Cumulative Exposure and Cardiovascular Risk: Predictors of Serious Adverse Outcomes Following Long-Term Intravenous...

Intravenous (IV) lidocaine has emerged as a non-opioid alternative for chronic pain management. However, the safety profile of repeated, long-term administration, particularly regarding cumulative exposure and cardiovascular comorbidities, remains poorly defined.

To identify risk factors for serious adverse outcomes (SAOs) following IV lidocaine infusion in chronic pain patients.

A retrospective cohort study examined 1,093 patients treated with IV lidocaine at a hospital-based pain clinic in Israel (2014-2022), totaling 15,820 infusions. SAOs were defined as emergency department visits within 14 days of infusion. Multivariable logistic regression and Generalized Estimating Equations (GEE) were used to assess predictors, including cardiovascular disease, cerebrovascular accident (CVA) history, diabetes mellitus, and cumulative infusion count, to distinguish between true dose-frequency effects and artifacts of cumulative exposure time. A secondary analysis retained only events plausibly attributable to lidocaine based on its pharmacological profile.

Fifty-five patients (5.0%) experienced SAOs. Cumulative exposure exceeding 50 infusions was the strongest predictor of adverse outcomes (OR = 12.58, p < 0.001). A GEE model accounting for repeated measures revealed that the risk per individual infusion remained stable and did not increase with the infusion sequence number (OR = 1.00, p = 0.854). CVA history was initially significant but lost significance in the secondary analysis when restricted to plausibly lidocaine-related events (n = 30), suggesting the association reflected disease progression rather than treatment effect. Conversely, pre-existing cardiovascular disease emerged as a significant predictor only in the refined analysis (OR = 3.88, p = 0.008), consistent with lidocaine's known cardiac electrophysiological effects.

IV lidocaine demonstrates a favorable safety profile with low SAO incidence. While the statistical probability of an event increases with total exposure time, the per-infusion risk remains stable across the treatment course suggesting an absence of cumulative physiological toxicity. Pre-existing cardiovascular disease, specifically ischemic heart disease and arrhythmias, remains a primary risk factor. These findings support the use of enhanced cardiac monitoring for patients with these specific cardiovascular comorbidities and periodic risk-benefit reassessments for high-utilization patients.