[Assessment of regional and systemic toxicity of isolated hyperthermic extremity perfusion with tumor necrosis factor-alpha and melphalan].
Following isolated limb perfusion (ILP) with TNF alpha and melphalan the damage to muscle tissue and its systemic consequences in terms of myoglobinemia and myoglobinuria as well as the activation of the cytokine cascade were investigated. We measured the compartmental pressure of 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. Following its course, the decision whether to perform a fasciotomy or not can be more reliably made. Serum myoglobin levels exceeded 200 times normal values and the increase occurred significantly earlier than that of CK, thus enabling judgement of the risk of renal failure (crush kidney syndrome). The elevation of serum IL-1 and IL-6 values correlated with the frequency of cardiopulmonary problems (hyperdynamic shock) and facilitated counter-maneuvers. Our data, although obtained from ILP with TNF alpha, could be used to monitor toxicity also when other drug regimens are administered.
Hohenberger
P
P
Abteilung Chirurgie und Chirurgische Onkologie, Robert-Rössle-Klinik für Onkologie am Max-Delbrück-Centrum für Molekulare Medizin, Virchow-Klinikum, Humboldt-Universität zu Berlin.
Haier
J
J
Kettelhack
C
C
Schulze
G
G
Schlag
P M
PM
D000293:Adolescent; D000328:Adult; D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage / Q000009:adverse effects*; D010478:Chemotherapy, Cancer, Regional Perfusion; D003131:Combined Modality Therapy; D003161:Compartment Syndromes / Q000097:blood / Q000139:chemically induced; D016207:Cytokines / Q000097:blood; D005121:Extremities; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006979:Hyperthermia, Induced; D008297:Male; D008545:Melanoma / Q000628:therapy*; D008558:Melphalan / Q000008:administration & dosage / Q000009:adverse effects*; D008875:Middle Aged; D009211:Myoglobin / Q000097:blood; D009212:Myoglobinuria / Q000097:blood / Q000139:chemically induced; D009364:Neoplasm Recurrence, Local / Q000628:therapy*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects; D012206:Rhabdomyolysis / Q000097:blood / Q000139:chemically induced; D012509:Sarcoma / Q000628:therapy*; D012878:Skin Neoplasms / Q000628:therapy*; D012983:Soft Tissue Neoplasms / Q000628:therapy*; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage / Q000009:adverse effects*
D018906:Antineoplastic Agents, Alkylating; D016207:Cytokines; D009211:Myoglobin; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D008558:Melphalan