Part 7: The Era of Reperfusion

Abstract

HomeCirculationVol. 102, No. suppl_1Part 7: The Era of Reperfusion Free AccessOtherDownload EPUBAboutView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessOtherDownload EPUBPart 7: The Era of Reperfusion Section 1: Acute Coronary Syndromes (Acute Myocardial Infarction) Originally published22 Aug 2000https://doi.org/10.1161/circ.102.suppl_1.I-172Circulation. 2000;102:I-172–I-203Other version(s) of this articleYou are viewing the most recent version of this article. Previous versions: August 22, 2000: Previous Version of Record Major Guidelines RecommendationsPrehospital CareImplementation of out-of-hospital 12-lead ECG diagnostic programs is recommended in urban and suburban paramedic systems (Class I).Out-of-hospital fibrinolytic therapy is recommended when a physician is present or out-of-hospital transport time is ≥60 minutes (Class IIa).When possible, patients at high risk for mortality or severe left ventricular (LV) dysfunction with signs of shock, pulmonary congestion, heart rate >100 beats per minute (bpm), plus systolic blood pressure (SBP) <100 mm Hg should be triaged to facilities capable of performing cardiac catheterization and rapid revascularization (PCI or coronary artery bypass graft surgery [CABG]). For patients <75 years of age, this is a Class I recommendation.Reperfusion TherapiesMany clinical trials have established early fibrinolytic therapy as a standard of care for acute ST-segment elevation myocardial infarction (MI) (Class I for patients <75 years old and Class IIa for patients >75 years old).Percutaneous coronary intervention (PCI), including angioplasty/stent, is a Class I recommendation for patients <75 years of age with acute coronary syndromes (ACS) and signs of shock.Patients in whom fibrinolytic therapy is contraindicated should be considered for transfer to interventional facilities when potential benefit from reperfusion exists (Class IIa).Heparin is currently recommended for patients receiving selective fibrinolytic agents (tissue plasminogen activator [tPA]/reteplase [rPA]) (Class IIa).Heparin dosing with fibrinolytics is changed to reduce the incidence of intracerebral hemorrhage (ICH) and minimize reocclusion. Give heparin in a 60-U/kg bolus followed by a maintenance infusion of 12 U/kg per hour (with a maximum of 4000 U bolus and 1000 U/h infusion for patients weighing >70 kg). The activated partial thromboplastin time should be maintained at 50 to 70 seconds for 48 hours.New Therapy for Unstable Angina/Non–Q-Wave MIGlycoprotein (GP) IIb/IIIa inhibitors are recommended for patients with non–ST-segment elevation MI or high-risk unstable angina (Class IIa).GP IIb/IIIa inhibitors have incremental benefit in addition to conventional therapy with unfractionated heparin (UFH) and aspirin (Class IIa).Low-molecular-weight heparin (LMWH) is an alternative to UFH for the treatment of non–Q-wave MI and unstable angina.Troponin-positive patients are at risk for major adverse cardiac events (MACE) and should be considered for aggressive therapy.IntroductionEvidence-based data for the management of acute myocardial infarction (AMI) has evolved dramatically in the past decade. AMI and unstable angina are now recognized as part of a spectrum of clinical disease collectively identified as acute coronary syndromes, which have in common a ruptured or eroded atheromatous plaque.12345 These syndromes include unstable angina, non–Q-wave MI, and Q-wave MI. The ECG presentation of ACS encompasses ST-segment elevation infarction, ST-segment depression (including non–Q-wave MI and unstable angina), and nondiagnostic ST-segment and T-wave abnormalities. The majority of patients with ST-segment elevation will develop Q-wave MI. Only a minority of patients with ischemic chest discomfort at rest who do not have ST-segment elevation will develop Q-wave MI and will eventually be diagnosed as non–Q-wave MI or unstable angina. A significant portion of patients with an initial diagnosis of angina will not have ischemic coronary disease. Sudden cardiac death may occur with each of these syndromes. ACS is the proximate cause of sudden cardiac death in most adult patients.678910The primary goals of therapy for patients with ACS are Reduction of myocardial necrosis in patients with ongoing infarctionPrevention of major adverse cardiac events (death, nonfatal MI, and need for urgent revascularization)Rapid defibrillation when ventricular fibrillation (VF) occursTo date >750 000 patients with ACS have been studied worldwide in randomized clinical trials, producing an abundance of outcome-based data for healthcare providers. Several consensus panels,11121314151617 including the American College of Cardiology (ACC)/American Heart Association (AHA) Guidelines Committees for the Management of Acute Myocardial Infarction and Unstable Angina1112131416 and the European Society of Cardiology and European Resuscitation Council,1517 have considered the clinical impact of this data and have published guidelines for the management of ACS. The guidelines that follow are a refinement of these international guidelines for healthcare providers who treat patients with ACS within the first several hours after onset of symptoms. These guidelines address out-of-hospital, emergency department (ED), and critical-care issues. Regional practices vary as a result of differences in out-of-hospital and in-hospital resources, availability of healthcare professionals, expertise, and skill. Therefore, these guidelines are designed to provide general directions for care.PathogenesisUnderstanding the principles of management of ACS requires a knowledge of developing concepts of thrombus initiation and coronary plaque pathobiology.11819 Patients with coronary atherosclerosis in whom these clinical syndromes develop have various degrees of coronary artery occlusion. Typically ACS is caused by rupture of a lipid-laden plaque with a thin cap.135 Most of these plaques are not hemodynamically significant before rupture.2021 However, an inflammatory component present in the subendothelial area further weakens the plaque and predisposes it to rupture.22 Blood flow velocity and turbulence as well as vessel anatomy may also be important contributing factors to plaque disruption. Superficial erosion of a plaque occurs in approximately 25% of patients who also manifest increased systemic markers of inflammation.23 The degree and duration of occlusion, as well as the presence or absence of collateral vessels, determine the type of infarction that occurs.After plaque rupture or erosion, a monolayer of platelets covers the surface of the ruptured plaque (platelet adhesion). Additional platelets are recruited (platelet aggregation) and activated. Fibrinogen cross-links platelets, and the coagulation system is further activated by thrombin generation. A partially occluding thrombus produces symptoms of ischemia that may be prolonged and may occur at rest. At this stage the thrombus is platelet-rich. Therapy with antiplatelet agents, such as aspirin and GP IIb/IIIa receptor inhibitors, is most effective at this time. Fibrinolytic therapy is not effective and paradoxically may accelerate occlusion by causing the release of clot-bound thrombin, which further activates platelets.2425An intermittently occlusive thrombus may cause distal myocyte necrosis in the region supplied by the culprit artery, producing non–Q-wave MI. As the clot enlarges, microemboli originating in the thrombus may embolize and lodge in the coronary microvasculature, causing small elevations of cardiac troponins, new sensitive cardiac markers.10192627 Microvascular dysfunction is now understood to be an additional determinant of myocardial dysfunction in patients with ACS and those treated with PCI.27282930 Patients with such a thrombus are at highest risk for progression to MI. This process is known as minimal myocardial damage. Other mechanisms for myocardial ischemia and minimal necrosis include intermittent dynamic occlusion and spasm at the thrombus site.31 If the thrombus occludes the coronary vessel for a prolonged period of time, Q-wave MI occurs. The clot causing Q-wave MI is rich in thrombin and fibrin.32 In these patients, fibrinolysis or PCI (eg, angioplasty/stent) may limit the size of the infarct if performed sufficiently early in the course.Out-of-Hospital ManagementEarly DefibrillationHalf of the patients who die of AMI do so early, before reaching a hospital (see Figure 1). In most of these deaths the presenting rhythm is ventricular tachycardia (VT)/VF.333435 The major risk of VF occurs during the first 4 hours after onset of symptoms.363737A VF that occurs during the acute phase (usually within the first few hours) of an MI is called “primary VF”; it occurs in 4% to 18% of patients with infarction.37A3839Once the patient is admitted to the hospital, the incidence of in-hospital VF is approximately 5%.40 VF incidence appears to be declining even further in the modern era of reperfusion. Investigators in the Gruppo Italiano per lo Studio della Streptochinasi nell’Infarto Miocardico Study (GISSI) found a 3.6% incidence of early VF and a 0.6% incidence of late VF. Fibrinolytic therapy reduced the occurrence of VF primarily within the first 3 hours; the occurrence of VF did not predict reperfusion.4142 The presence of primary VF increases in-hospital mortality and complications4143 but does not appear to increase long-term mortality.44All emergency medical services (EMS) and dispatch systems should have a trained and dedicated staff to respond to cardiac emergencies. Because the incidence of VF is highest out of hospital, every emergency vehicle that responds to cardiac emergencies should carry a defibrillator with staff skilled in its use. The AHA, the European Resuscitation Council, and the International Liaison Council on Resuscitation endorse the position that all emergency personnel, including first responders both in-hospital and in the field, should be trained to operate a defibrillator.4546Automated external defibrillators (AEDs) have been used safely and effectively by first responders with minimal training.4748495051 Whether greater availability of AEDs and access to them will increase survival is the subject of ongoing evaluation.525354 The AHA public health initiative public access defibrillation proposes to achieve more widespread early defibrillation through placement of AEDs throughout the community, making them available to a large number of trained lay community and nontraditional emergency responders. (See “Part 4: The Automated External Defibrillator.”)Ideally an EMS system should have enough trained personnel that a first responder can be at a victim’s side anywhere in the system within 5 minutes. Early access is promoted by an emergency phone system with a dedicated number for that area (or region or country), with dispatchers trained to prioritize responses to these calls (see “Part 3: Adult Basic Life Support,” Emergency Medical Dispatchers). Because patients with AMI have a high risk of sudden cardiac death during the first hour after onset of symptoms, an out-of-hospital EMS system that can provide immediate defibrillation is mandatory. Every ambulance that transports cardiac patients should be equipped with a defibrillator and personnel proficient in its use. If VF occurs under observation and immediate defibrillation is available, many patients will survive (see Figure 1).When patients with ACS, including MI and other ischemic syndromes, reach the ED and hospital critical care unit (CCU), their risk of sudden cardiac death due to lethal arrhythmias falls dramatically.40 This decline in risk stems from a combination of early reperfusion, administration of β-blockers, and other adjunctive agents used in the reperfusion era.5556 The deaths that do occur during this period are due to VF/VT, LV power failure with congestive heart failure (CHF) and cardiogenic shock, reocclusion with extension of the infarct, or mechanical complications of cardiac rupture and structural damage (Figure 1). For these reasons, healthcare professionals should focus on limiting the size of the infarct, treating arrhythmias, and preserving LV function.Patient Education and Delays in TherapyDelays in therapy after the onset of symptoms for ACS occur during 3 periods: during the interval from onset of symptoms to patient recognition, during out-of-hospital transport, and during in-hospital evaluation. Potential delay during the in-hospital evaluation period may occur from door to data, from data (ECG) to decision, and from decision to drug; these 4 major points of in-hospital therapy are commonly referred to as the “4 D’s.”57Because myocardial salvage is time dependent, with the greatest potential benefit in the first few hours of ACS, it is imperative that patients arrive at the treating hospital and receive evaluation and therapy as quickly as possible. Delay by patients, EMS personnel, and hospitals significantly prolongs the time to reperfusion therapy,5859 reducing the effectiveness of fibrinolytic therapy and increasing mortality.Patient delay to symptom recognition constitutes the longest period of delay to treatment. Prodromal symptoms are common among patients with ACS,60 but these symptoms are frequently denied or misinterpreted. The elderly, women, persons with diabetes, and hypertensive patients are most likely to delay, partly because they tend to have atypical symptoms or unusual presentations.61626364 In the US Rapid Early Action for Coronary Treatment (REACT) trial, the median out-of-hospital delay was ≥2 hours in non-Hispanic blacks, the elderly and disabled, homemakers, and Medicaid recipients. The decision to use an ambulance was an important variable that reduced out-of-hospital delay and persisted after correction for variables associated with severity of symptoms.65 Other factors that have an impact on the patient’s arrival at the hospital include time of day, location (eg, work or home), and the presence of a family member.66A69 The REACT trial also found that community members recognized the value of EMS systems and warning signs of heart attack when they were involved as bystanders but often failed to act on their own behalf when having similar symptoms.66AOut-of-hospital transport time constitutes only 5% of delay to treatment time, whereas in-hospital evaluation constitutes 25% to 33% of delay to treatment.6768 EMS systems, hospitals, and communities should educate patients about symptoms of cardiac ischemia, rapidly triage patients to appropriate care, and provide rapid defibrillation and medical care to patients with ischemic-type chest discomfort.Education of patients is the primary intervention to reduce denial or misinterpretation of symptoms. The physician and family members of patients with known coronary disease should reinforce the need to seek medical attention when symptoms recur, because these patients paradoxically present later than patients with no known disease. Public education campaigns have been effective in increasing public awareness and knowledge of the symptoms and signs of heart attack.69 The results of these campaigns, however, have been transient and unrewarding. An educational program emphasizing early recognition of symptoms and reasons for misinterpretation or denial of symptoms is important. Physicians should also educate their patients about the local EMS system and encourage early activation for appropriate symptoms.70 Physicians should discuss prompt and appropriate use of nitroglycerin (glyceryl trinitrate in Europe) and aspirin, EMS activation, and location of the nearest hospital that offers 24-hour emergency cardiac care.Out-of-Hospital FibrinolysisClinical trials have shown the benefit of initiating fibrinolysis as soon as possible after onset of ischemic-type chest pain. Because the potential for myocardial salvage is greatest very early in AMI, a number of researchers have studied administration of fibrinolytics during the out-of-hospital period. Several studies demonstrated the feasibility and safety of out-of-hospital fibrinolytic administration,7172 but early small trials yielded conflicting results about the efficiency and efficacy of this strategy.737475767778Physicians in the Grampian Region Early Anistreplase Trial (GREAT) administered fibrinolytic therapy to patients at home 130 minutes earlier than to patients at the hospital and noted a 50% reduction in mortality in those treated earlier.77 At the 5-year follow-up examination, investigators found that fewer patients (25%) in the out-of-hospital treatment group had died compared with a greater number (36%) in the hospital treatment group (log-rank test, P<0.025).79 Delaying fibrinolytic treatment by 30 minutes reduced average life expectancy by approximately 1 year. Delaying fibrinolytic treatment by 1 hour increased the hazard ratio of death by 20%, which is equivalent to the loss of 43 lives per 1000 patients within the next 5 years.The European Myocardial Infarction Project group (EMIP) found that patients in the out-of-hospital treatment group received fibrinolytic therapy a median of 55 minutes earlier than those in the in-hospital treatment group.7277 Death due to cardiac causes was significantly less common in the group treated out of hospital than in the group treated in-hospital (8.3% versus 9.8%; reduction in risk, 16%; 95% CI, 0% to 29%; P=0.049). Only a nonsignificant reduction in overall mortality was observed at 30 days in the out-of-hospital group (9.7% versus 11.1% in the hospital group; reduction in risk 13%; 95% CI, −1% to 26%; P=0.08).In the Myocardial Infarction Triage and Intervention (MITI) trial,71 no significant difference in mortality between out-of-hospital and in-hospital fibrinolysis was observed. In a retrospective analysis, however, researchers noted that any patient treated within a median time of 70 minutes, whether before or after hospital arrival, had a significantly improved outcome. A confounding variable in this trial was advance notification of hospital staff and the shortening of hospital treatment times compared with historic controls.80A meta-analysis of out-of-hospital fibrinolytic trials summarized by the EMIP group found a 17% relative improvement in outcome associated with out-of-hospital fibrinolytic therapy. The greatest improvement was observed when therapy was initiated 60 to 90 minutes earlier than in the hospital.81 More recently a meta-analysis evaluated time to therapy and impact of prehospital fibrinolysis on all-cause mortality. Pooled results of 6 randomized trials with >6000 patients found a significant 58-minute reduction in time to administration (P=0.007) and decreased all-cause hospital mortality (OR 0.83; CI 0.70 to 0.98).82 Although fibrinolytic therapy initiated out of hospital results in earlier treatment, the time savings can be offset in most instances by an improved hospital triage with a door-to-needle time ≤30 minutes.In summary, administration of fibrinolytics during the out-of-hospital period appears to reduce mortality when transport times are long (Figure 2). The 1996 ACC/AHA Task Force on Practice Guidelines recommended that out-of-hospital systems focus on early diagnosis and that fibrinolytics be administered in the field when a physician is present or transport time is >90 minutes.12 The European Society of Cardiology and the European Resuscitation Council recommend out-of-hospital fibrinolysis when transport time is >30 minutes or hospital door-to-needle time (beginning infusion of a fibrinolytic agent) is expected to be >60 minutes.17 The AHA Committee on Emergency Cardiovascular Care, the Evidence Evaluation Conference, and the international Guidelines 2000 Conference expert panelists evaluated these recommendations and recent data and practice. We recommend out-of-hospital fibrinolytic therapy only when a physician is present or out-of-hospital transport time is ≥60 minutes (Class IIa). Observations from trials of out-of-hospital fibrinolysis suggest that most EMS systems should focus on early diagnosis and rapid transport instead of delivery of therapy.Out-of-Hospital ECGsOut-of-hospital performance of electrocardiography and transmission of the ECG to the ED speeds the care of patients with AMI. Multiple studies have shown the feasibility of obtaining a 12-lead ECG during the out-of-hospital period.71838485868788899091 Diagnostic-quality ECGs can be successfully transmitted for approximately 85% of patients with chest pain who are eligible for 12-lead ECGs.84 Recording an ECG increases the time spent at the scene of an emergency by only 0 to 4 minutes.71848792 In addition, there is no difference between the quality of information collected out-of-hospital and that received by cellular transmission at the base station.83 A diagnosis of AMI can be made sooner when the 12-lead ECG is obtained before the patient arrives in the hospital than if the ECG is performed after arrival.The use of out-of-hospital ECGs and a chest pain evaluation form leads to more rapid initiation of reperfusion therapy without substantially delaying out-of-hospital time. A 12-lead ECG transmitted to the hospital speeds diagnosis and shortens time to fibrinolysis.85869394 Many studies have shown significant reductions in hospital-based time to treatment with fibrinolytic therapy in patients with AMI identified before arrival by a 12-lead ECG.87888995 Time savings in these studies ranged from 20 to 55 minutes.878889 Patients with an AMI identified by an out-of-hospital 12-lead ECG were more frequently treated in the ED than the CCU, and a trend toward more rapid ED and CCU treatment was demonstrated.96 The US National Heart Attack Alert Program recommends that EMS systems provide out-of-hospital 12-lead ECGs to facilitate early identification of AMI and that all advanced lifesaving vehicles be able to transmit a 12-lead ECG to the hospital.97A retrospective study of the US National Registry of Myocardial Infarction database showed a mortality benefit (reduction in mortality) for patients with AMI identified by an out-of-hospital 12-lead ECG.98 Canto et al evaluated the treatment and outcome of patients with and without an out-of-hospital 12-lead ECG. Although the median time from onset of infarction to arrival at the hospital was longer among patients in the out-of-hospital ECG group, the median time to initiation of fibrinolysis or primary angioplasty was significantly shorter. The out-of-hospital ECG group was also significantly more likely to receive fibrinolytic therapy, primary angioplasty, or CABG. The in-hospital mortality rate was 8% among patients with an out-of-hospital ECG and 12% among those without an out-of-hospital ECG (P<0.001).98By implementing the 12-lead ECG as a diagnostic procedure, the EMS system can expand its role in coordinating the community response to patients with signs and symptoms of ACS. Paramedics trained and equipped to obtain 12-lead ECGs in the field can provide the ED with a definitive diagnosis, allowing the administration of fibrinolytic agents (or primary angioplasty) soon after the patient’s arrival. The safety, feasibility, and practicality of obtaining out-of-hospital 12-lead ECGs are well documented.In summary, earlier diagnosis and faster treatment of AMI with fibrinolytic drugs is possible when a 12-lead ECG is obtained in the field and transmitted to the receiving emergency physician. Even shorter hospital delays have been observed in patients whose out-of-hospital identification by history and ECG was obtained as part of a protocol-driven out-of-hospital diagnostic strategy (out-of-hospital identification of fibrinolytic candidates) and whose out-of-hospital information was effectively communicated to the receiving physician before arrival at the hospital. Advances in computer interpretation of ECGs and development of predictive instruments have the potential to improve diagnostic sensitivity and enhance out-of-hospital evaluation of patients. Evidence supports the contention that out-of-hospital 12-lead ECG diagnostic programs are cost-effective and may be underused. We recommend implementation of out-of-hospital 12-lead ECG diagnostic programs in urban and suburban paramedic systems (Class I).Cardiogenic Shock and Out-of-Hospital Facility TriageControversy continues over whether fibrinolytic therapy or PCI is the best method of reperfusion (see below). Mortality among patients with cardiogenic shock is high in reported studies.99100101102 In recent years an increasing body of evidence has suggested that early hemodynamic stabilization is beneficial and reduces mortality in certain patients. The Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO-I) investigators retrospectively evaluated patients with cardiogenic shock after MI. The incidence of cardiogenic shock in the study was 11%, and an aggressive strategy (PCI) was associated with a lower mortality than that associated with fibrinolytic therapy.103 The use of early invasive interventions is more common in the United States than in other countries, but patients who underwent revascularization had better survival in all countries.104 In the Second National US Registry of Myocardial Infarction, the mortality rate in patients with AMI and shock was lower in those treated with PCI as a primary strategy than in those treated with fibrinolysis.105 In a large registry of patients with shock, mortality was also lower in AMI patients who received early revascularization with either PCI or CABG.106A recently completed randomized trial found reduced mortality among patients with cardiogenic shock treated aggressively with intra-aortic balloon pulsation (IABP) and mechanical or surgical revascularization. In the SHOCK trial 152 patients were randomly assigned to an early revascularization strategy (ERV) and 150 patients were assigned to a strategy of initial medical stabilization (IMS).106A The initial medical management strategy was aggressive for both the ERV and IMS groups; intra-aortic balloon pump (IABP) support was used in 86% of both groups. Sixty-three percent of the IMS group received fibrinolytic agents, and 25% underwent delayed revascularization. Of the ERV group of patients who underwent emergency early revascularization, >60% received PCI and 40% had surgical revascularization. The 30-day mortality rate for ERV patients was lower but not significantly lower than those with IMS. A secondary end point, mortality rate at 6 months, was significantly lower in the ERV group (50.3% versus 63.1%, P=0.027). In this study a prespecified subgroup analysis was performed for patients <75 years old. The analysis showed a 15.4% reduction in 30-day mortality with early revascularization (IMS group, 56.8% versus ERV group, 41.4%, P<0.01). Outcome for patients >75 years old was worse for the ERV group. These results were thought to mirror those in the SHOCK registry.107The 1999 update of the ACC/AHA Guidelines for the Management of Patients With Myocardial Infarction was revised to indicate a Class I recommendation for PCI in patients with shock who are <75 years of age. These recommendations were supported at the Guidelines 2000 Conference.13 Use of IABP followed by diagnostic cardiac catheterization and, where anatomically appropriate, coronary revascularization with either PCI or CABG may reduce mortality.108109110111112When possible, transfer patients at high risk for mortality or severe LV dysfunction with signs of shock, pulmonary congestion, heart rate >100 bpm, and SBP <100 mm Hg to facilities capable of cardiac catheterization and rapid revascularization (PCI or CABG) (for patients <75 years old, Class I). An out-of-hospital checklist can also identify patients who have contraindications to fibrinolytic therapy. Patients with contraindications to fibrinolytic therapy should be considered for transfer to interventional facilities when benefit from reperfusion exists (Class IIa).Initial General MeasuresImmediately begin continuous cardiac monitoring for patients with suspected ischemic-type chest pain and obtain intravenous access. Administer morphine, oxygen, nitroglycerin, and aspirin (“MONA”) to patients without contraindications. Determine the immediate treatment necessary, rapidly assess reperfusion eligibility, and administer necessary adjunctive treatments (Table 1 and Figure 3).OxygenAdminister oxygen to all patients complaining of ischemic-type chest discomfort. Also administer oxygen, usually by nasal cannula, to all patients with suspected ACS. Experimental evidence suggests that breathing supplemental oxygen may limit ischemic myocardial injury. There is also evidence that oxygen reduces the amount of ST-segment elevation, although it is not known whether this therapy reduces morbidity or mortality among patients with AMI. Results of early experimental studies aimed at reducing the size of the infarct suggested that oxygen might be beneficial. In addition, oxygen can reduce ST-segment elevation among patients with anterior infarction.113114If a patient has overt pulmonary congestion or if oxygen saturation is <90%, continue oxygen therapy until the patient’s condition has stabilized. If hypoxemia is persistent and respiratory muscle fatigue develops, consider early intubation with assisted mechanical ventilation and a higher fraction of inspired oxygen (Fio2). Hypoxemia and respiratory insufficiency can tax a marginal cardiac output substantially, leading to increased infarct size and cardiovascular collapse. No clinical studies, however, have shown a reduction in morbidity or mortality with the routine use of supplemental oxygen and current treatment regimens. In the absence of compellin