The correct answer is:

Errors in alteplase administration are associated with a higher rate of hemorrhagic conversion.

Key Point:

A 2021 retrospective review found that errors in alteplase administration occurred in nearly 20% (19.8%) of patients receiving alteplase for ischemic stroke. Errors were associated with a statistically significant increased conversion from ischemic to hemorrhagic stroke (7.1% for patients receiving correctly administered alteplase versus 12.7% for patients receiving incorrectly administered alteplase). Neither functional outcome (modified Rankin scale) nor the rate of discharges to home rates were altered by the occurrence of an alteplase error.

Explanation:

Alteplase is a complex drug that is infused as a bolus followed by an infusion – all of which must be calculated based on a mg/kg formula under extreme time pressure. Several reviews have found that this rendered alteplase a drug with a high administration error rate.

The 2021 review found that nearly 20% of their reviewed stroke patients received alteplase incorrectly. The 4 most common error were in descending order (1) most common - calculation error resulting in too high dose (>110% of correct dose), (2) calculation error resulting in too low dose (<90% of correct dose), (3) a missed contraindication, and finally (4) incorrect infusion rate (infusion after bolus lasting less or more than the recommended 60 minutes).

Of these 4 errors, 1.6% occurred at comprehensive stroke centers (CSC), 29.4% occurred at regional centers that were either designated as acute stroke ready regional hospitals (ASR) or primary stroke center regional hospitals (PSC). By far the largest portion of errors (69%) occurred at regional centers without a stroke center designation.

The single most common error, incorrect dose calculation (too high or too low), accounted for 23% of all errors, and was most commonly (16% all calculation errors) caused by reliance on erroneous patient weight information. The authors specifically mentioned that overweight patient’s weight was often underestimated (not overestimated). They did not comment on patient characteristics associated with the single most common error - overestimating a patient’s weight.

The authors of an earlier study (Barrow, 2016) concluded that the following 2 interventions would be most effective at decreasing the high error rate of alteplase infusion errors: (1) beds capable of weighing patients in the emergency department and (2) incorporation of a pharmacist into stroke protocols who is responsible for overseeing correct alteplase administration.

Review:

The recommended treatment dose of alteplase is 0.9 mg/kg total body weight, not to exceed 90 mg total treatment dose (this corresponds to a 96 kg or 211 lbs. patient) infused over 60 minutes. Of this total dose, 10% should be administered as an initial bolus over 1 minute.

(Minor detail: even though overdosing was the single most common error and would logically be expected to increase the rate of hemorrhagic conversion, the authors’ statement about increased hemorrhagic conversion was associated with ALL alteplase errors combined.)

References:

Dancsecs KA, Nestor M, Bailey A, et al. Identifying errors and safety considerations in patients undergoing thrombolysis for acute ischemic stroke. Am J Emerg Med 2021; 47: 90-94

Barrow T, Khan MS, Halse O, et al. Estimating Weight of Patients With Acute Stroke When Dosing for Thrombolysis. Stroke 2016; 47(1): 228-231; Published ahead of print November 10, 2015.

Monitor patients during and post Activase® administration. Genentech 2021 copyright.

Powers WJ, Rabinstein AA, Ackerson T, et al. Guidelines for the early management of patients with acute ischemic stroke: 2019 update to the 2018 guidelines for the early management of acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2019;50:e344-e418.