Wednesday, May 31, 2017

Was it a PE or Just Another Other?

I have the distinct advantage and pleasure of having an Internist as my spouse.  Rarely a dinner goes by without a case discussion.  Recently, she brought up an all-too-common case…

One of her ‘’favorite’’ ESRD patients had died suddenly at home after receiving his in-center hemodialysis.  The patient was relatively young, notoriously non-compliant, had frequent fistula complications, but no known cardiopulmonary disorders.  She asked, “what do you think did this?” “Could it have been a PE or something?”

Depending on your narrative, ESRD can be either a pro or anti-coagulant state.   After all, they are exposed to heparin, they’ve got uremic platelet dysfunction, etc.  However, multiple studies have revealed the incidence of PE is 7-fold higher in ESRD compared to those with normal renal function (an incidence of PE near that of patients with active malignancy). In fact, having a PE with ESRD carries twice the mortality rate and hospitalization rate compared to those with normal renal function. Post-mortem studies would argue pulmonary embolism was a rare cause of death in ESRD, only 6.5% of hospital deaths in ESRD patients were attributable to thromboembolism.  Does this really make sense? Along with the high chance of inherent bias in autopsy studies, the risk factors for thrombosis in ESRD are seemingly endless; recent surgery, central catheterization, access thrombectomy, hospitalization, proteinuria, immobility, inflammatory states, obesity, autoimmune diseases and so on.  

More puzzling, is that recent studies have shown that pulmonary hypertension (PH) in ESRD, so dubbed ‘Uremic Pulmonary Hypertension’ is a significant entity.  Some report a prevalence as high as 50% by echocardiographic criteria, and around 10% by RHC when corrected for left sided heart failure, so called pre-capillary pulmonary hypertension.  Currently the prevalence of chronic thromboembolic pulmonary hypertension in ESRD is not known.  

It would follow that a pulmonary embolism on an already strained right ventricle would seem a perfect storm for classic PE presentation.  In fact, it has been previously postulated by Kumar et al that increased co-morbidity burden, especially cardiovascular complications associated with both these diagnoses, lead to diminished cardiopulmonary reserve, increasing both severity of PE and associated mortality.  Yet, severe signs and symptoms like hypoxia, chest pain, volume overload or persistent hypotension are quite possibly overlooked, and sooner attributed to under or overaggressive ultrafiltration, heart failure or coronary artery disease.  There is a scarcity data on clinical manifestations of PE in the ESRD population, predominantly case reports and case series.  Even DVT’s have been shown to present atypically with less extremity discomfort and far more upper extremity DVT’s vs lower extremity (30% vs 10.8%).

Ok, but wouldn’t sudden death point us in the right direction?  The limited and outdated post-mortem data have not supported massive PE as a common cause of sudden death, and a recent ERA-EDTA registry review suggest the proportion of deaths attributable to PE among dialysis patients was only 0.7% over 2 years, barely above the general population, at 0.5%. However, around 25% were either Sudden Death or Other, and as a recent review by Makar and Pun pointed out the etiology of sudden death in ESRD is quite commonly unknown and a significant number of cardiac arrests are not shockable.   One study in their review showing as many as 33% of all sudden deaths in HD patients were non-ventricular arrhythmias including asystole and pulseless electrical activity. Previous studies estimated that massive pulmonary embolism accounts for up to 13% of unexplained cardiac arrests, and the predominant rhythm of those arrests is pea or asystole in 95% of cases.  It begs, are we missing VTE?

It may be justifiable to look for PE more often, and in fact all the registry data in the world means little if we’re missing the diagnosis in the first place.  It’s akin to dogs chasing cars, what would we do if we caught one? Can we accept the risks of anticoagulation for sub-segmental PE, or incidental PE? Would you feel safe using a NOAC?  I suppose it depends on your narrative.

Posted by Corey Cavanaugh DO
OGY-3 Internal Medicine Resident, University of Louisville
Yale Clinical Nephrology Fellow - July 2017

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