Are in-Hospital Delays Important Obstacles in Thrombolytic Therapy Following Acute Ischemic Stroke?

Thrombolytic therapy with recombinant tissue plasminogen activator (rt-PA) is the only proven treatment for ischemic stroke, when it is administered within 3 hours of the onset of symptoms.1, 2 Although 15-56% of the patients with acute ischemic stroke arrive at the emergency department (ED) within 3 hours of the onset of symptoms, currently only 2-8% of these patients receive thrombolytic therapy.3-5 A substantial proportion of patients who arrive early do not receive thrombolytic therapy due to avoidable reasons such as delays in physician evaluation and neuroimaging, incorrect application of criteria, and incorrect diagnosis.6-9 According to the guidelines for identifying and treating acute stroke,10 patients with acute stroke should be examined or notified to stroke expertise within 15 minutes of arrival at the ED. A computed tomography (CT) scan should be performed within 25 minutes, and the specific drug should be infused within 60 minutes. CT has been the principal neuroimaging modality in many previous studies investigating in-hospital delays in stroke therapy. 11-15 However, the development of multimodal magnetic resonance imaging (MRI) has led to this being increasingly used as the initial neuroimaging modality in acute stroke management. The aim of this study was to quantify the time delays in physician evaluation and neuroimaging in patients with acute stroke and to determine whether they are important obstacles to performing thrombolytic therapy.

This study revealed considerable in-hospital delays in neurology evaluation and neuroimaging relative to suggested guidelines. Overall, 37% of the patients were notified within 15 minutes, and only 26% of the patients received a neurology evaluation by a neurology resident or a neurologist within 15 minutes of arrival at the ED. Neuroimaging started within 25 minutes in only 15% of the patients. Only 8.7% and 20% of ischemic stroke patients who visited an ED within 24 hours and within 3 hours of the onset of symptoms, respectively, received rt-PA. Most patients who arrived early were excluded from thrombolytic therapy due to the presence of unavoidable reasons or absolute contraindications.

Previous studies found that minor neurologic deficits and rapidly improving symptoms were important reasons for the nonreceipt of thrombolytic therapy by patients who arrived early after the onset of symptoms. Other frequently reported absolute contraindications have been recent stroke, presence of intracerebral hemorrhage, bleeding tendency, high blood pressure, and early CT changes.5-9 However, 24-26% of patients reportedly did not receive thrombolytic therapy due to avoidable reasons such as delays in neurology evaluation or neuroimaging, incorrect diagnoses, and incorrect application of criteria.6-8 In the present study, in 12% of cases the patients did not receive thrombolytic therapy due to avoidable reasons such as incorrect application of criteria, not obtaining informed consent, and delayed neurology consultation. Although this represents a relatively small proportion of the patients, such avoidable factors are very important in acute-stroke management because, unlike absolute or unavoidable reasons, these problems can be resolved by educating personnel and making changes to hospital procedures.

The reported DNET and DNIT have varied greatly between studies due to different conditions, but many researchers have found that the severity of neurological deficit, use of an emergency medical service (EMS), and short onset-to-door time were significantly associated with reducing DNET or DNIT.11-15, 17 The severity of neurological deficit and onset-to-door time also significantly affected DNET and DNIT in the present study. Fifty-three percent of the patients used an EMS in this study. Although such use tended to reduce the onset-to-door time, DNET, and DNIT, the difference did not reach statistical significance, possibly because an EMS was used more frequently by patients who arrived later in this study.

MRI is more sensitive than CT in diagnosing acute ischemic stroke and is also useful for detecting hemorrhage.18, 19 Multimodal MRI can provide more details of ischemic tissue and thus may lengthen therapeutic windows in the acute treatment of ischemic stroke without increasing the incidence of cerebral hemorrhage.20 However, it is generally more expensive, time-consuming, and requires more knowledge for accurate interpretations. MRI was the initial neuroimaging modality in 56% of the patients in this study, and the rate of performing MRI did not differ significantly between patients who arrived within 3 hours of the onset of symptoms and those who arrived later than 3 hours. However, the median time delays to performing CT and MRI were 34 and 69 minutes, respectively, and the use of MRI significantly increased DNIT. Five of the 17 patients who received thrombolytic therapy underwent MRI as their initial neuroimaging modality, and the door-to-imaging time did not differ significantly between CT and MRI in these patients. However, screening all the patients with MRI before thrombolytic treatment would significantly delay neuroimaging because in our hospital MRI is performed by a technologist who is not present during the nighttime. The availability of MRI 24 hours a day reportedly results in no difference in the door-to-imaging time between CT and MRI.18, 21

Despite the presence of such prominent in-hospital delays, only a small proportion of our patients were excluded from thrombolytic therapy due these delays or other avoidable reasons. Because most patients who received thrombolytic therapy had severe neurological deficits (mean initial NIHSS score = 14.29), they were evaluated more rapidly than other patients. However, if patients present with only mild-to-moderate stroke symptoms (e.g., NIHSS score of 5-14), they may not receive thrombolytic therapy due to delays in physician evaluation and neuroimaging. Because stroke treatment is more effective when it is initiated earlier, we should therefore attempt to reduce door-to-physician evaluation or neuroimaging time as well as onset-to-door time. The main problem of the current system at our hospital is that DNET and DNIT are greatly affected by the severity of the stroke. Therefore, we need to organize our stroke team and develop a specific protocol so that every acute-stroke patient receives rapid evaluation and treatment.

This study was subject to several limitations. First, the study was performed at a single center, which may limit the generalizability of its findings. Second, we obtained all the in-hospital data retrospectively and many data on neurology notifications were not available. Because the purpose of this study was to quantify time delays in physician evaluation and neuroimaging at our hospital and to provide baseline data for organizing the stroke team and developing a specific protocol, DNET and DNIT might have been shorter (and more accurate) if we had collected the data prospectively. Third, the overall multivariate statistical models for DNET and DNIT showed only moderate correlations, suggesting that significant predictive variables were omitted from the analyses.

In conclusion, we found significant delays in neurology evaluation and neuroimaging of patients with acute ischemic stroke in this study. Although such in-hospital delays were not major obstacles to performing thrombolytic therapy, there is a greater probability of missing patients with mild-to-moderate stroke symptoms. More effective in-hospital organization is required to ensure the prompt evaluation and treatment of patients with acute ischemic stroke.