<b>Buffered Versus Non-Buffered Dental Local Anesthetics: A Systematic Review and Meta-analysis of Within-Subject Clinical Studies</b>

Buffered Versus Non-Buffered Dental Local Anesthetics: A Systematic Review and Meta-analysis of Within-Subject Clinical Studies ABSTRACT Background: Buffering dental local anesthetics (LAs) with sodium bicarbonate has been proposed to reduce injection pain and improve anesthetic performance; however, clinical evidence remains inconsistent and methodologically heterogeneous. Objectives: To evaluate the effects of buffered versus non-buffered dental LAs on anesthetic success, pain, onset time, and duration, restricting inclusion to within-subject study designs and exploring injection technique and buffering ratio as potential effect modifiers. Methods: A PRISMA-compliant systematic review and pairwise meta-analysis was conducted. Split-mouth and cross-over studies in adult patients receiving dental LAs were included. Primary outcomes were anesthetic success and duration; secondary outcomes were pain during puncture and injection, onset time, and adverse effects. Random-effects models were applied, with subgroup analyses and meta-regressions according to injection technique. Results: Fifteen studies (518 participants; 1,105 injections) were included, with 14 contributing to quantitative synthesis. Overall anesthetic success did not differ between buffered and non-buffered LAs (OR = 1.00; 95% CI 0.84–1.19; I² = 0%). Buffered solutions significantly reduced pain during puncture (MD = −0.90; p = 0.037) and showed technique-dependent effects for pain during injection and anesthesia duration, particularly for inferior alveolar nerve block (IANB). No consistent benefit was observed for onset time. Substantial heterogeneity was present for several outcomes. Conclusions: Buffering dental LAs does not improve anesthetic success but provides clinically relevant comfort benefits, particularly by reducing puncture-related pain and in selected injection techniques. Buffering should be regarded primarily as a comfort-oriented strategy rather than an efficacy-enhancing intervention.