Abstracts

Rationale: Seizures are a common occurrence in critically ill patients. The prevalence of seizures in this population has been reported to range between 17-27%. Among the antiseizure drugs with available intravenous (IV) formulations, lacosamide (LCM) is appealing for use in critically ill patients due to its novel mechanisms of action and low potential for drug-drug interactions. However, LCM has been associated with PR interval prolongation, which limits its use in patients at high-risk for developing cardiac arrhythmias or conduction abnormalities. We performed a retrospective chart review to elucidate the relationship (or lack thereof) between IV LCM use and PR interval prolongation among the critically ill. Our primary objectives were to 1) estimate the proportion of critically ill patients who have a PR interval increase of =20% from baseline after receiving at least one dose of IV LCM, and 2) estimate the proportion of critically ill patients whose PR interval shifts from a normal (=200 msec) to high (>200 msec) after receiving at least one dose of IV LCM. An analysis was performed to identify a high risk subgroup. Methods: We included 111 patients (18-89 years old) who were previously admitted to either a cardiac, medical, or neurological ICU and received at least 1 dose of IV LCM following admission at Abbott Northwestern Hospital between October 2008 and June 2017. Patients must have also had at least 1 PR interval reading within 24 hours before and after IV LCM administration. Percent change from baseline PR interval was calculated by subtracting the longest post-dose PR interval from the longest pre-dose PR interval and dividing by the longest pre-dose PR interval. Proportions of interest and 95% confidence intervals (CI) were calculated. Logistic regression analysis was used to estimate the effect of predictors on the odds of having a large increase (=20%) in PR interval following IV LCM administration. A high-risk subgroup analysis was performed. Results: Our study population had median pre- and post-dose PR interval of 180 msec (pre: 118-260 [sd: 30] msec; post: 131-320 [sd: 28] msec). Thirteen percent (95% CI [7,20]) of our patients had a =20% increase in PR interval after their first dose of IV LCM, and 14% (95% CI [6,21]) had a shift from normal to high PR interval. Our exploratory analysis found that a lower pre-dose PR interval and former smoking status increased the odds of having a =20% increase in PR interval. After adjusting for smoking status, as pre-dose PR interval increases by 1 msec, the odds of having a =20% increase in PR interval decreases by a factor of 0.92. However, after adjusting for pre-dose PR interval, having a “former” smoking status increases the odds by a factor of 26.5 compared to “never”. Conclusions: An increase of =20% in PR interval (13% of patients) and a change from normal PR interval to high PR interval (14%) were relatively common events in our study population. Due to the small sample size, the analysis was not powered to find/validate other possible predictors. To further investigate these findings, future work should include increasing the number of clinical sites, implementing a protocol requiring PR interval recordings pre- and post-dose, and adding a control group (ICU patients at the same site and observational time, who did not receive IV LCM). Funding: None