High plasma tumor necrosis factor (TNF)-alpha concentrations and a sepsis-like syndrome in patients undergoing hyperthermic isolated limb perfusion with recombinant TNF-alpha, interferon-gamma, and melphalan

• Published in: Critical care medicine Vol. 24; no. 5; p. 765
• Main Authors: Zwaveling, J H, Maring, J K, Clarke, F L, van Ginkel, R J, Limburg, P C, Hoekstra, H J, Koops, H S, Girbes, A R
• Format: Journal Article
• Language: English
• Published: United States 01.05.1996
• Subjects: Adolescent; Adult; Aged; Antineoplastic Agents, Alkylating - adverse effects; Chemotherapy, Cancer, Regional Perfusion - adverse effects; Combined Modality Therapy; Extremities; Female; Hemodynamics - drug effects; Humans; Hyperthermia, Induced - adverse effects; Interferon-gamma - adverse effects; Linear Models; Male; Melphalan - adverse effects; Middle Aged; Neoplasms - therapy; Prospective Studies; Recombinant Proteins; Severity of Illness Index; Systemic Inflammatory Response Syndrome - blood; Systemic Inflammatory Response Syndrome - chemically induced; Tumor Necrosis Factor-alpha - adverse effects; Tumor Necrosis Factor-alpha - metabolism
• ISSN: 0090-3493
• DOI: 10.1097/00003246-199605000-00007

To describe the postoperative course of patients who underwent hyperthermic isolated limb perfusion with recombinant tumor necrosis factor (TNF)-alpha and melphalan after pretreatment with recombinant interferon-gamma as treatment for recurrent melanoma, primary nonresectable soft-tissue tumors, planocellular carcinoma, or metastatic carcinoma. To measure systemic TNF-alpha concentrations and relate these values with indices of disease severity. A 12-bed surgical intensive care unit (ICU) in a university referral hospital. Prospective, descriptive study. Consecutive patients (n=25) treated with hyperthermic isolated limb perfusion. Blood samples were taken at regular intervals to determine TNF-alpha concentrations during and after hyperthermic isolated limb perfusion with recombinant TNF-alpha. Hemodynamic variables were obtained with a Swan-Ganz pulmonary artery catheter. All patients developed features of sepsis syndrome and required intensive care treatment. Most patients recovered quickly, with a median ICU stay of 2 days (range 1 to 25). Maximum systemic TNF-alpha concentrations ranged from 2284 to 83,000 ng/L (median 25,409) and returned to baseline values within 8 hrs. Despite these high concentrations of TNF-alpha, no patient died in the ICU, although the patient with the highest TNF-alpha concentration developed multiple organ failure and required continuous venovenous hemofiltration for 16 days. Linear regression analysis showed positive correlations between maximum TNF-alpha concentrations and systemic vascular resistance (p < .01), cardiac index (p < .02), Lung Injury Score (p < .02), prothrombin time (p < .02), and activated partial thromboplastin time (p < .05). Hyperthermic isolated limb perfusion with recombinant TNF-alpha leads to high systemic concentrations of TNF-alpha, probably due to leakage of recombinant TNF-alpha from the perfusion circuit, mainly through collateral blood flow. A sepsis-like syndrome is seen in all patients. Despite high concentrations of systemic TNF-alpha, this sepsis syndrome is short-lived and recovery is rapid and complete in most patients.