Transdermal Nicotine Replacement Therapy in Cigarette Smokers with Acute Subarachnoid Hemorrhage

Abstract

We evaluated the safety of nicotine replacement therapy (NRT) in active smokers with acute (aneurysmal) subarachnoid hemorrhage (SAH). A retrospective observational cohort study was conducted in a prospectively collected database including all SAH patients admitted to an 18-bed neuro-ICU between January 1, 2001 and October 1, 2007. Univariate and multivariable models were constructed, employing stepwise logistic regression. The primary endpoint was 3-month mortality. Delayed cerebral ischemia (DCI) due to vasospasm, angiographic and TCD evidence of vasospasm, and delirium were secondary endpoints. Active cigarette smokers admitted with SAH included 128 that received NRT and 106 that did not. Patients were well-matched for age, admission Hunt-Hess Grade, radiographic findings, and APACHE II scores, but those who received NRT were more likely to be heavy smokers (>10 cigarettes daily), diabetic, heavy alcohol users, and to have cerebral edema on admission. NRT was associated in multivariate analysis with a lower risk of death at 3 months (OR 0.12, 95% CI 0.04-0.37, P < 0.001). There were no differences in the frequency of DCI and most other medical complications, but delirium (19 vs. 9%, P = 0.006) and seizures (9 vs. 2%, P = 0.024) were more common in patients who received NRT. Despite vasoactive properties, administration of NRT among active smokers with acute SAH appeared to be safe, with similar rates of vasospasm and DCI, and a slightly higher rate of seizures. The association of NRT with lower mortality could be due to chance, to uncontrolled factors, or to a neuroprotective effect of nicotine in active smokers hospitalized with SAH, and should be tested prospectively.