Acute ST-elevation myocardial infarction: Prehospital fibrinolysis

INTRODUCTION — 

For all patients with acute ST-elevation myocardial infarction (STEMI) who will undergo fibrinolysis, early coronary artery reperfusion improves outcomes compared with later reperfusion. Prehospital fibrinolytic therapy, administered by paramedics or other prehospital personnel prior to arrival in the emergency department, may decrease the time to reperfusion. However, many factors may contribute to delays in fibrinolytic therapy, including patient-related factors and issues related to systems of care. Patients who present with STEMI in locations far from emergency departments or catheterization laboratory facilities may benefit from prehospital fibrinolysis.

This topic describes the management of prehospital fibrinolytic therapy, training, treatment protocols, and quality assurance programs needed to ensure a safe and effective prehospital fibrinolysis program.

Detailed information about the medications (including fibrinolytics) used to treat STEMI, data supporting the effectiveness of prehospital fibrinolysis, and general information about the diagnosis and management of acute coronary syndrome and STEMI are presented separately. (See "Acute ST-elevation myocardial infarction: Selecting a reperfusion strategy" and "Acute ST-elevation myocardial infarction: Management of fibrinolysis" and "Overview of the acute management of ST-elevation myocardial infarction" and "Initial evaluation and management of suspected acute coronary syndrome (myocardial infarction, unstable angina) in the emergency department".)

ROLE OF PREHOSPITAL FIBRINOLYSIS — 

The decision to proceed with prehospital fibrinolysis depends on the patient's characteristics, the availability of percutaneous coronary intervention (PCI), and the presence of a well-established system of care for the administration of prehospital fibrinolysis. In general, patients who may benefit from prehospital fibrinolysis are those who would benefit from fibrinolysis but who are too distant from a hospital that delivers fibrinolysis to receive such therapy in a timely manner (algorithm 1). Information on the decision to perform fibrinolysis and the relative efficacy of prehospital and hospital-based fibrinolysis are discussed separately. (See "Acute ST-elevation myocardial infarction: Selecting a reperfusion strategy", section on 'Approach in most patients' and "Acute ST-elevation myocardial infarction: Selecting a reperfusion strategy", section on 'Prehospital fibrinolysis'.)

ASPECTS OF FIBRINOLYTIC THERAPY

Choice of fibrinolytic agent — In general, the choice of fibrinolytic agent for prehospital use is similar to that for patients treated in an emergency department or hospital. Reteplase and tenecteplase are effective and easy to administer in an ambulance. Reteplase does not require a weight to dose, which is an advantage of reteplase compared with tenecteplase (table 1). The dosing and evidence for specific fibrinolytic agents are discussed separately. (See "Acute ST-elevation myocardial infarction: Management of fibrinolysis", section on 'Components of therapy'.)

Antiplatelet agents — In patients with STEMI who will undergo prehospital fibrinolysis, we administer aspirin and clopidogrel. The doses of aspirin and clopidogrel are described separately. (See "Acute ST-elevation myocardial infarction: Initial antiplatelet therapy", section on 'Fibrinolytic therapy'.)

This approach is consistent with European guidelines [1].

This approach to antiplatelet therapy differs from the approach in patients undergoing PCI; other P2Y₁₂ inhibitors (eg, prasugrel, ticagrelor) are relatively contraindicated in patients undergoing reperfusion with fibrinolysis. (See "Acute ST-elevation myocardial infarction: Management of fibrinolysis", section on 'Relative contraindications'.)

Anticoagulation — In patients who will undergo prehospital fibrinolysis, we suggest low molecular weight heparin (LMWH) rather than unfractionated heparin or other agents. This preference is primarily due to the ease of administration with LMWH (intravenous [IV] bolus and subcutaneous dosing). We use enoxaparin 30 mg IV push followed 10 minutes later by 1 mg/kg subcutaneously, administered with fibrinolysis. Patients over 75 years old receive enoxaparin 0.75 mg subcutaneously with no IV bolus. As an alternative, heparin can be administered as a weight-based IV bolus without a subsequent infusion (maximum bolus dose is 4000 units) [2-7].

This approach is similar to the approach in patients who will receive fibrinolysis and either no subsequent angiography or delayed angiography, which is described separately. (See "Acute ST-elevation myocardial infarction: Management of anticoagulation", section on 'Fibrinolytic therapy with or without planned PCI'.)

COMPLICATIONS

Bleeding — Bleeding is the primary complication of fibrinolytic therapy, and hemorrhagic stroke is the greatest concern. Thus, paramedics must screen patients carefully for contraindications to fibrinolysis and monitor patients closely following administration for signs of hemorrhagic stroke (table 2). In patients with acute intracerebral hemorrhage, common signs include deterioration in mental status, headache, nausea and vomiting, or a sudden rise in blood pressure. Further details on the clinical manifestations of stroke are discussed separately. (See "Overview of the evaluation of stroke".)

Failed fibrinolysis or threatened reocclusion — Following prehospital fibrinolysis, some patients may have recurrence of symptoms and signs of myocardial ischemia, suggesting reocclusion of the involved coronary artery. This may include recurrent or new ST-segment elevations. The management of failed fibrinolysis and threatened reocclusion is discussed separately. (See "Acute ST elevation myocardial infarction: Failed fibrinolysis".)

NECESSARY EQUIPMENT AND CAPABILITIES — 

Emergency medical services (EMS) systems that employ prehospital fibrinolysis must be able to identify the patient with STEMI, notify the receiving hospital of their arrival, and treat the patient en route to the hospital. Capabilities vary from system to system, and from country to country, but certain basic characteristics are required:

Prehospital 12-lead ECG — We recommend a model in which the electrocardiograms (ECGs) of prospective candidates for fibrinolysis are reviewed in real time by the medical control physician at the receiving emergency department or hospital prior to fibrinolysis to reduce the risk of misinterpretation. This is particularly important for those patients with ECGs that are difficult to interpret or have equivocal findings, such as bundle branch blocks or left ventricular hypertrophy. There are two strategies in use:

●Online control – Receiving facilities may have "online" control, in which the medical director interprets the ECG independently, discusses the patient with the prehospital provider, agrees or disagrees with the paramedic reading, and orders the administration of fibrinolytics. In this model, transmission of the ECG to the receiving hospital and interpretation by a physician therein are required. ECGs are transmitted using either analog or digital technology via land lines or cellular phones. The ECG can also be transmitted using some wireless handheld electronic devices equipped with a camera by using a photograph of the ECG.

One innovation used in India for a hub-and-spoke STEMI system was to use an ECG machine that would perform an ECG and transmit it to the hub-hospital on-call doctor for STEMI confirmation [8]. As a backup to reduce delays, the ECG was also sent to a dedicated tele-ECG center, which interpreted the ECG. The turnaround time was less than five minutes.

●Offline control – Other EMS systems have "offline" control, which allows the prehospital provider to interpret the ECG independently and administer fibrinolysis according to a protocol. Such is the case in many European countries and in Israel, where physicians are often present in the ambulance [9]. Paramedics must be trained to obtain a prehospital ECG rapidly and efficiently, interpret that ECG (with the help of computerized algorithms), and correlate the ECG with the patient's presenting symptoms [10].

In addition, our EMS crews regularly review ECGs after the case to improve their interpretation skills, and one way to reduce the number of missed STEMIs in patients with atypical symptoms (eg, dyspnea, weakness) is to perform a 12-lead ECG on every patient with a relevant chief complaint. This may not be practical in some instances, and we allow our EMS crews some latitude in deciding whether to obtain an ECG, but our chest pain protocol includes liberal criteria for obtaining an ECG. Atypical symptoms associated with acute coronary syndrome are discussed separately. (See "Initial evaluation and management of suspected acute coronary syndrome (myocardial infarction, unstable angina) in the emergency department", section on 'Atypical presentations'.)

Fibrinolysis checklist — Paramedics or prehospital providers must review the indications and contraindications to fibrinolytics to ensure that the patient meets eligibility criteria before administering the medication (table 2). The use of an explicit checklist ensures the best patient outcomes and minimizes medical and legal risks from inappropriate treatment [11]. An example of a table listing the absolute and relative contraindications to fibrinolysis and a separate flow sheet for the administration of fibrinolytic therapy are presented graphically (table 2 and algorithm 2).

Prehospital treatment protocol — Intravenous access and continuous cardiac monitoring should be in place before fibrinolytic medications are given. Fibrinolytics are given in the ambulance along with other therapies (if indicated) such as oxygen and medications including nitrates, beta blockers, antiplatelet agents (eg, aspirin, P2Y₁₂ receptor blockers), and anticoagulants (eg, heparin, bivalirudin, or low molecular weight heparin) (table 3). Essential clinical information about these medications, including doses and contraindications, must be included in the prehospital STEMI and fibrinolysis treatment protocols [2-7,12-17]. An example flow sheet is available for chest pain and is used by the paramedics at one author's home institution (algorithm 3).

Destination protocols — Patients treated with fibrinolysis in the prehospital setting should be transported to facilities capable of providing advanced cardiac care, including percutaneous coronary intervention (PCI), especially in the case of failed fibrinolysis, and the management of complications from STEMI [4,6,12,18,19]. Patients who are not eligible for prehospital fibrinolysis after evaluation are generally transported to the closest PCI-capable facility for primary PCI. This may include air transport if indicated.

Adequate storage of fibrinolytic agents — The preferred agents for fibrinolysis must be stored in refrigerated containers. The costs of refrigeration and expired vials of fibrinolytic medications can have profound financial implications for an emergency medical services (EMS) system [4,5].

Community support — In addition to the capabilities described above, community support is essential for any successful prehospital fibrinolysis program. All participants, including hospital administrators, EMS directors, emergency and cardiology department clinicians and support personnel, and paramedics must be fully informed and committed to the program's success.

Quality assurance — Quality assurance and quality improvement programs are essential for prehospital fibrinolysis to be successful. (See "Measuring quality in hospitals in the United States".)

Since STEMI treated with fibrinolysis is an infrequent occurrence for any single EMS system, it is important to use each case as a teaching tool. At one author's institution, each case, including those who did not receive fibrinolytics, is closely reviewed, with careful attention to the outcome and to process measures (eg, details, timing) of the following:

●Obtaining, interpreting, and transmitting the ECG

●Completing the fibrinolysis checklist

●Assessing the patient and discussing the case with the medical control physician

●Administering fibrinolytic medication, including dosing

●Providing feedback to EMS crew members on patient outcome and areas for improvement

REQUIREMENTS OF PREHOSPITAL PROVIDERS — 

The administration of fibrinolytics in the prehospital setting is held to the same standards as administration in the emergency department. As such, quality control and training are of the utmost importance. Professional societies have not published statements on the requirements for prehospital fibrinolysis programs. In this section, we describe the requirements for paramedics at one author's institution.

Patient assessment — Those providing prehospital care must be able to obtain important information about the patient and convey it to their medical control physicians or use such information to guide the administration of fibrinolytics. These requirements extend beyond typical paramedic capabilities and require additional training and experience. Therefore, the education and testing of paramedics participating in a prehospital fibrinolysis program should encompass the full breadth of chest pain evaluation, in addition to ECG interpretation and administration of treatments. Practical testing involving simulated STEMI patients is necessary for paramedics to demonstrate competency.

The details on the evaluation of chest pain and discomfort are described separately. (See "Approach to the adult with nontraumatic chest pain in the emergency department".)

ECG interpretation — At least one member of a paramedic-emergency-medical-technician or paramedic-paramedic team involved in prehospital fibrinolysis must have demonstrated proficiency in ECG interpretation and administration of fibrinolytic medication. Although these proficiencies are certified locally (eg, by the hospital), the process of demonstrating proficiency must be formalized. We recommend that a paramedic administering fibrinolytics should have at least one year of experience and should have successfully completed a 50-hour course on 12-lead ECG interpretation and fibrinolytic administration, including a written examination.

Checklist and lytic delivery — The paramedic should complete at least three fibrinolytic checklists and observe fibrinolytics being administered to three patients before giving the medication themselves. A checklist is provided and is used at one author's institution to assess paramedic performance in prehospital fibrinolysis competency testing (table 4).

Familiarity with personnel and systems of care — Time spent in the emergency department and catheterization laboratories of local referral hospitals helps paramedics familiarize themselves with the staff and capabilities of these departments.

Maintenance of skills — It is important that paramedics who are certified to provide prehospital fibrinolysis participate in periodic classes and reevaluations to ensure retention of necessary skills. We suggest quarterly classes (ie, every three months) on ECG interpretation and annual retesting to demonstrate proficiency. Within one author's EMS service, the ability of the crew to administer prehospital fibrinolytics serves as a motivational tool. Not all paramedics are certified to provide this therapy and it offers paramedics a coveted goal.

CHALLENGES TO PREHOSPITAL FIBRINOLYSIS — 

The challenges to more widespread use of prehospital fibrinolysis include [20]:

●Availability of physicians – For online medical control, a physician is needed to interpret the ECG and to order fibrinolytic therapy and must be available at all times.

●Rigorous maintenance of quality standards – Offline medical control does not require physicians to be readily available but does demand physician involvement for ongoing training and quality control.

●Cost of lytic agents – The cost of fibrinolytics can be substantial, especially in settings where use is infrequent.

●Shortage of trained personnel – At least one provider on each ambulance must be trained in ECG interpretation and fibrinolytic administration to operate an effective prehospital fibrinolysis system. Due to the specialized training required and low frequency of use, this is often not practical for communities that would benefit the most from prehospital fibrinolysis.

●Maintenance of certifications – The frequent oversight, retraining, and recredentialing requirements necessary to maintain competency are a high financial burden.

The feasibility of prehospital fibrinolysis is well-documented. The ER-TIMI 19 trial included 20 EMS systems in urban, semiurban, and rural areas in the United States and Canada [21,22]. A straightforward training program permitted paramedical personnel working with a remote medical control physician to screen patients with suspected MI by history, physical examination, and ECG. Patients with STEMI received fibrinolytic therapy within a median of 31 minutes after arrival of paramedical personnel compared with 63 minutes for in-hospital fibrinolysis in a control group.

SETTINGS WITHOUT HOSPITALS AND ASSOCIATED RESOURCES — 

The term prehospital fibrinolysis presupposes a well-developed STEMI network with advanced life support (ALS) ambulances staffed with trained emergency medical personnel who can safely and effectively institute fibrinolysis and other emergency care in the ambulance. Prehospital fibrinolysis also assumes that emergency care (eg, cardiac intensive care unit), if not rapidly available, is accessible.

In some settings, ALS ambulance services, hospitals with acute care capability, and percutaneous coronary intervention are not available. In these settings, in-ambulance fibrinolysis is not possible, but fibrinolysis could be delivered in medical facilities such as a primary health center staffed by primary care physicians. With similar training and innovations such as tele-coronary care unit (CCU) or tele-ECG, such medical facilities could develop the capability to deliver early fibrinolysis before transfer to a hospital with CCU for further management. The training, equipment, and medications at the "pre-CCU" facility would be similar to those discussed elsewhere in this topic for prehospital fibrinolysis in an ALS ambulance. (See 'Necessary equipment and capabilities' above and 'Requirements of prehospital providers' above.)

SOCIETY GUIDELINE LINKS — 

Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: ST-elevation myocardial infarction (STEMI)".)

SUMMARY AND RECOMMENDATIONS

●Role of prehospital fibrinolysis – The decision to proceed with prehospital fibrinolysis depends on the patient's characteristics, the availability of percutaneous coronary intervention (PCI), and the presence of a well-established system of care for the administration of prehospital fibrinolysis. In general, patients who may benefit from prehospital fibrinolysis are those who would benefit from fibrinolysis but who are too distant from a hospital that delivers fibrinolysis to receive such therapy in a timely manner (algorithm 1). (See 'Role of prehospital fibrinolysis' above.)

●Aspects of fibrinolytic therapy

•Choice of fibrinolytic agent – In general, the choice of fibrinolytic agent for prehospital use is similar to that for patients being treated in an emergency department or hospital. Reteplase and tenecteplase are effective and easy to administer in an ambulance. Reteplase does not require a weight to dose, which is an advantage of reteplase compared with tenecteplase (table 1). The dosing and evidence for specific fibrinolytic agents are discussed separately. (See "Acute ST-elevation myocardial infarction: Management of fibrinolysis", section on 'Components of therapy'.)

•Antiplatelet agents –In patients with ST-elevation myocardial infarction (STEMI) who will undergo prehospital fibrinolysis, we administer aspirin and clopidogrel. The doses of aspirin and clopidogrel are described separately. (See "Acute ST-elevation myocardial infarction: Initial antiplatelet therapy", section on 'Fibrinolytic therapy'.)

•Anticoagulation – In patients who will undergo prehospital fibrinolysis, we suggest low molecular weight heparin (LMWH) rather than unfractionated heparin or other agents (Grade 2C). This preference is primarily due to its ease of administration (intravenous [IV] bolus and subcutaneous dosing). (See 'Anticoagulation' above.)

●Complications – The complications of prehospital fibrinolysis are similar to those that occur with hospital-based fibrinolysis. At a minimum, emergency medical personnel should be prepared to monitor for the following complications (see 'Complications' above):

•Intracerebral bleeding. (See "Overview of the evaluation of stroke".)

•Failed fibrinolysis or threatened reocclusion. (See "Acute ST elevation myocardial infarction: Failed fibrinolysis".)

●Characteristics of systems required for prehospital fibrinolysis – Prehospital fibrinolysis is held to the same standards as hospital-based fibrinolysis. As such, systems of care designed to deliver prehospital fibrinolysis should have the necessary equipment, capabilities, and clinical training required to operate a safe and effective system of care. (See 'Necessary equipment and capabilities' above and 'Requirements of prehospital providers' above.)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Henderson McGinnis, MD, who contributed to earlier versions of this topic review.