Wednesday, February 24, 2016

Weighing In On Alteplase Dosing: Is Estimating Weight Harming Our Patients?

When a stroke victim rolls into the emergency department (ED) we know we have a limited time window to administer alteplase (recombinant tissue-type plasminogen activator [r-tPA]). The pressure of this narrow therapeutic window often pressures hospital staff to administer the potentially brain-saving medication as early as possible. Often, administration is hastened by estimating patient weight as a basis for calculating the critical 0.9 mg/kg weight-based dose.

However, the question remains if we are appropriately estimating patient weight and if not, what consequences does this bear on the patient?

A retrospective analysis by Barrow et al. recently published in Stroke is the largest study to date on this topic.1 The study analyzed 242 patients with stroke who received an alteplase dose based on an estimated body weight. Following determination of actual patient weight investigators calculated the dosing error. Primary outcome measures included improvement in National Institute of Health Stroke Scale (NIHSS) and modified Rankin Scale (mRS) scores.

Alarmingly, investigators found that 19.7% of patients received an inappropriate dose (as defined by a deviation of at least 10% from appropriate calculated dose). Clinicians in the study significantly over-dosed the lightest patients and under-dosed the heaviest patients.

Dosing errors did not significantly affect mRS scores or rate of intracranial hemorrhage (ICH). However, NIHSS score improvement was greater in the subset of patients of the lightest weight in comparison to the subset of patients of the heaviest weight (p = 0.048). These results conflict with earlier findings by Messé et al. citing an increased trend of ICH in patients who received higher doses due to overestimation of weight with no findings of decreased efficacy in patients who received lower doses due to underestimation of weight.2

Of notable importance, heavier patients in the study were associated with higher baseline NIHSS scores, implying that heavier patients had more severe strokes (p < 0.001).1 Thus, whether the heavier patients in the study had poorer outcomes due to under-dosing, higher stroke severity, or a combination of the two remains unclear.

What is clear? Estimating weight for alteplase dosing is clearly unreliable and an error rate of nearly 20% is alarming and consistent with prior findings.

Hall et al. found that an ED provider cohort made up of physicians, paramedics, nurses, and medical students appropriately estimated weight within 5 kg in only 28.1% of patients.3 Additional research from the WAIST-study also revealed an error rate of 33% and also described a trend of worse outcomes in under-dosed stroke patients.4

Based on the consistent erroneous findings of weight estimating in stroke patients across various studies, the utilization of beds in the ED with the capability of measuring weight should be used whenever possible in order to minimize weight-based dosing errors and their potentially negative impact on patient outcomes.

Laura C. Johnson, PharmD
PGY-1 Pharmacy Resident
Trinity Mother Frances Hospital
Tyler, Texas

Peer reviewed by:
Craig Cocchio, PharmD, BCPS


1. Barrow T, Khan MS, Halse O et al. Estimating weight of patients with acute stroke when dosing for thrombolysis. Stroke. 2016;47(1):228-31.
2. Messé SR, Tanne D, Demchuk AM et al. Dosing errors may impact the risk of rt-PA for stroke:
the Multicenter rt-PA Acute Stroke Survey. J Stroke Cerebrovasc Dis. 2004;13(1):35-40.
3. Hall WL, Larkin GL, Trujillo MJ et al. Errors in weight estimation in the emergency department: comparing performance by providers and patients. J Emerg Med. 2004;27(3):219-24.
4. Breuer L, Nowe T, Huttner HB et al. Weight approximation in stroke before thrombolysis: the WAIST-Study: a prospective observational "dose-finding" study. Stroke. 2010;41(12):2867-71.