Thrombolysis Dosing in Stroke: A Guessing Game?

Pauline Anderson

December 22, 2015

Doctors don't always correctly estimate the weight of stroke patients, especially overweight ones, which can result in underdosing of thrombolysis, a new study shows.

Missing the mark on dosing can affect clinical outcomes, the study authors say.

"We're not very good at guessing weight; we're worse at guessing weight when people are heavier, and in the western world people are heavier, so patients are getting the wrong dose and ending up with poorer outcomes," said study author Pankaj Sharma, MD, PhD, professor of neurology, University of London, United Kingdom.

Dr Pankaj Sharma

To address this problem, the researchers recommend that all hospital emergency departments have a bed that automatically weighs stroke patients.

The study, one of the largest to date on weight estimation in the acute stroke setting, was published online November 10 in Stroke.

Researchers studied 242 consecutive patients in a large London tertiary stroke center. For each patient, they recorded the estimated weight and calculated doses of the recombinant tissue-type plasminogen activator (r-tPA) alteplase using the recommended 0.9 mg/kg. This dose is limited to a maximum dose of 90 mg in patients weighing 100 kg or more.

A deviation of plus or minus 10% from 0.9 mg/kg dosing was considered an acceptable dose range.

"They determined thrombolysis treatment by guessing the weight, which is what normally happens pretty much everywhere," said Dr Sharma. "There's no time really to weigh patients in the ER [emergency room]; you guess the weight; you give the drug."

The following day, the patients were weighed by using clinical ward scales. "By knowing what their weight was, we were able to determine what dose the patient should have got instead of what they really got," said Dr Sharma.

Researches also recorded National Institutes of Health Stroke Scale (NIHSS) score both before tPA administration and 2, 24, and 72 hours after, as well as at discharge or 7 days.

The study showed that clinicians underestimated weights by a mean of 1.13 kg (P < .05). This remained after adjustment for age, sex, pre-tPA NIHSS score, oral anticoagulants, and comorbidities.

To determine whether extremes of weight affected estimates, researchers divided the weights into tertiles. The estimated weight error for the heaviest tertile (tertile 3, in which patients weighed 77.9 to 120 kg), was significantly different from that for the lower tertiles (P < .001), an association that remained significant after removal of patients with estimated weights greater than 100 kg and after adjustment for covariables.

Using the range 0.81 to 0.99 mg/kg as an acceptable dose, researchers divided patients into three groups: underdose, acceptable dose, and overdose. The dose for most patients (80.3%) was within the acceptable range.

Consistent with underestimation of weight, more patients were in the underdosed than the overdosed category (11.5% and 8.1%, respectively).

Patients in tertile 3 received an average dose of 77.6 mg, whereas they should have received 80.0 mg, a deficit of 3.0%. By contrast, tertile 1 received 51.54 mg, whereas they should have received 50.33 mg, leading to an overdose of 2.42%.

According to a dose error margin of plus or minus 10%, 7.1% of patients received an inaccurate dose (P = .01).

The heaviest patients had the largest mean deviation in dose: an average underdose of 0.04 mg/kg. This resulted in a 19.7% deviation of at least 10% from the recommended r-tPA dose.

Outcome Change

The researchers found that improvement on the NIHSS by discharge or by day 7 was significantly reduced in patients weighing more than 78 kg who got an incorrect dose compared with those who got a correct dose (a difference of 4.0 points; P < .05).

Those in tertile 2 (normal weight) were the most appropriately dosed and saw the greatest improvement in NIHSS score (5.30 points on average).

To achieve proper dosing, all emergency departments should have at least one bed that can automatically weigh a stroke patient, said Dr Sharma.

"You don't need every single bed to have this. Just put them on that one bed; and get their weight while you're doing everything else. This is time limited; they have to get this dose within 3.5 hours of the onset of symptoms."

Converting a normal emergency department bed to one capable of weighing patients costs only about $200, said Dr Sharma.

Yet this type of bed is rare. In the United Kingdom, he said, "nobody is using it" and he estimates that in Europe 95% are not using it. In the United States, it's probably a bit more common, with maybe 10% to 20% of emergency departments using it, he said.

While many drugs are dosed by weight, they don't have to be given within minutes or hours, "whereas these clot-busting drugs have to be given immediately," said Dr Sharma.

The authors acknowledged that worse outcomes of the heaviest patients may have been due to associated comorbidity instead of dosing errors but pointed to another large study addressing this issue in which this was not the case.

Asked to comment, David Z. Rose, MD, assistant professor, vascular neurology, medical director, neuro-ICU, Comprehensive Stroke Center, University of South Florida, Tampa, said the lack of beds that automatically weigh patients in the emergency department is "one of my pet peeves."

This was a "great article," said Dr Rose.

"Absolutely every stroke-certified hospital should have scales or beds capable of weighing patients, not only because we are generally inaccurate at 'guestimating' patients' weights, but also because a deviation of the appropriate dosing of such a powerful thrombolytic medication like tPA could potentially lead to a medical misadventure" he said.

"Either under- or overdosing tPA could in theory result in incomplete recanalization of clot in the brain, or hemorrhagic transformation of ischemic stroke, respectively," he said.

However, Dr Rose raised some "caveats" to the paper and to the idea of mandating all stroke-certified hospitals to use scales to weigh patients. These, he said, include the fact that the scales themselves may not always be accurate and require recalibration from time to time, or that they may not be used in the heat of treatment for a "brain attack."

Further, there is the cost of acquiring the scale to be considered, and he suggests that a prospective study, not just a retrospective one, should be planned before such a mandate is set.

"That being said, I'm all for this mandate and being as accurate on dosing any medication as possible," he concluded.

The authors have disclosed no relevant financial relationships.

Stroke. Published online November 10, 2015. Abstract

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