A Randomized Controlled Trial on the Hemodynamic and Molecular Responses to Lidocaine with Epinephrine Versus Mepivacaine in Hypertensive Patients Undergoing Dental Extraction

The use of local anesthetics with vasoconstrictors in hypertensive patients undergoing dental procedures remains a clinical concern due to potential adverse cardiovascular events. This study aimed to provide a comprehensive comparison of the hemodynamic, inflammatory, and genetic responses to lidocaine with epinephrine versus plain mepivacaine in controlled hypertensive patients undergoing tooth extraction.

This prospective, randomized, double-blind clinical trial included 80 controlled hypertensive patients scheduled for tooth extraction. Patients were randomly assigned to receive either 2% lidocaine with 1:80,000 epinephrine (Group L, n=40) or 3% mepivacaine plain (Group M, n=40). Hemodynamic parameters (systolic blood pressure [SBP], Diastolic Blood Pressure [DBP], Heart Rate [HR]) were recorded at baseline, 3 minutes post-injection, and 3 minutes post-extraction. Venous blood samples were collected at baseline and 30 minutes post-extraction to analyze inflammatory biomarkers (hs-CRP, IL-6, TNF-α) and for genotyping of CYP1A2 and ADRB2 polymorphisms.

Group L demonstrated significantly greater hemodynamic stability, with smaller fluctuations in SBP and HR compared to Group M (p<0.05). Post-procedure, Group M showed a significant increase in serum hs-CRP and IL-6 levels (p<0.01), whereas Group L showed no significant change. Patients with the CYP1A2 *1F allele (A/A genotype) showed slower lidocaine metabolism and a transient increase in DBP. A significant association was found between the ADRB2 Gly16Arg polymorphism and increased HR variability in both groups.

The finding of more significant hemodynamic instability and inflammatory response within the mepivacaine group suggests that inadequate anesthesia causes a substantial endogenous catecholamine stress response, which is likely more damaging than a minimal amount of exogenous epinephrine. Additionally, genetic differences in CYP1A2 and ADRB2 influence individual physiologic responses and support a biological explanation for the variability is seen across patients.

Lidocaine with epinephrine was associated with superior hemodynamic stability and a blunted systemic inflammatory response compared to plain mepivacaine. These findings suggest that the inclusion of a vasoconstrictor may offer a safer and more controlled anesthetic profile for hypertensive patients. Pharmacogenetic variations in CYP1A2 and ADRB2 may influence individual patient responses, highlighting the potential for personalized anesthetic strategies.