantification of biventricular performance when assessing cardiopulmonary function.

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.

Myocardial protection in the immature heart

In an era when essentially no congenital heart defect is considered inoperable, it is reasonable to carefully consider the essentials of neonatal myocardial physiology and biochemistry, especially comparisons between immature and adult myocardial responses to ischemia. Because many special clinical interactions dramatically affect myocardial protection, great care must be taken to analyze each case carefully with protection strategies in mind. Finally, cardioplegia composition and delivery are now quite similar to those used in adults, with new equipment facilitating delivery. Research is underway to supplement protection in immature hearts severely injured by adverse preoperative conditions.

Factors that predict the use of positive inotropic drug support after cardiac valve surgery.

Left ventricular dysfunction is common after cardiac surgery and is often treated with positive inotropic drugs (PIDs).We hypothesized that the use of PIDs after cardiac valve surgery would have significant associations with the valvular pathophysiology and surgical procedure, and unlike the case for patients undergoing coronary artery surgery, would be unrelated to duration of cardiopulmonary bypass (CPB) or of aortic clamping. One hundred forty-nine consenting patients undergoing cardiac valve surgery were studied. Patients with hepatic or renal failure, or New York Heart Association class IV cardiac symptoms, were excluded. Patients were considered to have received PIDs if they received an infusion of amrinone, dobutamine, epinephrine, or dopamine (>or=to5 [micro sign]g [center dot] kg-1 [center dot] min-1). PIDs were received by 78 patients (52%). In a univariate model, older age, history of congestive heart failure, decreasing left ventricular ejection fraction, longer durations of CPB, and concurrent coronary artery surgery significantly increased the likelihood of PID support. There was also significant variation by anesthesiologist in the administration of PIDs. The specific diseased valve and valvular stenosis or insufficiency did not influence the likelihood of receiving PID support. In a multivariable model, age, history of congestive heart failure, decreasing left ventricular ejection fraction, and anesthesiologist were significantly associated with the likelihood of PID support, but duration of CPB and concurrent coronary artery surgery were not. In conclusion, patient age and ventricular function, as well as physician preferences, predicted the need for inotropic drug support; however, neither the specific valvular lesion, nor duration of CPB were strongly predictive in a multivariable model. Implications: We evaluated factors related to use of positive inotropic drugs after cardiac valve surgery. The likelihood of a patient receiving these drugs increases with advancing age and with more severe preoperative left ventricular dysfunction, but was not influenced by the specific diseased valve or the duration of cardiopulmonary bypass. (Anesth Analg 1998;86:461-7)

Coronary artery endothelial dysfunction after global ischemia, blood cardioplegia, and reperfusion

This study tests the hypothesis that blood cardioplegia (BCP) attenuates endothelial dysfunction related to nitric oxide after global normothermic ischemia, cardioplegic arrest, and reperfusion in anesthetized open-chest dogs placed on cardiopulmonary bypass. The dogs were divided into five groups to identify the time when endothelial injury occurred: group 1 = control without ischemia; group 2 = 45 minutes of normothermic ischemia only; group 3 = 45 minutes of normothermic ischemia plus unmodified reperfusion; group 4 = 45 minutes of ischemia plus intermittent BCP without reperfusion; and group 5 = ischemia plus BCP and reperfusion. In vitro coronary vascular relaxation responses to the nitric oxide stimulator acetylcholine (endothelium-dependent, receptor-dependent), the calcium ionophore A23187 (endothelium-dependent, receptor-independent), and acidified NaNO2 (endothelium-independent) were measured at the end of the protocol. Maximum in vitro coronary vascular responses to acetylcholine were similar among groups 1, 2, and 4, indicating an absence of endothelial injury. In contrast, significantly impaired relaxations to acetylcholine were demonstrated in the two reperfused groups (groups 3 and 5). Relaxation responses to A23187 and NaNO2 were not altered markedly in any group. Electron microscopy showed intact endothelium in groups 1, 2, and 4. However, moderately severe endothelium damage was seen in groups 3 and 5. We conclude that morphologic and functional endothelial damage occurs after blood reperfusion with or without BCP, and 1-hour hypothermic BCP arrest after normothermic ischemia is not associated with extension of endothelial damage.