Improvement of outcomes after coronary artery bypass. A randomized trial comparing intraoperative high versus low mean arterial pressure.

BACKGROUND: The objective of this randomized clinical trial of elective coronary artery bypass grafting was to investigate whether intraoperative mean arterial pressure below autoregulatory limits of the coronary and cerebral circulations was a principal determinant of postoperative complications. The trial compared the impact of two strategies of hemodynamic management during cardiopulmonary bypass on outcome. Patients were randomized to a low mean arterial pressure of 50 to 60 mm Hg or a high mean arterial pressure of 80 to 100 mm Hg during cardiopulmonary bypass. METHODS: A total of 248 patients undergoing primary, nonemergency coronary bypass were randomized to either low (n = 124) or high (n = 124) mean arterial pressure during cardiopulmonary bypass. The impact of the mean arterial pressure strategies on the following outcomes was assessed: mortality, cardiac morbidity, neurologic morbidity, cognitive deterioration, and changes in quality of life. All patients were observed prospectively to 6 months after the operation. RESULTS: The overall incidence of combined cardiac and neurologic complications was significantly lower in the high pressure group at 4.8% than in the low pressure group at 12.9% (p = 0.026). For each of the individual outcomes, the trend favored the high pressure group. At 6 months after coronary bypass for the high and low pressure groups, respectively, total mortality rate was 1.6% versus 4.0%, stroke rate 2.4% versus 7.2%, and cardiac complication rate 2.4% versus 4.8%. Cognitive and functional status outcomes did not differ between the groups. CONCLUSION: Higher mean arterial pressures during cardiopulmonary bypass can be achieved in a technically safe manner and effectively improve outcomes after coronary bypass.

Impact of embolization during coronary artery bypass grafting on outcome and length of stay.

BACKGROUND: Transcranial Doppler ultrasonography detects emboli in most patients during coronary artery bypass grafting. However, the significance of these emboli has not yet been established. METHODS: We monitored 82 patients during coronary artery bypass grafting with this technique and related the numbers of emboli to the outcomes and length of hospital stay. RESULTS: We detected cerebral emboli in all patients. Patients with stroke (n = 4; 4.9%) had a mean of 449 emboli, as compared with 169 emboli in patients without stroke (n = 78) (p = 0.005). Patients with major cardiac complications (n = 7) had a mean of 392 emboli, as compared with 163 in patients without such complications (n = 75) (p = 0.003). The mean hospital stay of survivors was 8.6 days in patients with fewer than 100 emboli (n = 40), 13.5 days in patients with 101 to 300 emboli (n = 23), 16.3 days in those with 301 to 500 emboli (n = 16), and 55.8 days in patients with more than 500 emboli (n = 6) (p = 0.0007). This relation was unchanged when patients with complications were excluded. The correlation between embolization and outcome was independent of the extent of aortic atheroma or age. CONCLUSIONS: Emboli detected during coronary artery bypass grafting are significantly related to major cardiac and neurologic complications and affect length of stay in all patients, even in the absence of such specific complications.

Determination of size of aortic emboli and embolic load during coronary artery bypass grafting.

BACKGROUND: Embolic signals have been detected within both the aortic lumen and the intracranial vasculature during coronary artery bypass grafting. Total numbers of these emboli have been reported. The present study examined the size of individual emboli and the total volume of embolization. METHODS: Using transesophageal echocardiography, we continuously monitored the aortic lumen of 10 patients undergoing isolated coronary artery bypass grafting. We manually analyzed 720,000 individual echo frames over a 4-minute period after the release of aortic clamps to track and to calculate the volume of 657 individual particles. The embolic load for the entire procedure was calculated from mean volume based on analysis of 1,508 particles. We simultaneously monitored the middle cerebral artery using transcranial Doppler ultrasonography and compared numbers of emboli detected by the two techniques. RESULTS: Particle diameter ranged from 0.3 to 2.9 mm (mean, 0.8 mm), and particle volume from 0.01 to 12.5 mm3 (mean, 0.8 mm3). Twenty-eight percent of particles measured 1 mm or more, 44% measured 0.6 to 1.0 mm, and only 27% measured 0.6 mm or less in diameter. Aortic embolic load for the procedure ranged from 0.6 cm3 to 11.2 cm3 (mean, 3.7 cm3). Estimated cerebral embolic load for the procedure ranged from 60 to 510 mm3 (mean, 276 mm3). The fraction of aortic emboli entering the cerebral circulation was very variable (3.9% to 18.1%). Seventy-six percent of the embolic volume after the release of clamps occurred over a 20-second period. Only 1 patient was encephalopathic perioperatively. This patient had the largest estimated cerebral embolic load (510 mm3) and the second largest aortic embolic load (8.4 cm3). CONCLUSIONS: We determined the size of individual intraaortic embolic particles and the total volume of embolization during coronary artery bypass grafting, and found the proportion entering the cerebral circulation to be very variable. The constitution of these particles and the neurologic impairment resulting from such embolization remains to be determined.

Aortic atheroma is related to outcome but not numbers of emboli during coronary bypass.

BACKGROUND: The relation between aortic atheroma severity and stroke after coronary artery bypass grafting is established. The relation between atheroma severity and other outcome measures or numbers of emboli has not been determined. METHODS: Using transesophageal echocardiography, we determined the severity of atheroma in the ascending, arch, and descending aortic segments in 84 patients undergoing operations. Seventy patients were monitored using transcranial Doppler ultrasonography. RESULTS: The incidence of stroke was 33.3% among 9 patients with mobile plaque of the arch and 2.7% among 74 patients with nonmobile plaque (p = 0.011). Cardiac complications were not significantly related to atheroma severity in any aortic segment. Length of stay was significantly related to atheroma severity in the aortic arch (p = 0.025) and descending segment (p = 0.024). The presence of severe atheroma in both the arch and descending segments was associated with significantly longer hospital stays as compared with patients with severe atheroma in neither segment (p = 0.05). Numbers of emboli were greater in patients with severe atheroma at clamp placement, although the differences did not achieve statistical significance. CONCLUSIONS: Aortic atheroma severity is related to stroke and to the duration of hospitalization after coronary artery bypass grafting. The lack of correlation between numbers of emboli and atheroma severity suggests that m any emboli may be nonatheromatous in nature.

In vitro 1H and 31P NMR spectroscopic evidence of multiple aberrant biochemical pathways in murine trisomy 16 brain development.

Nuclear magnetic resonance (NMR) spectroscopy was used to evaluate cytosolic compounds and membrane phospholipids simultaneously in trisomy 16 (Ts16) and euploid (control) murine brain at fetal day 15 in order to examine the cellular biochemistry that underlies the neurodevelopmental consequences of chromosome triplication in this model of Down syndrome (DS). Proton NMR spectroscopic analysis of brain tissue extracts demonstrated decreased levels of choline and increased levels of myo-inositol (MI) in Ts16 brains compared with control. These data are consistent with the cholinergic deficits and elevated MI levels previously described in Ts16. Compared with euploid brains. Ts16 brains also possess higher levels of creatine, adenosine, and tyrosine. Increased levels of MI and creatine, compounds that are localized to glia, imply abnormalities in the trophic environment of Ts16 brain. Phosphorus NMR spectroscopic analysis of extracts further revealed elevated levels of anionic phospholipid membrane components, such as phosphatidylinositol (PtdIno) and phosphatidylethanolamine, in Ts16 brains. Since these compounds are confined to the inner leaflet of the membrane, the findings suggest that membrane composition is altered specifically in the cytosolic bilayer at this stage. Together our proton and phosphorus NMR spectroscopic results indicate that multiple biochemical pathways are affected in Ts16 brain development. Understanding the effects of these aberrations may elucidate the processes that lead to neural dysfunction and Alzheimer's disease (AD) neuropathology in DS individuals.

Transesophageal echocardiographic localization of an aortic valve papillary fibroelastoma during routine coronary artery bypass surgery.

Papillary fibroelastomas are rare, primary cardiac tumors most often diagnosed incidentally at autopsy. These tumors have been associated with embolism, neurologic injury, coronary ischemia and sudden death. We report a case of clinical detection of an asymptomatic aortic valve papillary fibroelastoma by transesophageal echocardiography. The mass was an incidental finding during routine coronary artery bypass surgery. This finding dictated a change in the operative approach to include resection of the aortic valve mass in addition to coronary revascularization.

The efficacy and safety of a pharmacologic protocol for maintaining coronary artery bypass patients at a higher mean arterial pressure during cardiopulmonary bypass.

A recent randomized trial of higher versus lower mean arterial pressure (MAP) during cardiopulmonary bypass (CPB) showed that higher MAP on CPB was associated with a lower incidence of overall cardiac and neurologic morbidity and mortality in coronary artery bypass graft surgery (CABG) patients. Cardiopulmonary bypass MAP was controlled pharmacologically while CPB flow was held constant for any given period. The objective of the present study was to assess the efficacy and safety of this pharmacologic protocol. Two hundred forty-eight patients participated in the study; the mean age was 65.8 +/- 9.4 years, 20% were women, and the mean preoperative ejection fraction was 48%. The low-flow corrected CPB MAP attained for the low and high MAP groups was 56.7 +/- 5.0 mmHg and 77.7 +/- 7.1 mmHg, respectively (p = 0.0001). Major cardiac and neurologic outcomes, postoperative blood loss, renal dysfunction, intensive care unit (ICU) stay, and duration of intubation were not found to be significantly associated with any drug in the pharmacologic protocol. These findings support that the pharmacologic protocol used to maintain CABG patients at higher MAP on CPB is both efficacious and safe.

Pseudocholinesterase hyperactivity with succinylcholine resistance: an unusual cause of difficult intubation.

We describe a case of difficult intubation, possibly due to marked pseudocholinesterase hyperactivity that caused rapid inactivation of succinycholine. Possible causes of difficult intubation and pseudocholinesterase hyperactivity are discussed. Literature on genetic variants associated with markedly increased pseudocholinesterase activity are reviewed. It is concluded that pseudocholinesterase hyperactivity may be a rare cause of difficult intubation. We recommend that pseudocholinesterase activity should be determined in all patients who appear to be resistant to the action of normal doses of succinylcholine or mivacurium.

Prevention of suction-induced hypoxemia by simultaneous oxygen insufflation.

The effects of endotracheal suctioning were studied in 38 patients. A significant decline in arterial oxygen tension and saturation was noted in all patients. A new double lumen suction catheter that simultaneously insufflates oxygen while suctioning was tested in these same patients and was found to prevent hypoxemia in all patients. We recommend that the insufflation catheter be added to the protocol of hyperventilation with 100% oxygen to help prevent suction-induced hypoxemia.

In vitro proton and phosphorus NMR spectroscopic analysis of murine (C57Bl/6J) brain development.

We report for the first time in vitro proton and phosphorus NMR spectroscopic analyses of murine brain development from fetal to adult stages. Chloroform-methanol extracts from C57B16/J mouse brain, at ages ranging from 15 days in utero (F15) to adult, permitted the simultaneous investigation of both cytosolic and membrane phospholipid compartments. The protein content of murine brain was determined and used for quantitation of individual metabolite levels. Proton NMR spectroscopy revealed that NAA, considered a neuronal marker, is undetectable at F15. Glutamate, GABA and creatine, however, are present at this time. All four compounds reach maximum levels at 21 days postnatal (P21). Choline and alanine levels are at their peak in fetal brain and progressively fall as the brain develops. Phosphorus NMR spectroscopy shows that phosphatidylcholine, phosphatidylinositol, sphingomyelin, and phosphatidylserine increase steadily from F15 to P21.

Detection of aortic emboli by transesophageal echocardiography during coronary artery bypass surgery.

OBJECTIVE: The purpose of this study was to determine whether emboli can be detected within the aortic lumen in patients undergoing coronary artery bypass surgery (CABG) and to relate the appearance of emboli to specific operative events. DESIGN: Twenty patients were prospectively studied intra-operatively. SETTING: Subjects were inpatients in an academic medical center. PARTICIPANTS: All participants were scheduled for elective, isolated CABG. INTERVENTIONS: Patients were continuously monitored using transesophageal echocardiography (TEE) from aortic cannulation to bypass discontinuation. After completion of the aortic examination, the probe was focused at the level of the aortic arch, just before the takeoff of the left subclavian artery. Emboli were defined as echogenic intraluminal signals not present in the same position on consecutive cross-sectional frames. RESULTS: Intraluminal emboli were detected in all subjects, with a mean number of 535 and range of 8 to 1,885. Embolization was unevenly distributed through the procedure. A mean of 224 (42%) of 535 were detected within 4 minutes of aortic cross-clamp release and another 140 (24%) appeared after partial occlusion clamp release. Together, clamp placement and release represented 84% of all emboli. Emboli detected after clamp release were large, echodense particles easily distinguishable from the small, indistinct, poorly echogenic signals observed at bypass initiation. CONCLUSIONS: Emboli can be visualized within the aortic lumen during CABG. Confirming previous reports, the majority of emboli detected are related to manipulation of aortic clamps. The composition and clinical significance of embolic material are unclear. The value of intraoperative TEE monitoring in predicting neurologic outcome remains to be determined.

Effect of electroconvulsive therapy on the electrocardiogram and echocardiogram.

Although electrocardiographic (ECG) ST segment depression is commonly induced by electroconvulsive therapy (ECT) for depression, it is unknown whether this reflects segmental myocardial ischemia, as is true under most circumstances, or a direct effect of central nervous system stimulation on cardiac repolarization in the absence of ischemic left ventricular regional wall motion abnormalities. We evaluated the association between ECG changes and left ventricular regional wall motion abnormalities detected by the echocardiograms performed before and after ECT in 11 patients. Immediately after ECT, three patients' ECGs revealed 1-mm downsloping or horizontal ST segment depression, one had a nonspecific ECG change (peaked T waves), and the ECG remained normal in seven. All patients had normal baseline echocardiograms. After ECT, at a time when the product of arterial blood pressure and heart rate was 100% above baseline values, five patients developed new left ventricular regional wall motion abnormalities that were confined to hypokinesia; no patient developed myocardial infarction or angina after ECT. Three patients with regional wall motion abnormalities developed ECG ST segment depression after ECT (sensitivity 60%), one had a nonspecific ECG change (peaked T waves), and the ECG of one patient remained normal. In conclusion, ECT may induce ECG changes with simultaneous regional wall motion abnormalities at a time when arterial blood pressure and heart rate are markedly elevated, findings that are highly suggestive of "demand" myocardial ischemia. In this small series, ECG or echocardiographic abnormalities did not predict clinical cardiac morbidity.

Comparison of transcranial Doppler ultrasonography and transesophageal echocardiography to monitor emboli during coronary artery bypass surgery.

BACKGROUND AND PURPOSE: Transcranial Doppler ultrasonography (TCD) is the standard technique for monitoring emboli in the cerebral circulation. Embolic signals have been detected with the use of this technique in most patients undergoing coronary artery bypass surgery. We previously reported that the majority of emboli are detected after release of aortic cross-clamps and partial occlusion clamps. In this study we compare the intraoperative use of TCD with transesophageal echocardiography (TEE) to monitor cerebral emboli. METHODS: We simultaneously monitored 20 patients undergoing coronary bypass surgery with TCD and TEE. All patients also underwent routine TEE examination of the aorta. RESULTS: Embolic signals were detected in all patients by both techniques. Mean total number of emboli was 535 +/- 109 by TEE compared with 133 +/- 28 by TCD. We found correlation between numbers of emboli detected by the two techniques at clamp placement and release (r = .65, P = .002). Clamp placement and release accounted for 84% of all emboli by TEE and 83% by TCD. By TEE, large, highly echogenic particles were detected after clamp release compared with small, barely echodense particles at the onset of bypass. No such distinction was apparent by TCD. We found correlation between severity of aortic atheroma and both TEE- (P = .003) and TCD-detected (P = .009) emboli. CONCLUSIONS: TEE and TCD can both be used to continuously monitor emboli during coronary artery bypass surgery. However, TEE is invasive and justified only if it is being performed for intraoperative assessment of aortic atheromatosis or cardiac function.

Computerized data collection in the operating room during coronary artery bypass surgery: a comparison to the hand-written anesthesia record.

OBJECTIVE: To investigate variability between hand-written and computerized anesthesia records and evaluate any associated bias. DESIGN AND MEASUREMENTS: A computer system that was used to collect intraoperative data for a study of hemodynamic management during coronary artery bypass graft surgery is described. The system collected and recorded hemodynamic data automatically downloaded from the anesthesia monitor as well as surgical events and drug administration data entered through menu options. The system then combined, summarized, and graphed the data as well as formatted it for export to a commercially available database program. In a sample of 14 patients, blood pressure data collected by the computer system was compared with the blood pressure data charted in the hand-written anesthesia record. MAIN RESULTS: Although general linear models controlling for within-patient variation and randomization assignment for mean arterial pressure range on cardiopulmonary bypass showed a significant relationship; low R2 values indicated that much of the variability could not be explained and that there was, therefore, poor agreement between the two records. Furthermore, a systematic bias in the hand-written anesthesia record was found when the computer system record was compared with the hand-written record and to the difference of the two records, so that extremes seen in the computer system record tended to be minimized in the hand-written anesthesia record. CONCLUSIONS: Because of the lack of explained variability between the computer system and hand-written anesthesia records and the bias in the hand-written anesthesia record, the hand-written anesthesia record should not be relied on as a source of accurate data for research purposes.

The effect of midazolam on left ventricular pump performance and contractility in anesthetized patients with coronary artery disease: effect of preoperative ejection fraction.

Forty patients undergoing coronary artery bypass grafting were studied, of whom 24 had depressed global left ventricular (LV) function at preoperative catheterization, to evaluate the effects of midazolam on LV pump performance and contractility. Transesophageal echocardiography and simultaneous hemodynamic measurements were used to assess LV preload, afterload, and systolic performance during inhalation of 100% O2 and after 0.1 mg/kg of midazolam. Systolic function indices were expressed as a percent of the predicted value for observed end-systolic stress to estimate LV contractility. In the entire study population, midazolam did not affect cardiac index. Heart rate and mean arterial pressure were reduced (63 +/- 13 to 59 +/- 12 bm; P < 0.0006 and 89 +/- 15 to 76 +/- 16 mm Hg; P < 0.0001) as were pulmonary capillary wedge pressure, central venous pressure, and systemic and pulmonary vascular resistance. Afterload, as measured by end-systolic stress, was reduced (55 +/- 33 to 48 +/- 26 kdyne/cm2; P = 0.007) with no change in fractional shortening or percent area change. As a result, systolic function decreased in relation to observed end-systolic stress, providing evidence of reduced LV contractility. Thus, midazolam administration (0.1 mg/kg) caused no change in cardiac pump performance but decreased LV contractility in the entire population. Myocardial contractility was lower at baseline and after the administration of midazolam in the depressed ejection fraction group, but the decrease in contractility was not exaggerated in the depressed ejection fraction group.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of nitrous oxide on left ventricular pump performance and contractility in patients with coronary artery disease: effect of preoperative ejection fraction.

To elucidate the effects of nitrous oxide (N2O) on left ventricular (LV) pump performance and contractility, 28 patients undergoing coronary artery bypass graft surgery were studied, of whom 15 had depressed global LV function at preoperative catheterization. Transesophageal echocardiography and simultaneous hemodynamic measurements were used to assess LV preload, afterload, and systolic performance during inhalation of 100% oxygen (O2) and 60% N2O:40% O2. Systolic function indices were expressed as a percent of the predicted value for observed end-systolic stress to provide estimates of LV contractility. In the entire study population, N2O reduced pump performance (cardiac index 2.4 +/- 0.8 to 2.2 +/- 0.6 L.min-1 x m-2; P < 0.02). Heart rate and mean arterial pressure were reduced (67 +/- 13 to 64 +/- 13, P < 0.01, and 87 +/- 9 to 80 +/- 15, P < 0.005) as were left and right ventricular stroke work index. Preload, as measured by end-diastolic stress, was unchanged but afterload, as measured by end-systolic stress, tended to decrease (88 +/- 31 to 78 +/- 28, P = 0.053). In the 13 patients with normal preoperative LV function, mean arterial pressure and LV stroke work index decreased significantly (91 +/- 8 to 84 +/- 14, P < 0.04, and 40 +/- 13 to 34 +/- 10, P < 0.04, respectively) and end-systolic stress tended to decrease (P = 0.054).(ABSTRACT TRUNCATED AT 250 WORDS)

Severity of aortic atheromatous disease diagnosed by transesophageal echocardiography predicts stroke and other outcomes associated with coronary artery surgery: a prospective study.

Advanced atheromatous disease of the thoracic aorta identified by transesophageal echocardiography (TEE) is a major risk factor for perioperative stroke. This study investigated whether varying degrees of atherosclerosis of the descending aorta, as assessed by TEE, are an independent predictor of cardiac and neurologic outcome in patients undergoing coronary artery bypass grafting (CABG). Intraoperative TEE of the descending aorta was performed on 189 of 248 patients participating in a randomized controlled trial of low (50-60 mm Hg) or high (80-100 mm Hg) mean arterial pressure during cardiopulmonary bypass for elective CABG. Aortic atheromatous disease was graded from I to V in order of increasing severity by observers blinded to outcome. Measured outcomes were death, stroke, and major cardiac events assessed at 1 wk and 6 mo. Nine of the 189 patients with TEE examinations had perioperative strokes by 1 wk. At 1 wk, no strokes had occurred in the 123 patients with atheroma Grades I or II, while the 1-wk stroke rate was 5.5% (2/36), 10.5% (2/19), and 45.5% (5/11) for Grades III, IV, and V, respectively (Fisher's exact test, P = 0.00001). For 6-mo outcome, advancing aortic atheroma grade was a univariate predictor of stroke (P = 0.00001) and death (P = 0.03). By 6 mo there were one additional stroke, three additional deaths, and one additional major cardiac event. Atheromatous disease of the descending aorta was a strong predictor of stroke and death after CABG. TEE determination of atheroma grade is a critical element in the management of patients undergoing CABG surgery.