The Cardiopulmonary Response to OKT3 in Orthotopic Cardiac Transplant Recipients: Conclusion

31 Oct

We sought to characterize the response to OKT3 administration when this therapy was applied within 72 hours of cardiac transplantation as a part of prophylactic immunosuppression. Despite chest roentgenograms without evidence of pulmonary edema and body weights of within 3 to 4 percent of preoperative weight (although not necessarily dry weight) achieved through the aggressive use of diuretic therapy, our patients exhibited a notable time-dependent cardiopulmonary response. Careful hemodynamic monitoring and the judicious use of pharmacologic and supplemental oxygen support prevented this clinical response from causing severe compromise of the patients stability. This parallels the experience of other investigators indicating that the side effects of OKT3 therapy did not necessitate its discontinuation.

The etiology of this cardiopulmonary perturbation is unclear. Within one hour of the administration of OKT3, there is a precipitous decrease in the number of circulating T3+ lymphocytes (to 10 percent of control values). This disappearance is thought to occur through two mechanisms: (1) lymphocytolysis; and (2) opsonization with clearance within the liver. It has been speculated that subsequent elaboration of mediators may contribute to the side effects of OKT3. Indeed, the febrile hyperdynamic response with subsequent alteration in vasomotor tone mimics some aspects of the septic state. Similar alterations in cardiac and pulmonary parameters have been reported following the administration of interleukin-215,16 or endotoxin to human subjects. Whether the lymphocyte-derived mediator interleulan-2 contributes to the OKT3 response remains to be clarified. Reading here
We postulate that following the exogenous nonphysiologic stimulus of OKT3, elaboration of endogenous mediators occurs, resulting in the delayed noncoincident onset of hemodynamic instability, hypoxemia, and fever. The time course suggests that either differential sensitivity occurs, or different mediators are responsible for the various components of the response. Further investigation of this phenomenon and its relationship to lymphocytolysis and opsonization is warranted.
For clinical purposes and the patients safety, we recommend observation in the ICU for recipients of orthotopic cardiac transplants during the 24-hour period encompassing administration of the first intravenous dose of OKT3. Prompt initiation of supportive care in those patients suffering from more extreme side effects may be required.