Post-Arrest Troponin Measurements Predict Little

Taking post-arrest patients to cardiac catheterization improves outcomes – as long as they have a cardiac occlusion as the underlying etiology of their arrest.  Otherwise, you’re simply delaying the diagnosis and treatment of alternative causes, as well as post-arrest ICU-level care.  Therefore, if there is some clinical feature that can be identified on initial Emergency Department evaluation that predicts a coronary occlusion, that would be of great value.

So, this is a retrospective analysis of a prospective registry of out-of-hospital arrests from Paris, where much of the post-arrest catheterization work has been done.  And, unfortunately, there isn’t any useful association – 92% of their patients had elevated troponin on initial evaluation.  There was a nonsignificant trend towards higher troponin levels in patients with coronary occlusion, but even at their “optimum” cut-off of 4.66ng/mL, the sensitivity and specificity were nearly coin-flip at 66% each.  A troponin of 31ng/mL was required for 95% specificity.

ST-segment elevation, incidentally, was more predictive of a coronary occlusion – OR 10.19 (CI 5.39 to 19.26).

“Can early cardiac troponin I measurement help to predict recent coronary occlusion in out-of-hospital cardiac arrest survivors?”
http://www.ncbi.nlm.nih.gov/pubmed/22488008

The Harmful Rush To Hypothermia

Mild hypothermia seems to be a clinically useful therapeutic modality for improving neurologic outcomes following return of spontaneous circulation in cardiac arrest.

However, like any emerging therapy, the precise details regarding which patients are most likely to benefit and how to best apply it are still in flux.  This is an Italian registry study that gathered prospective data on all individuals at 17 hospitals who underwent therapeutic hypothermia following cardiac arrest.  The specific question asked by these authors is regarding the optimal time for initiation of hypothermia – using 2 hours after ROSC as their cut-off.

Turns out, they found an association between “early” (< 2 hours to initiation) therapeutic hypothermia and worsened mortality – 47% mortality vs. 23% mortality in the ICU.  This ~20% absolute difference in outcomes holds up over the 6 month follow-up period.  No difference in cerebral performance category is observed between the two groups, although there is a nonsignificant trend towards better CPC in the “early” group.

Hard to know what to actually do with data.  Is early hypothermia truly harmful?  Because of the observational design, it’s hard to say whether there aren’t confounding baseline differences in the “late” population that produces selection bias for higher survival rates.  Or, are the mortality rates higher in the early group because patients are incompletely resuscitated before initiating hypothermia?

More questions, no answers.

“Early- versus late-initiation of therapeutic hypothermia after cardiac arrest: Preliminary observations from the experience of 17 Italian intensive care units”

Too Many Traumatic Arrests Are Transported

Traumatic arrest in the field – except in the narrowest of circumstances – has universally dismal outcomes.  Yet, As the authors of this study observe, a great number of these patients continue to be transported to hospitals.

This is a retrospective review of a prospective trauma registry at Sinai in Chicago in which all traumatic patients with pre-hospital arrest were considered.  Patients were excluded for pediatrics, medical causes, drowning/electrocution injuries, and if the prehospital time was less than 15 minutes.  Essentially, they were looking at guidelines from the ACS Committee on Trauma for termination of resuscitation in the out of hospital setting – pulseless, apneic, no organized ECG activity, or unresponsive to 15 minutes of resuscitation.

They identified 428 patients in their cohort – and found that 294 of them were transported in violation of guidelines.  Of the inappropriately transported patients, 93% were declared dead in the ED and the remaining 6.8% (20 patients) survived the ED.  Of those 20, 12 died in surgery, 8 made it to the ICU, and 7 died.  A single, neurologically devastated, patient survived to discharge to a long-term care facility with a GCS of 6.

The total hospital charges incurred for the futile resuscitation of these patients totaled $3.8 million – a figure that excludes the EMS charges as well as the long-term care facility charges for the patient with GCS 6.

And this is just a single hospital.

“The Consequences of Noncompliance With Guidelines for Withholding or Terminating Resuscitation in Traumatic Cardiac Arrest Patients”
http://www.ncbi.nlm.nih.gov/pubmed/21986740

Nitroprusside Saves Pigs – How About Humans?

Essentially, no ACLS medication therapy has been shown to be terribly efficacious with regard to meaningful patient outcomes.  Epinephrine – if we could find a way to satisfactorily preserve neurologic and cardiovascular status after return of spontaneous circulation – seems to have a small helpful effect, but has all sorts of deleterious effects on LV function and cerebral perfusion.  Otherwise, nothing is proving useful other than CPR, shock ventricular arrhythmias, and hope for the best.

I posted about this back in April, and it’s another article – from the same masters of porcine resuscitation up in Minneapolis – about a second series of protocols they used to evaluate “sodium nitroprusside enhanced CPR”(SNPeCPR).  The CPR is the same.  The SNPe part is multiple doses of IV sodium nitroprusside and an impedance threshold device, along with a more limited role for epinephrine administration.

They ran two protocols for this study.  Protocol A was a ventricular fibrillation model with 6 standard CPR pigs, 6 CPR + impedance threshold, and 12 SNPeCPR pigs.  Protocol A favored ROSC in SNPeCPR – 0/6, 0/6, and 12/12.

Protocol B was a PEA model with 8 pigs of standard CPR vs 8 pigs of SNPeCPR.  Protocol B favored ROSC in SNPeCPR – 0/6 vs. 7/8.

I think they might be onto something here, but I am still a little wary about the results because both these articles are from the same institution and they keep using these idealized perfusion platforms.  Other investigators should heed this research to evaluate whether their methods are externally valid and warrant human trials.

“Sodium nitroprusside-enhanced cardiopulmonary resuscitation improves resuscitation rates after prolonged untreated cardiac arrest in two porcine models”
www.ncbi.nlm.nih.gov/pubmed/21725236

Prolonged QT – Don’t Believe The Hype?

Much ado is made about the risk of QT prolongation and the development of malignant arrhythmias, particularly Torsades de Pointes – but how frequently does TdP actually occur in these patients who QT prolongation?  Should we be worried about every EKG that crosses our paths with a prolonged QT?

It seems, like so many things, the answer is yes and no.  This is a prospective observational study from a single institution that installed cardiac monitoring that enabled minute-by-minute measurement and recording of QT intervals in their monitored inpatient population.  They evaluated 1,039 inpatients for 67,648 hours worth of time, and found these patients spent 24% of their monitored time with a prolonged QTc (>500ms).  One single patient had a cardiac arrest event where TdP was evident on the monitoring strip – a comorbidly ill heart failure patient whose QTc ranged as high as 691ms.

The authors then went back to attempt to determine whether the prolonged QT was associated with all-cause mortality with the 41 patients who died during their study period, and they found that 8.7% had QT prolongation versus 2.6% who did not.  However, as you can imagine, there are massive baseline differences between the QT prolonged population and the non-QT prolonged population, many of which contribute greater effects to in-hospital all-cause mortality.  The authors attempt logistic regression and finally come up with an OR of 2.99 for QT prolongation for all-cause mortality – which is lower in effects than CVA, obesity, pro-arrhythmic drug administration, and high serum BUN.

It’s reasonable to say that patients with a prolonged QT are at higher risk for death – but it’s also reasonable to say that sick patients at a higher risk of death are more likely to have a prolonged QT.  Torsades was rare, even with the thousands of hours of QT prolongation noted.  I would not get over-excited about QT prolongation in isolation, but, rather, only in the context of multiple risk factors for mortality in acute illness.

“High prevalence of corrected QT interval prolongation in acutely ill patients is associated with mortality: Results of the QT in Practice (QTIP) Study”
http://www.ncbi.nlm.nih.gov/pubmed/22001585

Hypertonic Saline In Cardiac Arrest

There is a physiologic phenomenon observed in animal studies that a small increase in plasma osmolarity using hypertonic saline increases microperfusion, including myocardial and cerebral blood flow.  Therefore, in theory, hypertonic saline administration during resuscitation from cardiac arrest should be efficacious in improving survival and neurologic outcome.

These authors conduct a randomized prospective trial in which they prove that 100 patients in each arm is not enough to make valid claims about a secondary endpoint for which the study was not designed to evaluate.  There is no difference between groups in mortality – and not even non-significant trends – but a small, significant, absolute difference in neurologic impairment, 4.9% without neurologic impairment in the control group and 13% in the intervention group.

So, another study suggesting further study is needed.  If anything, it demonstrates how impossibly hard it is to evaluate treatments in the heterogenous population of out-of-hospital cardiac arrest, and to ensure internal and external validity.

“Randomised study of hypertonic saline infusion during resuscitation from

out-of-hospital cardiac arrest.”

Impedance Threshold Devices Are Useless

So, supposedly, impedance threshold devices installed inline for ventilation during CPR potentially improve hemodynamics via negative intrathoracic pressure.  This is a prospective, randomized, multi-center, placebo-controlled sham study that really meets a very high standard for internal validity.  Over 4000 patients in the ITD group, the sham ITD group, and the not-enrolled comparison cohort.

Short summary:
 – Minimal differences between groups.
 – 27.8% sham vs. 27.1% active device ROSC in the ED.
 – 8.2% sham vs. 8.2% active device discharge from the hospital.
 – No apparent harms from the ITD device, but no benefits either.

The most important point from this article is that we have gotten sloppy in our rush to implement supposedly new and beneficial therapies in medicine.  Hypothermia, TPA for stroke, Factor VIIa, direct thrombin inhibitors, etc. and we should add impedance threshold devices to the list.  The AHA has had ITD as a class IIa recommendation to improve hemodynamics since 2005 – six years of useless therapy and costs based solely on a theoretical model without proof of improved outcomes.  Hammering this point home never gets old.

“A Trial of an Impedance Threshold Device in Out-of-Hospital Cardiac Arrest.”
www.ncbi.nlm.nih.gov/pubmed/21879897

Epinephrine Neither Wins Nor Fails

The crux of the problem – epinephrine continues to improve short-term ROSC with uncertain long-term outcome improvement.

This is a prospective out-of-hospital arrest study from Australia in which epinephrine or saline placebo was given to patients during resuscitation by EMS.  And, like many studies before it, it fails to show a meaningful difference between patients receiving epinephrine and patients receiving placebo.  Rather, their primary outcome of survival to hospital discharge had 1.9% with placebo and 4.0% with epinephrine – but this result was not statistically significant with a p-value of 0.15.

Of course, what the lack of statistical significance means in this case is that this difference could have occurred by chance 15 times out of 100 times they performed this study – which, while not meeting the gold standard of 5 out of 100, is still a reasonably interesting clinical trend.  Like all studies before it, the short-term endpoints met statistical significance, including ROSC of 8.4% for placebo and 23.5% for epinephrine.  There are a few confounding differences between groups: more placebo patients had witnessed arrest, although the number with bystander CPR was the same; more placebo patients were endotracheally intubated in the field, which usually confers a survival disadvantage; and more epinephrine patients were ultimately transported to the hospital from the field.

So, there’s two ways to look at it: 1) epinephrine works, and we just need to figure out how to salvage more of those ROSC or 2) epinephrine is flogging far too great a number of lost husks back to life that will go on to consume ICU resources and expire regardless.

But, if we’re not going to give epinephrine, how do we otherwise look busy during a code?  And, what happens downstream to our epinephrine ROSC that fail to leave the hospital or the ER, and can we prevent it?

I am still not sure what the right answer is – like many diseases, cardiac arrest patients are a heterogenous group in which there is almost certainly a subset of patients that benefits from epinephrine, but we don’t yet know who that might be.

“Effect of adrenaline on survival in out-of-hospital cardiac arrest: A randomised double-blind placebo-controlled trial.”
www.ncbi.nlm.nih.gov/pubmed/21745533

Thanks to @cliffreid of Resus M.E! for first noting this article.

Sternal IO is the Best IO

All our cardiac arrest patients roll in these days with an IO in place – and we are full proponents of rapid, successful access in the uncontrolled field environment.  But, how effective is it really in the CPR situation?

So, this is an animal study that tries to address the theoretical efficacy of intraosseous access versus central venous access.  They use injection of dye tracers into Yorkshire swine for a comparison between intraosseous sternal, intraosseous tibial, and external jugular central venous cannulation.

Unfortunately, this is a good news/bad news study.  The good news – peak concentrations were achieved only slightly more slowly in the arterial circulation following sternal intraosseus injection than the gold standard central venous injection.  And, the peak concentrations were nearly identical.  Bad news, the tibial IO was half the speed and half the arterial peak concentration of the sternal IO.

In theory, this is of relative importance depending on which medication you’re using – presumably the speed of administration matters in CPR and peak concentration may matter as well.  Of course, this is limited as 1) pigs and 2) efficacy vs. effectiveness, because they’re not measuring clinical outcomes.

But it’s interesting to worry about.  Too bad it’s hard to do chest compressions with your access point where your hands are supposed to go.  It would be interesting to compare this result to a humeral head IO.

“Pharmacokinetics of Intraosseous and Central Venous Drug Delivery During Cardiopulmonary Resuscitation.”
http://www.ncbi.nlm.nih.gov/pubmed/21871857

Abdominal Aorta Pressure During CPR Increases CPP

I like that the big focus these days is on increasing cerebral perfusion pressure in cardiac arrest – sure, we can focus on more interventions to flog the heart back into coordinated activity, but, sometimes, it’s just not going to happen.  But, for when we are able to get the heart rolling again, unless you’re a big organ donation proponent, we need to preserve neurologic outcomes.  After all, that’s where a lot of our studies of ACLS fall off – we get short-term ROSC, but survival to hospital discharge is unchanged because the brain is unrecoverable.

Here’s another trick in pigs – sustained AA pressure resulting in measurable increases in CPP.  Better CPP = better neurologic outcomes in other studies.  Seems like a no-brainer.

I particularly like this intervention because it’s basically no-cost and should be easy to test for outcome efficacy in humans.

http://www.ncbi.nlm.nih.gov/pubmed/21550162