Don't just do something, stand there.

Bad things happen. Trauma and tragic illnesses take the young and old. The world is not kind or just. And we, emergency docs, work at the intersection of daily life and tragedy. We strive to mitigate illness and injury. But often we can’t. We’ve all seen tragedies and monsters. And we are haunted.

This monster story starts like this: I had a case once. (We’ve all had a case) An otherwise well, middle-aged person comes in sick, gray and moribund. They have a massive, fatal PE right in front of you. It sucks: for you and for everyone. Or maybe it’s worse: he/she came in yesterday, was undetectably half-sick with nonspecific complaints. And you took care of them. Sent them home or admitted them for something else. Who knows? Something bad happens and they drop dead. Now, you’re haunted.

PE is terrifying. Why?

We’re haunted (as above).
It’s a killer “H&T.”
We get it hammered in hard and early: “Did you consider PE?”, “What’s the Well’s?”, “Can they be PERC’ed out?”

Beyond the haunting, what’s the evidence behind killer PE epidemiology and mortality?

Turns out it’s paltry and not applicable to a low-risk ED population. There is an amazing review article by Mel Herbert, among others, in the Annals that deep-dives the dogma behind fear of missed PE.₁

Open any EM text and you find that the mortality of untreated PE is as high as 36%. Deadly: A don’t miss and gotta-treat disease. The root of this data is from one small study in 1960.₂35 very sick, hospitalized patients with clinical findings suggestive of PE were included. “Findings suggestive of PE” was defined by the authors as either signs of acute RV failure or of pulmonary infarction. These were hypotensive, hypoxic, or hemoptys-izing patients (not exactly a Wells <4 grouping). They were randomized to “anticoagulant” or placebo. Enrollment was whimsical and there was no gold-standard diagnosis of PE prior to enrollment. There were 5 deaths “due to PE” in the untreated group; there were none in the treatment group. The findings of this study have been extrapolated, reinterpreted and widely quoted.

This one study, with crippling shortcomings, represents nearly the entire evidence base for the quoted mortality of “untreated” PE. And as corollary, this same study is one of the only controlled-trials proving the efficacy of anticoagulants in thromboembolic disease. Wait, what!?!?! There is no good evidence to support anticoagulation in VTE?!? Let’s remind ourselves that poor evidence isn’t counter-evidence, so is there any good data to support the contrary? Well, kind of. As per Cochrane Review₃, there is one methodologically sound RCT on anticoagulation in ambulatory patients with DVT (half had silent PE). No one in the untreated group died₄.

Shocking, right? Check the NNT. http://www.thennt.com/nnt/anticoagulation-for-venous-thromboembolism/

So, we’re terrified of a disease of unclear epidemiology and mortality AND our treatments aren’t evidence-based? Hmmm. Well, are we doing any better than we used to?

1998 saw the advent of CT-Pulmonary Artery as the practical “gold-standard” for diagnosis of PE. Nowadays, we diagnose almost 3x as many PEs as we did in 1996.₅ Incidence is exploding: are we in the midst of an epidemic? No. We are witnessing overdiagnosis. As the incidence of PE has increased absolute mortality is the same and the case-fatality rate is way down. Instead of improving care, we are picking up clinically-insignificant PEs, i.e. not the disease we seek. And during this time, complications of anticoagulation are way up.

It’s like prostate or thyroid cancer screening. “If you seek it, you will find….something.” But what is that “it”? If we’re not saving any lives from killer PEs, then what exactly are we finding?

Clinically insignificant PEs. Some have proposed that an evolutionary function of pulmonary capillary beds is to filter clots and prevent them from becoming arterial. The existence of non-pathologic clots is supported by autopsy data. Autopsy studies of all-comers found up to 90% of patients had evidence of macro- and microscopic clots₇. Studies of those dying instantaneously from traumatic causes found that up to 20% had clots.₈

What’s the take home? Nihilism, maybe. We’ve got a scary disease that we don’t understand. Our tests find insignificant or maybe even factitious disease. Our treatments might work and definitely cause harm. And we want to do something, anything, so badly.

Should we stop anti-coagulating PEs and DVTs? No, and good luck trying. But maybe you’ll think twice before sending that dimer and/or CTA-ing the well-appearing, ambulatory 25 year old….because you’ll never know if what you find is what you seek.

If I piqued your interest, check out Herbert’s articles (reference #1), the NNT on anticoagulation in VTE, and David Newman’s SMARTEM on PE. We stand on the shoulders of giants.

Click to access The%20Mortality%20of%20Untreated%20Pulmonary%20Embolism%20in%20Emergency%20Department%20Patients.pdf

http://smartem.org/podcasts/pulmonary-embolism-diagnosis-and-treatment

Calder, Kirsten K., Mel Herbert, and Sean O. Henderson. “The mortality of untreated pulmonary embolism in emergency department patients.” Annals of emergency medicine3 (2005): 302-310.
Barritt, D. W., and S. C. Jordan. “Anticoagulant drugs in the treatment of pulmonary embolism: a controlled trial.” The Lancet7138 (1960): 1309-1312.
Cundiff, David K., Juliet Manyemba, and John C. Pezzullo. “Anticoagulants versus non-steroidal anti-inflammatories or placebo for treatment of venous thromboembolism.” Cochrane Database Syst Rev1 (2006).
NIELSEN, H. KRIEMER, et al. “Silent pulmonary embolism in patients with deep venous thrombosis. Incidence and fate in a randomized, controlled trial of anticoagulation versus no anticoagulation.” Journal of internal medicine5 (1994): 457-461.
Wiener R, Schwartz LM, Woloshin S. Time Trends in Pulmonary Embolism in the United States: Evidence of Overdiagnosis.Arch Intern Med. 2011;171(9):831-837.
Egermayer, P., and G. I. Town. “The clinical significance of pulmonary embolism: uncertainties and implications for treatment–a debate.” Journal of internal medicine1 (1997): 5-10.
Freiman DG, Suyemoto J, Wessler S. Frequency of pulmonary thromboembolism in man. N Engl J Med. 1965;272:1278-1280
Havig O. Deep vein thrombosis and pulmonary embolism: an autopsy study with multiple regression analysis of possible risk factors. Acta Chir Scand. 1977;478(Suppl):1-108