Adverse Effects of Intraparenchymal and Peritumoral Application of Isosulfan Blue Dye in Sentinel Lymph Node Mapping in Breast Cancer: A Systematic Review and Meta-Analysis.

We investigate the evidence for adverse effects of intraparenchymal and peritumoral application of isosulfan blue dye in sentinel lymph node (SLN) mapping in breast cancer patients. A meta-analysis on the adverse effects of intraparenchymal and peritumoral application of isosulfan application in SLN mapping was conducted using Medline and Embase databases up to 2023. Procedure-based adverse reactions were divided into three grades: Grade I (allergic skin reactions), Grade II (hypotension) and Grade III (requiring vasopressor support). Heterogeneity was expressed with I-squared and tau statistics. Subgroup analysis was conducted for administrative route. Univariable meta-regression was performed to assess dose-response effect on adverse reactions. Sensitivity analysis was conducted using fixed effect modelling. A total of 19,183 patients were identified from eight studies. The pooled total adverse event rate after isosulfan administration was 11.65 events per 1,000 patients [95% confidence interval (CI) 7.44-18.19]. The rate of Grade I reactions was 7.96 per 1,000 (95% CI 4.08-15.46); Grade II 0.08 per 1,000 (95% CI 0.00-1.31), Grade III 1.86 per 1,000 (95% CI 0.94-3.66), with no reported mortalities. Intraparenchymal administration was associated with 15.16 events per 1,000 (95% 8.64-26.45), versus 7.04 events per 1,000 (95% CI 5.24-9.45) in peritumoral administration (p=0.02). Univariable meta-regression did not show a significant association between volume of dye infused and total adverse events (-0.164 events per mL, 95% CI -0.864 to 0.534, p=0.645). Isosulfan has low adverse event rates regardless of injection technique or volume administered. Clinicians should have a high level of confidence in its use as an agent for SLN mapping, especially when administering it peritumorally.