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Impact of field-transmitted electrocardiography on time to in-hospital thrombolytic therapy in acute myocardial infarction
Impact of Field-Transmitted Electrocardiography On Time to In-Hospital Thrombolytic Therapy Acute Myocardial Infarction
in
Labros Karagounis, MD, Steve K. Ipsen, RN, Michael R. Jessop, Kirk M. Gilmore, MD, David A. Valenti, MD, Jeffrey J. Clawson, MD, Sam Teichman, MD, and Jeffrey L. Anderson, MD
To assess the impact of a field-transmitted electrocardiogram (ECG) on patients with possible acute myocardial infarction, randomized and open trials were performed with a portable electrocardiographic system coupled with a cellular phone programmed to automatically transmit EGGS to the base hospital. Consecutive patients served by the 6 units of the Salt Lake City Emergency Rescue System were studied; 71 patients were randomized to in-field EGG (n = 34) versus no ECG (n = 37). Time on scene was 16.4 f 9.7 minutes for the ECG group versus 16.1 f 7.0 minutes for the non ECG group (difference not significant). lime of transport averaged 18.2 f 9.9 and 17.6 f 13.1 minutes, respectively (difference not significant). Six of 34 patients with in-field ECG showed acute myocardial infarction, qualified for and received thrombolytic therapy at 46 f 12 minutes after hospital arrival (range 30 to 60) compared with 103 f 44 minutes (p
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From the Department of Medicine, Division of Cardiology and LDS Hospital, Salt Lake City, Utah. This study was supported in part by a grant from Genentech Inc., South San Francisco, California. Manuscript received January 3 1, 1990; revised manuscript received and accepted May 11, 1990. Address for reprints: Jeffrey L. Anderson, MD, Division of Cardiol;;:y,),DS Hospital, 8th Avenue and C Street, Salt Lake City, Utah
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n the past decade, thrombolytic reperfusion has become established therapy in acute myocardial infarction (AMI),1,2 now known to be precipitated by coronary thrombosis3,4 and to evolve rapidly after coronary occlusion.5 Early application of therapy has been shown to be important to achieve early reperfusion6,7 to improve left ventricular function and decrease infarct sizes-l4 and to decrease mortality.15-l7 Treatment given in <2 to 4 hours after symptom onset has consistently yielded greater benefit than later treatmentg-l 1,15+17 and even earlier therapy (within 1 to 2 hours) is desirable 11,15,17 Delays in administering thrombolytic therapy include not only patient delays and transport time, but also hospital delays after arrival.18-20 Paramedic transmission of an in-field, 1Zlead electrocardiogram (ECG) to physicians at the base hospital is a newly available approach to decreasing delay to AM1 diagnosis*l and treatment.22,23 However, additional experience from controlled studies would be useful to establish the reliability and impact of in-field ECG before embarking on its extensive use, including the guidance of in-field thrombolytic therapy. 22-24This study assessesthe feasibility and impact of field-transmitted ECG on the prehospital and early hospital care of patients with suspected AM1 in a randomized design. METHODS
The purpose of phase I of the Field Ambulance Study of Thrombolysis in Myocardial Infarction (FAST-MI) was to show the feasibility and advisability of using an in-field ECG to direct the initiation of thrombolytic therapy in a randomized, dry-run study design before initiating Phase II (currently underway) of the treatment study (initiating therapy in-field versus in-hospital). Study objectives and hypotheses: Specific study objectives were the following: to assessthe feasibility of obtaining and transmitting the in-field electrocardiogram (ECG) to the base hospital; to evaluate and compare the natural history of in-field evaluation and transport of chest pain patients both with and without knowledge of the field-transmitted ECG; and to determine the reliability and “safety” of paramedic/emergency physician diagnosis of AM1 and triage to thrombolytic therapy. We hypothesized that the in-field ECG could be obtained successfully and without substantial delay and that appropriate patient triage could be made. The study was approved by the LDS Hospital Institutional
Review Board and by the Utah State Department of Health, Emergency Services Division. Study design: The study was designed in 2 partsan education phase and a study phase. Education phase: The Salt Lake City Paramedic Rescue Units serve a population base estimated at 600,000 people. Initially, 2 training sessions were conducted in a prefield setting for the 6 paramedic units (50 personnel). Subsequently, in-field training was provided at least twice for each paramedic unit. Concurrently, training of emergency room physicians and nurses was undertaken in receiving and reviewing fieldtransmitted ECGs and in randomizing patients to “mock” in-field initiated versus emergency room initiated therapy. A start-up phase was then undertaken, consisting of a series of consecutive ECGs in chest pain patients (2 10 per paramedic unit) to show the ability to correctly use the equipment. Study phase: After study initiation, consecutively evaluated patients were selected for an ECG based on the clinical (paramedic’s) suspicion of possible AM1 (i.e., suggestive chest pain) alone. (Further clinical evalassessment of other inclusion/exclusion uation-e.g., criteria for “mock” thrombolytic therapy-was considered afterward in patients with a diagnostic ECG.) Paramedics randomized “ECG-eligible” patients at the scene to obtain or not to obtain an in-field ECG by opening a sealed envelope. Records were kept of the actual time spent in attending to the patient at the scene, the time in transport and the time to thrombolytic therapy if given after hospital arrival. Phase I was prospectively planned to run for 3 months or until >50 patients over the age of 35 years were evaluated. A flow chart of the study is shown in Figure 1. In-field electrocardiographic assessment: An infield la-lead ECG was performed by means of a battery-powered portable electrocardiograph weighing 28 lbs (Marquette, Inc.). The ECG was usually performed on-scene, but occasionally in-transport. Both an onscene 124ead ECG printout and a hospital printout, both with ECG interpretation (Marquette Diagnosis Program Software), were provided by the system with minimal delay (
A comparison between initial (emergency physician/ paramedic) and retrospective (cardiologist) assessment of AM1 was also made. Averaged data are generally presented as mean f standard deviation. A p value KO.05 was considered statistically significant. RESULTS Randomized phase: The randomized portion of Phase I was conducted over a period of 3 months (December 1988 to March 1989). A total of 180 calls were received for chest pain; 71 (39%) of these patients were
METHODS PARAMEDICS RESPOND PATIENTS WITH CHEST PAIN 1
TO
RANDOMIZED TO IN-FIELD ECG +
-
1
’ __)
STANDARD
CARE
ECG TRANSMITTED TO ER REVIEW BY M.D. DIAGNOSIS MADE + t
I STOP
REVIEW INCLUSION/EXCLUSION CRITERIA WITH M.D. + t
I __c
“MOCK”RANDOMIZATION
TO THERAPY
MOCK IN-FIELD TPA THERAPY
TPA
FlGtJRE 1. Flow chart showing sion tree. ECG = electrocardiogram;
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judged by paramedics to represent possible ischemia and were randomized; 34 were randomized to receive in-field ECG and 37 to no ECG. Impact of in-field electrocardiogram on prehospital time: Assignment to the in-field ECG group caused a
negligible overall impact on time spent at the scene (Figure 3) and on time in transport (Figure 4). Time spent on the scene averaged 16.4 f 9.7 minutes for the in-field ECG group (n = 34) and 16.1 f 7.0 minutes for the nonECG group (n = 37, difference not significant). The range of times at the scene was 2 to 36 minutes for the ECG group and 4 to 50 minutes for the nonECG group. Transport time from the scene to the hospital averaged 18.2 f 1.7 minutes in the ECG group and 17.6 f 2.2 minutes in the nonECG group. The range of transport times was 4 to 40 minutes for the ECG group and 3 to 50 minutes for the nonECG group. Diagnosis and confirmation of acute myocardial infarction based on in-field electrocardiogram: A total of
6 (17%) of the 34 patients receiving in-field ECG were
diagnosed by the emergency physician/paramedic team as having an AMI. On retrospective (cardiologist) electrocardiographic review, the diagnosis was confirmed in 5 and was equivocal in 1. The ECGs were confirmed to show no MI in the other 28. Two other patients were diagnosed as having AMI by in-field ECG among 16 additional patients with possible AM1 studied in the start-up phase, before beginning the randomization protocol. Of these 8 patients with AMI, 3 were ineligible, 2 because of age 176 years and 1 because of cardiac arrest requiring resuscitation measures, lime to thrombolytic therapy after in-field electrocardiogram: Of patients receiving in-field ECG, 5
showing AM1 qualified for and received thrombolytic therapy in-hospital. In these patients, the time from hospital arrival to initiation of therapy averaged 48 f 12 minutes (range, 30 to 60 minutes). This compares favorably with 103 f 44 minutes (p
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FIGURE 2. Paramedic information and questionnaire form for in-field patient screening and enrollment. FAST-MI = Field Ambulance Study of Thrombolysis in Myocardial Infaction.
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REMARKS:
29 minutes for 6 concurrently treated patients receiving thrombolytic therapy during the 3-month period of the Phase I study but not having in-field ECG. DISCUSSION Study summary: Phase I of our FAST-MI study showed the feasibility, efficiency and reliability of in-field ECG acquisition by a paramedic/emergency physician team in evaluating chest pain calls for a representative urban/suburban population. The equipment was easily adapted to paramedic use. During the education and start-up phases, a number of minor technical difficulties were addressed and overcome. In the randomized phase, increases beyond the previous average of 35 minutes total time at the scene and in transport were minimal (nonsignificant). Agreement between emergency physician (prospective) and cardiologist (retrospective) diagnosis of AM1 was good; no false negative diagnoses and only 1 equivocal false positive diagnosis occurred. However, these numbers are small and further observations are needed. Importantly, the time from hospital arrival to initiation of thrombolytic therapy was decreased by about 40 minutes compared with that in our recent study experience.’ A decrease of 20 minutes to therapy was also achieved when compared with a concurrent group of treated patients not receiving in-field ECG.
easons
for
delay
in
initiating
thrombolytic
thera-
Delays to thrombolytic therapy after hosptial arrival appear to contribute more to overall delay to thrombolytic therapy than either transport time or patient delay in seeking medical assistance.19 In a recent Minnesota study,20 in-hospital delays accounted for more than half of the total time from onset of symptoms to initiation of thrombolysis. Of the total hospital delay of 90 minutes, 20 minutes were due to the initial ECG. Other delays were less when drugs were administered in the emergency department (47 minutes) than after transfer to the coronary care unit (82 minutes). Similar hospital delays were observed in both our recent historical experience (108 minutes)’ and in an earlier Western Washington trial (102 minutes).22 In-hospital delays in initiating therapy include the following: administrative reasons (registration, triage, overcrowding/bed problems); diagnostic evaluation (nurse, physician evaluation; ECG, blood, x-ray tests); therapeutic needs (starting intravenous lines); medical/ political reasons (consultations among private physician, cardiologist, house staff); and pharmacy delays (obtaining, mixing, administering drug). lg py:
Impact
of in-field
electrocardiogram
on hospital
30
20
10
C
In Field ECG (n=34)
No ECG (rl=37)
FIGURE 3. Paramedic time (mean f standar spent on-scene for patient pickup in groups randomix ceiva an in-field EGG and no ECG.
de-
Transmission of an in-field ECG alerts the hospital-based medical care team in advance that an incoming patient has an AMT. These hospital delays may
lays:
In-Field ECG (n=34)
No ECG (n=37)
FlGURE 4. Transport time (mean rfr standard deviation [min]) om scene of patient pickup to hospital in groups randomize ts receive an in-field e~ectr~ardi~gram (ECG) and no EGG. TH IE AMERICAN
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then be shortened because the process of preparing for thrombolytic therapy may begin well in advance of patient arrival (about 30 minutes in our study). The time saved to the first ECG appears to be directly passed on in time saved to thrombolytic therapy. In the Seattle experience, in-hospital delay was decreased from 102 to 46 minutes after instituting an in-field ECG system22 (Figure 5). Similarly, we saw a decrease from 108 to 48 minutes (Figure 5). Part of this decrease may also reflect better training of emergency room personnel in screening patients and greater involvement in initiating therapy, as suggested by the decrease in delay noted recently in our studies (108 to 68 minutes) and in others’,20,22even in patients not receiving in-field ECG. Demography of chest pain patients evaluated by paramedics: Only a small minority of patients with
chest pain attended to by paramedics have electrocardiographic and clinical characteristics of AM1 that qualify them for thrombolytic therapy, an observation of importance to the planning of future intervention studies. In our study, 39% (71 of 180) of total chest pain calls were judged clinically to represent possible AM1 and of these, only 17% receiving in-field ECG showed AMI. Thus, only about 7% of chest pain calls were identified in-field as an AMI. Of the 8 patients showing AM1 by in-field ECG, 5 qualified for thrombolytic therapy (63% of AM1 patients but only 3 to 4% of all chest pain calls). Similarly, in the larger Seattle experience, 3% (83/2,465) of patients calling with chest pain met criteria for possible prehospital thrombolytic therapy.22 Patients were excluded most commonly because of a nondiagnostic ECG, pain >6 hours, age 175
Fast-Ml IF-ECG (n=6)
Historica Controls (n=51)
Western MIT1 Project Washingtor Phase 1 2nd Trial Seattle (n=89)
FIGURE 5. Times to thrombolytic therapy after hospital arrival. Left, patients with acute myocardial infarction who received an in-field electrocardiogram (IF-ECG) compared with recent historical control patients (right) not getting IF-ECG; Right, a literature comparison also showing treatment times for patients receiving IF-ECG (leff hand bar) and historical control subjects without IF-ECG (right hand bar).
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years and hypertension. 22 Further, of patients who gradually developed an AM1 in-hospital, only 20% met prehospital criteria for therapy and 22% more qualified for therapy after initial hospital evaluation. Similarly, in a New England study, only 23% (261 of 1,118) of patients who eventually developed an AM1 were candidates for thrombolysis in the emergency room based on age 175 years, pain for <4 hours and a diagnostic ECG,23 before accounting for exclusions due to contraindications to thrombolysis. Of some concern was their estimate that for every patient treated with true positive findings (based on the interpretation of a single ECG), 1 to 2 patients with false positive results might be treated. Fortunately, this last conjecture has not been substantiated in clinical trials in which, generally, 195% of patients have subsequently showed an
AMI.7,‘5,‘6
Implications for in-field thrombolysis: Our study supports the feasibility of initiating thrombolytic therapy in-field but also emphasizes the need for controlled trials before embracing in-field therapy. Our experience in the FAST-MI is consistent with that of others that suggest that a good, although not perfect, correlation exists between emergency physician/computer diagnosis of AM1 and cardiologist (retrospective) diagnosis. Using similar technology, the University of Washington group achieved a 70% sensitivity and a 100% specificity for a computer-based diagnosis algorithm (Marquette System Diagnosis Program) of AMI. Although this exceptional specificity will require further confirmation, the results do suggest that a computer based system may help prevent over-diagnosis of AMI’9,23 and potentially hazardous25 overuse of thrombolytic therapy by emergency room personnel less experienced in ECG interpretation. Improved accuracy in diagnosis and therapy might also be achieved by having well-trained physicians travel with paramedic units. 11,26However, this approach does not appear to be practical in the United States. Another approach to optimizing both safety and efficacy may be to use a small “priming” dose of a shortacting thrombolytic agent in the field to begin the process of thrombolysis. Review of the decision to give fulldose therapy could then be made in the emergency room and therapy effectively terminated if desired. Tissue plasminogen activator (alteplase) has the properties of excellent hemodynamic tolerance, rapidly acting thrombolytic effect and a short half-life. The efficacy and safety of “front-loaded” (bolus initiated) regimens of alteplase have been recently evaluated and appear to be promising.27 Based on these characteristics of alteplase, we believe that the administration of an in-field loading bolus (i.e., 20 mg) by paramedics, followed by continuation of a full-dose regimen upon hospital arrival, represents an appealing regimen to test (FAST-MI, Phase II). However, given the potentially dire consequences of misapplication of thrombolytic therapy25 and both medical and legal concerns about paramedic administration of thrombolytic therapy, we believe that streamlined in-hospital (emergency department) initiation of therapy should be currently viewed as the best
strategy for initiating thrombolytic therapy.rg Whether or not in-field initiation of therapy is safe and will give additional benefit must be addressed in ongoing or future studies.22,2s Acknowledgment/Appendix: We recognize the participation and performance of the following rescue units of the Salt Lake City Paramedic System: numbers 2, 3, 5, 7, 8 and 11. Hospitals receiving patients from the Salt Lake Paramedic System include the following: LDS Hospital; Holy CrossHospital; University of Utah Hospital; Veterans Administration Hospital; St. Marks’ Hospital; Cottonwood Hospital; and Lakeview Hospital. Principal investigators of the FAST-MI study were the following: Study principal investigator, Jeffrey L. Anderson; Co-investigator, Labros Karagounis; Study Coordinator, Steven Ipsen, RN; Co-coordinator, Ann Allen; and Graphics, John Carlquist, PhD. Specific hospital investigators were the following: LDS Hospital, L. Karagounis, J. Anderson; Holy Cross Hospital, S. Nichols, T. Keith; University Hospital, R. Freedman; Veterans Administration Hospital, R. Sutton; and St. Mark’s and Cottonwood Hospitals, J. Perry. We acknowledge the associated members of the Paramedic System and LDS Hospital Emergency Department, as well as the attending physicians and nurses. We recognize Sam Teichman, MD, Study Sponsor, Genentech, South San Francisco, California; and Mark Zyvoloski and Michael Fletcher, Marquette Inc., Milwaukee, Wisconsin.
REFERENCES 1. Mardcr VJ, Sbcrry S. Thrombolytic therapy: current status. N Engl J Med 1988;318:1512~1520,15851594. 2. Anderson JL. Thrombolytic and other antithrombotic therapies of the acute ischemic syndromes. In: Anderson JL ed. Critical Care Cardiology. New York: Karger 1988;15~62. 3. DeWood MA, Spores J, Notske R, Mouser LT, Burroughs R, Golden MS, Lang HT. Prcvalencc of total coronary inclusion during the early hours of transmural myocardial infarction. N Engl J Med 1980;303:897--902. 4. Davis MJ, Thomas AC. Plaque fissuring: the cause of acute myocardial infarction, sudden ischemic death, and crescendo angina. Br Heart .I 1985;53. 363-373. 5. Reimer KA, Lowe JE, Rasmussen MM, Jennings RB. The wavefront phenomenon of ischemic cell death: myocardial infarction size vs. duration of coronary occlusion in drugs. Circulntion 1977;.56:786-794. 6. Chesebro JH, Knatterud G, Roberts R, Borer J, Cohen LS, Dale” J, Dodge HT, Francis CK, Hillis D, Ludbrook P, Markis JE, Mueller H, Passamani ER, Powers ER, Rao AK, Robertson T, Ross A, Ryan TJ, Sobel BE, Willcrson J, Williams DO, Zaret BL, Braunwald E. Thrombolysis in Myocardial Infarction (TIMI) Trial, phase IA. Comparison between intravenous plasminogen activator and intravenous streptokinase. Circulation /987;76;142-154. 7. Anderson JL, Rothbard RL, Hackworthy RA, Sorensen SC, Fitzpatrick PC;, Dahl CF, Hagan AD, Browne KF, Symkoviak GP, Menlove RL, Barry WH, Eckcrson HW, Marder VJ, for the APSAC Multicenter Investigators. Multicenter reperfusion trial of intravenous anisoylatcd plasminogen streptokinase activator complex (APSAC) in acute myocardial infarction: controlled comparison with intracoronary streptokinase. J Am Coil Cardiol 1988:11:1153-1163.
8. Anderson JL, Marshall HW, Bray BE, Lutz JR, Frederick PR, Yanowitz FG, Frederick PD, Klausner SC, Hagan AD. A randomized trial of intracoronary streptokinase in the treatment of acute myocardial infarction. N Engl J Med 1983;308:1312-1318. 9. Span” JF, Sherry S. Coronary thrombolysis for evolving myocardial infarction. Drugs l984;28:465-483. 10. Sheehan FH, Mathey DG, Schofcr J, Dodge HT, Bolson EL. Factors that determine recovery of left ventricular function after thrombolysis in patients with acute myocardial infarction. Circulatron 1985;71:1121~//28. 11. Korcn G, Weiss AT, Hasin Y, Appelbaum D, Welber S, Rozeman Y, Lotan C, Moss& M, Sapoznikov D, Luria MH, Cotsman MS. Prevention of myocardial damage in acute myocardial ischemia by early treatment with intravenous streptokinase. N Engl J Med 1985313:1384-1389. 12. White HD, Norris RM, Brown MA, Takayama M, Maslowski A, Bass NM, Ormiston JA, Whitlock T. Effect of intravenous streptokinasc on left ventricular function and early survival after acute myocardial infarction. N Eng/ J Med 1987317:850-855. 13. O’Rourke M, Baron D, Keogh A, Kelly R, Nelson G, Barnes C, Raftos J, Graham K, Hillman K, Newman H, He&y .I, Woolridge J, Rivers J, White H, Whitlock R, Norris R. Limitation of myocardial infarction by early infusion of recombinant tissue-type plasminogen activator. Circulation 1988:77:13/l-1315. 14. Bassand J-P, Machccourt J, Cassagnes .I, Anguenot T, Lusson R, Bore1 E, Peycelon P, Wolf E, Ducellier D, for the APSIM Study Investigators. Multicenter trial of intravenous anisoylated plasminogen streptokinase activator complex (APSAC) in acute myocardial infarction: effects on infarct size and left ventricular function. J Am Co11 Cardiol 1989;13:988-997. 15. Gruppo Italian0 per lo Studio della Streptochinasi ncll’lnfarcto Miocardico (GISSI). Effectiveness ofintravenous thrombolytic treatment in acute myocardial infarction. Lancet 1986:1:397-401. 16. ISIS-2 Collaborative Group. Randomized trial of intravenous streptokinase, oral aspirin, both, or neither among 17,187 cases of suspected acute myocardial infarction: ISIS-2. Lancet 1988;2:349--360. 17. Maynard C, Althouse R, Olsufka M, Ritchie JL, Davis KB, Kennedy JW. Early versus late hospital arrival for acute myocardial infarction in the Western Washington thrombolytic therapy trials. Am J Cnrdiol 1989;63:1296~/300. 18. Kennedy JW, Atkins JM, Goldstein S, Jaffe AS, Lambrew CT, McIntyre KM, Mueller HS, Paraskos JA, Weaver WD. Recent changes in management of acute myocardial infarction: implications for emergency care physicians. J Am Cdl Cardiol 1988:11:446-449. 19. Ornate JP. Role of the emergency department in decreasing the time to thrombolytic therapy in acute myocardial infarction. Clin Cardiol1990;13:V-48 v-/-52. 20. Sharkey SW, Brunette DD, Ruiz E, Hession WT, Wyshanl DG, Goldcnberg IF, Hodges M. An analysis of time delays preceding thrombolysis for acute myocdrdial infarction. JAMA 1989;262:317/&3/74. 21. Grim P, Feldman T, Martin M, Donovan R, Nevins V, Childers RW. Cellular telephone transmission of 124cad clcctrocardiogrdms from ambulance to hospital. Am J Cardiol 1987;60:715-720. 22. Kennedy JW, Wcavcr WD. Potential use of thrombolytlc therapy before hospitalization. Am .I Cardiol 1989;64:8A -1lA. 23. Lee TH, W&berg MC, Brand DA, Rouan GW, Goldman L. Candidates for thrombolysis among emergency room patients with acute chest pain. Ann Intern Med /989:110:957-962. 24. Kudenchuk PJ, Ho MT, Litwin PE, Martin JS, Weaver WD. Accuracy of cardiologist vs. computerized ECG analysis in selecting patients for out-of-hospital thrombolytic therapy (abstr.). Circulntion 1989,fsuppl II)SO:II-354. 25. Blankenship JC, Almquist AK. Cardiovascular complications of thromboiytic therapy in patients with a mistaken diagnosis of acute myocardial infarction. J Am Co11 Cnrdiol 1989:14:1S79~1582. 26. Castaignc AD, Herve C, Duval-Moulin AM, Gaillard M, Dubois-Rande JL, Boesch C, Wolf M, Lellouche D, Jan F, Vernant P, Huguenard P. Prehospital use of APSAC: results of a placebo-controlled study. Am J Cardfol 1989;64:3OA33A. 27. Neuhaus K-L, Feurer W, Jeep-Tebbe S, Nicderer W, Vogt A, Tcbbe U. Improved thrombolysis with a modified dose regimen of recombinant tissue-type plasminogcn activator. J Am Co11 Cardiol 1989;14:1566-1569. 28. Weaver WD, Eisenberg MS, Martin JS, Litwin PE. Shaeffer SM, Ho MT, Kudenchuk P, Hallstrom AP, Cerquirra MD, Copass MK, Kennedy JW, Cofl LA, Ritchic JL. Myocardial infarction triage and intervention. Project-phase I: patient characteristics and feasibility of prehospital initiation of thrombolytic therapy. J Am Coil Cardiol 1990;15:925-931.
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Labros Karagounis, MD, Steve K. Ipsen, RN, Michael R. Jessop, Kirk M. Gilmore, MD, David A. Valenti, MD, Jeffrey J. Clawson, MD, Sam Teichman, MD, and Jeffrey L. Anderson, MD
To assess the impact of a field-transmitted electrocardiogram (ECG) on patients with possible acute myocardial infarction, randomized and open trials were performed with a portable electrocardiographic system coupled with a cellular phone programmed to automatically transmit EGGS to the base hospital. Consecutive patients served by the 6 units of the Salt Lake City Emergency Rescue System were studied; 71 patients were randomized to in-field EGG (n = 34) versus no ECG (n = 37). Time on scene was 16.4 f 9.7 minutes for the ECG group versus 16.1 f 7.0 minutes for the non ECG group (difference not significant). lime of transport averaged 18.2 f 9.9 and 17.6 f 13.1 minutes, respectively (difference not significant). Six of 34 patients with in-field ECG showed acute myocardial infarction, qualified for and received thrombolytic therapy at 46 f 12 minutes after hospital arrival (range 30 to 60) compared with 103 f 44 minutes (p
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From the Department of Medicine, Division of Cardiology and LDS Hospital, Salt Lake City, Utah. This study was supported in part by a grant from Genentech Inc., South San Francisco, California. Manuscript received January 3 1, 1990; revised manuscript received and accepted May 11, 1990. Address for reprints: Jeffrey L. Anderson, MD, Division of Cardiol;;:y,),DS Hospital, 8th Avenue and C Street, Salt Lake City, Utah
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n the past decade, thrombolytic reperfusion has become established therapy in acute myocardial infarction (AMI),1,2 now known to be precipitated by coronary thrombosis3,4 and to evolve rapidly after coronary occlusion.5 Early application of therapy has been shown to be important to achieve early reperfusion6,7 to improve left ventricular function and decrease infarct sizes-l4 and to decrease mortality.15-l7 Treatment given in <2 to 4 hours after symptom onset has consistently yielded greater benefit than later treatmentg-l 1,15+17 and even earlier therapy (within 1 to 2 hours) is desirable 11,15,17 Delays in administering thrombolytic therapy include not only patient delays and transport time, but also hospital delays after arrival.18-20 Paramedic transmission of an in-field, 1Zlead electrocardiogram (ECG) to physicians at the base hospital is a newly available approach to decreasing delay to AM1 diagnosis*l and treatment.22,23 However, additional experience from controlled studies would be useful to establish the reliability and impact of in-field ECG before embarking on its extensive use, including the guidance of in-field thrombolytic therapy. 22-24This study assessesthe feasibility and impact of field-transmitted ECG on the prehospital and early hospital care of patients with suspected AM1 in a randomized design. METHODS
The purpose of phase I of the Field Ambulance Study of Thrombolysis in Myocardial Infarction (FAST-MI) was to show the feasibility and advisability of using an in-field ECG to direct the initiation of thrombolytic therapy in a randomized, dry-run study design before initiating Phase II (currently underway) of the treatment study (initiating therapy in-field versus in-hospital). Study objectives and hypotheses: Specific study objectives were the following: to assessthe feasibility of obtaining and transmitting the in-field electrocardiogram (ECG) to the base hospital; to evaluate and compare the natural history of in-field evaluation and transport of chest pain patients both with and without knowledge of the field-transmitted ECG; and to determine the reliability and “safety” of paramedic/emergency physician diagnosis of AM1 and triage to thrombolytic therapy. We hypothesized that the in-field ECG could be obtained successfully and without substantial delay and that appropriate patient triage could be made. The study was approved by the LDS Hospital Institutional
Review Board and by the Utah State Department of Health, Emergency Services Division. Study design: The study was designed in 2 partsan education phase and a study phase. Education phase: The Salt Lake City Paramedic Rescue Units serve a population base estimated at 600,000 people. Initially, 2 training sessions were conducted in a prefield setting for the 6 paramedic units (50 personnel). Subsequently, in-field training was provided at least twice for each paramedic unit. Concurrently, training of emergency room physicians and nurses was undertaken in receiving and reviewing fieldtransmitted ECGs and in randomizing patients to “mock” in-field initiated versus emergency room initiated therapy. A start-up phase was then undertaken, consisting of a series of consecutive ECGs in chest pain patients (2 10 per paramedic unit) to show the ability to correctly use the equipment. Study phase: After study initiation, consecutively evaluated patients were selected for an ECG based on the clinical (paramedic’s) suspicion of possible AM1 (i.e., suggestive chest pain) alone. (Further clinical evalassessment of other inclusion/exclusion uation-e.g., criteria for “mock” thrombolytic therapy-was considered afterward in patients with a diagnostic ECG.) Paramedics randomized “ECG-eligible” patients at the scene to obtain or not to obtain an in-field ECG by opening a sealed envelope. Records were kept of the actual time spent in attending to the patient at the scene, the time in transport and the time to thrombolytic therapy if given after hospital arrival. Phase I was prospectively planned to run for 3 months or until >50 patients over the age of 35 years were evaluated. A flow chart of the study is shown in Figure 1. In-field electrocardiographic assessment: An infield la-lead ECG was performed by means of a battery-powered portable electrocardiograph weighing 28 lbs (Marquette, Inc.). The ECG was usually performed on-scene, but occasionally in-transport. Both an onscene 124ead ECG printout and a hospital printout, both with ECG interpretation (Marquette Diagnosis Program Software), were provided by the system with minimal delay (
A comparison between initial (emergency physician/ paramedic) and retrospective (cardiologist) assessment of AM1 was also made. Averaged data are generally presented as mean f standard deviation. A p value KO.05 was considered statistically significant. RESULTS Randomized phase: The randomized portion of Phase I was conducted over a period of 3 months (December 1988 to March 1989). A total of 180 calls were received for chest pain; 71 (39%) of these patients were
METHODS PARAMEDICS RESPOND PATIENTS WITH CHEST PAIN 1
TO
RANDOMIZED TO IN-FIELD ECG +
-
1
’ __)
STANDARD
CARE
ECG TRANSMITTED TO ER REVIEW BY M.D. DIAGNOSIS MADE + t
I STOP
REVIEW INCLUSION/EXCLUSION CRITERIA WITH M.D. + t
I __c
“MOCK”RANDOMIZATION
TO THERAPY
MOCK IN-FIELD TPA THERAPY
TPA
FlGtJRE 1. Flow chart showing sion tree. ECG = electrocardiogram;
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judged by paramedics to represent possible ischemia and were randomized; 34 were randomized to receive in-field ECG and 37 to no ECG. Impact of in-field electrocardiogram on prehospital time: Assignment to the in-field ECG group caused a
negligible overall impact on time spent at the scene (Figure 3) and on time in transport (Figure 4). Time spent on the scene averaged 16.4 f 9.7 minutes for the in-field ECG group (n = 34) and 16.1 f 7.0 minutes for the nonECG group (n = 37, difference not significant). The range of times at the scene was 2 to 36 minutes for the ECG group and 4 to 50 minutes for the nonECG group. Transport time from the scene to the hospital averaged 18.2 f 1.7 minutes in the ECG group and 17.6 f 2.2 minutes in the nonECG group. The range of transport times was 4 to 40 minutes for the ECG group and 3 to 50 minutes for the nonECG group. Diagnosis and confirmation of acute myocardial infarction based on in-field electrocardiogram: A total of
6 (17%) of the 34 patients receiving in-field ECG were
diagnosed by the emergency physician/paramedic team as having an AMI. On retrospective (cardiologist) electrocardiographic review, the diagnosis was confirmed in 5 and was equivocal in 1. The ECGs were confirmed to show no MI in the other 28. Two other patients were diagnosed as having AMI by in-field ECG among 16 additional patients with possible AM1 studied in the start-up phase, before beginning the randomization protocol. Of these 8 patients with AMI, 3 were ineligible, 2 because of age 176 years and 1 because of cardiac arrest requiring resuscitation measures, lime to thrombolytic therapy after in-field electrocardiogram: Of patients receiving in-field ECG, 5
showing AM1 qualified for and received thrombolytic therapy in-hospital. In these patients, the time from hospital arrival to initiation of therapy averaged 48 f 12 minutes (range, 30 to 60 minutes). This compares favorably with 103 f 44 minutes (p
FAST - MI (Field
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FIGURE 2. Paramedic information and questionnaire form for in-field patient screening and enrollment. FAST-MI = Field Ambulance Study of Thrombolysis in Myocardial Infaction.
6. IrSynok>8OmdS2CO? 7. Is Diilit
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REMARKS:
29 minutes for 6 concurrently treated patients receiving thrombolytic therapy during the 3-month period of the Phase I study but not having in-field ECG. DISCUSSION Study summary: Phase I of our FAST-MI study showed the feasibility, efficiency and reliability of in-field ECG acquisition by a paramedic/emergency physician team in evaluating chest pain calls for a representative urban/suburban population. The equipment was easily adapted to paramedic use. During the education and start-up phases, a number of minor technical difficulties were addressed and overcome. In the randomized phase, increases beyond the previous average of 35 minutes total time at the scene and in transport were minimal (nonsignificant). Agreement between emergency physician (prospective) and cardiologist (retrospective) diagnosis of AM1 was good; no false negative diagnoses and only 1 equivocal false positive diagnosis occurred. However, these numbers are small and further observations are needed. Importantly, the time from hospital arrival to initiation of thrombolytic therapy was decreased by about 40 minutes compared with that in our recent study experience.’ A decrease of 20 minutes to therapy was also achieved when compared with a concurrent group of treated patients not receiving in-field ECG.
easons
for
delay
in
initiating
thrombolytic
thera-
Delays to thrombolytic therapy after hosptial arrival appear to contribute more to overall delay to thrombolytic therapy than either transport time or patient delay in seeking medical assistance.19 In a recent Minnesota study,20 in-hospital delays accounted for more than half of the total time from onset of symptoms to initiation of thrombolysis. Of the total hospital delay of 90 minutes, 20 minutes were due to the initial ECG. Other delays were less when drugs were administered in the emergency department (47 minutes) than after transfer to the coronary care unit (82 minutes). Similar hospital delays were observed in both our recent historical experience (108 minutes)’ and in an earlier Western Washington trial (102 minutes).22 In-hospital delays in initiating therapy include the following: administrative reasons (registration, triage, overcrowding/bed problems); diagnostic evaluation (nurse, physician evaluation; ECG, blood, x-ray tests); therapeutic needs (starting intravenous lines); medical/ political reasons (consultations among private physician, cardiologist, house staff); and pharmacy delays (obtaining, mixing, administering drug). lg py:
Impact
of in-field
electrocardiogram
on hospital
30
20
10
C
In Field ECG (n=34)
No ECG (rl=37)
FIGURE 3. Paramedic time (mean f standar spent on-scene for patient pickup in groups randomix ceiva an in-field EGG and no ECG.
de-
Transmission of an in-field ECG alerts the hospital-based medical care team in advance that an incoming patient has an AMT. These hospital delays may
lays:
In-Field ECG (n=34)
No ECG (n=37)
FlGURE 4. Transport time (mean rfr standard deviation [min]) om scene of patient pickup to hospital in groups randomize ts receive an in-field e~ectr~ardi~gram (ECG) and no EGG. TH IE AMERICAN
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then be shortened because the process of preparing for thrombolytic therapy may begin well in advance of patient arrival (about 30 minutes in our study). The time saved to the first ECG appears to be directly passed on in time saved to thrombolytic therapy. In the Seattle experience, in-hospital delay was decreased from 102 to 46 minutes after instituting an in-field ECG system22 (Figure 5). Similarly, we saw a decrease from 108 to 48 minutes (Figure 5). Part of this decrease may also reflect better training of emergency room personnel in screening patients and greater involvement in initiating therapy, as suggested by the decrease in delay noted recently in our studies (108 to 68 minutes) and in others’,20,22even in patients not receiving in-field ECG. Demography of chest pain patients evaluated by paramedics: Only a small minority of patients with
chest pain attended to by paramedics have electrocardiographic and clinical characteristics of AM1 that qualify them for thrombolytic therapy, an observation of importance to the planning of future intervention studies. In our study, 39% (71 of 180) of total chest pain calls were judged clinically to represent possible AM1 and of these, only 17% receiving in-field ECG showed AMI. Thus, only about 7% of chest pain calls were identified in-field as an AMI. Of the 8 patients showing AM1 by in-field ECG, 5 qualified for thrombolytic therapy (63% of AM1 patients but only 3 to 4% of all chest pain calls). Similarly, in the larger Seattle experience, 3% (83/2,465) of patients calling with chest pain met criteria for possible prehospital thrombolytic therapy.22 Patients were excluded most commonly because of a nondiagnostic ECG, pain >6 hours, age 175
Fast-Ml IF-ECG (n=6)
Historica Controls (n=51)
Western MIT1 Project Washingtor Phase 1 2nd Trial Seattle (n=89)
FIGURE 5. Times to thrombolytic therapy after hospital arrival. Left, patients with acute myocardial infarction who received an in-field electrocardiogram (IF-ECG) compared with recent historical control patients (right) not getting IF-ECG; Right, a literature comparison also showing treatment times for patients receiving IF-ECG (leff hand bar) and historical control subjects without IF-ECG (right hand bar).
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years and hypertension. 22 Further, of patients who gradually developed an AM1 in-hospital, only 20% met prehospital criteria for therapy and 22% more qualified for therapy after initial hospital evaluation. Similarly, in a New England study, only 23% (261 of 1,118) of patients who eventually developed an AM1 were candidates for thrombolysis in the emergency room based on age 175 years, pain for <4 hours and a diagnostic ECG,23 before accounting for exclusions due to contraindications to thrombolysis. Of some concern was their estimate that for every patient treated with true positive findings (based on the interpretation of a single ECG), 1 to 2 patients with false positive results might be treated. Fortunately, this last conjecture has not been substantiated in clinical trials in which, generally, 195% of patients have subsequently showed an
AMI.7,‘5,‘6
Implications for in-field thrombolysis: Our study supports the feasibility of initiating thrombolytic therapy in-field but also emphasizes the need for controlled trials before embracing in-field therapy. Our experience in the FAST-MI is consistent with that of others that suggest that a good, although not perfect, correlation exists between emergency physician/computer diagnosis of AM1 and cardiologist (retrospective) diagnosis. Using similar technology, the University of Washington group achieved a 70% sensitivity and a 100% specificity for a computer-based diagnosis algorithm (Marquette System Diagnosis Program) of AMI. Although this exceptional specificity will require further confirmation, the results do suggest that a computer based system may help prevent over-diagnosis of AMI’9,23 and potentially hazardous25 overuse of thrombolytic therapy by emergency room personnel less experienced in ECG interpretation. Improved accuracy in diagnosis and therapy might also be achieved by having well-trained physicians travel with paramedic units. 11,26However, this approach does not appear to be practical in the United States. Another approach to optimizing both safety and efficacy may be to use a small “priming” dose of a shortacting thrombolytic agent in the field to begin the process of thrombolysis. Review of the decision to give fulldose therapy could then be made in the emergency room and therapy effectively terminated if desired. Tissue plasminogen activator (alteplase) has the properties of excellent hemodynamic tolerance, rapidly acting thrombolytic effect and a short half-life. The efficacy and safety of “front-loaded” (bolus initiated) regimens of alteplase have been recently evaluated and appear to be promising.27 Based on these characteristics of alteplase, we believe that the administration of an in-field loading bolus (i.e., 20 mg) by paramedics, followed by continuation of a full-dose regimen upon hospital arrival, represents an appealing regimen to test (FAST-MI, Phase II). However, given the potentially dire consequences of misapplication of thrombolytic therapy25 and both medical and legal concerns about paramedic administration of thrombolytic therapy, we believe that streamlined in-hospital (emergency department) initiation of therapy should be currently viewed as the best
strategy for initiating thrombolytic therapy.rg Whether or not in-field initiation of therapy is safe and will give additional benefit must be addressed in ongoing or future studies.22,2s Acknowledgment/Appendix: We recognize the participation and performance of the following rescue units of the Salt Lake City Paramedic System: numbers 2, 3, 5, 7, 8 and 11. Hospitals receiving patients from the Salt Lake Paramedic System include the following: LDS Hospital; Holy CrossHospital; University of Utah Hospital; Veterans Administration Hospital; St. Marks’ Hospital; Cottonwood Hospital; and Lakeview Hospital. Principal investigators of the FAST-MI study were the following: Study principal investigator, Jeffrey L. Anderson; Co-investigator, Labros Karagounis; Study Coordinator, Steven Ipsen, RN; Co-coordinator, Ann Allen; and Graphics, John Carlquist, PhD. Specific hospital investigators were the following: LDS Hospital, L. Karagounis, J. Anderson; Holy Cross Hospital, S. Nichols, T. Keith; University Hospital, R. Freedman; Veterans Administration Hospital, R. Sutton; and St. Mark’s and Cottonwood Hospitals, J. Perry. We acknowledge the associated members of the Paramedic System and LDS Hospital Emergency Department, as well as the attending physicians and nurses. We recognize Sam Teichman, MD, Study Sponsor, Genentech, South San Francisco, California; and Mark Zyvoloski and Michael Fletcher, Marquette Inc., Milwaukee, Wisconsin.
REFERENCES 1. Mardcr VJ, Sbcrry S. Thrombolytic therapy: current status. N Engl J Med 1988;318:1512~1520,15851594. 2. Anderson JL. Thrombolytic and other antithrombotic therapies of the acute ischemic syndromes. In: Anderson JL ed. Critical Care Cardiology. New York: Karger 1988;15~62. 3. DeWood MA, Spores J, Notske R, Mouser LT, Burroughs R, Golden MS, Lang HT. Prcvalencc of total coronary inclusion during the early hours of transmural myocardial infarction. N Engl J Med 1980;303:897--902. 4. Davis MJ, Thomas AC. Plaque fissuring: the cause of acute myocardial infarction, sudden ischemic death, and crescendo angina. Br Heart .I 1985;53. 363-373. 5. Reimer KA, Lowe JE, Rasmussen MM, Jennings RB. The wavefront phenomenon of ischemic cell death: myocardial infarction size vs. duration of coronary occlusion in drugs. Circulntion 1977;.56:786-794. 6. Chesebro JH, Knatterud G, Roberts R, Borer J, Cohen LS, Dale” J, Dodge HT, Francis CK, Hillis D, Ludbrook P, Markis JE, Mueller H, Passamani ER, Powers ER, Rao AK, Robertson T, Ross A, Ryan TJ, Sobel BE, Willcrson J, Williams DO, Zaret BL, Braunwald E. Thrombolysis in Myocardial Infarction (TIMI) Trial, phase IA. Comparison between intravenous plasminogen activator and intravenous streptokinase. Circulation /987;76;142-154. 7. Anderson JL, Rothbard RL, Hackworthy RA, Sorensen SC, Fitzpatrick PC;, Dahl CF, Hagan AD, Browne KF, Symkoviak GP, Menlove RL, Barry WH, Eckcrson HW, Marder VJ, for the APSAC Multicenter Investigators. Multicenter reperfusion trial of intravenous anisoylatcd plasminogen streptokinase activator complex (APSAC) in acute myocardial infarction: controlled comparison with intracoronary streptokinase. J Am Coil Cardiol 1988:11:1153-1163.
8. Anderson JL, Marshall HW, Bray BE, Lutz JR, Frederick PR, Yanowitz FG, Frederick PD, Klausner SC, Hagan AD. A randomized trial of intracoronary streptokinase in the treatment of acute myocardial infarction. N Engl J Med 1983;308:1312-1318. 9. Span” JF, Sherry S. Coronary thrombolysis for evolving myocardial infarction. Drugs l984;28:465-483. 10. Sheehan FH, Mathey DG, Schofcr J, Dodge HT, Bolson EL. Factors that determine recovery of left ventricular function after thrombolysis in patients with acute myocardial infarction. Circulatron 1985;71:1121~//28. 11. Korcn G, Weiss AT, Hasin Y, Appelbaum D, Welber S, Rozeman Y, Lotan C, Moss& M, Sapoznikov D, Luria MH, Cotsman MS. Prevention of myocardial damage in acute myocardial ischemia by early treatment with intravenous streptokinase. N Engl J Med 1985313:1384-1389. 12. White HD, Norris RM, Brown MA, Takayama M, Maslowski A, Bass NM, Ormiston JA, Whitlock T. Effect of intravenous streptokinasc on left ventricular function and early survival after acute myocardial infarction. N Eng/ J Med 1987317:850-855. 13. O’Rourke M, Baron D, Keogh A, Kelly R, Nelson G, Barnes C, Raftos J, Graham K, Hillman K, Newman H, He&y .I, Woolridge J, Rivers J, White H, Whitlock R, Norris R. Limitation of myocardial infarction by early infusion of recombinant tissue-type plasminogen activator. Circulation 1988:77:13/l-1315. 14. Bassand J-P, Machccourt J, Cassagnes .I, Anguenot T, Lusson R, Bore1 E, Peycelon P, Wolf E, Ducellier D, for the APSIM Study Investigators. Multicenter trial of intravenous anisoylated plasminogen streptokinase activator complex (APSAC) in acute myocardial infarction: effects on infarct size and left ventricular function. J Am Co11 Cardiol 1989;13:988-997. 15. Gruppo Italian0 per lo Studio della Streptochinasi ncll’lnfarcto Miocardico (GISSI). Effectiveness ofintravenous thrombolytic treatment in acute myocardial infarction. Lancet 1986:1:397-401. 16. ISIS-2 Collaborative Group. Randomized trial of intravenous streptokinase, oral aspirin, both, or neither among 17,187 cases of suspected acute myocardial infarction: ISIS-2. Lancet 1988;2:349--360. 17. Maynard C, Althouse R, Olsufka M, Ritchie JL, Davis KB, Kennedy JW. Early versus late hospital arrival for acute myocardial infarction in the Western Washington thrombolytic therapy trials. Am J Cnrdiol 1989;63:1296~/300. 18. Kennedy JW, Atkins JM, Goldstein S, Jaffe AS, Lambrew CT, McIntyre KM, Mueller HS, Paraskos JA, Weaver WD. Recent changes in management of acute myocardial infarction: implications for emergency care physicians. J Am Cdl Cardiol 1988:11:446-449. 19. Ornate JP. Role of the emergency department in decreasing the time to thrombolytic therapy in acute myocardial infarction. Clin Cardiol1990;13:V-48 v-/-52. 20. Sharkey SW, Brunette DD, Ruiz E, Hession WT, Wyshanl DG, Goldcnberg IF, Hodges M. An analysis of time delays preceding thrombolysis for acute myocdrdial infarction. JAMA 1989;262:317/&3/74. 21. Grim P, Feldman T, Martin M, Donovan R, Nevins V, Childers RW. Cellular telephone transmission of 124cad clcctrocardiogrdms from ambulance to hospital. Am J Cardiol 1987;60:715-720. 22. Kennedy JW, Wcavcr WD. Potential use of thrombolytlc therapy before hospitalization. Am .I Cardiol 1989;64:8A -1lA. 23. Lee TH, W&berg MC, Brand DA, Rouan GW, Goldman L. Candidates for thrombolysis among emergency room patients with acute chest pain. Ann Intern Med /989:110:957-962. 24. Kudenchuk PJ, Ho MT, Litwin PE, Martin JS, Weaver WD. Accuracy of cardiologist vs. computerized ECG analysis in selecting patients for out-of-hospital thrombolytic therapy (abstr.). Circulntion 1989,fsuppl II)SO:II-354. 25. Blankenship JC, Almquist AK. Cardiovascular complications of thromboiytic therapy in patients with a mistaken diagnosis of acute myocardial infarction. J Am Co11 Cnrdiol 1989:14:1S79~1582. 26. Castaignc AD, Herve C, Duval-Moulin AM, Gaillard M, Dubois-Rande JL, Boesch C, Wolf M, Lellouche D, Jan F, Vernant P, Huguenard P. Prehospital use of APSAC: results of a placebo-controlled study. Am J Cardfol 1989;64:3OA33A. 27. Neuhaus K-L, Feurer W, Jeep-Tebbe S, Nicderer W, Vogt A, Tcbbe U. Improved thrombolysis with a modified dose regimen of recombinant tissue-type plasminogcn activator. J Am Co11 Cardiol 1989;14:1566-1569. 28. Weaver WD, Eisenberg MS, Martin JS, Litwin PE. Shaeffer SM, Ho MT, Kudenchuk P, Hallstrom AP, Cerquirra MD, Copass MK, Kennedy JW, Cofl LA, Ritchic JL. Myocardial infarction triage and intervention. Project-phase I: patient characteristics and feasibility of prehospital initiation of thrombolytic therapy. J Am Coil Cardiol 1990;15:925-931.
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