Treating the Post-Cardiac Arrest Syndrome: The Time Is Now
Pub Date: Thursday, October 23, 2008
Author: Karl B. Kern, MD
During this last decade, incremental improvements in long-term survival after cardiac arrest have occurred. The availability of smaller, less expensive, automatic, external defibrillators has allowed communities the opportunity to institute local programs of public access defibrillation. Though these efforts have generally been modestly successful, the survival impact of such a strategy has been less than anticipated.
Recently, emphasis on uninterrupted chest compressions to produce better circulation during out-of-hospital resuscitation has resulted in substantially improved survival, with some communities more than doubling their survival rates compared to historical controls.[2-5] The magnitude of improvement seen in these reports has been more than expected, causing some to doubt their validity. The "Hawthorne effect" is a commonly espoused explanation; however, a recent follow-up report showing persistent improvement in survival rates after 3 years suggests such improvements are neither temporary nor merely secondary to enthusiasm resulting from protocol changes.
The success seen with providing more circulation through less interruption of chest compressions brings forth this question: "Where will we find the next real incremental improvement in long-term survival following cardiac arrest?" The most promising area appears to be in the patient's postresuscitation care.
Published in this issue of Circulation is a joint statement from the American Heart Association (AHA) and the International Liaison Committee on Resuscitation (ILCOR) concerning the importance of the "post-cardiac arrest syndrome," a previously somewhat neglected area of resuscitation. As this important statement highlights, there are currently more questions than answers concerning optimal postresuscitation care.
Nonetheless, several things are known concerning the importance of aggressive post-cardiac arrest therapy. It is now clear that initial restoration of spontaneous circulation does not equal improved long-term outcome. Numerous reports have shown that the vast majority of those initially resuscitated from out-of-hospital cardiac arrest do not survive to hospital discharge.[7-10] Indeed, 70% of such patients have historically succumbed while in the hospital. Such a high in-hospital loss of those who were initially resuscitated is unacceptable and highlights the great need and opportunity for significantly improving our current survival rates through more successful post-cardiac arrest care. Simply formalizing our approach to postresuscitation care can improve long-term survival. A landmark study by Sunde et al. in 2007 showed that by using a formal protocol for post-cardiac arrest care, they increased survival to hospital discharge with a favorable neurological outcome (cerebral performance category [CPC] 1 or 2) from 26% to 56% (p <0.001). Their postresuscitation care protocol included the use of therapeutic hypothermia, early coronary reperfusion after cardiac arrest, hemodynamic support of post-arrest stunned myocardium, rapid weaning from positive pressure ventilation, and glycemic control.
Though this comprehensive AHA/ILCOR report on the "post-cardiac arrest syndrome" illustrates that many questions and issues remain, at least two important treatments must be included to optimize postresuscitation care. Therapeutic hypothermia post-cardiac arrest and early coronary angiography combined with appropriate percutaneous coronary intervention (PCI) for rapid reperfusion therapy can increase long-term neurologically intact survival.
Therapeutic hypothermia (combined with hemodynamic support when needed) was shown in two randomized trials in 2002 to improve not only survival but also the proportion of survivors with good neurological function.[12,13] Several criticisms have been made of these trials, centered primarily on the fact that only a small percentage of out-of-hospital cardiac arrest patients were included, namely those with ventricular fibrillation cardiac arrest of less than 15 minutes prior to their resuscitation. Many communities have moved forward in providing therapeutic hypothermia for comatose victims of out-of-hospital cardiac arrest. Subsequent nonrandomized data collection registries (similar to postmarketing surveillance data collection) have continued to show favorable neurologically intact outcomes when therapeutic hypothermia is employed. Online resources are now available to help interested medical centers initiate and successfully establish therapeutic hypothermia programs for the comatose post-cardiac arrest patient.
The AHA/ILCOR statement calls for more aggressive use of early coronary angiography and percutaneous intervention for the survivors of out-of-hospital cardiac arrest. This is a relatively unappreciated but important aspect of post-cardiac arrest care. There are now substantial data supporting such an approach. The majority of out-of-hospital cardiac arrests are precipitated by an ischemic myocardial event, and sudden death is frequently the first manifestation of previously unknown coronary artery disease. There are a number of observational clinical reports of increased survival among cardiac arrest patients who were successfully resuscitated and then actively reperfused by coronary angiography and PCI. Early studies showed the feasibility of such an approach [15,16], later studies showed its safety [17,18], and most recently a number of studies have shown its beneficial effects on increasing neurologically intact survival.[17-27] All these studies were historically controlled. Table 1 summarizes these various studies and their results.
Several important details concerning the use of early cardiac catheterization and angioplasty postresuscitation deserve comment. Perhaps the most important question is exactly who should receive such therapy. The data suggest that all successfully resuscitated victims of out-of-hospital cardiac arrest secondary to an acute ST elevation myocardial infarction (MI) should be treated in the same way as those without cardiac arrest: namely, with timely primary PCI. The 90-minute goal for "door to reperfusion" time should be applied to all ST elevation MI patients, regardless of whether they required resuscitation from cardiac arrest or not. Some common sense is obviously needed in selecting which post-cardiac arrest patients should go emergently to the catheterization suite, specifically considering the length of their resuscitation effort and their associated comorbid conditions. However, age itself does not appear to be a prohibitive factor. We recently had an active 87-year-old patient who was taken to the catheterization laboratory immediately postresuscitation from out-of-hospital cardiac arrest and was percutaneously reperfused. This patient had an excellent neurological and functional recovery, albeit after a somewhat prolonged 11-day hospital course.
The level of consciousness immediately after cardiac arrest should not be the determining factor for or against early catheterization. Some data suggest that ST elevation MI patients who are conscious post-cardiac arrest have the same long-term outcome after primary angioplasty as ST elevation MI patients without cardiac arrest. Though ST elevation MI patients with decreased level of consciousness after cardiac arrest do not do quite as well, they still benefit greatly, nearly doubling their long-term neurologically normal survival rate compared to such patients who did not have early coronary angiography and PCI.[17-27]
But what of those patients postresuscitation who have no obvious ST elevation on their 12-lead electrocardiogram (ECG)? Should they be taken emergently to the catheterization suite for early angiography and possible PCI? Spaulding et al. showed that after cardiac arrest, the absence of electrocardiographic ST elevation did not rule out the possibility of a total coronary occlusion. In other words, the ECG is not a sensitive marker of total coronary occlusion in the postresuscitation population. Our experience at the University of Arizona has included several patients post-cardiac arrest with relatively normal ECGs, manifesting sinus tachycardia but no evidence of ischemia, who at early cardiac catheterization were found to have acutely occluded epicardial coronary vessels. Therefore, it seems reasonable that all patients who are successfully resuscitated from out-of-hospital cardiac arrest should be strongly considered for early cardiac catheterization and possible angioplasty. This should be done within 90 minutes of arrival, just as one would treat an ST elevation MI patient. Coma alone is not a legitimate reason to deny postresuscitation patients such therapy. Long-term survival rates are doubled (typically from 30% to 60%) in this high-risk population post-cardiac arrest with an early invasive approach (Table 1). Importantly, more than 80% who survive long term after early angiography and PCI are neurologically intact (Table 1).
It is important to recognize that though the comatose, post-cardiac arrest population is at high risk and their prognosis is worse than those ST elevation MI patients without cardiac arrest, their treatment is not futile. In the past, some have suggested that post-cardiac arrest patients should not be aggressively managed until their long-term neurological status is known. Unfortunately, as this joint AHA/ILCOR statement notes, such a stance requires a lapse of several days before legitimate central nervous system prognostication can be made. During such a wait, the opportunity to intervene and improve outcome is lost. Though there are no randomized trials comparing these two strategies, clinical studies and experience in the last few years have shown improved patient outcome with a more aggressive approach, including emergent catheterization and coronary reperfusion when needed. Current "best practice" now suggests this more aggressive, less nihilistic approach for post-cardiac arrest victims.
Finally, a significant and continuing obstacle to widespread implementation of early catheterization and percutaneous reperfusion for those resuscitated from cardiac arrest is that, despite doubling long-term survival rates, a significant proportion of these patients will still die (30% to 50%). Such deaths typically occur days or even weeks later, often from refractory cardiogenic shock or central nervous system injuries. In most of today's health care reporting systems, such deaths are tabulated as percutaneous coronary interventional deaths. Such data collection and interpretation remains a barrier for interventionalists and catheterization laboratories in providing what should be optimal post-cardiac arrest patient care. The AHA in conjunction with the American College of Cardiology and the European Society of Cardiology should acknowledge two facts: first, the importance and value of early coronary angiography and emergent reperfusion for successfully resuscitated out-of-hospital cardiac arrest victims and, second, the very high risk for poor long-term outcome in such patients. These societies should concede that a higher death rate is to be anticipated in this high-risk population and that such deaths should not generally be categorized as a death related to the PCI, particularly when death occurs from noncoronary causes days after the procedure.
The very best long-term outcomes after cardiac arrest are seen when both therapeutic hypothermia and early PCI are used (Table 2). With these combined therapies, long-term, neurologically intact survival reaches 80%! Our current approach at the University of Arizona Sarver Heart Center is immediate institution of hypothermia on arrival and activation of our "CLOT" (Coronary Lysis On Time) team for emergent coronary angiography and potential reperfusion. Hypothermia can be instituted quickly upon arrival in the emergency department and does not need to delay efforts for reperfusion. We typically use a commercially available external cooling device, with radiolucent pads that do not impede angiographic views or quality. Other cooling techniques can be used including invasive devices or simple iced saline and ice packs. In our experience, the patient will often achieve target temperature of 34° centigrade in the catheterization suite during the procedure.
In attempting to provide the best care available for cardiac arrest victims in the State of Arizona, the Arizona Department of Health and Emergency Services has moved forward with a program designating "Cardiac Arrest Centers" for the formalized treatment of resuscitated victims of out-of-hospital cardiac arrest. Medical centers desiring to care for these patients must provide a certain standard of postresuscitation care that includes therapeutic hypothermia and capability for emergent cardiac catheterization and PCI, 24 hours a day, 7 days per week. This initiative has been led and espoused by the state EMS director and has been met with enthusiasm throughout the state. Thus far, seven medical centers in Arizona have qualified and are now designated by the Arizona Department of Health as "Cardiac Arrest Centers."
As this joint AHA/ILCOR statement, "Post-Cardiac Arrest Syndrome: Epidemiology, Pathophysiology, Treatment, and Prognostication" highlights, now is the time to move forward. Truly this is a call to action for improving long-term survival through recognition and treatment of the post-cardiac arrest syndrome. It is no longer acceptable to simply watch and wait, hoping such patients will improve and survive long term without significant central nervous system deficits. Now is the time to actively pursue quality and aggressive postresuscitation care if further improvements in neurologically intact long-term survival are to be realized.
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-- The opinions expressed in this commentary are not necessarily those of the editors or of the American Heart Association