Month: November 2011

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”

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

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

Health Information Exchanges Might Save Money

Though, from this data, it’s not clear through what mechanism.

This is an retrospective billing database evaluation of Memphis Emergency Department visits between 2007 and 2008.  In Memphis, 12 EDs participate in an online data repository, which may be accessed by secure web connection.  The authors compared patients presenting to the Emergency Department for whom this medical record was accessed to patients for whom this record was not.

There were no baseline differences between the demographics of the study groups, although, this retrospective evaluation cannot account for the factors contributing to why physicians chose to access the information exchange for individual patients.

The results are rather odd.  The authors cite cost savings as a result of an OR of 0.27 for inpatient hospitalization after accessing the information exchange.  However, the frequency of basically every other type of activity stayed flat or increased – in fact, the OR for Head CT was 5.0 and a chest x-ray was 4.3 if information exchange records were accessed.

More tests?  Fewer admissions?  I’m not sure it’s practical to generalize the effects of an information exchange on medical decision making in a retrospective fashion such as this.

“The financial impact of health information exchange on emergency department care.”
www.ncbi.nlm.nih.gov/pubmed/22058169

Skipping the LP in Infants 30-90 Days – Eh.

This is another one of those “practice-changing” types of articles, where the authors try to debunk some specific aggressive diagnostic or therapeutic modality that is over-utilized in a low-prevalence, high-risk population.  This article, which you may have already seen, is regarding the need for a lumbar puncture in infants between 30 and 90 days.

They perform a retrospective review of nonconsecutive infants between 30 and 90 days of age who presented to the Emergency Department and received the “septic workup” – urinalysis/culture, blood culture, and lumbar puncture/CSF culture.  They analyze a data set of 392 infants, the overwhelming majority of which are completely culture negative.  52 of them are culture positive on their urinalysis, 13 are culture positive in the blood, and 4 are CSF culture positive.  The authors note that only one patient who had a positive urinalysis also had a positive CSF fluid culture – and that infant did not qualify as a low-risk infant by the Rochester criteria – so a well-appearing infant with a positive urinalysis need not undergo LP.

So, essentially, this study tells us only that meningitis is rare and that UTIs are common.  The authors attempt to make the flawed logical argument against LP in their discussion by emphasizing the negative predictive value for meningitis in the setting of an abnormal UA is 98.2%.  However, they erroneously discount the negative likelihood ratio of 0.87 (95% CI, 0.5–1.5).  Therefore, statistically speaking, based on their results, repeating this study 100 times could lead to nearly half the study results showing a positive urinalysis favored concomitant meningitis.

Now, in a clinical sense, the authors are likely correct.  An infant who looks well, meets the Rochester criteria, has an identified source for fever, and will be receiving antibiotics is at low risk for meningitis – by prevalence alone, not by anything this study shows – and is probable to have a good clinical outcome since they’re receiving antibiotics (in the event that same organism is resulting in a well-appearing, subclinical systemic and cerebrospinal bacteremia).  The argument should not be that you can generate a zero-risk population with their combination of +UA and Rochester, but that the risk of bad outcome may be similar to the risk of harms associated with the lumbar puncture, false positives, and follow-on treatment/testing.

“Is a Lumbar Puncture Necessary When Evaluating Febrile Infants (30 to 90 Days of Age) With an Abnormal Urinalysis?”

ED Nursing Hand-Offs & Stroke Outcomes

Yet again, in the “little things matter more” series of dull, but important, Emergency Department literature.  TPA or no, what matters more in terms of their ultimate outcome is everything that happens down the line.

This is a retrospective review of consecutively-collected prospective registry data for acute ischemic stroke patients in Louisiana, looking at patients who were present in the ED during shift change.  They simply reviewed and compared the outcomes of 366 consecutive patients, looking at good outcome, neurologic worsening, discharge status, and development of pneumonia.

There are, unfortunately, huge, irreconcilable differences between the shift-change and non-shift change groups – the group that was in the ED had milder strokes and was less likely to have TPA 9.5% vs. 4.5% – but still ended up developing more pneumonia.  After their mathematical adjustments for various baseline differences, being present during shift change ended up with a five-fold increased odds of developing pneumonia, resulting in decreased likelihood of discharge to home or rehab.  The authors attribute this primarily to non-adherence with stroke unit dysphagia precautions, which is probably reasonable.  This is just retrospective and observational, but it probably identifies an important operations issue for the Emergency Department.

So, perhaps it does matter whether you give TPA or not – if TPA gets them out of the ED faster, that will help more than anything.

“Emergency Department Shift Change Is Associated With Pneumonia in Patients With Acute Ischemic Stroke”
http://stroke.ahajournals.org/content/42/11/3226.short