I have decided to post interesting true cases that I come across in the hospital every now and then for discussion. Other people should feel free to post interesting cases as well.

Case Number 1:
Pulmonary Consult Service

CC: new onset shortness of breath/hypoxia

HPI: 61 yo WF with PMHx significant for multiple myeloma s/p BMT in 5/03 admitted to the BMT team 2 days ago with new onset SOB, and b/l lower lobe pleural effusions, R>L seen on CXR and and chest CT. Pt has been immunosupressed since her BMT with multiple medications, and she has been through several rounds of chemotherapy, but it is unclear which chemotherapeutic agents she has tried in the past. Her only chemotherapeutic agent now is Velcade, last dose 5 days ago, which she has been tolerating well. ID has already been consulted, and wrote in their note that they "strongly recc that patient receive a bronchoscopy or thoracentesis from pulmonary" because they were concerned about multiple infectious etiologies since she is immunosuppressed. Pt has also been noted to be confused since her admission and is a poor historian, despite being A+OX3. Her pulse ox was noted to be ~68% on room air, 95% on 5L O2 by mask. She complains of DOE after only a few steps. Otherwise, pt in her usual state of health.

PMHx: MM s/p allogenic BMT, PJP (PCP) pneumonia in the past

Meds: Multiple immunosuppresants, Velcade as out patient. lasix, gatifloxacin, imipenim, and bactrim were all added on as in-pt meds

FHx: non-contributory

SHx: denies any tob/EtOH/illicit drug use

ROS: no f/c, no n/v/d, no dysuria, she does report that she previously experienced b/l LE edema up until 1 month ago that resolved by itself and subsequent neuropathy from that edema. She states that the etiology of the b/l edema was never determined, possibly chemotherapy related.

PE:
Vitals: P: 89, BP: 134/80, R: 22, T: 98.5, POx: 96% on 5L O2
Gen: Pt resting comfortably in upright bed
CVS: RRR, no m/r/g
Chest: b/l crackles heard in lower lung fields, R>L
Ext: no c/c/e
Neuro: A+OX3

Labs: Hgb: 8, Hct: 28, Plt: 64 (s/p multiple PRBC and platelet transfusions), WBC: 3, chem 7 and LFT's normal

CXR and Chest CT: B/L lower lung pleural effusions, smaller pocket in the L then right, should be tappable under fluro

So the heme-onc fellow and her attending were strongly pushing for us to tap this patient with a thoracentesis under fluro. ID wanted us to do a bronchoscopy to determine the infectious etiology.

Question: What is your next step? Do you want to know anything else before you do a procedure? Which, if any of the two procedures would you do and why? What's your differential?

Answers to be revealed later :)

Interesting case, not much personal exposure to BMT before but my best crack at it would be as follows.

First I would wonder about the patient's cardiac status. No mention of any coronary or CHF history, could it be new onset? Chemo-induced (something like doxyrubicin) heart failure? I'd go back and check for neck veins and listen for extra heart sounds. Would also get a quick EKG. May need cards consult and echo.

Second, before you tap, this dude(tte)'s platelet is 64! Would be very reluctant to tap, especially given the already tenuous respiratory status, the risk of dropping a lung is bad. I'd get bleeding time, PTT and INR and repeat plt. Would repeat CXR and will only tap if effusion is getting worse or patient's respiratory status continues to decline.

From infectious standpoint, no fever or white count but immunosuppression can impair systemic inflammatory response. Given PCP history, would suspect infectious. Needs respiratory isolation, AFB sputum x 3, bld cx, fungal culture, etc and probably will need bronch. I would go back to look at the most recent CT scan and look for "tree and bud" pattern. Will need to continue broad empiric coverage.

From pulmonary standpoint, many possible causes of SOB is possible, many listed above. No history of COPD. Some chemo can also give pulmonary consolidation and respiratory failure such as bleo and methotrexate. Although unlikely, the history of malignancy and new onset dyspnea always make me wonder about PE, but not really a good idea to start anticoagulation at this point, but SCD's is probably a good idea, so is lower extremity dopplers.

Heme-wise, would be very careful and transfusion threshold would be low. Anemia of marrow suppression +/- chronic disease would easily cause SOB --> increasing cardiac output as compensatory -->overworked heart -->heart failure ----> transudative effusion ---> worsen SOB. May need anemia work-up and EPO in the long term.

Would also check a calcium level.

Very good case, superman..er ckent, and great ideas by Renovar.

I assume the CT chest was not a PE protocol... I would chase down a PE as well as infectious. History of LE edema. The amount of effusion is most likely not sufficient to be the etiology of a 68% pulse oximetry reading without infection or PE.

Thrombocytopenia is not an absolute contraindication to anticoagulation. Is the patient actively bleeding? No note of a rectal.

I'd want a rectal exam. The creatinine was WNL; rehydrate, get a good helical CT. However, I agree with the infectious workup as well, in addition to isolation.

If the CT is positive for PE, I would anticoagulate and watch platelets and coags closely. If pt is heme positive, would consider inferior vena caval filter in lieu of above.

Tap most likely lower yield than bronch. However, I would follow with daily CXR to document stable effusion. A small effusion would most likely, if drained, be a less-than-therapeutic tap. And you'd get bugs in the bronch if planning on doing both anyway. Question: what would be the role of tapping this patient; ie why do so if not for therapeutic benefit? Is there a diagnostic advantiage?

Thanks for participating in my case conference guys. You both had some good thoughts about this case.

I chose to present this case because I thought that this was a classic example of "when all you have is a hammer, everything starts to look like a nail". The ID fellow and attending were both certain that an infectious process was the cause of the pt's symptoms. ID was sure to the point of having the patient on all of those antibiotics, and writing in their note that the BMT team should "strongly push" pulmonary to do a bronchoscopy. Heme onc first just wanted us to tap it so they could determine if the fluid was an exudate or transudate, later, they were pushing for the bronch too. Being a lowly medical student, I will admit that that is exactly what I thought that we were going to do. It is a fairly standard work up for patients with pulmonary infiltrates who are immunocompromised to receive a bronchoscopy in order to see if we are able to determine what infectious agent is causing the patient's symptoms. However, there are a couple of things that suggest a non-infectious etiology.

First was the distribution of the pleural fluid. It would be unusual for patients, even immunocompromised patients, to have what essentially was pleural fluid in that particular distribution (b/l, on both lower lobes). Most of the times, when patients with infections get pleural fluid, it's unilateral. R>L pleural effusion is also a classic distribution for heart failure. Also, the patient was afebrile throughout her course. This probably is not that unusual for an immunocompromised patient (I'm no BMT pt expert either), but it does help add to the evidence against infection.

I also left something out on physical exam, not on purpose, but because I did not initially pick it up in my physical exam. The patient really was a poor historian, she couldn't recall any other symptoms besides shortness of breath. She actually denied having sx of orthopnea, nocturia, pnd, or any heart failure sx. When my attending got there though, after hearing my hx, the first thing that he did was lower the bed. Sure enough, the patient started feeling more short of breath. Also, although crackles can be heard with infectious processes, b/l crackles, again, could clearly described as "fluid" outside of lungs. Remember that our patient only had a white count of 3. Also remember that the pulmonary edema that you can sometime see with infections is actually caused by white cells infiltrating and secreting cytokines, causing exudate. The fact that she did have such a low white cell count, and such rapid changes seen on chest x-ray (seen immediately after symptoms, normal one a few weeks ago) would suggest a non-infectious cause as patients with low white counts (particularly neutropenic patients) radiographs are usually slow to change. That would all suggest that the etiology of her pulmonary edema, found on physical exam and seen on the scan, was non-infectious in origin.

Her history of bilateral lower extremity swelling with normal protein levels might also point you in the direction of a cardiogenic origin.

So does that mean that we would refuse to bronch or tap the patient because we don't think that she has an infection? Certainly not, the patient is immunocompromised, until we determine the etiology of her symptoms, we dare not rule out infection because if it is infectious, that will kill her. So we ordered 2 test. An echo (naturally) and BNP levels.

BNP: 4,950 :eek:
Previous echo before BMT: EF: 50%
New echo: EF: 50%

So the patient had new onset CHF. We recc'ed a cardiology consult, who started the patient on digoxin and more lasix to further diurese the patient. I don't recall seeing any other meds started, I think because the patient ended up being a hospice patient as her multiple myeloma was recurring (Velcade is used as a last ditch chemo agent). Turns out that the cardio consult was able to find the usage of doxorubicin in her medication history. Not sure if that's what caused the CHF though, because the only paper that I was able to find on doxorubicin and BNP levels only showed elevations of BNP's in the 10's to 100's. Other potential causes of an elevated BNP include lung cancer, hypoxia, COPD, ESRD, amyloidosis (associated with multiple sclerosis). However, a medline search of all of these causes only showed elevation of BNP levels to the several hundreds at most. When BNP levels rise above 1000, the test has so far shown to be very, very specific (NEJM says close to 100% in recent article) for CHF. A cardiologist we talked with said that was the first time he had encountered levels that high, but there is going to be a paper published soon that talks about finding BNP levels in the 5000 range and how it is associated with a 60% increase mortality rate in 6 months or so.

Anyways, hope that you guys enjoyed the case!

I would also like to comment on some of your guys thoughts as well. Realize that I'm only an MS4, so your thoughts may be more correct then my thoughts, but I will just add mine anyways.

Cardio w/u: Right on, good job.

Medications as a possible etiology is a great thought. We asked the fellow if she thought that was possible, but she said that there were no pulmonary toxic medications that the patient was on that she could remember. She couldn't recall all of the patient's meds though.

Some good thoughts about the tap too. One of the reasons that heme onc wanted us to do the tap was because they believed that it would be therapeutic, ie that the fluid was making the patient hypoxic. However, the fluid was such a small amount (ie the need for fluro), that it couldnt' possibly be causing the patient to be as symptomatic or as hypoxic as she was becoming. Sorry I couldn't post the patient's actual films, they are on computer here but they have the patient's name on it so I wouldn't want to violate patient confidentiality. Also, I didn't want to post a random CHF film up and pretend that it was her as that would be too obvious, her films were not obvious about CHF at all (heart normal size).

PE is a good thought given her malignancy status and likely bedridden status as well. However, that would be an unusual distribution for PE (bilateral lower lung lobes). The CT that was ordered might have been PE protocol, I can't recall. Checking for DVT's would be smart if the CT was negative though if the edema was in a more PE distrubution (unilateral and small, usually if bilateral should pick up on CT). Also, because the patient was noted to be pancytopenic and thrombocytopenic for a long time, the probability of her throwing a clot to her lungs was lower on the differential.

Interesting that you guys wanted to discuss the patient's anemia. My thought was that the patient was pancytopenic, so I didn't think very much of it to tell the truth, I assumed that it was part of her BMT and immunosuppressive drugs. Anemia is another potential cause of SOB though. Usually, I believe that patients with anemia do not become hypoxic though (expecially on pulse oximetry). I actually hadn't even thought of the chronic anemia as the cause of the patient's CHF renovar, that's a good thought too. I would have expected her heart to be enlarged if that were the case though, and by ECG and echo, I believe that her heart was normal size.

Regarding your question pimple popper: Heme onc mainly wanted the tap becaue they thought that it would be therapeutic (ie they thought that it was causing the hypoxia). A tap could be diagnostic in figuring out if it were an exudate or transudate as well (although a bronch with a bronchoalveolar lavage should tell you the same information with a cell differential and cell count). I do believe that a bronch would be more diagnostic then a tap though, in terms of figuring out infectious causes, particularly in an immunosuppressed patient on multiple antibiotic/fungal drugs. There are some cases in which a tap might be more diagnostic for malignancy. Not sure about that one though.

Rectal exam: Sure, we could suggest it. Part of the great part of being a consult is that you can always suggest stuff, but you don't necessarily have to do it if it doesn't involve your specialty.

The heme onc fellow on this particular team was not very good. Besides misreading the small amount of fluid as the cause of the patients symptoms, she was still insisting that we do a bronch and therapeutic/diagnostic tap to make sure that it was CHF :rolleyes: . We actually had to get our attending to talk to theirs before she left us alone. And ID should also be faulted for just not considering anything other then infection. That's why the medical subspecialties all have to do 3 years of general IM first. Anyways, like I said, it all was ultimately in vain as the patient ended up going to hospice for multiple myeloma recurrence and now her heart failure.

Thanks for participating in my case guys!

Originally posted by ckent
PE is a good thought given her malignancy status and likely bedridden status as well. However, that would be an unusual distribution for PE (bilateral lower lung lobes). The CT that was ordered might have been PE protocol, I can't recall. Checking for DVT's would be smart if the CT was negative though if the edema was in a more PE distrubution (unilateral and small, usually if bilateral should pick up on CT). Also, because the patient was noted to be pancytopenic and thrombocytopenic for a long time, the probability of her throwing a clot to her lungs was lower on the differential.

Regarding your question pimple popper: Heme onc mainly wanted the tap becaue they thought that it would be therapeutic (ie they thought that it was causing the hypoxia). A tap could be diagnostic in figuring out if it were an exudate or transudate as well (although a bronch with a bronchoalveolar lavage should tell you the same information with a cell differential and cell count). I do believe that a bronch would be more diagnostic then a tap though, in terms of figuring out infectious causes, particularly in an immunosuppressed patient on multiple antibiotic/fungal drugs. There are some cases in which a tap might be more diagnostic for malignancy. Not sure about that one though.

Rectal exam: Sure, we could suggest it. Part of the great part of being a consult is that you can always suggest stuff, but you don't necessarily have to do it if it doesn't involve your specialty.


Thanks for participating in my case guys!

Good case!

thoughts:
-- thrombocytopenia does NOT decrease the chance of thrombosis in malignancy. Malignancy can do many things to clotting factors as well as platelets. Platelets may be increased in number, but also may be activated. Coagulation factors as well as various tissue factors, depending on the malignancy, can play a prothrombotic role. The bilateral effusion would not sway me in any direction regarding ruling in/out PE.

-- Still unsure on diagnostic benefits of tap vs bronch.

-- Good call on CHF. Forces us to keep in mind multiple disease processes can be occurring simultaneously. CHF can be at play in addition to infx, in addition to PE, in addition to x.

Originally posted by PimplePopperMD
Good case!

thoughts:
-- thrombocytopenia does NOT decrease the chance of thrombosis in malignancy. Malignancy can do many things to clotting factors as well as platelets. Platelets may be increased in number, but also may be activated. Coagulation factors as well as various tissue factors, depending on the malignancy, can play a prothrombotic role. The bilateral effusion would not sway me in any direction regarding ruling in/out PE.

-- Still unsure on diagnostic benefits of tap vs bronch.

-- Good call on CHF. Forces us to keep in mind multiple disease processes can be occurring simultaneously. CHF can be at play in addition to infx, in addition to PE, in addition to x.

Tap in itself is not a good method of making an infectious diagnosis. It is a method of symptomatically relieving someone with pleural effusion >1cm, symptomatic effusions, or parapneumonic loculations. Obviously, you can only tap someone when they have an effusion, and you can ONLY get tests on the effusion. When bugs (or malignant cells, etc) are found in the effusion, great. When it is not, you can't say one way or another. So, say if you suspect someone with a pleural effusion to have TB, and you tap and it is negative for AFB, you can't rule it out. Obviously, the quality of effusion (transudative or exudative) may be helpful in pinpointing the underlying diagnosis. Just remember that transudate + exudate = exudate, so if you see an exudative effusion, you can't completely rule out stuff like CHF, cirrhosis, etc.

Bronch on the other hand, is a primary diagnostic tool. You can look, lavage, biopsy, etc with it, and you can rule stuff out if it is negative on bronch. This is the test you want to get if you want to make/rule out a diagnosis. It obviously does not give any information about the effusion.

Originally posted by Renovar

Bronch on the other hand, is a primary diagnostic tool. You can look, lavage, biopsy, etc with it, and you can rule stuff out if it is negative on bronch. This is the test you want to get if you want to make/rule out a diagnosis. It obviously does not give any information about the effusion.

Actually, bronchoalveolar lavage only gives you an organism ~60% of the time for immunocompromised patients. Don't know what the probability of finding an organism in immunocompetent patients is, as we generally don't do bronch's in them. I would imagine that if you had something to biopsy on bronch, it would be more sensitive then a BAL too. Generally, you can't take someone off all of their antibiotics/antifungals if you don't find anything on bronch. It's only helpful in that you can take them off certain abx/fungals if you find something on the bronch, and you can get sensitivites if you do get an organism. Open lung biopsy is supposedly the most sensitive test for getting organisms, but it's not considered a first line test because it's surgery. Anyways, with my patient, ID was satisfied with our clinical assessment without a bronch, so they d/ced all of the abx's and antifungals except for the prophylactic ones. With her improvement in dyspnea, I think that was a safe call. They could have restarted her abx/fungals if her dypsnea did not improve with her new heart medicines. And with her BNP so high, I think that you could argue that HF could explain all of her sx, so there was no need to add another disease to her dx.

With respect to a bilateral PE, my thought was that if she was throwing enough PE's to cause 2 different pleural effusions, the probability that you would see it on high res chest CT would be high enough that you could rule it out with a CT. At my school, spiral CT is considered sensitive enough to r/out most PE's, especially ones large enough to cause symptoms. I'm not sure if they actually have studies that prove that "belief" though. With her high BNP, I think that the thought was that all of her sx were probably caused by her HF. I agree that PE would have been an important one to r/o in the beginning though. I was also thinking that PE itself could be a cause of thrombocytopenia, so having thrombocytopenia really probably isn't a good way to exclude having a PE for that reason and the reasons that you mentioned.

Anyways, good thoughts again guys.

Originally posted by ckent
BNP: 4,950 :eek:

BNP=brain natriuretic peptide? I am just a second-year, but in pathology the other day my professor mentioned BNP as a marker for ventricular dilation due to CHF. Is this a pretty common test when doing a CHF workup?

Originally posted by Idiopathic
BNP=brain natriuretic peptide? I am just a second-year, but in pathology the other day my professor mentioned BNP as a marker for ventricular dilation due to CHF. Is this a pretty common test when doing a CHF workup?

BNP=Brain naturiuretic peptide. I think that it's only called "brain" because it was first found in the brain. It's getting to be a more common test as BNP has important implications in prognastic factors as well as diagnosing CHF. Generally, the higher your BNP, the more likely you will die soon. Some residents believe that you should order a BNP level for everyone who comes in with a CHF exacerbation. It's particularly useful in cases like the one which I presented where you aren't sure about the etiology of whatever is causing their symptoms.

Originally posted by ckent
With respect to a bilateral PE, my thought was that if she was throwing enough PE's to cause 2 different pleural effusions, the probability that you would see it on high res chest CT would be high enough that you could rule it out with a CT. At my school, spiral CT is considered sensitive enough to r/out most PE's, especially ones large enough to cause symptoms. I'm not sure if they actually have studies that prove that "belief" though.

I agree that BAL cannot rule out infx, and i remember hearing the 60% statistic as well, though i never read it.

the pe question: a spiral ct is a great test, but it does not rule out pe. not anywhere. it's unfortunate. the subsegmental (3rd generation) emboli will not usually be visualized, as well as smaller subsegmental ones. Why do we care about these? they are "warning shots" so to speak; they can be the harbinger of the big saddle embolus.

Originally posted by PimplePopperMD
I agree that BAL cannot rule out infx, and i remember hearing the 60% statistic as well, though i never read it.

the pe question: a spiral ct is a great test, but it does not rule out pe. not anywhere. it's unfortunate. the subsegmental (3rd generation) emboli will not usually be visualized, as well as smaller subsegmental ones. Why do we care about these? they are "warning shots" so to speak; they can be the harbinger of the big saddle embolus.

I think I may have mis-spoken. It's true that lavage can't r/o infection or malignancy (although a positive test will rule something in), but a bronchoscopy with tissue/granuloma biopsy certainly can.

Originally posted by PimplePopperMD
I agree that BAL cannot rule out infx, and i remember hearing the 60% statistic as well, though i never read it.

the pe question: a spiral ct is a great test, but it does not rule out pe. not anywhere. it's unfortunate. the subsegmental (3rd generation) emboli will not usually be visualized, as well as smaller subsegmental ones. Why do we care about these? they are "warning shots" so to speak; they can be the harbinger of the big saddle embolus.

Those are good points Pimple popper, and the current guidlines do agree with you, however, there is still some controversy regarding this. Besides the controversy over the sensitivity of the spiral CT (found to be 53-60% compared with angiograph in my text), this number is always changing, with increasing resolution of CT's and more experience in reading them, many attendings at my school would argue that the senstivity of CT's is actually much higher now. And with regards to putting people who the spiral CT "misses" on anticoagulation (small, peripheral emboli), I believe that those studies are still pending as well if the outcomes are in fact improved when those patients are anticoagulated. That being said, I don't think that anyone would disagree with a more thorough work up of a patient's dypsnea/tachycardia/chest pain if CT was negative, yet another etiology could not be determined. I had one patient that a medical team was pushing for an angiography on while I was on pulmonary service, but my attending was saying that even with angiography, those can be difficult to interpret with unexperienced eyes since the pulmonary vasculature is so complicated, and most pulmonary angiographers do not get very much practice these days. This team actually ordered D-dimers and found them to be elevated, therefore decided to empirically anticoagulate even though CT and DVT's were negative. They changed their mind a couple of days later though and took the patient off anticoagulation, but the patient was discharged before we could find out why or what was going on with the patient. Crackles were only heard in 40-58% of patients acocrding to PIOPED and UPET (PE studies), but I suspect that almost all o fthose would have been unilateral crackles. Anyways, here are some clinical guidelines, but I don't think that they (like most guidelines) are completely up to date:

http://www.guideline.gov/summary/summary.aspx?doc_id=2381
http://www.guideline.gov/summary/summary.aspx?doc_id=2592