Beyond the Golden Hour: Treating Acute Stroke in the Platinum 30 Minutes

Anantbir S. Randhawa, MD; Fatima Pariona-Vargas, MD; Sidney Starkman, MD; Nerses Sanossian, MD; David S. Liebeskind, MD; Gilda Avila, MD; Samuel Stratton, MD; Jeffrey Gornbein, DrPH; Latisha Sharma, MD; Lucas Restrepo-Jimenez, MD; Miguel Valdes-Sueiras, MD; May Kim-Tenser, MD; Pablo Villablanca, MD; Robin Conwit, MD; Scott Hamilton, MD; Jeffrey L. Saver, MD

Disclosures

Stroke. 2022;53(8):2426-2434. 

In This Article

Abstract and Introduction

Abstract

Background: To emphasize treatment speed for time-sensitive conditions, emergency medicine has developed not only the concept of the golden hour, but also the platinum half-hour. Patients with acute stroke treated within the first half-hour of onset have not been previously characterized.

Methods: In this cohort study, we analyzed patients enrolled in the FAST-MAG (Field Administration of Stroke Therapy–Magnesium) trial, testing paramedic prehospital start of neuroprotective agent ≤2 hours of onset. The features of all acute cerebral ischemia, and intracranial hemorrhage patients with treatment starting at ≤30 m of last known well were compared with later-treated patients.

Results: Among 1680 patients, 203 (12.1%) received study agents within 30 minutes of last known well. Among platinum half-hour patients, median onset-to-treatment time was 28 minutes (interquartile range, 25–30), and final diagnoses were acute cerebral ischemia in 71.8% (ischemic stroke, 61.5%, TIA 10.3%); intracranial hemorrhage in 26.1%; and mimic in 2.5%. Clinical features among platinum half-hour patients were largely similar to later-treated patients and included age 69 (interquartile range, 57–79), 44.8% women, prehospital Los Angeles Motor Scale median 4 (3–5), and early-postarrival National Institutes of Health Stroke Scale deficit 8 (interquartile range, 3–18). Platinum half-hour acute cerebral ischemia patients did have more severe prehospital motor deficits and younger age; platinum half-hour intracranial hemorrhage patients had more severe motor deficits, were more often female, and less often of Hispanic ethnicity. Outcomes at 3 m in platinum half-hour patients were comparable to later-treated patients and included freedom-from-disability (modified Rankin Scale score, 0–1) in 35.5%, functional independence (modified Rankin Scale score, 0–2) in 53.2%, and mortality in 17.7%.

Conclusions: Prehospital initiation permits treatment start within the platinum half-hour after last known well in a substantial proportion of acute ischemic and hemorrhagic stroke patients, accounting for more than 1 in 10 enrolled in a multicenter trial. Hyperacute platinum half-hour patients were largely similar to later-treated patients and are an attainable target for treatment in prehospital stroke trials.

Graphic Abstract: A graphic abstract is available for this article.

Introduction

It is well-known that timely treatment in stroke is essential to improve patient functional outcomes.[1] For acute ischemic stroke, reperfusion therapy with intravenous thrombolysis and with endovascular thrombectomy are both highly time dependent and in preclinical models neuroprotective agents also show a strong time dependency.[2–5] For intracerebral hemorrhage, substantial clinical trial evidence suggests that blood pressure lowering and start of prothrombotic agents are also beneficial in only a short time window and, within this window, the sooner the better for treatment start.[6,7]

Stroke is one of several emergency conditions in which patient outcome is heightened by accelerated treatment initiation; others include trauma, shock, status epilepticus, and cardiac arrest. To emphasize the importance of treatment speed for time-sensitive conditions, Emergency Medicine has developed several rubrics for different treatment time windows. The concept of the golden hour—the first 60 minutes after illness onset—is the most well-known,[8–10] but other useful time labels have also been promulgated. The terms platinum 30 minutes and platinum 10 minutes have been advanced for the most challenging and most beneficial time windows for intervention, when disease processes are least advanced and most reversible.[11–14]

For patients with stroke, sparse, but at least some, studies have delineated the clinical characteristics and treatment outcomes of golden hour patients. However, to our knowledge, the frequency, characteristics, and outcomes of platinum 30 minute patients has not been previously well characterized. These patients are generally not captured in studies of patients evaluated and treated in the Emergency Department. Even at the optimal attainable speed, the cumulative time intervals of symptom detection to 911 call (3–7 minutes), dispatcher phone assessment leading to ambulance activation (1–2 minutes), ambulance travel to scene (5–10 minutes), paramedic assessment and stabilization of patient and loading of patient into ambulance (10–20 minutes), ambulance travel from scene to Emergency Department door (5–10 minutes), and initial physician assessment in the ED (0–10 minutes) results in almost all patients with acute stroke arriving and assessed in the ED beyond the platinum 30 minutes.[15] Prehospital assessment and treatment is the only practical approach to achieving interventions for patients with stroke within the first 30 minutes after onset. Further, given the time needed to perform and review brain imaging, even Mobile Stroke Units are generally not able to achieve treatment times within the first 30 minutes.[16]

In contrast, standard ambulances staffed by paramedics are a widely available resource for potentially delivering stroke therapy in the platinum 30 minutes. However, patients with stroke assessed and treated by paramedics with neurovascular-targeted agents in the platinum 30 minutes have not been previously well-delineated. Understanding this population better is essential to the design of future trials focused upon the hyperacute period and to planning for implementation of trial-based treatments in practice. Accordingly, to achieve this objective, we analyzed this population in the National Institutes of Health FAST-MAG (Field Administration of Stroke Therapy—Magnesium) Phase 3 trial, a large, multicenter randomized trial assessing start of a potentially neuroprotective agent by paramedics in the field before hospital arrival.

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