ASSESSMENT OF REGIONAL AND SYSTEMIC TOXICITY OF ISOLATED LIMB PERFUSION

Following isolated limb perfusion (ILP) with TNF alpha and melphalan t he damage to muscle tissue and its systemic consequences in terms of m yoglobinemia and myoglobinuria as well as the activation of the cytoki ne cascade were investigated. We measured the compartmental pressure o f the limb during and after perfusion and determined the serum changes of myoglobin, creatine kinase (CK), interleukin (IL)-6, IL-1, s-IL-2- receptor, TNF-receptor, and ICAM-1 levels. The compartmental pressure rose significantly during ILP and decreased after reperfusion. Followi ng its course, the decision whether to perform a fasciotomy or not can be more reliably made. Serum myoglobin levels exceeded 200 times norm al values and the increase occurred significantly earlier than that of CK, thus enabling judge ment of the risk of renal failure (crush kidn ey syndrome). The elevation of serum IL-1 and IL-6 values correlated w ith the frequency of cardiopulmonary problems (hyperdynamic shock) and facilitated countermaneuvers. Our data, although obtained from ILP wi th TNF alpha could be used to monitor toxicity also when other drug re gimens are administered.