Critical care medicine · 1996
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.
Клиническое исследованиеСтатьяНазвание и аннотация: Перевод в очереди
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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
Аннотация
OBJECTIVES: 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.
SETTING: A 12-bed surgical intensive care unit (ICU) in a university referral hospital.
DESIGN: Prospective, descriptive study.
PATIENTS: Consecutive patients (n=25) treated with hyperthermic isolated limb perfusion.
INTERVENTIONS: 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.
MEASUREMENTS AND MAIN RESULTS: 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).
CONCLUSIONS: 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.
SETTING: A 12-bed surgical intensive care unit (ICU) in a university referral hospital.
DESIGN: Prospective, descriptive study.
PATIENTS: Consecutive patients (n=25) treated with hyperthermic isolated limb perfusion.
INTERVENTIONS: 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.
MEASUREMENTS AND MAIN RESULTS: 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).
CONCLUSIONS: 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.
Предметные рубрики MeSH
AdolescentAdultAgedAntineoplastic Agents, AlkylatingChemotherapy, Cancer, Regional PerfusionCombined Modality TherapyExtremitiesFemaleHemodynamicsHumansHyperthermia, InducedInterferon-gammaLinear ModelsMaleMelphalanMiddle AgedNeoplasmsProspective StudiesRecombinant ProteinsSeverity of Illness IndexSystemic Inflammatory Response SyndromeTumor Necrosis Factor-alpha