TY - JOUR
T1 - Dexmedetomidine promotes metastasis in rodent models of breast, lung, and colon cancers
AU - Lavon, H.
AU - Matzner, P.
AU - Benbenishty, A.
AU - Sorski, L.
AU - Rossene, E.
AU - Haldar, R.
AU - Elbaz, E.
AU - Cata, J. P.
AU - Gottumukkala, V.
AU - Ben-Eliyahu, S.
N1 - Publisher Copyright:
© 2017 British Journal of Anaesthesia
PY - 2018/1
Y1 - 2018/1
N2 - Background: Perioperative strategies can significantly influence long-term cancer outcomes. Dexmedetomidine, an α2-adrenoceptor agonist, is increasingly used perioperatively for its sedative, analgesic, anxiolytic, and sympatholytic effects. Such actions might attenuate the perioperative promotion of metastases, but other findings suggest opposite effects on primary tumour progression. We tested the effects of dexmedetomidine in clinically relevant models of dexmedetomidine use on cancer metastatic progression. Methods: Dexmedetomidine was given to induce sub-hypnotic to sedative effects for 6–12 h, and its effects on metastasis formation, using various cancer types, were studied in naïve animals and in the context of stress and surgery. Results: Dexmedetomidine increased tumour-cell retention and growth of metastases of a mammary adenocarcinoma (MADB 106) in F344 rats, Lewis lung carcinoma (3LL) in C57BL/6 mice, and colon adenocarcinoma (CT26) in BALB/c mice. The metastatic burden increased in both sexes and in all organs tested, including lung, liver, and kidney, as well as in brain employing a novel external carotid-artery inoculation approach. These effects were mediated through α2-adrenergic, but not α1-adrenergic, receptors. Low sub-hypnotic doses of dexmedetomidine were moderately beneficial in attenuating the deleterious effects of one stress paradigm, but not of the surgery or other stressors. Conclusions: The findings call for mechanistic translational studies to understand these deleterious effects of dexmedetomidine, and warrant prospective clinical trials to assess the impact of perioperative dexmedetomidine use on outcomes in cancer patients.
AB - Background: Perioperative strategies can significantly influence long-term cancer outcomes. Dexmedetomidine, an α2-adrenoceptor agonist, is increasingly used perioperatively for its sedative, analgesic, anxiolytic, and sympatholytic effects. Such actions might attenuate the perioperative promotion of metastases, but other findings suggest opposite effects on primary tumour progression. We tested the effects of dexmedetomidine in clinically relevant models of dexmedetomidine use on cancer metastatic progression. Methods: Dexmedetomidine was given to induce sub-hypnotic to sedative effects for 6–12 h, and its effects on metastasis formation, using various cancer types, were studied in naïve animals and in the context of stress and surgery. Results: Dexmedetomidine increased tumour-cell retention and growth of metastases of a mammary adenocarcinoma (MADB 106) in F344 rats, Lewis lung carcinoma (3LL) in C57BL/6 mice, and colon adenocarcinoma (CT26) in BALB/c mice. The metastatic burden increased in both sexes and in all organs tested, including lung, liver, and kidney, as well as in brain employing a novel external carotid-artery inoculation approach. These effects were mediated through α2-adrenergic, but not α1-adrenergic, receptors. Low sub-hypnotic doses of dexmedetomidine were moderately beneficial in attenuating the deleterious effects of one stress paradigm, but not of the surgery or other stressors. Conclusions: The findings call for mechanistic translational studies to understand these deleterious effects of dexmedetomidine, and warrant prospective clinical trials to assess the impact of perioperative dexmedetomidine use on outcomes in cancer patients.
KW - dexmedetomidine
KW - neoplasm metastasis
KW - perioperative care
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U2 - 10.1016/j.bja.2017.11.004
DO - 10.1016/j.bja.2017.11.004
M3 - Article
C2 - 29397129
AN - SCOPUS:85047410217
SN - 0007-0912
VL - 120
SP - 188
EP - 196
JO - British journal of anaesthesia
JF - British journal of anaesthesia
IS - 1
ER -