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Biomedical subjects

M F Newman

Publications and source records attributed to M F Newman.

71 records · Page 4Linked to original sources

Multicenter preoperative stroke risk index for patients undergoing coronary artery bypass graft surgery. Multicenter Study of Perioperative Ischemia (McSPI) Research Group.

BACKGROUND: The paradox of present cardiac surgery is that the more elderly and debilitated patients benefit most from cardiac surgery compared with medical therapy, yet they sustain greater overall risk for morbidity and mortality after cardiac surgery. The goal of the present study was to develop a preoperative index predicting major perioperative neurological events in patients undergoing coronary artery bypass graft surgery. METHODS AND RESULTS: As part of a prospective, multicenter, observational study (McSPI Research Group), we enrolled 2417 patients at 24 academic medical centers in the United States. Patients who died intraoperatively or had concomitant open-heart procedures were excluded from analysis, resulting in a total of 2107 for analysis. Sixty-eight patients (3.2%) developed adverse neurological events, defined as cerebrovascular accident, transient ischemic attack (TIA), or persistent coma. Bivariate analysis was applied to determine associations between preoperative variables and neurological events. Significant bivariate predictors were identified then logically grouped, and for each cluster, a score was calculated based on principal components. Key predictor variables were age, history of previous neurological disease, diabetes, history of vascular disease, previous coronary artery surgery, unstable angina, and history of pulmonary disease, the coefficients for which were used to develop a preoperative stroke risk index that was validated by bootstrap (c-index = 0.778). Stroke risk could then be determined for each patient, calculating a patient's risk for stroke within 95% confidence intervals. CONCLUSIONS: With the McSPI stroke risk index developed in this study, neurological risk can be estimated, and the most appropriate group for perioperative therapy can be identified. Further refinement and validation of this index, however, are necessary and are under way in current studies.

Adult↗

Effect of perfusion pressure on cerebral blood flow during normothermic cardiopulmonary bypass.

BACKGROUND: We have recently shown that during hypothermic cardiopulmonary bypass (CPB), cerebral autoregulation has a positive slope such that for every 10 mm Hg change in pressure, a 0.86 mL.100 g-1.min-1 change in cerebral blood flow (CBF) is predicted. The purpose of this study was to define the influence of mean arterial blood pressure (MAP) on CBF during normothermic CPB. METHODS AND RESULTS: CBF was measured by use of 133Xe washout and alpha-stat blood gas management during nonpulsatile CPB. CBF measurements were made at a pump flow of 2.4 L.min-1.m-2 at stable normothermia and approximately 15 minutes later after the MAP was increased or decreased > or = 20%. A third data set was recorded after the pressure was returned to the initial value. Forty-five patients were entered into the study. Temperature was held constant. We found a significant effect (P = .016) of change in MAP on change in CBF during normothermic CPB. For a 10 mm Hg increase in MAP, an increase in CBF of 1.78 mL.100 g-1.min-1 is predicted. Along with change in CBF, significant increases in both cerebral metabolic rate and cerebral oxygen delivery were observed. CONCLUSIONS: This information, along with our previous data shows that autoregulation during CPB has a positive slope that is greater with normothermia than hypothermia. Although it is unlikely that these small changes in flow are an important primary effect in the development of hypoperfusion, increased metabolic rate with increased CBF may indicate pressure-dependent collateral flow potentially in regions embolized during CPB.

Adult↗

Defining neuropsychological dysfunction after coronary artery bypass grafting.

BACKGROUND: Despite the large body of literature documenting the presence of cognitive decline after coronary artery bypass grafting, there is little consensus as to the frequency and extent of cognitive impairment. One potential reason for this lack of agreement is the absence of uniform criteria for assessing cognitive decline. METHODS: Two hundred thirty-two patients underwent cognitive testing the day before operation and were examined before discharge, and at 6 weeks and 6 months after grafting. For comparative purposes, five different sets of criteria were used to define cognitive decline. RESULTS: There was little agreement between the criteria as to which patients declined at each test period. The incidence of decline ranged from 66% to 15.3% before discharge, 34% to 1.1% at 6 weeks, and 19.4% to 3.4% at 6 months. CONCLUSIONS: A large variation in reported incidence of cognitive decline after coronary artery bypass grafting can be attributed to the different criteria used to define cognitive impairment.

Aged↗

Long-term survival benefits of coronary artery bypass grafting and percutaneous transluminal angioplasty in patients with coronary artery disease.

The purpose of this study was to evaluate long-term survival benefits of bypass surgery and angioplasty versus medical therapy in 9263 patients at Duke University Medical Center between 1984 and 1990 with coronary artery disease confirmed by cardiac catheterization to involve one, two, or three vessels. Clinical data were prospectively entered into an established cardiovascular database, and annual follow-up was 97% complete for a mean interval of 5.3 years and a maximal interval of 10 years. Outcomes were analyzed with the Coronary Artery Surgery Study "method A" to define patient groups treated by medicine (n = 2449), angioplasty (n = 2924), or bypass surgery (n = 3890). Differences among treatment groups in baseline characteristics were adjusted by Cox proportional hazard models. The anatomic severity of coronary artery stenosis best defined survival benefit from bypass surgery and angioplasty versus medical treatment. One or both interventional treatments provided better long-term survival than did medical treatment for all levels of disease severity. All patients with single-vessel disease, except those with at least 95% proximal left anterior descending stenosis, benefited from angioplasty versus bypass. All patients with three-vessel disease and those two-vessel patients with > or = 95% proximal left anterior descending stenosis benefited from bypass surgery versus angioplasty. All other patients with two-vessel disease and those with > or = 95% proximal left anterior descending stenosis only had similar survival with either interventional treatment. The absolute survival benefit was greatest for patients with severe three-vessel disease treated with bypass surgery.

Angioplasty, Balloon, Coronary↗

Maintenance of therapeutic plasma aprotinin levels during prolonged cardiopulmonary bypass using a large-dose regimen.

Aprotinin concentrations in the range of 127-191 kallikrein inactivator units (KIU)/mL at the end of cardiopulmonary bypass (CPB) (< 2 h duration) reduce transfusion requirements. It has been suggested that prolonged CPB may require higher infusion rates which significantly increase cost. We tested the hypothesis that large-dose aprotinin maintains therapeutic plasma levels during prolonged periods of CPB (< 2 h). Aprotinin was administered as follows: 2 x 10(6) KIU upon skin incision; 0.5 x 10(6) KIU/h x 4-h infusion on initiation of CPB; and 2 x 10(6) KIU added to the CPB prime solution. Aprotinin activity was measured 1) 30 min after initiation of drug administration (Pre-CPB); 2) 30 min after initiation of CPB (CPB + 30); 3) 90 min after initiation of CPB (CPB + 90); and 4) at CPB termination (End CPB). CPB duration (mean +/- SD) was 158 +/- 51 min. Plasma aprotinin concentrations (KIU/mL, mean +/- SD) were: 234 +/- 30 at Pre-CPB; 229 +/- 35 at CPB + 30; 184 +/- 27 at CPB + 90; and 179 +/- 22 at End CPB. In all patients, aprotinin levels at the completion of CPB were in the range previously reported to be effective. The authors conclude that large-dose regimen limited to 6 x 10(6) KIU maintained therapeutic plasma aprotinin concentrations during prolonged CPB.

Aprotinin↗

Methodological issues in the assessment of neuropsychologic function after cardiac surgery.

This report reviews critical issues facing investigators interested in neuropsychologic sequelae after cardiac operations: (1) experimental design; (2) selective attrition; (3) selection of instruments; (4) moderating factors; (5) definitions of cognitive decline; (6) statistical analysis; and (7) clinical significance. Implications for further research in the area are discussed.

Cognition Disorders↗

Predictors of cognitive decline after cardiac operation.

Despite major advances in cardiopulmonary bypass technology, surgical techniques, and anesthesia management, central nervous system complications remain a common problem after cardiopulmonary bypass. The etiology of neuropsychologic dysfunction after cardiopulmonary bypass remains unresolved and is probably multifactorial. Demographic predictors of cognitive decline include age and years of education; perioperative factors including number of cerebral emboli, temperature, mean arterial pressure, and jugular bulb oxygen saturation have varying predictive power. Recent data suggest a genetic predisposition for cognitive decline after cardiac surgery in patients possessing the apolipoprotein E epsilon-4 allele, known to be associated with late-onset and sporadic forms of Alzheimer's disease. Predicting patients at risk for cognitive decline allows the possibility of many important interventions. Predictive power and weapons to reduce cellular injury associated with neurologic insults lend hope of a future ability to markedly decrease the impact of cardiopulmonary bypass on short-term and long-term neurologic, cognitive, and quality-of-life outcomes.

Age Factors↗

Comparing two strategies of cardiopulmonary bypass cooling on jugular venous oxygen saturation in neonates and infants.

BACKGROUND: Cerebral protection during deep hypothermic circulatory arrest is predicted on efficient and complete cerebral cooling. Institutions approach cooling quite differently. We compared two different cooling strategies in terms of measured jugular venous bulb saturations in 39 infants undergoing deep hypothermic cardiopulmonary bypass to evaluate the effect of institutional cooling practices on jugular venous bulb saturation, an indirect measure of cerebral cooling efficiency. METHODS: The patients were grouped based on the method of core cooling. In group A (n = 17), core cooling was achieved rapidly by setting the water bath temperature of the heat exchanger at 4 degrees to 5 degrees C, and the patient was cooled until rectal temperature and nasopharyngeal temperature were 15 degrees C or lower. In group B (n = 22), the heat exchanger was initially set at 18 degrees C and slowly lowered to 12 degrees C. Hypothermic temperatures of 12 degrees C were maintained until the nasopharyngeal temperature was 18 degrees C or less and the rectal temperature was 20 degrees C or lower. Once cooling was complete, blood samples were analyzed by cooximetry for determination of arterial oxygen saturation and jugular venous bulb saturation. RESULTS: In group A, the measured jugular venous bulb saturation was 98.0% +/- 0.9% and the oxygen saturation to jugular venous bulb saturation difference was 0.3% +/- 0.5%, measured at the time that institutional cooling objectives were achieved (total cooling time, 15.0 +/- 0.45 minutes). In group B, jugular venous bulb saturation was 86.2% +/- 12% and the oxygen saturation to jugular venous bulb saturation difference was 10.8% +/- 12.2%, measured at the time that institutional cooling objectives were achieved (total cooling time, 17.5 +/- 1.1 minutes (p < 0.01). CONCLUSIONS: Differences in cardiopulmonary bypass cooling techniques may alter the rate at which jugular bulb saturations rise. We believe this represents an indirect measure of the efficiency of brain cooling and therefore of cerebral protection.

Body Temperature↗

Differential age effects of mean arterial pressure and rewarming on cognitive dysfunction after cardiac surgery.

Central nervous system dysfunction is a common consequence of otherwise uncomplicated cardiac surgery. Many mechanisms have been postulated for the cognitive dysfunction that is part of these neurologic sequelae. The purpose of our investigation was to evaluate the effects of mean arterial pressure (MAP) during cardiopulmonary bypass (CPB) and the rate of rewarming on cognitive decline after cardiac surgery. Two hundred thirty-seven patients completed preoperative and predischarge neuropsychologic testing. MAP and temperature were recorded at 1-min intervals using an automated anesthesia record keeper. MAP area less than 50 mm Hg (time and degree of hypotension), as well as the maximal rewarming rate, were determined for each patient. Multivariable linear regression revealed that the rate of rewarming and MAP were unrelated to cognitive decline. However, interactions significantly associated with cognitive decline were found between age and MAP area less than 50 mm Hg on one measure, and between age and rewarming rate in another, identifying susceptibility of the elderly to these factors. Although MAP and rewarming were not the primary determinates of cognitive decline in this surgical population, hypotension and rapid rewarming contributed significantly to cognitive dysfunction in the elderly.

Aged↗

Cerebral physiologic effects of burst suppression doses of propofol during nonpulsatile cardiopulmonary bypass. CNS Subgroup of McSPI.

Central nervous system (CNS) complications are common after cardiac surgery. Death due to cardiac causes has decreased, but the number of deaths due to CNS injury has increased. As a first stage in the evaluation of its cerebral protection potential, we evaluated the cerebral physiologic effects of burst suppression doses of propofol during nonpulsatile cardiopulmonary bypass. Thirty patients without history of cerebral vascular disease were randomized to two study groups: control group (n = 15) who received sufentanil and vecuronium, or propofol group (n = 15) who received the control anesthetic and propofol infused to maintain electroencephalogram (EEG) burst suppression. Catheters were placed in the radial artery and right jugular bulb for sampling of systemic arterial and jugular bulb venous blood. 133Xe clearance was used to determine cerebral blood flow (CBF) at the start of normothermic bypass, during stable hypothermia, and when rewarmed to 35-37 degrees C nasopharyngeal temperature. Pharmacologic burst suppression with propofol produced a statistically significant reduction in CBF, cerebral oxygen delivery (DO2), and cerebral metabolic rate (CMRO2) at each measurement interval (P < 0..05 vs control). Cerebral arterial venous oxygen difference (C(a-v)O2), and jugular bulb venous oxygen saturation (SJvO2) were not statistically different between groups, indicating maintenance of cerebral metabolic autoregulation (coupling). The reduction in CBF and CMRO2, prominent during the normothermic phases of cardiopulmonary bypass (CPB), indicates a potential for propofol to reduce cerebral exposure to the embolic load during CPB.

Aged↗

Jugular bulb saturation and mixed venous saturation during cardiopulmonary bypass.

Systemic venous oxygen saturation is clinically used as an indicator of a satisfactory oxygen supply demand balance on cardiopulmonary bypass (CBP). Cerebral desaturation has been associated with postoperative cognitive dysfunction and has an incidence of 17% to 23% on bypass. We tested the hypothesis that systemic venous saturation did not correlate with jugular bulb venous saturation. Blood was drawn from the radial artery, jugular bulb catheter, and venous return line for determination of pH, oxygen tension and saturation, and carbon dioxide tension at four times during bypass: warm 1 (following initiation of CPB); cold 1 (stable hypothermia); cold 2 (hypothermia prior to rewarm); and warm 2 (nasopharyngeal temperature 36 degrees C to 37 degrees C). Correlations of jugular bulb and systemic venous saturation at cold 1 were r = 0.29, r2 = 0.08, and p = 0.0005, and at warm 2 were r = 0.22, r2 = 0.05, and p = 0.007. We conclude that systemic saturation is a poor indicator of cerebral saturation. The poor association of jugular and systemic pump venous saturations underscores our inability to evaluate adequacy of cerebral perfusion. Jugular saturation is lower than pump venous return blood, especially at times of lower oxygen delivery, thus either continuous invasive or noninvasive evaluation of cerebral oxygenation is required to evaluate the adequacy of cerebral perfusion.

Aged↗

Jugular bulb saturation and cognitive dysfunction after cardiopulmonary bypass.

Inadequate cerebral oxygenation during cardiopulmonary bypass may lead to postoperative cognitive dysfunction in patients undergoing cardiac operations. A psychological test battery was administered to 255 patients before cardiac operation and just before hospital discharge. Postoperative impairment was defined as a decline of more than one standard deviation in 20% of tests. Variables significantly (p < 0.05) associated with postoperative cognitive impairment are baseline psychometric scores, largest arterial-venous oxygen difference, and years of education. Jugular bulb hemoglobin saturation is significant if it replaces arterial-venous oxygen difference in the model. Factors correlated with jugular bulb saturation at normothermia were cerebral metabolic rate of oxygen consumption (r = -0.6; p < 0.0005), cerebral blood flow (r = 0.4; p < 0.0005), oxygen delivery (r = 0.4; p < 0.0005), and mean arterial pressure (r = 0.15; p < 0.05). Three measures were significantly related to desaturation at normothermia and at hypothermia as well: greater cerebral oxygen extraction, greater arterial-venous oxygen difference, and lower ratio of cerebral blood flow to arterial-venous oxygen difference. We conclude that cerebral venous desaturation occurs during cardiopulmonary bypass in 17% to 23% of people and is associated with impaired postoperative cognitive test performance.

Aged↗

Effect of aging on cerebral autoregulation during cardiopulmonary bypass. Association with postoperative cognitive dysfunction.

BACKGROUND: Age is a predictor of cognitive dysfunction after cardiac surgery, but the mechanism is unknown. The purpose of our study was to determine whether age-related decrements in cognition are associated with cerebral blood flow (CBF) autoregulation during cardiopulmonary bypass (CPB). METHODS AND RESULTS: Cognitive function testing was completed before surgery and before hospital discharge in 215 patients undergoing elective coronary artery bypass grafting (CABG) surgery. The battery consisted of seven tests with nine measures designed to evaluate memory, mood changes, and visuomotor speed and function. Pressure-flow and metabolic-flow cerebral autoregulation during hypothermic cardiopulmonary bypass were determined using the 133Xe clearance CBF method and radial artery and jugular bulb effluent to calculate cerebral metabolic rate (CMRO2) and cerebral AV difference (C[AV]O2). Pressure-flow autoregulation was tested by using two CBF measurements at stable hypothermia: one at stable mean arterial pressure (MAP) and the second 15 minutes later when MAP had increased or decreased > or = 20%. Metabolism-flow autoregulation was tested by varying the temperature (CMRO2) and measuring the coupling of CBF and CMRO2. Individual patient autoregulation was correlated with changes in cognitive measures. Cognitive performance declined in 6 of 9 measures after CABG surgery. Age predicted cognitive decline in 7 of 9 measures; short-term memory showed the greatest effect of age. Pressure-flow autoregulation during hypothermic CPB showed a small but significant (P < .0001) effect of pressure on CBF. There was no effect of age on the slope of CBF response to changes in MAP (pressure-flow autoregulation). There was a major effect of temperature on CBF during CPB (P < .0001). Coupling CBF and CMRO2 with changing temperature was unaffected by age. Changes in cognition were not associated with measures of cerebral autoregulation. However, increasing C(AV)O2 is associated with cognitive deficits in 5 of 9 measures; these associations were independent of age. CONCLUSIONS: Increased age predisposes to impaired cognition after cardiac surgery. This decline in cognitive function in the elderly is not associated with age-related changes in cerebral blood flow autoregulation. The association of increased oxygen extraction with decline in some measures of cognitive function suggests that an imbalance in cerebral tissue oxygen supply, which is unrelated to age, contributes to acute cognitive dysfunction after cardiac surgery. Cognitive dysfunction after CPB in the elderly cannot be explained by impaired CBF autoregulation.

Aging↗