The Risks of Missing Dialysis

Hemodialysis patients have an elevated risk of death – and it’s even higher for patients on scheduled dialysis during their “weekend.”

Most scheduled plans are every other day Mon-Wed-Fri or Tue-Thu-Sat, which leads to a two-day interval between dialysis – resulting in an extra day of fluid retention and electrolyte abnormalities.  Bad hearts + extra fluid results in a much higher incidence of essentially any kind of mortality or morbidity associated with cardiovascular causes – significantly more myocardial infarction, congestive heart failure, stroke, and dysrhythmia.  Overall, there were 22.1 vs. 18.0 deaths per 100 person-years on the long-interval days than the others.  Retrospective registry data-mining, but it probably illuminates a logical truth.

This particular article caught my eye because we have a significant population at our county facility that comes for “compassionate dialysis”.  Non-U.S. citizens that do not qualify for scheduled dialysis, they “live” a tortured existence in which they can only receive “emergency dialysis”, as in, we routinely wait until they’re at the precipice of death – with strict criteria of pulmonary edema, K+ > 6.0, bicarbonate less than 10, etc. – before pulling them back a small increment and sending them home to repeat the cycle in another week.  Barbaric.  I can’t even imagine what their outcomes are like….

“Long Interdialytic Interval and Mortality among Patients Receiving Hemodialysis”
http://www.ncbi.nlm.nih.gov/pubmed/21992122

Yet Another Highly Sensitive Troponin – In JAMA

…peddling the same tired phenomenon of magical thinking regarding the diagnostic miracle of highly sensitive troponins.  However, this one is different because it’s been picked up by the AP, CBS News, Forbes, etc. saying: “Doctors are buzzing over a new blood test that might rule out a heart attack earlier than ever before” and other such insanity.  Yes, our hearts are in atrial flutter around the water cooler about a new assay that changes sensitivity from 79.4% to 82.3% at hour 0 and 94.0% to 98.2% at hour 3.


Unless you actually read the article.

Somehow, contrary to every other high-sensitivity troponin study, this particular highly-sensitive troponin had increased specificity as well – which simply doesn’t make sense.  If you’re testing for the presence of the exact same myocardial strain/necrosis byproduct as a conventional assay, it is absolutely inevitable that you will detect a greater number of >99th percentile values in situations not reflective of acute coronary syndrome.  The only way to increase both sensitivity and specificity is to measure something entirely different.


Or, if it suits your study aims, you can manipulate the outcomes on the back end.  In this study, the final diagnosis of ACS “was adjudicated by 2 independent cardiologists” whose diagnostic acumen is enhanced by financial support including Brahms AG, Abbott Diagnostics, St Jude Medical, Actavis, Terumo, AstraZeneca, Novartis, Sanofi-Aventis, Roche Diagnostics, and Siemens.

I am additionally not impressed by their results reporting – sensitivity and specificity, followed by the irrelevant positive predictive and negative predictive values.  Since the PPV and NPV are determined by the incidence of disease in their cohort, they’re giving us numbers that are potentially not externally valid.  Rather, they should be reporting positive and negative likelihood or odds ratios – which are relatively cognitively unwieldy, but at least not misleading, but conceptually facile, like PPV and NPV.

And this is from JAMA.  Oi.

“Serial Changes in Highly Sensitive Troponin I Assay and Early Diagnosis of Myocardial Infarction”

How Frequently Is The Cath Lab Cancelled?

In North Carolina – a fair bit, actually.

This is a 14-hospital registry of cardiac catheterization activations for which the authors retrospectively evaluated how many were subsequently cancelled after activation.  They don’t delve into a great deal of detail regarding specific findings that accounted for the cancellation – they simply observe the broad categories of cancellation.

Of all cath lab activations, it was judged that 15% were “inappropriate”, with the gold standard being the consulting cardiologist opinion.  Of the cancellations, 40% were based on the EMS ECG, 31% were ED ECG, and the remainder were “not cath lab candidates”.  The author’s main focus in their conclusion is on the difference between EMS ECG cancellation and ED ECG cancellation due to ECG reinterpretation following activation.

What’s more interesting from the paper, however, is when they break it down to the precise cohorts of activation and arrival – and note that 24.7% of EMS activations were subsequently judged inappropriate.  It is also interesting that 13% of non-PCI center activations were inappropriate vs 8% of PCI center activations.  Reading between the lines, there’s probably some experiential component to the differences in activation rates, but this study doesn’t specifically look at volume and training.

“Rates of Cardiac Catheterization Cancelation for ST Elevation Myocardial Infarction after Activation by Emergency Medical Services or Emergency Physicians: Results from the North Carolina Catheterization Laboratory Activation Registry (CLAR)”
http://www.ncbi.nlm.nih.gov/pubmed/22147904

Happy Holidays!

Holiday break – intermittent and ineloquent blogging will be the norm.  I count 209 blog posts for the year – more than enough to keep anyone busy reading the archives.

But, if you’re done with those, Life In The Fast Lane has a lovely Christmas-themed blog post with great articles including:

“What was wrong with Tiny Tim?”
http://www.ncbi.nlm.nih.gov/pubmed/1340779

“Children’s Nomenclatural Adventurism and Medical Evaluation study”
http://www.ncbi.nlm.nih.gov/pubmed/20415998

“No poinsettia this Christmas”
http://www.ncbi.nlm.nih.gov/pubmed/16866065

Ranitidine Kills Neonates

Specifically, 24 to 32-week premature neonates, but it’s still an interesting demonstration of the unanticipated dangers of reducing the body’s nonimmune defense mechanisms.

This is a non-randomized, controlled, prospective, observational study from Italy that simply looked at how many premature neonates in their NICU received ranitidine treatment for acid suppression.  The secondary endpoints of the study were any observed associations between ranitidine use/non-use and NEC, mortality, sepsis, length of hospitalization, etc.  This is still non-randomized observational data, so the associations may be affected by other unknown confounders – but mortality in the non-ranitidine group was 1.6% and the mortality in the ranitidine group was 9.8%.  This difference is probably all attributable to infection, considering 25.3% of the ranitidine group developed sepsis compared to 8.7% in the non-ranitidine group.

An impressive difference, even in a non-randomized cohort.  Not a lot of obviously significant differences between groups.  We’ve seen similar, smaller increases in infection in ICU adults receiving acid-suppression medication – I wonder if these effects extend to young infants on ranitidine as well?

“Ranitidine is Associated With Infections, Necrotizing Enterocolitis, and Fatal Outcome in Newborns”
http://www.ncbi.nlm.nih.gov/pubmed/22157140

Dexmedetomidine Is Not For ED Sedation

They use alpha-2 agonists for sedation all the time in veterinary medicine – but it doesn’t look like it has a role here in the Emergency Department.

This is a small case-series out of Australia in which they gave dexmedetomidine (Precedex) to the acutely behaviorally challenged – a high-risk population in the Emergency Department, both for the patient and for staff.  Patients became eligible for dexmedetomidine if they had acute behavioral disturbance requiring physical and chemical restraint.  In this hospital, their protocol was to use droperidol 10mg IV for chemical sedation, then a second 10mg dose, and then they became eligible for second-line agents.

Their study population is thirteen patient enrollment over 21 months constituting a heterogenous mix of toxicologic and psychiatric agitation.  Five of the thirteen patients received an IV loading dose only, and the remaining eight received loading dose and infusion.  Of the five who received the loading dose, 2 had effective sedation without adverse effects – and the other 3 were not sedated and one became hypotensive.  Of the other eight, three had effective sedation, one of which developed hypotension and atrial fibrillation.  The other five had only transient or no sedation, four became hypotensive, and two were intubated for persistent agitation.

So, in all, five of the thirteen had adequate sedation using dexmedetomidine as rescue after initial attempts at chemical sedation – but seven had adverse effects.  The authors then conclude that, while it provides an additional, reasonable alternative for sedation, monitoring and managing the adverse effects would be too resource intensive.

Seems reasonable enough.

“Dexmedetomidine in the emergency department: assessing safety and effectiveness in difficult-to-sedate acute behavioural disturbance”
http://www.ncbi.nlm.nih.gov/pubmed/22158533

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

Under/Overtesting in Fever Without a Source

A curious study that observes, from the NHAMCS dataset, the testing performed by Emergency Physicians on children who have fever without a source between the ages of 3 and 36 months.

The general point of the authors, while acknowledging the limitations of this sort of data-dredging, is that testing strategies by Emergency Physicians appear to be generally non-conforming with the American Academy of Pediatrics recommendations for testing in otherwise well-appearing children.  They are hesitant to critique the patients who received laboratory testing – because they have no data on how well-appearing the child may have been or other comorbidities that might indicate testing – but they do take issue with the fact that only 43% of females under age 2 with a fever received a urinalysis and culture.  The 2008 Pediatrics guidelines – not endorsed by ACEP – would recommend that all of them receive UA and culture.  Considering the prevalence of UTI in febrile females under 2 years of age ranges from 8-17%, their criticism is probably valid.
Other trivia: 20% of children with no testing performed received antibiotics.  This could be due to missing ICD-9 data about another clinical diagnosis – but more likely due to simply treating fever unnecessarily.  
And, finally, children from zip codes with higher median incomes were more likely to receive CBC and UA.  More UAs, probably good.  More CBCs, probably bad.
Just an interesting summation of observational data.

Early Heparin Does Not Save Lives in Pulmonary Embolism

Or, if it does, this is not the article that shows it.  It tries to show it – and Rick Bukata, who I love, includes it as part of his PE review in this month’s Emergency Physician’s Monthly.  It’s a year and a half old, but I had to pull it because I’ve presented other articles showing the diagnosis and treatment of pulmonary embolism isn’t changing mortality.

This is from the Mayo clinic, and it’s observational, retrospective cohort data, which is red flag #1 for drawing practice-changing conclusions.  They reviewed charts on 400 symptomatic pulmonary embolism identified on CTPA that were subsequently admitted to the hospital and anticoagulated with systemic heparin.  In their introduction, they set out to show that outcomes are improved in pulmonary embolism if you initiate heparin in the Emergency Department.  In the end, their conclusion is essentially summarized by this graphic:

Seems pretty convincing, eh?

And, it’s true, there was a significant association between heparin in the ED and 30-day survival.  There was also, however, a significant association between 30-day survival and: tachycardia, Wells score, leukocytosis, elevated troponin, malignancy, recent surgery, ICU admission, and hemorrhagic events.  So, did patients die because they didn’t get heparin, or did they die because they were more acutely ill – and/or had a hemorrhagic event after initiating heparin?  The big one for me is the difference between positive (>0.01 ng/mL) troponins – 26.4% in their survivors and 47.8% in the non-survivors.  Considering the criteria for diagnosis of submassive pulmonary embolism – patients who occupy a different level of risk for poor outcomes – includes elevated troponins indicative of right heart strain, I think this study doesn’t properly support anything it tries to imply regarding the time to heparin and survival.

“Early Anticoagulation Is Associated With Reduced Mortality for Acute Pulmonary Embolism”
www.ncbi.nlm.nih.gov/pubmed/20081101

Your Residents Would Love a Wiki

It’s not a terribly profound paper – along the lines of “we did this and we liked it” sort of thing – but it is a relevant educational application of wikis in medicine.

The BIDMC Internal Medicine department undertook an initiative to essentially convert all their little handbooks and service guides to an online reference.  They chose the wiki interface so anyone could update information or add pages while allowing updates to be tracked and rolled back as necessary.  They promoted it during their intern orientation and made a significant effort both to get people to update it and use it.  And, for the most part, they were successful.  Most residents (92%) thought it was useful, it was mostly used to find phone numbers and rotation specific clinical information, and, overall, about half of the PGY-2 and -3s updated the site during the 2009-10 year.

It probably takes a lot of effort and requires just the right collaborative environment, but there are a lot of residencies, departments, or other clinical organizations that could also probably benefit from something similar – particularly if there are a lot of rotating students/residence between difference services or sites.

“Adoption of a wiki within a large internal medicine residency program: a 3-year experience”
http://www.ncbi.nlm.nih.gov/pubmed/22140210