The third episode features Marjorie Lazoff, MD covering cardiac arrest, including the following:
- Indicators of neurological survival
- Socioeconomic disparities in survival
- Cardiac arrest medicines used in resuscitation
Marjorie Lazoff, MD
ClinicalKey Point of Care
Dr. Lazoff is board certified in internal medicine and practiced academic emergency medicine for over 7 years at Temple University Hospital’s ER, where she also served as their director of quality assurance. Marjorie graduated from the University of Cincinnati College of Medicine and completed a residency in internal medicine at the Hospital of University of Pennsylvania in Philadelphia.
Dr. Lazoff, the first study you’ll be discussing comes from a recent Archives of Internal Medicine. It is titled, “A validation prediction tool for initial survivors of in-hopsital cardiac arrest” Why did you select it for this month’s podcast?
Seasoned hospitalists and ER physicians are all too familiar with the ethical “dis-ease” we suffer every time a survivor of a cardiac arrest sustains significant, non-reversible neurological damage as a result of resuscitative efforts. When to continue and when to stop resuscitative efforts – the inevitability of death vs. the goal to keep a patient alive, whatever the quality of that life.
In my experience, most physicians fall somewhere in the middle of that spectrum. We tend to give maximum resuscitative efforts to younger, generally healthy patients who had good neurologic function and quality of life prior to the arrest – and, no surprise, these are among the eleven variables that Paul Chan and the Get With the Guidelines Resuscitation Registry Investigators found were associated with favorable neurological survival, using their Cardiac Arrest Survival Post resuscitation In-hospital (or CASPRI) score.
The authors evaluated nearly 43,000 patients from over 500 acute-care hospitals who sustained a cardiac arrest while a patient in the hospital. Two-thirds of the patients were used to develop the CASPRI score, and the rest were used to test the score’s validity and reliability. Validation was excellent; favorable neurological survival differed by only 0.1% between the two groups.
How do the authors define favorable neurological survival?
Very clinically — either defined as absence of severe neurological deficits, or based on the Cerebral Performance Category with a score of 1 or 2 out of 5. A “2” is defined as moderate cerebral disability, but with sufficient cerebral functioning for independent activities of daily life plus the ability to work in sheltered environment. (Full CPC available on the Web at http://www.fda.gov/ohrms/dockets/ac/05/briefing/2005-4100b1_03_CPC%20Scale.pdf).
Were there unexpected variables that correlated with favorable neurological survival?
Not really. After testing a total of 37 variables, the only other variables that correlated with favorable neurological outcome was an initial rhythm of VFib or pulseless VTach that was defibrillated within 2 minutes – the group of patients most likely to survive a cardiopulmonary perspective. Another variable was arrest location in a monitored setting (such as an ER or ICU), and finally the absence of hypotension prior to arrest, which assumes some form of pre-arrest monitoring as well.
The variables that contributed the greatest impact on the score were time to resuscitation, arrest rhythm, and pre-arrest neurologic status.
All CASPRI variables are pre-arrest in patients under medical care at the time of arrest, as opposed to the traditional post-arrest markers used to assess and predict neurological function in all patients — such as pupillary and motor response after 72 hours, EEG background; level of serum markers of brain injury such as neuron-specific enolase or NSE; and diffusion MRI.
How predictive were the pre-arrest variables?
Those patients who fell in the top 10% of their prediction tool had about a 70% probability of favorable neurological survival whereas those in the bottom 10% had less than a 3% probability of favorable neurological survival.
Were there any limitations with the study or in interpreting its results?
Well, some physicians might protest aspects of the study design and statistical methods, as did Doctors Huszti and Nichol out of University of Washington – Harborview Center for Prehospital Emergency Care in an accompanying commentary. There was also no information regarding how therapeutic hypothermia might impact score results.
To some physicians, the ability to predict who is likely to survive with good neurological outcome during a code might encourage further resuscitation efforts beyond the ordinary, although other physicians might argue that such a prediction is fraught with potential error and misuse.
It will be interesting to see if, as Doctors Huszti and Nichol predict, improvement in cardiac arrest outcomes result more from increased use of new monitoring technologies pre-arrest rather than physicians adjusting resuscitative efforts during a code. In fact, with current trends in technology, the future of monitoring may soon include out-of-hospital high-risk patients using mobile devices and other interactive tools, thereby improving mortality among out-of-hospital cardiac arrests as well.
A second study on cardiac arrest was recently published in the New England Journal of Medicine, where Dr. Sasson and colleagues analyzed data from the Cardiac Arrest Registry to Enhance Survival (or CARES), to better understand the known socioeconomic disparities in survival among various racial and ethnic groups as related to bystander-initiated CPR.
What is that study about?
The authors analyzed over 14,000 patients with an out-of-hospital cardiac arrest using a three-level regression model that considered the neighborhood, and individual patient and bystander-resuscitator characteristics. The study found a direct relationship between the probability that a person would receive bystander-initiated CPR, and a neighborhood with a higher median income and white composition. Independent of the neighborhood’s socioeconomic status, blacks and Hispanics were about 30% less likely than whites to receive bystander-initiated CPR, and those who received CPR were more likely to be male than female.
All patients were less likely to receive bystander-initiated CPR if they had a cardiac arrest in a neighborhood that was low-income or predominantly black, so the authors suggest that public health efforts target low-income black neighborhoods for CPR training. But I wonder what public health initiative we target to remove the race and sex disparities in rates of CPR reported here that are independent of the neighborhood?
Tell us about the third article – a literature review on cardioactive drugs?
In their recent article published in the American Journal of Emergency Medicine, Doctors Boyd and Brady describe the rise and not-always-a-fall in popularity with the 5 most common cardiac arrest medicines used in resuscitation. Indeed, after reviewing the evidence, the authors agree with the most recent AHA published guidelines on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care (2010), which now places greater emphasis on the immediate recognition and activation of emergency response team, effective chest compressions, rapid defibrillation, and integrated post resuscitation care than on ACLS medication.
Epinephrine is the core stable drug of CPR. What are its known benefits?
As most physicians know, the use of the “epi x3” during a code is based on tradition and animal models and not human research. Epinephrine causes a number of favorable short-term cardiac and cerebral changes, resulting mainly from its role as an alpha-receptor agonist, but increased survival is found only in animals, not humans. During the 1990s, use of high dose epinephrine was all the rage, but then fell totally out of favor when studies could not document any improved long-term outcome measures. There is even a suggestion of some adverse effect, with high dose epinephrine.
What about Vasopressin?
Also in in the 1990s, discovery of increased levels of plasma vasopressin concentrations in successfully resuscitated patients resulted in the flurry of studies on vasopressin, either alone or with epinephrine, in coding patients. Hemodynamic changes after vasopressin administration were even more impressive than those found with epinephrine, but results in individual trials were mixed. Then, in 2005, a meta-analysis published in the Archives of Internal Medicine found no statistical difference between vasopressin and epinephrine – not in return of spontaneous circulation, death before admission, 24-hour survival, or hospital discharges. The authors here note that some physicians still favor replacing one dose of epinephrine with vasopressin, but that practice is not supported by evidence in the literature.
Lidocaine is also a common cardioactive drug.
Lidocaine is used to treat a number of cardiac arrhythmias. In the early 2000s, it was discovered that about 80% of patients who undergo successful defibrillation had a subsequent recurrence of ventricular fibrillation, and so lidocaine was tested both as a prophylaxis against recurrent VFib, and also to terminate stable Vtach, in arrest and pre-arrest patients — without success.
Amiodarone has also been used during cardiac arrests.
Yes, in the late 1980s and early 1990s, amiodarone replaced lidocaine as the “miracle drug” based on several retrospective studies and then randomized controlled trials that demonstrated increased immediate survival among patients given a Hail Mary dose of amiodarone after seemingly futile resuscitative efforts. However, there are no studies confirming long-term survival in patients who received amiodarone.
Is Atropine still used in cardiac arrests?
Not really. There are relatively few studies on atropine use in a cardiac arrest, and in fact the AHA has recalled their recommendation to routinely administer Atropine in pulseless electrical activity or in a systole.
What about combinations of medications?
The authors review 5 studies that examined ACLS drugs as a group and did not find any long-term benefit to their use.
If medications aren’t effective in resuscitating patients, is anything helpful?
Rather than drugs, the authors concur with the 2010 AHA guidelines, where current evidence supports that we “redirect our focus more to the quality of CPR provided and early defibrillation, each of which has been shown to be more important than ACLS medication.”
Chan PS, Spertus JA, Krumholz HM et al for the Get With the Guidelines–Resuscitation Registry Investigators, A Validated Prediction Tool for Initial Survivors of In-Hospital Cardiac Arrest. Arch Intern Med 2012; 172(12):947-953 (http://archinte.jamanetwork.com/article.aspx?articleid=1162169)
Sasson C, Magid D, Chan P for the CARES Surveillance Group. Association of Neighborhood Characteristics with Bystander-Initiated CPR. N Engl J Med 2012; 367:1607-1615 (http://www.nejm.org/doi/full/10.1056/NEJMoa1110700)
Boyd T, Brady W. The “Code Drugs in Cardiac Arrest”—the use of cardioactive medications in cardiac arrest resuscitation. The American Journal of Emergency Medicine Volume 30, Issue 5, June 2012, Pages 811–818. (http://www.ajemjournal.com/article/S0735-6757%2811%2900166-5/abstract)