Category: Resuscitation

Mostly Dead is All Dead – Neuro Outcomes in OHCA Without Prehospital ROSC

A guest post by Anand Swaminathan (@EMSwami) of EM Lyceum and Essentials of EM fame.

Over the last two weeks there has been a lot of buzz around the NEJM study on targeted temperature management in out of hospital cardiac arrest (OHCA) with return of spontaneous circulation (ROSC). This blog has been no exception. This article we’re going to discuss here addresses the care of a very different population: the patient with OHCA without ROSC in the field.

Over four years, 398,121 adults with OHCA and no ROSC in the field were prospectively entered into a database. The overall survival was dismal (1.89%) with even fewer patients having a good neurologic outcome (0.49%).  Neurologic outcome was defined using the Cerebral Performance Category (CPC) scale with a CPC 1 or 2 as a good neurological outcome. Using logistic regression, the authors identified nine factors that were associated with a CPC 1 or 2 outcomes. The authors further stated that there were four critical factors predictive of a good neurological outcome in these patients: initial non-asystole rhythm; age < 65 years, EMS witnessed arrest and hospital arrival time (from call) < 24 minutes. They further broke down the outcomes by type of non-asystolic rhythm:

There are a number of interesting findings in this study. If there’s no ROSC in the field, the chance of achieving good neurologic status is minimal. Survivors were 3-4 times more likely to have a poor neurologic outcome (i.e. severe cerebral disability, coma or brain death) than a good one (1.89% vs. 0.49%). The presence of the previously mentioned four factors was associated with a higher incidence of better outcomes. In particular, a presenting rhythm of ventricular fibrillation had an adjusted OR of 9.37 for a good outcome. Additionally, this study showed, as others have in the past, that epinephrine use increased the rate of ROSC but did not increase the rate of good neurological outcomes (see also Stiell 2004, Hagihara 2012).

How does this change what we do? We’ve all been working when EMS brings in an unwtinessed arrest patient that never had ROSC. The entire ED team mobilizes to care for this patient even though we know the potential for a good outcome is miniscule. This study provides preliminary information on which patients are more likely to have a good neurologic outcome. It should be the basis of further studies looking at protocols to stop resuscitation in the field and avoid transport to the hospital.

References
Goto Y, Maeda T, Nakatsu-Goto, Y. Neurological outcomes in patients transported to hospital without prehospital return of spontaneous circulation after cardiac arrest. Critical Care 2013; 17:R274 doi: 10.1186/cc13121 [Open Access]

Stiell IG et al. ACLS in OHCA. NEJM 2004; 351: 647-56.

Hagihara A et al. Prehospital Epinephrine Use and Survival Among Patients with OHCA. JAMA 2012; 307(11): 1161-68

What Santa Claus, the Tooth Fairy and Low-Dose Dopamine Have in Common

A guest post by Rory Spiegel (@CaptainBasilEM) who blogs on nihilism and the art of doing nothing at emnerd.com.

We have known for some time that the renal sparring effects of low-dose dopamine is a story we tell to our cardiologists to tuck them in at night. Despite a large meta-analysis published in 2005, finding no evidence of this theoretical renal benefit, the authors of the recent Renal Optimization Strategies Evaluation (ROSE) felt that this question was again worth investigating. Nesiritide, a drug made infamous for causing renal failure, was also examined for its renal sparing attributes.

A total of 360 patients with acute heart failure and renal dysfunction (GFR between 15-60 mL/min) were, in a convoluted fashion (to reduce unnecessary use of central lines), randomized to either low-dose dopamine (2mcg/kg/min), low dose nesiritide (0.005 mcg/kg/min) or placebo infusion for a 72-hour period. The two co-primary end points assessed were urine output and change in cystatin C level over a 72-hour period. There was no benefit of either low dose dopamine or low dose nesiritide when added to standard therapy of acute heart failure in any of the authors’ primary, secondary or tertiary (yes tertiary) endpoints. Though there was no statistical increase in adverse events seen in either the dopamine or nesiritide groups, this is far too small a cohort to truly assess safety.
With the publication of this trial surely it has come time to close the book on low dose dopamine. So next time a consultant requests we start a dopamine infusion for its renal sparring properties, may I suggest we sit him or her down and politely explain that like Santa Claus and the Tooth Fairy, there is no such thing as renal dose dopamine.
“Low-Dose Dopamine or Low-Dose Nesiritide in Acute Heart Failure With Renal Dysfunction” http://www.ncbi.nlm.nih.gov/pubmed/24247300

What Santa Claus, the Tooth Fairy and Low-Dose Dopamine Have in Common

A guest post by Rory Spiegel (@CaptainBasilEM) who blogs on nihilism and the art of doing nothing at emnerd.com.

We have known for some time that the renal sparring effects of low-dose dopamine is a story we tell to our cardiologists to tuck them in at night. Despite a large meta-analysis published in 2005, finding no evidence of this theoretical renal benefit, the authors of the recent Renal Optimization Strategies Evaluation (ROSE) felt that this question was again worth investigating. Nesiritide, a drug made infamous for causing renal failure, was also examined for its renal sparing attributes.

A total of 360 patients with acute heart failure and renal dysfunction (GFR between 15-60 mL/min) were, in a convoluted fashion (to reduce unnecessary use of central lines), randomized to either low-dose dopamine (2mcg/kg/min), low dose nesiritide (0.005 mcg/kg/min) or placebo infusion for a 72-hour period. The two co-primary end points assessed were urine output and change in cystatin C level over a 72-hour period. There was no benefit of either low dose dopamine or low dose nesiritide when added to standard therapy of acute heart failure in any of the authors’ primary, secondary or tertiary (yes tertiary) endpoints. Though there was no statistical increase in adverse events seen in either the dopamine or nesiritide groups, this is far too small a cohort to truly assess safety.
With the publication of this trial surely it has come time to close the book on low dose dopamine. So next time a consultant requests we start a dopamine infusion for its renal sparring properties, may I suggest we sit him or her down and politely explain that like Santa Claus and the Tooth Fairy, there is no such thing as renal dose dopamine.
“Low-Dose Dopamine or Low-Dose Nesiritide in Acute Heart Failure With Renal Dysfunction” http://www.ncbi.nlm.nih.gov/pubmed/24247300

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

Houston Resus Podcast

Featuring ACEP Teaching Award recipients Pratik Doshi & Yashwant Chathampally, I’m happy to point the way to a new University of Texas – Houston Emergency Medicine publication:  the Houston Resus Podcast.

Another new #FOAMed resource, driven primarily by our resident enthusiasm for teaching and critical care.

The full site is here:
http://www.houstonresus.com

And the iTunes link to the Podcast is:
https://itunes.apple.com/us/podcast/houston-resus-ut-houston-emergency/id685819529

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

Angiography After Cardiac Arrest

This is the worst sort of paper – nuggets of truth mired in systematic flaws.  There’s certainly no ill intent by the authors to mislead, it’s simply the nature of this sort of retrospective review.

The PROCAT consortium has been publishing studies of their post-arrest protocols for several years.  They’re huge proponents of early coronary angiography following resuscitation for out-of-hospital arrest – and this is another in a string of articles demonstrating that patients going to coronary angiography after out-of-hospital arrest have improved outcomes.  Of the 1274 patients in their cohort, 745 received early coronary angiography, 447 identified a culprit lesion, and 347 underwent PCI.  The survival rate was 46% in patients undergoing PCI.

However, this number is conflated by other confounding variables known to be associated with good outcomes following cardiac arrest – coronary lesions are likely to be associated with VT/VF, which were also associated with good outcomes.  Additionally, significantly more survivors received therapeutic hypothermia than non-survivors, illustrating the massive problem with viewing this sort of report with anything other than reasoned curiosity: rampant selection bias.  Patients survived because they were selected for interventions based on individualized prognostic features, treatments were not applied evenly across the population.

There is absolutely a subset of OHCA that benefits from early coronary angiography – but this benefit should not be generalized to the inappropriate allocation of resources associated with taking all OHCA to the cath lab after resuscitation.

“Benefit of an early and systematic imaging procedure after cardiac arrest: Insights

from the PROCAT (Parisian Region Out of Hospital Cardiac Arrest) registry”
www.ncbi.nlm.nih.gov/pubmed/22922264

End-Tidal to Predict Operative Intervention in Trauma

In penetrating trauma, sometimes it’s very simple to predict operative intervention.  However, sometimes, the perfusion states of our patients are less easy predict – vital signs frequently obfuscate the underlying clinical picture as the body compensates.

This is a prospective study that indirectly aims to validate end-tidal CO2 as a predictor of operative intervention in penetrating trauma by correlating it to serum lactate levels.  And, as their primary outcome, these investigators observed a strong correlation between ETCO2 and lactate levels (R^2 = 0.74).  For secondary endpoints – unsurprisingly, considering it was correlated with lactate – ETCO2 was also predictive of operative intervention.  In fact, the authors report ETCO2 was more predictive of intervention than lactate, although it seems a little odd to significantly outperform lactate, given the strength of their linear correlation.

Compared with systolic blood pressure, the test performance characteristics essentially tell us what we already know: normal blood pressure isn’t helpful, low blood pressure is obviously helpful (98% specificity).  Lactate and ETCO2 are more sensitive to hypoperfusion states not reflected in vital signs, although, in this small study, even elevated ETCO2 would miss 1 in 5 operative interventions (sensitivity 82%) and would incorrectly predict 1 operative intervention for every 4 correct predictions (specificity 82%).

If prospective study confirms that ETCO2 outperforms lactate levels as an indicator of hypoperfusion, perhaps it adds something to the trauma bay evaluation.  Otherwise, it seems the most useful function might be to add to prehospital triage protocols – an environment where lactate wouldn’t be available.

“Nasal cannula end-tidal CO2 correlates with serum lactate levels and odds of operative intervention in penetrating trauma patients: A prospective cohort study”
http://www.ncbi.nlm.nih.gov/pubmed/23117381