Thank you, Jesse Platt, for walking us through the complicated case of a 66 year old man with months of worsening dyspnea and hypoxia of unclear origin who was diagnosed with (very) severe pulmonary hypertension, and is thought to have either PVOD or pulmonary capillary hemangiomatosis (PCH)!
We went through the classification of pulmonary hypertension:
Suggested approach to etiologic workup of PH
Physical exam (look for clubbing, parasternal heave, S2, crackles on lung exam, signs of cirrhosis, etc)
Chest X-ray (look for venous congestion, prominent PA, ILD)
CT chest (looking for ILD, parenchymal lung disease, nodules, mosaic attenuation (what is that?) which may suggest areas of heterogenous blood flow or air trapping)
Transthoracic echo (with bubble/contrast): looking for intracardiac (early bubbles) or intrapulmonary (late bubbles), estimate of RV and PA pressures, signs of RV dilation or volume/pressure overload
Ventilation/perfusion (V/Q) scan: this is the gold standard for ruling out CTEPH. Remember that CTEPH doesn’t require a history of repeated PEs; it really represents a dysregulated healing response to vasoactive cytokines from even a single PE in the past!
Consider PFTs and nocturnal polysomnography (to rule out OSA)
Consider ABG (to confirm hypoxia, and also if concern for shunt physiology)
Consider blood testing for other causes of PH (HIV, ANA [only send dsDNA, RNP if ANA+ ), RF, ANCA)
Right heart catheterization: gold standard for diagnosing/confirming PH (defined as a mean PA pressure >25mm Hg)
Ultimately, this patient’s testing (RHC w/ severe pHTN, TTE w/ LVEF 60% but moderate RV dilation and late bubbles suggestive of pulmonary AVMs, CT chest w/ scattered basilar nodules with diffuse mosaic attenuation) suggested a diagnosis of PVOD vs PCH as the diagnosis.
In brief, PVOD is characterized by smooth muscle hypertrophy within pulmonary veins and venules, whereas PCH is marked by atypical capillary proliferation; both cause pulmonary hypertension, and can be difficult to differentiate from PH of other causes.
We learned that severe hypoxia (10L O2 in this case) is uncommon with most causes of PH, and should make you think of:
Large intracardiac/intrapulmonary shunt
See this table to see a comparison of PH, PVOD and PH:
Two final pearls
PVOD and PCH patients are at a higher risk of pulmonary edema with vasodilator therapy given their capillary hemodynamics
PASPs from echos are derived from the maximum tricuspid valve velocity; but this is reliant on good views on echo, and varies based on underlying comorbidities, etc. Generally TTE PASPs are thought to be off from RHC PASPs by about 10mm Hg (want more info?)
There are case reports of PCH being treated with doxycycline, which apparently has anti-angiogenic properties! (see #1 below)
Today we discussed a patient diagnosed with early localized Lyme with persistent fevers >72 hours after initiating doxy found to have babesia co-infection.
We reviewed the various stages of Lyme disease and how this affects treatment duration and PO vs. IV antibiotics as well as treatment for babesia (Atovaquone + Azithro vs. Clinda + Quinidine — depending on severity).
In different areas of the country (especially in New England) the rates of co-infection with babesia can be as high as 39% (1) and, in these areas, patients diagnosed with Lyme disease should probably be screened for babesia as well. We discussed approaching co-infection by identifying the regional tick species, in this case, Ixodes. Co-infections based off of the Ixodes tick include, Anaplasma, Babesia, Lyme and Powassan.
We also reviewed Lyme mimickers including STARI (carried by the Lone Star tick — which also carries Ehrlichiosis), but that geographically this was ruled out in our case.
As Dr. Gluckman pointed out, early localized Lyme is a CLINICAL diagnosis and no lab testing was necessary to MAKE the diagnosis — but that serologies later can be used to confirm the diagnosis.
Lastly we reviewed the 2016 NEJM article which discussed screening the US blood supply for Babesia microti (2) — it hasn’t been rolled out to the Red Cross yet, but keep your eyes peeled!
Just as a quick reminder and plug for the Philadelphia Department of Public Health — they track Lyme disease every year (among a million other things) — and we see a LOT of it in areas you might not expect.
Below is the 2016 info-graphic for number of cases of Lyme by Zip Code (3).
Vannier et al. Human Babesiosis. NEJM 2012; 366:2397-406.
Moritz ED et al. Screening for Babesia microti in the U.S. Blood Supply. NEJM 2016; 375:2236-45.
Thanks to Dr. Francis DeRoos for walking us through a case of a young woman who presented with shock, and was ultimately found to have overdosed on calcium-channel blockers.
First, we talked about the importance of (1) the physical exam and (2) the EKG in diagnosing and risk stratifying patients with toxic ingestions. Assessing the skin, pupils, and sweat/lack thereof can give you valuable clues. See the toxidromes post from a few months ago for more info.
Here’s a cute chart that illustrates that:
We also talked about various causes of drug-induced bradycardia:
Lithium tends to cause bradycardia most commonly in patients with underlying cardiac disease. Amiodarone has particularly been known to cause bradycardia in concert with certain of the new HCV medications (sofosbuvir or daclatasvir), including slow VT!
CCB toxicity can cause a variety of ECG changes, including sinus bradycardia and varying degrees of AV blockade. Remember to look at the rhythm strip carefully to make sure you’re not missing complete heart block!
Treatment options for CCB toxicity
Calcium: may improve inotropy and blood pressure. You can give either calcium gluconate (short acting, can give peripherally but lower Ca content) or calcium chloride (3x the Ca content of Ca gluconate, must give centrally given risk of tissue damage w/ extravasation).
Pacing: unlikely to be of much benefit even in hemodynamically significant bradycardia, given that the CCB is still bathing cardiomyoctes with its negative chronotropic effect.
Vasopressors: something (like norepinephrine) with inotropic and vasoconstrictive effects is best, but there’s no trial proving the superiority of one vs another. Large doses may be needed.
High-dose insulin/euglycemic therapy: CCBs block the calcium-dependent release of insulin from pancreatic beta cells, while at the same time increasing glycogenolysis. Insulin is also postulated to have a positive inotropic effect, especially in these patients in whom CCBs are exerting a negative inotropic effect. Massive doses of insulin (to the tune of 0.5-1U/kg/hour) may be needed given (along with dextrose) to maintain euglycemia.
Lipid formulations: intravenous lipid rescue (initially used for bupivicaine toxicity) can be used as a ‘lipid sink’ to bind up unbound CCB. This is not without risks, as it can cause lipemic serum and higher rates of pancreatitis!
ECMO/CPB: with refractory shock, there is also a role for putting patients on ECMO while using adjunctive therapies (above) to support them
Lastly, the paper of the day– which suggests that earlier Lasix administration in patients with decompensated heart failure may have a mortality benefit! See their central illustration, which suggests that there is a critical period (<60 min) where early diuretic administration might be particularly beneficial:
Many thanks to Dr. Steve Messe for walking us through some amazing advances in stroke care- namely intra-arterial thrombectomy.
The NIH stroke scale (<5 mild, 5-15 moderate, >15 severe) is used to assess stroke severity, and has great inter-rater reliability. It’s less sensitive for brainstem and cerebellar infarcts and those in the primary hand motor cortex (since it only assesses proximal arm strength). It’s a great predictor of short and long-term outcome.
Mechanical intra-arterial (IA) thrombectomy has been shown in multiple trials (MR CLEAN, ESCAPE, REVASCAT) to be safe and effective, with NNTs ranging from 3-7 (!) to prevent bad neurologic outcomes
According to guidelines, IA thrombectomy technically should be used within 6h of proximal large artery occlusion in patients with an NIHSS >6. That being said…
…unpublished data from the DAWN study suggests that IA thrombectomy up to 24 hours after occlusion had significantly better neurological outcomes- a 73% relative risk reduction in disability in those that received thrombectomy!
A brief note on tPA: the old teaching used to be that older patients (>80) didn’t benefit from tPA, but recent analyses suggest that older patients may actually benefit even more than younger patients. Also remember that tPA can now be used up to 4.5 hours after symptom onset (or last known normal)
Remember that as with anything, tPA use is a risk-benefit decision; even if someone has a low NIHSS, they may still benefit from tPA if they would otherwise be disabled (ex: distal arm/hand immobility in a laborer, artist, etc)
Lastly- the paper of the day. It suggests that combining Vitamin C and thiamine with hydrocortisone in septic shock may come with a mortality benefit, but this is clearly not a randomized trial and thus more experience is probably needed. See this excellent blog post on PulmCrit for a more detailed analysis.
Marik, P. et al. 2017. Hydrocortisone, Vitamin C, and Thiamine for the Treatment of Severe Sepsis and Septic Shock A Retrospective Before-After Study. Chest. PMID 27940189