PREHOSPITAL ADMINISTRATION OF TENECTEPLASE FOR ST-SEGMENT ELEVATION MYOCARDIAL INFARCTION IN A RURAL EMS SYSTEM

Joseph S. Crowder, MHS, NREMTP, Michael W. Hubble, PhD, MBA, NREMTP, Sanjay Gandhi, MD, Henderson McGinnis, MD, Stacie Zelman, MD, William Bozeman, MD, James Winslow, MD
ABSTRACT Introduction. In the setting of ST-segment elevation myocardial infarction (STEMI), early reperfusion yields better patient outcomes. Emergency medical services (EMS) is the rst medical contact for half of the aficted population, and prehospital thrombolysis may result in considerably faster reperfusion compared with percutaneous coronary intervention (PCI) in rural settings. However, there are few reports of prehospital thrombolysis in rural EMS systems. Objective. To describe a rural EMS systems experience with tenecteplase in STEMI. Methods. Data were retrospectively abstracted from the medical records of patients receiving tenecteplase using standard chart review guidelines. Primary outcomes included time saved by EMSinitiated thrombolysis, aborted infarctions, serious bleeding events, and in-hospital mortality. Secondary outcomes included reinfarction, rescue angioplasty, and appropriateness of treatment. Time savings was dened as transport time after tenecteplase administration plus 90 minutes, which is the typical door-to-balloon time for PCI laboratories. Aborted infarction was dened as resolution of the cumulative STsegment elevation to 50% of that on the initial electrocardiogram (ECG) within two hours after treatment, and peak creatine kinase (CK)/CK-MB levels less than or equal to twice the upper limit of normal. Results. Seventy-three patients received prehospital tenecteplase; this treatment was determined to be appropriate in 86.4% of cases. The mean patient age was 59 years, and 71.6% of the patients were male. Mean ( standard deviation) scene-arrival-to-drug time was 26.2 (11.4) minutes, the mean scene-arrival-tohospital-arrival time was 73.0 (20.6) minutes, and the mean transport time was 46.0 ( 11.1) minutes. Tenecteplase was administered 35.9 (25.0) minutes prior to hospital arrival, and the estimated reperfusion time savings over PCI was 125.9 (25.0) minutes. Aborted infarctions were observed in 24.1% of patients, whereas 9.6% suffered reinfarction, 47.9% underwent rescue angioplasty, and 16.7% required coronary artery bypass grafting (CABG). Serious bleeding events occurred in 15 patients (20.5%), and four (5.5%) died. Conclusion. In this retrospective review of rural STEMI patients, tenecteplase was administered 36 minutes prior to hospital arrival, saving approximately two hours over typical PCI strategies and resulting in aborted infarctions in one-fourth of patients. In a rural setting with lengthy transport times to PCI facilities, tenecteplase appears to be a feasible prehospital intervention. Randomized controlled trials are needed to fully evaluate the safety and effectiveness of this intervention prior to widespread adoption. Ke ywords thrombolytic; myocardial infarction; emergency medical services; prehospital; paramedic; tenecteplase; STEMI; rural EMS PREHOSPITAL EMERGENCY CARE 2011;15:499505

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INTRODUCTION
Received December 19, 2010, from the Emergency Medical Care Program (JSC, MWH), Western Carolina University, Cullowhee, North Carolina; and the Departments of Cardiology (SG) and Emergency Medicine (HM, SZ, WB, JW), Wake Forest University Baptist Medical Center, Winston-Salem, North Carolina. Revision received April 18, 2011; accepted for publication April 18, 2011. The authors acknowledge the follow persons for their assistance with this project: Edward Price, BS, EMT-P, Operations Ofcer, Wilkes County Emergency Medical Services; Tammy Rhoades, Administrative Assistance, Wilkes County Emergency Medical Services; Daria Kring, PhD, RN-BC, Director of Nursing Research, Forsyth Medical Center; Jeannie Kiger, RN, BBA, CPHQ, CV Outcomes Manager, Forsyth Medical Center; and Bob Greco, Operations Manager, Advanced Imagine Solution, Inc. This project received no external funding. The authors report no conicts of interest. The authors alone are responsible for the content and writing of the paper. Reprints are not available. Address correspondence to: Joseph S. Crowder, MHS, NREMTP, 9677 Cleatwood Drive, Leland, NC 28451. e-mail: nallyying@ hotmail.com doi: 10.3109/10903127.2011.598609

Over the past two decades, cardiovascular disease mortality rates have decreased substantially, in part because of better standards of care and secondary prevention.1 In the acute phase, timely reperfusion of the occluded coronary vessel, using either brinolysis or percutaneous coronary intervention (PCI), is the mainstay of treatment for ST-segment elevation myocardial infarction (STEMI) patients.1,2 With either of these treatment approaches, the time from symptom onset to the reestablishment of blood ow through the affected coronary artery is a key determinant of patient outcome.2 Primary PCI can achieve higher artery patency than in-hospital brinolytics and is the approach preferred by consensus guidelines when medical-contact-to-balloon time is less than 90 minutes.2 However, the realized benet of direct transport of patients to a PCI center is limited by delays to reperfusion time that often exceed 90 minutes. Often, such delays can be attributed to the geographic separation of the patient and the PCI center, and is 499

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particularly problematic in rural areas. Only 25.5% of acute care hospitals in the United States have PCI facilities, and patients may require transfer from a local hospital to the nearest PCI center.3 As an alternative strategy, emergency medical services (EMS) ambulances may bypass the local hospital in favor of direct transport to a PCI center. However, reestablishing vessel patency may still be delayed because of ambulance transport times and internal delays at the PCI center. Nallamothu and Bates demonstrated that the mortality benet of primary PCI is lost when medical-contact-toballoon time is greater than 62 minutes as compared with brinolysis door-to-needle time.4 Unfortunately, in large-scale trials, the time from symptom onset to the initiation of therapy at a hospital has remained unchanged at 1.5 to 6.0 hours,5 and fewer than 5% of patients are treated within the 62-minute window of opportunity.2,4 Emergency Medical Services (EMS) is the rst medical contact for half of the aficted population, and prehospital thrombolysis may result in considerably faster reperfusion compared with percutaneous coronary intervention (PCI) in rural settings. Given the clear association between time to reperfusion and patient outcome, as well as logistic difculties in the timely delivery of STEMI patients to a PCI laboratory, compounded by treatment delays encountered at the PCI laboratory, a rural EMS system instituted prehospital thrombolysis in carefully selected STEMI patients in 2001. The objective of this study was to describe the use of tenecteplase in a case series of STEMI patients encountered by a rural EMS system with long transport times to a PCI laboratory.

are staffed with at least one paramedicwith the additional crew member being an emergency medical technician (EMT), an EMT-Intermediate, or a second paramedicand all paramedics within the system are trained in 12-lead electrocardiogram (ECG) interpretation. A community hospital is located in the county, but no interventional cardiovascular services are available. The closest major medical facilities capable of interventional cardiovascular services require a 4575minute ground transport from much of Wilkes County to either a large teaching hospital or a tertiary care facility that is community-based. Consecutive patients presenting with an onset of chest pain that met criteria for prehospital thrombolytics (Table 1) and received tenecteplase between January 1, 2001, and April 1, 2010, were eligible for inclusion in the study. Patients with incomplete medical records that precluded sufcient analysis were excluded from the study.

Treatment Protocol
As part of routine treatment protocols for Wilkes County EMS, paramedics perform a physical examination and obtain an appropriate history on all chest pain patients. The standard chest pain treatment algorithm includes 12-lead ECG, oxygen, 324 mg of aspirin, 0.4 mg of sublingual nitroglycerin (nitro) spray or tablet, followed by 1 inch of nitro paste, 24 mg of intravenous morphine sulfate for pain, and ondansetron or promethazine for nausea and vomiting as needed, as well as metoprolol in the setting of hypertension. Patients are evaluated for thrombolytic eligibility utilizing a standardized form that reviews both exclusion and inclusion criteria, including a screen for occult hemorrhage. In the rst quarter of 2004, the thrombolytic protocol was revised to replace heparin with enoxaparin and also to add clopidogrel. The treatment protocol did not dictate how much assessment/treatment was to be performed on scene vs. during transport. After obtaining the initial 12-lead ECG, the ECG of a patient with suspected STEMI is transmitted to a receiving station located at the medical control hospital. In the beginning of this study, this transmission was linked from the ECG monitor and a receiving station by Physio-Control RS 100 (Physio-Control, Inc., Redmond, WA). This was later replaced with Inmotion Gateway (Inmotion Technology, New Westminster, BC, Canada). The on-duty emergency physician (most of the emergency physicians are emergency medicine board-certied) evaluates the ECG and verbally reviews the assessment ndings and history of present illness with the paramedic. If indicated, tenecteplase is administered at the direction of the physician. From 2001 to 2005, the majority of the patients receiving prehospital tenecteplase were transported to the local

METHODS
This retrospective case series design describes the nineyear experience of a rural EMS system in the use of tenecteplase in the prehospital management of patients experiencing acute STEMI. This study received institutional review board approval from Western Carolina University as well as approval from all participating hospitals.

Setting and Patient Selection

Wilkes County is a rural county located in northwestern North Carolina with a land mass of 760 square miles and total population of 67,182. Cardiovascular disease deaths account for 20% of the total deaths in the county, second only to cancer deaths in 2008.6 Wilkes County EMS is a third-service, county-based EMS system with an annual call volume of 10,525 in 2009. This emergency medical service deploys four 24hour ambulances, one 12-hour ambulance, and one quick-response vehicle providing primary 9-1-1, interfacility, and nonemergency transports. All vehicles

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TABLE 1. Wilkes County Emergency Medical Services Inclusion and Exclusion Criteria for Tenecteplase Administration
Inclusion Exclusion

Chest pain (15 minutes12 hours) Age: males >35 years, females >40 years Alert and oriented to person, place, and time 12-Lead ECG meets criteria for AMI

Active internal bleeding CNS neoplasm, AV malfunction, or CNS aneurysm CNS surgery in past two months Severe, uncontrolled hypertension (> SBP 180/DBP110 mmHg) Bleeding disorder Aortic dissection: >15-mmHg difference in SBP between the right and left arms

AMI = acute myocardial infarction; AV = arteriovenous; CNS = central nervous system; DBP = diastolic blood pressure; ECG = electrocardiogram; EMS = emergency medical services; SBP = systolic blood pressure.

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hospital, and transfer arrangements to the regional medical center were made thereafter. Beginning in 2006, patients who received tenecteplase were transported directly to a medical facility with PCI capabilities. Patients who were considered critical and unstable were transported to the local hospital for stabilization, and additional transport arrangements were completed if applicable.

Data Extraction
Study investigators strived to adhere to standard chart review methodology.7 The personnel used as chart abstractors included the principal investigator, who is an EMT-paramedic (EMT-P), as well as attending-level physicians. All abstractors received the same training on how to abstract the data. Data were abstracted directly to an Excel (Microsoft Corp., Redmond, WA) spreadsheet, and an identical spreadsheet was used by all abstractors. The principal coinvestigator at the academic center also regularly monitored and reviewed the data abstraction of all abstractors. At the end of data abstraction, the principal investigator and the coinvestigator reviewed all abstracted data for accuracy. The abstractors who reviewed the 12-lead ECGs were blinded as to the nal diagnosis of the patient. Follow-up data on patient outcomes were obtained from the participating hospitals. The ECGs from the patient record were analyzed independently by one blinded cardiologist and one blinded emergency physician external to the EMS system for the purpose of determining the appropriateness of tenecteplase administration. In the event of discordant opinion between physicians, an additional blinded emergency physician was used to evaluate the ECGs. An additional physician performed ST-segment deviation calculations. All physicians involved with ECG review are coauthors of this study.

Outcome Measures and Statistical Analysis

The primary end points of the study included a description of the patients receiving prehospital tenecteplase, the amount of time saved by prehospital administration of tenecteplase compared with

estimated in-hospital PCI times, aborted infarctions, serious bleeding events, and in-hospital mortality. Secondary end points included reinfarction, rescue angioplasty, and appropriateness of therapy. For this study, time savings was dened as transport time after tenecteplase administration plus 90 minutes, which is the typical door-to-balloon time for PCI laboratories.2,8 This door-to-balloon time is a target achieved by 80% of hospitals as reported by the Hospital Quality Alliance and the National Cardiovascular Data Registrys CathPCI Registry.8 For the purposes of calculating transport times and reperfusion time savings, only the subset of patients transported directly to the PCI facility were used. Serious bleeding complications were dened as a decrease in hemoglobin level of 3 g/dL from baseline, any blood transfusion not associated with coronary artery bypass grafting (CAGB), or intracranial hemorrhage (ICH). The number of aborted infarctions was calculated based on the denition described by Taher et al.9 : 1) resolution of the cumulative ST-segment elevation to less than or equal to 50% of the initial ECG within two hours after treatment using the STRES criteria10 and 2) peak creatine kinase (CK) or CKMB level less than or equal to twice the upper limit of normal. A patient was considered to have experienced reinfarction if there was a subsequent infarction (based on ECG and cardiac enzyme results) between resolution of the primary incident and prior to hospital discharge. Given the retrospective study design, we were unable to differentiate between rescue angioplasty and diagnostic angioplasty for all cases. Consequently, any angioplasty performed within three hours after tenecteplase administration was considered to be rescue angioplasty. In addition to the primary and secondary end points, descriptive statistics were compiled regarding patient demographics, treatment and transport times, coronary artery involvement, and ischemia severity using sigma ST deviation (the sum of ST elevation added to the sum of ST depression) as described by Schroder et al.11 Abstracted data were compiled and analyzed using SPSS version 18 (SPSS Inc., Chicago, IL). Continuous variables are presented as means ( standard deviation [SD]), and categorical variables are

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presented using relative frequency distributions and percentages. Time intervals are presented as means (SD). Continuous variables were compared with Students t-test, with statistical signicance established at p 0.05.

TABLE 3. Frequency of Myocardial Infarction Pattern Based on Initial Prehospital Electrocardiogram Interpretation
AMI Pattern Frequency (N = 73) Percent

RESULTS
Between January 1, 2001, and April 1, 2010, a total of 75 patients were determined to have STEMI and received tenecteplase based on the paramedic screening. Two patients were excluded because of incomplete medical records, leaving a total of 73 patients for nal analysis. Sixty-six (66) of the included patients had prehospital ECGs for review, with seven ECGs missing from the collected prehospital medical record. The mean age of the study participants was 59 (11.4) years, with male patients accounting for 71.6% of the sample. The mean delay from symptom onset, dened as the patients rst episode of chest pain, to requesting EMS assistance was 91.7 (123.6) minutes. The mean response time was 13.7 (8.0) minutes, which was calculated as the time interval between call dispatch and arrival on scene. The mean interval between scene arrival and scene departure was 26.97 (9.4) minutes, and the mean scene-arrival-todrug time was 26.2 (11.4) minutes. The mean ground transport time was 46.0 (11.1) minutes. Tenecteplase was administered 35.9 ( 25.0) minutes prior to hospital arrival. The mean time savings, calculated as the transport interval after drug administration plus 90 minutes, was 125.9 (25.0) minutes (Table 2). Seventytwo patients were transported to a PCI facility, either after an evaluation at the local community hospital or directly from the scene. Thirty-six (49.3%) of the study participants were received at either the large teaching hospital or tertiary care facility through the emergency department, whereas 31 (42.5%) were transported directly to the ICU. Five (6.8%) were transported directly to the catheterization laboratory, and the one (1.4%) remaining patient was transported to and remained at a local hospital that does not provide cardiac catheterization services.
TABLE 2. Treatment Times
Treatment Interval Time (minutes SD)

Inferior Septal Anterior Lateral Inferolateral Anterolateral Posterior Inferior with RVI Anteroseptolateral Anteroseptal Other

39 3 4 3 3 8 1 2 1 8 1

53.4 4.1 5.5 4.1 4.1 11.0 1.4 2.7 1.4 11.0 1.4

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Percentages do not total to exactly 100.0% because of rounding. AMI = acute myocardial infarction; RVI = right ventricular involvement.

The most frequent area of acute myocardial infarction, based on ECG, was the inferior region (53.4%), followed by anteroseptal (11.0%), anterolateral (11.0%), anterior (5.5%), septal (4.1%), lateral (4.1%), and inferolateral (4.1%) (Table 3). Inferior with right ventricular involvement accounted for 2.7%, with posterior, anteroseptolateral, and undocumented locations each with a prevalence of 1.4%. Based on catheterization laboratory reports, the most frequent coronary artery involvement was the right coronary artery (50.7%), followed by the left anterior descending artery (28.8%), the circumex artery (11.0%), the left coronary artery (1.4%), and missing or not recorded (8.2%) (Table 4). Complete laboratory and ECG data for determining aborted infarctions were available for 58 patients, of whom 14 (24.1%) met both aborted infarction criteria. Independent evaluation of each variable in the aborted infarction criteria revealed that 44 of 58 (60%) had ST-segment resolution to 50% of baseline, while 19 of 73 (26%) and six of 73 (8.2%) had peak CK and CK-MB values less than or equal to twice their upper limit of normal, respectively (Table 5). The mean time from symptom onset to tenecteplase administration was 122.0 (118.1) minutes, and there was no difference in this time between patients who met the criteria for aborted infarctions and those who did not (116.3 minutes vs. 112.0 minutes, p = 0.91). The majority (76%) of the patients were treated within 120 minutes after symptom onset.
TABLE 4. Coronary Artery Involvement
Artery Involved Frequency (N = 73) Percent

Symptom Onset to 911 Call EMS Response Times On Scene to Departure Arrival on Scene to drug Transport Time Tenecteplase Administration to ED Arrival Scene Arrival to Hospital Arrival Time Saved (transport +90 minutes)

91.7 ( 123.6) 13.7 ( 8.0) 26.97 ( 9.4) 26.2 ( 11.4) 46.0 ( 11.1) 35.9 ( 25.0) 73.0 ( 20.6) 125.9 ( 25.0)

ED = emergency department; EMS = emergency medical services; SD = standard deviation.

Left anterior descending artery Circumex artery Right coronary artery Left coronary artery Not recorded Missing

21 8 37 1 5 1

28.8 11.0 50.7 1.4 6.8 1.4

Percentages do not total to exactly 100.0% because of rounding.

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503 to be the optimal treatment for STEMI. However, patients in rural areas are often located considerable distances from local hospitals, and even greater distances from PCI centers. For this rural population, prehospital thrombolysis may represent the most appropriate treatment, potentially resulting in earlier reperfusion and improving outcomes. A meta-analysis of prehospital brinolysis demonstrated a considerable savings in time from symptom onset to treatment between the prehospital administration of thrombolytics compared with in-hospital administration (104 vs. 162 minutes).13 This 58-minute reduction in time to treatment was associated with a 17% relative reduction (1.7% absolute reduction) in mortality13 equating to a number needed to treat of 62 to save one life.14 However, despite evidence that prehospital brinolysis reduces time to treatment,13,1517 and the meta-analysis by Morrison et al. demonstrating improved survival,13 few EMS systems in the United States have adopted prehospital thrombolysis. Of those that have, most are situated in urban centers with rapid transport times and short door-toneedle times,13 thus offering limited benet over inhospital thrombolysis or primary PCI. Moreover, no U.S. system has reported on the use of tenecteplase, a Food and Drug Administration (FDA)-approved single-bolus thrombolytic agent that is easier to administer and is associated with a signicantly lower rate of dosing errors when compared with an infusion agent.18,19 Tenecteplase has also been demonstrated to have a lower rate of ICH in STEMI patients than other thrombolytic regimens. In our case series of 73 patients, tenecteplase was administered an average of 36 minutes prior to arrival at the PCI-capable hospital. When taking into consideration the door-to-balloon times of most hospitals (estimated at 90 minutes),8 our results suggest a potential time savings of two hours to initiation of reperfusion therapy compared with a PCI strategy. Although our study design does not permit us to estimate the true benet of this time savings, the overall incidence of aborted infarction was 24%, which compares favorably with the 10.4% to 17.1% rate of previous studies of prehospital thrombolysis.9,2023 However, prehospital activation of the catheterization laboratory has been shown to reduce door-to-balloon times to considerably less than 90 minutes,24,25 and thus the actual time savings and clinical benet of prehospital brinolysis would tend to be reduced by this effect.26 Our complication rates were similar when compared with those found in previous works. Our inhospital mortality rate of 5.5% was similar to those previously reported, which ranged between 3.4% and 5.7%.10,17,27 Intracranial hemorrhage has been reported in 0% to 2.2% of cases, which is similar to our rate of 2.7%.10,2729 We did, however, observe higher

TABLE 5. Summary of Outcomes

Time Savings compared with PCI (minutes, SD) Aborted MI (N,%) 50% ST segment resolution CKMB less than 8 UI/L CK less than 464 UI/L In-hospital Mortality (N,%) CABG Serious Bleeding Event Hemoglobin decrease 3 g/dL from baseline Blood transfusion not associated with CABG ICH Secondary Outcomes Reinfarction Rescue Angioplasty Appropriate Therapy 125.9 ( 25.0) 44/58 (60%) 6/73 (8.2%) 19/73 (26%) 4/73 (5.5%) 11/66 (16.7%) 15/73 (20.5%) 8/73 (10.9%) 6/73 (8.2%) 2/73 (2.7%) 7/73 (9.6%) 35/73 (47.9%) 59/66 (89.4%)

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CABG- Coronary artery bypass graft; PCI- Percutaneous Coronary Intervention; MI- Myocardial Infarction; CKMB- Creatine Kinase-MB; CK- Creatine Kinase; ICH- Intracranial Hemorrhage; SD- Standard deviation

Serious bleeding events were encountered in 15 of 73 cases (20.5%). Of these, two patients suffered ICH, eight experienced a decrease in hemoglobin level of 3 g/dL from baseline, and six required transfusions not associated with CABG. Minor bleeding events included one patient with oral bleeding and one with a large hematoma formation at the PCI insertion site. Overall in-hospital mortality was four of 73 patients (5.5%). The causes of death for these four patients were ICH, cardiogenic shock, cardiac arrest following PCI, and undocumented. Reinfarction occurred in seven patients (9.6%), and 35 patients (47.9%) required rescue angioplasty. Twelve patients (16.7%) received CABG during their hospital stay (Table 5). The overall appropriateness of administration of tenecteplase was determined by evaluation of prehospital 12-lead ECGs and review of the medical record. The emergency physician reviewer determined that 59 of 66 (89.4%) patients received appropriate treatment based on ECG, compared with the cardiologist reviewer, who determined 54 of 66 (81.8%). The two blinded physicians gave an identical ECG interpretation 82% of the time (kappa = 0.29). Disagreement occurred with 11 patients and was adjudicated by a third emergency medicine physician. There was consensus that 57 of 66 (86.4%) met the criteria and the treatment was appropriate. Seven patients (10.6%) received tenecteplase when it was inappropriate. All of these cases were due to ECG misinterpretation by the paramedic and online medical control physician. None of these patients suffered a bleeding event or death. Using the criteria of ECG evidence, biomarkers, and cardiac catheterization reports described by Diercks and Hollander,12 59 of 73 patients (80.9%) ruled in for STEMI.

DISCUSSION
The relationship between reperfusion and patient outcomes is well established, and early PCI is considered

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rates of reinfarction (9.6%) than in previous studies (3.1%5.0%),10,2729 as well as higher rates of rescue angioplasty (47.9% vs. 18.5%27.2%).10,2729 We surmise, however, that our rate of rescue angioplasty is likely due to our denition of rescue angioplasty and our inability to differentiate between rescue and diagnostic angioplasty from the data available in the medical record. When evaluating patients in our study for appropriateness of care, STEMI was conrmed in 80.9% of patients who met prehospital ECG criteria and received tenecteplase. The success of any STEMI treatment strategy is contingent upon prompt recognition of signs and symptoms of a cardiac event and proper activation of the 9-1-1 system. In our patient series, the mean delay in symptom onset to calling EMS was 92 minutes, and the interval between symptom onset and injection of tenecteplase was 122 minutes. Thus, 75% of the treatment delay seen was the result of delays in symptom recognition and calling EMS. The only way to further reduce treatment delays in this study setting is likely to be community educational efforts aimed at reducing patient delays. Historically, however, such efforts have had minimal lasting effects.30 The time savings of prehospital thrombolysis compared with hospital reperfusion strategies is mitigated to some extent by the additional time required to properly screen the patient for prehospital thrombolytics. In our case series of STEMI patients, the on-scene time was 27 minutes, which is consistent with the 29-minute on-scene time reported by the Milwaukee Prehospital Chest Pain Project, of which 4 minutes was attributed to acquiring the 12-lead ECG and completing the thrombolytic checklist.31 However, our data set did not permit us to determine how much scene time was extended for thrombolytic screening and administration. Between 2001 and 2005, all patients experiencing STEMI were transported to the local hospital with transfer decisions made by the on-duty emergency physician. Beginning in 2006, all patients who received prehospital thrombolysis were transported directly to a PCI-capable facility unless determined to be unstable. It is unclear what impact this may have had on our results. Although the use of thrombolytics in the setting of STEMI in the rural environment appears promising, the success of this treatment is reliant on a systems approach to care that begins with prompt symptom recognition and activation of the EMS system. It also requires appropriate initial and ongoing education of the prehospital providers as well as strict medical oversight to ensure overall appropriateness. The success of this treatment is also conditional on a coordinated effort between receiving hospitals and EMS to ensure that once the patient arrives, treatment continues without delays.

LIMITATIONS
This was a retrospective case series and suffers from the usual limitations of this study design, including incomplete data for some patients. We attempted to reduce the problems associated with this study design by using standard chart review methodology.7 In addition, the sample is small and the lack of a comparison group limits the utility of the ndings. Furthermore, the data are derived from a single EMS system, and the generalizability of the ndings to other rural settings is unclear. During the nine-year study period, there were several changes to the eld treatment protocols. At the beginning of the study, EMS transported patients to the local hospital, and the patients were later transferred to one of the regional medical facilities. Because we calculated transport time intervals and time savings only for those patients transported directly to the PCI centers, this reduced the sample size used for these calculations. Additionally, time savings were estimated based on typical door-to-balloon times reported in the literature, as we did not have a PCI comparison group for determining actual time savings. From this review, one cannot estimate the accuracy of thrombolytic administration in those patients screened and not given thrombolytic therapy. All recorded times and time intervals were abstracted from the prehospital medical records, which have a built-in error due to lack of synchronization of clocks in the communication center, EMS equipment, and EMS personnel. No data were collected by EMS on patients who experienced onset of chest pain, received a prehospital 12-lead ECG, but were determined by the paramedic not to meet STEMI or thrombolytic criteria.

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CONCLUSION
We demonstrated that a rural EMS agency was able to successfully administer tenecteplase for STEMI. The average time of administration of tenecteplase was 36 minutes prior to hospital arrival. We estimate that the prehospital administration of tenecteplase resulted in initiation of reperfusion approximately two hours sooner than PCI strategies. Approximately one-fourth of the patients had aborted infarctions. Complication rates were similar to those shown by prior studies of prehospital thrombolytic therapy, with the exception of higher rates of reinfarction and rescue angioplasty. In a rural setting with lengthy transport times to PCI facilities, tenecteplase administration appears to be a feasible prehospital intervention. Randomized controlled trials are needed to fully evaluate the safety and effectiveness of this promising intervention prior to widespread adoption.

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