Heparin-coated cardiopulmonary bypass circuits: hemostatic alterations and postoperative blood loss.

This prospective, randomized study involving patients undergoing isolated coronary artery bypass grafting investigated whether the use of heparin-coated bypass circuits with an uncoated cardiotomy reservoir (n = 10) compared with standard uncoated bypass circuits (n = 10) resulted in differences in patient outcome and hemostatic alterations. There were no differences in postoperative blood loss, transfusion requirements, and routine coagulation test results between groups. Immunoassays for platelet alpha-granule constituents platelet factor 4 and beta-thromboglobulin, thrombin generation by-product F1.2, fibrinopeptide A, thrombin-antithrombin complex, and fibrinolysis by-product D-dimer also demonstrated no significant differences between groups, although trends for lower platelet secretion with heparin coating were noted. Increases were found in beta-thromboglobulin and platelet factor 4 concentrations at 10 (p < 0.03) and 30 minutes (p < 0.001) of CPB, respectively, and continuing throughout CPB (p < 0.001) for both groups versus values measured before incision. No significant differences were seen between levels 5 minutes prior to aortic cross-clamp release and those obtained 8 and 45 minutes after cross-clamp release. Conversely, no significant increases in F1.2, thrombin-antithrombin complex, and D-dimer were seen prior to release of the aortic cross-clamp, but afterward increases occurred that were highly significant (p < 0.001). The temporal data suggest that platelet activation occurs primarily as a result of contact with the cardiopulmonary bypass circuitry, whereas thrombin generation and fibrinolytic activity are not significant until reperfusion of the heart and lungs.(ABSTRACT TRUNCATED AT 250 WORDS)

Deleterious effects of cardiopulmonary bypass on early graft function after single lung allotransplantation: evaluation of a heparin-coated bypass circuit.

Clinical lung transplantation may necessitate the use of cardiopulmonary bypass during the procedure, resulting in increased morbidity with more severe early graft dysfunction and increased blood loss. A heparin surface-coated cardiopulmonary bypass circuit is now available with improved biocompatibility and reduced systemic heparin requirements and may offer advantages compared with standard uncoated cardiopulmonary bypass circuits. This study investigates in a canine model of single-lung allotransplantation whether cardiopulmonary bypass adversely affects early graft function and whether a heparin-coated cardiopulmonary bypass circuit with reduced systemic heparin dosage improves results compared with standard uncoated cardiopulmonary bypass systems. Fifteen dogs underwent left single-lung allotransplantation with occlusion of the contralateral pulmonary artery and bronchus 1 hour after reperfusion. In one group, five animals underwent the procedure without cardiopulmonary bypass. In the group with uncoated circuits, five animals underwent the procedure with the use of standard uncoated cardiopulmonary bypass circuits with full systemic heparin dosage. In the group with heparin-coated circuits, five animals underwent the procedure with the use of heparin-coated cardiopulmonary bypass circuits and reduced systemic heparin dosage. Early graft function was evaluated by arterial oxygenation, pulmonary mechanics, lung water measurements, and histologic analysis. Hemodynamics and postoperative blood loss were also measured. Two hours after reperfusion, partial pressure of oxygen in arterial blood on an inspired oxygen fraction = 1.0 was significantly greater (p < 0.001) in the group without cardiopulmonary bypass (467 +/- 58 mm Hg) than in the group with uncoated circuits (114 +/- 90 mm Hg) and the group with heparin-coated circuits (193 +/- 105 mm Hg), with no significant difference between the groups undergoing bypass procedures. Lung compliance decreased and lung water increased in all transplanted lungs without significant differences between groups. Histologic analysis did not differentiate between the groups. After reperfusion, cardiac index and mean arterial pressure were significantly reduced in the groups with uncoated circuits and with heparin-coated circuits compared with the group that did not undergo cardiopulmonary bypass (p < 0.001). Postoperative blood loss was significantly less (p < 0.002) in the group that did not undergo cardiopulmonary bypass (90 ml +/- 38 ml) compared with both the group with uncoated circuits (750 +/- 15 ml) and the group with heparin-coated circuits (690 +/- 387 ml), with no significant difference between the groups that underwent bypass. The use of cardiopulmonary bypass with systemic heparinization is detrimental to early graft function in this canine model of left single-lung allotransplantation.(ABSTRACT TRUNCATED AT 400 WORDS)

Incomplete ventricular septal tear after blunt chest trauma: medical management with serial echocardiographic follow-up.

Incomplete ventricular septal tears are uncommon or probably underreported cardiac lesions caused by blunt chest trauma. This report describes two cases of incomplete ventricular septal tears that were not suspected clinically. Transthoracic and transesophageal echocardiography provided the diagnostic information in both of these cases. Despite associated valvular lesions, the patients' stable in-hospital course lead to the decision to treat them medically with no specific treatment to the incomplete ventricular septal tears. Accordingly, these two cases were observed for a mean period of 1.5 years with serial echocardiographic studies to track the natural history of these lesions. During the follow-up period, both of these cases did not manifest any changes in the extent of ventricular septal tear, septal structure, or any left-to-right shunting through the tear. There were no significant changes in left ventricular size, shape, or systolic function. Thus echocardiographic imaging proved to be useful both in initial diagnosis and follow-up.

Acute rejection of lung allografts with various immunosuppressive protocols.

Between February 1990 and December 1991, 69 patients who survived for a minimum of 5 days after single-lung (27), double-lung (32), or heart-lung transplantation (10) were studied to learn the incidence and severity of acute rejection and the possible effects of various immunosuppressive protocols on this rejection. Acute rejection was less common (2.1 versus 3.1 episodes/patient) after transplantation in those 30 candidates who received rabbit antithymocyte globulin for the first 5 postoperative days versus the 28 who were maintained on cyclosporine, azathioprine, and prednisone alone (p < 0.05), but no patient escaped at least one episode. Patients given cyclosporine received more 3-day courses of methylprednisolone (p < 0.02) than those given rabbit antithymocyte globulin (2.5 versus 1.7 courses). Although no disadvantage in terms of infectious morbidity was noted in the rabbit antithymocyte globulin group, no obvious intermediate advantage was noted in survival (85% at 12 months) or grade of rejection or airway flows. The most common histopathologic grades were mild (A2) and moderate (A3); the average grade was A2.3. FK 506 was tested in 11 patients, and early results are promising relative to low early and likely fewer late episodes of rejection. No differences were noted in the likelihood of rejection for any procedures.

Clinical trial of FK 506 immunosuppression in adult cardiac transplantation.

The new immunosuppressive agent FK 506 was used as primary immunotherapy in conjunction with low-dose steroids and azathioprine in 72 patients subsequent to orthotopic cardiac transplantation. Overall patient survival at a mean follow-up of 360 days was 92%. The number of episodes of cardiac rejection (grade 3A or greater) within 90 days of transplantation was 0.95 per patient. The actuarial freedom from rejection at 90 days was 41%. Achievement of this level of immunosuppression is comparable with that of cyclosporine-based triple-drug therapy with OKT3 immunoprophylaxis. Thirty percent of patients were tapered off all steroids, and the average steroid dose in the group who received steroids was 8.6 mg of prednisone per day. The incidence of infection reflected the diminished necessity for steroids: seven major infections (10%) and 11 minor infections (16%). Renal dysfunction occurred during the perioperative period in most patients in this trial. However, the incidence of hypertension was 54% compared with 70% during the cyclosporine era. Ten adults underwent successful rescue therapy with FK 506 after cardiac rejection refractory to conventional immunotherapy. Side effects of FK 506 were notably few, and the results of the trial are encouraging for the future of the cardiac transplant recipient.

Evolving experience with mechanical circulatory support.

Since 1985 total mechanical circulatory support for mortally ill transplant candidates has been progressively integrated into the authors' program. During this period 379 patients underwent transplantation. Of this group of patients, 62 required some form of mechanical support other than the intra-aortic balloon pump. Because intra-aortic balloon pump assist was limited in therapeutic effect and was associated with patient immobility and line-related sepsis, the next logical step toward support was the artificial heart. Of 20 patients implanted with the Jarvik heart, 17 underwent transplantation, but only 9 of these survived to discharge. In 1988, the authors abandoned the preferential use of the total artificial heart because of excessive cumulative probability of death from wound infection. They began to use the Novacor electrical assist device with the percutaneous power cord because they believed that univentricular support would be adequate for most patients, because its heterotopic position would reduce the likelihood of infection, and because it had the potential for chronic implantation. Twenty-three patients with biventricular failure (right ventricular ejection fraction less than 20%, 18/23) received the electrical assist device for an average of 50.4 days (range 1-193 days). All 17 transplanted patients survived until discharge. Only one of the five deaths that occurred after implantation, but without transplantation, was due to infection (candidiasis). Remarkably, all patients who survived the perioperative period ultimately survived with univentricular support alone. Based on this experience, survival of mechanically supported patients is now comparable to that of those less mortally ill.

Cardiac transplantation at the University of Pittsburgh: 1980 to 1991.

When examining survival rates following cardiac transplantation, it is important to examine the risk factors for both early (30-day) and late (greater than 30-day) survival as they may well be different. Factors affecting early survival appear related more to the preoperative condition of the patient (including degree of pulmonary hypertension) as well as advances that have been made in postoperative care. It is not immediately obvious why gender has such a profound effect on early survival and why primary graft failure rates appear higher in this group. Donor organ factors did not appear to relate to this difference. On the other hand, late survival appears to be influenced mainly by immunologic factors such as panel reactive antibody level and immunosuppressive protocol. A less dramatic effect of transpulmonary gradient appears to have a lasting effect on recipients even when they survive the initial 30-day period. Thus, pulmonary hypertension may have prolonged effects on the cardiac allograft which as yet we do not understand completely. The majority of late mortality is still due to graft atherosclerosis, infection, and acute cellular rejection, the latter 2 occurring most frequently within the first year after transplantation whereas death from graft atherosclerosis becomes most prominent beyond 5 years. Despite persistent improvements in 30-day survival, late survival following cardiac transplantation will only improve with the advent of better tissue matching and improved immunosuppression. The results with FK506, for example, are promising.

LVAS pump performance following initiation of left ventricular assistance.

Prevention of disturbed flow (e.g., flow stasis) and consequent thrombosis in heart pumps is based upon design characteristics determined during laboratory bench tests. These tests employ optimal filling and emptying characteristics, such as the full-fill to complete empty mode in the Novacor left ventricular assist system. Filling characteristics of the Novacor LVAS were examined during the first 48 hours after implantation in 14 patients. Fill volume of the pump was reduced in pathologic states, such as cardiac tamponade, and following the initiation of right ventricular mechanical circulatory support. In addition, multiple regression analysis revealed that right ventricular function measured by the amount of inotropic support required, the right ventricular ejection fraction, and the total pulmonary resistance, significantly predicted left ventricular assist pump fill volume during the first 48 hours of support. Flow visualization simulating these clinical conditions of incomplete filling suggest inadequate valve washing, particularly around the inlet valve and its conduit, which may predispose to thrombus formation.

Recurrent hyperparathyroidism due to implantation of parathyroid tissue.

Recurrence of hyperparathyroidism after initially successful primary operation is usually caused by inadequate resection of diseased tissue or recurrent carcinoma. Since it is known that normal parathyroid tissue may be autotransplanted into a muscle bed, it is plausible that inadvertent implantation of parathyroid tissue spilled at operation may occur. In four of 23 reoperations for hyperparathyroidism in an 11 year period, we found evidence that iatrogenic parathyroid implantation had occurred. Two of the four patients had multiple parathyroid implants in the previous operative field, and one of these patients had documented spillage of a cystic adenoma during the original operation. Another two of the four patients were found to have recurrent adenomas containing suture material at sites of previous excision of the adenomas. No patient had gross or histologic evidence of parathyroid carcinoma. We conclude that inadvertently spilled parathyroid tissue may implant in the neck or mediastinum and cause persistent or recurrent hypercalcemia. Therefore, all efforts should be made to handle the parathyroid glands only by their pedicles and not to crush, suture, or violate the capsule. Needle aspiration of parathyroid cysts could lead to implantation along the needle tract.

Barrett's esophagus: its prevalence and association with adenocarcinoma in patients with symptoms of gastroesophageal reflux.

The pathologic reports of all 1,020 esophageal biopsy specimens obtained between 1975 and 1981 in patients with symptoms of gastroesophageal reflux were reviewed. Barrett's esophagus was identified in 84 patients (8 percent). The 362 patients seen between 1980 and 1981 were reviewed in detail. The symptoms in patients with Barrett's esophagus differed from those of the patients without Barrett's esophagus. Dysphagia was more often present in the former group (34 percent versus 16 percent, p less than 0.05) and epigastric distress was less frequent (11 percent versus 27 percent, p less than 0.05). Objective findings of hiatal hernia, esophageal stricture, and esophageal ulcers occurred more commonly in patients with Barrett's esophagus than in those without Barrett's esophagus (70 percent versus 48 percent, 31 percent versus 4 percent, and 14 percent versus 6 percent, respectively, p less than 0.05). Mid esophageal strictures were associated almost exclusively with Barrett's esophagus (five of six patients). At esophagoscopy, erythema was seen more commonly with Barrett's esophagus. The diagnosis was suspected by the endoscopist in only 34 percent of patients subsequently demonstrated histopathologically to have Barrett's esophagus. There was no significant difference in the prevalence of a positive Bernstein test result or gastroesophageal reflux on upper gastrointestinal series in patients with and without Barrett's esophagus. However, a hypotensive lower esophageal sphincter was found more commonly in patients with Barrett's esophagus (100 percent versus 53 percent, p less than 0.05). Thirteen of the 84 patients with Barrett's esophagus (15 percent) had a coexistent adenocarcinoma arising from Barrett's mucosa. These patients, when compared with the patients with Barrett's esophagus without carcinoma, were more often male (77 percent versus 51 percent, p = 0.1), more often had dysphagia (69 percent versus 34 percent, p less than 0.05), and more frequently had a comparatively short duration of symptoms (67 percent versus 36 percent, p less than 0.05). Our findings suggest that patients with Barrett's esophagus have a high risk of development of carcinoma. Because the entity is often not recognized at endoscopy, routine esophageal biopsy should be performed on all patients undergoing esophagoscopy for symptoms of gastroesophageal reflux. Patients with known Barrett's esophagus should be followed closely with repeated endoscopy and biopsy.

Pathogenesis, diagnosis and treatment of acute gastric mucosal lesions.

Stress ulcers are multiple superficial mucosal lesions which occur mainly in the fundus of stomachs of seriously ill patients and should be differentiated from reactivation of a pre-existent ulcer diathesis, Cushing's ulcer following head injury, or drug-induced gastritis. It is generally agreed that luminal acid and pepsin are required for ulceration to develop. Experimental evidence suggests that backdiffusion of acid is closely related to the formation of ulcers. In the absence of overt disruption of the gastric mucosal barrier, ischaemia appears to compromise the ability of the gastric mucosa to dispose of backdiffusing acid, which then results in a decrease in intramural pH and ulceration. Reflux of duodenal contents and diffusion of urea from the blood may contribute to the formation of ulcers. Although endoscopic studies have demonstrated gross mucosal injury within hours of the stressful event in nearly 100 per cent of patients examined, most stress ulcers heal when normal gastric defence mechanisms are restored. However, in a small percentage of patients, stress ulceration may lead to frank gastrointestinal haemorrhage requiring medical and/or surgical intervention. Endoscopic findings in conjunction with the history usually differentiates stress ulcer from other bleeding lesions. Angiography may be used if endoscopy fails to identify the bleeding site. Most episodes of bleeding from stress ulceration resolve on medical management consisting of saline lavage, antacids, and adequate supportive measures. Pharmacoangiography with selective infusion of vasopressin or embolization may be of benefit in selected patients with continued bleeding. Surgery is a last resort and has a predictably high mortality. The operation of choice is controversial, but vagotomy, pyloroplasty and oversewing the ulcers may be a good initial operation. Continued bleeding subsequent to vagotomy and pyloroplasty would require near total gastrectomy. Since results of surgical therapy in established stress ulcer disease are poor, the prevention of bleeding is the most rational approach to the management of this disease. The key to prophylaxis is the maintenance of normal intragastric pH. Antacids appear to be superior to cimetidine in preventing bleeding from stress ulcers, so long as the gastric content is buffered to a pH of 3.5 or greater. In seriously ill patients found in respiratory-surgical intensive care units, hourly titration with antacids is the standard against which other forms of prophylaxis must be rigidly compared.