Editorial Comment—Over-the-Counter Cold Remedies and Stroke

Abstract

Background and Purpose-Phenylpropanolamine (PPA) and pseudoephedrine are sympathomimetics contained in over-the-counter cold preparations. A case-control study linked PPA use with hemorrhagic stroke in women. Twenty-two patients with stroke associated with use of these drugs are described. Methods-In a consecutive stroke registry since 1988, 22 patients had stroke associated with over-the-counter sympathomimetics. Sympathomimetic dosage and type, time interval until stroke onset, and neuroimaging findings are described. Results-Ten male and 12 female patients were included. Intracerebral hemorrhage occurred in 17 patients, subarachnoid hemorrhage in 4, and ischemic stroke in 1. Stroke was associated with PPA use in 16 patients (dose 75 to 675 mg), with pseudoephedrine in 4 (dose 60 to 300 mg), and with others administered by the nasal route in 2 (oxymetazoline and phenylephrine). Stroke occurred after a single dose in 17 patients and after daily use during several days in 5. The interval between drug exposure and clinical onset varied from 30 minutes to 24 hours. Stroke occurred after recommended doses of PPA (50 to 75 mg) in 32% and pseudoephedrine (60 mg) in 50% of patients. Eight patients had acute hypertension at stroke onset. Cerebral angiography was normal in 8 cases and showed diffuse vasospasm or beading in 10 patients. Conclusions-Stroke related to over-the-counter sympathomimetics was associated with acute hypertension and/or vasospasm or angiitis mechanisms, most related to the use of PPA; however, stroke also occurred with the use of other sympathomimetics, particularly pseudoephedrine. Although stroke complications occurred when doses were used that were higher than recommended doses, apparently there is also a stroke risk when these agents are taken properly.

Postpartum Phenylpropanolamine-Induced Intracerebral Hemorrhage

“…Spurred by these reports, in 1992 the FDA and PPA manufacturers collaborated to study the association between PPA and hemorrhagic stroke [3]. The Kernan study found that women age 18–49 who had taken PPA as a cold remedy had an increased odds ratio of 3.13 for intracranial hemorrhage.…”

“…The mechanism behind this outcome has variously been described as necrotizing angiitis, vascular spasm, and hypertensive crisis [1, 2]. PPA is not unique in causing adverse events; ephedra, phenylephrine, and pseudoephedrine have all been associated with hypertension, stroke, seizure, and death [3]. …”

Stroke associated with pseudoephedrine in a child with rhabdomyosarcoma

“…Ischemic and hemorrhagic strokes have occurred in ephedrine users, and intracranial hemorrhage has followed pseudoephedrine use. 2,3 Case reports describe cerebral infarction and retinal artery branch occlusion in chronic intranasal abusers of sprays and drops containing phenoxazoline or oxymetazoline. Proposed mechanisms involve surges of hypertension, cerebral vasospasm (sometimes evident at angiography), and vasculitis.…”

“…Although extensive studies have not been performed, acquired anticoagulant protein deficiencies may be associated with stroke in special clinical settings includ- ing malignancies. 2,3,5 Our patientÕs primary disease was rhabdomyosarcoma and no other drug known to increase the risk of stroke had been administered.…”

“…Intracerebral hemorrhage secondary to a number of sympathomimetic drugs has been reported and pseudoephedrine has been found responsible for some strokes in children. [1][2][3] We report a 4-year-old girl with nasopharyngeal rhabdomyosarcoma who developed stroke while on pseudoephedrine therapy.…”