The permanent effects of stroke, a deadly brain injury characterized by reduced blood flow, can be limited by the timely administration of a drug called tissue plasminogen activator (tPA). tPA helps restore blood flow to the affected brain region. While administration of this drug is a common practice, not much is known about the effectiveness of different “loading dosages,” or boluses. It is a percentage of the total dose, typically 10% or 15%, that is administered to the patient within minutes. The rest of the drug is administered intravenously over the course of about one hour.

Drug dosages are often given as a proportion of someone’s body weight, such as milligrams per kilogram, or mg/kg. For tPA, the recommended administration is between 0.6 mg/kg and 0.9 mg/kg, which represent low and high doses, respectively. For example, a 75 kg person might be prescribed a dosage of 75 kg x (0.6 mg/kg) = 45 mg of tPA.

drug vial

“plain” is licensed under CC0 1.0

Taiwanese neurologists were the first to compare outcomes in stroke patients who were treated with either 10% or 15% of low dose tPA as a bolus. Stroke severity, brain scans, and health outcomes were recorded for 214 patients treated at the Chia-Yi Christian Hospital in Taiwan. For patients of all stroke severity, the 15% bolus group had higher rates of good outcomes than in the 10% bolus group.

Interestingly, the 15% bolus dose was associated with a lower risk of poor outcomes for patients with severe and very severe strokes only. This was not the case for mild or moderate stroke patients. Given these findings, people with strokes of greater severity might require higher loading doses to restore blood flow to the affected brain region.

In this study, the researchers only administered “low dose” tPA, or 0.6 mg/kg. Similar studies have looked at stroke outcomes, but only with high doses of tPA (i.e. 0.9 mg/kg). Thus, the present findings help create a more robust literature surrounding tPA administration.

When stroke patients requiring tPA arrive to the hospital, physicians have the following question to consider: what dosage should be administered, and at what bolus dose?

Other work has associated higher doses with adverse outcomes, prompting the Taiwanese researchers to focus on the effectiveness of low dose tPA. Combined with the present findings, 0.6 mg/kg of tPA with a 15% bolus dose is likely the most effective combination. This information can help better inform physicians when making time-sensitive, life or death decisions.

 

Citations
Wong Y.S., Sung S.F., Wu C.S., Hsu Y.C., Su Y.H., Hung L.C., and Ong C.T. 2020. The impact of loading dose on outcome in stroke patients receiving low-dose tissue plasminogen activator thrombolytic therapy. Drug Design, Development and Therapy 14: 257-263.