Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2012 Dec;17(3):361-6.
doi: 10.1007/s12028-012-9776-z.

Confounding by indication in retrospective studies of intracerebral hemorrhage: antiepileptic treatment and mortality

Thomas W K Battey  1 , Guido J Falcone, Alison M Ayres, Kristin Schwab, Anand Viswanathan, Kristen A McNamara, Zora Y DiPucchio, Steven M Greenberg, Kevin N Sheth, Joshua N Goldstein, Jonathan Rosand
Affiliations

Confounding by indication in retrospective studies of intracerebral hemorrhage: antiepileptic treatment and mortality

Thomas W K Battey et al. Neurocrit Care. 2012 Dec.

Abstract

Introduction: Intracerebral hemorrhage (ICH) is a highly fatal disease with few proven treatments. Data to guide clinician decisions for therapies, including antiepileptic drugs (AED), are limited. Published studies on AED treatment in ICH have provided conflicting results. We investigated the effect of AED treatment on 90-day mortality after ICH in a large prospectively ascertained cohort.

Methods: We conducted a retrospective analysis of a prospectively assembled cohort of patients with ICH in the supratentorial regions, comparing 90-day mortality and modified Rankin Score among 543 patients treated with AED during hospitalization and 639 AED-free ICH. Supratentorial ICH location was categorized as lobar or deep hemispheric.

Results: Multivariate analysis demonstrated an association between AED treatment and reduced 90-day mortality in supratentorial ICH (OR = 0.62, 95 % CI 0.42-0.90, p = 0.01) and the subset of lobar ICH (OR = 0.49, 95 % CI 0.25-0.96, p = 0.04). When analyses were restricted to subjects surviving longer than 5 days from ICH, however, no association between AED treatment and a 90-day outcome, regardless of hemorrhage location (all p > 0.15), was detected, despite more than adequate power to detect the originally observed association.

Conclusion: These results suggest that AED treatment in acute ICH is not associated with 90-day mortality or outcome and that any detected association could arise by confounding by indication, in which the most severely affected patients are those in whom AEDs are prescribed. They provide a cautionary example of the limitations of drawing conclusions about treatment effects from observational data.

PubMed Disclaimer

Comment in

References

    1. Qureshi AI, Tuhrim S, Broderick JP, Batjer H, Hondo H, Hanley DF. Spontaneous intracerebral hemorrhage. N Engl J Med. 2001;344(19):1450–60. - PubMed
    1. Van Asch CJ, Luitse MJ, Rinkel GJ, van der Tweel I, Algra A, Klijn CJ. Incidence, case fatality, and functional outcome of intracerebral haemorrhage over time, according to age, sex, and ethnic origin: a systematic review and meta-analysis. Lancet Neurol. 2010;9:167–76. - PubMed
    1. De Herdt V, Dumont F, Henon H, Derambure P, Vonck K, Leys D, Cordonnier C. Early seizures in intracerebral hemorrhage: incidence, associated factors, and outcome. Neurology. 2011;77(20):1794–800. - PubMed
    1. Vespa PM, O’Phelan K, Shah M, et al. Acute seizures after intracerebral hemorrhage: a factor in progressive midline shift and outcome. Neurology. 2003;60(9):1441–6. - PubMed
    1. Messe SR, Sansing LH, Cucchiara BL, Herman ST, Lyden PD, Kasner SE. Prophylactic antiepileptic drug use is associated with poor outcome following ICH. Neurocrit Care. 2009;11(1):38–44. - PubMed

Publication types

Substances