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Emergency Medicine - Special Aspects Of Emergency Medicine

Last Updated: June 22 @ 2006

Author: José G Cabañas, MD , Staff Physician, Department of Emergency Medicine, University of Puerto Rico School of Medicine, Federico Trilla University Hospital; Vice President of Operations, First Response Emergency Medical Services Inc, San Juan

Coauthor(s): Salvadore E Villanueva, MD, FACEP , Assistant Professor, Department of Emergency Medicine, University of Puerto Rico School of Medicine; Craig Feied, MD, FACEP, FAAEM, FACPh , Director, National Institute for Medical Informatics, Director, Federal Project ER One, Director of Informatics, Washington National Medical Center, Director, National Center for Emergency Medicine Informatics ; Jonathan A Handler, MD , Director of Informatics, Assistant Professor, Department of Emergency Medicine, Northwestern Memorial Hospital

José G Cabañas, MD, is a member of the following medical societies: American College of Emergency Physicians, American Heart Association, National Association of EMS Physicians, and Society for Academic Emergency Medicine

Editor(s): William Gossman, MD , Assistant Professor, Department of Emergency Medicine, Rosalind Franklin University of Medicine and Science, Project Medical Director, Department of Emergency Medicine, Mount Sinai Hospital; Francisco Talavera, PharmD, PhD , Senior Pharmacy Editor, eMedicine; Gary Setnik, MD , Chair, Department of Emergency Medicine, Mount Auburn Hospital; Assistant Professor, Division of Emergency Medicine, Harvard Medical School; John Halamka, MD , Chief Information Officer, CareGroup Healthcare System, Assistant Professor of Medicine, Department of Emergency Medicine, Beth Israel Deaconess Medical Center; Assistant Professor of Medicine, Harvard Medical School; and Charles V Pollack, Jr, MD, MA, FACEP , Associate Professor of Emergency Medicine, University of Pennsylvania School of Medicine; Chairman, Department of Emergency Medicine, Pennsylvania Hospital)

Clinical problems associated with thrombosis

Thrombosis is an important part of the normal hemostatic response that limits hemorrhage from microscopic or macroscopic vascular injury. Physiologic thrombosis is counterbalanced by intrinsic antithrombotic properties and physiologic fibrinolysis. Under normal conditions, thrombus is confined to the immediate area of injury and does not obstruct flow to critical areas, unless vessel lumen is diminished already such as in atherosclerosis.

Under pathological conditions, thrombus can propagate into otherwise normal vessels. Thrombus that has propagated where it is not needed can obstruct flow in critical vessels and can obliterate valves and other structures that are essential to normal hemodynamic function. The principal clinical syndromes that result are acute myocardial infarction (MI), deep vein thrombosis, pulmonary embolism, acute ischemic stroke, acute peripheral arterial occlusion, and occlusion of indwelling catheters.

Pathophysiology of thrombosis

Both hemostasis and thrombosis depend on the coagulation cascade, vascular wall integrity, and platelets response. Several cellular factors are responsible for thrombus formation. When a vascular insult occurs, immediate local cellular response takes place. Platelets migrate to the area of injury where they secrete several cellular factors and mediators. These mediators promote the clot formation.

During thrombus formation, circulating prothrombin is activated by platelets. In this process, other major steps take place such as fibrinogen converted to fibrin, which then creates the fibrin matrix. All this takes place while platelets are being adhered and aggregated. Fibrin-bound plasminogen will be converted by thrombolytic drugs to plasmin, the rate-limiting step in thrombolysis.

It is important to state that the thrombolysis process works on recently formed thrombi. Older thrombi have an extensive fibrin polymerization that makes thrombi more resistant to thrombolysis. Hence, the importance of time for thrombolytic therapy.

Pathological thrombosis can occur in any vessel at any location in the body. Several causes that predispose to thrombosis include the following:

Atherosclerosis (plaque rupture)

Blood flow changes

Metabolic disorders (diabetes mellitus, hyperlipidemia)

Hypercoagulable states

Smoking

Trauma

For excellent patient education resources, visit eMedicine's Circulatory Problems Center . Also, see eMedicine's patient education article Blood Clot in the Legs .

Thrombolytic agents

Thrombolytic agents available today are serine proteases that work by converting plasminogen to the natural fibrinolytic agent plasmin. Plasmin lyses clot by breaking down the fibrinogen and fibrin contained in a clot.

Urokinaselike plasminogen activators are produced in renal cells. They circulate in blood and are excreted in the urine. Their ability to catalyze the conversion of plasminogen to plasmin is affected only slightly by the presence or absence of local fibrin clot.

Tissue-type plasminogen activators are found principally in vascular endothelial cells. Their activity is enhanced in the presence of fibrin, and they have been described as clot specific despite the fact that their activity in the general circulation is approximately equal to that of urokinase.

No single agent has been approved by the US Food and Drug Administration (FDA) to be labeled for every indication, and new agents and new dosing regimens are under constant investigation. A choice of lytic agents must be based upon the results of ongoing clinical trials and upon the clinician's experience. The most appropriate agent and regimen for each clinical situation will change over time and may differ from patient to patient.

The information presented here is based on clinical and investigational experience as reported in the current literature to the authors' best knowledge, without respect to FDA approval for a particular indication. Where the literature does not suggest an effective dose for a lytic agent in a particular clinical setting, no dose information is presented.

The most available agents today are reteplase (r-PA), alteplase (tPA), tenecteplase (TNKase), urokinase, prourokinase, anisoylated purified streptokinase activator complex (APSAC), and streptokinase itself. However, streptokinase is not frequently used anymore because of availability of newer agents and clinical interventional facilities for emergent conditions.

Reteplase

Reteplase (r-PA, Retavase) is a second-generation recombinant tissue-type plasminogen activator that seems to work more quickly and to have a lower bleeding risk than the first-generation agent alteplase.

Reteplase is a synthetic nonglycosylated deletion mutein of tissue plasminogen activator containing 355 of the 527 amino acids of native tissue plasminogen activator. The drug is produced in Escherichia coli by recombinant techniques. Reteplase does not bind fibrin as tightly as native tissue plasminogen activator, allowing the drug to diffuse more freely through the clot rather than binding only to the surface the way tissue plasminogen activator does. In high concentrations, reteplase does not compete with plasminogen for fibrin-binding sites, allowing plasminogen at the site of the clot to be transformed into clot-dissolving plasmin. These 2 modifications help explain the faster clot resolution seen in patients receiving reteplase than in those receiving alteplase.

The modifications also resulted in a molecule with a faster plasma clearance and shorter half-life (about 11-19 min) than alteplase. Reteplase undergoes renal (and some hepatic) clearance. The shorter half-life makes the drug ideal for double-bolus dosing. The result is more convenient administration and faster thrombolysis with reteplase than with alteplase, which is given by a bolus followed by an intravenous (IV) infusion.

The agent may be readministered as necessary, as it is not antigenic and almost never is associated with any allergic manifestations.

Alteplase

Alteplase (tPA, Activase) was the first recombinant tissue-type plasminogen activator and is identical to native tissue plasminogen activator. In vivo, tissue-type plasminogen activator is synthesized and made available by cells of the vascular endothelium. It is the physiologic thrombolytic agent responsible for most of the body's natural efforts to prevent excessive thrombus propagation. Alteplase is the fibrinolytic agent most familiar to emergency departments and is the lytic agent most often used for the treatment of coronary artery thrombosis, pulmonary embolism, and acute ischemic stroke.

In theory, alteplase should be effective only at the surface of fibrin clot. In practice, however, a systemic lytic state is seen, with moderate amounts of circulating fibrin degradation products and a substantial systemic bleeding risk.

The agent may be readministered as necessary, as it is not antigenic and almost never is associated with any allergic manifestations.

As of today, alteplase is the only thrombolytic drug approved for acute ischemic stroke.

Urokinase

Urokinase (Abbokinase) is the fibrinolytic agent most familiar to interventional radiologists and the one that has been used most often for peripheral intravascular thrombus and occluded catheters. Recently, urokinase was made available once again from the manufacturer. After some years hold from the market due to manufacturer issues with the FDA, it has been reintroduced. The package insert was revised and since then has an indication only for pulmonary embolism. During the time this drug was not available, the FDA encouraged the off-label use of reteplase and alteplase for local-regional lysis of venous and arterial thrombus at any location. As of today, this drug is readily used for this purpose in different clinical and interventional settings.

Urokinase is a physiologic thrombolytic agent that is produced in renal parenchymal cells. Unlike streptokinase, urokinase directly cleaves plasminogen to produce plasmin. When purified from human urine, approximately 1500 L of urine are needed to yield enough urokinase to treat a single patient. Urokinase is also commercially available in a form produced by tissue culture, and recombinant DNA techniques have been developed for urokinase production in E coli cultures.

In plasma, urokinase has a half-life of approximately 15 minutes. Allergic reactions are rare, and the agent can be administered repeatedly without antigenic problems.

Prourokinase

Prourokinase is a new fibrinolytic agent that is currently undergoing clinical trials for a variety of indications. It is a relatively inactive precursor that must be converted to urokinase before it becomes active in vivo. Its advantages over other plasminogen activators are that it is inactive in plasma and does not bind to or consume circulating inhibitors. As with tissue-type plasminogen activator, prourokinase is somewhat clot specific, since the presence of fibrin enhances the conversion of prourokinase to active urokinase by an unknown mechanism.

Streptokinase

Streptokinase is the least expensive fibrinolytic agent, but unfortunately it is highly antigenic and produces a high incidence of untoward reactions. This drawback limits the usefulness of streptokinase in the clinical setting.

Streptokinase is produced by beta-hemolytic streptococci. It was first isolated in 1933 and entered clinical use in the mid-1940s. Streptokinase by itself is not a plasminogen activator, but it binds with free circulating plasminogen (or with plasmin) to form a complex that can convert additional plasminogen to plasmin. Streptokinase activity is not enhanced in the presence of fibrin.

The principal plasma activity half-life of streptokinase is about 20 minutes, but an unbound fraction (about 15%) has a half-life of 80 minutes. Since it is produced from streptococcal bacteria, it often causes febrile reactions and other allergic problems. Streptokinase usually cannot be administered safely a second time within 6 months, because it is highly antigenic and results in high levels of antistreptococcal antibodies.

Anisoylated purified streptokinase activator complex

APSAC is a complex of streptokinase and plasminogen that does not require free circulating plasminogen to be effective. It has many theoretical benefits over streptokinase but suffers antigenic problems similar to those of the parent compound.

The half-life of APSAC in plasma is somewhere between 40 and 90 minutes.

Tenecteplase (TNKase)

TNKase was approved by the FDA as a fibrinolytic agent in 2000. This drug has a similar mechanism of action as alteplase (tPA). It is the latest thrombolytic agent approved for use in clinical practice. As of today, TNKase is currently indicated for the management of acute myocardial infarction.

Tenecteplase is produced by recombinant DNA technology using Chinese hamster ovary cells. This drug is a 527 amino acid glycoprotein, which sustained several modifications in amino acids molecules. These modifications consist of a substitution of threonine 103 with asparagine, asparagine 117 with glutamine, and a tetra-alanine substitution at amino acids 296-299 in the protease domain. This change permits TNKase to have a longer plasma half-life and more fibrin specificity. Tenecteplase has a half-life ranging initially from 20-24 minutes up to 130 minutes final clearance, most of it by liver metabolism.

Because of amino acids modifications, TNKase has the advantage for a single bolus administration and decreased bleeding side effects due to high fibrin specificity. The ASSENT-2 trial showed risk of major bleeding events to be less compared with alteplase 4.7% versus 5.9%. The incidence of hemorrhagic stroke was 0.9%, a little higher than alteplase, which showed 0.7% risk in the GUSTO trials.

Several clinical trials are in progress seeking new indications for this drug such as in acute ischemic stroke.

THROMBOLYTIC THERAPY FOR ACUTE MYOCARDIAL INFARCTION

Reteplase

The adult dose of reteplase for acute MI is 2 IV boluses of 10 units each. Each bolus is given over 2 minutes, with the second bolus given 30 minutes after initiation of the first bolus injection.

Alteplase

tPA can be administered in either an accelerated (1.5 h) infusion or a long (3 h) infusion.

Must reconstitute with 100 mL sterile water for 1 mg/mL.

The accelerated infusion of alteplase (tPA) for acute MI is 15 mg IV, followed by 0.75 mg/kg (up to 50 mg) IV over 30 minutes, then 0.5 mg/kg (up to 35 mg) IV over 60 minutes, with a maximum total dose of 100 mg. This is the most common alteplase infusion parameter use for acute myocardial infarction.

The previous 3-hour infusion consists of 10 mg IV bolus over 2 minutes. Then, give 50 mg over the first hour. This is followed by 20 mg/h infusion for the next 2 hours.

Urokinase

Intravenous urokinase is effective for acute MI but has been less well studied than some other agents. The most commonly used rapid-treatment regimen is 2 million U given as an IV bolus, followed by 1 million U over the next 60 minutes.

Streptokinase

The adult dose of streptokinase for MI is 1.5 million U in 50 mL D5W given IV over 60 minutes. Allergic reactions force the termination of many infusions before a therapeutic dose can be administered.

APSAC

The adult dose of APSAC for MI is 30 U given IV over 2-5 minutes.

Tenecteplase (TNKase)

To reconstitute, mix the 50 mg vial in 10 mL sterile water (5 mg/mL).

TNKase is administered 30-50 mg IV bolus over 5 seconds. Dosage is calculated based on the patient's weight.

<60 kg - 30 mg (6 mL)

> 60 kg to <70 kg - 35 mg (7 mL)

> 70 kg to <80 kg - 40 mg (8 mL)

> 80 kg to <90 kg - 45 mg (9 mL)

> 90 kg - 50 mg (10 mL)

THROMBOLYTIC THERAPY FOR PULMONARY EMBOLISM

The evidence is overwhelming that fibrinolysis can dramatically reduce the mortality and morbidity rates associated with massive or recurrent pulmonary thromboembolism. As of today, thrombolytic therapy in pulmonary embolism is still controversial. As for patients with an acute MI, the risk of hemorrhagic complications is far less than the survival benefit in most patients with suspected or diagnosed pulmonary embolism.

In the absence of any specific major contraindication, fibrinolytic therapy is mandatory for all patients with pulmonary embolism who are unlikely to survive further episodes of embolization. Most such patients fall into one of the following categories:

Patients whose cardiopulmonary reserves have been exhausted, as demonstrated by the presence of significant hypoxemia or by any degree of hemodynamic compromise

Patients with echocardiographic evidence of right-ventricular dysfunction secondary to pulmonary embolism

Patients with massive pulmonary embolism

Patients with underlying cardiopulmonary disease that reduces their baseline reserves

Patients with cor pulmonale from prior pulmonary embolism

Patients in hypotensive shock or a shock index > 1

Shock index = HR / systolic BP

Pulmonary embolism is a disease of progressive recurrences, in which additional amounts of peripheral venous thrombus may embolize at any time. Death is correlated with the total amount and location of thromboembolus, but not with the size of the initial embolism. For this reason, many believe that the benefit of fibrinolysis may outweigh the risks for all patients with pulmonary embolism, no matter how small the initial insult.

Patients with pulmonary thromboembolism often decompensate suddenly, and once hemodynamic compromise has developed, the mortality rate is extremely high. When the decision is made to use thrombolysis, the fastest-acting available thrombolytic agent with an acceptable safety and efficacy profile should be chosen. Many centers prefer off-label regimens to the slower on-label regimens that have been approved by the FDA.

In the worst clinical scenario, pulmonary embolism can cause cardiac arrest. The most common cardiac arrest initial rhythms documented include PEA and asystole. Cardiac arrest in the event of pulmonary embolism has a mortality of about 70%. Recently numerous case reports state the use of thrombolytic boluses in cardiac arrest due to pulmonary embolism, with apparent heroic results. The clinician main goal should focus on avoiding the cardiac arrest and identifying patient candidates for thrombolytic in the event of a PE.

Reteplase

Reteplase has not been labeled by the FDA for any indication except acute MI, but it is widely used for acute deep vein thrombosis and pulmonary embolism. The dosing used is the same as that approved for patients with acute MI: 2 IV boluses of 10 U each, administered 30 minutes apart.

Alteplase

The FDA-approved regimen for pulmonary thromboembolism is 100 mg as a continuous infusion over 2 hours.

First 15-mg bolus followed by 85 mg over a 2-hour infusion. Heparin drip must be discontinued during alteplase infusion.

Some centers prefer to use front-loaded regimens that appear to be faster acting, safer, and more efficacious than the 2-hour infusion. A commonly used accelerated regimen is 15 mg tPA as an initial IV bolus, followed by 50 mg over the next 30 minutes and another 35 mg over the next hour. For small patients, a weight-adjusted regimen is used: 0.2 mg/kg bolus, 0.7 mg/kg over the first 30 minutes, and 0.5 mg/kg over the subsequent hour.

Urokinase

The FDA-approved regimen is 4400 U/kg as a loading dose over 10 min, followed by a drip of 4400 U/kg/h for 12-24 h or until resolution of thromboembolus can be demonstrated.

A newer regimen that has gained favor is 3 million U of urokinase given over 2 hours, with the first 1 million U given as a loading dose over 10 minutes. This regimen appears to be equal in safety and efficacy to the accelerated treatment regimens used with tPA, and the 2-hour regimen is preferred to a prolonged infusion for many reasons. Patients should be pretreated with 1500 mg of acetaminophen to prevent rigors during the infusion.

Streptokinase

The FDA-approved regimen for pulmonary embolism is 1 million U infused over 24 hour.

THROMBOLYTIC THERAPY FOR DEEP VEIN THROMBOSIS

Reteplase

For lysis of venous thrombus, a catheter-directed infusion of 1.0 U/h is maintained for 18-36 hours.

Alteplase

For lysis of venous thrombus, a 5-mg bolus is delivered directly into the clot, followed by a catheter-directed infusion of 1.0 mg/h for 12-24 hours.

Urokinase

The usual systemic dose for deep venous thrombosis is 4400 U/kg as an IV bolus, followed by a maintenance drip of 4400 U/kg/h. The drip is continued for 1-3 days, until clinical or laboratory investigations demonstrate thrombus resolution. When available, intrathrombus delivery of urokinase can avoid a systemic lytic state. The dose for this route of administration is 500 U/kg/h. If clot lysis is inadequate, the infusion rate can be increased gradually up to 2000 U/kg/h.

Streptokinase

The usual dose regimen for deep venous thrombosis is an IV bolus of 250,000 U followed by a maintenance drip at 100,000 U/h. The drip is continued for 1-3 days, until clinical or laboratory investigation shows thrombus resolution.

THROMBOLYTIC THERAPY FOR BLOCKED CATHETERS

Reteplase

For lysis of catheter-associated thrombus and fibrin sheaths, an infusion of 1 U/h is maintained for 3 hours.

Alteplase

A solution of 1 mg/mL of reteplase is instilled in a volume sufficient to fill the cannula and is allowed to dwell for up to 4 hours. If the catheter flows forward freely but is obstructed for withdrawal, pericatheter thrombus or fibrin sleeve is lysed using an infusion through the catheter of 1 mg/h for 3 hours.

Urokinase

The dose of urokinase for catheter clearance is 1 mL of urokinase that has been diluted to 5000 U/mL. From this 1 mL of diluted urokinase, the amount needed to fill the catheter volume is injected into the blocked catheter.

Streptokinase

Slowly instill 250,000 U of streptokinase in 2 mL of solution into each occluded limb of the cannula. Clamp off the cannula limb(s) for 2 hours, and after treatment aspirate the contents of the cannula limb(s), flush with saline, and reconnect the cannula.

THROMBOLYTIC THERAPY FOR ACUTE ISCHEMIC STROKE

Alteplase

Alteplase is the only drug that has been studied and approved by the FDA for use in acute ischemic stroke with well-established time of symptom onset ( < 3 h). It is likely that other agents (eg, reteplase and tenecteplase) are equally effective and might even offer a reduction in bleeding risk, but the risk-benefit calculation depends so heavily on small differences in bleeding risk that recommending an agent that has not been studied intensively for this indication is impossible. As of today, several clinical trials are running with third-generation thrombolytic drugs in order to evaluate their efficacy and safety in stroke.

Patient must arrive preferably to an institution with a stroke center. Time of symptom onset must be well established ( <3 h) and presenting with a measurable neurologic deficit. Stroke severity must be assessed with NIH stroke scale (maximum score 42). Patients with a score above 22 are considered high risk for hemorrhagic conversion due to the probability of a large infracted area. Contrary patients with a score less than 4 have only minor neurologic deficits for which thrombolytic therapy is not indicated. High-risk patients often have early CT scan changes showing a large area of edema or mass effect. Despite the increased risk of hemorrhage in patients with a massive stroke, fibrinolysis remains indicated whenever other exclusion criteria are absent, because the potential benefit is tremendous in this population of patients, who almost always have a dismal outcome if therapy is withheld. Inclusion and exclusion criteria must be reviewed before administration of thrombolytic. Be aware ofsubarachnoid hemorrhages that present early without CT scan findings.

Start 2 peripheral IV lines, one for alteplase infusion and the second one to manage any complication that may occur. The recommended dose of alteplase for acute ischemic stroke is 0.9 mg/kg (maximum of 90 mg) infused over 60 minutes, with 10% of the total dose administered as an initial IV bolus over 1 minute. The patient must be admitted to a critical care area in order to provide frequent neurologic assessments and blood pressure and cardiovascular monitoring. The clinician must be ready to recognize and manage possible complications mentioned below. The effectiveness of thrombolytic therapy in stroke is strictly associated to strict patient selection within the inclusion and exclusion criteria.

THROMBOLYTIC THERAPY FOR PERIPHERAL ARTERIAL DISEASE

Low-dose intra-arterial thrombolytic therapy is being used for acute arterial occlusions. Primary fibrinolysis is the initial treatment of choice for many patients with acute peripheral arterial occlusions. The ability to perform catheter-directed fibrinolysis with subsequent angioplasty and stenting has reduced the need for arterial surgery in many settings. Patients with limb-threatening ischemia are not candidates for local fibrinolysis. Usually it takes between 6 and 72 hours to achieve clot lysis. These patients require emergent embolectomy. Local thrombolytic therapy is reserved for patients with non–life-threatening limb ischemia due to in situ thrombosis. Consider that patients with thrombosis for more than 30 days old are not likely to respond to local fibrinolysis.

Reteplase

0.5 U/h by intra-arterial infusion

Alteplase

Standard regimen: 0.05 to 0.1 mg/kg/h intra-arteriallyHigh-dose regimen: 3 doses of 5.0 mg over 30 min, then 3.5 mg/h for up to 4 h

Urokinase

4000 U/min until initial recanalization, then 1000-2000 U/min until complete lysis, all given intra-arterially

Streptokinase

5,000-10,000 U/h intra-arterially

THROMBOLYTIC THERAPY COMPLICATIONS

The most feared complication of fibrinolysis is intracranial hemorrhage, but serious hemorrhagic complications can occur from bleeding at any site in the body.

Common hemorrhagic problems seen after thrombolytic therapy include reperfusion arrhythmia, hypertension, gastrointestinal bleeding, retroperitoneal bleeding, pericardial bleeding, genitourinary bleeding, epistaxis, ecchymosis, gingival bleeding, and bleeding from puncture sites. Large hematomas at peripheral arterial puncture sites occasionally can cause a compartment syndrome. Clinicians must be prepared to handle such complications in a timely manner.

Risk factors for hemorrhagic complications include increasing age, elevated pulse pressure, uncontrolled hypertension, recent stroke, recent injury and recent surgery, the presence of a bleeding diathesis, severe congestive heart failure, and recent vascular puncture.

Overdoses of fibrinolytic agents can cause severe hemorrhagic complications. Overdose most often occurs when a full dose of a fibrinolytic agent is given to a small patient with a low body weight.

In patients receiving fibrinolysis for MI, the overall incidence of hemorrhagic complications is about 10%, and the incidence of intracranial hemorrhage is about 0.7%. In patients receiving fibrinolysis for acute stroke, the incidence of intracranial hemorrhage is higher.

Patients receiving thrombolytic therapy for acute ischemic stroke must have constant neurologic and cardiovascular reevaluation. Blood pressure checks must be every 15 minutes for 2 hours, then every 30 minutes for 6 hours and finally every hour for 16 hours. Strict blood pressure monitoring is essential during and after thrombolytic treatment in order to prevent complications. If a patient has signs of neurologic deterioration, stop thrombolytic therapy and obtain an emergent CT scan. Consider immediate expert consultation.

If a patient treated with fibrinolytic medications develops serious bleeding complications, the first step is cessation of the fibrinolytic agent and cessation of any anticoagulation therapy. Supportive therapy should be instituted. This often includes volume repletion and transfusion of blood factors. When possible, direct pressure should be used to control bleeding. If the patient has also been receiving heparin, protamine sulfate may be used to reverse the heparin effect.

Aminocaproic acid (Amicar) is a specific antidote to fibrinolytic agents. In adults, 4-5 g of aminocaproic acid is administered IV over the first hour, then a continuous infusion of 1 g/h is given for 8 hours or until the bleeding is controlled. Fresh frozen plasma and/or cryoprecipitate may be used to replenish fibrin and clotting factors.

Aminocaproic acid should not be given unless hemorrhage is life threatening, because it inhibits intrinsic fibrinolytic activity and can precipitate runaway thrombosis with end-organ damage at many sites. The drug worsens disseminated intravascular coagulation, including that associated with heparin-induced thrombocytopenia.

THROMBOLYTIC THERAPY IN CARDIAC ARREST

Recently, several articles have presented thrombolytic therapy as a potential beneficial drug during cardiac arrest. Some clinical trials found no benefit to give fibrinolytic drugs during cardiac arrest.

Several reports of adult patients have documented successful resuscitation after thrombolytic administration during cardiac arrest. In most case reports, acute pulmonary embolism was the suspected cause; these patients failed initially to standard CPR Guidelines and ACLS protocols. Today, evidence to support the routine use of thrombolytic drugs during cardiac arrest is not sufficient. The clinician may consider it on a case-by-case basis. Active CPR is clearly not a contraindication for thrombolytic therapy. It is highly probable that in the future thrombolytic therapy during cardiac arrest might be considered beneficial.

OUT-OF-HOSPITAL THROMBOLYTIC THERAPY

As of today, prehospital 12-lead ECG programs have been recommended for urban and rural EMS systems. Medical literature still supports this recommendation because of its benefits in early diagnosis and earlier treatment. Several studies have documented the ability for trained prehospital professionals to adequately acquire STEMI with 12-lead ECGs. Paramedics can provide advance notification to the receiving facility when they encounter an acute coronary syndrome, being able to provide a 12-lead ECG of such patients allows the institution to prepare for reperfusion strategies. It is also recommended that EMS personnel start screening for possible thrombolytic therapy in patients who may be having a STEMI in order to further decrease the time for reperfusion.

For some years, controversy has existed regarding the administration of thrombolytic drugs in the prehospital setting. Previously, out-of-hospital fibrinolysis was recommended when patient transport time was more than 1 hour. However, today several studies and clinical trails have demonstrated contrary. Out-of-hospital fibrinolysis is safe and reasonable. It can be performed by skilled, trained paramedics, nurses, or physicians under strict protocols. For EMS systems to implement out-of-hospital thrombolytic programs, several quality standards are required. Protocols must include thrombolytic checklists, 12-lead ECG interpretation and transmission, ACLS-trained personnel, and medical direction must be available at all times. These programs should have an adequate quality evaluation process to evaluate efficacy and safety. [/font:c1a2d5197e]

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