The Impact of Loading Dose on Outcome in Stroke Patients Receiving Low-Dose Tissue Plasminogen Activator Thrombolytic Therapy

Abstract

Background

Intravenous tissue plasminogen activator (tPA) (0.9 mg/kg, maximum 90 mg) with a bolus of 10% of the total dose given within 1–2 mins is the standard therapy for patients receiving thrombolytic therapy. Low-dose (0.6 mg/kg) tPA is also approved for thrombolytic therapy for ischemic stroke patients. Low-dose tPA is associated with a low bolus dose. It is unknown whether increasing the bolus dose in patients receiving low-dose tPA thrombolysis may improve outcomes or increase the risk of hemorrhagic transformation (HT).

Aim

This study investigated the impact of the bolus dose on the outcome in ischemic stroke patients receiving low-dose tPA thrombolytic therapy.

Methods

In this retrospective, observational study, we enrolled 214 ischemic stroke patients receiving low-dose tPA thrombolytic therapy. Of these 214 patients, 107 patients received 10% of the total dose as a bolus dose, and 107 patients received 15% of the total dose as a bolus dose. The National Institutes of Health Stroke Score (NIHSS) were evaluated before tPA infusion, 24 h after thrombolytic therapy, and at discharge. Stroke severity was categorized as mild (0–5), moderate (6–14), severe (15–24), or very severe (≥25). Neurological improvement (NI) was defined as an improvement of 6 or more points in the NIHSS, and no response (NR) was defined as an increase in the NIHSS of ≤4 points or a decrease ≤6 points. Neurological deterioration (ND) was defined as an increase in the NIHSS >4 points. A good outcome was defined as a modified Ranking Score (mRS) of 0 or 1. We compared the NI, NR, and ND rates at 24 hrs after thrombolytic therapy and discharge between the 15% and 10% bolus dose groups.

Results

In patients with mild and moderate stroke, there was no significant difference in the NI, NR, ND, and HT rates and 6-month outcomes between the 15% and 10% bolus groups. In patients with severe and very severe stroke, outcomes at 6 months were significantly better in the 15% bolus group than in the 10% bolus group. The factors affecting the outcomes of severe and very severe stroke patients are hypertension and bolus dose.

Conclusion

In severe and very severe stroke patients receiving low-dose tPA thrombolytic therapy, a bolus dose of 15% of the total dose can improve outcomes.

Keywords:

• ischemic stroke
• tPA
• thrombolysis
• hypertension
• outcome

Disclosure

The authors report no conflicts of interest in this work.