Table 3.

Preclinical and clinical studies provide considerable evidence of how agents with antiadrenergic or anti-inflammatory properties, along with other specific anesthetic techniques, could have beneficial effects as possible perioperatory strategy.

Perioperative intervention		Mechanism of action	Impact on the development of metastasis	Clinical evidence
Actions that favor the Metastatic development	General anesthetics: • Inhaled agents	Increased levels of HIF-1α, VEGF, MMP, and TGF-β.	Increased migration and invasion of tumor cells.	Due to their negative impact on cancer prognosis, no specific clinical studies have been carried out, but rather these techniques have been used as a comparison against the possibilities that could be of benefit.
	•Intravenous agents • Opioid	Increased catecholamine synthesis.	Increased neuroendocrine stress response: – Immunosuppression – Increased angiogenesis.
		Increased synthesis of proinflammatory mediators: PGE2.	Proinflammatory Microenvironment Formation (NPM): – Tumor proliferation – Metastatic progression
		Decreased activity of lymphocytes, macrophages, and NK cells.	Immunosuppression.
		Decreased activity of NK cells.	Immunosuppression.
Decrease in the use of opioids	• Propofol	Anti-inflammatory effect, antioxidant.	Inhibition of the migration of tumor cells.	– Retrospective analysis of 7,030 patients compares survival in patients receiving anesthetic agents vs. propofol-based anesthesia (RH = 1.46 95% CI: 1.29–1.66) (103, 117). – Retrospective analysis associates propofol-based anesthesia in mastectomies with higher survival, compared to inhaled anesthesia (HR: 0.55, 95% CI: 0.31–0.97) (103, 117).
		Maintenance of NK cell function.	Immunoprotection.
	Local anesthetics • Epidural anesthesia	Inhibition of the synthesis of catecholamines, proinflammatory mediators and cortisol.	Decreased neuroendocrine stress response: – Immunoprotection – Decreased angiogenesis – Decreased tumor spread	– Meta-analysis obtained positive association for neuroaxial anesthesia and survival improvement compared to general anesthesia (HR = 0.85, 95% CI: 0.741–0.981, p = 0.026) (14). – Prospective study of 42,000 patients older than 66 years with colorectal cancer. The use of AE is associated with a higher median survival (OR = 0.91 95% CI: 0.87–0.94, p < 0.001) (52).
Prevention	β-Blockers	B-adrenergic antagonism: inhibits the response to catecholamines (stress response).	– Decreased deleterious effect of catecholamines: Immunoprotection? – Reduction of tumor proliferation and colonization? – Nowadays, the potential effect of β-blockers has low-level evidence (112)	– Administration of β-blockers in the perioperative period as an increase in survival in patients with breast, lung, prostate and ovarian cancer (106, 113, 114) are in controversy with a recent meta-analysis: administration of β-blockers had no effect on disease-free survival or overall survival in patients with cancer.
	NSAIDs • COX-2 inhibitor • COX-2 inhibitorsand β-Blockers	Reduction in PGE2 levels. VEGF inhibition. NK cell activity maintenance	– Inhibits the formation of the proinflammatory microenvironment. – Angiogenesis reduction. – Immunoprotection	– Retrospective study: 15,574 patients undergoing liver resection. Administering perioperative NSAIDs reduces tumor recurrence and increases survival (HR = 0.81, 95% CI: 0.73–0.90) (103, 117). – The use of perioperative NSAIDs is associated with prognostic improvement in breast and colorectal cancer (103, 117). – Combination of propanolol (40 mg daily) and etodolac (800 mg daily) 5 days prior to breast cancer surgery during the perioperative period reduces neoplasic cells malignancy potential (111).
		Lower increase in serum inflammatory markers. Reduced expression of prometastatic transcription factors and epithelial-mesenchymal transition.	Blockage of neuroinflammatory signaling.