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The Journal of Emergency Medicine, Vol. 29, No. 4, pp. 405–408, 2005Copyright © 2005 Elsevier Inc.

Printed in the USA. All rights reserved0736-4679/05 $–see front matter

doi:10.1016/j.jemermed.2005.05.002

OriginalContributions

TISSUE PLASMINOGEN ACTIVATOR FOR ACUTE ISCHEMIC STROKE: A NEWYORK CITY EMERGENCY MEDICINE PERSPECTIVE

Yu-Feng Chan, MD,*† Thomas G. Kwiatkowski, MD,† Joseph G. Rella, MD,* William P. Rennie, MD,†Robert K. Kwon, MD,* and Robert A. Silverman, MD†

*University of Medicine and Dentistry of New Jersey, Newark, New Jersey, †Long Island Jewish Medical Center,New Hyde Park, New York

Reprint Address: Yu-Feng Chan, MD, Department of Surgery, Division of Emergency Medicine, University of Medicine and Dentistry of

New Jersey, 30 Bergen Street, ADMC II, Room 1110, PO Box 1709, Newark, NJ 07101

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Abstract—Nationally, only 2–3% of patients with acuteschemic stroke (AIS) currently receive tissue plasminogenctivator (TPA). To better understand the reasons, we in-estigated the practice patterns, level of familiarity andcceptance of TPA for AIS among emergency physicians inew York City (NYC). Fifty-seven 911-receiving hospital

mergency department directors were surveyed regardingPA use. Of those responding, 37% had never used TPA to

reat AIS. Lack of neurological support was reported by3%. Departments with formal protocols were more likelyo use TPA for AIS. In conclusion, there is considerableariation in the practice, knowledge, and attitudes regard-ng the use of TPA for AIS in NYC emergency departments.mproved educational efforts and institutional support maye necessary to ensure the appropriate use of TPA bymergency physicians. © 2005 Elsevier Inc.

Keywords—cerebrovascular accident; tissue plasmino-en activator; emergency medicine

INTRODUCTION

cute ischemic stroke (AIS) is responsible for 85% ofhe approximately 750,000 new stroke cases each year1,2). Outside of highly specialized centers, intravenous

The abstract was presented at the 25th International Strokeonference in New Orleans, Louisiana, February 13, 2000.

ECEIVED: 15 March 2004; FINAL SUBMISSION RECEIVED: 1

CCEPTED: 24 May 2005

405

issue plasminogen activator (TPA) is the only treatmento open blocked intracranial arteries. TPA can be givenafely and appropriately by emergency physicians (EPs)3,4). The National Institute of Neurological Disordersnd Stroke rt-PA Stroke Study Group (NINDS) demon-trated that timely treatment of AIS with TPA signifi-antly decreased the incidence and severity of disabilityt 1 year after treatment (5). Additionally, a cost-effec-iveness analysis projected a substantial cost savings tohe health care system when TPA is used for this clinicalntity (6).

However, despite consensus statements and practiceuidelines published by the Stroke Council of the Amer-can Heart Association (AHA) recommending TPA, only–3% of all patients with new AIS currently receivehrombolytic therapy (7,8). Specific treatment guidelinesimit the number of patients who are eligible for thisherapy, notably time from onset of symptoms untilnfusion. The controversy surrounding whether TPAhould ever be used for AIS is another factor loweringhe number of patients receiving this treatment. Theedical community remains concerned about the in-

reased risk of intracerebral hemorrhage (ICH), how torticulate this risk to potential patients, and various in-erpretations of quality of life, among others (9–12).

We created a survey to assess the experience, knowl-dge, and attitudes of New York City’s (NYC) EPs

uary 2005;

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egarding thrombolytic therapy for AIS. We chose tourvey emergency department (ED) directors. Use ofPA for stroke requires an institutional commitment. Wessume that ED director responses would best reflectheir institution’s practices. By comparing the responsesf those who have used TPA in the past with those whoave not, we hope to determine some of the factors thatimit TPA usage. In particular, we are interested in dis-overing what effect physician attitudes have in theirecision to use TPA. A more complete understanding ofhese factors can illuminate what actions, if any, may beecessary to improve delivery of patient care in cases ofIS.

METHODS

e mailed a 17-question survey to the ED director atach of 59 Emergency Medical Services (EMS) re-eiving hospitals in NYC. The survey contained threeections addressing attitudes, experience, and knowl-dge. The attitude section asked questions about effi-acy and level of acceptance. The experience sectionnquired about practice patterns and factors limitingPA use. The knowledge portion assessed the level of

amiliarity regarding TPA for AIS. Questions concern-ng attitudes and practice patterns were designed byhe authors and were based on concerns expressed inhe literature. Knowledge questions were based on theuidelines recommended by the American Heart As-ociation (AHA) (8).

Each survey was mailed with a cover letter explaininghe survey and its purpose. In this letter, ED directorsere asked to answer knowledge-based questions re-arding TPA, based on their own knowledge, but theyere asked to answer questions on attitudes towards

reatment and experience from a departmental and insti-utional perspective. Envelopes were marked to track theespondents.

We made the initial mailing, consisting of a surveyith a stamped, addressed envelope, in January 1999. Ifsurvey was not returned within a month, the ED direc-

or received a telephone call and the questionnaire wasompleted over the phone after obtaining assent. Datarom the initiating institution were excluded, as wereata from an additional facility because a single directoranaged both sites.

RESULTS

esponses were obtained from 52 (91%) of the 57 eli-ible directors. Of the 52 respondents, 33 (63%) had

sed TPA to treat AIS and 19 (37%) had not. Of the A

sers, 32 (97%) intend to use it again whereas 9 (47%) ofhe non-users intend to use it in the future, resulting in 4179%) in favor of employing thrombolytic therapy forIS. Of the 33 ED directors who have used TPA, 6

18%) have used it once, 21 (64%) have used it 2–3imes, 5 (15%) have used it 4–5 times, and only 1 (3%)sed it 6–10 times. The median number of years ofxperience of ED directors who used TPA one or moreimes was similar to that of ED directors who had neversed TPA (14.6 vs. 12.2, respectively).

The experience section of the questionnaire inquiredbout the barriers to TPA use in AIS (Figure 1). Theost commonly perceived limitation is lack of neurolog-

cal support, which was reported by 17 (33%) of allespondents. Lack of neurological support was usuallyescribed as neurologist-based opposition toward the usef TPA and development of a stroke team approach tohe treatment of AIS. Other barriers included lack ofadiological and neurosurgical support, lack of rapidomputed tomography (CT) scan and interpretationvailability, suboptimal nursing and ancillary staff sup-ort, and a general lack of institutional support. Usersere more likely than non-users to report that they per-

eived no barriers to TPA use at their institution (64% vs.2%, respectively). ED directors who had trained atnstitutions that possessed an Emergency Medicine Res-dency program were as likely to have used TPA to treatIS as those who had not (33% vs. 37%, respectively).Formal TPA protocols were in use in 73% of surveyed

ospitals. Among hospitals with a formal protocol, usageates were significantly higher as compared to hospitalsithout a formal protocol (91% vs. 42%, respectively).e asked specific questions regarding knowledge of

PA administration for AIS according to AHA guide-ines (Table 1). As a group, physicians who have usedPA showed greater knowledge about its use, althoughoth populations had significant shortcomings in theirnowledge base. Only 58% of users knew the maximumllowable blood pressure (BP) when using TPA to treat

igure 1. Limiting factors to TPA use.

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TPA for Acute Ischemic Stroke 407

Table 2 lists the statements respondents were asked togree or disagree with regarding their attitudes towardPA use. Two-thirds of the respondents believed that, ifsed properly, TPA is an appropriate and safe treatmentith the potential benefits outweighing the risks.eventy-five percent of respondents agreed that EPsould give TPA safely alone, whereas 25% felt that ithould be given only when a neurologist is present.

DISCUSSION

he Food and Drug Administration approved the use ofPA for AIS in 1996. Three years later, only a fractionf the patients potentially eligible for thrombolytic ther-py received this intervention (1,2). Although patientligibility may be limited by a number of pre-morbidactors, we explored the perceptions and attitudes of themergency physician as another potential limiting factor.

We identified a number of perceived barriers to these of TPA, including CT access, radiological back upor head CT scan interpretation, nursing, and institutionalttitudes. It is not clear to what extent these have pre-ented TPA administration. Both users and non-usersncountered these potential barriers with similar fre-uency. The most frequently perceived barrier as re-

able 1. Knowledge Base of TPA Users vs. Non-users (%Correct Responses)

Knowledge questionsUsers(%)

Non-users(%)

hat is the current FDA status of TPA fortreatment for AIS?

85 79

re you familiar with the NIH strokescale?

85 63

f yes, have you ever used the NIH strokescale?

39 21

hat is the time window allowed for TPAadministration from the onset of AIS?

94 63

hat is the incidence of ICH in patientstreated with TPA for AIS?

82 78

hat is the maximum BP allowed whenusing TPA for AIS?

58 42

hould patients treated with TPA for AISreceive heparin?

70 58

s age greater than 75 years acontraindication for treatment of AISwith TPA?

73 68

s TPA indicated in the treatment ofpatients with recurrent or crescendoTIAs?

73 74

ave you attended lectures orpresentations devoted to use ofthrombolytics in stroke?

82 79

IS � acute ischemic stroke; FDA � Food and Drug Adminis-ration; NIH � National Institutes of Health; TIA � transientschemic stroke; TPA � tissue plasminogen activator.

ealed by this survey is the lack of neurological support.

lthough the majority of those surveyed felt that EPs canive TPA safely alone, 25% of those surveyed felt that aeurologist should be present during the drug’s admin-stration. This sharply contrasts with the attitude of neu-ologists reported in the Villar-Cordova study who feltverwhelmingly that EPs should not give TPA on theirwn (13).

ED directors surveyed were not particularly well versedegarding the use of TPA for AIS. Users, who scored betterhan non-users on knowledge questions, answered only5% of the questions correctly. If this is an indication ofeneral EP knowledge, education is needed. Protocol vio-ations have resulted in excess risk of intracerebral hemor-hage without observable benefit (14).

Our study also revealed discordance between willing-ess to use TPA to treat AIS and ED directors’ attitudesegarding its safety. Although nearly all users indicated theyould use it again, only 66% stated that TPA is an appro-riate agent for the treatment of AIS or that it was safehere the potential benefits outweighed the risks. Likewise,3% of users stated that more studies are needed beforePA can be given safely. It is worth noting that even among

espondents who had used TPA to treat AIS in the past,ver 80% reported three or fewer uses and only one EDirector had used it six or more times.

When the NINDS and ECASS studies were pub-ished, physicians were concerned that the only availablereatment for AIS carried a higher risk of ICH thanlacebo-treated patients, with similar mortality rates at0 days post-treatment, and included only relativelymall numbers of treated patients (15,16). Early ischemic

able 2. Attitudes Regarding TPA for Stroke: Users vs.Non-users

Attitude statementsUsers(%)

Nonusers(%)

PA is an appropriate agent fortreatment of AIS

Agree 64 63Neutral 30 26Disagree 6 11

f used properly, TPA is safe andthe potential benefits outweighthe risks

Agree 67 63Neutral 24 32Disagree 9 5

ore studies are needed beforeTPA can be given safely

Agree 36 58Neutral 19 16Disagree 45 26

PA is potentially dangerous andshould not be used for AIS

Agree 9 16Neutral 12 16Disagree 79 68

PA should be adminstered forAIS only in hospital with astroke team

Agree 55 58Neutral 15 16Disagree 30 26

PA should be adminstered onlywhen a neurologist is presentin the ED

Agree 24 26Neutral 34 32Disagree 42 42

PA can be given safely by EPs Agree 82 63Neutral 3 16

Disagree 15 21

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408 Y.-F. Chan et al.

hanges on CT scan were initially difficult to interpretegarding patient eligibility for TPA treatment. Studyesigns did not incorporate patients’ value systems re-arding quality of life and acceptable disability and areot addressed by Rankin scores (12). More recently,riticism is directed toward what are considered by someo be outdated treatment guidelines that focus on rapidityf treatment rather than making the correct diagnosis byaking advantage of new imaging technologies (17). Oururvey results may be interpreted as the ED directorsho already use TPA for AIS are willing to continuesing the only available treatment for this potentiallyevastating event due to a paucity of other treatments,ut they are also aware that the science behind theherapy still has some way to go before the fear ofausing harm is reduced further.

LIMITATIONS

his single-city survey did not determine the experience,nowledge, and attitudes of New York City’s EPs directly.nstead, we asked ED directors to answer knowledge andxperience questions based on their own personal knowl-dge and experience of TPA treatment for AIS, and toxpress what they felt their staff attitudes were regardingPA use for stroke. Any conclusions drawn from thisurvey will be limited by the small number of directorsurveyed and how well they represent their staff in attitudesnd knowledge. The small number of EDs surveyed limitshe ability to detect statistically significant differencesmong subgroups. Additionally, the single urban geo-raphic region sampled may not represent EP or institu-ional practices in other regions.

It is possible that the cover letter and the questionsnd statements in the survey may have biased the results.lthough we attempted to keep the language neutral, EDirectors may have discerned our hypothesis that physi-ian attitudes play a role in the small numbers of patientsho receive TPA for AIS.

CONCLUSION

rmed with the knowledge that the timely use of TPAay decrease the incidence and severity of disability that

esults from AIS, EPs finally have a real opportunity to1

mprove the outcome of what has historically been aevastating event. There is considerable variation in theractice, knowledge, and attitudes regarding the use ofPA for AIS in NYC emergency departments. This may

eflect the general controversy surrounding this use ofPA for AIS. There seems to be a need for improving thenowledge of EPs regarding the use of TPA.

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