Multimodal Imaging Does Not Delay Intravenous Thrombolytic Therapy in Acute Stroke

Discussion

There were 2 principal findings in this study. First, the use of multimodal imaging in patients with acute stroke did not delay administration of IV tPA beyond a goal of 60 minutes from patient arrival. Second, variables that predicted IV tPA use within the 60-minute goal included prehospital stroke alert notification, a longer time from symptom onset to arrival, and a shorter time from arrival to CT examination.

Similar to our findings, prehospital stroke notification has been shown to decrease door-to-needle time and increase the percentage of patients who received IV tPA.^8–10 Kim et al¹⁰ implemented a prehospital notification hotline and increased the percentage of patients receiving IV tPA from 6.4% to 14.3%. Abdullah et al⁸ increased, from 21% to 41%, the percentage of patients receiving IV tPA with advanced EMS notification.

Romano et al¹¹ previously observed an inverse relationship between arrival and thrombolysis. We also believe the most likely explanation for the inverse relationship we observed is that a sense of urgency was lacking in patients arriving with sufficient time to initiate IV tPA, leading to in-hospital delays. This observation is reflected in the delayed time from CT interpretation to IV tPA for patients with unenhanced CT versus multimodal CT (56 minutes versus 43.5 minutes), though the difference did not reach statistical significance (P = .07).

There are several advantages to performing a multimodal CT scan for diagnosis and treatment management. First, stroke differentiation (infarct versus salvageable ischemic stroke) helps clinicians determine whether a patient is a candidate for IA therapy. Even though IA tPA is not approved by the US Food and Drug Administration to treat acute ischemic stroke, there are advantages to arterial-versus-venous administration of tPA, including higher rates of recanalization, potential expansion of the time window out to 6 hours, lower doses of thrombolytic agent used compared with systemic or intravenous tPA, and treatment for patients who were not able to receive IV tPA (bleeding risk, pregnant, other medical contraindication). One-third of patients who were examined with multimodal CT received IV and IA tPA in our study (n = 35). CT angiography was used to identify the origin of infarction and the site of cerebral artery occlusion by assessing the intra- and extracranial vasculature, while CT perfusion was used to predict which tissue was salvageable with reperfusion and which would die without it.³ CT angiography is more sensitive (70%) in detecting early irreversible ischemia versus unenhanced CT (40% sensitivity) and more accurately predicts final infarct volume.² Multimodal CT increases the sensitivity of stroke detection as well as the prediction of the final size of the infarct, compared with unenhanced CT, CTA, and PCT alone.¹² Moreover, these CT methods can be used immediately after unenhanced CT, they can be used to exclude hemorrhage, imaging time is fast (< 5 minutes), and no special hardware is required.¹³

Second, fewer trips to the CT scanner during a patient's hospital stay reduce both transfer-related complications and clinicians' and CT technologists' workloads, increasing efficiency. Transports can impact patients in 2 ways: The actual movement (acceleration, changes in posture) can influence neurologic and physiologic changes, and changes in the environment (noise, surface changes, and equipment changes) can generate added physiologic stress to critically ill patients.¹⁴ A recent observational study revealed 66 adverse events among 290 intrahospital transports of critically ill patients from the ED to the intensive care unit, including some admissions after a CT scan.¹⁵ The multimodal CT imaging protocol reduces the need for a second trip to the CT scanner, which would otherwise be warranted in critically ill patients to determine candidacy for IA tPA.

Finally, obtaining scans that may be done eventually during the hospital stay has been shown to be cost-effective. In 1000 patients 70–74 years of age with acute stroke, the most cost-effective strategy was to scan all patients immediately (reducing costs and increasing independent survival) versus scanning immediately only patients on anticoagulants or having life-threatening conditions, or scanning no patients immediately.¹⁶

Three primary disadvantages to performing multimodal imaging before the decision for IV tPA exist. First, there is the potential for delayed treatment with IV tPA because the scanning/processing times are shorter for unenhanced CT versus multimodal imaging (approximately 5 minutes versus 15 minutes, respectively), and the sooner IV tPA can be given the greater the benefit.¹ Our original intent of performing multimodal CT on all patients with an acute stroke alert was to remove the guesswork concerning who should be scanned with CTA/PCT to determine candidacy for IA thrombolytics. Our results show that multimodal imaging neither increased door-to-needle time nor increased the time from CT to IV tPA initiation. We believe that using this standard-of-care protocol may not extend the door-to-needle time because the protocol removes the decision-making step of whether to perform multimodal CT imaging based on various clinical indices (severity of and changes in NIHSS score, specific symptom, and so forth).

Second, performing CT by using a contrast agent without obtaining creatinine levels could lead to a small but significant risk of renal problems. Mehdiratta et al¹⁷ reported that 8% (n = 11) of patients would have been ineligible to receive contrast on the basis of elevated creatinine levels. However, 10 of 11 patients had a known history of renal disease. The authors concluded that given the reversibility of contrast-induced nephropathy, the benefits of CTA/PCT outweigh the risks if a proper history is taken. During the study period, our practice was to take a thorough history and perform CTA/PCT before obtaining creatinine results. We recently began using a point-of-service device that allows a creatinine reading within 5 minutes of ED arrival so that multimodal CT is not performed in patients with elevated creatinine levels.

Third, performing multimodal CT involves longer scanning times and the use of nonionic contrast agent, which increases a patient's exposure to radiation. CT examinations in the United States have increased more than 3-fold from 1993 to 2009.¹⁸ In a previous study performed at SMC, we identified the cumulative effective dose of radiation from head CT and CT of the head and neck following trauma to be 3.86 and 9.04 mSv, respectively.¹⁹ The Biological Effects of Ionizing Radiation Report VII estimates that 1 in 1000 patients would develop cancer from a CT exposure of 10 mSv.²⁰ MR imaging has also been suggested as an alternative to CT to avoid the risk associated with radiation dose.²¹

Although MR imaging may be diagnostically superior to CT,^22–24 recent studies reported delays to imaging or IV tPA for MR imaging versus CT. In a study of 195 patients with acute stroke in Korea, the median delay to imaging was 34 minutes with CT versus 69 minutes for MR imaging.²⁵ Kang et al²⁶ observed a significant increase in door-to-needle time with MR imaging versus CT (87 minutes versus 68 minutes, respectively); however, discharge modified Rankin Scale scores were not affected by time to treatment or the use of MR imaging. At our stroke center, MR imaging technologists are on call after 10 pm; in general, MR imaging is more expensive, time-consuming, and difficult to interpret than CT. For these reasons, we prefer multimodal CT versus multimodal MR imaging.

Limitations to the study exist. Primarily, there were only 15 patients in the group who did not undergo multimodal CT. We did not find any differences in patient and clinical demographics in the multimodal CT subgroup, but this finding may be due to the small sample size in the patients examined with unenhanced CT alone. We do not believe that a selection bias exists; there are some patients whose conditions are not appropriate for multimodal imaging but may still be appropriate for tPA, including patients with small vessel strokes. Even if patients were selected to be examined with unenhanced CT only, this selection should not have resulted in a delay in IV tPA. Patients underwent unenhanced CT because multimodal CT was contraindicated (iodine allergy, elevated creatinine levels) or multimodal CT could increase the potential for harm (contrast agent, superfluous radiation) without providing additional benefit because IA therapy was not a consideration.

Second, this analysis was conducted in a single high-volume primary stroke center. The results of this study may not be applicable to other centers where interventional neuroradiology is not available. In addition, at our center, the neurologist is in the ED within 5 minutes of stroke alert, is present during the CT examination, and reads and interprets the findings of the CT examination with the radiologist in real-time. Smaller centers and centers with fewer resources may not have the capability to perform a multimodal CT examination in the IV tPA window.

Third, all data were collected retrospectively from 2 data bases: the Get with the Guidelines data base (http://www.americanheart.org/presenter.jhtml?identifier=3016522) and our in-house Stroke Tracker data base (http://www.fileguru.com/apps/free_key_stroke_tracker). There are potentially unmeasured differences in the population, in the multimodal CT imaging subgroup, which we were not able to examine due to the use of pre-existing data. Errors in data entry and data collection are also more common in retrospective analyses than in data that are collected prospectively. Finally, due to data-retrieval limitations, we were unable to examine time to tPA with unenhanced CT before the institution of the multimodal CT protocol (before 2003).