• M Soledad Cepeda, Aikaterini Tzortzopoulou, Michael Thackrey, Jana Hudcova, Preeti Arora Gandhi, and Roman Schumann.
• Pharmacoepidemiology, Johnson & Johnson Pharmaceutical Research and Development, PO BOX 200, M/S K304, Titussville, NJ, USA, 08560.
• Cochrane Db Syst Rev. 2010 Jan 1(12):CD006581.

BackgroundLidocaine administration produces pain due to its acidic pH.ObjectivesThe objective of this review was to determine if adjusting the pH of lidocaine had any effect on pain resulting from non-intravascular injections in adults and children. We tested the hypothesis that adjusting the pH of lidocaine solution to a level closer to the physiologic pH reduces this pain.Search StrategyWe searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, to June 2010); Ovid MEDLINE (1966 to June 2010); EMBASE (1988 to June 2010); LILACS (1982 to June 2010); CINAHL (1982 to June 2010); ISI Web of Science (1999 to June 2010); and abstracts of the meetings of the American Society of Anesthesiologists (ASA). We checked the full articles of selected titles. We did not apply any language restrictions.Selection CriteriaWe included double-blinded, randomized controlled trials that compared pH-adjusted lidocaine with unadjusted lidocaine. We evaluated pain at the injection site, satisfaction and adverse events. We excluded studies in healthy volunteers.Data Collection And AnalysisWe separately analysed parallel-group and crossover trials; trials that evaluated lidocaine with or without epinephrine; and trials with pH-adjusted lidocaine solutions < 7.35 and ≥ 7.35. To explain heterogeneity, we separately analysed studies with a low and higher risk of bias due to the level of allocation concealment; studies that employed a low and a higher volume of injection; and studies that used lidocaine for different types of procedures.Main ResultsWe included 23 studies of which 10 had a parallel design and 13 were crossover studies. Eight of the 23 studies had moderate to high risk of bias due to the level of allocation concealment.Pain associated with the infiltration of buffered lidocaine was less than the pain associated with infiltration of unbuffered lidocaine in both parallel and crossover trials. In the crossover studies, the difference was -1.98 units (95% confidence interval (CI) -2.62 to -1.34) and in the parallel-group studies it was -0.98 units (95% CI -1.49 to -0.47) on a 0 to 10 scale. The magnitude of the pain decrease associated with buffered lidocaine was larger when the solution contained epinephrine. The risk of bias, volume of injection, and type of procedure failed to explain the heterogeneity of the results.Patients preferred buffered lidocaine (odds ratio 3.01, 95% CI 2.19 to 4.15). No adverse events or toxicity were reported.Authors' ConclusionsIncreasing the pH of lidocaine decreased pain on injection and augmented patient comfort and satisfaction.

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