1. Age Adjusted D-Dimer in PE Rule Out

 Practice Change: An age adjusted d-dimer cut off for PE evaluation is a safe and effective way to evaluate patients over 50 years old for PEs.  I think we should talk to the lab about changing how we report our negative results and start using this ASAP.

Background: The rule: AGE x 10 = D-dimer Cut Off was derived and validated from 4 prospectively gathered data sets in 5182 patients published in BMJ 2010.

This is the external validation study of this rule.

Age-Adjusted D-Dimer Cutoff Levels to Rule Out Pulmonary Embolism: The ADJUST-PE Study  

– JAMA 2014

Design/Background: Prospective Multicenter Validation study from 19 centers in Europe to evaluate the previously derived Age Adjusted PE rule.

Population: Consecutive Emergency Department patients with concern for PE

Intervention: For patients with clinically suspected PE, initially evaluated as low risk with Geneva or Wells Score and followed with a ddimer +/- CTPA.

Cut off for d-dimer was AGE x 10 for patients over the age of 50.

Patients between 500 and age cut off did NOT get a CT scan and were followed up for outcome at 3 months.

Primary Outcome: Were there any failures in the patients between 500 and the age adjusted cut off at 3 month FU?

Secondary Outcomes: How many patients did not require CT?

Results: 3346 patients included in the study Of those, 817 were low risk and had a d-dimer <500 331 were low risk and had a d-dimer between 500 and their age adjusted cut off. These patients did NOT get a CT.

  • One patient in this group had a non-fatal PE in the next 3 months. (0.3%)


% pts ruled out with d-dimer >500 cut off Age Adjusted Cut off
All Patients 28% 40%

Patients >75 yo



Conclusions: This prospective validation study demonstrates age adjusted d-dimer to be a safe and effective way to rule out patients at low risk for PE.  If I can safely rule these folks out without the added time of a CT scan and the added risk of contrast, it seems like a win for everyone.

Posted in *PRACTICE CHANGING, Pulmonology | Tagged , ,

2A, 2B: Tranexamic Acid and CRASH-II

Practice Change: If Tranexamic Acid is not on your short list of life saving medications in trauma, it should be!  It is inexpensive and has a mortality benefit in hemorrhaging trauma with a NNT of 67 to save a life.   I will be giving it early and often in the ED.

Background on TXA:

What is TXA?

An amino acid that improves hemostasis.

Tranexamic acid (TXA) has been used for 30 years in cardiac, orthopedic, OB, vascular surgery, etc, to prevent blood loss. A Cochran review of 25,000 pts showed a reduced need for transfusion of 39% with the use of TXA during these high risk surgeries.

We are not completely certain how it works, but the most popular theory is that it is an antifibrinolytic that stabilizes clots once formed. It would do this by binding plasmin (required for clot breakdown) and preventing fibrin lysis.

CRASH-II was published in 2010 and evaluated the effect of TXA on bleeding in trauma. Basically the majority of what we do is from the CRASH-II study, which has been sub-analyzed several times. A second study set (MATTERs 1 and 2) are military registry studies that confirm effect, but probably aren’t as applicable to our population in the ED — (part E).

A.    CRASH-II Protocol


— Lancet – 2010

Study Design: Randomized, Placebo Controlled study in 274 hospitals, 40 countries

Population: 20,211 patients with risk of or evidence for or suspected need for transfusion due to blood loss from trauma within 8 hours of injury.

Inclusion Criterion: Injury within 8 hours and any of these:

  1. SBP < 90
  2. HR >110 OR
  3. If the treating physician felt there was risk of significant hemorrhage**.

** This was a pragmatic trial where essentially it is meant for ease of use in the ED.

à ISOLATED Intracranial Hemorrhage was an exclusion criterion based on prior poor outcomes (seizures and hematoma expansion) with medical SAH and postoperative cardiac patients who got similar medications or 2 – 10X doses of TXA.

Intervention: Randomized tranexamic acid (loading dose 1 g over 10 min followed by infusion of 1 g over 8 h).

Comparison: Placebo

Primary Outcome: Mortality at 28 days

All cause mortality at 28 days:

  • Placebo = 16% (1613 pts) vs
  • TXA = 14.5% (1463 pts) (p=.0035, RR=0.91)July9

NNT to save one life at 28 days: 67

COST of TXA per Year of Life gained: $64.

Secondary Outcomes:

HARMS: NO evidence of HARM

Since the theory is this stabilizes clots, the concern would be too much thromboembolic disease in the treated group.

# Pts with TXA Placebo
PE 72 71
DVT 40 41
CVA 57 66

Slight decreased risk of MI   35 in TXA vs 55 in Placebo

Amount of blood given: 6.06 vs 6.29 Units – not significant.

?? So, if TXA is supposed to stabilize clots and decrease bleeding, but there was no difference in amount of blood transfused, why did it show a significant mortality benefit??

The best explanation I have heard is that it is an effect of survivor benefit – basically that patients in the TXA lived more frequently for longer, so they got the opportunity to get more blood products.

Conclusion: TXA has a small, but real 1.5% benefit in mortality in trauma patients with few dowsides.



— Lancet 2011

Design: Subgroup analysis of the CRASH-II Trial

Evaluation:  TIME from injury to TXA treatment and rates of death from hemorrhage

Outcome:  Greatest benefit in death due to hemorrhage in EARLY TREATMENT and HARM at treatment >3 hours:

% Died From Bleeding TXA Placebo
< 1 hour from injury 5.3% 7.7%             p<.0001
1-3 hours 4.8% 6.1%            p=0.03
> 3 hours 4.4% 3.1% ** HARM p=0.004

 TXA’s effect on Mortality — HARM after 3 Hours

           BENEFIT   :        HARMJuly6


Conclusion: Use TXA as early as possible for the most benefit.  If you think its needed, give it, don’t wait for a trauma surgeon to tell you to use it.

Posted in *PRACTICE CHANGING, Trauma | Tagged , ,

2C. TXA in Head Injury?

What About Use In Head Injuries?

Take Home: Our system’s trauma protocol suggests stopping TXA once there is a head injury discovered, BUT given this data, I wouldn’t be too worried that we had caused harm in the patient by giving TXA early.


— BMJ 2011


Design/Background: Essentially a small “nested” study within the CRASH II trial

Population: Patients in India and Columbia who met CRASH-II criterion (SBP<90, HR>110, likely transfusion) but also had:

  • GCS of <14 and
  • CT showing Brain Hemorrhage

Intervention and Control: Same as CRASH-II (TXA vs Placebo)

Primary Outcome: How much did the ICH grow on repeat CT scan at 24-48 hours?

Secondary Outcomes: multiple radiographic and patient outcomes

Results: 270 patients (133 allocated to tranexamic acid and 137 allocated to placebo) were recruited.

–>Non-significant benefit or harm, but TRENDING towards benefit (see below).   This gives us hope, but really can’t be used in practice yet.

TXA Placebo
How much did hemorrhage grow 5.9 mL 8.1 mL
Death 11% 18%
Disabled at DC 22% 26%
Mass Effect observed on CT 47% 60%

Given these results, a second study was done to try to prove good outcomes, but unfortunately they didn’t end up getting bigger numbers enrolled.

Tranexamic acid for patients with traumatic brain injury: a randomized, double-blinded, placebo-controlled trial.

— BMCC Emerg Med 2013


Design: Similar small numbers – 238 pts, GCS 4-12, <8 hrs after injury

Outcome: New or expanding ICH

Results: Worsening in 21 (18%) of 120 patients allocated to TXA and in 32 (27%) of 118 patients allocated to placebo. The difference was not statistically significant [RR = 0.65]


“TXA may reduce [intracranial hemorrhage progression] in patients with TBI; however, the difference was not statistically significant in this trial. Large clinical trials are needed to confirm and to assess the effect of TXA on death or disability after TBI.”



SO with 2 underpowered studies in the literature, in order to finally answer this question, Crash 3 is underway. Goal is 10,000 pts for ICH with TXA. 4065 enrolled so far.

Conclusion: TXA has not been shown benefit or harm in brain injured trauma patients.  Larger studies are on the way.

Posted in Trauma | Tagged , ,

2D. TXA in Mature Trauma System

Take Home: TXA works in an established trauma system.

July 3

– Annals of Surgery 2015

Study: Prospective Observational Cohort done in England of patients while their trauma system initiated use of TXA therapy in their Massive Transfusion Protocols

Patients: Trauma patients >15 yo with ISS >15 (sick):

  1. SBP <90
  2. Poor response to Fluids bolus AND
  3. Suspected Hemorrhage

They also gathered information on “shock” defined as an ABG showing a base deficit of > 6 mEq/L.

Intervention: “CODE RED” was called, and treated with 1g over 10 min, and infusion of 1g of TXA

Comparison: Patients who did NOT get TXA – this group was very different than the TXA group.

Outcomes: Mortality, Multi-organ system failure, Infection, VTE, and Stroke/MI amongst other outcomes.

Results: 160 patients got TXA, 225 did not. TXA patients were much sicker, which made analysis difficult.

Multivariate analysis showed: TXA improved Mortality and Multiorgan Failure in Hypotensive patients only, with no effect in normotensive patients.


Conclusion: This is a smaller study that seems to show effect mostly in patients with shock, though how they got there and their measurement of shock as a base excess is a bit unusual.

Posted in Trauma | Tagged , ,

2E. Military TXA Studies – TXA looks good in multiple settings.

Military Studies

 Take Home: TXA seems effective in multiple settings and multiple studies.

There are several other studies evaluating TXA in a military setting. TXA does seem effective in these studies as well, but because the protocols are different and they are less applicable to our setting, I have only given basic info below.  Links are there to read on your own if you wish.

MATTERs Study – Military Application of Tranexamic Acid in Trauma Emergency Resuscitation (MATTERs) Study



Design: Retrospective observational study of 896 pts (293 given TXA) in Afghanistan.

Intervention: Bolus doses of TXA

Outcome: Mortality at 30 days from injury


  • Death in TXA: 17.4% (in a MORE severely injured cohort).
  • Death in No TXA: 23.9% 

Matters II study:

Association of Cryoprecipitate and Tranexamic Acid With Improved Survival Following Wartime Injury: Findings From the MATTERs II Study


Design: Prospective data registry from US and UK

Intervention: Bolus TXA or placebo +/- Cryoprecipitate

Outcome: Death 30 days after injury

Results: 1332 pts, evaluated cryoprecipitate as well.

Death % Cryoprecipitate No Cryoprecipitate
TXA 11.6% 21.4%
Placebo 18.2% 23.6%

Conclusions: While having very different protocols than are used in civilian population, TXA still seems to have significant mortality benefit in a different patient population.

Posted in Trauma | Tagged , ,

EM ONE – June 2015 Still Up All Night – Urology Dogma Challenge Especiale!

Kidney Stone Dogma Challenge

Here is the June Late Night Lit Review. There have been several good, potentially practice changing, articles on the management of kidney stones in the last year. I decided to do a deep dive on the management of Renal Colic, and what you can do to make your patients better faster.

  1. US vs CT for diagnosis (practice changer)**
  2. What a “negative” Renal US means in suspected Kidney stones?
  3. Tamsulosin (Flomax) is dead for kidney stones (practice changer)**
  4. Renal Colic PAIN – what works best?
  5. Lidocaine for renal colic
  6. IV Fluids don’t seem to help.

If you need some music to read to, here are, the Kidney Stones… kinda Gogol Bordello-esqe (Song 1) one song, then moves on to Dropkick Murphy (song 3)…


Posted in Monthly THUMBNAIL

1. US for Kidney Stones is Safe and Effective

Practice Change: In patients I suspect of having renal colic, an US will be my first imagining study.   I can always get a CT later if I’m not satisfied with the workup. I may talk to the patients about possible need for further imaging if we don’t have a diagnosis, but if 2/3 patients avoid a CT scan, that is a win.

Ultrasonography versus Computed Tomography for Suspected Nephrolithiasis

— NEJM from Sept 2014



Population: Prospective Randomized PRAGMATIC trial of patients aged 18 – 76 with abdominal or flank pain that was presumed to be due to kidney stone by the treating ED physician.

** Patients thought to be at risk for other serious intra-abdominal pathology like appendicitis, AAA, bowel disorder were excluded.

**Pregnant patients excluded


 Intervention: Randomization to 3 groups

  1. Bedside US by the ED physician (EDUS)
  2. Radiology US (RUS)
  3. CT scan per local protocol (CT)

This is a “pragmatic trial” in that just the INITIAL imaging study (CT vs US) was randomized. All other care was left up to the treating physician, including the possibility of obtaining a CT scan later in the patient’s ED stay if their initial imaging was randomized to an US and the clinician felt it was indicated.

 Control: The CT group

Primary Outcomes:

A. Were there missed diagnoses with complications?

B. Amount of Radiation within 6 mos of randomization.

Secondary Outcomes:

  1. Follow up at 3,7, 30, 90, and 180 days, lots of data points


Results: 2759 patients randomized equally to the three groups.

  • 41% with h/o nephrolithiasis
  • 52% with CVA Tenderness
  • 63% with hematuria 

Primary Outcomes:

          A. Missed Diagnoses at 30 days:

11 (0.4%) Total Missed Diagnoses 

  • NO significant difference between groups: (0.7% EDUS, 0.3%RUS, 0.2% CT)

         B. Radiation in 6 months :

Less radiation in both US groups (10.1mSv EDUS, 9.3mSv (RUS), 17.1mSv (CT) p<.0001

We all know radiation is bad, but how bad is it? 

www.xrayrisk.com estimates your lifetime risk of cancer from radiation

SO, For a 25 yo F with a typical 14 mSv abdominal/pelvis CT, the additional lifetime risk of cancer rises by 1/452.

Secondary Outcomes

  1. No difference in diagnostic accuracy between the three groups for nephrolithiasis  — 84-86% Sens, 50-53% Spec for all three groups.
  2. 27% of patients in RUS, 41% in EDUS group got a CT scan on initial visit
    1. (So only about 1/3 total got any CT scans at initial ED visit)
  3. NO difference in serious adverse events or missed diagnoses between groups.

Conclusions: This study demonstrates that a plan of initial evaluation of a possible kidney stone with US provides the benefit of decreasing radiation exposure for patients without risking any more missed diagnoses or adverse events. 

Posted in *PRACTICE CHANGING, Urology | Tagged , ,