May 2014 – Emergency Medicine Literature of Note

Predicting Past Massive Transfusion Practices

Traumatic resuscitation is evolving – and reasonably so – to an aggressive, early-intervention strategy. The current evidence seems to suggest patients benefit from early, whole blood volume replacement in the setting of hemorrhage.

But, in order to aggressively intervene early, it’s necessary to predict such need equally early in the initial trauma assessment process. Therefore, a variety of prediction decision-instruments have been derived, such as this one from Japan. These authors looked retrospectively at 119 severely injured trauma patients, developed odds ratios for massive transfusion via logistic regression, and then created a scoring system with a cut-off predicting massive transfusion. They then subsequently validated this score on another retrospective cohort of 113 patients from the same institution. Their score contains, essentially, the expected elements – age, lactic acid level, systolic blood pressure, FAST exam findings, and pelvic fracture type – and a score of 15 or higher was 97.4% sensitive and 96.2% specific for massive transfusion.

However, what this rule predicts is not the population that needs massive transfusion – but, because both steps were performed retrospectively, it simply describes the consistency in the authors’ general practice at this single institution. At the authors’ institution, the patients that looked like the ones described by the rule – elderly, hypotensive, positive FAST, etc. – are the ones that received massive transfusion. Therefore, when they look back to derive a decision instrument – they’ll find it simply reflects their general practice. Subsequently, to validate the instrument – again, if their practices haven’t changed, the decision rule will simply accurately reflect the continued practice pattern from which it was derived. The authors do not mention whether they had a formal early massive transfusion protocol or practice in place, but, if so, this would further skew the decision instrument to reflect the guidelines guiding practice, rather than actual patient need. Finally, for one last hit to external generalizability, a “massive transfusion” was defined as 10 units of PRBCs – which, in Japan, are about 1/3rd the volume of those in the United States.

Despite its reportedly excellent performance, this rule cannot be relied upon until prospective, external study validates its use.

“Predicting the need for massive transfusion in trauma patients: The Traumatic Bleeding Severity Score”
http://www.ncbi.nlm.nih.gov/pubmed/24747455

Infections & Transfusions

We love our transfusions down in the Emergency Department. We especially love them in our trauma patients – and, if anything, the move is to provide earlier, more aggressive volume replacement, and to use more FFP, cryoprecipitate, and platelet product to maintain optimal coagulation parameters.

The downside? Besides cost, over-utilization of a limited resource, and the various adverse reactions that may occur – there’s a bit of an infection risk.

This JAMA meta-analysis pools together the results of 18 trials comparing “restrictive” vs. “liberal” transfusion strategies for PRBCs. These trials ranged across medicine from cardiovascular settings, the critically ill, sickle cell disease, and other surgical settings. In most trials, the restrictive transfusion setting ranged from a Hgb of 7 to 9 g/dL, while the liberal strategies were typically goals above 10 g/dL. These authors simply looked at the pooled incidence of “serious infection”, which was typically reported as wound infection, bacteremia, pneumonia, or a broad definition of sepsis.

In the “restrictive” transfusion group, there was an overall pooled risk of infectious complication of 11.8% (95% CI, 7.0%-16.7%), compared with an infectious complication rate of 16.9% (95% CI, 8.9%-25.4%) in the “liberal” transfusion group. The authors estimated a “number needed to harm” between 20 and 38, depending on the restrictive transfusion threshold.

This study does not, by itself, indicate transfusions ought to be withheld when indicated. Rather, these authors primarily suggest, in order to fully describe the risks and benefits of any transfusion strategy, that infectious complications be included in data collection during trials. This ought to be of even greater importance in the new surveillance of massive transfusion protocols – as PRBC products aren’t typically even the highest-risk for subsequent infectious complications.

“Health Care–Associated Infection After Red Blood Cell Transfusion”
http://www.ncbi.nlm.nih.gov/pubmed/24691607

Grilling Injuries on Memorial Day

If life were a generic action movie, otherwise idyllic backyard food preparation activity would be interrupted by nonsensical brawling. And, invariably, the injuries occurring would probably include those suffered from direct contact – in effect, to grill the villainy out of the antagonist.

Reality is rather less sensationalist. Indeed, apparently, the grilling injury of note is rather from the wire bristles on the grill cleaning implement. These wire bristles become inadvertently detached, embedded in the culinary creations, and ultimately ingested. As this CDC Morbidity and Mortality Weekly Report report on a small case series of grilling injuries states:

“The severity of injury ranged from puncture of the soft tissues of the neck, causing severe pain on swallowing, to perforation of the gastrointestinal tract requiring emergent surgery.”

Yet another hidden danger in the home!

“Injuries from ingestion of wire bristles from grill-cleaning brushes – Providence, Rhode Island, March 2011-June 2012.”
http://www.ncbi.nlm.nih.gov/pubmed/22763887

More of the Same Inappropriate Antibiotic Prescribing

There is no debate regarding the correct treatment of acute bronchitis in patients without underlying immunodeficiency or pulmonary structural disease. The correct antibiotic treatment is: none. This is not a controversial subject. Indeed, as this research letter in JAMA notes, since 2005 the National Committee of Quality Assurance has published a measure in the Healthcare Effectiveness Data and Information Set stating the correct rate of antibiotic prescribing in acute bronchitis is: zero.

If you’re hoping this next part is where I excitedly share a successful reduction in inappropriate antibiotic use, you’ll be more than a little disappointed.

Using The National Ambulatory Medical Care Survey and National Hospital Ambulatory Medical Care Survey, these authors found, unfortunately, that 71% of patients with acute bronchitis are receiving a prescription for antibiotics in outpatient settings. There was essentially no difference in prescribing rates over any of the NAMCS samples – we were just as irresponsible in the 2008-2010 survey period as we were in the 1996-1998 period. There was no difference in rate between Emergency Department and primary care settings, nor in race, age, insurance status, nor care location. 41% of patients received an extended macrolide – azithromycin – followed most commonly by fluroquinolones, aminopenicillins, and cephalosporins.

Yes, Virginia, a self-limited condition for which antibiotics confer no benefit frequently receives fluoroquinolone therapy.

Words fail me. I will simply quote the authors’ conclusion:

“Avoidance of antibiotic overuse for acute bronchitis should be a cornerstone of quality health care. Antibiotic overuse for acute bronchitis is straightforward to measure. Physicians, health systems, payers, and patients should collaborate to create more accountability and decrease antibiotic overuse.”

“Antibiotic Prescribing for Adults With Acute Bronchitis in the United States, 1996-2010”
http://jama.jamanetwork.com/article.aspx?articleid=1872806

The Struggles of tPA Consent

Providing informed consent for any therapeutic intervention can be challenging. And, then there’s stroke. Acute stroke spans the gamut from mildly limiting to profoundly disabling – with a non-linear relationship between the NIHSS and disability. There are folks with NIHSS score of 4 who can walk into the Emergency Department, and there are folks with the same score or lower who are functionally incapacitated. All this means it’s a struggle to provide an individualized estimate of the benefits, risks and alternatives in consent for tPA.

This is a lovely, short, qualitative survey of a handful of (mostly) neurology consultants in the United Kingdom, asking a few questions regarding the diagnostic process, shared decision-making, and consent for thrombolysis. Not all consultants surveyed seemed to appreciate the challenges, but others recognized limitations in the data, as well as how difficult it made informed consent:

“I think there needs to be em, err a minimum standard, standardised information available based on what you believe is the right interpretation of the trial. We have to remember that this is based on em, err limited number of randomised trials ….. This is a particularly heterogeneous disease it cannot be applied to a single patient, I think the predictions em in model could be designed but again I don’t think it can be predicted for an individual group of pa-, individual patients so we believe these are the kind of risks and benefits but you know it cannot be predicted to the individual patient.”

Other physicians commented upon the challenges of making a rapid, certain diagnosis, and the inadequate demands made upon patients and families to choose in a time-compressed setting. Overall, it’s an interesting little read.

“Risk communication in the hyperacute setting of stroke thrombolysis: an interview study of clinicians”
http://emj.bmj.com/content/early/2014/05/16/emermed-2014-203717.short

Your Patients Will Abuse Opiates

Hydrocodone is now the most commonly prescribed medication in the United States. And, your patients will abuse it.

This small study is a prospective follow-up of 85 patients discharged from an urban Emergency Department in Rhode Island. All patients were prescribed an opiate pain reliever – mostly hydrocodone and oxycodone. The authors followed them up at 3 and 30 days to evaluate for self-reported misuse, as well as other clinical characteristics that might predict misuse.

At 30 days, 42% reported they had misused the opiates as prescribed. The most common misuse, described by 92% of misusers, was exceeding the prescribed dose. Half of those exceeding the prescribed dose also exceeded the daily recommended limit of acetaminophen. An additional 39% of misuse patients took opiates diverted from another source, and another 36% stated they used surplus opiates recreationally. Patients with pre-existing disability, chronic pain, and prior opiate use were the most likely to misuse. Any non-zero risk category on the Drug Abuse Screening Test (DAST-10) gave an odds ratio of 18 for misuse, compared with those who received opiates but did not misuse.

This study is limited in its generalizability and has other bias issues associated with enrollment. However, it is yet another window into what happens to the opiates we inject in the healthcare ecosystem and our need for judicious prescribing.

“Prescription opioid misuse among ED patients discharged with opioids”
http://www.ncbi.nlm.nih.gov/pubmed/24726759

Nausea? We’ve Got Placebo For That

Turns out, there’s truth inside those late-night infomercials and flashing banner ads on the Internet: the power to cure does, in fact, lie within ourselves. Or, possibly at least, decrease nausea.

This is a randomized, blinded, placebo-controlled trial comparing 4mg IV ondansetron vs. 20mg IV metoclopramide vs. saline solution placebo in Emergency Department patients with nausea & vomiting. 258 patients were evaluated, mostly evenly distributed between groups, and with similar causes of nausea. 30 minutes after administration, similar decreases in nausea were noted in each group, best visualized in this graph:

There were no differences in patient satisfaction with therapy, but fewer patients in the metoclopramide group required rescue therapy, and a greater number of placebo patients failed to have any symptom improvement (non-significant).

What lesson can be drawn from this? Uncertain. It is probably fair to say there is some placebo effect at work, and, considering there are centrally-acting mechanisms for nausea, they may in fact be curative. More likely, however, is that many of these causes of nausea & vomiting are simply self-limited, and resolve regardless of therapy. Further research might evaluate which specific causes resolve without therapy, and thus reduce costs and adverse effects associated with anti-emetic therapy.

“Antiemetic Use for Nausea and Vomiting in Adult Emergency Department Patients: Randomized Controlled Trial Comparing Ondansetron, Metoclopramide, and Placebo”
http://www.ncbi.nlm.nih.gov/pubmed/24818542

tPA: We Don’t Need No Stinkin’ Consent!

Yes, this the brave future imagined by pro-tPA colleagues: there are neurologists in a van down by the river, and they’ll drive right to your house and give you tPA – without your consent!

This is a research letter from JAMA, in which researchers from UCSF performed a survey of patient preferences through an online cohort representative of the adult U.S. population over 50 years of age. These authors, as they would lead you to believe, asked participants to compare their desire to receive CPR after cardiac arrest with their desire to receive tPA after a stroke. 75.9% of surveyed participants wanted CPR and 76.2% wanted tPA. Therefore, these authors conclude:

“… there are equally strong empirical grounds for presuming individual consent to thrombolysis for stroke as for presuming individual consent to CPR.”

I am not an ethicist, so I’m unable to precisely articulate how odd this comparison is at face value. Would any therapy patients would choose 75% of time mean we ought to presume consent? Is CPR the “gold standard” for emergency consent? There are interesting questions regarding how this data ought to be interpreted in the context of emergency consent I’m not qualified to answer.

However, I am qualified to comment on their methodology, i.e., the best way to get the answer you want: ask a question in such a way they’ll answer how you intend. How did they ask patients if they wanted CPR? They showed them a “depiction of probabilistic outcomes after paramedic-initiated CPR”. This depiction is not provided in the text, only a reference to an article they used to make it. For tPA? They used a graphical depiction of the benefits of tPA from this article. They do not specify which graphical depiction they used, but the final product of the previous pro-tPA physicians was this, Figure 3:

With a graphic like this, is it any wonder the patients surveyed were amenable to tPA? Interestingly, the authors who created the graphical depiction state this graphic “complements the numeric text of a national patient education tool developed jointly by US neurology, emergency medicine, and stroke patient organizations.” The link in their citations is broken, but I have found a reproduction here, which contains the following fantastic isolated quote:

“If given promptly, 1 in 3 patients who receive tPA resolve their symptoms or have major improvement in their stroke symptoms.”

It boggles the mind ACEP was complicit in approving this horrible flyer. As you can now see, this seemingly trivial document has since catastrophically mutated into the terrifying basis of giving tPA without informed consent.

“Testing the Presumption of Consent to Emergency Treatment for Acute Ischemic Stroke”
http://jama.jamanetwork.com/article.aspx?articleid=1861784

VUR, Renal Scarring and other Fictitious Maladies

A guest post by Rory Spiegel (@EMNerd_) who blogs on nihilism and the art of doing nothing at emnerd.com.

As Emergency Physicians, one of the more vexing tasks asked of us is to identify the otherwise well appearing patient who has an occult illness that, if not identified, will lead to poor outcomes. With this in mind, we now turn our attention to the well appearing febrile infant and our unfounded obsession with urine. The fear that these children are quietly infarcting their nephrons is one of the more far fetched tales in emergency medicine.

  In a recent NEJM article published by the RIVUR Trial Investigators, the authors examined whether prophylactic antibiotics for children with voiding cystourethrogram (VCUG) confirmed vesicoureteral reflux(VUR) were effective in preventing recurrent infections and more importantly, decreasing the extent of renal scarring (as per DMSA scan). Patients were randomized to either daily trimethoprim-sulfamethoxazole (TMP-SMX) suspension or placebo for one year. Authors found that children treated with prophylactic antibiotics had an absolute decrease in the recurrence of urinary tract infections by 12%. Meaning, you would have to treat 8 children for 12 months to prevent one case of recurrent UTI. More importantly the rate of renal scaring at follow up was identical.   Among the children who experienced their first recurrent UTI, the rates of E. coli resistance to to TMP-SMX was 63% in the active group vs 19% in the controls.

Though this trial fails to address the futility of our quixotic attempts to diagnose and treat every UTI, clearly the utility of searching for and diagnosing VUR in febrile children in the hopes of preventing future renal scarring is a flawed concept. Furthermore it is unclear whether the surrogate endpoint of renal scarring, as seen on DMSA, is clinically relevant. Not only are we most likely treating a fictitious disease process, but as the RIVUR authors demonstrated we are doing so ineffectively.

“Antimicrobial Prophylaxis for Children with Vesicoureteral Reflux.” http://www.ncbi.nlm.nih.gov/pubmed/24795142

There’s Been A Drive-By Lysing!

If you’ve been keeping up, a couple weeks ago JAMA had a theme issue for Neurology – which nowadays, apparently, is mostly tPA. And, the latest and greatest – concierge Neurology! In which they come to your house to give you lytics.

This is the Prehospital Acute Neurological Treatmentand Optimization of Medical care in Stroke Study (PHANTOM-S), conducted in Berlin, Germany, using the Stroke Emergency Mobile (STEMO) vehicle. They compared time-to-thrombolysis during 46 weeks of standard care with 46 weeks of STEMO period – and, within STEMO period, operation of the vehicle was a week-on/week-off deployment. Unsurprisingly, driving the tPA to the patient shaves 25 minutes off the alarm to tPA time. Success!

MedPage Today, with it’s usual insightful analysis, breaks out a table of glowing secondary outcomes – improvements in in-hospital all-cause mortality, discharge to home, symptomatic intracranial hemorrhage, and overall tPA complications …

… before acknowledging all these improvements occurred even when the STEMO wasn’t deployed, and it was rather general stroke care improvements over the study period reflected in these secondary outcomes. Additional praise is provided by James Grotta, who has started his own mobile stroke unit in Houston. And, finally, Associated Editor Jeff Saver, of endless tPA conflict-of-interest disclosures, chimes in for the Editor’s audio summary.

I think it’s clear, between this and its preceding pilot study, that it is possible to drive a bus around with a stroke neurologist and a CT scanner and rule out intracranial hemorrhage. The main concern might be over-treatment of stroke mimics, but these authors state the same number of patients treated in all observation windows ultimately received non-stroke diagnoses. However, they report a baseline stroke mimic treatment rate of 2.2% – which is line with other literature describing institutions that don’t go looking very hard for non-stroke diagnoses after tPA. Other institutions that require MRI signs of ischemic lesions have stroke mimic rates up to 15.5%, so I wouldn’t place much stock in this specific statistic as a measure of quality.

The last issue – a reasonable case can be made for safety as long as there’s a neurologist riding shotgun in the ambulance. However, you’ll have to find neurologists willing to take such emergency call and support their salaries while they wait for deployment, which will end up being logistically and financially unworkable. The next step, I presume, will be pre-hospital telestroke where paramedics are supervised by a remote neurologist. A bright, or dim, future, depending on your view of tPA.

“Effect of the Use of Ambulance-Based Thrombolysis on Time to Thrombolysis in Acute Ischemic Stroke”
http://jama.jamanetwork.com/article.aspx?articleid=1861800