Pharmacokinetics of epsilon-aminocaproic acid in patients undergoing aortocoronary bypass surgery.

BACKGROUND: Epsilon-aminocaproic acid (EACA) is commonly infused during cardiac surgery using empiric dosing schemes. The authors developed a pharmacokinetic model for EACA elimination in surgical patients, tested whether adjustments for cardiopulmonary bypass (CPB) would improve the model, and then used the model to develop an EACA dosing schedule that would yield nearly constant EACA blood concentrations. METHODS: Consenting patients undergoing elective coronary artery surgery received one of two loading doses of EACA, 30 mg/kg (group I, n = 7) or 100 mg/kg (group II, n = 6) after CPB, or (group III) a 100 mg/kg loading dose before CPB and a 10 mg x kg(-1) x h(-1) maintenance infusion continued for 4 h during and after CPB (n = 7). Two patients with renal failure received EACA in the manner of group III. Blood concentrations of EACA, measured by high-performance liquid chromatography, were subjected to mixed-effects pharmacokinetic modeling. RESULTS: The EACA concentration data were best fit by a model with two compartments and corrections for CPB. The elimination rate constant k10 fell from 0.011 before CPB to 0.0006 during CPB, returning to 0.011 after CPB. V1 increased 3.8 l with CPB and remained at that value thereafter. Cl1 varied from 0.08 l/min before CPB to 0.007 l/min during CPB and 0.13 l/min after CPB. Cl2 increased from 0.09 l/min before CPB to 0.14 l/min during and after CPB. Two patients with renal failure demonstrated markedly reduced clearance. Using their model, the authors predict that an EACA loading infusion of 50 mg/kg given over 20 min and a maintenance infusion of 25 mg x kg(-1) x h(-1) would maintain a nearly constant target concentration of 260 microg/ml. CONCLUSIONS: EACA clearance declines and volume of distribution increases during CPB. The authors' model predicts that more stable perioperative EACA concentrations would be obtained with a smaller loading dose (50 mg/kg given over 20 min) and a more rapid maintenance infusion (25 mg x kg(-1) x h(-1)) than are typically employed.

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.

Case report. Aortic pseudoaneurysm with aortobronchial fistula: diagnosis with CT angiography.

We report the case of an 82-year-old man with a 12-month history of recurrent hemoptysis caused by an aortobronchial fistula. Twenty-five years earlier, the patient underwent placement of an aortic graft for aortic transection sustained in a motor vehicle accident. Chest radiography and bronchoscopy showed nonspecific abnormalities. We emphasize the role of CT angiography with 2D and 3D reconstructions for the diagnosis of and surgical planning for this rare but potentially lethal aortic postoperative complication.

Mediastinal staging of non-small-cell lung cancer with positron emission tomography.

To determine the usefulness of positron emission tomography with fluoro-2-deoxyglucose (PET-FDG) in assessing mediastinal disease in patients with non-small-cell lung cancer (NSCLC) and to compare its yield to that of computed tomography (CT), we performed a prospective consecutive sample investigation in a university hospital and its related clinics. In 30 patients with NSCLC with clinical stage I (T1-2, NO, MO) disease, we compared the results of chest CT and PET-FDG with the findings at surgical exploration of the mediastinum. Seven (77%) of nine patients with surgically proven mediastinal metastasis were identified by the PET-FDG results, with four false-positives in 21 patients with negative lymph node dissections (p = 0.004). Using the results of pathologic examination of mediastinal lymph nodes as the criterion standard, the diagnostic sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) for PET-FDG imaging of mediastinal metastases were 78%, 81%, 80%, 64%, and 89%, respectively. The sensitivity, specificity, accuracy, PPV, and NPV for chest CT in the detection of mediastinal metastasis were 56%, 86%, 77%, 63%, and 87%, respectively. CT and PET-FDG results agreed in 21 patients. The diagnostic accuracy of the combined imaging modalities was 90%. We concluded that mediastinal uptake of FDG correlates with the extent of mediastinal involvement of NSCLC and may contribute to preoperative staging. PET-FDG imaging complements chest CT in the noninvasive evaluation of NSCLC, and strategies for its use merit further investigation.

Predictive value of blood clotting tests in cardiac surgical patients.

This study prospectively evaluated numerous tests of clotting function in 897 consecutive adult cardiac surgical patients over 18 months. This included coronary operation, valve replacement, and reoperative patients. The tests included activated clotting time, activated partial thromboplastin time, prothrombin time, thrombin time, fibrinogen, fibrin/fibrinogen degradation products, platelet count, and Duke's earlobe bleeding time. Other variables such as age, sex, and cardiopulmonary bypass duration were included in the multivariate analysis. Statistically significant correlations were found between 16-hour mediastinal drainage and activated partial thromboplastin time, fibrinogen, activated clotting time, fibrin/fibrinogen degradation products, platelet count, and prothrombin time. Scatter plots indicate that these relationships, although statistically significant, had little predictive value and were largely significant as a result of the large number of patients in each group, which permitted weak correlations to reach statistical significance. The best multivariate model constructed could explain only 12% of the observed variation in postoperative blood loss. Because the predictive values of the tests are so low, it does not appear sensible to screen patients routinely using these clotting tests shortly after cardiopulmonary bypass.

Thoracic complications of dental surgical procedures: hazards of the dental drill.

CASE REPORTS: Dental surgical procedures occasionally result in intrathoracic complications that may subsequently be encountered by clinicians. We report four patients with such complications, including pneumomediastinum, fatal descending necrotizing mediastinitis, and Lemierre's syndrome. In each of these patients, the commonly used dental handpiece with exhausted air directed to the working drill point was an important, but unrecognized, predisposition to their intrathoracic complication. CONCLUSION: Clinicians should be aware of the spectrum of these problems and, in particular, of the potential hazards of pressurized nonsterile air blown into open surgical sites by the dental drill.

Regional cerebrovascular reactivity to carbon dioxide during cardiopulmonary bypass in patients with cerebrovascular disease.

In patients with cerebrovascular disease, hypercarbia may cause redistribution of regional cerebral blood flow from marginally perfused to well-perfused regions (intracerebral steal), as evidenced by regional cerebral blood flow studies during carotid endarterectomy. During hypothermic cardiopulmonary bypass, the pH-stat method of acid-base management produces relative hypercarbia. To determine whether pH-stat management produces relative hypercarbia. To determine whether pH-stat management induces intracerebral steals, we investigated nine patients with cerebrovascular disease undergoing coronary artery bypass grafting. During hypothermic cardiopulmonary bypass, arterial carbon dioxide tension was varied in random order between 40 mm Hg and 60 mm Hg (uncorrected for body temperature). Regional cerebral blood flow was measured by clearance of 133 xenon injected into the arterial inflow cannula. Nasopharyngeal temperature (26.8 degrees-28.0 degrees +/- 2.2 degrees-3.0 degrees C), perfusion flow rate (2.14-2.18 +/- 0.70-0.73 L/min/m2), mean arterial pressure (67-68 +/- 6-9 mm Hg), arterial carbon dioxide tension (302-308 +/- 109-113 mm Hg), and hematocrit (23% +/- 4%) were maintained within narrow limits in each patient during arterial carbon dioxide tension manipulation. Global mean cerebral blood flow values were similar to previously reported values in patients free of cerebrovascular disease; patients in this study averaged 15.2 +/- 2.5 ml/100 gm/min at an arterial carbon dioxide tension of 46.1 +/- 8.4 mm Hg and 25.3 +/- 6.1 ml/100 gm/min at an arterial carbon dioxide tension of 71.1 +/- 11.8 mm Hg. Carbon dioxide reactivity, defined as mean global cerebral blood flow (in ml/100 gm/min) divided by arterial carbon dioxide tension (in mm Hg), was similar in the region having the lowest regional cerebral blood flow and in the brain as a whole. No patient developed evidence of an intracerebral steal at the higher arterial carbon dioxide tension. During hypothermic cardiopulmonary bypass, higher levels of arterial carbon dioxide tension, such as those associated with the pH-stat management technique, are apparently not associated with potentially harmful redistribution of cerebral blood flow in patients with cerebrovascular disease.

Systolic pressure measurement in the ascending aorta: augmentation at the aortic cannula sideport.

To assess whether arterial blood pressure measured at the sideport of the aortic cannula mirrors that measured within the ascending aorta, the two pressures were compared in 10 consecutive patients undergoing cardiopulmonary bypass. The mean arterial pressures (MAP) were equal both before and after bypass, but the sideport systolic arterial pressure (SAP) was 6.0 +/- 0.8 mm Hg higher than the aortic SAP before bypass and 9.1 +/- 0.5 mm Hg higher than the aortic SAP after bypass (P less than 0.001). Hematocrit, blood temperature, cardiac output, and heart rate did not correlate with the differences in SAP, suggesting that the higher SAP seen at the sideport was generated within the tube connecting the oxygenator to the aorta. This theory was investigated by decreasing the tube length distal to the sideport in three patients in this group who had sideport SAPs higher than their aortic SAPs, a measure that decreased the SAP difference between the two sites. At the end of cardiopulmonary bypass in 20 other consecutive patients, the effect of shortening the aorta-oxygenator tube from 1.8 to 0.25 m was tested. The SAP in the sideport decreased by 4 to 12 mm Hg in 12 of the 20 patients, while the MAP was unaffected by this maneuver. It is concluded that the MAP measured at the sideport of the aortic cannula closely reflects the MAP in the ascending aorta, whereas the SAP measured at the sideport does not reflect the aortic SAP. Thus, when aortic pressure is measured at the sideport to confirm an artificially low radial arterial pressure, systolic amplification at the sideport might simulate or exaggerate radial artery hypotension.

Subxiphoid pericardial window for pericardial effusive disease.

A subxiphoid pericardial window made in 123 patients allowed drainage and diagnosis of pericardial effusions. In 40 patients with malignancy and effusions, median drainage was 450 ml; cytology was positive in 17 or 36 (47%), and pericardial biopsy showed cancer in 13 (43%) of 30 patients. In 11 patients with malignancy, both cytology of effusions and biopsy of the pericardium were negative. In 83 patients with benign effusions, median drainage was 400 ml. Effusions recurred in 14 of the 123 patients (11%); nine patients in the benign group and five in the malignant group. Five of these 14 underwent thoracotomy (3 to 542 days postoperatively); two underwent median sternotomy and one underwent pericardiocentesis. Two intraoperative deaths resulted from cardiac arrest. Mortality at 30 days was 25% (10/40 patients) in the malignant group and 11% (9/83 patients) in the benign group. No deaths resulted from recurrent effusions. The establishment of a subxiphoid pericardial window allows rapid and safe drainage of pericardial effusions with sampling for cytology and pericardial biopsy. It has minimal morbidity and few recurrent effusions.

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)

Current treatment of traumatic aortic disruptions.

Eighteen patients with traumatic disruptions of the descending thoracic aorta were treated at the Wake Forest University Medical Center from 1979 through 1986. Their preoperative evaluation and operative management are presented, with emphasis being placed on methods for preventing complications related specifically to aortic cross-clamping. Two patients died, for an operative mortality of 11 per cent. One of the two patients had exsanguinating hemorrhage with profound shock on the way to the operating room; in the second patient, the aorta was occluded just beyond the disruption, and there had been no distal perfusion for several hours before operation. Four patients (22%), three of whom had not had a shunting procedure, had major neurologic complications relating to the spinal cord. Thus, shunting procedures during repair of descending aortic disruption appear to offer some protection from neurologic deficits.

Coronary revascularization in patients with bilateral internal carotid occlusions.

Coronary revascularization that is neurologically uneventful in patients with bilateral totally occluded internal carotid arteries has not been previously reported. We performed saphenous vein coronary artery bypass grafting on three such patients and observed them for 6 to 23 months. Preoperatively two of our patients had chronic stable symptoms of cerebrovascular insufficiency, and one had received cerebral revascularization via a superficial temporal-to-middle cerebral artery bypass. Controversy exists regarding proper cerebral protective maneuvers during coronary revascularization for patients with advanced cerebrovascular disease. Cerebral protection for our patients during cardiopulmonary bypass included hypothermia and high perfusion flows and pressures. Two patients also received prophylactic sodium thiopental. None of these three patients had a stroke perioperatively or during the follow-up period. We believe that these case histories strongly suggest that the functional state of the cerebral collateral circulation, as judged by preoperative neurological symptoms, predicts neurological outcome after coronary revascularization better than the specific occlusive anatomy of the extracranial carotid arteries.

Open mitral commissurotomy: long-term results with echocardiographic correlation.

Over 11 years, 91 patients with isolated mitral stenosis underwent open mitral commissurotomy. Twenty-nine were 50 or more years old; 15 had had prior commissurotomies. Four (4.4%) died perioperatively; 87 were followed for one to nine years (average: five years). Overall actuarial survival was 94% at 5 years. Sixty-nine patients (79%) were NYHA Functional Class (FC) I or II at latest follow-up. Arterial embolism occurred in five patients; 14 patients (16%) had a second valve operation. Patients who remain in FC I or II and who are free of embolism and reoperation are classified as complication-free. Actuarial analysis demonstrated 76% to be so classified at five years after operation. Actuarial curves show that age older than 40 years, sex, previous commissurotomy, and "radical" versus simple open mitral commissurotomy did not influence survival or the incidence of good results. Follow-up M-mode and 2D echocardiograms were obtained in 42 patients. The estimated mitral orifice accurately separated FC I patients (orifice equal to or larger than 2 cm2) from FC II and FC III patients (orifice smaller than 2 cm2), and showed that echocardiographic evidence of a 2 cm2 or larger mitral orifice correlates with a good result.

Bilateral brachial paralysis from watershed infarction after coronary artery bypass. A report of two cases and review of the predisposing anatomic and physiological mechanisms.

Bilateral brachial paralysis and bilateral visual field defects developed after coronary artery bypass in two patients. These deficits, caused by cerebral watershed infarctions, probably resulted from global cerebral hypoperfusion during cardiopulmonary bypass, although bypass had been maintained with high perfusion flows (2.0 to 3.0 L/min/m2) and perfusion pressures from 50 to 90 mm Hg. No systemic hypoperfusion or hypotension occurred before or after cardiopulmonary bypass. Cerebral watershed infarctions occur predominantly in the boundary zones between the anterior, middle, and posterior cerebral arteries. In previous reports, watershed infarctions most often occurred as preterminal events in patients after sustained episodes of obvious hypoperfusion. The occurrence of such major neurological deficits in two patients without systemic hypoperfusion suggests that traditionally accepted flows and perfusion pressures do not assure adequate cerebral blood flow during cardiopulmonary bypass.

Computed tomography for evaluation of mediastinal lymph nodes in lung cancer: correlation with surgical staging.

Computed tomography (CT) of the chest (late model) was done preoperatively in 56 candidates for resection of lung cancer. Precise borders for each node region were defined by the American Thoracic Society modification of the classification of the American Joint Committee for Cancer Staging and were used to "map" nodes seen on CT and nodes removed surgically. Metastatic involvement of mediastinal nodes was proven by mediastinoscopy in 11 patients; nodes were removed from multiple regions at thoracotomy in 45 patients. The mediastinum was clearly delineated by CT in 46 patients with determinate scans and was judged normal in 32 (CT-negative scans) and abnormal in 14 (CT-positive scans). A node was considered metastatically involved if it measured greater than 1.5 cm in diameter. Positive nodes were found at surgical staging in 3 of 32 patients with CT-negative scans and in all patients with CT-positive scans. Thus, for the 46 patients with determinate scans, sensitivity was 82%, specificity was 100%, and accuracy (true positive and true negative) was 93%. The high accuracy of CT in these patients suggests that mediastinoscopy is not necessary before thoracotomy in the patient with a CT-negative scan, but that for the patient with a CT-positive or CT-indeterminate scan, the indications for mediastinoscopy remain the same.

A prospective study of sternal wound complications.

Eight hundred seventy patients were enrolled in a prospective study to identify risk factors for sternal wound complications following open-heart operations. The 0.8% incidence of major sternal complications was similar to that reported in the literature by other centers. The effects of age, sex, weight, operative time, type of procedure, resident versus attending surgeon, prolonged ventilatory support, reoperation for bleeding, external cardiac massage, and Dacron versus wire suture for sternal closure were assessed by stepwise logistic regression. Prolonged ventilation and female sex both strongly increased the risk of major sternal complications. Age and weight exerted lesser, but statistically significant, effects on the incidence of such complications. None of the other factors was associated with an increased risk of major sternal complications.

Tumors of the heart: surgical considerations.

A series of 23 cardiac tumors is reported. Six were diagnosed at autopsy; 17 tumors were surgically explored. Eleven of the 17 were myxomas within the left atrium. Eight of the 17 patients presented with congestive heart failure; peripheral and cerebral emboli were also common. The diagnosis was made preoperatively in 10 patients. Two-dimensional echocardiography was the most reliable diagnostic tool. Follow-up averages 55 months; there have been no late deaths or recurrences. The other six surgically treated tumors were: a left ventricular rhabdomyoma, a septal lipoma, a right atrial calcified endocardial mass, a right ventricular fibrosarcoma, a rhabdomyosarcoma, and a sarcoma metastatic to the pericardium and right atrium. From this series and a review of the literature, we concluded that: benign cardiac tumors can usually be excised with a low morbidity and excellent long-term results; malignant cardiac tumors have a dismal prognosis, and operation is primarily diagnostic; tumors metastatic to the heart should be operated upon only if successful palliation seems possible.

Digoxin and propranolol in the prophylaxis of dysrhythmias after coronary artery bypass grafting.

Serious tachydysrhythmias occur in 10% to 30% of patients early after coronary artery bypass grafting (CABG). We studied the effects of digoxin and propranolol in preventing these dysrhythmias over the first week after CABG (average number of grafts, 2.7/patient). Consecutive patients (n = 179) undergoing CABG were randomized to a drug (group 1) or a control (group 2) group. Excluded were patients given digoxin before CABG and those with ejection fractions of less than 40%, those with dysrhythmias within 18 hr after CABG, those being pacer dependent, and those with low-output syndrome after CABG. Risk factors were comparable in both groups. Electrocardiographic examination showed perioperative myocardial infarction in five patients (2.8%). Digoxin (1 mg iv given over 24 hr, then 0.25 mg/day) and propranolol (10 mg given every 6 hr) were started 6 hr after CABG. Supraventricular dysrhythmias requiring treatment occurred in 3.4% of 89 group 1 patients and in 30% of 90 group 2 patients (p less than .001); ventricular dysrhythmias occurred in 1.1% of group 1 and 8.9% of group 2 patients (p less than .01). In this study, a regimen of post-CABG digoxin and propranolol significantly reduced the incidence of supraventricular and ventricular dysrhythmias without causing adverse reactions.