Norepi Vs Dopamine

A 75M presents with several days of cough, fever, and progressive lethargy.
CXR demonstrates RLL pneumonia.
BP 70/50. HR 130. Lactate 5. T38.0
2L bolus NS given.
Antibiotics started.
Bedside sono shows noncollapsing IVC, hyperdynamic LV.
Recheck BP 72/50. Lactate 5.0
DX: Septic shock.
Plan: Central line, start a pressor, then intubate.

Question: What pressor do you want to start with, and why?

We’re going to narrow this down to dopamine versus norepinephrine.

I went into this review expecting an open and shut case for one of these pressors (norepi).

Norepinephrine has alpha 1 and beta adrenergic effects, resulting in vasoconstriction and increased chronotropy and inotropy.

Dopamine, while being the precursor to norepinephrine and epi, has alpha1 and beta adrenergic effects as well.

Of note, dopamine receptors are present in vascular structures, which promote vasodilation when exposed to low levels of dopamine. It has been theorized and shown in models that dopamine via D1 and D2 receptors cause splanchnic and renal vasodilation, so for some time in critical care low dose dopamine was given to critically ill patients with the theoretical hope that it may be protective in improving renal blood flow, diuresis, and decrease the need for dialysis. However this was not borne out in a large multicenter trial and a meta-analysis in 2000 and 2001, and low dose dopamine for renal protection is no longer generally accepted in the critical care literature.

Recent Trials, Reviews, and Recommendations in vasopressor selection:

Comparison of Dopamine and Norepinephrine in the Treatment of Shock
NEJM, 2010

Randomized multicenter trial in Europe. 1679 patients Pts >18 years old who required a vasopressor for treatment of shock were randomized to norepinephrine or dopamine. No significant differences in mortality were found between the two arms. Among subgroups, no mortality difference was noted among those with septic shock, however rate of death in patients with cardiogenic shock was significantly higher in those who received dopamine.

There were more arrhythmic events in patients treated with dopamine than among those treated with norepinephrine (207 events [24.1%] vs. 102 events [12.4%], P<0.001).


Efficacy and Safety of Dopamine versus Norepinephrine in the Management of Septic Shock.
Shock, 2010

USA: 252 patients with septic shock were randomized to norepinephrine or dopamine as a first line pressor. There was no significant mortality difference. There were significantly more arrhythmias in the dopamine group, but again, no mortality difference.

There are several meta-analyses published recently, including:

COCHRANE Review: Vasopressors for Hypotensive Shock

23 randomized controlled trials, 6 vasopressors, 3212 patients, with 1629 mortality outcomes.
Cochrane review concluded that there was no difference in mortality among pressors, and suggested that the choice of vasopressor in shock does not influence the outcome. “There is not sufficient evidence that any one of the investigated vasopressors is clearly superior over others.”

The analysis did not use pre-defined subgroups, meaning they did not comment on pressor choice on particular states of shock (septic, cardiogenic, etc).


Meta-analysis using Bayesian network model.
Journal of critical care, 2014

14 studies with 2811 patients.
The review found that norepinephrine reduced mortality compared to Dopamine (OR: 0.80 [95% CI 0.65-0.99]).
The structure of the meta-analysis the authors used is nontraditional and beyond my understanding of study design, but they offer this explanation:
“The approach used in our current study differs from traditional meta-analyses… it is possible to combine the results of direct comparisons to indirect comparisons extrapolated by trials that have treatments in common…”


2012 Surviving Sepsis Campaign Guidelines:
Use vasopressors to target a MAP of 65.
Norepinephrine is recommended as first line vasopressor (grade 1B).


In examining recent prospective, randomized trials, I was unable to find a mortality benefit for norepinephrine over dopamine in shock, including septic shock. The Cochrane review is also unable to find a mortality difference. A meta-analysis found a mortality difference using advanced statistics, but I need a Newman consult for further clarity on their methods. There is evidence for increased arrhythmias on dopamine, but not in a manner that affected patient mortality.

With that said, the surviving sepsis campaign advocates for norepinephrine as our first line pressor in septic shock, and it is generally accepted in EM practice for now to start norepinephrine as the initial vasopressor in septic shock. So for our gentleman, let’s start norepinephrine.

My take away from this review is that the declaration of “standard care” may rest on RCT results that aren’t as decisive as one expected.


Bellomo, R, Chapman, M, Finfer, S, et al Low-dose dopamine in patients with early renal dysfunction: a placebo-controlled randomised trial Australian and New Zealand Intensive Care Society (ANZICS) Clinical Trials Group.Lancet2000;356,2139-2143

De Backer D, Biston P, Devriendt J, Madl C, Chochrad D, Aldecoa C, Brasseur A,
Defrance P, Gottignies P, Vincent JL; SOAP II Investigators. Comparison of
dopamine and norepinephrine in the treatment of shock. N Engl J Med. 2010 Mar
4;362(9):779-89.Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, Opal SM, Sevransky JE,

Sprung CL, Douglas IS, Jaeschke R, Osborn TM, Nunnally ME, Townsend SR, Reinhart
K, Kleinpell RM, Angus DC, Deutschman CS, Machado FR, Rubenfeld GD, Webb SA,
Beale RJ, Vincent JL, Moreno R; Surviving Sepsis Campaign Guidelines Committee
including the Pediatric Subgroup. Surviving sepsis campaign: international
guidelines for management of severe sepsis and septic shock: 2012. Crit Care Med.
2013 Feb;41(2):580-637

Havel C, Arrich J, Losert H, Gamper G, Müllner M, Herkner H. Vasopressors for
hypotensive shock. Cochrane Database Syst Rev. 2011 May 11;(5)

Kellum JA, Decker JM. “Use of dopamine in acute renal failure: a meta-analysi” Crit Care Med. 2001 Aug;29(8):1526–31.

Oba Y, Lone NA. Mortality benefit of vasopressor and inotropic agents in
septic shock: A Bayesian network meta-analysis of randomized controlled trials. J
Crit Care. 2014 Oct;29(5):706-10.

Patel GP, Grahe JS, Sperry M, Singla S, Elpern E, Lateef O, Balk RA. Efficacy
and safety of dopamine versus norepinephrine in the management of septic shock.
Shock. 2010 Apr;33(4):375-80.

Healthcare Update Satellite — 08-28-2014

Good news is that the number of medical malpractice cases in Pennsylvania is decreasing. Bad news is that if you practice medicine in the Philadelphia area, you’ve got a big target painted on your back. Philadelphia accounts for only 12 percent of the state’s population yet in 2013, 40 percent of medical malpractice trials resulting in verdicts took place in the city. Philadelphia medical malpractice plaintiffs won 45% of trials, more than any other jurisdiction and significantly higher rate than the national average.
Looks like we’ve found another place to avoid when looking for your next place to practice medicine.

Regulating a longstanding practice out of existence. Remember going to your doctor’s office and seeing those walls full of pictures of babies that the doctor delivered? Yeah, that’s illegal. Violates HIPAA.

Travelers from Liberia still being transferred via commercial flights to Delhi and Mumbai. A few with fevers were quarantined … after they arrived … while the others were required to be tracked daily by local authorities for the following month.
Meanwhile, most major airlines are suspending service to the “crisis zones.”

With the ebola hysteria comes hysterical actions. Woman on a Delta Airlines flight in Florida was kicked off the airplane because she “looked tired and drowsy.” Staff stated that if she did not get off the flight, they would call the authorities. Delta gave her a $20 voucher for tea and soup, then let her on the next flight. Because tea, soup, and an hour wait in the lovely airport atmosphere are more than enough to kill any potential communicable diseases that cause people to look tired and drowsy.

Study in Journal for Healthcare Quality shows that diagnostic errors double the odds of malpractice payout totaling $1 million or more. There were 6,130 such “catastrophic payouts” between 2004 and 2010 and those payments amounted to .05% of the total health care expenditures each year. Years of practice and number of prior paid claims had no bearing on the odds of a catastrophic payout.
However, failure to order diagnostic testing absolutely contributes to diagnostic errors. Kind of flies in the face of the whole “lets cut back on testing” mantra, doesn’t it?

Obamacare mandates having an effect even on Major League Baseball. Cubs grounds crew hours cut to keep them under 130 hours per month so that they don’t meet “full time worker” criteria and get insurance coverage under Obamacare. During rain delay at a recent Cubs game, the understaffed grounds crew wasn’t able to get the tarp properly positioned on the infield – leading the umpires to call the game off due to poor infield conditions.

Neat idea in Singapore to curb non-urgent emergency department care. Hospital and local primary care physicians teamed together to create a “GP First” scheme. If a patient goes to their primary care physician for a problem and then has to be referred to the emergency department, they get $50 off of the $108 emergency department bill. So far, the hospital has seen a decrease in non-urgent cases by 10-12%. The resulting decrease in patient volume also caused about a 20% decrease in emergency department wait times.
Now why wouldn’t such a plan work in the US?

Flying drone delays medical helicopter’s landing at Ohio’s Miami Valley Hospital. What are we going to ban after this incident?
Once we had a guy taking pictures/video with his phone who wouldn’t get away from the helipad in the hospital parking lot while the chopper was landing. Security literally had to tackle him and drag him away.

Louisiana pays extra $18 million to keep Baton Rouge General’s emergency department open. The hospital emergency department is seeing an additional 400 uninsured patients per month with numbers of uninsured psychiatric visits up 60% and number of uninsured surgery patients up 70%. After Louisiana State closed its Earl K Long Medical center in an attempt to privatize charity hospital care, the patients had to find other care. Now Baton Rouge General is losing $1 million per month. Another story on the topic here.
I’ve been saying this for years. When hospitals close, the patients going to those hospitals don’t just disappear. They seek care elsewhere. The costs of providing uncompensated and poorly compensated (Medicaid and “Obamacare”) care at the remaining open hospitals then compounds on itself until the next hospital closes under the weight uncompensated care. Every hospital that closes causes a decrease in access and decrease in available medical care.
Wait. Wasn’t that what the “Affordable” CARE Act was created to solve?
Louisiana better write at least double that $18 million into its yearly budget. It’s trying to cure a hemorrhage by using a Bandaid and we all know how well that will work out.

Another hospital shooting near Philadelphia. Man pulls gun in hospital room then kills wife and shoots himself. Fourth hospital shooting in the Philadelphia area this year. Wait. Isn’t this the same place that has such the high rate of successful malpractice cases? Another reason to consider whether you really want to practice medicine in the Philadelphia area.

Joan Rivers goes into cardiac arrest during throat surgery and is brought to the Mt. Siani emergency department. Reportedly stable. Good job, team!
I can’t wait to hear all of the jokes about this incident.

Quality Sepsis Care: ACEP’s Mission, Advocacy and Research in Action

Sama preferred photo

Dr. Sama

By Andrew E. Sama, MD, FACEP

With nearly two-thirds of all admitted septic patients presenting to the ED, and with the clear time sensitivity that exists between recognition, treatment, and outcomes, our members are on the front lines to save lives from this frequently fatal disease. In the CY 2015 IPPS rule, in which CMS cited the fact that “that patients admitted through the ED had a 17% lower likelihood of dying from sepsis than when directly admitted,” CMS finalized NQF #0500: Early Management Bundle for Severe Sepsis and Septic Shock, which mandated the invasive monitoring of CVP and ScVO2 via the placement of a central line in the ED. However, late on Friday, CMS notified hospitals, that it will suspend data collection for the Severe Sepsis and Septic Shock: Management Bundle measure (NQF #0500) until further notice.

Emanuel Rivers, MD, MPH, and his team improved mortality and raised the awareness of the EM community about sepsis through their Early Gold Directed Therapy (EGDT) study in the early 2000s. A few years later, the measure was initially endorsed by the NQF in 2008 without the requirement for a central line for the emergency department. While it is certain that early intervention does reduce mortality, not all elements of the sepsis composite bundle were equally evidence-based.  Many studies over the years have demonstrated dramatic improvements in sepsis-related mortality after the implementation of early interventions for septic patients, which included early antibiotic administration, source control, and aggressive fluid resuscitation without invasive monitoring of CVP and ScVO2. One study addressing this, authored by Dr. Alan Jones and colleagues, was conducted at three EDs in the US, and compared two protocols that both included central venous pressure measurement; however, one used lactate clearance and the other used central venous oxygenation monitoring as a way to guide resuscitation. Dr. Jones’ 2010 study found no differences in mortality, suggesting that using central venous oxygenation to guide resuscitation may not be necessary.

In 2012 the measure underwent routine NQF maintenance review for re-endorsement in 2012-2013.  During those proceedings, under the leadership of David Seaberg, MD, FACEP and myself ACEP commented that central venous pressure (CVP) was not the only reliable measure of intravascular volume. Several members of ACEP’s Quality and Performance Committee (QPC) including chair Jeremiah D. Schuur, MD, MHS, FACEP, Michael Phelan, MD, RDMS, FACEP, Todd Slessinger, MD, FACEP, FCCM, FCCP, Christopher Fee, MD, FACEP, and others testified on conference calls and at in-person meetings, that there were equally effective and less invasive methods for monitoring septic patients.  Nonetheless, the NQF endorsed the requirement for the central line, noting that they would re-consider if additional evidence warranted it.

Within a few months the Protocolized Care for Early Septic Shock (ProCESS) trial was published on March 18, 2014 and under Dr. Alexander Rosenau’s leadership ACEP immediately requested that NQF #0500 undergo an ad hoc review given the impact that this new data would have on this quality measure. After reviewing the data from the ProCESS trial, NQF questioned whether NQF #0500’s item ‘F’, which measures central venous pressure and central venous oxygen saturation, should be retained or removed from the measure. During the review, one of the PIs, Donald Yealy, MD, FACEP engaged in a scientific debate noting that the ProCESS trial enrolled 1,341 patients, with a power to detect a 6-7 percent absolute difference, yet demonstrated no difference in mortality 60-day mortality 90-day mortality, one year mortality, or the need for organ support. The ProCESS also noted no benefit in any outcome when using CVC- guided care and the simpler approaches that stressed early and ongoing care produced the same good outcomes.

CMS, NQF, and others are now also convinced that honing the sepsis bundle is a move forward for our septic patients, with or without invasive monitoring depending on the progression of their disease, their unique circumstances, and the resources available at the ED where they are being treated. As it is ACEP’s mission, we will continue to advocate on behalf of our patients presenting with a diagnosis of sepsis to ensure that they receive the highest quality of emergency care. We look forward to continuing to work with the measure developer to ensure that all septic patients receive the timely, effective care they need, and to continue to save lives from this deadly disease.

Dr. Sama is ACEP’s Immediate Past President and Chair of the Board of Directors

Tips para mejorar la intubación

Una de las 4 charlas de Conceptos14.

Aprovecharé de dejar 2 papers que encuentro que son fundamentales para el conocimiento de todos

1. Preoxigenation and Prevention of Desaturation During Emergency Airway Management
Weingart, Annals of Emergency Medicine, Volume 59, Issue 3, 165 – 175.e1
2. Preoxigenation, Reoxigenation, and Delayed Sequence Intubation in the Emergency Department
Weingart, Journal of Emergency Medicine, Volume 40, Issue 6 , 661 – 667

Nos vemos en #CONCEPTOS14

9 Hours of Chest Pain and Deep Q-waves: Is it too late for Thrombolytics? (Time Window for Reperfusion; Acuteness on the ECG)

A 50 year old hypertensive presented with 9 hours of central crushing chest pain.  BP was 250/120, and after placement on an IV nitroglycerine drip, BP declined to 170/90.  Here is the presenting ECG:
There is diagnostic ST elevation with large T-waves.  However, there are deep QS-waves.  
1. How do we know these QS-waves do not represent LV aneurysm?
2. Do these Q-waves imply that the STEMI is too far progressed for benefit from tPA?

Let's answer question 1: The T-waves are too tall for LV aneurysm!  You can use this LV Aneurysm Rule to Determine whether there is acute STEMI or ST elevation due to LV aneurysm.
Question 2 is answered extensively below.

Time window for thrombolytics: The GISSI and the LATE trial both established that late thrombolysis, up to 12 hours after onset of chest pain, is beneficial for STEMI.  The FTT collaborative group meta-analysis confirmed this, and the benefit at various time points after pain onset is best described in the paper by Boersma (see Table below).  There are many STEMI, however, which will benefit beyond 12 hours of chest pain: the time onset of chest pain is not necessarily the time of onset of irreversible ischemia.  Many MIs have dynamic occlusion and reperfusion of the infarct-related artery and the pain can go on for days without any significnat necrosis.

The best indicator of MI "Acuteness" is the ECG, with these as indicators of high acuteness:
1. Absence of Q-waves
2. High ST segments
3. Large size of T-waves
4. Absence of T-wave inversion all indicators of high acuity.
At the bottom, I have reprinted a section that I wrote on "Acuteness" that comes from a chapter on reperfusion thereapy that I wrote with Bill Brady.

In this case, the ST segments are high, the T-waves are large, and there is no T-wave inversion.  The Q-waves are the only indicator of prolonged ischemia.  Moreover, the chest pain is less than 12 hours.  Unless there are important contraindications to reperfusion (i.e., high bleeding risk), then either tPA or PCI are indicated.

Case Progression
The physician could not get the interventionalist to take the patient for PCI (I am not sure why).  

The emergency physician sent this case to me real time, wondering if the QS-waves (absence of any R-wave) were a contraindication to tPA.  Before I could answer that, "no" they are not a contraindication, he gave tPA.

Shortly after tPA, this ECG was recorded:
There is significantly lower ST elevation, T-waves are no longer acute (tall) and have begun to invert.  These are signs of reperfusion.

In addition, and importantly, the pain completely resolved with thrombolytics.

An echocardiogram showed akinesis of the mid-apical portion of the anterior septum and mid-apical portion of the inferior septum.  There was no thinning to suggest old MI (not LV aneurysm). This was consistent with acute anterior STEMI.

Subsequently, the interventionalist agreed to take the patient for rescue PCI (even though the thrombolytics had clearly lysed the thrombus).  Angiogram revealed a severely stenotic mid-LAD lesion with no more thrombus present and TIMI-3 flow (excellent).  Thus, the artery had opened.  It was stented.

How long after onset of chest pain are thrombolytics effective (how long is the time window)?

Table 33-1 (from my book: The ECG in Acute MI): Time to thrombolysis and mortality reduction.  From: Boersma et al., Early thrombolytic treatment in acute myocardial infarction: reappraisal of the golden hour. Lancet October 21, 1996, 348:771-775.  (This applies to all MI: anterior, inferior, lateral)
Time Window
Lives saved per 1000 patients treated (confidence intervals)
0-1 hour
65 (38-93)
1-2 hours
37 (20-55)
2-3 hours
26 (14-37)
3-6 hours
29 (19-40)
6-12 hours
18 (7-29)
12-24 hours
9 (-5-22) (not statistically significant)

What is the significance of pathologic Q-waves on the inital ECG?

Q-waves are often seen in the first hour after pain onset.  Raitt et al. found in a subgroup of 432 first MI patients whose ECG was recorded within the first hour after onset of chest pain that pathologic Q-waves were already present, and this was particularly true for anterior MI patients.  These patients had larger final infarct size, but equal benefit from thrombolytic therapy. 

More recently, Armstrong et al. showed that Q-waves on the baseline ECG are an independent marker of worse clinical outcome and, importantly, "after multivariable adjustment, baseline Q-wave but not time from symptom onset was significantly associated with a 78% relative increase in the hazard of 90-day mortality and a 90% relative increase in the hazard of death, shock, and CHF."  Thus, another study shows that the ECG is a better marker of "acuteness" of the ECG than is time of symptom onset.

Lastly, when is it too late for emergent PCI?  Never, if there is persistent chest pain.

How about if the chest pain is resolved, but there is still ST elevation?  That was assessed in this study by Schomig et al. (this is linked to full text; reference and abstract below). They randomized patients who had at least one chest pain episode of at least 20 minutes that occurred between 12 and 48 hours before presentation, and had no persistent symptoms (!), but had unequivocal ischemic ST elevation on the ECG.  Randomized to immediate angiogram with PCI vs. later unplanned invasive evaluation and treatment if they developed recurrent severe angina, hemodynamic and electrical instability, severe congestive heart failure and/or pulmonary edema, mechanical complications, new relevant electrocardiographic changes (new or reelevation of ST-segments of 0.2 mV in 2 contiguous precordial leads or 0.1 mV in 2 adjacent limb electrocardiographic leads), reelevation of creatine kinase or creatine kinase-MB by at least 50% above the trough level after documentation that the level was decreasing prior to this re-elevation, or signs of induced ischemia during exercise testing.

It is taken as a given that if there are persistent symptoms, emergent PCI is indicated!!

Mechanical Reperfusion in Patients With Acute Myocardial Infarction Presenting More Than 12 Hours From Symptom Onset: A Randomized Controlled Trial.  Schomig et al. 
JAMA. 2005;293:2865-2872


Context: No specifically designed studies have addressed the role of primary percutaneous 
coronary intervention in patients with acute ST-segment elevation myocardial infarction (STEMI) presenting more than 12 hours after symptom onset. Current guidelines do not recommend reperfusion treatment in these patients.
Objective: To assess whether an immediate invasive treatment strategy is associated with a reduction of infarct size in patients with acute STEMI, presenting between 12 and 48 hours after symptom onset, vs a conventional conservative strategy. Design, Setting, and Patients International, multicenter, open-label, randomized controlled trial conducted from May 23, 2001, to December 15, 2004, of 365 patients aged 18 to 80 years without persistent symptoms admitted with the diagnosis of acute STEMI between 12 and 48 hours after symptom onset.
Interventions: Random assignment to either an invasive strategy (n=182) based predominantly
on coronary stenting with abciximab or a conventional conservative treatment
strategy (n=183).
Main Outcome Measures: The primary end point was final left ventricular infarct size according to single-photon emission computed tomography study with technetium Tc 99m sestamibi performed between 5 and 10 days after randomization in 347 patients (95.1%). Secondary end points included composite of death, recurrent MI, or stroke at 30 days.
Results: The final left ventricular infarct size was significantly smaller in patients assigned to the invasive group (median, 8.0%; interquartile range [IQR], 2.0%-15.8%) vs those assigned to the conservative group (median, 13.0%; IQR, 3.0%-27.0%; P .001). The mean difference in final left ventricular infarct size between the invasive and conservative groups was −6.8% (95% confidence interval [CI], −10.2% to −3.5%). The secondary end points of death, recurrent MI, or stroke at 30 days occurred in 8 patients in the invasive group (4.4%) and 12 patients in the conservative group (6.6%) (relative risk, 0.67; 95% CI, 0.27-1.62; P=.37).
Conclusion: An invasive strategy based on coronary stenting with adjunctive use of
abciximab reduces infarct size in patients with acute STEMI without persistent symptoms
presenting 12 to 48 hours after symptom onset.

This is a section on "Acuteness" that I wrote in a Chapter on Reperfusion therapy that I wrote with Bill Brady in Critical Decisions in Emergency and Acute Care Electrocardiography.  I have updated it here.

Here are a couple posts that demonstrate the issue of acuteness.

Acuteness—when is it too late for reperfusion?  
In deciding on reperfusion, particularly on fibrinolytic therapy, it is important to assess the amount of viable injured myocardium at risk of infarction.  This is traditionally done by assessing time since pain onset, and randomized trials of fibrinolytics found no significant advantage if pain duration was greater than 12 hours.[12, 32, 49]  However, time since pain onset is a crude way of assessing amount of infarcted (irreversible), vs. ischemic (viable, salvageable), myocardium.  Often, occlusion is incomplete, or collateral circulation maintains the viability of ischemic myocardium, or there is ischemic preconditioning, and myocardium that is fully salvageable may have pain duration of days.  Fortunately, the ECG is a better indicator of salvageable myocardium than pain duration. 
            High ECG “acuteness” is associated with significant salvageable myocardium.   An ECG has a high acuteness score if it has tall T-waves, and lower acuteness if there are Q-waves or T-wave inversion is present.[50]  In 395 patients, this score was shown to add the most value in situations of data disagreement: 1) in acute anterior MI when the history indicates symptom onset of greater than 2 hours but the acuteness score is high, or 2) in acute inferior MI, if history indicates a time since symptom onset less than 2 hours but the acuteness score is low.[51]  More recently, a high acuteness score was found on SPECT scanning and Cardiac MRI to be associated with more salvageable myocardium, and to be superior to time since pain onset for determining myocardium at risk (but not yet infarcted).[52]  This corresponds to other data showing that tall T-waves are an independent marker of benefit from fibrinolytics.[53] and that, among those with positive T waves, mortality after thrombolytics is the same for those who have greater than 2 hours vs. less than 2 hours of symptoms.[54]  It is also important to know that QR-waves are present in 50% of anterior MI within the first hour, and represent ischemia of the conducting system, not infarction.[55]      
            There are no randomized fibrinolytic trials based on EKG characteristics of acuteness.  However, PCI is proven beneficial in a randomized trial of patients with persistent ST elevation at greater than 12 hours after onset, even though they were pain free.[56] 
            Finally, ischemic discomfort is far less predictive of on ongoing ischemia than is persistent STE and tall T-waves.  ECG acuteness should not be ignored because of resolution of symptoms.[57]
            In summary, tall T-waves indicate a large amount of viable, salvagable, myocardium.  Q-waves indicate lower acuteness, but may be present early in anterior MI; thus, in anterior MI, T-waves are more important.   Inverted T-waves signify either low acuteness or an open artery (see chapter 11 on reperfusion).

12.       LATE Study Group, Late assessment of thrombolytic efficacy (LATE) study with alteplase 6-24 hours after onset of acute myocardial infarction. Lancet, 1993. 342: p. 759-766.
32.       Fibrinolytic Therapy Trialists' (FTT) Collaborative Group, Indications for fibrinolytic therapy in suspected acute myocardial infarction: collaborative overview of early mortality and major morbidity results from all randomised trials of more than 1000 patients. Lancet, 1994. 343: p. 311-322.
49.       EMERAS (Estudio Multicentro Estreptoquinsa Republicas de America del Sur), Randomised trial of late thrombolysis in patients with suspected acute myocardial infarction. Lancet, 1993. 342(8874): p. 767-772.
50.       Wilkins, M.L., et al., An electrocardiographic acuteness score for quantifying the timing of a myocardial infarction to guide decisions regarding reperfusion therapy. Am J Cardiol, 1995. 75(8): p. 617-620.
51.       Corey, K.E., et al., Combined historical and electrocardiographic timing of acute anterior and inferior myocardial infarcts for prediction of reperfusion achievable size limitation. Am J Cardiol, 1999. 83(6): p. 826-831.
52.       Engblom, H., et al.  The evaluation of an electrocardiographic myocardial ischemia acuteness score to predict the amount of myocardial salvage achieved by early percutaneous coronary intervention : Clinical validation with myocardial perfusion single photon emission computed tomography and cardiac magnetic resonance.  Journal of Electrocardiology 44(5):525-532; Sept-Oct 2011.
53.       Hochrein, J., et al., Higher T-wave amplitude associated with better prognosis in patients receiving thrombolytic therapy for acute myocardial infarction (a GUSTO-1 substudy).  Global Utilization of Streptokinase and Tissue plasminogen activator for Occluded Coronary Arteries. Am J Cardiol, 1998. 81(9): p. 1078-1084.
54.       Herz, I., et al., The prognostic implications of negative T-waves in the leads with ST segment elevation on admission in acute myocardial infarction. Cardiology, 1999. 92(2): p. 121-127.
55.       Raitt, M.H., et al., Appearance of abnormal Q waves early in the course of acute myocardial infarction: implications for efficacy of thrombolytic therapy. J Am Coll Cardiol, 1995. 25(5): p. 1084-1088.
56.       Schomig, A., et al., Mechanical reperfusion in patients with acute myocardial infarction presenting more than 12 hours from symptom onset: a randomized controlled trial. Jama, 2005. 293(23): p. 2865-72.
57.       2007 Writing Group to Review New Evidence and Update the ACC/AHA 2004 Guidelines for the Management of Patients With ST-Elevation Myocardial Infarction, 2007 Focused Update of the ACC/AHA 2004 Guidelines for the Management of Patients with ST-Elevation Myocardial Infarction. J Am Coll Cardiol, 2008. 51(2).