Emergency Department: Rapid Identification and Treatment of Patients With Acute Myocardial Infarction—National Heart Attack Alert Program Coordinating Committee

SPECIAL CONTRIBUTION

Emergency Department: Rapid Identification and Treatment of Patients With Acute Myocardial Infarction From the National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland. Receivedfor publication September20, 1993. Acceptedfor publication September22, 1993.

National Heart Attack Alert Program CoordinatingCommittee, 60 Minutes to Treatment Working Group

[National Heart Attack Alert ProgramCoordinating Committee, 60 Minutes to TreatmentWorking Group: Emergency department: Rapid identification and treatment of patients with acute myocardial infarction Ann EmergMedFebruary 1994;23:311-329.] FOREWORD Time is a crucial factor in the identification and treatment of patients with acute myocardial infarction (AMI) because of the demonstrated benefit of early treatment with thrombolytic therapy in the first one to two hours after the onset of symptoms and because of the everpresent threat of sudden death. (Sudden death is defined as that occurring in the first hour of symptom onset. Sudden death accounts for more than half of all AMI deaths.) Treatment within the first hour after onset of symptoms is an ideal goal for patients with ST-segmentelevation AMI because it helps achieve maximal myocardial salvage, the ultimate goal of reperfusion therapy. After the first two hours, the incremental benefit of thrombolytic treatment is less, although benefit can be derived up to at least 12 hours after symptom onset. A fundamental barrier to timely treatment of individuals with symptoms and signs of AMI is delay--by the patient, in the emergency medical services (EMS) system, and in the emergency department. In June 1991, the National Heart, Lung, and Blood Institute launched the National Heart Attack Alert Program (NHAAP) to promote the rapid identification and treatment of AMI, with the goal of reducing AMI morbidity and mortality, including AMI-related sudden death. The NHAAP Coordinating Committee was formed to help develop, implement, and evaluate the program. This committee is composed of representatives from 39 national scientific, professional, governmental, and voluntary organizations interested in AMI and sudden cardiac death. The NHAAP Coordinating Committee has recommended that the program's initial educational activities be

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directed toward health professionals and EMS systems. Future activities will be directed toward high-risk individuals and the general public. By educating ED and prehospital professionals first, these providers will be better equipped to appropriately manage the expected increase in chest pain patients after anticipated public education efforts are undertaken nationally. This report presents the NHAAP Coordinating Committee's first published recommendations, addressing time delays associated with ED management of AMI patients. It is targeted to emergency physicians, emergency nurses, and other health professionals who practice in EDs, as well as cardiologists, internists, and family physicians who care for AMI patients. This paper presents the scientific basis for early thrombolytic therapy and recommends that EDs strive to treat all AMI patients within 30 minutes of arrival. This is concordant with the American Heart Association Emergency Cardiac Care Committee's minimum time-to-treatment recommendation for EDs: That eligible AMI patients be treated with thrombolytic therapy within 30 to 60 minutes of their arrival in the ED. Four major points ("The Four Ds") where delay can occur in the ED management of AMI patients are identified and described: arrival and triage (door), obtaining an ECG (data), deciding to treat with thrombolysis (decision), and initiating thrombolytic therapy (drug). This paper proposes changes in ED processes that can reduce delays at each point. It also presents an ED algorithm for treatment of AMI and encourages all EDs to establish a protocol to ensure rapid identification and treatment of AMI. Finally, the paper challenges EDs to implement a system of continuous quality improvement to identify and reduce delays in the treatment of AMI patients. It provides EDs with tools for assessing their AMI management processes and for tracking critical AMI timepoints. OVERVIEW

Coronary heart disease continues to be the leading cause of death among adults in the United States. Despite a remarkable 54% decline in age-adjusted mortality due to coronary heart disease, from 220.3 per 100,000 population in 1963 to 101.0 per 100,000 in 1990, the United States still has a substantially higher age-adjusted coronary heart disease mortality rate than many other industrialized countries. As many as 1.25 million people will experience an AMI in 1993, and nearly 500,000 will die. 1 More than half of these deaths will occur suddenly, within an hour of onset of symptoms, and outside of a hospital.

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Both acute mortality and subsequent prognosis are related to the extent to which the myocardium is damaged by the infarction.2,3 Clinical observations implicating occlusive coronary thrombosis as the cause of AMI, experimental observations indicating that early reperfusion can prevent myocardial necrosis, and clinical trials with thrombolytic agents demonstrating a significant reduction in AMI mortality have dramatically changed the treatment paradigm for eligible AMI patients. Reperfusion therapy with thrombolytic agents is now the standard of care for AMI patients who meet current criteria and have no contraindications. Other therapeutic interventions that reduce AMI mortality and morbidity include aspirin, 4 heparin, nitrates, and [3-blockers. 5 The benefit of magnesium sulfate in reducing AMI mortality, as reported by Woods et al, 6 is being investigated further in the International Study of Infarct Survival (ISIS) IV trial. These agents are effectively used as adjunctive or conjunctive (aspirin and heparin) therapy to thrombolysis. Mechanical reperfusion by percutaneous transluminal coronary angioplasty (PTCA) or revascularization through coronary artery bypass graft (CABG) surgery may be beneficial for patients whose ischemia is not controlled pharmacologically or who are in shock. Although initial reports suggest a role and comparable efficacy of reperfusion through PTCA compared with thrombolytic therapy in the treatment of AMI, further studies evaluating this strategy need to be performed. 7-9 Thrombolytic therapy for AMI is generally safe and effective. Controlled trials of thrombolytic agents have shown significant and substantial reductions in acute mortality, with benefit markedly outweighing risk. lo-16 However, only a minority of AMI patients actually receive thrombolytic therapy. According to recent data from a national registry, 39% of AMI patients were treated with thrombolytic therapy. 17 Patients are often excluded from treatment because they do not meet the criteria for age, chest pain duration, and a qualifying ECG such as used in major clinical trials. 18 For example, Weaver et all9 reported that 29% of patients less than 75 years of age were treated with a thrombolytic agent compared with only 5% of patients older than 75 years, based on 3,256 consecutive patients hospitalized for AMI in the greater Seattle metropolitan area. Many patients who develop enzyme evidence of myocardial necrosis do not present with ST-segment elevation or new bundle branch block, the currently accepted ECG criteria for administration of thrombolytic therapy. Physicians may exclude some patients because they have real or perceived contraindications, and they may decide not to treat other patients

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because of a "preference" that reflects discomfort with the treatment protocol or concern about the risk of bleeding. A number of patients in selected major centers are reperfused through primary angioplasty instead of thrombolytic therapy. Of those receiving thrombolytic agents, very few--3% in the Thrombolysis in Myocardial Infarction (TIMI) II trial, 2.6% in the Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries (GUSTO) trial, and 10.9% in the Gruppo Italiano per lo Studio delia Streptochinasi nell'Infarto Miocardico (GISSI) I trial--are treated in the first hour. 11,2°,21 Late arrival at the hospital is a frequently cited reason for not giving a thrombolytic drug. 22 The factors responsible for delay in the care of AMI patients can be grouped into three phases: patient/bystander, prehospital, and hospital. 23-25 Patient/bystander factors are those that keep the patient from seeking immediate medical care through the emergency response system. Prehospital delay factors are those that occur from the time the patient decides to seek medical attention by accessing the EMS system until the patient arrives at a hospital ED for definitive treatment. (When the emergency response system is bypassed, the prehospital phase is defined as the time from initiating travel to the hospital to arriving at the hospital.) Hospital factors are those that delay definitive care, specifically reperfusion therapy, once the patient has arrived in the ED. The ED was the site for diagnosis and initiation of definitive care for the overwhelming majority of US AMI patients in 1992.26, 27 Time to Treatment: The Relationship of Outcome to the Time Between Coronary Occlusion/Symptom Onset and Reperfusion Early treatment of eligible patients with thrombolytic therapy is critical because of the dramatic relationship that has been demonstrated between the onset of AMI symptoms to reperfusion and outcome. Specifically, the time to reperfusion* versus benefit curve is steep in the first one to two hours but then levels off and eventually reaches a plateau. It is likely that the reduction in mortality among patients who are treated with thrombolytic drugs within the first two hours of the onset of symptoms is predomi*The reperfusion time is the time when a coronary artery is recanalized spontaneously, by a thrombolytic agent, by surgery or angioplasty, or experimentally by removal of a ligature. A thrombolytic agent does not recanalize an artery instantly after administration; rather, it takes 30 to 180 minutes for the drug to work. The "time to reperfusion" is the time between closure of the artery and reopening of the artery. Clinically, the time of artery closure is taken to be the time of symptom onset. The exact time of artery reopening can be determined only by angiegraphy, This time can sometimes be suggested by relief of pain, resolution of ST-segment elevation, or accelerated idioventricelar rhythm. Because of the impracticalities of performing immediate angiography and the unreliability of the bedside markers of raperfusion, outcomes are related, in most clinical trials, to the interval from pain onset to the time the drug is started. This surrogate measure, the time between pain onset and treatment initiation, roughly measures the duration of profound regional ischamia subsequent to coronary occlusion.

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nantly a result of myocardial salvage. 27-30 The benefit for patients treated after this two-hour interval is more modest. While some myocardial salvage may contribute to the mortality reduction in this latter group, the primary benefit may relate to the creation of an open artery sooner than might be expected from spontaneous reperfusion and possible associated mechanisms such as less adverse ventricular remodeling, better healing, improved collateralization, and improved electrophysiologic stability (Figure 1). 31-33 The greatest reduction in mortality occurs among patients treated early with thrombolytic agents, especially those treated within an hour of the onset of symptoms. Patients who are treated between one and 12 hours also have lower mortality than control patients. 11,12,34 The ISIS II trial findings suggest benefit that outweighs risk among patients treated up to 24 hours after onset of symptoms. ]4 The degree of benefit compared with risk in patients treated more than six hours after onset of syrup-

Figure 1. Time to reperfusion versus benefit curve. For the animal studies, the figure showsan inverse relationship between myocardial salvage and the length of time between coronary artery occlusion and reperfusion. The concordance of the superimposed mortality reduction in patients with AMI from the GIS5I I trial to myocardial salvage in dogs is remarkable. Benefit (%)

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Bergmannet al, 1982.37Myocardial salvagerelated to time betweenthrombotic occlusion of coronaryartery to repeffusionthrough )ysis in dogs.

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GISSII, 1986,11Reductionin mortality related to time betweenonset of symptomsand treatment with IV streptokinase in patients with AMI. Adapted from Tiefenbrunn and Sobel,33and reproducedwith permission.

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toms has been the focus of the Estudio Multicentrico Estreptoquinasa Republicas de America del Sur (EMERAS) and the Late Assessment of Thrombolytic Efficacy (LATE) trials. The LATE investigators found a 27% decrease in 35-day mortality in patients treated with tissue plasminogen activator (tPA), heparin, and aspirin six to 12 hours after onset of symptoms compared with placebo-treated patients, but no significant decrease in mortality among patients treated 12 to 24 hours after the onset of symptoms) 4 The EMERAS trial (using streptokinase) found small but not statistically significant benefit accruing to those treated within six to 12 hours, and no definitive benefit accruing to those treated after 12 hours. 35 Both experimental observations and clinical trials thus support the concept that the beneficial effect of reperfusion is a function of the length of time between symptom onset and treatment. In fact, this concept is fundamental to the paradigm that explains the benefits of reperfusion therapy. The major theoretical basis for early reperfusion has been confirmed by a number of experimental models and is supported by evidence from multiple clinical trials. The wave-front phenomenon of ischemic cell death described by Reimer and associates 36 is the basis for this paradigm of myocardial salvage from reperfusion. These investigators describe how myocardial necrosis progresses in the canine infarct model from the subendocardium to the epicardium after an experimental coronary occlusion. Release of the occlusion after variable periods of time demonstrates that early release produces a smaller infarct characterized by less transmural progression of the necrosis. Similar in vivo canine studies using thrombosis mod-

Figure 2.

Differences in left ventricular function. Pooled results of 3,066 ventriculographic observations. From Granger et aPS and used with permission. LV Ejection Fraction (%) 70 • Thrombolytic • Control 60

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els of coronary occlusion and thrombolytic therapy to achieve reperfusion (and thus more closely simulating the clinical situation) have had similar results. 3r The rate of progression of myocardial necrosis differs with the species studied (Figure 1).33 The 40% to 50% reduction in mortality observed in patients treated in the first hour and the overall 25% to 30% mortality reduction seen in randomized clinical trials support the hypothesis that the pathophysiology of myocardial necrosis in patients with coronary thrombosis superimposed on atheromatous coronary disease follows a course similar to that observed in animal models. In most trials, myocardial salvage has been evaluated by measuring systolic left ventricular function using either left ventriculography or nuclear studies. Multiple clinical trials have compared left ventricular function in patients administered a placebo with that of patients treated with a thrombolytic agent at various times after infarction. Overall, the differences in left ventricular function have been small, despite significant mortality reduction in the treated groups, although meta-analysis demonstrates that these differences are statistically significant (Figure 2). 38 The relationship between time to treatment and residual left ventricular ejection fraction has been relatively weak, with either marginal or no difference in ejection fraction demonstrated as a function of time to treatment. 39,4o Early patency resulting in myocardial salvage is the key benefit of thrombolytic therapy. The angiographic substudy of 2,431 GUSTO patients corroborated the findings of the animal studies that are the basis for this hypothesis. Preserved left ventricular function and associated significantly lower mortality at both the 24-hour and the 30-day endpoints were related to angiographic patency at 90 minutes. 2o The disparity between a clear, striking reduction in mortality versus minimal improvements in left ventricular function in earlier trials must be explained. In the Western Washington Intracoronary Streptokinase Trial, one-year mortality was significantly lower among patients with angiographically patent infarct-related arteries at hospital discharge than it was among those with occluded arteries, but ejection fraction was not higher in survivors with an open artery.41 Ejection fraction as an endpoint in clinical trials of thrombolytic agents may be an insensitive endpoint for a number of reasons. Values in patients who die early are not available, and there are substantial numbers of surviving patients for whom the assessment of ejection fraction is not made. Survivors with significantly impaired left ventricular function who might have died had they not been treated with a thrombolytic drug contribute to a lower average ejection fraction in the treated group as

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compared with the control group. 42 Compensatory chahges in the function of noninfarcted myocardium, the phenomenon of myocardial "stunning," and the timing of the study may compromise the utility of global ejection fraction as a reproducible and reliable measure of treatment effect. Finally, most studies that have assessed left ventricular function by ejection fraction have included few patients treated within two hours of symptom onset, the period when maximal myocardial salvage might be expected. Several relatively small studies that have evaluated very early treatment with thrombolytic therapy in the prehospital environment also have been able to evaluate systolic function in patients treated within two hours of symptom onset. Koren and colleagues,3° in a study comparing IV streptokinase begun at home by a physician in a mobile care unit to treatment initiated in a hospital, found that vessel patency was independent of time to treatment, but residual left ventricular function was time dependent. Patients treated within 1.5 hours after the onset of chest pain had a significantly higher ejection fraction, infarctrelated regional ejection fraction, and a lower QRS score than did patients receiving treatment between 1.5 and four hours after onset of pain. Patients treated by the mobile care unit had much better left ventricular ejection fractions (67%) than did patients treated in the hospital (48%). The recently completed Myocardial Infarction, Triage, and Intervention (MITI) trial randomly assigned patients to field thrombolytic therapy or hospital thrombolytic therapy if they had clinical and ECG evidence of AMI. The median time from symptom onset to treatment was 1.5 hours. Although the study did not provide evidence that field treatment was superior, the short time from symptom onset to treatment in both the prehospital and hospital treatment groups was associated with much smaller infarct size, better systolic left ventricular function, and lower mortality than with later treatment. No residual evidence of infarction was detected by thallium scintigraphy in 39% of the 360 patients in the trial,

Table 4.

Median ED treatment time intervals for AMI patients

Time Interval I (door to data) Interval II (data to decision) Interval III (decision to drug) Cumulative (door to drug)

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Kline et al, 199257 (min)

Gonzalez et al, 19925s (min)

11 22 37 70

6 20 20 46

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despite ECGs with diagnostic ST elevation and subsequent enzyme elevation. In 69% of patients, there was either no damage or only a very small infarction involving less than 10% of the left ventricle. Whether patients were treated in the field or in the hospital, treatment within 70 minutes of symptom onset was associated with a 50% smaller infarct size than that found in those who received later treatment. Systolic left ventricular function measurements mirrored these findings. After 1.5 hours, no incremental association between time to treatment and smaller infarct size could be demonstrated. All patients in the MITI trial were treated within three hours of symptom onset. There were no baseline characteristics other than time to treatment that could account for the results in the group treated in less than 70 minutes. There were many more patients with minimal infarct size in the MITI trial than in previous trials by the western Washington investigators, when treatment was given an average of two to 4.3 hours after symptom o n s e t . 27

Clinical trials support the conclusion that early treatment reduces mortality. In the TIMI II trial in which all patients received tPA, heparin, and aspirin, overall mortality at six weeks for patients treated within four hours after the onset of chest pain was 4.9%. The average time between onset of chest pain and treatment was 2.6 hours. For the 3% of patients treated within the first hour, mortality was only 3.2% compared with 3.7% for those treated during the second hour, 5.2% for those treated during the third hour, and 6.2% for those treated in the fourth hour after pain onset. 43 In the MITI trial, the mortality among patients treated within 70 minutes was 1.3% compared with 8.7% in those treated later. 2r This important relationship between time to thrombolytic therapy and mortality also has been found in larger randomized, controlled trials. GISSI I, the first large mortality trial of thrombolytic therapy, demonstrated an overall 18% reduction in 21-day mortality in patients treated up to 12 hours after the onset of symptoms over that of control patients. However, the mortality reduction in those treated within one hour of symptom onset was 47 percent, compared with 14% in those treated within one to three hours,*and 17% in those treated between three and six hours. Of the 11,712 patients included in this analysis, 10.9% were treated within one hour after the onset of symptoms. Of the 20,020 patients not randomized, 51.2% were excluded because they presented more than 12 hours after the onset of symptoms. 1~,~2The *The GISSI I data are generally reported for time intervals of less than one hour, less than three hours, between three and six hours, bebNeensix and nine hours, and between nine and 12 hours from symptom onset.

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recently completed GUSTO trial showed that mortality increased substantially with later (four to six hours) as opposed to earlier (0 to two hours) treatment. 44 Honan and colleagues45 pooled data from 42 randomized trials comparing thrombolytic therapy with placebo or conservative treatment. This analysis involved 44,346 patients and 4,692 deaths; the exact time to treatment was not available for each patient. Patients were pooled as closely as possible into time-to-treatment categories based on the published data. The analysis demonstrated a strong relationship between time to treatment and the odds ratio of death (Z2 = 7.6, P = .006). This relationship was basically linear except for patients treated in the first hour. There was a much greater reduction in the odds ratio of death in that group than would have been predicted by the regression equation developed on the entire population. This same meta-analysis of the limited studies (1,638 patients) with autopsy documentation demonstrated a direct relationship between time to treatment and risk of cardiac rupture. Patients treated within five hours of symptom onset had a lower risk of cardiac rupture, while those treated later had a progressively increasing risk of rupture. The results of the GISSI I trial were almost identical to this meta-analysis. Despite the increased risk of car-

Figure 3.

Time to reperfusion versus degree of benefit. This figure depicts combined human and animal data and represents the time-dependent benefit anticipated, depending on the length of the interval between coronary artery occlusion and reperfusion. Adapted from Tiefenbrunn and Sobel, 33 and reproduced with permission. Benefit(%) 100

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diac rupture, the meta-analysis revealed that there was still a beneficial effect of therapy on overall mortality until at least 14 hours (and possibly 21 hours) after symptom onset. A unifying hypothesis that explains the clinical data requires the assumption that reperfusion therapy improves survival by several mechanisms. The data on left ventricular function and on mortality indicate that in most human beings myocardial necrosis occurs at a rapid pace and that thrombolysis within one to two hours of symptom onset produces myocardial salvage (time-dependent) that affects both survival and left ventricular function. The time-benefit curve is very steep during the first one to two hours. Thrombolysis more than two hours after symptom onset reduces mortality, but with less dramatic benefits. Improvement of left ventricular function as measured by global ejection fraction is less obvious, despite the reduction in mortality. The slope of the timebenefit curve reaches a plateau (time-independent). While limited myocardial salvage may contribute to the benefit from thrombolysis after two hours, especially in patients with a stuttering, prolonged course reflecting a cycle of intermittent occlusion and spontaneous reperfusion, or presence of collateral blood supply, mechanisms other than infarct size reduction are primarily responsible for improved survival in this longer time-to-treatment group. These other mechanisms may relate to the opening of the occluded artery and may include improved myocardial healing, less adverse ventricular remodeling, reduced occurrence of ventricular aneurysm, increased blood flow to myocardium still in jeopardy, and improved electrophysiologic stability. These mechanisms are assumed to be more time independent. The Importance of lime to Treatment Thrombolytic therapy of AMI patients has significantly greater benefit for

those treated within the first or second hours after the onset of symptoms than those treated in the third to fifth hours. There is modest but significant benefit for patients treated between six to 12 hours after the onset of symptoms. Although myocardial salvage may still be possible in patients who present after the second hour, this is not to imply that delays in thrombolysis are acceptable (Figure 3). Furthermore, the hazard of myocardial rupture increases with time and may temper the benefit of reperfusion. The ideal strategy would be to initiate reperfusion in every eligible patient with AMI within the first hour after the onset of symptoms. In the Seattle experience, delay in presentation was a significant predictor of early mortality from AMI (odds ratio of 1.1 per one hour of delay).46 Any

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program that results in earlier access to EMS and earlier treatment of AMI also would benefit the problem of sudden, unexpected, out-of-hospital cardiac arrest, which continues to account for substantial mortality from coronary heart disease. Kuller and colleagues47 reported that 60% to 70% of the deaths from coronary heart disease among men ages 35 to 44 in Allegheny County, Pennsylvania, occurred outside the hospital, and approximately 60% of these deaths could be classified as sudden and unexpected. Primary ventricular fibrillation, a major cause of mortality in panents with MI, usually occurs soon after the onset of the acute injury. Therefore, if ventricular fibrillation that occurs soon after the onset of symptoms is to be prevented or treated successfully, ~t is essential that any patient with an unstable ischemic syndrome seek medical attention as soon as possible after the onset of symptoms. In the MITI trial, all patients were treated within 180 minutes after dialing 911: 50% received thrombolytic therapy within 90 minutes after the onset of symptoms. It is clear that the strikingly low mortality rates for patients treated early would not have occurred had patients not entered the EMS system within the first hour after the onset of symptoms. COMMON CAUSES OF DELAY IN TREATMENT AND SUGGESTED PROTOCOLS FOR MANAGEMENT OF THE AMI PATIENT IN THE ED

Overview of Sources of Delay The great majority of AMI patients do not receive the benefit of thrombolytic and other treatments within the first hour of onset of their

Figure 4. Cumulative distribution of time from arrival at hospital to treatment (based on 1,423 patients). Adapted from Kline et al, 57 and used with permission.

symptoms. 23-25,48,49 Between 26% and 44% of patients delay more than four hours before seeking care. 5°-52 Median patient delays range from just under two hours to 6.5 hours. 53'54 Mean time delays are considerably longer because individual patients may wait many hours or even days before coming to the hospital for treatment. A number of variables have been reported to be associated with patient delay times and have been described elsewhere.55 Once a decision to seek care is made, access issues related to getting to the hospital arise. Only half the patients with suspected AMI call the EMS system. Many transport themselves or wait for someone other than EMS personnel to take them to the hospital. 24,5°,56 Other patients far removed from an emergency facility spend considerable time being transported to a hospital. Still others who use the EMS system experience considerable delay during evaluation and transport by EMS personnel. In one study of eight American cities, an average of 46 minutes passed between the time the patient dialed 911 and the time the patient arrived at the hospital. 23 Substantial delays occur between the time a patient arrives in the hospital and initiation of thrombolytic therapy Overall, the average time that elapses during this interval ranges from 60 to 90 minutes, 23,24,57,58 although shorter delays have recently been reported. 59 Kereiakes and associates23 reported an average 83.8-minute delay Sharkey et a124 reported that the interval was 81 minutes. Gonzalez et a159 reported a median time of 50 minutes in

Figure 5. Process timepoints and intervals through which the AMI patient passes until treatment in the ED

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ED patients from a broad cross section of 13 Virginia hospitals not involved with ongoing research protocols. The GUSTO trial evaluated inhospital delays as part of the GUSTO Time to Treatment Substudy, an ancillary study in

Figure B.

ED algorithm~protocolfor patients with symptoms and signs of AMI

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80 North American hospitals. Overall, the median time from hospital arrival to treatment with the thrombolytic drug was 70 minutes; fewer than 5% of patients were treated within 30 minutes of arrival (Figure 4). 57 The American Heart Association has recently recommended treatment of all AMI patients who are eligible to receive thrombolytic therapy within 30 to 60 minutes of arrival in the ED. 6o The working group supports this recommendation but advocates that EDs strive for the minimum American Heart Association goal of treatment within 30 minutes of ED arrival. It makes this recommendation based on the belief that an ideal overall time-to-treatment goal should be 60 minutes from the onset of symptoms and on the likelihood that precious time has already transpired due to delays in the patient/bystander and prehospital phases. Components of Delay in the ED The AMI patient who receives thrombolytic therapy in the ED passes through a sequence of steps that can be used to define process timepoints: onset of symptoms (Time 0: Onset); arrival in the ED (ED Time 1: Door); initial ECG (ED Time 2: Data); decision to administer thrombolytic therapy (ED Time 3: Decision); and actual infusion of the thrombolytic agent (ED Time 4: Drug) (Figure 5). The four ED timepoints define three component intervals that comprise the doorto-drug time. These intervals are: 1, the time between arrival in the ED and the initial ECG; 2, the time between the initial ECG and the decision to treat with thrombolytic therapy; and 3, the time between the decision regarding treatment and the initiation of treatment. Dividing the door-to-drug time into these three component intervals allows a more precise determination of where delays occur. Two aspects of the concept of "onset of symptoms" of AMI merit comment. The first is that symptom onset is being used as a clinical marker for the time of coronary artery occlusion. It is a good marker, but not a perfect one. It will produce its share of false-positive and falsenegative errors when used as a surrogate for onset of thrombotic occlusion. Second, many patients cannot explicitly state when their symptoms began. In some, symptoms follow a stuttering course, and it is unclear which time should be labeled as the onset. By contrast, the four ED timepoints are all precisely defined. Several investigators have studied the time spent on various components of the process of identifying and treating AMI patients in the ED. An analysis of data from 51 patients treated at a hospital participating in the TIMI II trial revealed that patients waited an average of 19.9 _+ 17.8

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minutes for an initial ECG and an additional 70 + 40 minutes (for an average of 89.9 minutes) before tPA infusion was begun. 24 The detailed GUSTO Time to Treatment Substudy evaluated specific components of the delay in treatment (Table 1).57 Gonzalez et a159 prospectively assessed the timing and nature of key decisions and clinical events in the treatment of AMI with thrombolytic therapy and identified problems encountered with thrombolytic administration in these patients. They reported median times for four times culminating in treatment with thrombolytic therapy in the ED: ECG time, from ED arrival to recording the 12-lead ECG (six minutes); decide time, from the initial 12-lead ECG to the decision to administer thrombolytic therapy (20 minutes); process time, from the decision to use a thrombolytic agent to the actual infusion of the agent (20 minutes); and door-to-needle time, from ED arrival to actual infusion of the thrombolytic agent (46 minutes) (Table 1). There are also several global themes that help explain why ED care for the AMI patient may not be as rapid as is either optimal or possible. ED protocols for identification and treatment of the AMI patient may be outdated; ED processes for managing the AMI patient that may have been appropriate a few years ago are not necessarily appropriate now. Poor coordination between the ED and other hospital departments (eg, ECG service and pharmacy) may impede a seamless response to the AMI patient. 58 Disputes among medical staff constituencies---emergency physicians, cardiologists, internists, and family physicians--may impede rapid treatment. 59 If the AMI patient is to be treated expeditiously and effectively, all of these underlying causes of delay must be addressed and corrected. Guidelines and protocols for ED care will help streamline the time to therapy. Every EMS system and hospital ED needs a specific protocol for identifying and treating AMI patients. There are several reports of "fast-track" protocols and processes for management of AMI that have reduced ED treatment times.24,58,61 Figure 6 is an algorithm that an ED can adopt to facilitate rapid and appropriate treatment of patients with symptoms and signs of AMI. This figure does not represent the best or only way for an ED to care for the AMI patient, but rather is intended to convey the approximate level of detail and effort required by an ED to improve its performance. ED "lime 1: Door

Causes of delay. Patients are brought to the ED by ambulance or walk in on their own. Both groups of

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patients must register and undergo a triage process; the order of these processes varies from hospital to hospital. In many EDs, ambulance patients are evaluated initially by a nurse who performs triage, whereas ambulatory patients often first encounter a registration clerk. Triage of the ambulance patient may be delayed if no qualified person is available to greet and assess the patient on arrival. The prehospital care provider may fail to communicate the patient's symptoms accurately, or the ED personnel may incorrectly assess the potential severity of the patient's condition. Either may occur because of the nurse's or prehospital care provider's lack of experience or inadequate training, inappropriate ED triage protocols, the patient's unsophisticated communication skills or fear, or symptoms that are atypical of AMI. Even if the initial ED health care provider properly assesses the patient, an ED stretcher or treatment site may not be available. Once the patient is placed on a stretcher, there may not be an established method for alerting the emergency physician that a patient with a possible AMI has arrived. Even greater barriers to timely care may await the AMI patient who chooses to come to the ED by private vehicle or public transportation. That patient may be delayed initially by the inability to find the ED entrance or to locate an available parking space close to the ED. Patients may be planning to meet their personal physician in the ED and choose to wait for that physician to arrive before entering the clinical ED care system. Intimidation or overcrowding at the entry point to the ED, be it at registration or triage, may cause delays. The ambulatory patient's initial encounter may be with a registration clerk who is not sufficiently trained to identify patients who might be having symptoms of cardiac ischemia. In that situation, the registration clerk conducts a lengthy interview before the patient is assessed by a medical professional. Even a well-trained registration clerk may not appreciate the nature or significance of symptoms if the patient presents with atypical symptoms or is unable to communicate them well. If the patient is assigned to the normal stream of nonurgent patients, there may be a long lag time between registration and triage. Once the patient does receive the attention of a triage nurse, all of the factors that could delay a patient who arrives by ambulance can also cause further delay for the patient who arrives on his or her own. Reducing delay. For patients arriving by ambulance, prehospital care providers may alert the ED to the impending arrival of a suspected AMI patient, allowing preparation that will speed time to treatment. Shorter hospital time delays have been observed for patients whose

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prehospital identification by history or ECG was obtained as part of a protocol-driven prehospital diagnostic strategy and whose diagnosis of AMI was made before arrival in the hospital.23, 2r However, detailed information from the prehospital care provider should not preclude efficient, rapid, and safe transport of the patient to the hospital. Currently, three methods are available for communicating with the base hospital emergency physician or another member of the emergency health care team. Standard land-line telephone communication from the patient's home may be used effectively when the patient lives in a remote area not accessible by radio contact because of distance or terrain, or lack of coverage by a Cellular teleFigure 7.

Guidelines for ED reffzstration clerk's and~or triage nurse's

identification of AMI patients Registration/Clerical Staff Patients mere than 30 years old with the following chief complaints require immediate assessment by the triage nurse and shouldbe referred for further evaluation: Chief Complaint Chest pain, pressure, tightness, or heaviness; radiating pain in neck, jaw, shoulders, back, or one or both arms Indigestion or "heartburn"/nausea and/or vomiting Persistent shortness of breath Weakness/dizziness/lightheadedness/less of consciousness Triage Nurse Patients with the following symptoms and signs require immediate assessment by the triage nurse for initiating the AMIprotocol: Chief Complaint Chest pain. Patients more than 30 years old with chest pain or severe epigastric pain, nontraumatic in origin, having componentstypical of myocardial ischemia or infarction: Central/substernal compression or crushing chest pain Pressure, tightness, heaviness, cramping, burning, aching sensation Unexplained indigestion/belching Radiating pain in neck, jaw, shoulders, back, or one or both arms Associated dyspnea Associated nausea/vomiting Associated diaphoresis If these symptoms are present, obtain stat ECG. Medical History The triage nurse should do a brief, targeted, initial history assessingfor current or past history of: CABG, angioplasty, coronary artery disease, or AMI Nitroglycerin use to relieve pain Risk factors, including smoking, hyperlipidemia, hypertension, diabetes mellitus, family history, and cocaine use This brief history must not delay entry into the AMI protocol. Special Considerations Questions have been raised as to whether women may present more frequently with atypical chest pain and symptoms. Diabetic patients may have atypical presentations due to autonomic dysfunction. Elderly patients may have stroke, syncope,or change in mental status.

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phone network. In appropriate areas, radio frequency communication not only allows voice contact but also permits transmission of a single-lead rhythm strip to the receiving hospital from the home or ambulance. Cellular telephone networks in many cities may provide clear voice communication from a moving ambulance when radio communication is a problem. Cellular telephone communication also allows digitized transmission of a 12-lead ECG that is identical to the tracing obtained by prehospital care providers in the field. 62 Such data transmission has permitted prehospital delivery of thrombolytic therapy through emergency physician order.63,64 A computer algorithm for identifying AMI on the basis of ST-segment elevation in the 12-lead ECG has been demonstrated to have suitably high diagnostic sensitivity.65 Such a computerized ECG can alert EMS personnel to a prehospital ECG consistent with AMI, and both the 12-lead ECG and its preliminary interpretation can be transmitted to the base station hospita!.27,64 This capability may prove beneficial in identifying patients for prehospital thrombolytic therapy should such a strategy be more effective than hospital treatment. It also should have utility for alerting the receiving hospital to the arrival of an AMI patient, thereby expediting rapid treatment. Indeed, prehospital identification of AMI patients by 12-lead ECG using cellular telephone transmission has decreased the time to treatment in the ED by considerably shortening the door-to-decision time.63,66 Anecdotal evidence from several studies suggests that hand de!ivery of the 12-lead ECG for emergency physician interpretation decreases the time to the administration of thrombolytic therapy. 67 It may be less expensive to upgrade standard monitors to 12-lead capability than to use cellular technology Development of cost-effective, reliable technology and strategies for transmitting the 12lead ECG from the field to the ED should be considered. Patients brought to the ED directly by ambulance may receive facilitated care by nurses who have experience working with individuals presenting with symptoms and signs of myocardial ischemia and AMI. 68 Immediate triage to an acute care bed with cardiac monitoring and oxygen delivery capabilities allows initiation of the AMI protocol. The nurseg identification of a potential AMI patient should be communicated to the emergency physician. Patients who walk into EDs in which the first encounter is with a registration representative should be evaluated immediately by a triage nurse if the presenting problem is chest pain or an equivalent syndrome. EDs should have an explicit list of "chief complaints" that

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AMI PATIENTS National Heart Attack Alert Program Coordinating Committee

mandate immediate triage nurse evaluation. Further registration information should be obtained from these patients only after the patient has undergone early diagnostic and therapeutic maneuvers, such as placement of cardiac monitoring leads and an IV cannula (Figure 7). The time of entry of a patient into the ED should be recorded as ED Time 1: Door. ED Time 2: Data

Causes of delay. At a minimum, diagnosis of an AMI requires a clinical history and an ECG. As already stated, some prehospital care systems obtain a 12-lead ECG on appropriate patients prior to their arrival in the hospital. However, for most emergency care systems, the 12-lead ECG is obtained after the patient arrives. This phase of patient evaluation requires three steps: deciding to obtain an ECG, taking the ECG, and presenting the ECG to the treating physician for interpretation. In some EDs, only a physician may order an ECG, so any delay in the physician's seeing the patient delays the ECG. In other EDs, nurses are permitted to order an ECG, but no protocol exists to delineate which patients should have one. Even if a protocol does exist, its criteria may not be comprehensive enough to include patients with atypical symptoms. If the patient is unstable or if rapid intervention is required, the order for an ECG may be lost in the press of emergency care. Once the ECG is ordered, other delays may occur. In some EDs, the ECG machine is not kept in the ED. Even if the ECG machine is housed in the ED, there may not be ED personnel skilled in performing the procedure. In EDs that use an ECG technician who is not based there, the arrival of the technician may be delayed. Once the ECG is obtained, it may sit unread on the patient's chart, thus delaying interpretation by the treating physician and a treatment decision. Reducing delay. An ECG should be considered part of the vital signs that emergency nurses monitor in patients with chest pain. ED nurses should be provided with a standing order to obtain a 12-lead ECG on any patient suspected of having myocardial ischemia or AMI. The patient should be placed simultaneously on a cardiac monitor and the heart rhythm assessed continuously. The ECG machine and ECG technician should be available in the ED within five minutes of paging. Locating an ECG machine in the ED is strongly recommended. Nurses or emergency technicians must be trained and able to record a 12-lead ECG in case the ECG technician is not available to the patient within five minutes. Some EDs are sufficiently busy that a seemingly stable patient having an ST-segment-elevation MI can go unno-

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ticed and unevaluated in the midst of other more visibly unstable patients. Emergency nurses should be trained to recognize ECG changes indicative of AMI, particularly if they are responsible for obtaining the tracing. In any case, the 12-lead ECG should be given immediately to the emergency physician for interpretation. Results from two regional, multicenter studies conducted in the early to mid-1980s showed that between 2% and 4% of AMI patients presenting to the ED were sent home.69, ro A computerized preliminary ECG interpretation that is highly sensitive and specific for myocardial injury could assist the emergency physician in making the diagnosis of AMI and initiating prompt protocol-driven therapy.65 However, whether such a protocol is safe and effective in supplementing physician decision making remains to be demonstrated in a prospective clinical trial. 71 In addition to having standing orders to obtain an ECG, emergency nurses should have standing orders to initiate the following diagnostic and therapeutic interventions for patients with suspected myocardial ischemia or AMI: Administration of aspirin for unstable angina or suspected AMI in patients without allergy to aspirin products; cardiac monitor; oxygen therapy; IV access; laboratory tests (eg, hematocrit, hemoglobin, baseline creatine kinase (CK), creatine kinase and isoenzyme MB (CKMB)); and nitrates (in some EDs, standing orders for nitrates, sublingual or spray, may be desirable and feasible for selected patient groups, such as individuals already using sublingual or transdermal nitroglycerin). None of these tests or procedures should delay a decision about whether or not to use thrombolytic therapy. The time that the ECG is obtained should be recorded as ED Time 2: Data. ED Time 3: Decision

Causes of delay. Many factors affect the capacity of the treating emergency physician to diagnose AMI, to decide if thrombolytic therapy is indicated, and to decide if other therapy should be initiated. The presence of an unusual symptom complex or equivocal ST-segment elevation on the ECG may make diagnosis difficult. ECG abnormalities may be subtle or open to different interpretation, such as early repolarization or pericarditis. Only borderline or minimal STsegment elevation may be present, and the emergency physician may be uncertain of its significance. The presence of left bundle branch block or left ventricular hypertrophy may complicate ECG diagnosis. The emergency physician may suspect that the ST elevation is old, but a previous ECG may be unavailable for comparison. The computer interpretation of the ECG on which some physicians rely may be incorrect. The emergency physician may not be

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sufficiently trained to recognize certain ECG patterns as signs of AMI. There may be no protocols or system for providing the emergency physician with cardiologic consultation for ECG interpretation. Use of a "GI cocktail" (usually consisting of a mixture of an antacid, an antiperistaltic medication, and sometimes a local anesthetic) as a diagnostic test to differentiate between gastrointestinal and cardiac causes of the patient's symptoms is inappropriate and may lead to erroneous conclusions. Relief of symptoms does not rule out a diagnosis of AMI or another ischemic syndrome. In some patients, the time of onset of symptoms, presence of contraindications to thrombolytic therapy, and certainty of acute infarction may not be clear. Echocardiography and other helpful diagnostic tests may not be available in the ED. Currently available enzyme markers of necrosis are not of value in facilitating treatment in the

Figure 8.

Generally accepted eligibility~exclusioncriteria: Thrombolytic therapyfor AMI Eligibility Criteria Clinical-Chest pain or chest-pain-equivalent syndrome consistent with AMI of 12 hours or less from symptom onset with ECG 1 mm or more ST elevation in two or more contiguous limb leads 2 mm or more ST elevation in two or more contiguous precordial leads New bundle branch block Cardiogenic shock-Emergency catheterization and revascularization if possible; consider thrombolysis if catheterization not immediately available Contraindications Absolute-Require consideration of other reperfusion strategy, such as PTCA or CABG Altered consciousness Active internal bleeding Known spinal cord or cerebral arteriovenous malformation or tumor Recent head trauma Known previous hemorrhagic cerebrovascular accident Intracranial or intraspinal surgery within two months Trauma or surgery within two weeks, which could result in bleeding into a closed space Persistent blood pressure of more than 200/120 mm Hg Known bleeding disorder Pregnancy Suspected aortic dissection Previous allergy to a streptokinase product (but not a contraindication to use of other thrombolytic agents) Relative Active peptic ulcer disease History of ischemic or embolic cerebrovascular accident Current use of oral anticoagulants Major trauma or surgery two weeks to two months earlier History of chronic, uncontrolled hypertension (diastolic >100 mm Hg), treated or untreated Subclavian or internal jugular venous cannulation

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first hour, but may be useful in establishing a diagnosis of AMI in patients who present later. In these situations of unclear clinical history and events, consultation with the patient's treating physician or with a cardiologist may be appropriate; however, consultations can increase the time to definitive treatment. In the GUSTO Time to Treatment Substudy, consultation with a cardiologist added 15 minutes to the median time to t r e a t m e n t s On the other hand, cardiology consultation by telephone or facsimile ECG may add little delay in time to treatment. 59 Reducing delay. The development of protocols for identifying and rapidly treating patients presenting to the ED with AMI requires negotiation by departments responsible for acute care, including emergency medicine, cardiology, internal medicine, family medicine, and nursing. Together, these departments should develop protocols for delegating responsibility for initiation of thrombolytic therapy to the physician responsible for initial evaluation of the patient. It is imperative that protocol-driven delivery of thrombolytic therapy be provided to all eligible patients in the hospital ED. Variations in individual internist or cardiologist treatment strategies may lead to confusion and unnecessary delay. These can be minimized if there is an agreed-on hospital protocol for general use by all physicians, nurses, and other health care professionals treating AMI patients. Checklists of inclusion and exclusion criteria for thrombolytic therapy and lists of absolute and relative contraindications should be available in the ED (Figure 8). Physical examination shoud be brief and focused around the acute event, and should not delay initiation of therapy, which can occur concurrently. Unless there is a history suggestive of gastrointestinal bleeding, a rectal examination is not needed. The emergency physician should be vested with the authority to initiate thrombolytic therapy in cases of AMI that meet accepted criteria for its use. 5 Emergency physicians have generally demonstrated their ability to use thrombolytic therapy promptly and appropriately in patients with typical presentations of AMI. 59 McKendall et a172 have reported that determination of thrombolytic therapy eligibility by emergency physicians reduces the delay in thrombolytic therapy initiation by approximately 50%. Requiring communication with the family physician, internist, or cardiologist before initiating thrombolytic therapy is inappropriate for patients who have typical and uncomplicated presentations of AMI and may result in unnecessary delays because consultants

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must be located and may need to return telephone calls or actually come to the ED. For patients with complicated presentations, relative contraindications to thrombolytic therapy, or unclear diagnosis, pretreatment consultation between the emergency physician and the consulting cardiologist, internist, or family physician who will ultimately assume in-hospital care of the patient may be indicated. Appropriate consultants should be readily accessible to the emergency physician to minimize delays. Facsimile transfer of the ECG to the consultant may be helpful, as noted. Other measures to facilitate decisionmaking in the ED diagnosis of AMI in patients with questionable symptoms and ECG findings include the following: Echocardiography, which may demonstrate a wall motion abnormality, may help the physician determine the significance of borderline ST-segment elevation in a patient with atypical chest pain and no prior cardiac condition. Continuous ST-segment monitoring in the ED in patients whose initial ECG does not show ST-segment elevation is being investigated.r3, 74 Serial 12-lead ECGs in patients with waxing and waning chest pain should be performed if the initial ECG is not diagnostic of AMI. The value of rapidly available assays for enzymes that are released soon after the onset of necrosis (CK isoforms, troponin, myoglobin) is unknown at this time. The time that the decision is made to initiate thrombolytic therapy should be recorded as ED Time 3: Decision. ED Time 4: Drug Causes of delay. Once the decision is made to treat with a thrombolytic agent, additional delays still can occur. The patient may refuse treatment until his or her personal physician can be contacted or the rationale for care understood. Hospital treatment protocols requiring that thrombolytic therapy be administered only in the coronary care unit incur the additional delay of transporting the patient. If thrombolytic therapy is administered in the ED, the emergency physician may not inform the patient of the benefits and risks of therapy in an effective and efficient manner. The performance of a procedure that increases the risk of bleeding (eg, an attempt at subclavian vein catheterization that inadvertently punctures the subclavian artery) can delay or preclude administration of thrombolytic therapy. Thrombolytic agents may not be stored in the ED; there may be delays while these agents are ordered and then mixed and delivered by the pharmacy. The high cost of some thrombolytic drugs may

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inhibit administration or limit the choice of therapy. ED personnel may be insufficient in number or too overwhelmed with other patients to initiate definitive therapy in a timely manner. Administration of other therapies including aspirin, heparin, nitrates, and p-blockers, whose efficacy may not be as time-dependent as thrombolytic therapy--may be forgotten. If the patient requires emergency cardiac catheterization, there may not be protocols and systems for the rapid mobilization of a catheterization team or, alternatively, for the expeditious transfer of the patient to a hospital that has that capability. Reducing delay. In general, thrombolytic agents may be stored in the ED to avoid delays while drugs are mixed and transported from the pharmacy. 59 The shelf life of thrombolytic agents is typically six months to two years. The drug supply should be inspected each week to ensure that the expiration date has not been exceeded. In some hospitals, however, the system for pharmacy delivery of thrombolytic medication is so rapid that having the ED stock the drug yields no benefit. The patient should always be informed of his or her condition, prognosis, and the benefits and potential risks of therapy. When thrombolytic therapy is indicated, the patient should be informed of the benefits and risks of this therapy, including the risk of stroke. If family members are present, they may be involved in this discussion unless the patient objects. The decision about whether to receive thrombolytic therapy remains the patient's. The content of the discussion and the presence of family members should be documented in the patient's chart. Informing the patient is a process, not a form; having the patient read and sign a form regarding thrombolytic therapy is not helpful and therefore not recommended. Once the decision is made to treat with thrombolytic therapy, treatment should be administered immediately in the ED and not delayed by transporting the patient to another area of the hospital. Several investigators have reported that the time between the initial ECG and initiation of thrombolytic treatment was less when the drug was administered in the ED than if it was administered after transfer to the coronary care unit. Sharkey et a124 reported that the time between the initial ECG and the initiation of treatment with the thrombolytic agent was 46.8 + 23.4 minutes when the drug was administered in the ED versus 82.1 + 34.7 minutes when it was administered after the patient was transferred to the coronary care unit. Gonzalez et a159 reported that the median door-todrug times were shorter when the drug was administered in the ED (median, 49 minutes; range, 37 to 70 minutes)

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than when it was given in the coronary care unit (median, 105 minutes; range, 98 to 120 minutes). Similarly, Birkhead75 found that the median time from arrival in the hospital to thrombolysis was 80 minutes (range, 75 to 85 minutes) for patients treated in the cardiac care unit and 31 minutes (range, 25 to 35 minutes) for those treated in the EDs in six district general hospitals in Britain. Administration of aspirin, heparin, [~-blockers, or nitrates is effective therapy for most patients with an unstable ischemic syndrome if not contraindicated and if tolerated, and should be initiated while the decision about thrombolytic therapy is being considered. Any hospital offering emergency care must be able to care for AMI patients, including initiating thrombolytic therapy. Certain AMI patients may need to be transferred to tertiary care institutions capable of performing cardiac catheterization and primary angioplasty. Patients in cardiogenic shock may benefit from being transported to facilities capable of mechanical reperfusion (percutaneous transluminal coronary angioplasty or coronary artery bypass graft). Mutually approved, written transfer agreements should contain clearly stated transfer indications and guidelines in protocol form. Protocols should be available in the EDs of both hospitals. Studies suggest that patients receiving thrombolytic therapy during helicopter or ground transport have no increase in complication rates when compared with patients receiving this therapy in the hospital setting. 76 The time of initiation of thrombolytic therapy should be recorded as ED Time 4: Drug. STANDARD PROCESS FOR EVALUATING AND IMPROVING ED TREATMENT OF AMI PATIENTS

The working group recommends that each ED implement a system of continuous monitoring, evaluation, and modiFigure 9. Additional ED timepoints

g.

Y Interval I

324

Y Interval II

Y Interval III

fication of its process of care for AMI patients to reduce delays in rendering definitive treatment. EDs should articulate and examine the specific processes by which they render care to the AMI patient, collect data that measure how well those processes are functioning, analyze and review the data on a regular basis, change processes for patient identification and treatment when the data suggest that improvement is necessary or possible, and then reanalyze the data to see if the changes improved performance. This system of continuous review and corrective intervention is based on the W Edwards Deming model of continuous quality improvement (CQI). The CQI process involves repetitive sequences of evaluation, corrective intervention, and re-evaluation that continuously improve quality.77,78 The CQI system requires an explicit knowledge of the process of care. Aspects of the care system that are illogical or ill conceived, that have evolved for reasons that are no longer applicable, or that do not primarily serve the interests of the patient may become apparent when the entire process is scrutinized in detail. Changes cannot be made in a system that functions poorly unless there is an understanding of how the system works. Each ED has its own set of systems, problems, strengths, weaknesses, and solutions that can be revealed only through close scrutiny. Such assessments of ED processes culminating in thrombolytic therapy have been shown to shorten arrival-to-treatment times. MacCallum et a179 achieved a median time of 17 minutes from admission to initiation of thrombolysis in 50 consecutive patients after instituting a performance-monitoring program in the ED. The program consisted of paramedic identification of possible candidates for thrombolytic treatment (by taking prehospital ECGs and notifying the receiving hospital of possible candidates), use of exclusion checklists for thrombolytic therapy, and recording of arrival and "doorto-needle" times. CummingsSO reported a decrease in mean time from arrival in the ED to initiation of treatment and an increase in the percentage of people treated within an hour; these changes occurred after a quality assurance audit was conducted to improve the speed of delivery of thrombolytic therapy for AMI in an ED. After an initial audit and feedback, ED nurses were educated about the importance of ordering ECGs rapidly, and physicians were encouraged to make treatment decisions before consulting a patient's private physician. As a result of these measures, mean time from ED arrival to thrombolytic therapy decreased from 63 minutes in 1988 to 47 minutes in 1989 and to 38 minutes in 1990.

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The number of patients treated within one hour rose from 45% in 1988, to 67% in 1989, and to 96% in 1990. This paper proposes two tools to help EDs improve care. The first is a series of questions whose answers may expose problems in the care of AMI patients. The second is a record of the time of onset of symptoms and a minimum of four timepoints in the sequence of care of AMI patients. The following questions about each of the four timepoints of care may help an ED examine and refine its care of AMI patients. Door: Is there appropriate prehospital communication with rescue units? How does a patient who arrives ambulatory with symptoms suggesting AMI move into a clinical treatment area? How does a patient who the prehospital care provider or triage nurse suspects may be having an AMI come to the attention of the treating physician? Data: Who has the authority to order an ECG on an ED patient, and what criteria are used to determine whether it is needed? How rapidly is an ECG obtained once it is ordered? What is the process and how swift is it for getting the ECG and/or its interpretation to the treating physician? Decision: Who has the authority to order thrombolytic therapy for an ED patient having an ST-segment-elevation AMI? What is the mechanism for obtaining appropriate consultation when the emergency physician is uncertain of what to do? Drug: Is thrombolytic therapy routinely administered in the ED or deferred to the coronary care unit? What is the process by which the thrombolytic drug is prepared for infusion once the decision to use it has been made? Are aspirin, heparin, nitrates, and [3-blockers appropriately administered to AMI patients in the ED without delaying initiation of thrombolytic therapy? Is the information needed to obtain the patient~ informed consent presented clearly and efficiently? CQI is data driven. Accurate, quantifiable information that reflects the quality of the process must be collected on an ongoing basis. These data must be documented at the time care is rendered because in retrospect clinicians often underestimate the actual time it took to render care. 23 At a minimum, EDs should record the times of onset of symptoms, arrival in the ED, initial ECG (and time of the "qualifying" ECG if it is not the initial one), decision to treat with thrombolytic therapy, and initiation of treatment. Other times should be recorded, as necessary, to facilitate analysis. For example, the time from patient arrival to the administration of the ECG is unac-

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ceptably long, the time from patient arrival in the acute care area of the ED to the ordering of the ECG should be recorded and the derivative times calculated and analyzed (Figure 9). There are several obstacles to precise data collection. As noted, the time of symptom onset in AMI patients is subjective and difficult to obtain. This information, however, is needed to assess public education and prehospital care system efforts to urge suspected AMI patients to come to the hospital as rapidly as possible after their symptoms begin. Although the time of arrival of the patient in the ED, time the ECG is obtained, and time of delivery of thrombolytic therapy are usually recorded concurrently on the patient's chart or ECG, the time of the physician~ decision to treat with thrombolytic therapy may be difficult to obtain unless it is documented specifically and concurrently. The time that the thrombolytic drug is first ordered can be used as a surrogate measure for ED Time 3: Decision. The general documentation of care, as well as the recording of these specific timepoints, may be enhanced by using an AMI flowsheet that prompts ED personnel to document events and observations as they occur. Furthermore, flowsheets may lessen lapses in protocol and, if properly filled out, greatly simplify the review process (Figure 10). Some institutions have established chest pain emergency centers, which typically are areas within or adjacent to the wider ED setting, for evaluation of patients presenting with

Figure 10. AMI time-to-treatment flowsheet ClockTime Time 0: Onset I

~t~me Interval I [ ~

I "~

I Timelntervalll ~ f EDTime Z:" Data . ~ (EDTime3minus I . , 14 I ~ EDTime2) ~ L ] I EOTime 3: Decision I I Timelntervallll ~ r I I (EDTime4minus [ . I"~ I ~ Time3) ~ L L " N EDTime 4: Drug ~1~ ~

"~1 . % "

i" EDTime 1: Door

I (EDTime2 minus I . I ,,~ [ EDTimel} I mmutesl L

~ ~

t -

~ ~

OnsetofAMI symptoms Arrivalin ED EeGobtained Drugordered(decision to treatwith thrombolyticagent) Thrombolyticdrug infusionstarted

Total Door-to DrugTime

I (EDTime4minusEDTime!; IntervalsI + II + III)

Total Time FromOnsetof Symptomsto I_._ ._ I ThrombolyticDrugAdministration

(EDTime4 minusTimeO)

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AMI PATIENTS National Heart Attack Alert ProgramCoordinatingCommittee

a chief complaint of chest pain. 8t Although these centers have a goal of more rapid identification and treatment of these patients, outcome data showing benefit over "routine" ED care are not currently available. Patients who are deemed not to have chest pain of ischemic origin that warrants hospital admission should be reassured that they acted appropriately in seeking care. Such patients should be instructed to seek immediate care again in the event that they, or others with whom they may be associated, experience symptoms and signs suggestive of an AMI. If cardiovascular disease risk factors are noted, the emergency physician or nurse should discuss these with the patient and refer the patient to a physician or other community resource for management. Published studies of AMI patients will provide normative national data for comparison of identification and treatment times. In the same manner that patients "know their numbers" with respect to serum cholesterol, hospitals should "know their numbers" with respect to the time to treatment with thrombolytic therapy for their AMI patients. A hospital should be able to measure itself against the performance of its peer institutions and adapt processes from those institutions that have been successful in improving care.23,24,57,59,64 This evaluation process should emphasize how each ED can improve its own times instead of competing with other institutions. Hospitals must avoid overemphasizing time-reductions at the sacrifice of other aspects of quality of care. Treatment of the AMI patient in the ED requires a coordinated team effort of hospital personnel from the medical, nursing, registration, technical support, central administration, and pharmacy staffs; the review process should be conducted by a similar, broadly based group. Furthermore, central hospital administration must demonstrate commitment to improving the care of the AMI patient by being willing to commit the necessary resources for these improvements. CONCLUSION

Time is critical to an optimal outcome for AMI patients. Major trials of thrombolytic therapy--the definitive therapy for AMI in 1993--have documented maximum treatment benefit during the first one to two hours following symptom onset. In addition, half of AMI deaths occur suddenly, within one hour of the onset of symptoms. An ultimate goal of the NHAAP is to reduce the time between the onset of symptoms and definitive treatment in the ED. This paper examines the ED's contribution to overall delay and recommends measures that will shorten

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the time that lapses between the patientg arrival in the ED and the administration of thrombolytic therapy. The American Heart Association has recommended that thrombolytic treatment of eligible AMI patients occurs within 30 to 60 minutes of their arrival in the ED.6O The working group recommends that EDs strive to achieve the minimum 30-minute, door-to-drug time goal recommended by the American Heart Association for patients with a clear diagnosis of AMI. Published reports and analyses of AMI diagnosis and treatment have demonstrated that a door-to-drug time of 30 minutes for the clearly defined AMI patient is feasible and reasonable. EDs can move toward this goal by assessing the time they spend on each critical time and instituting policies and protocols to evaluate and expedite the care processes for patients with symptoms and signs of AMI. Recommendations for changes in care should be based on an analysis of the data coupled with an understanding of the operational characteristics unique to that ED. Changes should be made while timeinterval data and other aspects of patient care are monitored. Continued refinements should be based on ongoing data analysis. It is hoped this will aid EDs in treating AM[ patients with the same sense of urgency as victims of trauma. Other educational efforts will need to be undertaken to bring these patients to the ED early after symptom onset so that they can receive maximum benefit from the stateof-the-art care. National Heart Attack Alert Program Coordinating Committee, 60 Minutes to Treatment Working Group Chairmen CostasT Lambrew, MD Professorof Medicine University of Vermont Director, Division of Cardiology Maine Medical Center Portland Mark S Smith, MD Chairman and Professor Departmentof EmergencyMedicine Director, The RonaldReaganInstitute of EmergencyMedicine The GeorgeWashington University Medical Center Washington, DC

Members George G Annas, JD, MPH Chairman, Health Law Department Director, The Law, Medicine and Ethics Edward R Utley Professorof Law and Medicine Boston University Schoolsof Medicine and Public Health Boston, Massachusetts RobertR Bass.MD. FACEP Associate Professorof EmergencyMedicine Georgetownand GeorgeWashington Universities Medical Director, District of Columbia Fire and EmergencyMedical ServicesBureau Washington, DC

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AMI PATIENTS National Heart Attack Alert ProgramCoordinatingCommittee

Julie Bracken,RN, MS Adjunct Clinical Professor University of Illinois ChicagoCircle Nurse Manager EmergencyDepartment Hinsdale Hospital Hinsdale, Illinois Robert Califf, MD Associate Professorof Medicine Director, CardiacCareUnit Duke University Medical Center Durham, North Carolina Charles K Francis,MD Professor of Clinical Medicine Columbia University Collegeof Physiciansand Surgeons Director Department of Medicine Harlem Hospital Center New York W Brian Gibler, MD, FACEP Assistant Professorof EmergencyMedicine ResidencyDirector Department of EmergencyMedicine University of Cincinnati Medical Center Cincinnati, Ohio Mary Beth Hartman, RN, MSN Director of Nursing Unit Department of EmergencyMedicine The 6eorge Washington University Medical Center Washington, DC Mary Ho, MD, MPH Seattle, Washington StevenJ Lewis, MHA Manager, Clinical ServicesDevelopment American Hospital Association Chicago Joseph P Ornato, MD Chief Internal Medicine Sectionof EmergencyMedical Services Professorof Internal Medicine and Cardiology Medical Collegeof Virginia Richmond Roger B Rodrigue,MD, MPH Commission of Public Health and Scientific Affairs American Academyof Family Physicians Section Chief--Geriattic Medicine Associate ProgramDirector Department of Family and CommunityMedicine Medical Centerof Delaware Wilmington

Staff John C Bradley, MS National Heart Attack Alert ProgramSupportContract Manager NHLBI EducationProgramsSupportContract University ResearchCorporation Bethesda,Maryland Mary McDonald Hand, MSPH, RN CoordinatorNational Heart Attack Alert Program Office of Prevention,Education,and Control National Heart, Lung, and Blood Institute National Institutes of Health Bethesda, Maryland Michael Horan, MD, ScM Director Division of Heart and VascularDiseases Natienal Heart, Lung,and Blood Institute National Institutes of Health Bethesda,Maryland

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EugenePassamani.MD Former Director Division of Heart and VascularDiseases National Heart, Lung,and Blood Institute National Institutes of Health Bethesda, Maryland

Acknowledgments Mickey Eisenberg,MD, PhD Professorof Medicine University of Washington Director, EmergencyMedical Service University of Washington Medical Center Seattle Deborah D Smith, RN, BSN ResearchNurse Coordinator GUSTOClinical Trial Duke University Medical Center Durham, North Carolina EricJ Topoi, MD Director, Centerfor Thrombosisand VascularBiology Chairman, Departmentof Cardiology ClevelandClinic Foundation Professorof Medicine Ohio State University Cleveland W DouglasWeaver, MD Professor of Medicine Director, CardiovascularCritical Care University of Washington Seattle

National Heart Attack Alert Program Coordinating Committee Member Organizations Agencyfor Health Care Policyand Research American Academyof FamilyPhysicians American Academyof InsuranceMedicine American Association of Critical CareNurses American Association of OccupationalHealth Nurses American Collegeof Cardiology American Collegeof ChestPhysicians American Collegeof EmergencyPhysicians American Collegeof Occupationaland EnvironmentalMedicine American Collegeof Physicians American Collegeof PreventiveMedicine American Heart Association American Hospital Association American Medical Association American Nurses' Association, Inc American PharmaceuticalAssociation American Public Health Association American Red Cross Association of Black Cardiologists Centersfor DiseaseControl and Prevention Department of Defense, Health Affairs Department of VeteransAffairs EmergencyNursesAssociation Federal EmergencyManagementAgency Foodand DrugAdministration Health Care FinancingAdministration Health Resourcesand ServicesAdministration international Association of Fire Chiefs National Association of EmergencyMedical Technicians National Association of EMS Physicians National Association of State EmergencyMedical ServicesDirectors National Black Nurses' Association, Inc National Centerfor Health Statistics National Heart, Lung, and Blood Institute National Highway Traffic Safety Administration National Medical Association

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NHLBI Ad Hoc Committee on Minority Populations Society for Academic EmergencyMedicine Society of General Internal Medicine

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44. Horton R. Thrombolysis:tPA fast by GUSTO.Lancet1993;341:1188. 45. Honan MR, Harrell FE, Reimer KA, et ah Cardiac rupture, mortality and the timing of thrombolytic therapy: A meta-analysis. JAm Coil Cardie11990;16:359-367. 46. KudenchukPJ, Li~in PE, Dewhurst TA, et al: Early predictors of hospital mortality in acute myocardial infarction (abstract). JAm Coil Cardio11992;19(3Suppl A):153A. 47. Kuller LH, Traven ND, Rutan GH, et al: Marked decline of coronary heart disease mortality in 35-44-year-oldwhite men in Allegheny County, Pennsylvania.Circulation1989;80:261-266. 48. Mathey DG, Sheehan FH, Schofer J, etal: Time from onset of symptoms to thrombolytic therapy: A major determinant of myocardial salvage in patients with acute transmural infarction. J Am Coil Cardio11985;6:518-525.

68. Bonnono C, HedgesJR, Peterson C, et al: Initial nursing impression in patients with chest discomfort. J EmergNurs1992;18:28-33. 69. Lee TH, RouanGW, Weisberg MC, et ah Clinical characteristics and natural history of patients with acute myocardial infarction sent home from the emergency room. Am J Cardiel 1987;60:219-224. 70. McCarthy BD, BeshanskyJR, D'Agostino RB, et al: Missed diagnosis of acute myocardial infarction in the emergencydepartment: Results from a multicenter study. Ann EmergMed 1993;22:579-582. 71. Selker HP: Coronarycare unit triage decision aids: How do we know when they work? (editorial) Am J Med 1989;87:491-493.

49. National Registry of Myocardial Infarction: Presentation and treatment profile: National summary. Cumulative data report: Non-transfer patients. Figures2, 3, and 6; Table 2. (Facsimile transmission to Mary McDonald, NHLBI, February5, 1993)

72. McKendall GR, Woolard R, McDonald MJ, et ah Administration of thrombolytic therapy by cardiologists delays treatment: Impact of initiation by emergencydepartment physicians (abstract). Circulation1992;86(4Suppl 1):1-730.

50. He MT, Eisenberg MS, Litwin PE, et ah Delay between onset of chest pain and seeking medical care: the effect of public education. Ann EmergMed 1989;18:727-731.

73. Gibler WB, Walsh RA, Levy RC, et ah Rapid diagnostic and treatment center in the emergency department for patients with chest pain (abstract). Circulation1992;86(4Suppl 1):1-15.

51. Leitch JW, Birbara T, FreedmanB, et al: Factors influencing the time from onset of chest pain to arrival at hospital. MedJAust1989;150:6-10.

74. Krucoff MW, Trollinger KM, Veldkamp RF, et ah Cyclic changes in coronary flow: Underlying disease, result of therapy, or both? (abstract) J Am Coil Cardio11993;21:349A.

52. Wielgosz ATJ, Nolan RP, EarpJA, et al: Reasonsfor patients' delay in responseto symptoms of acute myocardial infarction. CanMed AssecJ 1988;139:853-857.

75. Birkhead JS (on behalf ef the joint audit committee of the British Cardiac Society and a cardiology committee of Royal College of Physiciansof London):Time delays in provision of thrombolytic treatment in six district hospitals. Br MedJ1992;305:445-448.

53. Cooper RS, Simmons B, CastanerA, et ah Survival rates and prehespital delay during myocardial infarction among black persons. Am J Cardio11986;57:208-211. 54. Maynard C, Althouse R, Olsufka M, et al: Early versus late hospital arrival for acute myocardial infarction in the Western Washington thrombolytic therapy trials. Am J Cardiel 1989;63:1296-1300. 55. Dracup K, Moser DK: Treatment-seeking behavior among those with signs and symptoms of acute myocardial infarction. HeartLung1991;20(5Pt 2):570-575. 56. Herlitz J, Hjalmarson A, Holmberg S, et al: Mortality and morbidity in suspected acute myocardial infarction in relation to ambulance transport. EurHeartJ1987;8:503-509. 57. Kline EM, Smith DD, Martin JS, et ah In-hospital treatment delays in patients treated with thrombolytic therapy: A report of the GUSTOTime to Treatment Substudy(abstract). Circulation 1992;86(4 Suppl 1):1-702.

76. Gore JM, Corrao JM, Goldberg RJ, et ah Feasibility and safety of emergencyinterhospital transport of patients during early hours of acute myocardial infarction. Arch InternMed 1989;149:353-355. 77. Doming WE: Quality, productivity and competitive position. Cambridge,Massachusetts, Massachusetts Institute of Technology Center for Advanced EngineeringStudy, 1982. 78. Scherkenbach~Ah/V:The Deming route to quality and productivity. Washington, DC: Creed Press Books, 1987. 79. MacCallum AG, Stafford PJ, Jones C, et ah Reduction in hospital time to thrombolytic therapy by audit of policy guidelines. EurHeartJ 1990;1l(Suppl F):48-52. 80. Cummings P: Improving the time to thrombolytic therapy for myocardial infarction by using a quality assurance audit. Ann EmergMed 1992;21:1107-1110.

58. Moses HW, BartolozziJJ, Koester DL, et al: Reducingdelay in the emergencyroom in administration of thrombolytic therapy for myocardial infarction associated with ST elevation. Am J Cardie11991;68:251-253.

81. Bahr RD: Access to early cardiac care: Chest pain as a risk factor for heart attacks, and the emergence of early cardiac care centers. Md Med J 1992;41:133-137.

59. GonzalezER, Jones LA, Ornate JP, et al: Hospital delays and problems with thrombolytic administration in patients receiving thrombolytic therapy: A multicenter prospective assessment. Ann EmergMed 1992;21:1215-1221.

Reprint no. 47/1/53235

60. American Heart Association/EmergencyCardiacCare Committeeand Subcommittees: Guidelinesfor cardiopulmonaryresuscitationand emergencycardiac care, Ill: Adult advanced cardiac life support. JAMA 1992;268:2199-2241.

Address for reprints: Mary McDonald Hand, MSPH, RN National Heart Attack Alert Program

61. Poll ACH, Miller HC, RobertsonCE, et ah Effect of "fast track" admissionfor acute myocardial infarction on delay to thrornbolysis. Br MealJ 1992;304:83-87.

National Heart, Lung, and Blood Institute

62. Grim P. FeldmanT, Martin M, et al: Cellulartelephonetransmissionof 12-leadelectrocardiograms from ambulanceto hospital.Am J Cardio11987;60:715-720.

9600 Rockville Pike

63. Kereiakes DJ, Gibler WB, Martin LH, et ah Relative importance of emergencymedical 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 HeartJ 1992;123(4 Pt 1):835-840.

National Institutes of Health

Building 31, Room 4A18 Bethesda, Maryland 20892

64. Weaver WD, EisenbergMS, Martin JS, et al: Myocardial infarction triage and intervention project--phase I: Patient characteristicsand feasibility of prehospital initiation of thrombotytic therapy. J Am CoilCardie11996;15:925-931. 65. KudenchukPJ, He MT, Weaver WD, et al (for the MITI Project Investigators): Accuracy of computer-interpreted electrocardiography in selecting patients for thrombolytic therapy. JAm Coil Cardiol 1991;17:1486-1491. 66. Karagounis L, Ipsen SK, Jessop MR, et ah Impact of field-transmitted electrocardiography on time to in-hospital thrombelytic therapy in acute myocardial infarction. Am J Cardiol 1990;66:786-791. 67. Gibler WB, Kereiakes DJ, Dean EN, et ah Prehospital diagnosis and treatment of acute myocardial infarction: A North-South perspective. Am HeartJ 1991;121(1 Pt 1):1-11.

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