Research Roundup (formerly articles of the month)

Given than it has been 3 months since the last version, I think it has officially become ridiculous to call these posts “articles of the month”. This is a summary of the papers Casey and I discussed for the BroomeDocs Journal Club. Most of the papers will have been covered in individual blog posts, but there are always a few gems thrown in to keep things interesting.

Simulation saves lives!

Josey K, Smith ML, Kayani AS, et al. Hospitals with more-active participation in conducting standardized in-situ mock codes have improved survival after in-hospital cardiopulmonary arrest. Resuscitation. 2018; 133:47-52. PMID: 30261220

A paper demonstrating improved clinical outcomes from an educational intervention probably warrants its own blog post, especially when that improved outcome is mortality. However, I think we always need to be careful with observational data, which is why it gets the lead position in this post instead. This is an interesting observational study that takes place in a single hospital system that contains 28 hospitals (26 of which participated). They divided hospitals into large, medium, and small, and then compared hospitals that were performing more in situ mock codes than the median to those who were performing less. The more active hospitals averaged 18 in situ mock codes per 100 beds in the hospital per year. The less active hospitals averaged 3/100 beds/year. The primary outcome was the in hospital cardiac arrest survival rate, and it was higher in the hospitals that did more simulation (43% vs 32%, p<0.0001). This difference was maintained when they adjusted for potential confounders. This is a big and potential important difference. The hospitals who did more sim were more likely to defibrillate (during simulation) in less than 2 minutes (35% vs 26%, p=0.05), but there were no other observed differences, and that could simply be a marker of comfort with simulation rather than resuscitation quality. They calculate that you would only have to perform 1 extra in situ mock code per 100 beds per year to save a life, and that would clearly be a worthwhile investment. However, I think we need to be cautious with our conclusions because of the observational nature of the data. Why were certain hospitals doing more sim? Might it be a marker of better hospitals, or more engaged staff? The chance for an unobserved confounder is reasonably high. They do cite 2 other studies with similar outcomes, which is good news, but they have similar problems. This is a good paper to have. If you are looking for sim funding, I would throw this around liberally (but maybe avoid repeating my skeptical comments).

Bottom line: I am thrilled that we now have an in situ simulation program running in my emergency department. I am not sure it will reduce mortality, but we are already finding many ways that we can improve.

Which salty water do you prefer?

A lot of people hate “normal saline”, but after reviewing three huge trials, I am not sure it is all that bad:

SPLIT: Young P, Bailey M, Beasley R, et al. Effect of a Buffered Crystalloid Solution vs Saline on Acute Kidney Injury Among Patients in the Intensive Care Unit: The SPLIT Randomized Clinical Trial. JAMA. 2015; 314(16):1701-10.PMID: 26444692

Physiologically speaking, normal saline is not all that normal. It has a very low pH, and the electrolyte balance looks nothing like plasma. However, based on the results of this RCT, I have been fairly comfortable with using it as my first line fluid in the emergency department. This is a double blind cluster randomized RCT at 4 ICUs in New Zealand, in which all adult ICU patients were randomized to either normal saline or buffered crystalloid (Plasma-lyte 148) as their primary IV fluid. In 2278 patients, there was no difference in the primary outcome of renal dysfunction. There were also no differences in any of the secondary outcomes. The amount of fluid used wasn’t huge and the primary outcome wasn’t patient oriented, but overall this is a good study that shows pretty equivalent results.

The full write up can be found here.

SMART: Semler MW, Self WH, Wanderer JP, et al. Balanced Crystalloids versus Saline in Critically Ill Adults. The New England journal of medicine. 2018; 378(9):829-839. PMID: 29485925 [free full text]

This is another ICU based study comparing normal saline to a balanced IV fluid (Ringer’s or Plasma-Lyte-A). Unlike SPLIT, it was unblinded, and not really randomized. The fluid you got depended on the month you were admitted to the ICU. There were 15,802 patients in the trial, and the primary outcome (a composite of death, dialysis, and doubling of creatinine) might have been statistically better in the balanced group, although when I do the math I get a p value of 0.06 (14.3% vs 15.4%; OR 0.91, 95% CI 0.84-.099, p=0.04). It is a small difference, if it is real, and none of the individual components of the composite were statistically different on their own (in a massive trial). The big problem is that this trial isn’t blinded, which can easily introduce bias, and with such small differences in a composite outcome, I think the potential for bias is a huge deal. The methods of the SPLIT trial are significantly stronger, so these result don’t trump SPLIT in my mind.

The full write up can be found here.

SALT-ED: Self WH, Semler MW, Wanderer JP, et al. Balanced Crystalloids versus Saline in Noncritically Ill Adults. The New England journal of medicine. 2018; 378(9):819-828. PMID: 29485926 [free full text]

The last IV fluids trial is an emergency department trial. It was done at the same centres at the same time as SMART. It is again a pragmatic, unblinded trial, alternating between normal saline and a balance fluid (Ringers or Plasma-Lyte-A) based on the month. They included 13,347 patients and for the primary outcome of hospital free days by day 28, there was no difference (25 days in both groups, OR 0.98, 95%CI 0.92-1.04, p=0.41). As a secondary outcome, there was a slightly lower incidence of major adverse kidney events at 30 days in the balanced crystalloid group (4.7% vs 5.6%, OR 0.82, 95% CI 0.7-0.95, p=0.01). Unfortunately, they didn’t have baseline creatinine values for 35% of the population, which makes the secondary renal outcome a little more questionable (and it was only a secondary outcome to begin with).

The full write up can be found here.

Overall bottom line: We have 2 negative trials, and one unblinded trial with a questionable, small benefit to using a balanced crystalloid. If you are already using Ringer’s as your go to, this reinforces that practice. However, the results indicate that saline is probably safe, and considering various logistic issues in resuscitation, will continue to be my first line fluid.

I need to get used to saying adrenaline – or maybe not?

Perkins GD, Ji C, Deakin CD, et al. A Randomized Trial of Epinephrine in Out-of-Hospital Cardiac Arrest. The New England journal of medicine. 2018. PMID: 30021076 [full text]

Moving to New Zealand, I probably need to shift my vocabulary from epineprhine to adrenaline. However, it could be a moot point if I never order the drug anymore. This is the hugely discussed PARAMEDIC2 RCT of epinephrine versus placebo in out of hospital cardiac arrest. There are a lot of opinions about this paper, but I think it mostly confirms what we already knew: epinephrine puts a lot of people in hospital, but very few (or none) of them have good outcomes. Overall survival was marginally improved, but neurologically intact survival was not.

The full write up can be found here.

Bottom line: I think this paper indicates that epinephrine should be removed from routine use in out of hospital cardiac arrest, as the harms likely outweigh any potential benefit.

Plasma in trauma

Again, we get multiple papers on the same topic. Again, they seem to say different things.

PAMPER: Sperry JL, Guyette FX, Brown JB, et al. Prehospital Plasma during Air Medical Transport in Trauma Patients at Risk for Hemorrhagic Shock. The New England journal of medicine. 2018; 379(4):315-326. PMID: 30044935

This paper got a lot of people excited because of the unbelievable decrease in mortality. It is a pragmatic, multi-centre, cluster-randomized trial comparing 2 units of plasma to crystalloid in prehospital adult trauma patients at risk for hemorrhagic shock. (Prehospital included being transferred from a community hospital). In 501 patients, there was a 10% decrease in mortality in the plasma group (23% vs 33%, p = 0.03). A 10% decrease in mortality would be groundbreaking, but there are reasons to be skeptical. The trial was not blinded and they only included 500 patients out of more than 7,000 screened). Also, the 95% confidence interval is huge. And, there was another similar trial with very different results….

The full write up can be found here.

COMBAT: Moore HB, Moore EE, Chapman MP, et al. Plasma-first resuscitation to treat haemorrhagic shock during emergency ground transportation in an urban area: a randomised trial. Lancet. 2018; 392(10144):283-291. PMID: 30032977

This study is pretty similar. They looked at adult prehospital trauma patients with signs of shock and compared saline to 2 units of plasma. This time, in 144 patients, there was no statistically significant difference, but mortality was actually 5% higher in the plasma group (15% vs 10%; OR 1.54; 95% CI 0.60 – 3.98; p=0.37).

The full write up can be found here.

Overall bottom line: We need more research. After reading PAMPER, I started to reconsider my skeptical stance on the entirely unproven, but very popular concept of “balanced transfusion”. Looking at these papers together, I am still not convinced plasma helps our patients, and all blood products cause harm. Prehospital plasma is definitely not ready for primetime, and I am still uncertain about the balanced transfusions we use as part of massive transfusion protocols.

Who has heard of fou rie prodromique?

Özel G, Maltête D, Lefaucheur R. Pathological Laughter as a Symptom of Middle Cerebral Artery Stroke. The Journal of emergency medicine. 2018; [30249344]

This is an interesting case report, sent in by Dr. Andy Tagg, of a patient whose first presentation of a stroke was pathological laughter, or fou rie prodromique. (Should I have heard of that before? Did I skip too many classes in medical school?) Apparently, “pathological laughter is a rare neuropsychiatric disorder associated with a wide range of brain disorders, including vascular pseudobulbar palsy, tumors, amyotrophic lateral sclerosis, and multiple sclerosis”. They lament the fact that, because this is a rare presentation, there was a delay to diagnosis, meaning that the patient did not receive “optimal management” with thrombolytics. I think it would be a really bad idea to lyse anyone with this presenting symptom. I think it is probably a bad idea to lyse anyone, but that is a different conversation. Clearly this patient is not represented by NINDS, and the differential is broad enough that clinical judgment would hopefully lead us away from the experimental medication with significant known harms.

Is it broken, or just fractured?

Ouellette L, Hamati M, Hawkins D, Bush C, Emery M, Jones J. Penile fracture: Surgical vs. conservative treatment. The American Journal of Emergency Medicine. 2018;

I am surprised this one is in an emergency medicine journal. We are not going to be making decisions about surgery in penile fractures, but I think it is good to know the surgical literature, so we are not surprised by their recommendations for our patients. This is chart review of 32 patients with penile fractures. Average age was 37 (range 14 to 59). Guys, unsurprisingly, didn’t rush to the emergency department with these injuries. The average duration of symptoms was 21 hours by the time they arrived. Mechanism of injury was “sexual maneuvers” in 66%, masturbation in 13%, rolling over (I don’t believe it) in 6%, and fall onto erect penis (seems unlikely) in 6%. The diagnosis was made clinically in all cases – you don’t need an ultrasound. 14 patients (44%) were treated conservatively, with outpatient follow up. 5 of these patients ultimately had surgery. Therefore conservative management is OK for some patients, but this paper doesn’t indicate that these two strategies are equal. Patients weren’t randomized, and healthier patients (minimal pain/swelling, ability to urinate, and small tears seen on ultrasound) were selected to the conservative treatment group.

Bottom line: I am talking to urology every time, but won’t be surprised in a relatively well patient if they suggest conservative measures and outpatient follow-up.

Cheesy Joke of the Month

It’s very rare for a defibrillator to fail…
but when it does, no one is shocked.