Neal D. Kon

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.

Comparison of implantation techniques using freestyle stentless porcine aortic valve

Stentless porcine aortic valves demonstrate superior hemodynamic performance when compared with their stented counterparts. The technical considerations for implanting these valves can be demanding. The Medtronic Freestyle aortic root bioprosthesis resembles an allograft, has zero-pressure-fixed leaflets treated with an antimineralization agent, and can be implanted using a variety of techniques. In this study of that valve, total root replacement (TRR) was compared with a partial scallop aortic inclusion technique (PSI). Implications were performed in 75 patients (49 PSI and 26 TRR). There were no significant differences with respect to age, sex, or incidence of concomitant procedures. Mean aortic cross-clamp times were significantly less in the PSI group than in the TRR group (51.8 +/- 11.7 minutes versus 125.5 +/- 19.7 minutes; p = 0.0001). At discharge, mean systolic gradients seen on color-flow Doppler echocardiography were less in the TRR group than in the PSI group (6.17 +/- 3.66 versus 10.01 +/- 4.83 mm Hg; p = 0.014). Discharge echocardiography revealed trivial valve regurgitation in 8.3% of the TRR group and in 41.7% of the PSI group (p = 0.004). No patient experienced any significant valvular regurgitation on discharge echocardiography. We conclude that early experience with the Medtronic Freestyle aortic root bioprosthesis shows excellent short-term function regardless of implantation technique. Shorter cross-clamp times, comparable with those of stented valve procedures, occurred with PSI implantation. We anticipate that effects on long-term durability will be beneficial.

Eight-year results of aortic root replacement with the freestyle stentless porcine aortic root bioprosthesis

BACKGROUND Stentless porcine aortic valves offer several advantages over traditional valves. Among these are superior hemodynamics, laminar flow patterns, lack of need for anticoagulation, and perhaps improved durability. METHODS One hundred four patients were operated on from September 17, 1992, to October 31, 1997, as part of a multicenter worldwide investigation of the Medtronic Freestyle stentless porcine bioprosthesis. All patients received a total aortic root replacement. The patients were evaluated postoperatively at discharge, at 3 to 6 months, and yearly by clinical examination and color flow Doppler echocardiography. RESULTS Operative mortality was 3.9%. No patient experienced structural valve deterioration, nonstructural deterioration, perivalvular leak, or unacceptable hemodynamic performance. At 8 years, survival was 59.8%. Freedom from thromboembolic complications was 83.3%. Freedom from postoperative endocarditis was 96.9%. Freedom from reoperation was 100%. Mean systolic gradients did not change over the time period studied. They were 6.4 +/- 3.8 mm Hg at 1 year and 6.7 +/- 2.6 mm Hg at 8 years. Correspondingly, effective orifice area was 1.9 +/- 0.7 cm2 at 1 year and 1.8 +/- 0.8 cm2 at 8 years. The incidence of any aortic insufficiency also did not change over the length of follow-up. At 1 year, 98% of patients had no or trivial aortic insufficiency and 2% had mild aortic insufficiency. At 8 years, 100% of patients evaluated were free of any aortic insufficiency. CONCLUSIONS The Medtronic Freestyle aortic root bioprosthesis can be used safely to replace the aortic root or aortic valve for aortic valve and aortic root pathology. Total root replacement allows optimal hemodynamic performance with no significant aortic regurgitation. Results up to 8 years show excellent survival and no signs of degeneration. Further follow-up is still needed to determine valve durability.

Feasibility, Accuracy, and Incremental Value of Intraoperative Three-Dimensional Transesophageal Echocardiography in Valve Surgery

In this prospective trial, intraoperative 2-dimensional (2-D) and 3-dimensional (3-D) transesophageal echocardiography (TEE) examinations were performed on 60 consecutive patients undergoing cardiac valve surgery. Both 2-D (including color flow and Doppler data) and 3-D images were reviewed by blinded observers, and major valvular morphologic findings recorded. In vivo morphologic findings were noted by the surgeon and all explanted valves underwent detailed pathologic examination. To test reproducibility, 6 patients also underwent 3-D TEE 1 day before surgery. A total of 132 of 145 attempted acquisitions (91%) were completed with a mean acquisition time of 2.8 +/- 0.2 minutes. Acquisition time was significantly shorter in patients with regular rhythms. Reconstructions were completed in 121 of 132 scans (92%) and there was at least 1 good reconstruction in 56 of 60 patients (93%). Mean reconstruction time was 8.6 +/- 0.7 minutes. Mean effective 3-D time, which was the time taken to complete an acquisition and a clinically interpretable reconstruction, was 12.2 +/- 0.8 minutes. Intraoperative 3-D echocardiography was clinically feasible in 52 patients (87%). Three-D echocardiography detected most of the major valvular morphologic abnormalities, particularly leaflet perforations, fenestrations, and masses, confirmed on pathologic examination. Three-D echocardiography predicted all salient pathologic findings in 47 patients (84%) with good quality images. In addition, in 15 patients (25%), 3-D echocardiography provided new additional information not provided by 2-D echocardiography, and in 1 case, 3-D echocardiographic findings resulted in a surgeons decision to perform valve repair rather than replacement. In several instances, 3-D echocardiography provided complementary morphologic information that explained the mechanism of abnormalities seen on 2-D and color flow imaging. In the reproducibility subset, preoperative and intraoperative 3-D imaging detected a similar number of findings when compared with pathology. Thus, in routine clinical intraoperative settings, 3-dimensional TEE is feasible, accurately predicts valve morphology, and provides additional and complementary valvular morphologic information compared with conventional 2-D TEE, and is probably reproducible.

Radial Artery-to-Aorta Pressure Difference after Discontinuation of Cardiopulmonary Bypass

To test whether the radial artery-to-aorta pressure gradient seen in some patients after cardiopulmonary bypass (CPB) is due to reduction in hand vascular resistance, the authors compared pressures in the ascending aorta with pressures in the radial artery before and after CPB in 12 patients. They increased hand vascular resistance by briefly occluding the radial and ulnar arteries at the wrist and recorded that effect on the radial artery-to-aorta pressure relationship. They also recorded the effect of wrist compression on radial artery pressures before and after CPB in 38 patients not having aortic pressure measurements. Before CPB in the first 12 patients, the radial systolic arterial pressure (SAP) was significantly higher (P less than 0.05) than the ascending aortic SAP, and wrist compression did not significantly affect that difference (P greater than 0.05). After CPB, the radial artery and aortic SAPs were not statistically different (P greater than 0.05), but wrist compression restored the higher radial artery SAP. The mean arterial pressure (MAP) was equal in four patients and 1-3 mmHg higher or lower in eight patients before CPB, and wrist compression did not alter those relationships. After CPB, MAP was equal in four patients; radial MAP was 1-3 mmHg higher or lower in six patients, and 7 and 10 mmHg lower in the last two patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of preoperative enoxaparin versus unfractionated heparin on bleeding indices in patients undergoing coronary artery bypass grafting

BACKGROUND We examined the effects of preoperative administration of enoxaparin (ENOX), a low-molecular-weight heparin, on bleeding indices and transfusion rates in patients undergoing coronary artery bypass grafting (CABG). METHODS Patients undergoing isolated CABG between 1997 and 2002 who received preoperative ENOX or a continuous infusion of unfractionated heparin (UFH) were randomly divided into three groups: continuous UFH, ENOX last administered more than 12 hours before surgery (ENOX > 12), and ENOX administered less than 12 hours before surgery (ENOX < 12). Perioperative hemoglobin values, transfusion rates, and bleeding complications were compared. RESULTS A total of 69, 58, and 34 patients comprised the UFH, ENOX > 12, and ENOX < 12 groups, respectively. Preoperative demographics and hematologic data were similar among the groups. Compared with the UFH group, the ENOX < 12 group had significantly lower postoperative hemoglobin values (9.6 +/- 1.3 g/dL versus 10.4 +/- 1.2 g/dL, p < 0.05), higher transfusion rates (73.5% versus 50.7%, p < 0.05), and required more total packed red cells per patient (882 +/- 809 mL versus 472 +/- 626 mL, p < 0.05). A nonsignificant increase was noted in the risk of returning to the operating room for bleeding in patients who had received ENOX compared with patients receiving UFH (6.5% versus 2.9%). CONCLUSIONS The preoperative use of ENOX less than 12 hours before CABG is associated with lower postoperative hemoglobin values and higher rates of transfusion than continuous UFH.

Combined inotropic effects of amrinone and epinephrine after cardiopulmonary bypass in humans

Amrinone, a phosphodiesterase inhibitor, and epinephrine, an alpha- and beta-adrenergic receptor agonist, are inotropic drugs used during cardiac surgery to reverse myocardial depression after cardiopulmonary bypass. However, these drugs have not been compared separately, or in combination, in this patient population. We hypothesized that the combination might have complementary actions in improving myocardial function. We, therefore, compared amrinone, epinephrine, and the combination of amrinone and epinephrine in a randomized, blinded, placebo-controlled study in patients undergoing coronary artery bypass grafting. Forty patients with ejection fractions > 0.45 were studied. Right ventricular ejection fraction pulmonary artery catheters and radial arterial catheters were inserted before fentanyl-midazolam anesthesia. After separation from bypass, patients received either a placebo (n = 20) or amrinone bolus (1.5 mg/kg, n = 20) at time 0 and a placebo (n = 20) or epinephrine (30 ng.kg-1.min-1, n = 20) infusion at time 5 min. This resulted in four study groups, n = 10 in each group. Data were collected every 2.5 min for 10 min. Epinephrine, amrinone, and the combination of both drugs significantly increased cardiac output, stroke volume, O2 delivery, and left ventricular stroke work. The increase in stroke volume (P < 0.05) was 12 +/- 6, 16 +/- 4, and 30 +/- 4 mL/beat with epinephrine, amrinone, and the combination of amrinone and epinephrine, respectively. The amrinone-epinephrine combination increased stroke volume as much as the sum of amrinone and epinephrine given separately. Systemic vascular resistance and pulmonary vascular resistance decreased with amrinone and amrinone-epinephrine, but not with epinephrine. Epinephrine increased mean arterial and mean pulmonary arterial pressures. Right ventricular ejection fraction did not significantly increase (P = 0.09) with epinephrine, but increased significantly with amrinone (0.45 to 0.53, P = 0.01), and with the combination (0.43 to 0.55, P = 0.006). These data indicate that amrinone and epinephrine effectively increase myocardial performance during cardiac surgery. Right ventricular function especially was improved with amrinone and the combination of amrinone and epinephrine. The combined effects of amrinone and epinephrine may be useful in patients recovering from the ischemia and reperfusion injury resulting from coronary artery bypass grafting.

Benefit of glyceryl trinitrate on arterial stiffness is directly due to effects on peripheral arteries

Objective: To determine how the vasodilator glyceryl trinitrate (GTN) alters arterial stiffness and improves left ventricular afterload. Methods: Ascending aortic pressure waves were measured with fluid filled catheters of high fidelity in 50 patients undergoing cardiac surgery, before cardiopulmonary bypass, both before and after intravenous infusion of GTN. In all 50 patients, wave reflection was identifiable as a secondary boost to late systolic pressure, permitting the pressure wave to be separated into a primary component, attributable to left ventricular ejection and properties of the proximal aorta, and a secondary component, attributable to reflection of the primary wave from the peripheral vasculature. Results: GTN infusion caused no change in amplitude of the primary wave (mean (SD) 0.0 (1.4) mm Hg, not significant) but substantial reduction (14.6 (9.6) mm Hg, p < 0.0001) in amplitude of the secondary reflected wave. Fall in mean pressure was attributable to a mix of arteriolar and venous dilatation, with relative contributions unable to be separated. Conclusion: Favourable effects of GTN on arterial stiffness can be attributed to effects on peripheral muscular arteries, causing reduction in wave reflection. Results conform with previous invasive studies on vasodilator agents and their known effects on calibre and compliance of muscular arteries.

Aortic root replacement with the freestyle stentless porcine aortic root bioprosthesis

BACKGROUND Stentless porcine prosthetic valves offer several advantages over traditional valves. Among these are superior hemodynamics, laminar flow patterns, lack of need for anticoagulation and perhaps improved durability. METHODS One hundred and twelve patients were operated on from September 17, 1992 to April 13, 1998 as part of a multi-center worldwide investigation. All patients received a total aortic root replacement. Patients were evaluated postoperatively at discharge, 3 to 6 months, and yearly by clinical exam and color flow Doppler echocardiography. RESULTS There were 4 deaths either in the hospital or within 30 days after surgery for an operative mortality of 3.6%. No patients experienced structural valve deterioration, non-structural valve deterioration, paravalvular leak, unacceptable hemodynamic performance, or postoperative endocarditis. The linearized rates for survival and thromboembolic complications at 5 years were 82.8% and 90.5% respectively. Excellent hemodynamic function is demonstrated by very low gradients, large EOA, and an exceedingly low incidence of any aortic regurgitation. CONCLUSIONS The Medtronic Freestyle aortic root bioprosthesis can be used safely to replace the aortic root for aortic valve and aortic root pathology. Root replacement allows optimal hemodynamic performance with no significant aortic regurgitation. Early and intermediate results are encouraging, but further follow-up is needed to determine valve durability.

A randomized, blinded, placebo-controlled evaluation of calcium chloride and epinephrine for inotropic support after emergence from cardiopulmonary bypass

Forty hemodynamically stable patients were randomized to receive an intravenous bolus of either calcium chloride (5 mg/kg) (n = 20) or placebo (n = 20) (phase I). Six minutes later, they received either an epinephrine (30 ng.kg-1.min-1) (n = 20) or placebo (n = 20) infusion (phase II). Hemodynamic and ionized calcium measurements were obtained in phase I at baseline and at 3 and 6 min after the bolus, and in phase II, at 3 and 6 min (study times 9 and 12 min) after initiation of the infusion. Compared with placebo, calcium did not significantly increase cardiac index but significantly increased mean arterial pressure. Calcium improved cardiac index from 2.46 +/- 0.12 (mean +/- SEM) to 2.74 +/- 0.12 L.min-1.m-2; likewise, placebo improved cardiac index from 2.51 +/- 0.15 to 2.74 +/- 0.15 L.min-1.m-2. Mean arterial blood pressure increased with calcium from 74 +/- 2 to 82 +/- 3 mm Hg compared with a placebo change of 74 +/- 2 to 76 +/- 2 mm Hg. Patients who received the epinephrine infusion (n = 20) demonstrated a significant increase in cardiac index at time 12 min compared with patients receiving only placebo (n = 20). Cardiac index of the epinephrine group increased from 2.56 +/- 0.15 to 2.92 +/- 0.22 L.min-1.m-2, whereas in the placebo group it decreased from 2.86 +/- 0.13 to 2.78 +/- 0.12 L.min-1.m-2. Prior administration of calcium did not alter the subsequent response to epinephrine (n = 10) compared with patients receiving epinephrine alone (n = 10). We conclude that cardiac index improves with time without drug therapy after bypass. Calcium chloride increases mean arterial blood pressure but not cardiac index immediately after cardiopulmonary bypass, whereas low-dose epinephrine significantly increases both cardiac index and mean arterial blood pressure without causing tachycardia in these patients. Calcium chloride (5 mg/kg) did not augment or inhibit the hemodynamic response to an epinephrine infusion.