Aprotinin, cardiac surgery, and factor V Leiden.

BACKGROUND: Aprotinin has been shown to reduce blood transfusion in cardiac surgery. Aprotinin inhibits activated protein C (APC). Patients with factor V (FV) Leiden have an inherited resistance to APC proteolysis. If the inhibition of APC by aprotinin contributes to its beneficial effect in cardiac surgery, then patients with FV Leiden undergoing cardiac surgery might be expected to require less transfusion than patients without FV Leiden. However, the use of aprotinin in such patients also could compromise the protein C regulatory pathway and precipitate a clinical thrombotic event. STUDY DESIGN AND METHODS: Patients undergoing cardiac surgery were studied for the presence of the FV Leiden defect by the use of a Russell's viper venom clot-based assay and polymerase chain reaction. The total amount of blood transfused was recorded for each patient. The effect of aprotinin on the plasma of normal and FV Leiden patients was studied. Further studies were performed on the direct inhibition of APC by aprotinin. RESULTS: Over an 18-month period, 162 patients were studied, of whom 13 (8%; 95% CI, 4.3-13.3%) were positive for FV Leiden. These 13 had a smaller requirement for blood transfusion than the to 13 matched controls. In vitro, aprotinin induced a FV Leiden defect in normal plasma and exacerbated the defect in the plasma of FV Leiden patients. Aprotinin inhibited APC in a dose-dependent manner, and kinetic analysis showed competitive inhibition with an inhibition constant of 4.5 microM (250 Kallikrein inhibitor units/mL). CONCLUSION: The inhibition of APC by aprotinin may contribute to its hemostatic effect. The use of aprotinin in patients with FV Leiden could cause extreme dysfunction of the protein C regulatory pathway, which could result in clinical thrombosis.

Pulmonary resection for invasive Aspergillus infections in immunocompromised patients.

Standard antifungal medical therapy of invasive pulmonary aspergillosis that occurs in immunocompromised patients with hematologic diseases with neutropenia or in liver transplant recipients results in less than a 5% survival. In view of these dismal mortality rates, we adopted an aggressive approach with resection of the involved area of lung along with systemic antifungal therapy when localized invasive pulmonary aspergillosis developed in these patients. Between January 1987 and December 1993, 14 patients with hematologic diseases and 2 liver transplant recipients underwent resection of acute localized pulmonary masses suggestive of invasive pulmonary aspergillosis a median of 7.5 days (range 1 to 45 days) after the diagnosis was clinically suggested and confirmed by chest computed tomographic scans. Operative procedures done included two pneumonectomies, one bilobectomy with limited thoracoplasty, nine lobectomies, and five wedge resections (one patient with hematologic disease had two procedures). All patients were treated before and after the operation with antifungal agents. Nine (64%) of 14 patients with hematologic disease and 2 (100%) of 2 liver transplant recipients survived the hospitalization with no evidence of recurrent Aspergillus infection after a median 8 months of follow-up (range 3 to 82 months). The five hospital deaths (all patients with hematologic diseases) occurred a median of 20 days after operation from diffuse alveolar hemorrhage in three, graft-versus-host disease in one, and multiple organ system failure with presumed disseminated Aspergillus infection in one. Four of the five deaths were in patients with allogeneic bone marrow transplants. Two of the three patients requiring resection of multiple foci of infection died, as did the only patient who was preoperatively ventilator dependent. In immunocompromised patients with hematologic diseases or liver transplantation with invasive pulmonary aspergillosis, early pulmonary resection should be strongly considered when the characteristic clinical and radiographic pictures appear.

Techniques to simplify esophagogastric circular stapled anastomoses.

Stapling devices for end-to-end anastomoses (EEA) have facilitated more rapid and reliable reestablishment of esophagogastric continuity following esophageal resections. Despite their ease of use, various intraoperative problems can arise, especially with the esophageal pursestring or the insertion of the anvil into the fragile, commonly contracted lumen. This paper describes various technical details that are useful adjuncts to allow creation of rapid, consistently successful EEA stapled esophagogastric anastomoses. These techniques are of particular value in the resident teaching setting.

Intrapleural fibrinolytic treatment of multiloculated thoracic empyemas.

Acute multiloculated thoracic empyemas incompletely drained by tube thoracostomy alone usually require operation. To avoid a thoracotomy yet treat this difficult problem, intrapleural fibrinolytic agents were employed. Between April 1, 1990, and April 1, 1993, 13 consecutive patients presenting with a fibrinopurulent empyema were demonstrated to have incomplete drainage. To facilitate drainage, streptokinase, 250,000 units in 100 mL 0.9% saline solution (3 patients), or urokinase, 100,000 units in 100 mL 0.9% saline solution (10 patients), was instilled daily into the chest tube, and the tube was clamped for 6 to 12 hours followed by suction. This routine was continued daily for a mean of 6.8 +/- 3.7 days (range, 1 to 14 days) until resolution of the pleural fluid collection was demonstrated by computed chest tomography and clinical indications. This regimen was completely successful in 10 of 13 patients (77%), who had resolution of the empyema, eventual withdrawal of chest tubes, and no recurrence. Two patients, both pediatric liver transplant patients, had an initial good response but eventually required decortication. One patient with a good radiographic response became increasingly febrile during streptokinase therapy and underwent a thoracotomy, but no significant undrained fluid was found. This patient's continued fever was believed to be a streptokinase reaction. Urokinase was used subsequently. No treatment-related mortalities or complications occurred. Intrapleural fibrinolytic agents, especially urokinase, are safe, cost-effective means of facilitating complete chest tube drainage, thereby avoiding the morbidity of a major thoracotomy for 77% of a group of multiloculated empyema patients who traditionally would have required open surgical therapy.

Valve replacement in the right side of the heart in children: long-term follow-up.

Twenty-five patients (16 male, 9 female) underwent right-sided valve replacement (10 pulmonary valve replacement, 14 tricuspid valve replacement, 3 tricuspid plus pulmonary valve replacement, and 2 replacements of a single atrioventricular valve) at the University of Nebraska Medical Center from June 1977 to December 1986. Twenty-one patients (84%) are long-term survivors with 2,035 months follow-up (range, 41 to 143 months; mean, 96.9 months). Twenty-three Carpentier-Edwards bioprosthetic valves, one Ionescu-Shiley bioprosthetic valve, and nine St. Jude Medical valves were inserted. Follow-up of 17 patients with a Carpentier-Edwards valve ranged from 5 years 9 months to 11 years 9 months (mean, 8 years 11 months). To date there has been one reoperation after 3 years 4 months in this group. One patient who received an Ionescu-Shiley bioprosthesis required re-replacement at 20 months after operation. Three of 4 patients who received St. Jude mechanical valves and are long-term survivors have required replacement after 36 to 56 months. We conclude that the Carpentier-Edwards bioprosthetic valve is a viable option in the right side of the heart in the young age group when annular size is adequate to accommodate an appropriate bioprosthesis.

Dissecting intramyocardial hematoma masquerading as a pseudoaneurysm of the left ventricle.

This report presents a case of left ventricular intramyocardial dissection masquerading as a ventricular pseudoaneurysm, as documented by echocardiography, magnetic resonance imaging, and angiography with subsequent confirmation at operation.

Classic versus modified Blalock-Taussig shunts in neonates and infants.

Between July 1979 and October 1984, 61 systemic-pulmonary arterial shunts were created in 45 patients. Clinical and angiographic results with 23 classic Blalock-Taussig shunts (BTSs) and 35 modified Blalock-Taussig shunts (MBTSs) with polytetrafluoroethylene grafts between the subclavian and pulmonary arteries were compared. Forty-three of the patients studied were infants: 28 were less than 1 month old, and 19 were less than 1 week old. Weights were 1.1 to 19 kg (mean 2.9 kg). Diagnoses were complex tetralogy of Fallot (18 patients), transposition of the great arteries with small left ventricle or left ventricular outflow tract obstruction (six patients) pulmonary atresia (seven patients) with intact ventricular septum (three) and ventricular septal defect (four), tricuspid atresia (four patients), univentricular heart (six patients), atrioventricular septal defect (canal) with pulmonary stenosis (three patients), and double-outlet right ventricle (one patient). Comparison groups were concurrent and were equivalent for age, weight, and complexity of anomaly. Patients were removed from the study population at the time of subsequent open heart surgery or at death. All patients were followed for a minimum of 6 months and for up to 5 1/2 years (BTS 1 1/2 to 5 1/2 years, mean 33 months; MBTS 6 months to 3 years, mean 20 months). There were no intraoperative deaths in either group. Among the 23 BTSs, three failed at 1, 3, and 19 days, resulting in two deaths (17%). One premature infant died despite a second shunt, one died during attempted intracardiac repair at 13 days of age, and the other was well after revision of the shunt. Eight patients underwent subsequent intracardiac repair 1 to 5 years (mean 34 months) after the initial procedure. Another four patients died from complex intracardiac anomalies with patent shunts. Three patients are alive 2 to 4 years after receiving shunts and have not undergone subsequent surgery. Late postoperative angiograms demonstrate a disturbing incidence (21%) of stenosis and right pulmonary arterial deformity despite satisfactory immediate postoperative studies and good clinical function. Eight patients required a second shunt, two for anatomic discontinuity of the pulmonary arteries and six because of inadequate blood flow through the first shunt. Among the 35 patients receiving the MBTS, two required early revision (technical error and ductal tissue at the anastomosis). There were no shunt-related deaths, but three (6%) occurred within 30 days of operation from left ventricular infarct, cerebral hemorrhage, sepsis, and severe aortic stenosis with arrhythmias.(ABSTRACT TRUNCATED AT 400 WORDS)

Management of penetrating cardiac injuries: the role of emergency room thoracotomy.

Sixty-four consecutive patients with penetrating cardiac injuries were treated between January, 1977, and January, 1983, at the University of Maryland Hospital. Twenty-eight patients had major associated injuries of other organs. The patients were divided into groups according to their clinical status on arrival. An aggressive approach was utilized including early emergency room (ER) thoracotomy for "lifeless" or deteriorating patients. Three patients required immediate cardiopulmonary bypass for repair of their injuries. Twenty-one (57%) of the 37 patients undergoing ER thoracotomy survived; most of the deaths occurred in patients arriving "lifeless" from gunshot wounds. Twenty-four (89%) of the 27 patients who were in stable enough condition to undergo initial repair in the operating room (OR) survived. Overall survival was 45 patients (70%). Though superficial wound infections developed in 18 patients, there were no deep or systemic infections. None of the survivors sustained severe neurological sequelae. Five patients underwent late reoperations for closure of a ventricular septal defect (2), mitral valve replacement (1), and pericardiectomy (2) with no deaths. Though repair of penetrating cardiac injuries should preferably be carried out in the OR, immediate thoracotomy for "lifeless" or deteriorating patients can be performed in the ER with a low incidence of direct surgical complications and with high patient survival.

Pharmacologic inhibition of scar contracture of intracardiac prosthetic patches.

Significant fibrosis and contracture often cause complications of pericardial and Dacron grafts within the heart. Both continue to be utilized because more suitable materials are unavailable. Newer prosthetic materials and the administration of drugs that might minimize intracardiac fibrosis and contracture after implantation were studied. Measured patches of three prosthetic materials were implanted into the right atrium of 18 dogs: 6 with expanded polytetrafluoroethylene (PTFE or Gore-Tex--W. L. Gore & Associates, Elkton, Md.), 6 with glutaraldehyde-preserved bovine pericardium, and 6 with Dacron patches. The animals were sacrificed after 8 weeks and gross and microscopic pathologic examinations were performed. The patch materials did not intrinsically shrink but all demonstrated marked distortion from the growth of surrounding scar tissue. In a fourth group of eight dogs with intraatrial Dacron patches, four were treated for 8 weeks with oral 3-aminopropionitrile fumarate, and four were not treated. A blinded observed evaluated the adhesions on a scale of 0 = no adhesions or patch distortion, to 4 = dense adhesions with marked distortion of the patches. The untreated dogs had dense adhesions of the lung and pericardium and the patches were encased in scar tissue with marked distortion. The average score was 3.5. The treated dogs had only minimal pleural adhesions and only a thin neointimal covering of the patch with virtually no distortion. The average score was 1.0 (P = 0.0032). The tensile strength of the healed atriotomies was evaluated with stress testing. The intact atrial wall ruptured at a force of 2.60 +/- 0.37 kg/m/sec2, the untreated atriotomy wound at 2.38 +/- 0.18 kg/m/sec2, and the treated atriotomy wound at 2.60 +/- 0.17 kg/m/sec2. There was no statistically significant difference among these groups. No other side effects of the 3-aminopropionitrile fumarate were noted, with only a single superficial wound infection caused by early postoperative trauma. Pharmacologic inhibition of scar formation minimized distortion and contracture of intracardiac prosthetic patches and decreased adhesions. Though further experimental evaluations are necessary, prolonged low-dose oral administration of beta-aminoproprionitrile (BAPN) may be beneficial in preventing complications of prosthetic implants and reoperative cardiac surgery in children.

Subclavian flap repair of coarctation of the aorta in neonates. Realization of growth potential?

The subclavian flap repair for coarctation of the aorta allows potential for growth by utilizing autogenous tissue. Although well documented in young children, its promise in the tiny neonate warrants further evaluation. Since August, 1979, 29 patients, including 24 infants, have undergone subclavian flap repair at the University of Maryland Hospital. Weights ranged from 1.4 to 5 kg (mean 3.2 kg). All patients less than 6 months old had associated intracardiac defects and were in severe congestive failure. Fifteen responded to preoperative prostaglandin infusions. The overall early mortality was 14%; among the neonates it was 21%; and among those operated upon within the first week of life, 33%. There was one intraoperative death among the eight patients who underwent simultaneous pulmonary artery banding. There were no deaths among patients older than 5 days at operation. Four of the five neonates who died had some variant of hypoplastic left heart syndrome, with severe stenosis or atresia of the systemic atrioventricular valve, critical aortic stenosis, or hypoplastic left ventricle. Twenty-two survivors continue to do well up to 3.7 years postoperatively (mean follow-up 26 months). At follow-up all patients are normotensive with brisk lower extremity pulses. Patients now weigh 1.3 to 6.9 (mean 2.3) times their operative weight, and only one patient has a measured arm-to-leg gradient greater than 10 mm Hg (mean gradient 3.7 mm Hg). Seven of the neonates have undergone repeat catheterization, and all had satisfactory growth of the subclavian flap segment of repair and no gradient. Two older patients (3 and 4 years old at operation) have undergone exercise testing 3.7 years after repair, with peak exercise gradients of only 7 and 15 mm Hg. We therefore continue to utilize this technique for the treatment of coarctation even in tiny neonates.