Saturday, December 24, 2011

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

Thursday, December 22, 2011

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

Wednesday, December 21, 2011

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

Monday, December 19, 2011

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.

Sunday, December 18, 2011

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