Category: Cardiac Arrest

Giving Hypothermia the Cold Shoulder

Modern resuscitation has many components – emphasis on pre-hospital CPR, distribution of defibrillators, cardiac catheterization … and hypothermia.  And, now we’re not so sure about that last one.

Therapeutic hypothermia is based on two randomized trials, published in 2002, enrolling a grand total of 352 patients.  Recommendations include rapid cooling after emergency stabilization to a target temperature between 32° and 34°C, and subsequent adoption of this practice spawned a cottage industry of expensive, specialized cooling devices.  But, these temperature targets were always somewhat arbitrary, and the question persisted as to whether lower temperatures in fact conferred a neurologic survival advantage.

Nope.

Enrolling nearly a thousand patients, this randomized trial of out-of-hospital cardiac arrest randomized half to 33°C and half to 36°C.  Groups were well-balanced on typically expected features favoring survival – comorbidities, bystander CPR, arrest rhythm, and follow-up treatment.  And, after cooling for 24 hours, no difference was detected in early deaths, late deaths, or in any measure of cerebral or functional performance.  One impressive feature of this trial is the standardized withdrawal of care criteria, reducing patient heterogeneity through that mechanism.

None of this says “hypothermia doesn’t work”.  But, a sense of lacking in terms of a dose-response relationship between hypothermia and neurologic survival causes some concern.  Why did we observe such profound benefit in the early trials?  Erroneous rejection of the null hypothesis due to poor statistical power, unmeasured confounders, or something more sinister?  Adding in the pre-hospital hypothermia study from JAMA, both dose-dependent and time-dependent effects are now less certain.

The utility of hypothermia following ischemic insult seems biologically plausible, but, as the editorial comments, perhaps it’s not so much hypothermia as the maintenance of normothermia.  Already part of modern post-stroke care, treating and preventing fever improves outcomes – it may simply be the observed benefits are due to intensive antipyresis, rather than hypothermia.

It seems still reasonable to use gentle cooling as a prophylaxis against hyperthermia, but more importantly, it is time, yet again, to reflect on how better evidence refines established practice.  Without continuing to recognize the limitations of our knowledge, we must caution ourselves against rushing to generalize implementation from small sample sizes (see: tPA in acute ischemic stroke).

“Targeted Temperature Management at 33°C versus 36°C after Cardiac Arrest”
http://www.nejm.org/doi/full/10.1056/NEJMoa1310519

“Temperature Management and Modern Post–Cardiac Arrest Care”
http://www.nejm.org/doi/full/10.1056/NEJMe1312700

Post-Arrest Catheterization Delusions

We have, yet again, another favorable publication espousing the benefit of cardiac catheterization after cardiac arrest.  There is not a great deal of ambiguity regarding the management of post-arrest STEMI.  However, the cohort these authors examine – those without obvious cardiac cause for arrest – is harder to to judge.

Unfortunately, this article is the same level of evidence as the prior publications in this field – by which I mean, practice change followed by retrospective, observational case-series.  These authors look back at their cohort cohort of VT/VF that was not STEMI – a reasonable initial stratification based on presenting rhythm and likely association with acute coronary syndrome.  Of 269 patients meeting this definition, 122 underwent early catheterization and 147 did not.  The outcomes were more favorable in the cohort that underwent catheterization, and thus, the conclusion:

“In comatose survivors of cardiac arrest without STEMI who are treated with TH, early CC is associated with significantly decreased mortality.”

But, these authors are unable to pin down exactly what element of post-arrest care in the catheterization lab leads to this decreased mortality.  Only 26.2% of patients undergoing early catheterization had a lesion amenable to intervention (the authors call this level of incidence “high” – hum), and intervening on a coronary lesion conferred no specific survival advantage.  Therefore, it’s not the PCI that benefited these patients.  There was an increased incidence of post-resuscitation shock in the catheterization cohort, and these underwent left-ventricular support more frequently – which may or may not have resulted in improved outcomes.  Furthermore, the median time to therapeutic hypothermia in the catheterization cohort was an hour faster as well – suggesting this baseline difference in treatment may have influenced cognitive outcomes.

Unfortunately, retrospective studies like this suffer critically from selection bias – patients in the arm receiving cardiac catheterization may have had other unreported features favorable for cognitively intact outcomes, leading clinicians to treat them differently/more aggressively.  It would be inappropriate to generalize this observational association with causation and send all post-arrest to catheterization.  Certainly, some subset of VT/VF arrest benefits from early cardiac catheterization, but this study unfortunately does little to delineate which.

“Early cardiac catheterization is associated with improved survival in comatose survivors of cardiac arrest without STEMI”
www.ncbi.nlm.nih.gov/pubmed/23927955‎

CPR, Epinephrine … Vasopressin and Steroids?

Considering we’re still mighty skeptical regarding the ill effects of epinephrine on coronary and cerebral blood flow during resuscitation, I have to say I’m a little doubtful regarding the addition of a second vasopressor, along with steroids.

But, these authors, building on their prior work, attempt a randomized, placebo-controlled evaluation of epinephrine versus a combination of epinephrine, vasopressin, and methylprednisolone – along with a 7-day course of additional stress-dose steroids vs. placebo if post-ROSC hypotension was observed.  At hospital discharge, there were over twice as many neurologically intact survivors in the combination group as the epinephrine group – 18/130 vs. 7/138 – and thusly the authors conclude:

“Among patients with cardiac arrest requiring vasopressors, combined vasopressin-epinephrine and methylprednisolone during CPR and stress-dose hydrocortisone in postresuscitation shock, compared with epinephrine/saline placebo, resulted in improved survival to hospital discharge with favorable neurological status.”

Regrettably, with such a concisely worded conclusion, the authors devote barely two sentences to their limitations.  Indeed, for a study with so much to discuss, the authors compose a discussion section that occupies far less than even a full page.

There are a couple glaring problems with this study – not the least of which are the baseline differences between groups.  Despite randomization, the epinephrine group was saddled with quite different causes of cardiac arrest, almost certainly favoring the intervention group.  A randomization of additional patients with hypotension as their primary cause of arrest to the steroid group is almost certainly an allocation of a more favorable cohort, whereas “metabolic” causes of arrest are probably not corticosteroid deficient.  Similarly, the epinephrine group had far more asystole than the combination group – another poor prognostic feature.  Indeed, in their multivariate logistric regression (supplemental appendix), the cause of arrest and initial rhythm had statistically similar association with good outcome as intervention group membership.

The second issue is the problem of multiple interventions.  It is not clear whether the observed effect, if present, is secondary to the vasopressin-epinephrine-methylprednisolone cocktail during resuscitation or the stress-dose hydrocortisone given to nearly all survivors of the intervention group.  55% of the epinephrine group is alive 4 hours after ROSC vs. 66% of the intervention group, which, along with their physiologic data, implies the resuscitation intervention has some treatment effect.  Then, it’s unclear what favorable effect the stress-dose steroids has – particularly considering some of the epinephrine-only group then received open-label stress-dose hydrocortisone.  After resuscitation, different numbers of each group underwent PCI and similar numbers in each group received therapeutic hypothermia – but not all, leading to potential further confounding through selection bias.

Ultimately, it’s a mess – and it’s difficult to generalize these findings from a heterogenous and unbalanced cohort to routine practice.  The authors should be applauded for their ambitious goals, but a larger study, with a more effective randomization protocol, is yet needed.

“Vasopressin, Steroids, and Epinephrine and Neurologically Favorable Survival After In-Hospital Cardiac Arrest”
www.ncbi.nlm.nih.gov/pubmed/23860985‎

The Return of Lidocaine?

Lidocaine as adjunctive treatment following cardiac arrest in the context of ventricular fibrillation/ventricular tachycardia has generally fallen out of favor and been replaced with amiodarone, a result of historical data and more recent trials.  However, the quality of the evidence is generally poor, and confounders are frequent.

So, here’s some more chaotic, retrospective evidence gathered over the course of 16 years.  This is the King County registry of OHCA, of which 1,721 patients with VF/VT and ROSC were identified.  Of these, 1296 patients received prophylactic lidocaine after ROSC, in theory, to prevent re-occurrence of VF/VT.  And, in both their unadjusted, adjusted, and propensity matched cohorts, there was a reduction in recurrence of VT/VF.  However, in their propensity-matched cohort – which may or may not be a better tool for comparing two groups than their multivariate adjustment – there was no difference in admission rate or survivors to hospital discharge.

At the least, as these authors suggest, this data provides the clinical equipoise needed to justify prospective OHCA trials exempt from informed consent.

“Prophylactic lidocaine for post resuscitation care of patients with out-of-hospital ventricular fibrillation cardiac arrest”
www.ncbi.nlm.nih.gov/pubmed/23743237‎

Autopulse Advertisement in Critical Care Medicine

We’ve all seen folks come in via EMS with mechanical devices performing automated chest compressions.  These probably do a lovely job of freeing up paramedics from performing uninterrupted CPR, but their relationship to outcomes has been typically uncertain.

This meta-analysis and systematic review, however, reports these devices are superior to manual chest compression – with an OR of 1.6 towards increased return of spontaneous circulation.  Considering the copious evidence towards improved outcomes by minimizing interruptions during CPR, this would be an important finding, and tailors nicely with the expected advantage of mechanical compression devices.

However, this COI statement covering each of the four authors might also be in some fashion related to the positive results reported here:
“Dr. Westfall has received modest research grant support from ZOLL Medical Corporation. Mr. Krantz has received significant research grant support from ZOLL Medical Corporation. Mr. Mullin has served as a consultant for ZOLL Medical Corporation. Dr. Kaufman is an employee of ZOLL Medical Corporation.”

Unsurprisingly, these authors also demonstrate one of the overlooked evils of meta-analyses – the obfuscation of source COIs.  This JAMA article from 2011 does a lovely job describing this critical problem, and, as expected, these conflicted authors ignore the pervasive sponsorship bias present in their selected review.  Additionally, half the articles are only conference abstracts, suffering from results and methods not subject to the same level of rigorous peer review.

It really ought to be rather embarrassing for the editors of this journal to be approving such a clearly flawed vehicle – essentially blatant advertising for their $15,000 medical device – for publication.  No better, Journal Watch Emergency Medicine gives this article a bland and un-insightful thumbs-up.

“Mechanical Versus Manual Chest Compressions in Out-of-Hospital Cardiac Arrest: A Meta-Analysis”
www.ncbi.nlm.nih.gov/pubmed/23660728‎

Sometimes, the Dead (by Ultrasound) Rise

This article received a little bit of dissemination, with the assertion that some apparently futile resuscitations may yet be salvaged despite the lack of cardiac activity on ultrasound.

But, this article doesn’t necessarily tell the entire story.  It’s a systematic review of several small, poor-quality cardiac arrest cohorts for whom bedside cardiac ultrasonography was performed.  In aggregate, there were 378 patients with no cardiac activity visualized during resuscitation – and 9 went on to have return of spontaneous circulation.  They calculate this out as an LR of 0.18 for ROSC after finding no cardiac activity.

The problem is, this is the only information we have regarding the context of the ultrasound findings or the performance characteristics of the ultrasonographers at work.  The authors also appropriately note that ROSC is not necessarily the ultimate patient-oriented outcome of interest – since we know that most ROSC after cardiac arrest admitted to the hospital still goes on to have a dismal outcome.  

I’m not entirely sure what my takeaway should be from this study, and it’s not going to significantly modify my practice.  In the appropriate clinical context, a lack of cardiac activity will still lead me to cease resuscitative efforts.  It would be extraordinarily helpful to have a larger body of data specifically regarding the patient characteristics of those who did have ROSC despite lack of cardiac activity, to see if there is a usable pattern to this small population of exceptions.

“Bedside Focused Echocardiography as Predictor of Survival in Cardiac Arrest Patients: A Systematic Review”

Still Overpromising Benefit of PCI After Cardiac Arrest

The folks in France have been promoting PCI universally after cardiac arrest for quite some time.  It’s an appealing concept – when you look at subgroups of out-of-hospital cardiac arrest, there’s a significant portion of folks who clearly have a primary cardiac cause, and clearly will benefit from emergency or early PCI.

However, this study inappropriately tries to make the case for all patients to receive PCI and therapeutic hypothermia after out-of-hospital cardiac arrest.  This is a retrospective, cohort study spanning eight years of resuscitation, coordinated between Paris, France and Seattle, Washington.  They used vital records follow-up to determine patient status for each OHCA patient surviving to hospital discharge, and then looked for associations between survival and whether they received PCI or hypothermia in-house.  The most absurd statement is as follows:

“A beneficial survival association was evident among those with and without ST-elevation MI. This finding is provocative given the current debate about whether patients without evidence of ST elevation following resuscitation can benefit from PCI and should undergo early and routine coronary catheterization.”

Retrospective studies such as this suffer from substantial selection bias, in which the patients who are selected for particular therapies have interactions and confounders that simply cannot be controlled or adjusted.  Patients benefit from PCI when they have a disease process amenable to intervention – and this is clearly not every cardiac arrest patient. The patients in this study who received PCI – and hypothermia – likely had specific features that identified them to treating physicians as candidates to benefit from these therapies.

The reasonable conclusion from the data presented is exactly that – cardiac arrest patients that have specific features that make them candidate for these therapies will benefit.  PCI following cardiac arrest should not be considered to be “routine”.

“Long-Term Prognosis Following Resuscitation From Out of Hospital Cardiac Arrest – Role of Percutaneous Coronary Intervention and Therapeutic Hypothermia” 

Longer Resuscitation “Saves”

This article made the rounds a couple weeks ago in the news media, probably based on the conclusion from the abstract stating “efforts to systematically increase the duration of resuscitation could improve survival in this high-risk population.”


They base this statement off a retrospective review of prospectively gathered standardized data from in-hospital cardiac arrests.  Comparing 31,000 patients with ROSC following an initial episode of cardiac arrest with a cohort of 33,000 who did not have ROSC – the authors found that patients who arrested at hospitals with higher median resuscitation times were more likely to have ROSC.  Initial ROSC was tied to survival to discharge, where hospitals with the shortest median resuscitation time having a 14.5% adjusted survival compared to 16.2% at hospitals with the longest resuscitations.


Now, if you’re a glass half-full sort of person, “could improve survival” sounds like an endorsement.  However, when we’re conjuring up hypotheses and associations from retrospective data, it’s important to re-read every instance of “could” and “might” as “could not” and “might not”.  They also performed a horde of patient-related covariates, which gives some scope of the difficulty of weeding out a significant finding from the confounders.  The most glaring difference in their baseline characteristics was the 6% absolute difference in witnessed arrest – which if not accounted for properly could nearly explain the entirety of their outcomes difference.


It’s also to consider the unintended consequences of their statement.  What does it mean to continue resuscitation past the point it is judged clinically appropriate?  What sort of potentially well-meaning policies might this entail?  What are the harms to other patients in the facility if nursing and physician resources are increasingly tied up in (mostly) futile resuscitations?  How much additional healthcare costs will result from additional successful ROSC – most of whom are still not neurologically intact survivors?


“Duration of resuscitation efforts and survival after in-hospital cardiac arrest: an observational study“

www.thelancet.com/journals/lancet/article/PIIS0140…9/abstract

It’s Nothing Like “ER”

This is a fun little article regarding the realism of the Emergency Medicine environment showcased on the popular U.S. television show “ER”.  As the authors state in their introduction, the viewers of the show have been surveyed, and a significant portion of the viewers believe the content of the show to be valid clinical information.  However, the televised outcomes are frequently unrealistic (CPR success rates, patients emerging from comas, etc.), and lead to inaccurate public perceptions.

This team of authors watched all 22 episodes from a single season of “ER” to evaluate the types of patient encounters depicted, and then compared their findings with representative data from the NHAMCS dataset.  Overall, there were 192 patients during the 22 episodes, and they differed from the real-world by:
 – Weighted heavily towards 25-44 years of age, rather than infants and elderly.
 – More male and white, rather than black and female.
 – Depictions of lower pain levels.
 – Far more traumatic injuries.

And, this analysis only observed the patients – the responsibilities and skills of the treating medical students, residents, and attendings are also wildly dramatized, of course.

So, it’s nothing like “ER”.  It’s really more like “Scrubs”….

“ER vs. ED: A comparison of televised and real-life emergency medicine.”
http://www.ncbi.nlm.nih.gov/pubmed/22766407

Uninterrupted CPR is Better Than Interrupted

This is from King County, which has been publishing retrospective pre- and post- intervention outcomes related to out-of-hospital cardiac arrest for several years now.  This article focuses on the AHA guidelines for PEA and asystole, and the changes that were made in 2004 and 2005.  Those changes, if you recall, involve fewer pauses for pulse and rhythm checks and decreasing the number of ventilations.


Good news!  You were 1.5 times more likely to survive neurologically intact to hospital discharge after the introduction of the new guidelines.  Bad news: good neurological outcome was still only 5.1%, up from 3.4%.  So, yes, this is another piece of evidence supporting the “uninterrupted, high-quality CPR” concept, but perhaps the other important question that need be asked at the same time is:  how can we reduce the unnecessary resource expenditure associated with attempted resuscitation for the 95% that doesn’t benefit?


“Impact of Changes in Resuscitation Practice on Survival and Neurological Outcome After Out-of-Hospital Cardiac Arrest Resulting From Nonshockable Arrhythmias”
http://www.ncbi.nlm.nih.gov/pubmed/22474256