To test the efficacy of murine monoclonal CD-3 antibody (OKT3) in early prophylaxis for cardiac allograft rejection, we conducted a 6-month trial, prospectively assigning 51 patients to receive either equine antithymocyte globulin-based (n = 25) or OKT3-based (n = 26) early prophylaxis. ATG patients received 8 days of ATG (10 mg/kg), with the first dose given preoperatively. OKT3 patients received 14 days of OKT3 (5 mg) beginning on the second postoperative day. Corticosteroid and azathioprine administration were similar during early prophylaxis. Cyclosporine was begun preoperatively in ATG patients and on the fourth postoperative day in OKT3 patients. In addition, patients in both groups were randomized to receive or not receive eight weekly administrations of vincristine (0.025 mg/kg). While infection rate (0.8 +/- 0.2 infections/patient in both groups [mean +/- SEM]) and mortality (1 patient in each group) did not differ, OKT3-based early prophylaxis delayed the first rejection episode (76 +/- 11 days vs. 36 +/- 8 days, P = 0.005) and decreased the risk of rejection during the 6-month follow-up (P less than 0.001, product-limit analysis). Overall, the OKT3 group manifested 1.5 +/- 0.2 episodes of rejection/patient compared with 2.2 +/- 0.2 episodes/patient in the ATG group (P = 0.036). Despite similar 6-month cumulative cyclosporine and azathioprine dosages, six month average corticosteroid administration was less in the OKT3 group (12.2 +/- 1.5 mg prednisone equivalent/m2/day versus 19.3 +/- 2.1 mg prednisone equivalent/m2/day, P = 0.008), fewer OKT3 patients subsequently required additional cytolytic therapy for rejection (2 [8%] versus 12 [48%], P = 0.001), and more patients in the OKT3 group were successfully weaned off maintenance corticosteroids (22 [88%] versus 11 [46%], P = 0.002). We conclude that, relative to an equine ATG-based protocol, OKT3-based early prophylaxis results in less rejection, permitting less chronic corticosteroid administration.

The impact of protective isolation on the incidence of infection in 60 cardiac transplant recipients (mean age, 49.2 years) was studied in a prospective randomized trial. Thirty patients were randomized to protective isolation, which consisted of private room, hat, mask, sterile gown, and handwashing. Thirty patients were randomized to no isolation, which meant they recovered in a crowded, open intensive care unit and were adjacent to recipients of liver transplants or patients who were on the trauma, neurosurgical, and general surgical services, many of whom had an infection of the incision or a pulmonary infection. There was no difference between groups in the proportion of patients in whom infection developed (chi 2[1] = 0.27; p = 0.6), the number of infection-related deaths (2 in each group), the types of infection (bacterial, viral, fungal, or protozoal), or the overall outcome. Because protective isolation offered no benefit over standard care in protecting these patients from infections or the associated complications, we have discontinued its routine use after cardiac transplantation.

Improvement in the outcome from cardiac transplantation can be attributed to recent advances in immunosuppression, including the use of OKT3, a new monoclonal antibody. The first dose of OKT3 induces side effects such as dyspnea in other transplant populations. We studied cardiopulmonary responses to OKT3 in 23 recipients of cardiac transplants. Despite pretreatment including antihistamines, hydrocortisone, and acetaminophen, OKT3 administered within 72 hours of transplantation, as part of prophylactic immunosuppression, induced a biphasic systemic response. Within the first hour, patients developed fever, hyperdynamia, hypertension, and tachycardia. By five to seven hours after the dose, there was mild hypotension, hypoxemia, and decreased indices of vascular resistance. Eighteen of the 23 patients required supplemental oxygen or vasopressor support (or both). Our findings define a complex cardiovascular response to OKT3 exhibited by the delayed noncoincident onset of hemodynamic instability, hypoxemia, and fever. Close observation in an ICU is recommended during the initial administration of OKT3 for prompt intervention when reactions occur.

Several recent reports have demonstrated an increased incidence of allograft renal vascular thrombosis in patients receiving cyclosporine alone or as part of multiple drug regimens when compared with patients receiving azathioprine (AZA) and prednisone (P). To determine whether CsA therapy is indeed a risk factor for renal artery or vein thrombosis, we examined the incidence of these complications in 224 adult renal allograft recipients who were prospectively randomized and stratified by risk to treatment with either CsA-P (n = 117) or AZA-P-antilymphocyte globulin (n = 107) between September 1980 and October 1983, and in 452 adult and 87 pediatric patients on triple (AZA-P-CsA) or quadruple (AZA-P-CsA-ALG) therapy protocols between July 1984 and November 1987. In the randomized trial, one of 107 AZA-P-ALG patients (0.9%) and two of 117 CsA-P patients (1.7%) developed renal vein thrombosis (P = 0.94), and there were no cases of arterial thrombosis. Though CsA levels were elevated in one of the two CsA-treated patients at the time of their events, and both these patients demonstrated other predisposing factors for thrombosis. In the triple/quadruple therapy era, there were no cases of renal vein thrombosis, and the only case of renal artery thrombosis occurred in a pediatric recipient who was not receiving CsA at the time. These data, when taken together with a critical review of the conflicting literature, strongly suggest that factors other than immunosuppression with CsA, including surgical technique, allograft rejection, use of multiple artery and/or pediatric donor kidneys, and postoperative hypotension, are important in the pathogenesis of allograft renal vascular thrombosis. It seems possible, however, that high initial dosing of CsA might trigger this complication in the early posttransplant period when other predisposing factors are present.