Ryan Radecki

It’s Another Chest Pain Prediction Rule!

Yet again, the insanity of the race to a zero-miss culture funds another chest pain discharge prediction rule. In fact, the most telling part of this paper is in the very end when they compare the chest pain admission rates of the Canadian hospitals in this article to the U.S. hospital – 18% and 20% in Canada compared to 96% in the U.S. (combined ED observation status and inpatient). The difference in those numbers is insane – and I’m sure people could easily debate which is the preferred side of those numbers to be on.

In any event, the study is a prospective, observational data-gathering study of 64 variables related to the presentation of chest pain – some of which are objective and some of which are historical. It’s an interesting read – in part because the inter-observer kappa for a lot of the historical variables is so terrible they weren’t even usable. After collecting all their data, they did 30-day telephone follow-up or vital records review to evaluate the combined endpoint of death, myocardial infarction, or revascularization.

Via the magic of recursive partitioning, a patient without new EKG changes, a negative initial troponin, no history of CAD, atypical pain, and age less than 40 years separated out 7.1% of their study population that had zero 30-day outcomes. Adding a second negative troponin six hours later for the 41-50 year group gives another 11.2% of patients that had zero outcomes. So, a facility that admits 96% of their patients could potentially reduce admissions – but it might have less utility in Canada.

I’d rather see a two-hour second troponin than a six-hour one; it might reduce sensitivity, but it’s wholly impractical to tie up a bed in the ED for 6 hours for a patient you want to send home. And, like most of these articles, the combined endpoint of death, MI, and revascularization is irritating. Considering there were twice as many revascularizations as myocardial infarctions, there really ought to be more granularity in these sorts of studies with regard to the actual coronary lesions identified rather than simply lumping them into a combined endpoint.

“Development of a Clinical Prediction Rule for 30-Day Cardiac Events in Emergency Department Patients With Chest Pain and Possible Acute Coronary Syndrome”
www.ncbi.nlm.nih.gov/pubmed/21885156

Mistakes In Cardiac Arrest Cause Bad Outcomes

Not surprising, of course, but an interesting analysis of a large data set.

The authors pulled 108,636 in-hospital cardiac arrest cases out of the National Registry of Cardiopulmonary Resuscitation and evaluated them for “errors” – such as multiple intubation attempts, incorrect medication administration, delays in code team activation, etc. After attempting to control for all the differences (of which there were many) in level of care and type of patient suffering cardiac arrest, they finally find that any documented error in resuscitation led to a 9.9% increase in adjusted hazard ratio for death in non-VF/pVT, and a 34.2% increase in VF/pVT patients.

Specifically, when they break out the different types of errors, essentially all the effect size was related to delays in medication administration for non-VF/pVT, and delays in medication and failure to defibrillate in VF/pVT.

“Impact of resuscitation system errors on survival from in-hospital cardiac arrest”
www.ncbi.nlm.nih.gov/pubmed/21963583

Physician Profiteering From Self-Referral

Unfortunately, another distasteful – and likely more common than the authors estimate – assessment of the unethical behavior of physicians.

This is from JAMA. It’s a health-insurance carrier records review regarding differences in rate of ordering nuclear stress testing and stress echocardiography depending on the cardiologist financial conflict-of-interest. Basically, they were asking the question – if the ordering cardiologist had a financial interest in the imaging performance and interpretation, would they order more tests?

Sadly, as you might imagine, the answer is yet. If the physician billed technical and professional fees for the nuclear stress, the adjusted OR for ordering a nuclear stress was 2.3 compared to physicians who had no financial interests in the nuclear stress. For stress echocardiography, the adjusted OR was 12.6.

I have no doubt the same sort of thing happens with neurologists who own their own MRI facilities, etc. Money corrupts physicians just the same as any other human being.

“Association Between Physician Billing and Cardiac Stress Testing Patterns Following Coronary Revascularization”
jama.ama-assn.org/content/306/18/1993

C1-Esterase Inhibitor Might Improve Some Sepsis Outcomes

…or it might not. This is a tiny study using a very expensive medication that probably works only on a few patients, but it’s interesting nonetheless.

As part of the inflammatory cascade, C1-esterase inhibitor (C1INH) modulates the coagulation cascade, impacts leukocyte activation, enhances bactericidal activity, and prevents endotoxin shock in sepsis models. So, sounds like a good thing – let’s give it to patients and see what happens!

This was an open-label, randomized, controlled study in Moscow and St. Petersburg with 62 ICU patients – 20 controls and 42 treatment patients – that met inclusion criteria. There were, unfortunately, a lot of differences between the control group and the treatment group. These differences included a lot more post-operative patients, much more pneumonia, and more on the ventilator, and probably favored the treatment group. The mortality is way better for the treatment group – 12% dead versus 45% – but it’s simply impossible to attribute all the effects to C1INH with all the other confounding differences.

That being said, this study is consistent the effects from other small studies. Therefore, we will likely hear more about C1INH after larger, manufacturer-sponsored trials also undoubtedly find a way to spin positive results.

“C1-esterase inhibitor infusion increases survival rates for patients with sepsis”
www.ncbi.nlm.nih.gov/pubmed/22080632

ED Blood Pressure Management In Acute Stroke Is Terrible

This is a non-TPA article regarding the medical management of hypertension in acute ischemic stroke in the Emergency Department.

The authors remind us that for every 10 mmHg drop in SBP <150 mmHg, there is a 17.9% increase in risk for death at 14 days. They additionally remind us that antihypertensive therapy is only recommended for BP >220/120 mmHg, with a 15-25% goal decrease in the first 24 hours.

This is a retrospective review of cases from 16 Cincinnati region hospitals looking at the blood pressure observed in the ED along with any treatment. They found 1739 cases, 1520 of whom did not receive treatment and 219 who did. It turned out that 2.6% of the non-treated patients should have had some blood pressure lowering – oops. But, amazingly even worse, only 31.5% of patients who did receive treatment actually required lowering.

Of the 217 patients that were treated, 52 of them had greater than a 20% drop in blood pressure in the Emergency Department. So, we treat a lot of blood pressure that shouldn’t be treated – and when we treat it, it is not uncommon to treat it too aggressively.

Stop it!

“Emergency Department Adherence to American Heart Association Guidelines for Blood Pressure Management in Acute Ischemic Stroke”
http://www.ncbi.nlm.nih.gov/pubmed/22033993

Computer Reminders For Pain Scoring Improve Treatment

This is a paper on an important topic – considering the CMS quality measures coming up that will track time to pain medication for long bone fractures – that demonstrates a mandatory computer reminder improved pain treatment more than an educational campaign did.

This is a prospective study of 35,628 patients visiting an Australian emergency department in which they went through several phases of intervention, the most salient in their minds was requiring assessment of a pain score at triage. They started by simply observing their performance, then they altered their electronic medical record with a mandated input of the pain score at triage. After the mandated scoring, time to analgesia went from median of 123 minutes to 95 minutes. After the mandate phase, the ED staff underwent an education program regarding pain management in the ED – and the time to analgesia didn’t improve any further.

So, it is reasonable to infer that mandating the pain score at triage had the desired effect on decreasing time to analgesia. However, 95 minutes until analgesia is still terrible. It would be far more interesting of an article if it truly broke down all the times – such as time to triage, time to room, time to physician, time to analgesia order, etc., because there are a lot more data points to gather.

Additionally, it seems it might simply be higher yield if – in addition to asking pain in triage – they had a triage protocol to treat the pain immediately at that point, rather than later downstream.

“Mandatory Pain Scoring at Triage Reduces Time to Analgesia”
www.ncbi.nlm.nih.gov/pubmed/21908072

False-Negative Abdominal CTs

This is an article from the radiology literature that essentially tries to say that CT is not the imaging modality of choice for upper abdominal pain.

It’s a retrospective review of 235 patients over a four-year period who had CTs of the abdomen reported as “normal” or “non-diagnostic” in the setting of upper abdominal pain. They determine false-negative studies if another diagnostic modality eventually provided a definitive diagnosis for the patient’s symptoms. Out of the 235, 81 were lost to follow-up and 27 were excluded for other reasons. Of the remaining 127, 46 were classified as false-negative and 81 were classified as true-negative.

The misses? 23 cases of pancreaticobiliary disease (biliary colic, cholecystitis, choledocholithiasis), 12 cases of gastritis/gastric ulcer disease, and 6 miscellaneous cases that included Mediterranean fever and prosthetic valve endocarditis.

So, yes, there is some inkling that CT of the upper abdomen is going to miss a segment of pathology. On the other hand, this paper presents incomplete data regarding the true positives and false positives – making evaluation of this specific imaging indication incomplete other than to remind clinicians that the evaluation may need to continue in the setting of a negative CT.

“Negative predictive value of intravenous contrast-enhanced CT of the abdomen for patients presenting to the emergency department with undifferentiated upper abdominal pain”
www.ncbi.nlm.nih.gov/pubmed/22072086

TPA Is “Safe” In Prior Stroke and Diabetics

Another recent Journal Watch article about TPA – relaying the manufacturer-sponsored message that TPA can, in fact, be given to the patients who were excluded from ECASS III because of diabetes or prior stroke.

Papers like this are fabulous. I am 100% in agreement with the physiologic premise that timely reperfusion of the ischemic penumbra is beneficial in acute stroke. I am less enthusiastic about using systemic thrombolysis, because it’s akin to smashing a teacup with a sledgehammer. But, until PCI-like therapy is available/safe for the brain, it’s all we have.

I am really tired of endless papers from the TPA literature with authors falling all over themselves to present fundamentally flawed data as definitive evidence. In this paper, the authors take the non-randomized TPA population from the SITS-ISTR – and compare it to the non-randomized, non-thrombolyzed population from the VISTA registry. Why is this a problem? Because even though the relative differences are large, the absolute differences are small – and we’ve already see that what makes the largest absolute difference is stroke after-care, and that all stroke centers are not created equal. The authors acknowledge this, but then justify their results by stating that their numbers are similar to prior, retrospective, non-randomized comparisons performed on subsets of registry data. It’s a self-fulfilling prophecy.

They conclude with “Hence, we find no justification to exclude patients from receiving alteplase for acute ischemic stroke if they have a [prior stroke] and also have [diabetes mellitus]” – which is true, unless it bothers you that the mRS 6 (dead) group nearly doubles when TPA is given to the stroke/diabetes groups. Imagine what the reaction to ECASS III would be if TPA wasn’t 52% good outcome vs 6.7% death – and was one of these 29% good outcome vs. 23% death, or 25% good outcome vs. 28% death comparisons from the registry data (totally different baseline severity vs. ECASS III, just throwing the numbers out there for hyperbole).

…and, the obligatory:

“Dr. Mishra reports no disclosures. Dr. Ahmed is an employee of SITS International, which received a grant from Boehringer Ingelheim for the SITS-MOST/SITS-ISTR study with alteplase. Dr. Davalos has received speaker or consultancy honoraria from AstraZeneca, Boehringer Ingelheim, Lundbeck Inc., ev3, Ferrer, and Talecris Biotherapeutics. Dr. Iversen has served on scientific advisory boards for Boehringer Ingelheim and Allergan, Inc.; and has received research support from the Danish National Advanced Science Foundation. Dr. Melo reports no disclosures. Dr. Soinne serves on speakers’ bureaus for and has received speaker honoraria from Boehringer Ingelheim, Pfizer Inc, and Siemens; and has served as a consultant for Boehringer Ingelheim. Dr. Wahlgren serves as Chairman of the SITS Scientific Committee; has served on scientific advisory boards for Boehringer Ingelheim and ThromboGenics NV; has received funding for travel and speaker honoraria from Boehringer Ingelheim, Lundbeck Inc., and Ferrer; and serves on the editorial boards of Stroke and Cerebrovascular Diseases. Dr. Lees serves on scientific advisory boards for Boehringer Ingelheim, Talecris Biotherapeutics, Lundbeck Inc., Ferrer, and PhotoThera; and has received speaker honoraria from Boehringer Ingelheim, Lundbeck Inc., ThromboGenics NV, and Talecris Biotherapeutics.”

I want to use TPA to treat stroke without reservations, but the literature is broken. Still hoping IST-3 will help define a low-risk population that benefits.

“Thrombolysis outcomes in acute ischemic stroke patients with prior stroke and diabetes mellitus”

http://www.ncbi.nlm.nih.gov/pubmed/22094479

We Overestimate CAD Pretest Probability

The ACC/AHA clinical practice guidelines have a set of reference values for the pretest probability of >50% stenotic coronary artery disease based on the type of pain and age. These values range from 2% in a 30 year old woman with non-anginal pain to 94% in a 60 year old man with typical angina.

And, turns out, this is way off.

This is a CTCA registry study of patients undergoing coronary angiography, 14,048 consecutive patients with suspected CAD, looking at both the incidence of 50% luminal narrowing (clinically interesting) and the incidence of 70% luminal narrowing (potentially flow-limiting), and correlating it to asymptomatic, non-anginal, atypical angina, typical angina, or “dyspnea only”.

The meaningful tables of results somewhat defy summarization, but, they have plenty of hypertensives with dyslipidemia – but not very many diabetics or smokers – in their cohort. In the end, however, none of the observed CAD was anywhere close to the predicted pretest probabilities. The cohort with the highest prevalence of CAD was the typical angina in age 70+ males – but even that led to only 53% having a 50% lesion. More than anything, age and gender the most significant predictors of CAD – with no population of women having greater than 29% incidence.

It’s an interesting table worth looking at – CAD really doesn’t kick in until after age 40, and, even then, only mostly in men, and, even then, only in patients with typical symptoms. Once you hit age 50 in men, however, there’s CAD everywhere, even with atypical (or no) symptoms.

There was also some variability by study site – with the 2,225 from Korea having very little CAD and the 29 from the Swiss site having markedly more, but the remainder are relatively similar.

I love studies that just present reams of data and don’t try to push any particular sponsored agenda.

“Performance of the Traditional Age, Sex, and Angina Typicality–Based Approach for Estimating Pretest Probability of Angiographically Significant Coronary Artery Disease in Patients Undergoing Coronary Computed Tomographic Angiography”
http://www.ncbi.nlm.nih.gov/pubmed/22025600

Another Call to Retire Dopamine

The slow, gradual shift from dopamine to norepinephrine as the vasopressor of choice in septic shock has another piece of ammunition – this time a meta-analysis of the observational and randomized trials.

They perform two separate analyses – an analysis of five observational trials and an analysis of six randomized trials. They find heterogeneity and no difference in the observational analysis – and then drop the observational trial responsible for the heterogeneity, and find an RR for mortality of 1.23 favoring norepinephrine. Then, with the randomized trials, they find an RR for mortality of 1.10 favoring norepinephrine. The RR for arrhythmias associated with dopamine use was 2.34 in their pooled analysis.

Of the RCTs, most of the patients came from one trial with 1044 patients and includes four trials with fewer than 50, so it’s not exactly as though this analysis adds a lot of statistical power – but it’s enough to reinforce the trends from each trial.

It is reasonable to suggest that norepinephrine is superior to dopamine – but I would also suggest the magnitude of that difference, given the data we have so far, has only been shown to be small.

“Dopamine versus norepinephrine in the treatment of septic shock: A meta-analysis”
http://www.ncbi.nlm.nih.gov/pubmed/22036860