Current Events in Cardiac Arrest Research

Ever since the first care report of successful modern CPR was published in 1960, research aimed at refining it has grown exponentially.1 Early AHA guidelines for ACLS, in 1974, were quite different than current ones, although many core components have persisted.2, 3 Even across recent years, standards of care have changed dramatically; it wasn’t long ago that capnography was relatively unknown to EMS and placing the tube was priority number one. At present, the AHA guidelines are updated every five years, most recently in 2010. Guideline changes are based on a literature review performed by experts in various fields across the world, a process that has already begun for the 2015 update. The International Liaison Committee on Resuscitation (ILCOR) is the coordinating body that sifts through reviewers’ recommendations and proposes changes. As the frontline providers in cardiac arrest care, it is important for EMS providers to not only be up to date on cardiac arrest standards, but also to understand the studies underpinning them. This article reviews recent literature that may soon change the way you care for your most ill patients.

Medication Use in Cardiac Arrest

It has been more than 10 years since bretylium, isoproterenol and high-dose epinephrine were questioned for their usefulness in cardiac arrest, and removed from both the guidelines and ambulances.4 More recently, in 2005, lidocaine was largely replaced by amiodarone.5 Only two years ago, with the 2010 changes, was atropine removed.6 Today, standard epinephrine, vasopressin and even the antiarrhythmics are being questioned in large research trials. A recent editorial in the Journal of the American Medical Association (JAMA) claimed, “The best available observational evidence indicates that epinephrine may be harmful to patients during cardiac arrest, and there are plausible biological reasons to support this.”7

Epinephrine, long considered a core component of cardiac arrest management, has never been properly studied for effectiveness. In fact, neither have most of the cardiac arrest medications until recently. It was only in 2003 that a group of researchers in Norway decided to evaluate medication effectiveness in a six-year randomized trial in which patients received either a normal regimen of IV drugs by paramedics or none. The results were surprising: although return of spontaneous circulation (ROSC) rates were improved (32% in the control group receiving normal medications vs. 21% in the trial group receiving placebo), there was no change in all other outcomes. These other outcomes included survival to discharge, favorable neurological outcome and one-year survival.8 These results raised an important question that healthcare providers are obligated to consider: What is considered good outcome? Is more ROSC really a good thing when survival to discharge and neurological outcome are unchanged? Put in a population-based context, this question becomes: Is this the best use of healthcare resources?

In 2006, a group in Western Australia performed a randomized trial that put epinephrine against placebo. Similar to the Norway study, paramedics gave either real epinephrine or placebo to cardiac arrest patients without knowing which was which—a “blinded” study. This study again showed a higher ROSC in the epinephrine group (23.5%) than the placebo group (8.4%). However, this study also showed there was no statistically significant change in survival to discharge, prompting the same questions as the previous study.9 Difficulties with the execution of this study highlighted some important issues for EMS providers to consider as our field becomes increasingly research-driven and evidence-based. Although planned as a multicenter study to include a larger number of patients, four out of five EMS services refused to participate as they felt it unethical to “withhold the standard of care,” meaning epinephrine. As EMS providers we need to decide what is truly unethical: that, or relying on an unproven medication, which may not help or may even harm patients, simply because “that’s how it’s always been done.” The lack of agency participation and negative press led to this study being halted early. As the authors of this study put it, barriers to research such as this “serve only to ensure such interventions remain unproven.”

In March 2012, a Japanese research group looked prospectively at ED admissions for cardiac arrest that received either epinephrine or nothing during initial treatment, which was based on the type of responder on scene. In looking at over 400,000 patients they found similar results: ROSC was improved (18% vs. 5% here) but one-month survival was unchanged, and, most interestingly, neurological outcomes were worse. Although the difference was small—1.4% in the epinephrine group had good functional status at one month as opposed to 2.2% in the placebo group—this was a very statistically significant change in such a large study and should force us to question the treatment we call the standard of care.10

The authors of the Japanese Hagihara study propose some theories for their findings based on previous animal-based research of epinephrine. They report it has been shown to increase lactate and over-constrict the microcirculation throughout the body, which could lead to an overall net increase in metabolic debt created during the arrest that is unrecoverable post-arrest. Further, epinephrine has been shown to promote post-arrest arrhythmias and to activate platelets, both of which may worsen outcomes.

Although the epinephrine debate is still some time from being settled, a large-scale multicenter trial in North America is about to begin that will help settle another medication controversy. The “Amiodarone, Lidocaine or Neither (Placebo) for Out-Of-Hospital Cardiac Arrest Due to Ventricular Fibrillation or Tachycardia (ALPS)” study, headed out of the University of Washington, will compare amiodarone, lidocaine and placebo use by EMS in cardiac arrest. The results of this study, and possible future epinephrine studies, will help the resuscitation community determine the best treatment for our patients. A final bit about vasopressin, which is still considered to be an adequate alternative to epinephrine in cardiac arrest: A 2012 meta-analysis of six randomized controlled trials that compared epinephrine against vasopressin found no improvement in sustained ROSC, long-term survival or favorable neurological outcome. It did, however, find a slightly higher long-term survival in asystole patients.11

Intubation & Supraglottic Airways

Airway control methods in the field for cardiac arrest and other unstable patients have been a heavily debated topic for some time. It was a study out of Los Angeles published in 2000 that surprised many when it clearly demonstrated outcomes for pediatric cardiac arrest patients intubated in the field were no better, and possibly worse, than those who were managed with a BVM.12 While now accepted as a reasonable alternative to not intubate pediatric cardiac arrests in the field in lieu of BVM ventilation per current PALS guidelines, it remains unclear what is best for adults. The 2010 ACLS guidelines state, “If advanced airway placement will interrupt chest compressions, providers may consider deferring insertion of the airway until the patient fails to respond to initial CPR and defibrillation attempts, or demonstrates ROSC,” and since their publication new studies have continued to suggest intubation may not be the most optimal treatment in the field.13

Supraglottic airways (SGA), such as King tubes, laryngeal mask airways (LMA), Combitubes and others, have emerged as useful alternatives to endotracheal intubation (ETI) over the past few years. A Japanese study of witnessed non-traumatic out-of-hospital cardiac arrests (OHCA) included over 5,000 patients and showed favorable neurologic outcome was the same (3.6%) regardless of whether an endotracheal tube or SGA was used. A longer time to placement was noted for ETI, though, which could lead to longer scene times for these patients.14

The National EMS Information System (NEMSIS) data has been adding to our understanding of airway management outcomes in the United States. A look at NEMSIS data from 16 states and 4.3 million EMS calls in 2008 showed a dramatic 10% improvement (87% vs. 77%) in successful airway management when an SGA was used as opposed to ETI. “Successful airway management” was defined as the ability to ventilate, and SGAs included the Combitube, LMA, esophageal obturator airway (EOA) and King LT.15 Besides strongly supporting SGAs as the preferred method, this paper raised important questions regarding the ability of EMS providers to intubate in the field (a 77% success rate was shown in just over 10,000 intubation attempts). This was in contrast to a meta-analysis published a year earlier that reported an 86.3% success rate in field intubation; the reason for this disparity is unclear.16

Smaller retrospective studies continue to be published regarding field intubation in cardiac arrest, and they are nearly universally supportive of abandoning the practice. Data from three states published in 2010—Michigan, California and North Carolina—showed poorer outcomes for intubated patients in cardiac arrest. In Michigan, VF/VT survival to discharge was decreased with field intubation.17 In California, survival to discharge was over four times greater for patients treated with BVM ventilation as opposed to intubation.18 Finally, in North Carolina ROSC was over five times more likely in nonintubated patients.19 While none of these studies are conclusive, taken together they should force the EMS community to consider the use of alternative airways if they aren’t already doing so.

Vascular Access

With the advent of rapid intraosseous (IO) access thanks to various drill-based devices, the best method for obtaining primary vascular access in cardiac arrest must be questioned. A randomized trial in North Carolina had paramedics start a tibial IO, a humeral IO or a peripheral IV (PIV) as first-line access in cardiac arrest patients to evaluate this. The results speak for themselves: access was obtained on the first attempt in 91% of tibial IO patients as opposed to 51% for humeral IO and 43% for PIV. The time taken for initial success was quickest with a tibial IO as well.20 The AHA clearly supports the use of these devices in adults, and it is reasonable for EMS agencies to consider using them for first-line access in cardiac arrest.

CPR Devices & Pumps

Various adjuncts to CPR have been developed and used in an attempt to optimize or enhance the manual delivery of compressions and ventilations. Two of the more common mechanical compression devices are the load-distributing band CRP model (the ZOLL AutoPulse) and the mechanical piston model (Physio-Control LUCAS). Despite a natural inclination to believe these devices would improve CPR, field research trials have to date been unsupportive.

The AutoPulse was studied in a multicenter randomized trial in 2004, during which EMS providers either used the AutoPulse or performed regular CPR. The study was halted early due to safety concerns after an interim review of results showed survival to discharge in the AutoPulse groups to be over 40% lower than the regular CPR group. Survival at four hours, however, was similar.21 A number of reasons were suggested for this finding, including a learning curve for the device, delayed time to device deployment, a Hawthorne effect (control group doing more effective CPR than normal since they were being monitored) and enrollment bias (using the AutoPulse on people who normally would have been pronounced in the field).

The Lund University Cardiac Arrest System (LUCAS) device has not yet been properly studied in a randomized fashion; however, such a study is scheduled to begin in the United States soon and a European one is ongoing. A pilot study in Sweden showed the device led to no improvement in early survival though, so the AHA has yet to endorse the routine use of this product.22 Given the risks of performing CPR in a moving ambulance and the necessary gaps in compressions during patient movement, an automated compression device seems like good fit for EMS. The current and upcoming LUCAS trials will help answer the important question of if our patients truly benefit from it.

Impedance threshold devices (ITD) were the subject of a multicenter randomized controlled trial in the U.S. and Canada that was halted early in 2009 for futility. The ITD had been shown to improve hemodynamics and survival in animal studies, and this trial attempted to reproduce that effect in human patients. By blocking passive inflow of air into the chest during CPR compression recoil, the device increases negative intrathoracic pressure and therefore increases venous return leading to a higher cardiac output. Patients in the study were assigned to receive care with either an actual ITD or a sham ITD, and paramedics were blinded to which they were using. After an interim evaluation of over 8,000 patients showed no difference in survival between the two study groups, it was decided further enrollment would not change the outcome.23

Although this study demonstrated no benefit to using the ITD, one area of ongoing discussion is the use of it in conjunction with active compression-decompression CPR. One study showed a survival benefit when used together and as such that remains a reasonable approach to care.24

The AHA recognized in 2010 that the field of CPR adjuncts was rapidly evolving; however, they were unable to provide a positive recommendation for their use at the time. The authors of the guidelines made the following statement immediately following their non-recommendation: “The experts are aware of several clinical trials of the devices listed below that are underway and/or recently concluded, so readers are encouraged to monitor for the publication of additional trial results in peer-reviewed journals and AHA scientific advisory statements.”25

STEMI Centers & Cardiac Arrest Centers

Regionalizing care in the U.S. through the creation of specialty centers has been effective for many years at reducing the mortality of trauma patients, burn patients and pediatric patients. Stroke centers were a more recent innovation and while initially shown to be effective, they now are coming under scrutiny. Recent research shows the stroke center hospitals were better in providing stroke care even before the stroke center designation, and even after implementation gains in survival and neurologic recovery are modest.26,27

STEMI and cardiac arrest centers are the newest iteration of this movement and it appears the survival gains may be modest here as well. A recently published study compared the outcomes of STEMI patients between hospitals in North Carolina participating in a regionalization model with those that weren’t, and also with national trends. It showed that, although mortality has improved, the improvement in STEMI centers was no better than in the preexisting system.28 As the authors of this study noted, this raises important questions for system administrators as they develop their own regionalized STEMI center systems. Further, this brings into question the proposed model of cardiac arrest centers emerging in many cities, as it is largely based on the stroke and STEMI models.

Defibrillation Timing & Dosing

Since the 2005 AHA guideline revision, an extra step was included in the defibrillation decision making tree. If a patient was found in cardiac arrest by EMS, and no bystander CPR was being performed, then the provider was to perform two minutes of CPR prior to defibrillation. However, if bystander CPR was in progress, the provider should immediately proceed to defibrillation. If the arrest was witnessed by EMS, defibrillation should be done immediately as well. This was based on the hypothesis that CPR prior to defibrillation could improve myocardial perfusion, thereby improving the likelihood of a successful defibrillation.29

Whether this theory leads to better outcomes was evaluated in a multicenter trial in North America by the Resuscitation Outcomes Consortium (ROC) investigators from 2007 to 2009. They found there was no difference in outcomes of cardiac arrest patients for whom 30–60 seconds of CPR (enough time to place pads and prepare the defibrillator) or 180 seconds of CPR was performed. Additionally, their data suggested a possible decrease in survival for patients in ventricular tachycardia or ventricular fibrillation who received 180 seconds of CPR.30

Resuscitation Research

The International Liaison Committee on Resuscitation (ILCOR) promotes and coordinates resuscitation research and guideline development worldwide. It is made up of representative organizations from the United States (American Heart Association), Europe (European Resuscitation Council), Canada (Heart and Stroke Foundation of Canada), and other nations and regions, such as the Australian and New Zealand Committee on Resuscitation, Resuscitation Councils of Southern Africa, Inter American Heart Foundation and Resuscitation Council of Asia. During their meetings, research is reviewed and guidelines are developed through consensus. It is from these meetings that the AHA guidelines here in the U.S. largely arise. Learn more at www.ilcor.org.

Conclusion

Cardiac arrest management is the bread and butter of the EMS skill set. Of all the fields and specialties in healthcare, EMTs and paramedics stand out as the experts, capable of managing these critical patients in suboptimal settings often with inadequate personnel. The foundation of this knowledge and skill set is built in the original EMT and paramedic courses and refined throughout years of BCLS, ACLS and PALS refresher courses. As this review demonstrates, the hypotheses and science behind these guidelines are critically evaluated in a constant fashion. As healthcare providers on the front lines we must stay up to date on the research and understand the findings in order to provide the best possible care to our patients.

References

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16. Hubble MW, Brown L, Wilfong DA, et al. A meta-analysis of prehospital airway control techniques, part I: orotracheal and nasotracheal intubation success rates. Prehosp Emerg Care, 2010; 14: 377–401.

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18. Hanif MA, Kaji AH, Niemann JT, et al. Advanced airway management does not improve outcome of out-of-hospital cardiac arrest. Acad Emerg Med, 2010 Sep; 17(9): 926–31.

19. Studnek JR, Thestrup L, Vandeventer S, et al. The association between prehospital endotracheal intubation attempts and survival to hospital discharge among out-of-hospital cardiac arrest patients. Acad Emerg Med, 2010 Sep; 17(9): 918–25.

20. Reades R, Studnek JR, Vandeventer S, et al. Intraosseous versus intravenous vascular access during out-of-hospital cardiac arrest: a randomized controlled trial. Ann Emerg Med, 2011 Dec; 58(6): 509–16.

21. Hallstrom A, Rea TD, Sayre MR, et al. Manual chest compression vs. use of an automated chest compression device during resuscitation following out-of-hospital cardiac arrest: a randomized trial. JAMA, 2006 Jun; 295(22): 2620–8.

22. Smekal D, Johansson J, Huzevka T, et al. A pilot study of mechanical chest compressions with the LUCAS device in cardiopulmonary resuscitation. Resuscitation, 2011 Jun; 82(6): 702–6.

23. Aufderheide TP, Nichol G, Rea TD, et al. A trial of an impedance threshold device in out-of-hospital cardiac arrest. NEJM, 2011 Sep; 365(9): 798–806.

24. Aufderheide TP, Frascone RJ, Wayne MA, et al. Standard cardiopulmonary resuscitation versus active compression-decompression cardiopulmonary resuscitation with augmentation of negative intrathoracic pressure for out-of-hospital cardiac arrest: a randomized trial. Lancet, 2011; 377: 301–311.

25. Cave DM, Gazmuri RJ, Otto, CW, et al. 2010 AHA guidelines for CPR and ECC science, part 7: CPR techniques and devices. Resuscitation, 2010; 122: S720–S728.

26. Lichtman JH, Allen NB, Wang Y, et al. Stroke patient outcomes on U.S. hospitals before the start of the Joint Commission Primary Stroke Center certification program. Stroke, 2009 Nov; 40(11): 3574–9.

27. Litchman JH, Jones SB, Wang Y, et al. Outcomes after ischemic stroke for hospitals with and without Joint Commission-certified primary stroke centers. Neurology, 2011 Jun 7; 76(23): 1976–82.

28. Glickman SW, Greiner MA, Lin L, et al. Assessment of temporal trends in mortality with implementation of a statewide ST-Segment Myocardial Infarction (STEMI) regionalization program. Ann Emerg Med, 2011 Apr; 59(4): 243–52.

29. AHA. 2005 American Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care. Circulation, 2005; 112: IV1–203.

30. Stiell IG, Nichol G, Leroux BG, et al. Early versus later rhythm analysis in patients with out-of-hospital cardiac arrest. NEJM, 2011; 365: 787–97.

Sean M. Kivlehan, MD, MPH, NREMT-P, is an emergency medicine resident at the University of California San Francisco and a former New York City paramedic for 10 years. Contact him at sean.kivlehan@gmail.com.

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