Anne T. Rogers

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.

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.

Response of cerebral blood flow to phenylephrine infusion during hypothermic cardiopulmonary bypass: influence of PaCO2 management.

Twenty-eight adult patients anesthetized with fentanyl, then subjected to hypothermic cardiopulmonary bypass (CPU), were studied to determine the effect of phenylephrine-induced changes in mean arterial pressure (MAP) on cerebral blood flow (CBF). During CPB patients managed at 28° C with either alpha-stat (temperature-un-corrected PaCo2 = 41 ± 4 mmHg) or pH-stat (temperature-uncorrected PaCo2 = 54 ± 8 mmHg) PaCo2 for blood gas maintenance received phenylephrine to increase MAP ≥ 25% (group A, n = 10; group B, n = 6). To correct for a spontaneous, time-related decline in CBF observed during CPB, two additional groups of patients undergoing CPB were cither managed with the alpha-stat or pH-stat approach, but neither group received phenylephrine and MAP remained unchanged in both groups (group C, n = 6; group D, n = 6). For all patients controlled variables (nasopharyngcal temperature, PaCo2, pump flow, and hematocrit) remained unchanged between measurements. Phenylephrine data were corrected based on the data from groups C and D for the effect of diminishing CBF over time during CPB. In patients in group A CBF was unchanged as MAP rose from 56 ± 7 to 84 ± 8 mmHg. In patients in group B CBF increased 41% as MAP rose from 53 ± 8 to 77 ± 9 mmHg (P < 0.001). During hypothermic CPB normocarbia maintained via the alpha-stat approach at a temperature-uncorrected PaCo2, of ∼40 mmHg preserves cerebral autoregulation; pH-stat management (PaCo2 ∼57 mmHg uncorrected for temperature, or 40 mmHg when corrected to 28°C) causes cerebrovascular changes (i.e., impaired autoregulation) similar to those changes produced by hypercarbia in awake, normothermic patients.

Heparin management protocol for cardiopulmonary bypass influences postoperative heparin rebound but not bleeding

A group of 63 adult patients undergoing cardiac surgical procedures requiring cardiopulmonary bypass (CPB) were studied to examine the relationship between heparin doses administered and postoperative bleeding. Patients were randomly assigned either to receive heparin 200 U/kg and additional heparin as needed to reach and maintain an activated clotting time (ACT) greater than 400 s for CPB (group A, n = 30), or to receive heparin 400 U/kg and additional heparin as needed to reach and maintain a whole blood heparin concentration greater than 4.0 U/ml for CPB (group H, n = 33). Groups were compared for the amount of postoperative bleeding, heparin rebound, homologous transfusion requirements, and standard laboratory coagulation tests. In the last 33 patients studied, additional tests of platelet aggregation and plasma levels of beta thromboglobulin (BTG), antithrombin III, and several markers of fibrinolysis were measured and compared by group. The mean heparin dose was 28,000 +/- 4,800 U for group A and 57,000 +/- 10,700 U for group H (P less than 0.05 for group A vs. group H). At 8 and 24 h postoperatively, mediastinal drainage did not differ significantly between groups (mean 24-h drainage +/- SD = 901 +/- 414 ml in group A, 1035 +/- 501 ml in group H), nor did the incidence of transfusion with homologous blood products.(ABSTRACT TRUNCATED AT 250 WORDS)

Rapid administration of a narcotic and neuromuscular blocker: a hemodynamic comparison of fentanyl, sufentanil, pancuronium, and vecuronium

High-dose narcotic anesthetic inductions usually avoid circulatory depression bettrthan do other techniques; however, the selection of a narcotic and neuromuscular blocker influences subsequent hemodynamic responses. One hundred-one patients having aortocoronary bypass graft (CABG) surgery were investigated using four combinations of a narcotic and neuromuscular blocker: group FP (fentanyl 50 μg/kg, pancuronium 100 μg/kg); group FV (fentanyl 50 μg/kg, vecuronium 80 μg/kg); group SP (sufentanil 10 μg/kg, pancuronium 100 μg/kg); and group SV (sufentanil 10 μg/kg, vecuronium 80 μg/kg), each combination being administered over 2 minutes. Hemodynamic functions were then monitored for 10 minutes before tracheal intubation. Significant changes included increases in heart rate in the groups receiving pancuronium and decreases in those receiving vecuronium. In all groups mean arterial pressure initially decreased; systemic vascular resistance index decreased significantly in all groups except SV. Cardiac index decreased significantly only in group SV. Circulatory depression requiring treatment with vasopressor or anticholinergic drugs was more common in patients given vecuronium. Cardiac arrhythmia occurred most often in group SP; only in group FP were there no arrhythmias, ischemic changes, or hemodynamic disturbances requiring intervention. Time to onset of neuromuscular blockade did not differ among the four groups, but transient chest wall rigidity occurred significantly more often with sufentanil than with fentanyl. Overall, the fentanyl/pancuronium combination afforded the greatest hemodynamic stability, whereas the sufentanil/vecuronium combination proved least satisfactory because of bradycardia and hypotension, requiring treatment in 35% of group SV patients. Differences in anesthetic premedication, social habits, preoperative medications, narcotic and muscle relaxant doses, and speed of anesthetic drug administration may also influence hemodynamicresponses and may explain differing results reported by others using the same drug combinations.

Emboli and Neuropsychological Outcome Following Cardiopulmonary Bypass

The dramatic decline in mortality related to cardiac surgery has resulted in over 330,000 surgeries involving cardiopulmonary bypass (CPB) being performed yearly in the United States. Although few patients die as a result of cardiac surgery, over two thirds of the patients demonstrate evidence of acute neuropsychological dysfunction postoperatively. The potential mechanisms contributing to post‐CPB neuropsychological deficits are many, but two major inter‐related etiologic factors, hypoperfusion and emboli, are suggested as the probable culprits. If embolism is the cause of the deficits, increasing cerebral perfusion would deliver more emboli and increase the amount and severity of injury. Conversely, if hypoperfusion is the cause of the injury, then decreasing brain blood flow to minimize embolic delivery would increase the likelihood of perfusion injury. By monitoring the carotid arteries of patients undergoing coronary artery bypass graft surgery, we have determined the frequency and quantity of embolic signals that occur during CPB. Although we have not been able to determine the nature of the embolus, gaseous or solid, we have demonstrated a relationship between the overall embolic load and the probability of having NP dysfunction.

Hypercarbia depresses cerebral oxygen consumption during cardiopulmonary bypass.

No human studies have systematically examined the relations among PaCO2, cerebral blood flow, and the cerebral metabolic rate for oxygen during hypothermic cardiopulmonary bypass. We varied PaCO2 during hypothermic (26-28 degrees C) cardiopulmonary bypass and estimated the cerebral metabolic rate for oxygen by multiplying cerebral blood flow (measured using xenon-133 clearance) by the cerebral arteriovenous difference in oxygen contents. Patients were randomly assigned to either of two methods of managing PaCO2 (uncorrected for body temperature). In group 1 (PACO2 32-48 mm Hg, n = 13) the mean +/- SD cerebral metabolic rate for oxygen was 0.40 +/- 0.11 ml O2 X 100 g-1 X min-1 at a mean +/- SD PaCO2 of 36 +/- 2.0 mm Hg and 0.40 +/- 0.14 ml O2 X 100 g-1 X min-1 at a mean +/- SD PaCO2 of 45 +/- 2 mm Hg. and 49-72 mm Hg, n = 12) the mean +/- SD cerebral metabolic rate for oxygen was 0.31 +/- 0.09 ml O2 X 100 g-1 X min-1 at a mean +/- SD PaCO2 of 55 +/- 3 mm Hg and 0.21 +/- 0.07 ml O2 X 100 g-1 X min-1 at a mean +/- SD PaCO2 of 68 +/- 2 mm Hg. Group 2 values differed significantly from those in Group 1 (p less than 0.05). In both groups, cerebral blood flow increased as PaCO2 increased. During cardiopulmonary bypass, increasing PaCO2 increases cerebral blood flow and decreases the cerebral metabolic rate for oxygen.

CEREBRAL BLOOD FLOW DECREASES WITH TIME WHEREAS CEREBRAL OXYGEN CONSUMPTION REMAINS STABLE DURING HYPOTHERMIC CARDIOPULMONARY BYPASS IN HUMANS

&NA; Recent investigations demonstrate that cerebral blood flow (CBF) progressively declines during hypothermic, nonpulsatile cardiopulmonary bypass (CPB). If CBF declines because of brain cooling, the cerebral metabolic rate for oxygen (CMRo2) should decline in parallel with the reduction in CBF. Therefore we studied the response of CBF, the cerebral arteriovenous oxygen content difference (A ‐ VDcereO2), and CMRo2 as a function of the duration of CPB in humans. To do this, we compared the cerebrovascular response to changes in the Paco2. Because sequential CBF measurements using xenon 133 (133Xe) clearance must be separated by 15‐25 min, we hypothesized that a time‐dependent decline in CBF would accentuate the CBF reduction caused by a decrease in Paco2, but would blunt the CBF increase associated with a rise in Paco2. We measured CBF in 25 patients and calculated the cerebral arteriovenous oxygen content difference using radial arterial and jugular venous bulb blood samples. Patients were randomly assigned to management within either a lower (32‐48 mm Hg) or higher (50‐71 mm Hg) range of Paco2 uncorrected for temperature. Each patient underwent two randomly ordered sets of measurements, one at a lower Paco2 and the other at a higher Paco2 within the respective ranges. Cerebrovascular responsiveness to changes in Paco2 was calculated as specific reactivity (SR), the change in CBF divided by the change in Paco2, expressed in mL‐100 g−1·min−1·mm Hg−1. In the entire group of 25 subjects, SR was 0.69 ± 0.33 mL·100g−1·min−1·mm Hg−1 (SD) if Paco2 was reduced and 0.10 ± 0.30 mL·100g−1·min−1·mm Hg−1 if Paco2 was increased (P < 0.001). In patients managed within the lower range of Paco2, SR was 0.63 ± 0.31 and 0.21 ± 0.17, respectively, when Paco2 was reduced or increased (P < 0.05), In patients managed within the higher range of Paco2, SR was 0.76 ± 0.38 and −0.01 ± 0.36, respectively, when Paco2 was reduced or increased (P < 0.01). Estimated CMRo2 remained constant within groups from the initial to the repeat measurements. These results confirm a significant time‐dependent decline of CBF during CPB. Moreover, by demonstrating that CMRo2 did not change significantly as Paco2 was altered in either direction, they suggest that the CBF reduction cannot be attributed to progressive brain cooling during stable, hypothermic, nonpulsatile CPB, but must result from an alteration in cerebrovascular resistance.

Baseline activated coagulation time should be measured after surgical incision

The activated coagulation time (ACT) is widely used to guide heparin and protamine dosing during cardiac surgery. A common protocol involves establishing a baseline ACT before administering heparin, then using this ACT as a target value for assessing the adequacy of heparin neutralization after cardiopulmonary bypass. Results vary in previous comparisons of baseline ACT to postprotamine ACT, with some showing postprotamine ACT significantly below baseline values. The present study examined ACTs at three possible baseline intervals in 68 patients at two institutions: (a) before anesthetic induction; (b) after anesthetic induction; and (c) after sternotomy. Baseline ACT decreased significantly with anesthesia and surgery. The poststernotomy baseline ACT best matched the postprotamine ACT. It appears likely that surgery induces a throm-boplastic response that decreases ACT. Establishing baseline ACT before anesthetic induction would predispose to false diagnoses of adequate protamine neutralization after cardiopulmonary bypass, because ACT is relatively insensitive to low concentrations of unneutralized heparin. Baseline ACTs should therefore be measured after surgical incision