thiopental and Neoplasm-Metastasis

Postoperative immunosuppression is partly ascribed to anesthesia and has been suggested to compromise patients' resistance to infection and tumor metastasis. We compared the effects of various anesthetics on natural killer (NK) cell activity and on resistance to experimental metastasis, and studied mediating mechanisms and prophylactic measures. Fischer 344 rats served as controls or were anesthetized for 1 h with ketamine, thiopental, halothane, or propofol. Anesthetized rats were either maintained in normothermia or left to spontaneously reach 33 degrees C-35 degrees C. Rats were then injected IV with MADB106 tumor cells, and 24 h later lung tumor retention was assessed, or 3 wk later, lung metastases were counted. Additionally, the number and activity of circulating NK cells were assessed after anesthesia. All anesthetics, except propofol, significantly reduced NK activity and increased MADB106 lung tumor retention or lung metastases. Hypothermia had no significant effects. Ketamine increased metastasis most potently, and this effect was markedly reduced in rats pretreated with a beta-adrenergic antagonist (nadolol) or with chronic small doses of an immunostimulator (polyriboinosinic:polyribocytidylic acid). Overall, the marked variation in the NK-suppressive effects of anesthetics seems to underlie their differential promotion of MADB106 metastasis. Prophylactic measures may include perioperative immunostimulation and the use of beta-blockers.. This study in a rat model of pulmonary metastasis demonstrates that some anesthetics, but not others, increase susceptibility to tumor metastasis, apparently by suppressing natural killer cell activity. Ketamine was most deleterious, and its effects were prevented by peripheral blockade of beta-adrenoceptors combined with low levels of immunostimulation.

Topics: Adjuvants, Immunologic; Adrenergic beta-Antagonists; Anesthetics; Anesthetics, Dissociative; Anesthetics, Inhalation; Anesthetics, Intravenous; Animals; Antiviral Agents; Female; Flow Cytometry; Halothane; Ketamine; Killer Cells, Natural; Lung Neoplasms; Male; Nadolol; Neoplasm Metastasis; Poly I-C; Propofol; Rats; Rats, Inbred F344; Thiopental; Tumor Cells, Cultured

Our previous studies indicated that anesthetic drugs cause acceleration of postoperative metastasis of mouse tumors. We tested whether this augmentation could be attributed to a decrease in natural killer (NK) activity. The results indicated that two of the anesthetic drugs used during excision of the Lewis lung carcinoma (3LL) tumor, halothane and ketamine, decreased NK activity, whereas the other two, thiopental sodium and N2O, had no effect on NK activity in in vitro assays. The observed decrease in NK cell activity was reversed following treatment with polyinosinic-polycytidylic acid (poly I:C), which is an NK cell potentiator. Treatment of mice with poly I:C abolished the accelerated growth of metastases following excision of the tumor under ketamine or halothane anesthesia. On the other hand, treatment with poly I:C seemed to have no effect on acceleration of postoperative metastasis in mice anesthetized with N2O or thiopental sodium.

Topics: Anesthesia, General; Anesthetics; Animals; Carcinoma; Female; Halothane; In Vitro Techniques; Ketamine; Killer Cells, Natural; Lung Neoplasms; Mice; Mice, Inbred C3H; Mice, Inbred C57BL; Neoplasm Metastasis; Nitrous Oxide; Poly I-C; Thiopental

Topics: Adolescent; Adult; Aged; Anesthetics; Body Temperature; Body Temperature Regulation; Chemical and Drug Induced Liver Injury; Fentanyl; Fever; Heating; Humans; Middle Aged; Neoplasm Metastasis; Neoplasms; Pain; Thiopental

Topics: Animals; Humans; Lung Neoplasms; Mice; Neoplasm Metastasis; Neoplasms, Experimental; Species Specificity; Thiopental

This set of experiments was devised to determine the effects of the commonly employed anesthetic induction agent, thiopental, on the incidence of pulmonary metastases in a murine fibrosarcoma system. A correlation was made with cell-mediated immune responses in vivo and in vitro. In two separate experiments, thiopental-treated mice had a significantly increased incidence of pulmonary metastases. This was correlated with an impaired delayed hypersensitivity reaction to the de novo antigen. 2,4-dinitrochlorobenzene (DNCB) and a suppressed mixed leukocyte culture (MLC) reaction. However, if animals were sensitized with DNCB 5 days prior to receiving pentothal, no impairment of DNCB reactivity was noted. This suggests strongly that the observed defect is in the afferent arm of the immune response. Thiopental suppresses cell-mediated immune responses in this system, and the observed biologic consequence is an increase in pulmonary metastases.

Topics: Anesthetics; Animals; Dinitrochlorobenzene; Fibrosarcoma; Hypersensitivity, Delayed; Immunosuppression Therapy; Lung Neoplasms; Lymphocyte Culture Test, Mixed; Mice; Mice, Inbred C57BL; Neoplasm Metastasis; Neoplasms, Experimental; Thiopental

Topics: Anesthesia, Inhalation; Atropine; Biopsy; Female; Halothane; Humans; Iliac Vein; Infant; Liver Neoplasms; Male; Neoplasm Metastasis; Nitrous Oxide; Pulmonary Artery; Pulmonary Embolism; Thiopental; Urography; Vaginal Neoplasms; Vena Cava, Inferior