Episode 10- Alteplase door-to-needle times and long-term outcomes

In this week’s installment of “Fresh Fruit” we review a study that has implications for almost all of us who work the ER. This study is entitled “Association between thrombolytic door-to-needle time and 1-year mortality and readmission in patients with acute ischemic stroke” and was published in JAMA on June 2, 2020.

For some background, In patients with acute ischemic strokes (AIS), giving IV tissue plasminogen activator (AKA “t-PA” or “alteplase”) improves functional outcomes. Earlier administration of alteplase is associated with lower risk of mortality and better functional outcomes at up to 90 days. This is where the phrase “time is brain” comes in. This study set out to determine if earlier thrombolytic therapy also has an effect on longer-term outcomes. Longer-term in this case means up to 1 year.

The American Heart and American Stroke Associations released a series of best practice strategies with goals of a door-to-needle time (meaning arrival to the ER and alteplase administration) of 60 minutes for at least 75% of patients and an additional goal of a door-to-needle time of 45 minutes for at least 50% of patients. In my ER, our goal is 30 minutes. This is important to all of us in the ER as the door-to-needle time is something we can tangibly affect.

Back to the study. This US cohort study looked at patients aged 65 years and older who received alteplase within 4.5 hours and also must not have been treated with intra-arterial reperfusion. The primary outcomes included 1-year all-cause mortality, 1-year all-cause readmission, and the composite of the two. They also looked at arrival information for patients arriving “on-hour”, defined as 7 AM to 6 PM on weekdays and “off-hour” defined as any other time including evenings, nights, weekends, and holidays, as studies have shown that presenting during off hours was associated with inferior quality of care and higher in-hospital mortality rates. This is something that is super disappointing as I work a lot of “off hour” shifts, as I’m sure many of you do. So, don’t take this too personally. I’m sure we are all doing a fantastic job.

Anyway, the study identified over 61,000 patients in over 1,600 hospitals. The median age was 80 years, about 40 % were male, and 80% were white. The patients treated during on-hour times and those treated in teaching hospitals had shorter door-to-needle times. The median door-to-needle time was 65 minutes, with 5% treated within 30 minutes, 20% within 45 minutes, and 44% within 60 minutes. Patients who received alteplase after 45 minutes of hospital arrival compared to those who received it in less than 45 minutes had worse long-term outcomes including significantly higher rates of mortality (35% vs 31%), all-cause readmission, and a composite of the two. Very striking was the finding that every 15 minute increase in door-to-needle time was significantly associated with higher all-cause mortality and all-cause readmission! But, a time of 30 minutes was not associated with better outcomes, so there seems to be a limit to how much we can truly affect patient outcomes based off of the speed of giving alteplase alone.

In conclusion, this study showed that patient treated with shorter door-to-needle times did significantly better over a long term with lower mortality and readmission rates. Patients who received alteplase within 45 minutes had the best outcomes, followed by those who received it within 60 minutes. The study did have some limitations of course, including the fact that rural and minority populations were underrepresented and that things such as quality of life and functional outcomes were not examined. Although not a perfect study, I hope that it is used as another reason to encourage timely management of these patients. We call all help.

For example, In my ER, a “CODE STROKE” is called by EMS and the patients are evaluated in a bed right next to the CT scanner, shortening time to arrival to CT imaging. We obtain information such as last known normal time, blood pressures, weight, blood glucose, and clinically evaluate the patient. While this is happening, the ER pharmacist will pull up the patient’s chart looking specifically for contraindications to alteplase. If we decide to give alteplase, the pharmacist will actually compound the alteplase at bedside, which only takes about 5-10 minutes. To further expedite administration, alteplase is kept in the Pyxis machines in our ER. These small changes alone have drastically reduced our door-to-needle times. There are a few studies that showed that the presence of having an ER pharmacist reduced overall alteplase administration times, reducing times by at least 20 minutes. Nursing is also heavily involved in this process, double-checking the pharmacist on the alteplase dose, setting up the IV pumps, and ensuring no contraindications exist, among the many other things the very busy nurses in my ER are already doing.

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