Combined spinal and general anesthesia attenuates liver metastasis by preserving TH1/TH2 cytokine balance.
BACKGROUND
Many studies have shown that regional anesthesia improves postoperative outcome and particularly lessens infection by attenuating perioperative immunosuppression related to the stress response to surgery and general anesthesia. However, it remains to be determined whether regional anesthesia improves oncologic outcome after surgery.


METHODS
C57BL/6 mice were subjected to laparotomy during sevoflurane general anesthesia alone or combined with spinal block achieved with bupivacaine (5 microg) and morphine (1.25 microg). Control groups were anesthetized only or were untreated. Liver was removed 5 h after surgery to assess antitumor killer cell activity and production of interferon gamma and interleukin 4 by liver mononuclear cells, or mice were inoculated intravenously with liver-metastatic EL4 cells and hepatic metastases were counted 12 days later.


RESULTS
Laparotomy during sevoflurane anesthesia significantly increased the number (+/- SD) of liver metastases from 15.5 +/- 8.7 (control) and 19.4 +/- 5.4 (sevoflurane alone) to 33.7 +/- 8.9. Sevoflurane anesthesia plus spinal block significantly reduced this increase to 19.8 +/- 9. The in vitro killer activity of liver mononuclear cells against EL4 cells decreased from 32.7% (control) and 29.4% (sevoflurane alone) to 18.5% after sevoflurane plus laparotomy, and the addition of spinal block increased activity to 26.6%. The interferon-gamma/interleukin-4 ratio decreased from 89.3 (control) and 95.7 (anesthesia alone) to 15.7 after sevoflurane plus laparotomy, and the addition of spinal block increased the ratio to 46.5.


CONCLUSIONS
The addition of spinal block to sevoflurane general anesthesia accompanying surgery attenuates the suppression of tumoricidal function of liver mononuclear cells, presumably by preserving the T helper 1/T helper 2 (Th1/Th2) balance, and thereby reduces the promotion of tumor metastasis.
Wada
Hiroki
H
Department of Anesthesiology, National Defense Medical College, Namiki, Tokorozawa, Japan.
Seki
Shuhji
S
Takahashi
Tetsuya
T
Kawarabayashi
Nobuaki
N
Higuchi
Hideyuki
H
Habu
Yoshiko
Y
Sugahara
Shinya
S
Kazama
Tomiei
T
D000701:Analgesics, Opioid / Q000494:pharmacology; D000768:Anesthesia, General / Q000379:methods; D000775:Anesthesia, Spinal / Q000379:methods; D019162:Anesthetics, Combined / Q000494:pharmacology*; D018685:Anesthetics, Inhalation / Q000494:pharmacology; D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D002045:Bupivacaine / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism*; D007371:Interferon-gamma / Q000096:biosynthesis / Q000187:drug effects; D015847:Interleukin-4 / Q000096:biosynthesis; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology; D008099:Liver / Q000276:immunology / Q000473:pathology*; D008114:Liver Neoplasms, Experimental / Q000276:immunology / Q000517:prevention & control* / Q000556:secondary; D016399:Lymphoma, T-Cell / Q000188:drug therapy* / Q000276:immunology; D008297:Male; D008738:Methyl Ethers / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D009020:Morphine / Q000494:pharmacology; D009362:Neoplasm Metastasis / Q000517:prevention & control*; D009368:Neoplasm Transplantation; D009407:Nerve Block / Q000379:methods; D000077149:Sevoflurane; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects* / Q000276:immunology; D014407:Tumor Cells, Cultured
D000701:Analgesics, Opioid; D019162:Anesthetics, Combined; D018685:Anesthetics, Inhalation; D000779:Anesthetics, Local; D016207:Cytokines; D008738:Methyl Ethers; D015847:Interleukin-4; D000077149:Sevoflurane; D009020:Morphine; D007371:Interferon-gamma; D002045:Bupivacaine