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NINDS: Stroke Proceedings: Pepe Overview

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Proceedings of a National Symposium on
Rapid Identification and Treatment of Acute Stroke
December 12-13, 1996

Overview: Prehospital Emergency Medical Care Systems

The Initial Links in the Chain of Recovery for Brain Attack: Access, Prehospital Care, Notification, and Transport

Paul E. Pepe, M.D., M.P.H., F.A.C.E.P., F.C.C.M., F.A.C.P. (Session Chair)
Allegheny University of the Health Sciences
Allegheny General Hospital, Pittsburgh, Pennsylvania

Synopsis

Beyond the clear need for public education initiatives, the currently available educational offerings and clinical approaches practiced in most emergency medical systems indicate that widespread re-education and re-orientation of prehospital care services are now clearly in order if we want to ensure the optimal management of patients with acute stroke.

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Introduction

With the recent recognition of the potential for reversing or ameliorating acute stroke through early intervention(s) (1-5), patients with brain attack have now joined the ranks of those with acute myocardial infarction and major trauma in terms of the need for: (a) rapid on-scene identification of the life-threatening problem, (b) rapid evacuation and prehospital interventions, (c) rapid pre-notification of appropriate receiving facilities, (d) rapid diagnosis and provision of definitive intervention at those facilities, (e) specialized treatment and evaluation, and (f) appropriate rehabilitation as necessary (6,7). As in the case of the trauma patient, professional responders must promptly begin certain limited interventions and rapidly evacuate the stroke patient to a prealerted specialty center capable of providing definitive interventions. Also, as in the case of a trauma center, experts must be available around the clock, ready to rapidly diagnose the stroke etiology and provide immediate intervention. Furthermore, those stroke specialists must be prepared to deal with the potential complications of their interventions and to evaluate the patient for predisposing or complicating conditions.

However, unlike the clinical scenario of bodily injury, the clinical presentation of stroke is often much more subtle. More importantly, the patient with acute stroke symptoms does not evoke the same level of anxiety or action as the patient with an abdominal gunshot wound. This relative lack of anxiety and responsiveness applies not only to the lay person witnessing the onset of symptoms, but also to the emergency medical personnel responsible for such patients. Such relatively blunted reactions to stroke patients cannot be thought of as insensitivities or lack of concern on the part of those medical care providers. Their reactions simply reflect the general "state-of-the-art" in current medical education, particularly for emergency medical services (EMS) personnel (8-11).

Up until the present time, acute stroke has largely been considered an unfortunate medical problem requiring only supportive care and monitoring. In turn, with the exception of those experiencing loss of consciousness and/or respiratory compromise, a sense of urgency regarding stroke patients generally has not been conveyed in either the training of 911 dispatchers or the training of responding EMS personnel. Compounding the problem has been the evolution of managed care (primary care screening) as well as sophisticated priority dispatch systems (911 centers) (12,13). Specifically, in some circumstances, dispatchers may purposefully triage and dispatch lesser trained personnel, using a non-emergent response mode (no emergency lights and sirens), when a life-threatening situation is not identified during the telephone in-take (13). In addition, few dispatch centers actually utilize triage algorithms that help to identify and, in turn, prioritize patients with "brain attack." Likewise, the responding EMS personnel have not been routinely trained to identify stroke victims and take them directly (and rapidly) to specific centers capable of providing immediate diagnosis and intervention (as is done in the case of trauma center triage and transportation) (14). In the following pages, the rationale for improved educational initiatives will be detailed, as will issues for further investigation and resolution.

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Background

Why There is a Time-Dependent Chain of Recovery for Stroke

Prior to 1995, most of the medical community considered the management of stroke to be largely supportive care. The recently published study of t-PA for acute stroke management, sponsored by the National Institute of Neurological Disorders and Stroke (NINDS), as well as other studies, helped to re-orient the mentality of most practitioners toward the urgency of managing stroke (1-5,15). Even those clinicians who are not entirely convinced about the relative benefit versus risk of t-PA administration within the first few hours after the onset of stroke symptoms have, at least, become more sensitized to the early care of the patient with brain attack (16). The ability to demonstrate enhanced rates of reversal of stroke manifestations clearly created a new paradigm that stroke could be amenable to interventions.

Like acute myocardial infarction (AMI), it was clear that the earlier the intervention, the better the results (4,5,7,17). But unlike the scenario of AMI, alternative procedures to t-PA administration such as direct angioplasty are not yet a key part of the therapeutic regimens available to stroke patients. Thrombolytic therapy, even if provided by more direct and selective catheterization, remains the main therapeutic approach to restoring obstructed blood flow to ischemic brain tissue. However, unlike the case of AMI, it appears that the longer it takes to provide the therapy, the greater the risk for the serious associated complication of intracerebral bleeding. An informal observation during the NINDS study was that, despite historical information regarding the onset of stroke symptoms, CT scans were generally more predictive in terms of identifying the duration of stroke (4). An accompanying observation was that the later it was in the time course of the stroke, the higher the risk of bleeding complications following thrombolytic therapy.

These observations only serve to underscore the clear need to achieve the earliest possible diagnosis and treatment for stroke. Perhaps the traditional educational concept describing the "golden hour" for achieving definitive trauma care should be more aptly applied to stroke management (6). Likewise, the cardiologists' mantra that "time's muscle" (regarding the salvage of myocardium in AMI) might then be expanded to "time's neurons" for the stroke patient as well.

Another informal observation during the NINDS study was that the control group also appeared to have relatively improved outcomes when compared to historical outcomes, implying a typical "study effect." But it also implies that there may be other benefits for stroke patients (short of thrombolytics) when they receive special attention and rapid supportive treatment. In addition, with the evolution of new neuroprotective agents, the case for rapid identification and intervention may become even stronger (15).

But rapid evacuation to definitive care depends on having a series of sequential, interdependent factors in place in order to optimize the outcome for acute stroke patients. Just as the American Heart Association(AHA) has fostered the concept of a Chain of Survival for patients with cardiac arrest, a similar educational metaphor is also befitting for stroke patients (18). In the AHA model, the sequential, interdependent links include access (e.g., 911 call); bystander CPR; early defibrillation; and early advanced cardiac life support (18). If one of the links is missing in this time-dependent situation, survival chances become bleak. A similar chain of survival has been described for trauma patients (6). In the case of stroke, a Chain of Recovery may be a more appropriate metaphor in that many untreated patients may survive, but do so with devastating neurological deficits that might have been reversed or ameliorated with earlier intervention. As in the case of cardiac arrest or trauma, it still takes a series of interdependent, sequential events during the emergency phase of care to make the chances of full recovery from stroke possible. As described previously, the key events, representing the emergency phase links in the chain, are (a) identification of the stroke signs and symptoms by the patient or bystanders, (b) immediate EMS system activation and appropriate dispatch with prearrival instructions, (c) rapid EMS response, assessment, evacuation, and appropriate prehospital care, (d) forewarning of the receiving stroke center for resource preparation and mobilization, and (e) rapid definitive diagnosis and treatment by experienced specialists at the stroke center.

If any of these individual links are missing or inadequate, the chances of recovery for the stroke patient may be compromised significantly. For example, if the patient or bystanders fail to recognize the onset of symptoms, care will be significantly delayed even if the dispatchers, EMS responders, and receiving facilities are all performing maximally. Likewise, even with early recognition and rapid EMS system activation, if the patient is taken to a facility incapable of immediately diagnosing and treating the stroke, again the chances of recovery are compromised. In other words, all of the individual links have to be in place and working optimally at all times for each patient.

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Why Stroke is a Time-Dependent Challenge for EMS Systems

The need to optimize the efficiency and strength of each link in the Chain of Recovery is underscored by the typical time that it takes to get someone to definitive care, even when everything is optimized. Assuming that stroke symptoms are recognized immediately, it still takes a finite time interval (perhaps 5 minutes or so) to recognize the emergency, make the call for help, and confirm the address and "call-back" telephone number for dispatchers. After the minute or two that it takes a dispatcher to prioritize the call and make the actual dispatch, the response interval for first-responders is usually a few minutes. In turn, transport ambulance crews will typically arrive at the scene after another several minutes. After leaving their vehicle, it may take 1 or 2 minutes more for the ambulance crew to reach the patient's side and begin assessment. Therefore, even in the best of EMS systems, professional identification of the stroke may still take 15 minutes or more after the initial recognition of the problem by the patient or bystanders. Aside from the neurological examination and historical assessment, other actions such as general history-taking and vital sign measurements will take several more minutes to accomplish, even when first responders have already obtained most of this information. Following specific actions for stroke patients, such as oxygen application, a more directed historical assessment, and measurement of serum glucose levels (particularly in those with altered mental status), it takes a finite amount of time to transfer and secure a patient onto a stretcher. This scenario also assumes that co-responders are available to simultaneously retrieve the stretcher from the ambulance during the on-scene assessment period. Even with lifting assistance from accompanying responders and assuming that the patient was found on a first-floor location, it would typically take another 5 to 10 minutes to secure a patient into an ambulance. Even if the glucose measurement and more directed assessment were deferred until the ambulance crew departed the scene, the total on-scene time would minimally approach another 10 minutes. More likely, the on-scene interval would be 15 to 20 minutes, even in the most efficient of EMS systems.

The sheer logistics of reaching and retrieving patients, even in a "scoop and run" mode, leads to significant time lapses, a concept often underappreciated by those unfamiliar with the delivery of emergency patient care in the out-of-hospital setting. In addition to the half-hour interval that it may minimally take, in the best of circumstances, to respond to and secure a patient in the back of an ambulance, it typically takes another 5 to 15 minutes to transport a patient to the hospital. Even with the assumption that managed care providers will, in the future, acknowledge the acceptability of transporting the stroke patient to the closest appropriate facility (as they do with trauma centers today), it can be assumed that patient arrival and transfer onto the emergency department stretcher will not take place for at least 30 to 45 minutes after the call for help is first placed into the 911 system. Adding more finite time delays for appropriate establishment of intravenous access, glucose measurements, and cardiac monitoring, prehospital time intervals may be even more protracted. In turn, even with state-of-the-art EMS programs that are already oriented toward rapid identification and transport of stroke patients, the typical time lapse prior to transfer of care to the in-hospital staff can be as much as 1 hour.

Following hospital arrival, it then takes more time to make screening assessments, perform initial procedures (blood work, electrocardiograph, intravenous access), and get the patient to the CT scanner. Therapy will still await the interpretation of the scan (19,20).

In short, assuming that the stroke is identified at its onset and that help is sought immediately, significant and obligatory logistical delays can use up substantial amounts of the time window accepted for thrombolytic therapy. When adding the uncertainty of stroke recognition by the patient (or bystanders), as well as the more typical time delays in calling for help once a problem is identified, one would certainly be pushing the limits of what are arguably the safer temporal windows for thrombolytic therapy. As a result, to date, only a small percentage of stroke patients are considered eligible for therapy. Therefore, the appropriate management of stroke can provide a clear time-dependent challenge for any EMS system. In turn, each EMS system must do whatever it can to strengthen and expedite each link in the Chain of Recovery for patients with acute stroke.

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Current Inadequacies in theChain of Recovery

While an initiative to ensure a Chain of Recovery for stroke appears to be conceptually plausible, in many communities there are historical, educational, fiscal, and even political obstacles that currently weaken the various links in the chain. More often than not, such weak links lead to complete breaks in the chain of recovery. As described below, these issues may be multifaceted.

Public education still remains the weakest link, particularly in EMS systems which have begun to develop advanced stroke management plans (such as those systems that participated in the recent NINDS study). In turn, this issue of public education is the major focus of another section of this monograph. Likewise, the in-hospital management links are also receiving independent attention (19,20). As a result, the specific focus of this section is to explore ways to strengthen the prehospital links of dispatch functions, prehospital medical care, hospital notification, and transport considerations.

Indeed, when one reviews the currently published training curricula for basic life-support (BLS) responders (e.g., firefighter or police first-responders or basic EMTs) as well as those available for advanced life-support (ALS) providers (e.g., paramedics, flight nurses), one does not yet find didactics that stress the urgency of stroke identification and intervention (8-11). Therefore, it is no surprise that the identification of stroke by EMS personnel is often lacking and that the time intervals to definitive evaluation and treatment are generally prolonged beyond the accepted therapeutic time windows (4,5).

The relatively blunted sense of urgency and responsiveness for stroke patients may also be reinforced by the reception and body language that can be currently observed at many receiving facilities. When the receiving medical staff do not display a sense of urgency regarding stroke patients, EMS personnel are less apt to be as reactive as perhaps they should be in their routines.

On another note, even when identification is made, the specifics of prehospital care and management have not been standardized in a consensus fashion as they have been for cardiac or trauma patients. These issues are particularly important for those patients who must be transported from rural areas or other venues that create difficulties in terms of the patient rapidly reaching definitive care. In the future, studies must be conducted to help determine the relative efficacy of the various potential management strategies to deal with such situations. For example, what is the advisability of providing therapy at a rural community hospital, particularly with the advent of ever-evolving telemedicine technologies or with the potential ability to have specialists rendezvous with the patient at the distant facility (via air medical transport)? Other access-to-care considerations include the advisability of utilizing air medical transport directly from a scene in order to expedite definitive care. Whatever studies are considered, standardized nomenclature and consensus definitions for minimum data sets should be prospectively established, as has been done for cardiac arrest and trauma patients.

To summarize, like weak links in a chain, inadequacies in EMS systems may break the chances for optimal recovery for patients with acute stroke. Even with immediate recognition of stroke onset by family members and the availability of sophisticated stroke centers, a lack of responsiveness and aggressive action on the part of dispatchers or EMS responders can become the weak link that will compromise the time-dependent chances for reversing or ameliorating an acute stroke in evolution. Therefore, it is quite appropriate that EMS system leaders strengthen each link and thus ensure the Chain of Recovery for brain attack patients in their communities.

In that respect, considerations should include the advisability of establishing enhanced 911 systems as well as the re-education and re-training of dispatch personnel regarding dispatch life support (DLS) for patients with acute stroke (6,12). Such dispatch-related recommendations should specifically address the feasibility and process of on-line identification and appropriate response triage for stroke patients as well as applicable prearrival instructions (i.e., dispatcher-guided actions that patients or bystanders can take prior to the arrival of professional responders). The discussions should also address the screening evaluations provided in managed care systems to ensure that stroke patients do not miss a therapeutic window.

Other issues to be addressed should include the training manuals and curricula provided to EMS personnel, both at the BLS and ALS levels. We should focus not only on patient assessment and rapid identification of stroke, but also on standardized patient care guidelines and documentation parameters. In addition, guidelines for the identification and designation of stroke centers as well as the triage criteria for direct transport to such centers should be considered and properly evaluated.

In the end, the distillate of all of these discussions must be targeted at those EMS system educators, supervisors, and medical directors who must eventually stress the urgency of accessing definitive care for patients with brain attack, just as they currently do for patients with abdominal gunshot wounds or those comatose patients with closed head injury. The discussions should also try to analyze and develop empirical guidelines for those extraordinary circumstances in which specialty care is not readily accessible. Simultaneously, with all of these discussions, topics for future research and evaluation should be identified and formally addressed by the scientific community.

In conclusion, to optimize the chances of recovery for patients with acute stroke, all of the links in the Chain of Recovery for brain attack must be strengthened. The key links include:

  • Immediate identification of stroke symptoms and appropriate reactions by bystanders (or the patients themselves).
  • Early access to EMS (e.g., through enhanced 911 priority dispatch systems that provide prearrival instructions).
  • Rapid EMS response, treatment, and evacuation to designated centers capable of immediately providing definitive diagnosis and treatment of stroke.
  • Early communication to alert the specialty receiving center (by radio or cellular telephone), thereby ensuring preparation and immediate mobilization of resources for the stroke patient.
  • Rapid diagnosis and intervention at those designated receiving centers.
  • Specialized treatment and evaluation of complications, precipitating factors, and accompanying conditions.
  • Appropriate rehabilitation when applicable.

If these links in the Chain of Recovery for brain attack are to be established on a widespread basis, it will clearly require a significant number of EMS system modifications for many communities across the United States. Beyond the clear need for public education initiatives, the currently available educational offerings and clinical approaches practiced in most EMS systems indicate that widespread re-education and re-orientation of prehospital care services are now clearly in order if we want to ensure the optimal management of patients with acute stroke.

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Consensus Issues

In the following pages, the consensus statements recommended at the National Symposium on Rapid Identification and Treatment of Acute Stroke are presented. The issues addressed were stimulated by the following questions, starting with those related to access and dispatch issues:

  • Should "enhanced" 911 systems be established on a universal basis so that digital displays of the caller's address and telephone number will be entered automatically onto the dispatchers' call screens?
  • Should priority dispatch systems be established and/or upgraded to re-prioritize stroke patients?
  • Should specific dispatch algorithms be established that will help to better identify stroke patients?
  • In tiered systems with ALS and BLS ambulances, should the closest available transport unit (ambulance), basic or advanced, be sent?
  • What type of specialized instructions, provided by dispatchers to those calling for help while EMS rescuers are responding ("prearrival instructions"), should be established for stroke patients? While EMS responders are en route to the scene, should the dispatchers try to ascertain additional information to relay to responding units ("Is the patient a diabetic?" "Did the patient recently fall or have a head injury?" "Is the patient snoring or having problems breathing? "What medicine is the patient taking?")?
  • Should policies be established that will better ensure that stroke patients will not miss windows of therapeutic opportunities because of managed care screening practices?
  • Can the dispatch center and/or medical communications center (EMS base station) receive and promptly provide pre-notification to staff at the receiving facility to prepare them for arrival of the possible stroke patient?
  • What educational initiatives should now be recommended for dispatchers, medical directors for dispatch offices, and EMS managers?
  • How can dispatchers receive feedback regarding stroke patients?
  • What research initiatives are now recommended regarding access and dispatch center activities?

Next, it is also important to address the issue of medical care and transport once the EMS system has been activated. Given the considerations of different EMS configurations and the potential for either ALS or BLS ambulance response (even by design as the closest available transport vehicle), it is important to develop recommendations that are useful for both basic and advanced care providers.

Before presenting specific questions to be addressed, it is important to provide some additional perspectives on this area of discussion. The concept of rapid response and evacuation to specialty centers is not a new concept for EMS personnel. Both BLS and ALS providers have been well-trained to rapidly transport patients with major injuries directly to trauma centers (6). However, stroke patients have not yet received the same priority and attention, either clinically or educationally. Simply put, an alert, reclining patient with slurred speech, slight facial droop, and a systolic blood pressure of 190 mm Hg generally does not evoke the same call to action that a gunshot wound to the abdomen does. Although we would now want that stroke patient to be approached just as aggressively as the abdominal gunshot wound patient, the concept of similar urgency for stroke patients has not yet percolated into EMS educational programs. Again, if one reviews the current texts and training courses available for both BLS and ALS personnel, it is clear that stroke is not considered an urgent situation short of monitoring the patient for respiratory compromise and providing supportive care for obtundation. At best, EMS personnel are asked to rule out hypoglycemia and to treat it if applicable.

Therefore, to correct the situation, it would be best to target future training initiatives for EMS personnel, both initial and continuing education courses and medical direction. Years ago, the slightly intoxicated 55-year-old man who could calmly point out a powder burn above his umbilicus might not have elicited as much immediate reaction either. However, years of educational efforts, national consensus, and constant reinforcement from quality assurance personnel have helped to establish the clear urgency of such situations. Such efforts have also helped to ensure the rapid evacuation of such patients to specialty (trauma) centers, often bypassing closer hospitals to achieve that goal of rapid definitive care in the hands of experienced experts. In turn, similar educational endeavors should be able to accomplish the same goals for stroke patients.

Given these issues, the symposium participants identified possible problems in the prehospital care of stroke patients and developed recommendations to deal with the existing weaknesses in the prehospital links of the Chain of Recovery. The following questions were addressed:

1. What modifications are necessary to appropriately update current EMS texts and training curricula regarding state-of-the-art stroke management?

2. What types of assessment skills do out-of-hospital BLS and ALS providers, respectively, need to learn and utilize? Which of these skills are mandatory and which are only "nice to know" and utilize?

3. What should first-response personnel (e.g., firefighters and police officers) be taught regarding identification of stroke patients and what actions should they take when dealing with a stroke patient?

4. What prehospital actions and interventions should always be attempted? When should they be aborted or deferred?

5. Under what circumstances should an ALS crew be summoned when a BLS ambulance crew is readily available to transport a patient?

6. Should dextrose be administered (parenterally or orally) for altered mental status without glucose measurement and, if not, should glucometers or reagent strips be recommended as routine equipment for all EMS responders, both basic and advanced?

7. Should hypertension ever be treated in the prehospital setting and, if so, with what therapeutic regimens?

8. What are the recommended airway procedures and under what conditions are they appropriate? What types of oxygen concentrations should be administered?

9. Should moribund (or comatose) patients receive other therapeutic interventions such as mannitol, lidocaine, diuretics, or other agents for reducing intracranial pressure?

10. Should stroke patients ever be provided a dose of aspirin or other antiplatelet agents?

11. Are there any neuroprotective agents that are appropriate for prehospital administration? Are clinical trials indicated?

12. What types of information (including names and phone numbers of witnesses) should be obtained to help more accurately assess the onset of the suspected stroke?

13. Should Neurological Intervention Centers (NICs) be designated and, if so, what would be the proposed triage criteria for recommending direct transport to such centers?

14. What would be the appropriate criteria for initiating early pre-notification of the receiving facility? Would there be various levels of alert depending upon the on-scene assessment of the patient?

15. What kind of feedback loops should be provided for EMS care providers (including dispatchers) regarding their involvement in the Chain of Recovery for stroke patients, including their specific management of individual patients as well as specific patient outcomes, particularly when there is a successful outcome as a result of their work?

16. Should model guidelines be developed for patient assessment, management, and hospital notification?

17. What are the educational initiatives that the NINDS should recommend for EMS personnel, their supervisors, their educators, and their medical directors? Should brief public service announcements or educational videos be developed?

18. What are the appropriate areas for research, both administrative and medical? How should educational initiatives be evaluated?

19. What are the appropriate data sets, and particularly the minimal data sets, needed to track and evaluate stroke management? Should stroke registries be established and, if so, what is the appropriate nomenclature for terminology and what are appropriate prospectively defined data points (e.g., definition of "door to needle time," "EMS response interval," or "EMS transport time")?

20. Should NINDS take a leadership role in terms of developing a model of standardized nomenclature and prospectively defined data points regarding stroke management?

In summary, the number and breadth of these current general questions underscore the need to help strengthen the various links in the prehospital Chain of Recovery for the patient with acute stroke.

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Special Considerations in Terms of Access to Care and Transportation to Definitive Care

As a final consideration it is important to address special situations outside the realm of most communities where specialty care is readily accessible to the average stroke patient. While the majority of the population lives within urban centers and in relative proximity to tertiary care facilities, access to care becomes a worrisome question once one ventures outside such venues. Small community hospitals traditionally have played a critical role in the initial evaluation and management of stroke patients, but should this role now be changed?

More specifically:

1. Should community hospitals now be bypassed by ambulances? Likewise, if suspected stroke patients arrive at their emergency centers, should community hospital staff members immediately transfer those patients to specialized NICs?

2. Should the staff of community hospitals first attempt to treat stroke patients empirically (or after consultation via telemedicine links)? Should they then transfer such patients? If so, would this paradigm create new training implications for the personnel who would be providing the transfers (i.e., paramedics, flight nurses, etc.)?

3. Should medical rescue helicopters be sent directly to the scene of a stroke patient as is typically done for trauma patients in remote locations? Are there defining criteria for such requests for air medical rescue and what are the circumstances that would contraindicate such a response?

4. Should stroke specialists be flown (or even transported emergently by ground) from specialty centers to the community hospital for evaluation and treatment of stroke patients through prospective practice agreements and contingency plans?

Are there feasible areas for research regarding these issues and how could these studies be executed?

In conclusion, patients with acute stroke pose a significant challenge to EMS personnel. From the dispatch office to the neurological intensive care unit and rehabilitation areas at specialized stroke centers, there are multiple links that help to ensure a patient's chance of obtaining full recovery from acute stroke. The strength of that Chain of Recovery depends upon the strength of each of the individual links. It is hoped that these discussions will be a starting point for another major step in achieving the goal of ensuring a strong Chain of Recovery for stroke patients. We hope that this goal can be achieved in each and every community and for each and every patient who can benefit from rapid intervention.

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References

1. Camarata PJ, Heros RC, and Latchow RE. "Brain attack": The rationale for treating stroke as medical emergency. Neurosurgery 1994;34(1):144-158.

2. Hund E, Grau A, and Hacke W. Neurocritical care for acute ischemic stroke. Neurologic Critical Care 1995;13(3):511-527.

3. Kay R, Wong KS, Yu YL, et al. Low-molecular-weight heparin for the treatment of acute ischemic stroke. N Engl J Med 1995;333:1588-1593.

4. The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. Tissue plasminogen activator for acute ischemic stroke. N Engl J Med 1995;333:1581-1587.

5. Donnan GA, Davis SM, Chambers BR, et al. Streptokinase for acute ischemic stroke with relationship to time of administration. JAMA 1996;276:961-966.

6. Pepe PE, and Lopass MK. Prehospital Care. In: Moore EE, et al, eds. Early Care of the Injured Patient. Toronto: B.C. Decker, Inc.; 1990:37-55.

7. Weaver WD, Cerqueira M, Hallstrom AP, et al. Prehospital-initiated vs hospital-initiated thrombolytic therapy: The Myocardial Infarction Triage and Intervention Trial. JAMA 1993;270(10):1211-1216.

8. Crosby LA, and Lewallen DG, eds. Emergency Care and Transportation of the Sick and Injured, 16th edition. Chicago: American Academy of Orthopaedic Surgeons; 1995.

9. McSwain NE, White RD, Patura JL, et al, eds. The Basic EMT: Comprehensive Prehospital Patient Care. St. Louis: Mosby Lifeline, 1997.

10. Stoy WA, ed. EMT Basic. St. Louis: Mosby; 1996.

11. Hafen BQ, Karren KJ, Mistorich JJ, eds. Prehospital Emergency Care, 5th edition. Englewood Cliffs, NJ: Brady (Prentice Hall); 1996.

12. Curka PA, Pepe PE, Ginger VF, et al. Emergency medical services priority dispatch. Ann Emerg Med 1993;22:1688-1695.

13. Hunt RC, Brown LH, Cabinum ES, et al. Is ambulance transport time with lights and siren faster than that without? Ann Emerg Med 1995; 25:507-511.

14. Kothari R, Barsan W, Brott T, et al. Frequency and accuracy of prehospital diagnosis of stroke. Stroke 1995;26:937-941.

15. Maniscalco PM, and Petrou ZG. New team approach to acute stroke starts with EMS. J Emerg Med Service 1997;22(5):18-20.

16. Bukata WR. Thrombolytics for strokes: The jury is still out. Emerg Med News 1997;19:20-23.

17. Kereiakes DJ, Gibler WB, Martin LH, et al. Relative importancy of emergency medical system transport and the prehospital electrocardiogram on reducing hospital time delay to therapy for acute myocardial infarction: A preliminary report from the Cincinnati Heart Project. Am Heart J 1992;123:835-840.

18. Cummins RO, Ornato JP, Thies W, et al. The American Heart Association Emergency Cardiac Care Committee's Subcommittee on Advanced Cardiac Life Support. Improving survival from sudden cardiac arrest: The "chain of survival" concept. Circulation1991;83:1832-1847.

19. Timerding BL, Barsan WG, Hedges JR, et al. Stroke patient evaluation in the emergency department before pharmacologic therapy. Am J Emerg Med 1989;7:11-15.

20. Bratina P, Greenberg L, Pasteur W, et al. Current emergency department management of stroke in Houston, Texas. Stroke 1995;26:409-414.

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Last Edited: July 01, 1999

National Institute of Neurological Disorders and Stroke
National Institutes of Health
Bethesda, MD 20892

Last updated June 19, 2008