More Discharges With HEART

Although, the observed improvements are probably more a result of their preposterously high initial admit rate.

The HEART score, already evangelized in multiple venues, is a tool for risk-stratifying chest pain patients in the Emergency Department.  Its advantage over other, competing scores such as GRACE and TIMI, is its specific derivation intended for use in the Emergency Department.  This trial, of note, is one of the first to do more than just observationally report on its effectiveness.  These authors randomized patients to the “HEART Pathway” or “usual care”.  The HEART Pathway was a local decision aid, combining the HEART score and 0- and 3-hour troponin measurements.  Patients with low-risk HEART scores (0 to 3) were further recommended to treating clinicians for discharge from the Emergency Department without additional testing.  The primary outcome was rate of objective cardiac testing, along with other secondary outcomes related to resource utilization.  Patients were also followed for 30-day MACE, with typical endpoints for cardiovascular follow-up.

With 141 patients each arm, the cohorts were generally well-balanced – specifically with regard to TIMI score >1 and accepted cardiovascular comorbidities.  Stunningly, 78% of the usual care cohort was hospitalized at the index visit.  Thus, the mere 60% hospitalized in the HEART pathway represented a massive improvement – and, such difference likely played a role in the 57% vs. 68% reduction in objective cardiac testing within 30 days.  17 patients suffered MACE, all at the index visit – and, even though the trial was not powered for safety outcomes, none occurred in the “low risk” patients of the HEART cohort.

The authors go on to state strict adherence to the HEART pathway could have eked out an additional 6% reduction in hospitalization.  Certainly, in a nearly 80% admit rate environment, scaling back to a 54% rate is an important reduction.  But, considering only 6% suffered an adjudicated MACE, there remains a vast gulf between the number hospitalized and the number helped.  Some non-MACE patients probably derived some benefit from their extended healthcare encounter as a result of better-tailored medical management, or detection of alternate diagnoses, but clearly, we can do better.

“The HEART Pathway Randomized Trial – Identifying Emergency Department Patients With Acute Chest Pain for Early Discharge”

Cellulitis Done … Strangely

The Infectious Disease Society of America updated their recommendations last year with very reasonable guidelines.  Simple, uncomplicated cellulitis requires nothing more than penicillin or a first-generation cephalosporin.  This recognizes the overwhelming preponderance of susceptible organisms implicated in such infections.  Now, in the era of increasingly endemic methicillin-resistant S. aureus, the current prevailing worry is the rate of treatment failure for such inexpensive and old-fashioned first-line agents.

So, why are these authors testing clindamycin versus trimethoprim/sulfamethoxazole?  Not only that, in addition to uncomplicated cellulitis, these authors are also testing these agents following abscess drainage – yet another uncertain indication for antibiotics.

But, so, yes – with 524 patients in the phase of the trial enrolling those with uncomplicated cellulitis, mixed abscess and cellulitis, and abscesses greater than 5 cm, the comparison was a wash.  Clindamycin and TMP/SMX had small differences favoring the former, but not large enough to reach statistical significance.  Each antibiotic has its own specific constellation of adverse effects and interactions, and with treatment failures at roughly 1 in 5 in the ITT population for each, other considerations are probably more important than any efficacy difference between the two.

Of the 296 patients for which cultures were obtained, 167 (31.9% of the total cohort) grew MRSA.  Oddly, the methods state non-suppurative lesions were not cultured, and they report only 47% of patients had purulent drainage.  Yet, cultures were obtained in 56%.  What sort of culture swab was performed on simple cellulitis?

And, of course, as with every trial, every possible comorbidity was excluded.  Someday, we’ll have the wherewithal to compare failure rates in our typical Emergency Department patient – the diabetic, obese, and renally insufficient!

The other arm of the trial, a “limited abscess” group comparing I&D plus antibiotics versus I&D plus placebo will be published separately.

“Clindamycin versus Trimethoprim–Sulfamethoxazole for Uncomplicated Skin Infections”
http://www.nejm.org/doi/full/10.1056/NEJMoa1403789

All You Need is A Good History

The oft-repeated mantra in medicine is the history and, to a lesser extent, physical examination, hold the vast majority of the clues necessary for appropriate diagnosis and treatment.  Such wisdom, handed down by sages trained in the pre-penicillin era, is reinforced throughout medical training.

While such platitudes may have an element of truth, unfortunately, the patient may in fact be the least-qualified person to provide said history.

These authors compared two data sources, the Medicare claims database and a self-reported Health and Retirement Study, looking for the diagnosis of acute myocardial infarction.  Of the 45,335 patients verified in both data sources, 3.1% self-reported having an acute MI during the preceding 2.5 years.  However, only 32.3% of those could be verified using Medicare claims data; using acute coronary syndrome as a broader definition of AMI verified the self-reported history in only 48.7%.  Conversely, of the 1.4% of patients for whom Medicare claims data indicated an acute MI, only 67.8% self-reported the event.  90.5%, at least, did state they had heart problems.

So, your undifferentiated elderly patient may or may not have had an acute MI, regardless of what they actually report.  These results are mildly surprising, considering it is reasonable to expect the general public to have sufficient health literacy to understand a major diagnosis like “heart attack”.  Then again, anyone working in the Emergency Department knows the profound challenges of extracting reliable information from the undifferentiated patient.

“Comparison of Self-Reported and Medicare Claims-Identified Acute Myocardial Infarction”
http://www.ncbi.nlm.nih.gov/pubmed/25747935

Thanks to @bloodman for the article!

SIRS – Insensitive, Non-Specific

In what is almost certainly news only to quality improvement administrators, this newly published work out of Australia and New Zealand confirms what most already knew: the Systemic Inflammatory Response Syndrome criteria are only modestly associated with severe sepsis.

This is a retrospective evaluation of 13 years of data from the Australia and New Zealand Intensive Care Society Adult Patient Database, comprising routinely collected quality-assurance data.  Of 1,171,797 patients admitted to adult ICUs, 109,663 were identified as having both an infection and organ failure – the general, clinical definition of severe sepsis.  First, the good news:  over the 13 year study period, mortality dropped substantially – from over 30% down to close to 15%.  Then, the bad news:  12.1% of patients in the severe sepsis cohort manifested 0 or 1 SIRS criteria.  Mortality was lower in SIRS-negative severe sepsis, but hardly trivial at 16.1% during the study period, compared with 24.5% in the SIRS-positive patients.

So, the traditional SIRS-criteria definition of severe sepsis, previously thought to have at least sensitivity at expense of specificity will miss 1 in 8 patients with organ failure and an underlying infection.  Considering only approximately 1/3rd of patients with two or more SIRS criteria in the Emergency Department have an underlying infection, the utility of these criteria is substantially less reliable than previously thought.  Sadly, I’m certain many of you are suffering under SIRS criteria-based alerts in your Electronic Health Record – and, if such alerts are introducing cognitive biases by decreased vigilance and alert fatigue, it ought to be obvious we're simply harming ourselves and patients.

“Systemic Inflammatory Response Syndrome Criteria in Defining Severe Sepsis”
http://www.nejm.org/doi/full/10.1056/NEJMoa1415236

Early Goal-Directed Waste For Sepsis

First there was ProCESS.  Then there was ARISE.  Now there is ProMISe.

If the prior two trials hadn’t already been celebrated and dissected, there would be much more to write regarding this one.  This, like the others, randomized patients to Early Goal-Directed Therapy for severe sepsis versus "usual care".  This, like the others, found the basic components of resuscitation – intravenous fluids and early antibiotics – are far more important than the specific targets and protocols enshrined by Rivers et al.

These authors screened 6,192 patients to randomize 1,260.  Half had refractory hypotension, and the mean lactate levels were 7.0 and 6.8 in the EGDT and usual care arms.  Patients were enrolled within 6 hours of presentation and randomized within 2 hours of meeting inclusion criteria, with the EGDT arm receiving catheter insertion capable of SCVO2 monitoring within ~1 hour.   EGDT protocol was adhered to for 6 hours following enrollment.

As expected, randomization produced some divergence in treatment due to the EGDT protocol.  The EGDT cohort received more frequent red cell transfusions during both the protocolized period and subsequent care.  Likewise, dobutamine use in the EGDT arm exceeded usual care.  However, some differences occurred outside of the protocol.  EGDT arm patients were more likely to be admitted to an ICU setting, more likely to receive any sort of central line, more likely to receive invasive blood pressure monitoring, and more likely to be placed on vasopressors.  The remaining treatment – crystalloid resuscitation, colloid resuscitation, and other transfusions were similar.

And, finally, 90-day mortality was similar: 29.5% EGDT vs. 29.2% usual care.

A financial analysis found EGDT was more costly, but the result did not reach statistical significance.  However, the cost analysis was performed using different financial models that may not be generalizable to the billing structure in the United States.  The difference in ICU admission and length-of-stay alone certainly has important ramification both from a cost and a resource utilization standpoint.

So, finally, we have the publication of the last of the triumvirate of EGDT trials.  If there were any lingering doubts (hopes?) regarding the necessity of the most resource-intensive interventions, they ought to be laid to rest.  However, as with each of these negative trials, it is important to acknowledge the role of Rivers’ work in aggressively seeking, recognizing, and treating severe sepsis.  Even as we discard the components of his protocol, the main thrust of his work has saved many, many lives.

“Trial of Early, Goal-Directed Resuscitation for Septic Shock”
http://www.nejm.org/doi/full/10.1056/NEJMoa1500896