Performance of prehospital fibrinolysis

INTRODUCTION — For all patients with acute ST-elevation myocardial infarction (STEMI), early coronary artery reperfusion improves outcomes compared with later reperfusion. Fibrinolytic therapy is an effective reperfusion strategy for many patients with STEMI when given within 12 hours of the onset of chest pain. The maximum benefit of fibrinolysis is seen when given early, preferably within three hours and optimally within one hour of symptom onset.

Many factors may contribute to delays in fibrinolytic therapy, including patient-related factors and issues related to STEMI network, STEMI systems of care, and systems issues. Patients who present with STEMI in rural locations may live far from emergency departments or catheterization laboratory facilities. In these settings, prehospital fibrinolytic therapy, administered by paramedics or other prehospital personnel prior to arrival in the emergency department, may decrease the time to reperfusion.

This topic describes the 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: The use of fibrinolytic therapy" 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" and "Acute ST-elevation myocardial infarction: The use of fibrinolytic therapy", section on 'Initiation of therapy'.)

RATIONALE — Administration of fibrinolytic therapy before hospital arrival (eg, in an ambulance) is an established practice in many geographies. The rationale for prehospital fibrinolysis is to shorten the time between the onset of symptoms and the restoration of coronary blood flow in the occluded artery [1-16]. (See "Acute ST-elevation myocardial infarction: The use of fibrinolytic therapy", section on 'Timing'.)

Treatment within the first hour saves twice as many lives as during the second hour (65 versus 37 lives saved per 1000 patients treated) [1,5,17]. For each 30-minute delay to reperfusion, there is approximately a 10 percent relative increase in mortality in patients with STEMI. Furthermore, studies have shown that 25 percent of those treated with fibrinolysis within the first hour have an "aborted MI" with normalization of electrocardiogram (ECG) and no evidence of myocardial necrosis [18].

Two meta-analyses comparing prehospital with in-hospital fibrinolysis found that a shorter time to fibrinolysis reduced all-cause hospital mortality [16,19].

FEASIBILITY AND EFFECTIVENESS — Achieving myocardial reperfusion as rapidly as possible is the key to improving survival and decreasing morbidity in patients with acute MI. Multiple studies have demonstrated the feasibility and effectiveness of prehospital fibrinolysis in reducing the time to treatment for patients with STEMI and improving outcomes. However, rural systems may face challenges in having the patient volume to support such prehospital care.

The practicability of using general community emergency medical services (EMS) to perform fibrinolysis has been demonstrated in several studies [13,20-24]. The ER-TIMI 19 trial included 20 EMS systems in urban, semiurban, and rural areas in the United States and Canada [20,25]. 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 in comparison to 63 minutes for in-hospital fibrinolysis in a control group.

A 2002 report examined the benefit of prehospital fibrinolysis in the French EMS system [21,26]. Importantly, the French EMS system had a physician in the ambulance during the initiation of onboard fibrinolysis. Of 1922 patients with STEMI, 180 (9 percent) received prehospital fibrinolysis. Mortality at one year was significantly lower among patients treated with prehospital fibrinolysis than among patients treated with either in-hospital fibrinolysis or primary percutaneous coronary intervention (6 versus 11 and 11 percent, adjusted relative risk 0.49, 95% CI 0.24-1.00).

As community prehospital fibrinolysis likely requires a high-volume EMS system and ongoing recertification to be safe and effective, rural systems may struggle to have enough patient encounters to meet training and performance standards [27]. In addition, at least one provider on each ambulance must be trained in ECG interpretation and fibrinolytic administration, and frequent oversight and retraining/recredentialing are necessary to maintain competency. Online medical control is needed to administer fibrinolysis appropriately, and many rural EMS systems employ offline control. Finally, the cost of fibrinolytics can be substantial, especially in settings where numerous ambulances require the drugs to be stocked but use is infrequent. For these reasons, some rural EMS systems have been reluctant to adopt prehospital fibrinolysis.

Maintaining high-volume may be difficult even in urban settings. In a report of two EMS studies performed in Tennessee and Ohio, fewer than 5 percent of patients presenting with chest pain were found to be candidates for fibrinolysis [28]. In addition, only 60 percent of field treatment decisions by emergency physicians using transmitted 12-lead ECGs were accurate. A decline in paramedic skills was noted because of infrequent administration of the fibrinolytic agent. As with any high-risk, low-frequency procedure, one approach to ensuring quality is to limit the EMS providers who can administer thrombolytics to those who have greater experience and receive regular training and assessment.

LOW- AND MIDDLE-INCOME COUNTRIES — The term prehospital fibrinolysis presupposes a well-developed STEMI network with clear transfer and destination pathways. This is seldom available in low- and middle-income countries. "Prehospital" refers to an advanced life support (ALS) ambulance staffed with trained emergency medical technicians or in some places, physicians, to institute fibrinolysis and emergency care in the ambulance. The "hospital" refers to a reperfusion-capable medical facility (percutaneous coronary intervention [PCI] or fibrinolysis) with a coronary care unit (CCU) for further management of the STEMI patient. There have been many models that have been successfully implemented in the United States and countries in Europe. The continued drop in cases of STEMI in these countries, the improved access to primary PCI, and logistical difficulties in instituting ambulance-based fibrinolysis have resulted in very slow expansion of this service.

On the other hand, low- and middle-income countries continue to use fibrinolysis as the main mode of reperfusion. However, advanced life support (ALS) ambulance services are usually not available in many of these countries, and the available service is usually inadequately equipped and staffed with poorly trained paramedics. In-ambulance fibrinolysis is not possible in most of these countries. An alternate approach is to consider fibrinolysis in medical facilities like a primary health center or similar facility, which are staffed by primary care physicians and do not have a CCU, and so are not considered as reperfusion centers. These medical facilities, could, with similar training and innovations like tele-CCU or tele-ECG, develop the capability to deliver early fibrinolysis before transfer to a hospital with CCU for further management. Thus, they could be more appropriately termed "pre-CCU" fibrinolysis rather than "pre-hospital" fibrinolysis. The training, equipment, and medications at the "pre-CCU" facility would be similar to those discussed below for prehospital fibrinolysis in an ALS ambulance.

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 capabilities are required:

●Prehospital 12-lead ECG – 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 [29].

●Prehospital ECG transmission capability – Prehospital 12-lead ECGs are usually transmitted to a receiving hospital or to the prehospital medical direction facility where an emergency physician or cardiologist can assess them. 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. 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 [30].

ECGs are transmitted using either analog or digital technology via land lines or cell 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 [31]. As a back-up to reduce delays, the ECG was also sent to a dedicated tele-ECG center, which interpreted the ECG. The turn-around time was less than five minutes.

●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. The use of an explicit checklist ensures the best patient outcomes and minimizes medical and legal risks from inappropriate treatment [32]. We have attached a table listing the absolute and relative contraindications to fibrinolysis in the setting of STEMI and a separate flow sheet for the administration of fibrinolytic therapy that is used by paramedics at the author’s home institution (table 1 and algorithm 1).

●Prehospital STEMI 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). Essential clinical information about these medications, including doses and contraindications, must be included in the prehospital STEMI and fibrinolysis treatment protocols [2,3,11,33-41]. An example flow sheet is available for chest pain and is used by the paramedics at one author's home institution (algorithm 2). A separate table summarizing the acute treatment of acute coronary syndrome is provided, as well as links to topics describing the medical management of STEMI (table 2). (See "Overview of the acute management of ST-elevation myocardial infarction" and "Acute ST-elevation myocardial infarction: Management of anticoagulation" and "Acute ST-elevation myocardial infarction: Antiplatelet therapy".)

●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 [2,34,36,42,43]. 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. It is imperative to have destination protocols and transport capabilities prepared in advance, prior to the implementation of any prehospital fibrinolysis protocol. (See "Diagnosis and management of failed fibrinolysis or threatened reocclusion in acute ST-elevation myocardial infarction" and "Percutaneous coronary intervention after fibrinolysis for acute ST-elevation myocardial infarction" and "Acute myocardial infarction: Mechanical complications" and "Ventricular arrhythmias during acute myocardial infarction: Incidence, mechanisms, and clinical features".)

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.

REQUIREMENTS OF PREHOSPITAL PROVIDERS — The administration of fibrinolytics in the prehospital setting is held to the same standards as those for the emergency department (ED). As such, quality control and training are of the utmost importance. Consensus statements regarding the requirements for prehospital fibrinolysis programs have yet to be published, but in this section, we describe the requirements for paramedics at one author's home institution, which could be adapted by any hospital considering implementing a prehospital fibrinolysis program.

At least one member of a paramedic-emergency-medical-technician or paramedic-paramedic team giving fibrinolytic therapy 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.

STEMI patients must be rapidly identified by 12-lead ECG as the first step in determining if they are candidates for fibrinolysis. Therefore, paramedics must be proficient in obtaining, interpreting, and transmitting an ECG rapidly. 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. In addition, the paramedic should observe fibrinolytics being administered to three patients before giving the medication themselves. Time spent in the ED and catheterization labs of local referral hospitals helps paramedics familiarize themselves with the staff and capabilities of these departments.

In addition to interpreting the ECG, completing the fibrinolysis checklist, and administering fibrinolytics and related medications, prehospital providers must be able to obtain important information about the patient and convey it to their medical control physicians prior to giving fibrinolytics. Such information includes:

●Patient age and sex.

●Chief complaint (usually chest pain).

●Characteristics of chief complaint (eg, onset, duration, quality, provocative and palliative factors, associated symptoms).

●Vital signs (eg, blood pressure, pulse rate, respiratory rate, and oxygen saturation).

●Signs of decompensated heart failure.

●Pertinent cardiac and medical history, medications, and drug allergies.

●Estimated time to arrival at the receiving facility.

The ability to obtain and understand this information, report it accurately, and discuss it in real time extends beyond typical paramedic capabilities and requires 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. A checklist is provided and is used at one author's home institution to assess paramedic performance in prehospital fibrinolysis competency testing (table 3).

It is important that paramedics who are certified to provide prehospital fibrinolysis participate in periodic classes and reevaluations to ensure skill retention. 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.

PATIENT ELIGIBILITY — Most patients diagnosed with an acute STEMI will benefit from reperfusion as soon as possible. In general, percutaneous coronary intervention (PCI) is the preferred method of reperfusion for STEMI patients. Patients in facilities without timely access to PCI may require fibrinolytic therapy. Such patients must be screened for absolute and relative contraindications, as fibrinolysis carries a risk of severe bleeding, including intracranial hemorrhage, when given inappropriately. A table listing the absolute and relative contraindications to fibrinolysis in the setting of STEMI is provided (table 1). Selection of the appropriate therapy for STEMI, the contraindications and risks associated with fibrinolysis, and the efficacy of the medications used for fibrinolysis are all reviewed separately. (See "Acute ST-elevation myocardial infarction: Selecting a reperfusion strategy" and "Acute ST-elevation myocardial infarction: The use of fibrinolytic therapy" and "Diagnosis and management of failed fibrinolysis or threatened reocclusion in acute ST-elevation myocardial infarction", section on 'Primary failure'.)

USE OF FIBRINOLYTIC THERAPY — In general, our use of fibrinolytics before hospital arrival is similar to that for patients being treated in an emergency department. (See "Acute ST-elevation myocardial infarction: The use of fibrinolytic therapy".)

Fibrinolytics that can be given as an intravenous bolus, such as tenecteplase or reteplase, are preferred over tissue plasminogen activator due to ease of administration. Reteplase can be given as 10 mg in the prehospital setting and another 10 mg 30 minutes later upon arrival at the hospital. Tenecteplase can be given as a weight-based intravenous bolus in the prehospital setting but requires documentation of the patient's weight (obtained by history, not measurement). (See "Acute ST-elevation myocardial infarction: The use of fibrinolytic therapy".)

Either fibrinolytic agent must be refrigerated. The costs of refrigeration and expired vials of fibrinolytic medications can have profound financial implications for an emergency medical services system [36,37].

OTHER MEDICATIONS — Prehospital clinicians (eg, paramedics) work in a difficult setting where speed and efficiency are of the utmost importance. As such, pharmacologic therapies must sometimes be modified to make dosing as simple as possible and maximize the speed of administration. In some cases, medications not typically used in the hospital must be included in the prehospital formulary. A table summarizing the medications used in the treatment of acute coronary syndrome (STEMI or non-ST-elevation MI) is provided (table 2). Below, we list important medications given to patients being treated with fibrinolytics in the prehospital setting for STEMI and some of the ways in which they are modified:

●Antiplatelet agents (see "Acute ST-elevation myocardial infarction: Antiplatelet therapy"):

•Aspirin is usually given as two to four chewable baby aspirin (ie, 162 to 325 mg) [40]. If the patient cannot swallow, intravenous (IV) aspirin may be used if available. Soluble or chewable aspirin (300 mg) may be given if available.

•Clopidogrel – Clopidogrel should be included among the medications available in any ambulance that administers prehospital fibrinolysis, and whenever possible we suggest giving clopidogrel (300 mg by mouth) as part of the prehospital treatment for STEMI. Patients above 75 years are given a loading dose of 75 mg only. If this is not possible, clopidogrel can be given when the patient arrives at the hospital or the catheterization laboratory [38-40]. (See "Acute ST-elevation myocardial infarction: Antiplatelet therapy", section on 'Patients receiving fibrinolytic therapy'.)

●Antithrombotic therapy (see "Acute ST-elevation myocardial infarction: Management of anticoagulation"):

•Heparin or low molecular weight heparin – Low molecular weight heparin is the preferred antithrombin agent in the prehospital setting due to its ease of administration (IV bolus and subcutaneous dosing). We prefer 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) [2,3,33,35-37].

●Nitrates – Nitrates may be part of a combined modality therapy for symptoms or signs of myocardial ischemia, heart failure, and hypertension in the patient with an acute STEMI. Medications requiring IV infusions are often omitted in the prehospital setting because they delay transport and require special equipment. However, if time and capability permit, IV nitroglycerin infusions may be initiated and titrated to pain and blood pressure en route to the hospital. (See "Nitrates in the management of acute coronary syndrome".)

●Morphine ‒ Morphine sulfate (2 to 4 mg slow IV push) can be given to patients with persistent discomfort or anxiety every 5 to 15 minutes. Smaller doses and larger intervals may be needed in patients with hypotension.

EFFICACY — The effectiveness of fibrinolytic therapy in the treatment of STEMI varies depending on multiple factors, including the time from symptom onset to therapy, the fibrinolytic medication selected, and the time delay to subsequent percutaneous coronary intervention if needed. Overall, when given appropriately, treatment is effective in approximately 70 percent of cases [15]. (See "Acute ST-elevation myocardial infarction: The use of fibrinolytic therapy".)

Several clinical findings suggest that fibrinolytic therapy has been effective. These include relief of symptoms, resolution of ST-segment elevation, and possibly the development of reperfusion arrhythmias, including accelerated idioventricular rhythm. A detailed discussion of the efficacy of fibrinolytic therapy is found separately. (See "Diagnosis and management of failed fibrinolysis or threatened reocclusion in acute ST-elevation myocardial infarction", section on 'Primary failure'.)

COMPLICATIONS — 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 stroke. Common signs include deterioration in mental status, headache, nausea and vomiting, or a sudden rise in blood pressure. Other potential complications include allergic reactions (seen primarily with streptokinase treatment). The complications associated with fibrinolysis are discussed in greater detail separately. There is no evidence that complication rates are higher when fibrinolytic therapy is given in an ambulance. (See "Acute ST-elevation myocardial infarction: The use of fibrinolytic therapy", section on 'Complications' and "Acute ST-elevation myocardial infarction: The use of fibrinolytic therapy", section on 'Contraindications'.)

Following prehospital fibrinolysis, some patients experience a recurrence of symptoms and signs of STEMI, suggesting reocclusion of the involved coronary artery. This may include recurrent or new ST-segment elevations. Recurrence is best treated with PCI. (See "Diagnosis and management of failed fibrinolysis or threatened reocclusion in acute ST-elevation myocardial infarction".)

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 emergency medical services (EMS) system, it is important to use each case as a teaching tool. At one author's institution, each case is closely reviewed, with careful attention paid to the performance of and the time required for each 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.

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

Patient outcome is closely followed as part of quality assurance. Review includes both patients treated with prehospital fibrinolytics and those with STEMI who do not receive prehospital fibrinolytics. Dosing of all medications is reviewed on a regular basis; all medications in the ambulance are regularly checked and clearly labeled.

We recommend that the ECGs of prospective candidates for fibrinolysis be reviewed in real time prior to fibrinolysis by the medical control physician at the receiving emergency department or hospital in order to avoid 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. This approach has helped us avoid giving fibrinolytics to patients without STEMI. In addition, our EMS crews regularly review ECGs after the case to improve their interpretation skills.

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'.)

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

●Appropriately designed and implemented programs for prehospital fibrinolysis can reduce delays in providing definitive care and improve outcomes for some patients with ST-elevation myocardial infarction (STEMI), particularly those without ready access to facilities capable of performing percutaneous coronary intervention. (See 'Feasibility and effectiveness' above.)

●Emergency medical services systems that employ prehospital fibrinolysis must be able to identify the patient with STEMI, communicate with the receiving hospital, and treat the patient en route. This requires specific equipment and capabilities, including well-trained paramedics, expert physician oversight, electrocardiogram interpretation and transmission, communications equipment and personnel, a fibrinolysis checklist and treatment protocol, a destination protocol, and necessary medications. (See 'Necessary equipment and capabilities' above and 'Requirements of prehospital providers' above.)

●Candidates for fibrinolysis must be screened for absolute and relative contraindications, as fibrinolysis carries a risk of severe bleeding, including intracranial hemorrhage, when given inappropriately (table 1). (See 'Patient eligibility' above.)

●In low- or middle-income countries, an alternate approach of utilizing medical facilities without coronary care unit (CCU) to perform early "pre-CCU" fibrinolysis may ensure early reperfusion. A strategy of taking fibrinolytic therapy to the patient rather than bringing the patient to a reperfusion center could more easily achieve the same results as in-ambulance fibrinolysis.

●Quality assurance is an essential aspect of any successful prehospital fibrinolysis program. (See 'Quality assurance' above.)