Skin barrier impairment and topical local anesthetics: a review of percutaneous absorption and systemic toxicity risks

Topical local anesthetics are widely used in dermatologic surgery, laser therapy, and minimally invasive aesthetic procedures. In intact skin, the stratum corneum typically restricts the percutaneous absorption of local anesthetics; however, following skin barrier impairment due to inflammatory dermatoses, ulcers, burns, or post-laser and microneedling treatment, altered local permeation and systemic exposure profiles may affect their safety margin. This narrative review presents a structured synthesis of evidence pertaining to skin barrier dysfunction and the safety of topical local anesthetics. The article outlines the structure and barrier function of the stratum corneum and compares the characteristics of three types of impairment: inflammatory dermatoses, wound-related barrier loss, and iatrogenic barrier disruption. Using Fick's law of diffusion as a conceptual framework, it analyzes the core determinants of percutaneous absorption and compares the pharmacological profiles of commonly used agents, including lidocaine, prilocaine, tetracaine, and benzocaine. Available case evidence is synthesized, and the clinical presentation and differential diagnosis of systemic toxicity are summarized. A clinical risk stratification framework is proposed for patients with compromised skin barriers, and the potential and limitations of emerging strategies, including nanocarrier delivery, microneedle patches, and cryoanalgesia, are discussed. Existing evidence is predominantly derived from case reports, in vitro or animal studies, and small-scale clinical observations; pharmacokinetic data quantitatively relating the severity of barrier impairment to systemic exposure remain limited. Dosing regimens validated in intact skin should not be directly extrapolated to patients with barrier impairment. Future research should focus on developing pharmacokinetic prediction models integrating barrier injury type, administration parameters, and patient characteristics.