Case presentation brain teaser.

[JayneCobb]

This forum seems a little slow, so let's try something to stimulate some discussion. I'll give a case presentation and get to a point where I come to a point where we discuss the pros and cons of a particular treatment.


Case #1: 90 yo Female, presents with fever, altered mental status.

PMH: recent Clinical dx of herpes encephalitis (bilateral temporal hyperintensities on MRI but family refused LP and no neurosurgeon for tissue dx) treated with 14 days of acyclovier with improvement, last dose 3 days ago. Alzheimer's, HTN, CAD,
PMH: Non-contributory
Allergies: none
social: crazy as a ding bat

Presentation: was brought in via paramedics after found slouched down in her bed by nursing home staff. brought in non-responsive (which is different from her baseline) tachycardic, tachypnic, febrile.

Diagnostic studies:

CXR: mild cardiomegaly, no infiltrates
CMP: BUN 41 Cr 1.7, ALT 275, AST 150 rest WNL
CBC: WBC 21, toxic granulation, 15% bands
UA: +3 ketone, +3 protein, + LE, +Nitrates, Bacteria TNTC, WBC TNTC
BC: pending
Lactate: pending.
ABG: mild resp alk
​

Diagnosis:

1) UTI
2) SIRS
3) end organ damage (elevated Cr/BUN, AST, ALT)
4) severe sepsis 2 to #1 + #2 + #3
5) AMS 2 to #2
6) H/o Alzheimer's
7) recent Herpes encphalitis, last dose of Acyclovir 3 days ago
8) Full code status.
9) usual old person risk factors
​

Plan:

1) ATSO: Dr you
2) IV ABX: empiric: Cipro, Ceftriaxone, and Vanc until C&S is back
3) Prayer

​

Question:

Do you institute Xigris? why or why not?
​

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[waterski232002]

empiric: Cipro, Ceftriaxone, and Vanc until C&S is back

Curious why that antibiotic regimen was given? What is ceftriaxone adding?

Cipro has gram negs, atypicals, and pseudomonas.... Vanc has gram pos... If you wanted a thrid antibiotic, why not go for anaerobic coverage or double coverage of pseudomonas since nursing home pts are at risk. Ceftriaxone doesn't cover either one of these, so it doesn't add anything to the cocktail. I think Cefepime or Ceftaz would have been a better choice as far as cephalosporins go.

Personally... I would go for Vanc, Cipro, Flagyl.... or Vanc, Zosyn. If I really wasn't worried about anything intrabdominal (simple urosepsis) I think Vanc, Cefepime would be fine alone as well. I'm not sure that anaerobic coverage is that important here.

 

[JayneCobb]

Curious why that antibiotic regimen was given? What is ceftriaxone adding?

Cipro has gram negs, atypicals, and pseudomonas.... Vanc has gram pos... If you wanted a thrid antibiotic, why not go for anaerobic coverage or double coverage of pseudomonas since nursing home pts are at risk. Ceftriaxone doesn't cover either one of these, so it doesn't add anything to the cocktail. I think Cefepime or Ceftaz would have been a better choice as far as cephalosporins go.

Personally... I would go for Vanc, Cipro, Flagyl.... or Vanc, Zosyn. If I really wasn't worried about anything intrabdominal (simple urosepsis) I think Vanc, Cefepime would be fine alone as well. I'm not sure that anaerobic coverage is that important here.

Basically it was for double coverage of the important Gram negatives since the biogram shows a 30% Cipro resistance of e. coli in this hospital. Cefepime does not penetrate CSF and I wanted to empirically cover meningitis since she recently had an assault which could putter at a higher risk, even though I believed the AMS was from sepsis. Ceftriaxone will both double cover the gram negatives and give some CSF coverage as well as hit the UTI. and you're right, I had no suspicion of intrabdominal bugs or anaerobes and I debated not starting vanc since I didn't the source is pretty obvious, but the vanc is there just to cover the bases until the C&S comes back.

And I try not to use Zoxyn or others unless I don't have another choice or I really am not sure what but I'm needing to treat, that's just me though.

 

[JayneCobb]

I guess I should come out and ask what I'm trying to stimulate the discussion towards.

Xigris has the contraindications of

active internal bleeding
recent hemorrhagic stroke 3 months
recent intraranial or intraspinal surgery or head trauma
trauma with increaed risk of life-threatening bleeding
presence of an epidural catheter
​

and warnings in

bleeding​

now Herpes Encephalitis has hemorrhagic properties in the temporal lobes.

So, does very recent HE qualify as an absolute or relative contraindication, or would it affect your decision to give Xigris?

 

[Eidolon6]

A good rule of thumb with Xigris, as taught to me by and G Bernard and A Wheeler, coauthors of the PROWESS trial, and its anticoagulant properties is to treat it like a heparin infusion. In other words...if indicated...would you put this patient on a full heparin infusion, targetting a an aPTT ~1.5-2X normal. Thats about equivalent to how "thinning" Xigris is. Also, you need to take note of the patient's platelets (not listed in the teaser) as if <50K, Xigris use would be contraindicated (though it is ironic that those patients with DIC did the *best* of all the organ failures listed in the trial)

With the threat of possible "hemorrhagic" conversion of temporal lobe encephalitis....I would be very wary of using Xigris in this patient with numerous comorbidities.

Primum non nocere is the rule here.

 

[Apollyon]

With the threat of possible "hemorrhagic" conversion of temporal lobe encephalitis....I would be very wary of using Xigris in this patient with numerous comorbidities.

Primum non nocere is the rule here.

I saw Xigris used once - in the Duke PICU, in a BMT kid who looked like the Stay-Puft marshmallow man, he was so edematous. Began bleeding through the ET tube.

90 years old and has Alzheimer's dx, then you say "altered mental", after herpes encephalitis (presumed)? And family refused LP - how in the WORLD would you convince them to go for Xigris?

This is NOT the optimal patient (which is my understatement of the day), and I say - strongly - save the $7K (and the patient).

 

[JayneCobb]

A good rule of thumb with Xigris, as taught to me by and G Bernard and A Wheeler, coauthors of the PROWESS trial, and its anticoagulant properties is to treat it like a heparin infusion. In other words...if indicated...would you put this patient on a full heparin infusion, targetting a an aPTT ~1.5-2X normal. Thats about equivalent to how "thinning" Xigris is. Also, you need to take note of the patient's platelets (not listed in the teaser) as if <50K, Xigris use would be contraindicated (though it is ironic that those patients with DIC did the *best* of all the organ failures listed in the trial)

With the threat of possible "hemorrhagic" conversion of temporal lobe encephalitis....I would be very wary of using Xigris in this patient with numerous comorbidities.

Primum non nocere is the rule here.

Ah, now I'd like to see this in writing if it's out there to add to my library. I spent a large chunk of time on OVID and google trying to find specific info like this and this would definitely reinforce my thinking at the time. I came to the conclusion that while I could start Xigris, it would probably not be the best idea.

Now, I don't suppose anyone knows of any case reports of anti-coagulation and worsening of the hemorrhage caused by H.E.?

90 years old and has Alzheimer's dx, then you say "altered mental", after herpes encephalitis (presumed)? And family refused LP - how in the WORLD would you convince them to go for Xigris?

This is NOT the optimal patient (which is my understatement of the day), and I say - strongly - save the $7K (and the patient).

Agreed, but the only problem with this family is they wanted everything done, but did not want any invasive testing. And after discussing with them that the yield rate of a LP is actually rather low at the time, the family (IMHO) made the right decision by declining the LP as it is really not that diagnostic until 6-14 days afterwards. But the reason why I feel that the H.E. was clinically strong enough to actually dx it as such was because the MRI had almost classic look. I believe that it's called sylvian sign?

 

[Eidolon6]

Finding a lot in writing, aside from case reports of novel patient uses of Xigris may be hard. As with most if not all controlled clinical trials....exclusion criteria eliminate those most interesting patients and leave us begging for answers to new questions. I have the benefit of working with the PROWESS designers and authors and I am privy to some of their observations that did not fit into the word count limited NEJM article.

Your patient would have been excluded from the study given her intracranial pathology.

In the appropriately selected patient (usually those who fit the PROWESS criteria + APACHE >25 (subgroup that did the best)), Xigris is a Surviving Sepsis Campaign Guideline supported adjunctive treatment for sepsis.

I have used and seen it used quite a bit and seen quite a few turn-arounds in those patients who received most of the 96 hr infusion. Of course we has seen a lot of failures as well as even with Xigris, total sepsis mortality is still high. The PROWESS trial only bore out a 6% reduction in sepsis mortality...an improvement but certainly not a stunning one.

 

[JayneCobb]

Finding a lot in writing, aside from case reports of novel patient uses of Xigris may be hard. As with most if not all controlled clinical trials....exclusion criteria eliminate those most interesting patients and leave us begging for answers to new questions.

I figured as much. But I do appreciate your input because this was something that I struggled with for a while before deciding not to administer it to this pt. But a reduction is a reduction and Xigris is the only thing which has been shown to reduce the mortality in any statistical significance, and it was hard not to offer her that additional chance of recovery.

 

[danielmd06]

Excellent case and teaching points.

Could we please hear more?