Brazilian Journal of Anesthesiology
Brazilian Journal of Anesthesiology
Original Investigation

Influence of exogenous opioids on the acute inflammatory response in the perioperative period of oncological surgery: a clinical study

Influência dos opioides exógenos na resposta inflamatória aguda no perioperatório de cirurgia oncológica: estudo clínico

Odirlei João Titon, Joana Perotta Titon, Janaína Carla da Silva, Mariane Okamoto Ferreira, Matheus Ricrado Garbim, Daniel Rech, Janoário Athanazio de Souza, Carolina Panis

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Recently, opioids have been related to trigger changes in cytokine release and tumor angiogenesis processes, influencing tumor growth, metastasis, and recurrence.

This is a prospective clinical study randomized to test whether if exogenous opioids used in the anesthesia during cancer surgery can affect the systemic inflammatory and immunological patterns. Patients were randomly allocated to the OP (opioid‐inclusive) or OF (opioid-free) anesthesia group. A total of 45 patients were selected, being carriers of prostate, stomach, pancreas, bile ducts, breast, colon, lung, uterus, kidneys, or retroperitoneum tumors. Plasma levels of IL-4, IL-12, IL-17A, and TNF-α, and their oxidative stress profile before and after surgery were evaluated in both groups. In vitro tests were performed by using healthy donor blood incubated with each isolated drug used in patients’ anesthesia for 1 hour, the same cytokines were measured in plasma.

There was a significant reduction in lipid peroxidation in both groups. Patients from OF group had a significant consumption of IL-12 in the perioperative period. The other cytokines evaluated did not vary. It was also observed a significant correlation between IL-12 and TNF-α levels in the OF-post group. Except for atracurium, all tested drugs led to a reduction in IL-12 levels.

This study demonstrated that there is a reduction of IL-12 in the OF-post patients, suggesting acute consumption and that this seems to be a general mechanism of anesthetic drugs, as demonstrated in vitro. Also, these findings bring us to reflect if IL-12 changes may influence the disease progression and recurrence.


Opioids;  Cancer;  Cytokines;  Anesthesia



Recentemente, os opioides têm sido relacionados a desencadear alterações na liberação de citocinas e nos processos de angiogênese tumoral, influenciando o crescimento tumoral, metástase e recorrência.


Este é um estudo clínico prospectivo randomizado para testar se os opióides exógenos usados ​​na anestesia durante a cirurgia de câncer podem afetar os padrões inflamatórios e imunológicos sistêmicos. Os pacientes foram alocados aleatoriamente no grupo de anestesia OP (inclusive com opioides) ou OF (sem opioides). Foram selecionados 45 pacientes, portadores de tumores de próstata, estômago, pâncreas, vias biliares, mama, cólon, pulmão, útero, rins ou retroperitônio. Os níveis plasmáticos de IL-4, IL-12, IL-17A e TNF-α e seu perfil de estresse oxidativo antes e após a cirurgia foram avaliados em ambos os grupos. Os testes in vitro foram realizados utilizando sangue de doadores saudáveis incubados com cada medicamento isolado utilizado na anestesia dos pacientes por 1 hora, as mesmas citocinas foram medidas no plasma.


Houve redução significativa da peroxidação lipídica em ambos os grupos. Os pacientes do grupo OF tiveram consumo significativo de IL-12 no período perioperatório. As demais citocinas avaliadas não variaram. Também foi observada correlação significativa entre os níveis de IL-12 e TNF-α no grupo OF-pós. Com exceção do atracúrio, todos os medicamentos testados levaram à redução dos níveis de IL-12.


Este estudo demonstrou que há redução de IL-12 nos pacientes pós-FO, sugerindo consumo agudo e que este parece ser um mecanismo geral das drogas anestésicas, conforme demonstrado in vitro. Além disso, esses achados nos levam a refletir se as alterações da IL-12 podem influenciar a progressão e a recorrência da doença.


Opioides; Câncer; Citocinas; Anestesia


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