Pharmacokinetics of 5-fluorouracil during hyperthermic pelvic isolation-perfusion.

The pharmacokinetics of 5-fluorouracil (5-FU) injected into a surgically isolated pelvic circuit during hyperthermic perfusion was studied in five patients with local recurrence of anorectal cancer. 5-FU doses ranged from 11 to 23 mg/kg. The geometric mean ratio of peak plasma 5-FU in the isolated to systemic circuits was 10, the ratio at the end of the 45-minute perfusion was 12.5. The mean half-life of 5-FU in the isolated circuit was 18.5 minutes. Total drug exposure for the isolated circuit was 7.8-fold greater than for the systemic compartment. These results demonstrate a large pharmacologic advantage for the use of the isolation-perfusion technique.

Correlations of Tc-99m pyrophosphate myocardial scintigraphy and the results of coronary-artery bypass surgery.

This study indicates that abnormal myocardial scintigrams with Tc-99m pyrophosphate tend to improve after coronary-artery bypass surgery, frequently changing from positive to normal. The significance of this change is uncertain. It does not correlate well with the clinical state but may simply reflect the natural course of myocardial scintigraphy in response to hospitalization, medical management, and presumably improved myocardial oxygenation. Postoperative myocardial scintigrams are useful in detecting perioperative infarction. ECG interpretation may be difficult in the immediate postoperative period and, in three cases, there were scintigraphic criteria of perioperative infarction without diagnostic changes on ECG. Patients with positive preoperative scintigrams, especially in association with Functional Class IV angina, are at increased risk during coronary-artery bypass surgery.

Erythrocyte survival following extracorporeal circulation. A question of membrane versus bubble oxygenator.

Five groups of seven dogs were studied. Each animal had 250 ml of blood withdrawn and tagged with Cr51. Group I (control) samples were combined with 500 ml of lactated Ringer's solution and reinfused into the respective animals after 3 hours of incubation at 37 degrees C. Group II samples were pumped in a closed-circuit bubble oxygenator with 500 ml of lactated Ringer's prime for 2 hours before reinfusion into the animals. Group III samples were pumped in a bubble oxygenator for 3 hours before reinfusion. Group IV samples were pumped in a closed-circuit membrane oxygenator for 2 hours, and Group V samples were pumped in a membrane circuit for 3 hours. All extracorporeal pump runs were performed at 37 degrees C. Blood samples were drawn from the dogs at regular intervals after bypass for 30 days. Erythrocyte survival was determined by Cr51 activity recorded by a gamma counter. The red cell half-life was determined for each dog. The control half-life was 24.1 +/- 2.03 days; Group II, 19.88 +/- 1.69 (p < 0.05); Group III, 9.63 +/- 1.4 (p < 0.001); Group IV, 19.4 +/- 1.65 (p < 0.05); and Group V, 9.13 +/- 1.45 (p < 0.001). These data indicate that serious red cell injury does occur with extracorporeal circulation but that the injury is a function of pump time, rather than of the type of oxygenator.

Preservation of myocardial ultrastructure.

This study compares the effects of 2 hour periods of normothermic anoxic arrest, continuous normothermic coronary perfusion, continuous cold coronary perfusion, and topical cooling of the ischemic myocardium on survival and ultramicroscopic structure of the canine myocardium. No animal survived 2 hours of normothermic anoxic arrest. Severe ultrastructural damage was observed in the nuclei, mitochondria, and myofibrils. Topical cooling of the ischemic myocardium to 15 degrees C. markedly improved survival and preservation of the myocardial fine structure. Continuous perfusion of the coronary arteries with cold blood resulted in 100 per cent survival through the experimental period, with preservation of the normal myocardial ultrastructure. The technique of cold coronary perfusion should be particularly useful in cardiac surgical patients in whom maximal preservation of myocardial function is essential for survival.

The problem of dizziness and syncope in old age: transient ischemic attacks versus hypersensitive carotid sinus reflex.

In the elderly, a transient ischemic attack (TIA) and a hypersensitive carotid sinus reflex (HCSR) often co-exist and can pose a diagnostic challenge. Seven cases are presented. HCSR is a relative condition; besides increased irritability of the receptor or target organs, susceptibility of the nerve center to ischemia probably is induced by a slow heart rate or low blood pressure in any patient with pre-existing occlusive cerebrovascular disease. Dizziness and syncope of this type represent hemodynamic TIA in contrast to thromboembolic TIA. The carotid sinus massage test is recommended for differentiating the two types of TIA; the treatments differ. At present there is no uniform management that can be applied to either TIA or HCSR routinely. Therefore, treatment should be approached on an individual basis, keeping in mind the different pathophysiologic factors operating in the specific patient.

Peripheral embolism resulting from unsuspected atheromatous aortic plaques.

Three cases of peripheral embolism resulting from atheromatous aortic plaques are reported. Although the majority of arterial thromboemboli are believed to have originated from mural thrombi within one of the cardiac chambers, there is reason to believe that embolism from atheromatous material within a major artery may occur more often than is represented in current literature. Successful management of this condition will necessitate (1) clinical awareness, (2) careful scrutinization of material recovered from embolectomy, (3) angiography to demonstrate the embolic source in the aorta or its main braches, and (4) appropriate remedy by either endarterectomy or graft replacement of the diseased artery segment. The pitfalls in the diagnosis of this condition are discussed.

Operative risk factors associated with unstable angina pectoris.

We performed a prospective study in 207 patients with unstable angina pectoris (UA) to identify factors associated with operative mortality (OM) and perioperative myocardial infarction (MI) from myocardial revascularization. The OM was 3.9% (8/207) and the incidence of MI was 11% (23/207). Clinical variables (age, prior MI, electrocardiographic evidence, symptoms, left ventricular function) and operative variables (incomplete revascularization, cardiopulmonary bypass time, cross-clamp time) did not correlate with OM or MI. Operative mortality was associated with critical triple-vessel disease, but not left main coronary artery disease, and accounted for seven of the eight deaths (P less than .01). Myocardial infarction was associated with elective surgery (22/167) as opposed to urgent surgery (1/40) (P less than .01). Therefore, patients with critical triple-vessel disease are the highest risk group for OM, and urgent operation seems to reduce the incidence of MI in patients with UA.

Three-year outcome of endovascular treatment of superficial femoral artery occlusion.

HYPOTHESIS: Patency after primary percutaneous transluminal angioplasty (PTA) and stenting of superficial femoral artery (SFA) occlusions is better than historical experience with PTA alone. DESIGN: Consecutive case series of primary PTA with stenting, and follow-up with duplex imaging every 6 months (mean +/- SD follow-up, 32 +/- 15 months). SETTING: Veterans Affairs medical center. PATIENTS AND METHODS: Patients were 57 previously untreated men with 71 limbs having chronic atherosclerotic SFA occlusion with suprageniculate reconstitution and patent tibial runoff. Critical ischemia (Society for Vascular Surgery [SVS] category, 4-6) was present in 7 (10%), the remainder had intermittent claudication only (SVS, 1-3). INTERVENTIONS: Guidewire recanalization followed by PTA, Wallstent deployment, and adjunctive thrombolysis as necessary; 19 limbs (27%) required thrombolysis to manage periprocedural thrombosis. MAIN OUTCOME MEASURES: Cumulative patency, limb salvage, and complications. RESULTS: Length (mean +/- SD) of occlusion was 14.4 +/- 9.9 cm. Length of stented artery was 24.3 +/- 11.1 cm. Ankle brachial index increased from 0.59 +/- 0.14 to 0.86 +/- 0.16 (P<.001) after stenting. One- and 3-year patencies were as follows: primary, 54.6% +/- 6.3% and 29.9% +/- 6.6%; assisted primary, 72.3% +/- 5.6% and 59.0% +/- 6.8%; and secondary, 81.6% +/- 4.8% and 68.3% +/- 6.5%. Three-year secondary patency when periprocedural thrombolysis was required was 35.7% +/- 12.5% compared with 70.6% +/- 7.4% for limbs not requiring periprocedural thrombolysis (P=.02); the differences in occlusion length and severity of ischemia were not significant between these 2 groups. Limbs undergoing adjunctive PTA during angiography 6 to 12 months after initial stenting had 63.0% +/- 13.3% patency at 3 years compared with 100% patency in limbs not requiring PTA at 6 to 12 months angiography (P=.046). Periprocedural mortality and morbidity were 2.8% and 15.5%, respectively. Three of the 7 limbs with critical ischemia underwent amputation during follow-up compared with 2 (3%) of 64 limbs with functional ischemia (chi(2) test, P<.006). A mean of 1.8 endovascular interventions per limb were performed. CONCLUSIONS: Percutaneous transluminal angioplasty and stenting yielded higher patency rates than historical controls undergoing PTA alone. When periprocedural thrombolysis is required, subsequent patency appears to be significantly worse. Poor results after PTA and stenting of limbs with critical ischemia and the need for additional endovascular therapy limit the technique's utility.

Computer-derived equations for predicting survival postoperatively. Their usefulness and limitations.

We used multivariate analysis to determine whether survival following perforations of the gastrointestinal tract could be accurately predicted from preoperative data. Of 12 variables tested, four were found to have predictive value. These were age, pulmonary disease, preoperative shock, and the attending surgeon. When these four variables were employed in a logistic regression equation on 42 patients, it correctly predicted which 21 patients died before leaving the hospital. To produce an equation useful for other hospitals, we recalculated it without the attending surgeon variable. Again, the equation was used to predict survival. The correlation of predicted vs observed outcome remained high, and, using a 2 x 2 chi 2 test, the correlation was significant. We then cross validated the three-variable model on data from a second hospital. The model accurately predicted the new data equally well. We believe that predictive models can identify risk factors in a variety of patient populations and can determine who is likely to benefit from specific treatment modalities.

Fatal complications of tracheotomy.

Thirty-six of 403 deaths after tracheotomy were direct complications of that procedure. Arterial hemorrhage caused three deaths, venous bleeding, seven. Airway obstruction resulted in six fatalities. Tracheoesophageal fistula caused five deaths. Eight deaths were due to infection and sepsis. Tension pneumothorax developed in one patient and the remaining six deaths were due to cardiopulmonary collapse. Many of the complications of tracheotomy can be avoided with accurate knowledge of anatomic variations, ideal operating conditions, proper technic, careful arterial and venous hemostasis, routine postoperative chest x-ray films, sterile suction technic, proper use of soft cuffed tracheotomy tubes, adequate humidification, and careful postoperative blood gas monitoring.

Changes in internal carotid blood flow after carotid endarterectomy correlate with preoperative stenosis.

BACKGROUND: The relationship between preoperative stenosis and the effect of carotid endarterectomy (CEA) upon internal carotid blood flow (ICF) is not well understood. With the intention of better characterizing this, we compared intraoperative measurements of internal carotid blood with the maximum single diameter stenosis found in preoperative angiograms. METHODS: Fifty-two patients undergoing 64 carotid endarterectomies (12 bilateral) had transit-time ultrasound perivascular probes used to measure ICF before and after CEA, and the percent change in ICF (% delta ICF) achieved was calculated. Maximum single-diameter stenosis was determined by comparing the least diameter in the flow path from the common carotid to the normal-appearing internal carotid just distal to bifurcation disease. RESULTS: The entire group had a mean of 53 +/- 21% stenosis found on preoperative angiograms, and % delta ICF averaged 64 +/- 92%. When divided into subgroups based on degree of stenosis, patients with 0% to 40% stenosis (n = 17) had % delta ICF of 32 +/- 46%, patients with 41% to 70% stenosis (n = 30) had % delta ICF of 72 +/- 105%, and patients with more than 70% stenosis had % delta ICF of 168 +/- 160%. The differences in % delta IC were significant for the > 70% group compared with the other groups (analysis of variance, P < 0.005), and marginally significant (P = 0.056) between the 0% to 40% and the 41% to 70% groups. The scatter plot of % delta ICF versus stenosis showed a significant second order direct correlation (r = 0.428, P < 0.001) and disproportionate increases in ICF above 60% stenosis. CONCLUSION: A curvilinear relationship between stenosis and immediate increase in ICF after CEA was demonstrated in agreement with theory, and in those patients with more than approximately 60% single-diameter stenosis, large disproportionate increases in blood flow were more frequently observed.

Heparinless left heart bypass for resection of thoracic aortic aneurysms.

Our clinical experience employing heparinless left heart bypass for the resection of twenty-three thoracic aneurysms is presented. In our current technic of heparinless left heart bypass, plastic tubing coated with nonthrombogenic polyurethane-polyvinyl-graphite material and a conventional roller pump are employed. The reduced size of the aneurysm below the aortic clamp during bypass facilitates careful dissection of the aneurysm and the aorta. Twenty-two of twenty-three patients underwent successful thoracic aneurysmectomy with this technic. None had subsequent paraplegia and the postoperative blood loss was minimal. Heparinless left heart bypass is a simple and safe procedure to facilitate thoracic aneurysm resection.

Surgical management of coronary arterial disease in the elderly.

Coronary artery angioplasty or bypass is being performed for increasing numbers of patients in their seventh, eighth, ninth and even tenth decades of life. Because of the cost involved, justification for performing these procedures in the elderly has become a topic of daily discussion among those responsible for funding healthcare. Both silent and overt coronary artery disease (CAD) are more common in the population over 65 years of age. Because CAD in the elderly often presents in an atypical manner, diagnosis of the disease is frequently delayed. Partly because of the delayed diagnosis and partly because of cost considerations, coronary arterial bypass (CABG) is more often performed as an emergency procedure in the elderly with the results that both operative mortality and costs are increased over those observed in a younger population. Nevertheless, it is clear that performance of coronary revascularization procedures in the elderly can both prolong life and improve the quality of life beyond what can be achieved using alternative methods of treatment. Greater efforts directed toward detection of ischemic heart disease in the these patients and earlier, elective surgery could significantly reduce both the mortality and disability associated with CAD in the elderly.

Retrograde aortic dissection during cardiopulmonary bypass.

Femoral artery perfusion for cardiopulmonary bypass is still employed for reoperation, procedures involving the thoracic aorta, and partial bypass in critical patients. Retrograde aortic dissection is the most significant complication of femoral perfusion. The reported incidence is from 0.6% to 14% with a mortality of 66%. Most of the deaths occurred in patients in whom the dissection was not recognized , or in whom the dissection was recognized but not treated appropriately. Our experience with retrograde dissection totals six patients of 640 (0.9%) in whom femoral inflow was used. Four of the six patients survived the dissection. Sudden increase in extracorporeal line pressure shortly after beginning cardiopulmonary bypass associated with decreased venous return, dampened radial arterial pressure, and the abrupt appearance of a bluish, bulging ascending aorta establishes the diagnosis. Survival is enhanced if cardiopulmonary bypass is promptly discontinued, aortic cannulation established, and bypass reinstituted with the induction of profound hypothermia. Circulatory arrest may then be employed to repair the false passage. In this series the proposed operation was completed in all six patients.

Hepatic trauma during cardiac surgery.

Two patients undergoing routine cardiac surgical procedures developed hypovolemic shock following cardiopulmonary bypass. They were found to have hemoperitoneum due to liver injuries. In the first case, intraabdominal hemorrhage was not diagnosed soon enough to save the patient. In the second case, immediate abdominal exploration led to prompt repair of the injury and resuscitation of the patient. We suggest that unexplained hypovolemic shock following cardiopulmonary bypass should be evaluated by immediate abdominal exploration to rule out hemoperitoneum.

Carbon monoxide and ventricular fibrillation threshold in normal dogs.

In a blind, randomized study, the effect of breathing 100 ppm of carbon monoxide versus compressed, purified air for 2 hr on ventricular fibrillation threshold was investigated in twenty anesthetized normal open-chested dogs. The mean arterial carboxyhemoglobin level was 1.12% in the air control period, 0.99% after air, 1.10% in the carbon monoxide control period, and 6.48% after carbon monoxide. Carbon monoxide increased the mean arterial carboxyhemoglobin (P less than .001). Mean ventricular fibrillation thresholds were 19.9 +/- 6.5 mA in the carbon monoxide control period, 15.7 +/- 5.6 mA after carbon monoxide 20.8 +/- 6.3 mA in the air control period, and 24.5 +/- 9.5 mA after air. Carbon monoxide decreased the ventricular fibrillation threshold (P less than .005). These data show that breathing 100 ppm of carbon monoxide for 2 hr reduces the ventricular fibrillation threshold in anesthetized normal open-chested dogs.