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  • Impact of current generation anticonvulsant prophylaxis on outcome after ICH

    Final Number:

    Carlton Christie BA; Nicole Matthews BA; Erik B. Lehman MSc; Kevin M. Cockroft MD

    Study Design:

    Subject Category:
    Intracranial Hemorrhage/Critical Care

    Meeting: AANS/CNS Cerebrovascular Section 2017 Annual Meeting

    Introduction: The role of prophylactic anticonvulsants in preventing seizures and/or improving outcome after intracerebral hemorrhage (ICH) remains controversial. Current guidelines recommend against prophylaxis. However, these recommendations are based on older studies primarily utilizing phenytoin (Dilantin) as the anticonvulsant of choice. Newer medications, such as levetiracetam (Keppra), have yet to be extensively studied.

    Methods: We performed a retrospective review of our clinical database from 2010 to 2015. All patients with the diagnosis of ICH were included. Patients were divided into those who received prophylactic anticonvulsants and those who did not. Patient demographics, as well as seizure data and outcomes were collected. Results were analyzed using binary logistic regression and quantile regression models, each analysis was corrected for age, gender, and initial NIHSS score. The primary outcomes included seizure frequency, discharge disposition and follow-up NIHSS/mRS.

    Results: A total of 522 patients were included in the study. Average age was 68 and 53.1% were male. Median initial NIHSS was 10 (IQR, 2-19), prophylaxis group 12 (IQR, 4-23), and no prophylaxis group 6 (IQR, 1-18.5), p=0.003). Of the 342 patients (65.5%) that received prophylactic anticonvulsants, 320 (94%) received levetiracetam and 27 (7.9%) had seizure events compared with 22 (12.2%) of those without prophylaxis. Patients treated with anticonvulsant prophylaxis had significantly lower odds of a seizure (adjusted OR, 0.44; 95%CI, 0.23-0.97). However, there were no significant differences in follow-up NIHSS, follow-up mRS, or discharge disposition between groups. Median length of stay was longer in patients that received prophylaxis (difference, 1.5 days; 95%CI, 2.4-0.6; p=0.001). Patients treated prophylactically also had higher total hospital charges (difference, $8441; 95%CI, 15215-1667; p=0.002).

    Conclusions: Administration of predominantly levetiracetam for anticonvulsant prophylaxis after ICH significantly reduced the odds of seizure, but was associated with a longer hospital stay and higher total hospital charges. Prophylaxis did not afford significant improvement in measures of clinical outcome.

    Patient Care: This research seeks to provide evidence of the ability of newer anticonvulsant prophylaxis to prevent seizure after ICH. In doing so, this research will improve patient care by informing future clinical trials and physician's opinions on the costs and benefits of administering newer anticonvulsant agents prophylactically after ICH.

    Learning Objectives: By the conclusion of this session, participants should be able to 1) Describe the importance of preventing seizure after ICH and the risk factors of seizure after ICH, 2) Discuss in small groups the evidence for newer generation anticonvulsants in preventing seizure after ICH. 3) Identify future directions that aim to resolve the controversy surrounding anticonvulsant prophylaxis after ICH.

    References: 1. Sykes L, Wood E, Kwan J. Antiepileptic drugs for the primary and secondary prevention of seizures after stroke. In: Kwan J, ed. Cochrane Database of Systematic Reviews. Chichester, UK: John Wiley & Sons, Ltd; 2014. doi:10.1002/14651858.CD005398.pub3. 2. Burn J, Dennis M, Bamford J, Sandercock P, Wade D, Warlow C. Epileptic seizures after a first stroke: the Oxfordshire community stroke project. BMJ. 1997;315(7122). 3. Kilincer C, Asil T, Utku U, et al. Factors affecting the outcome of decompressive craniectomy for large hemispheric infarctions: a prospective cohort study. Acta Neurochir (Wien). 2005;147(6):587-94; discussion 594. doi:10.1007/s00701-005-0493-7. 4. Beghi E, D’Alessandro R, Beretta S, et al. Incidence and predictors of acute symptomatic seizures after stroke. Neurology. 2011;77(20):1785-1793. doi:10.1212/WNL.0b013e3182364878. 5. De Herdt V, Dumont F, Hénon H, et al. Early seizures in intracerebral hemorrhage: incidence, associated factors, and outcome. Neurology. 2011;77(20):1794-1800. doi:10.1212/WNL.0b013e31823648a6. 6. Bladin CF, Alexandrov A V, Bellavance A, et al. Seizures after stroke: a prospective multicenter study. Arch Neurol. 2000;57(11):1617-1622. 7. Passero S, Rocchi R, Rossi S, Ulivelli M, Vatti G. Seizures after Spontaneous Supratentorial Intracerebral Hemorrhage. Epilepsia. 2002;43(10):1175-1180. doi:10.1046/j.1528-1157.2002.00302.x. 8. Hemphill JC, Greenberg SM, Anderson CS, et al. Guidelines for the Management of Spontaneous Intracerebral Hemorrhage. Stroke. 2015;46(7):2032-2060. doi:10.1161/STR.0000000000000069. 9. Gilmore EJ, Maciel CB, Hirsch LJ, Sheth KN. Review of the Utility of Prophylactic Anticonvulsant Use in Critically Ill Patients With Intracerebral Hemorrhage. Stroke. 2016;47(10).

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