Lidocaine is commonly used as a local anesthetic, though true allergies to local anesthestics are rare and often stem from the preservative methylparaben in multi-dose vials. Ester anesthetics like procaine and tetracaine may cause similar reactions due to their degradation product, para-amino benzoic acid (PABA). Single-dose lidocaine without preservatives can be a safer option, though differentiating between preservatives and anesthetics can be challenging. Although diphenhydramine has been explored as an alternative, injection of diphenhydramine may be painful and associated with various side effects. Despite this, the chemical structure of diphenhydramine is dissimilar enough to where the antigenicity is quite different to local anesthetics. For this reason, a 1998 randomized, double-blind trial compared 0.9% buffered lidocaine, 0.9% benzyl alcohol with epinephrine, and 1% diphenhydramine to assess pain of infiltration and anesthesia duration. Results showed that 1% diphenhydramine was associated with an increased pain of infiltration and less pronounced anesthetic effect. Nevertheless, this study suggests that diphenhydramine may still be a preferable alternative in patients with allergies to other local anesthetics and/or epinephrine due to these antigenic differences (see Table 1). [1]
A 2016 retrospective review assessed the safety of subcutaneous diphenhydramine administration in the hospice setting. Of note, this study evaluated the safety of subcutaneous diphenhydramine injections at a concentration of 5%, rather than 1%. Investigators collected data from six inpatient hospice units via a pharmacy database, and identified a total of 648 administrations of subcutaneous diphenhydramine injections in 109 individual patients. Doses of diphenhydramine administered were either 12.5, 25, or 50 mg. Notably, the findings revealed that no adverse reactions were reported post-administration, suggesting that subcutaneous diphenhydramine is a safe alternative to oral and other parenteral routes, along with those with “caine” allergies. However, despite these results, caution in interpretation is warranted as the efficacy of subcutaneous diphenhydramine injections was not assessed. [2]