title: Serum creatinine may indicate risk of symptomatic intracranial hemorrhage after intravenous tissue plasminogen activator (IV tPA).
abstract: Symptomatic intracranial hemorrhage (sICH) is a known complication following administration of intravenous tissue plasminogen activator (IV tPA) for acute ischemic stroke. sICH results in high rates of death or long-term disability. Our ability to predict its occurrence is important in clinical decision making and when counseling families. The initial National Institute of Neurological Disorders and Stroke (NINDS) investigators developed a list of relative contraindications to IV tPA meant to decrease the risk of subsequent sICH. To date, the impact of renal impairment has not been well studied. In the current study we evaluate the potential association between renal impairment and post-tPA intracranial hemorrhage (ICH). Admission serum creatinine and estimated glomerular filtration rate (eGFR) were recorded in 224 patients presenting within 4.5 hours from symptom onset and treated with IV tPA based on NINDS criteria. Neuroimaging was obtained 1 day post-tPA and for any change in neurologic status to evaluate for ICH. Images were retrospectively evaluated for hemorrhage by a board-certified neuroradiologist and 2 reviewers blinded to the patient's neurologic status. Medical records were reviewed retrospectively for evidence of neurologic decline indicating a "symptomatic" hemorrhage. sICH was defined as subjective clinical deterioration (documented by the primary neurology team) and hemorrhage on neuroimaging that was felt to be the most likely cause. Renal impairment was evaluated using both serum creatinine and eGFR in a number of ways: 1) continuous creatinine; 2) any renal impairment by creatinine (serum creatinine >1.0 mg/dL); 3) continuous eGFR; and 4) any renal impairment by eGFR (eGFR <60 mL/min per 1.73 m²). Student paired t tests, Fisher exact tests, and multivariable logistic regression (adjusted for demographics and vascular risk factors) were used to evaluate the relationship between renal impairment and ICH. Fifty-seven (25%) of the 224 patients had some evidence of hemorrhage on neuroimaging. The majority of patients were asymptomatic. Renal impairment (defined by serum creatinine >1.0 mg/dL) was not associated with combined symptomatic and asymptomatic intracranial bleeding (p = 0.359); however, there was an adjusted 5.5-fold increased odds of sICH when creatinine was >1.0 mg/dL (95% confidence interval, 1.08-28.39), and the frequency of sICH for patients with elevated serum creatinine was 10.6% (12/113), versus 1.8% (2/111) in those with normal renal function (p = 0.010). Our study suggests that renal impairment is associated with higher risk of sICH after administration of IV tPA. As IV tPA is an important and effective treatment for acute ischemic stroke, a multicenter study is needed to determine whether the observation that renal dysfunction is associated with sICH from this retrospective study holds true in a larger prospective trial.
authors.affiliation: From the Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Elisabeth B
authors.initials: EB
authors.lastname: Marsh
authors.forename: Rebecca F
authors.initials: RF
authors.lastname: Gottesman
authors.forename: Argye E
authors.initials: AE
authors.lastname: Hillis
authors.forename: Victor C
authors.initials: VC
authors.lastname: Urrutia
authors.forename: Rafael H
authors.initials: RH
authors.lastname: Llinas
mesh_terms: D061605:Administration, Intravenous; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002545:Brain Ischemia / Q000150:complications; D003404:Creatinine / Q000097:blood*; D005260:Female; D006801:Humans; D020300:Intracranial Hemorrhages / Q000097:blood / Q000139:chemically induced*; D008297:Male; D008875:Middle Aged; D051437:Renal Insufficiency / Q000097:blood / Q000150:complications*; D012189:Retrospective Studies; D012307:Risk Factors; D020521:Stroke / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage / Q000009:adverse effects* / Q000097:blood; D055815:Young Adult
chemical_list: D003404:Creatinine; D010959:Tissue Plasminogen Activator