Table 3.
Published clinical trials studying the dexmedetomidine-induced biological effects potentially related to oncological outcome.
| Cancer surgery | Study type | Study design | Biological effects of DEX | Ref |
|---|---|---|---|---|
| Appendiceal carcinoma-tosis | Retrospective | After matching: -study group DEX 0.075–0.3 µg/kg/h (n = 107); -control group NaCl + volatile (n = 107) |
No association with improved PFS or OS | 50 |
| Brain | RCT | Forty children randomly allocated in: -study group DEX 0.5 µg/kg/h (n = 20); -control group NaCl (n = 20) |
Decrease in CD3+, CD4+, CD4+/CD8+, NK and B cells at 1 h and at POD1 compared to pre-anesthesia but less than control group (p < 0.05) | 78 |
| Breast | RCT | Twenty-nine women randomly allocated in: -study group DEX total dose 2 µg/kg (n = 16); -control group NaCl (n = 13) |
Increase in proliferation, migration, and invasion of human breast cancer MCF-7 cells exposed to the serum of treated patients (p < 0.001) | 47 |
| Breast | RCT | One hundred and twenty-four patients randomly allocated in: -study group DEX 0.1 µg/kg/min (n = 62); -control group NaCl (n = 62) |
Decrease in NK, CD8+ (p < 0.05); increase in CD4+, CD4+/CD8+, INF-γ, IL-2, IL-6, IL-10 (p < 0.05) | 48 |
| Colon | RCT | One hundred and forty-one patients randomly allocated in: -study group DEX 1 µg/kg/h (n = 72); -control group NaCl (n = 69) |
Increase in CRP, IL-6 and IL-8 but less than control group Decrease in CD4+, CD4+/CD8+, Th1 and increase in Treg but less than control group (p < 0.05) |
61 |
| Colon | Prospective | One hundred and seventy-six patients allocated in: -study group DEX 200 µg (n = 92); -control group NaCl (n = 84) |
Decrease in CD3+, CD4+, CD4+/CD8+ but less than control group (p < 0.05) | 79 |
| Colon | Prospective | One hundred and forty patients randomly allocated in: -study group DEX 1 µg/kg (loading dose) then 0.2–0.7 µg/kg/h (continuous) (n = 80); -control group NaCl (n = 60) |
Increase in IL-6 but less than control group (p < 0.05) | 62 |
| Digestive | Meta-analysis | Seventeen studies (RCTs) = 1,619 patients | Decrease in CRP, TNF-α, and IL-6 (p < 0.01); increase in IL-10, CD4+, CD4+/CD8+ (p < 0.05) |
59 |
| Esophagus | RCT | Sixty-two patients randomly allocated in: -study group DEX 0.5 µg/kg (loading dose) then 0.2–0.4 µg/kg/h (continuous) then 0.06 µg/kg/h for 5 days (n = 31); -control group NaCl (n = 31) |
No changes in leucocytes, IL-6, IL-10, CRP | 55 |
| Gastric | RCT | Fifty-five patients randomly allocated in: -study group DEX 0.2–0.7 µg/kg/h (n = 18); -control group Remifentanil (n = 18); -control group Sufentanil (n = 19) |
Increase in serum levels of glucose, IL-6, β-EP and decrease in IFN-γ but less than other groups. Significant decrease in IL-10 and increase in IL-18 compared to other groups (p < 0.05) | 70 |
| Gastric | RCT | Seventy-four patients randomly allocated in: -study group DEX 0.2 µg/kg/h (n = 37); -control group NaCl (n = 37) |
Increase in IL-1β, IL-6, TNF-α, NF-κB and CRP but less than control group (p < 0.05); decrease in T cells, CD4+/CD8+ but less than control group (p < 0.05) | 63 |
| Gastric | Retrospective | One hundred and two patients allocated in: -study group DEX 0.5 µg/kg (loading dose) then 0.2–0.4 µg/kg/h (continuous) (n = 52); -control group NaCl (n = 50) |
Increase in serum levels of cortisol, ACTH, TNF-α, IL-6 but less than control group (p < 0.05) | 64 |
| Gastric | RCT | Forty patients randomly allocated in: -study group DEX 0.5 µg/kg (loading dose) then 0.4 µg/kg/h (continuous) (n = 20); -control group NaCl (n = 20) |
Increase in Th1/Th2 (p < 0.05); no significant increase in IL-6 and TNF-α | 56 |
| Gastric | RCT | Seventy-eight patients randomly allocated in: -study group DEX 0.1 µg/kg (loading dose) (n = 39); -control group NaCl (n = 39) |
Decrease in IL-1β, IL-6, TNF-α, CRP (p < 0.05) |
57 |
| Lung | Prospective | One hundred and three patients allocated in: -study group DEX (median 122 µg [118–146] i.v.) (n = 51); -control group NaCl (n = 52) |
Increase in M-MDSC (p < 0.0001) by α2-AR; MDSC more efficient in producing VEGF and in suppressing T cells proliferation (p < 0.01) |
26 |
| Lung | RCT | One hundred and sixteen patients randomly allocated in: -study group DEX 0.3 µg/kg/h (n = 58); -control group NaCl (n = 58) |
Increase in serum levels of IL-6, IL-8, TNF-α, MDA but less than control group (p < 0.05) | 65 |
| Lung | RCT | Ninety patients randomly allocated in: -study group DEX 1 µg/kg/h (n = 30); -study group lidocaine (n = 30); -control group NaCl (n = 30) |
Increase in IL-6 and TNF-α but less than control group (p < 0.05) | 66 |
| Lung | Retrospective | Ninety patients allocated in: -study group DEX 0.4 µg/kg/h (n = 48); -control group NaCl (n = 42) |
Increase in serum levels of IL-8, IL-10, TNF-α but less than control group (p < 0.05) | 67 |
| Lung | Prospective | One hundred and twelve patients allocated in: -study group DEX 1 µg/kg (loading dose) then 0.3 µg/kg/h (continuous) (n = 59); -control group NaCl (n = 53) |
Increase in serum levels of IL-8, TNF-α but less than control group (p < 0.05) correlated to the decrease in miR-10a expression; increase in MDA; decrease in SOD | 54 |
| Lung | RCT | One hundred and thirty-two patients randomly allocated in: -study group DEX 2 µg/kg/h (loading dose) then 0.5 µg/kg/h (continuous) then 0.25 µg/kg/h POD1 (n = 33); -study group lidocaine (n = 33); -study group DEX + lidocaine (n = 33); -control group NaCl (n = 33) |
Decrease in the production of NETs, MMP-3, MMP-9, VEGF (p < 0.001), effects potentiated by lidocaine (p < 0.001); decrease in NK and IFN-γ/IL-4 but less than control group (p < 0.05) | 72 |
| Lung | Retrospective | After matching: -study group DEX (n = 251) (median 100 µg [57.47–140] i.v.); -control group NaCl (n = 251) |
Decreased OS (HR = 1.25, 95%CI [1.03–1.59], p = 0.024) | 49 |
| Lung | Meta-analysis | Eleven studies (RCTs) = 1,026 patients | Decrease in IL-6, IL-8 and TNF-α (p < 0.01) | 60 |
| Lung | RCT | One hundred and twenty patients randomly allocated in: -study group DEX 0.7 µg/kg (loading dose) then 0.3 µg/kg/h (continuous) (n = 60); -control group NaCl (n = 60) |
Increase in serum levels of IL-1β, IL-6, IL-10, TNF-α but less than control group (p < 0.001) | 68 |
| Lung | RCT | Forty patients randomly allocated in: -study group DEX 0.5 µg/kg/h (n = 20); -control group NaCl (n = 20) |
Increase in IL-8 but less than control group (p < 0.05) | 69 |
| Lung | RCT | One hundred and forty-three patients randomly allocated in: -study group DEX 0.5 µg/kg/h (n = 73); -control group NaCl (n = 70) |
Significant decrease in IL-8 (p = 0.02), IL-10 (p = 0.002), epinephrine and norepinephrine (p < 0.001) | 53 |
| Oral | RCT | Sixty-eight patients randomly allocated in: -study group DEX 0.5 µg/kg (loading dose) then 0.4 µg/kg/h (continuous) (n = 34); -control group NaCl (n = 34) |
Decrease in CD3+, CD4+, CD4+/CD8+, DCs but less than control group Significant decrease in MDSC (p < 0.05) |
75 |
| Ovarian | Retrospective | Three hundred and forty-three patients enrolled in: -study group DEX (n = 169) i.v.; -control group MDZ (n = 174) |
Decrease in serum levels of TNF-α and IL-6 (p < 0.05) | 58 |
| Prostate | RCT | One hundred and forty-six patients randomly allocated in: -study group DEX 0.2–0.7 µg/kg/h (n = 73); -control group without opioid (n = 71) |
No impact on RFS | 51 |
| Thyroid | Prospective | Ninety-six patients allocated in: -study group DEX 0.5 µg/kg (n = 49); -control group NaCl (n = 47) |
Decrease in MCP-1, ACTH, NE (p < 0.001) | 71 |
| Uterus | RCT | One hundred patients randomly allocated in: -study group DEX 0.4 µg/kg/h (continuous) then 0.15 µg/kg/h POD1 (n = 50); -control group NaCl (n = 50) |
Increase in IFN-γ (p = 0.003); no difference on NK cell activity, inflammatory response; no difference in recurrence, metastases or death | 52 |
| Uterus | RCT | Ninety patients randomly allocated in: -study group DEX 2 µg/kg + bupivacaine (local infiltration) (n = 30); -study group ketamine + bupivacaine (local infiltration) (n = 30); -control group bupivacaine (local infiltration) (n = 30) |
DEX + bupivacaine: opioid-sparing effect; no increase in cortisol, prolactin and glucose compared to the control group (p < 0.05) | 80 |
Abbreviations: ACTH, adrenocorticotropic hormone; AR, adrenoceptor; β-EP, β-enkephalin; CI, confidence interval; CRP, C-reactive protein; DC, dendritic cell; DEX, dexmedetomidine; HR, hazard ratio; IFN, interferon; IL, interleukin; i.v., intravenous; MCP-1, monocyte chemotactic protein-1; MDA, malondialdehyde; MDSC, myeloid-derived suppressor cells; MDZ, midazolam; MMP, matrix metalloproteinase; NA, non-applicable; NaCl, normal saline; NE, norepinephrine; NETs, neutrophil extracellular traps; NF-κB, nuclear factor kappa B; NK, natural killer cell; OS, overall survival; PFS, progression-free survival; POD, postoperative day; RCT, randomized controlled trial; RFS, recurrence-free survival; SOD, superoxide dismutase; TNF, tumor necrosis factor; VEGF, vascular endothelial growth factor.