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1 From the Surgical Intensive Care Unit, Department of Anesthesiology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland
2 From the Pluridisciplinary Center for Oncology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland
Objective: To describe the systemic effects of high-dose recombinant tumor necrosis factor alpha (rTNF-
), recombinant interferon gamma (rIFN-
), and melphalan administered through hyperthermic isolation perfusion of the limbs (IPL) in patients with melanoma and malignant soft-tissue tumors.
Design: The clinical, hemodynamic, and biologic parameters were recorded after IPL during the postoperative period.
Setting: Surgical intensive care service of a 1,000-bed tertiary university medical center.
Patients: Nineteen patients referred to a pluridisciplinary Center for Oncology after relapse of regionally advanced melanoma or soft-tissues tumors, included in a phase 2 therapeutic study.
Results: Major systemic and hemodynamic changes were observed after IPL in all patients. Ninety-four percent (17/18) of the evaluable patients presented a shock unresponsive to fluid challenge, requiring the continuous perfusion of vasopressors, inotropic agents, or both. Analysis of hemodynamic data showed two distinctive patterns: a pure distributive shock in nine patients requiring norepinephrine, and a mixed distributive and cardiogenic shock in eight patients requiring vasopressor and inotropic agents. The oxygen parameters were characterized by an increase in both the delivery and the uptake of oxygen, with a prolonged reduced oxygen extraction ratio for most patients. The other observed effects were as follows: transient bilateral or mixed pulmonary infiltrates in all patients; some hematologic disturbances in 83% of patients; infection requiring a modification of the antibiotic prophylaxis in 61% of patients; and some liver toxic reactions in 50% of patients. Very high systemic TNF- serum bioactivity was found in 12 patients for whom serum samples were available, indicating an early and important rTNF- leakage from the IPL. No correlations could be found between the levels of TNF- and the observed systemic effects. Despite the severity of the hemodynamic disturbance, no patient died.
Conclusion: Major systemic effects, consisting mainly in cardiovascular, respiratory, and hematologic disturbances, were observed in patients after IPL with high-dose of rTNF-. The likely explanation for these observations is an early rTNF- leakage related to inadequate IPL technique. These data show that the iatrogenic administration of high circulating TNF levels lead to a "septic shock-like" syndrome without resulting in lethal organ dysfunction.
Key Words: distributive shock • isolated limb perfusion • interferon gamma • oxygen delivery • septic shock • tumor necrosis factor alpha
Submitted on January 18, 1994
Accepted on August 3, 2007
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