January 21st, 2013

Must-Read Piece: “Fever of Too Many Origins”

Every so often a commentary gets something just right, and fortunately we have an example in this week’s New England Journal of Medicine.

Entitled “Fever of Unknown Origin or Fever of Too Many Origins?”, it’s the best depiction I’ve read about doing ID consults in the intensive care unit (ICU). The author, Harold Horowitz (who has practiced ID in tertiary care hospitals for 3 decades), contrasts the classic Fever of Unknown Origin (FUO) with the arguably more common Fever of Too Many Origins (FTMO), which is all-too recognizable for those who do hospital-based patient care.

These are patients “who have traumatic brain injury, other neurologic events, or dementia; are mechanically ventilated; have some combination of urethral, central, and peripheral catheters placed; have recently undergone surgery; and are already receiving multiple broad-spectrum antibiotics.”

In other words, they might have originally had diverse medical and surgical problems, but they’ve now entered the narrow portion of the ICU funnel, and are strikingly similar.

There are many quotable passages, but the following is my favorite:

As the keeper of the antibiotics, should I be a conservative or a cowboy? Should the current antibiotics be continued, changed, or stopped? If there are no prescribed antibiotics, should I recommend some? These are interesting questions in the abstract, but there is a real patient suffering, a family with questions, and medical teams awaiting my opinion. There are no evidence-based studies and there is no guidance on which potential source of fever is the single appropriate one to treat. Frequently, the treatment approach is like playing Whac-A-Mole: positive cultures are treated sequentially — pneumonia, then catheter cultures, then urine cultures. When the fever persists, the cycle begins again.

Whac-a-Mole — what a great analogy! I’ve written before about my frustrations with ICU-related Infectious Diseases (here and here), but Horowitz does it better. I found myself nodding with recognition time and time again.

While the tone of the piece is understandably melancholy — these are patients not for ID case conference, but for “family conferences that include plans for palliative care” — I was left with a somewhat more hopeful thought. Namely, that once we recognize the eerie similarity of these ICU ID consults, then perhaps we can evaluate their optimal management in a controlled clinical trial. Something like this:

Inclusion criteria: ICU stay > 1 week; endotracheal intubation; fever > 101.5F; multiple possible sources of fever but no obvious single source (e.g. bacteremia).
Intervention:  Randomization to one of two treatment strategies:  1) Initiate or change to empiric broad-spectrum antibiotcs with cessation after 3 days if cultures are unrevealing and there is no objective clinical improvement; or 2) Standard of care.
Primary endpoint:  All-cause mortality.
Secondary endpoints:  Infection-related mortality, length of ICU stay, antibiotic exposure, adverse effects of antibiotics (including C diff), bacterial resistance, fungal superinfection, cost, etc.
Primary funding source:  The National Institutes of Allergy and Infectious Diseases.

Sure beats Whac-a-Mole.

11 Responses to “Must-Read Piece: “Fever of Too Many Origins””

  1. Kim Lucas says:

    When treating ICU patients durinng residency I called it the “final common pathway”. There was always a bevy of “chronic” patientsin the ICU. Many with ultimately terminal illnesses. More thought and consideration needs to go into who should go/stay in the ICU.

  2. Ringer Lactate says:

    As clinically useful as that study design would be, you know it would never happen.

    And if it did, would you want to be the protocol chair?


    I nominate YOU to be the protocol chair, Dr. Sax!

  3. Rebeca Plank says:

    It was TOO realistic!

  4. Jay Como says:

    Although I am only three years out from my fellowship training, even I could strongly relate to the frustrations voiced in Dr. Horowitz’s article (which I thoroughly enjoyed) and Dr. Sax’s blog (ditto). While I’m sorry to hear such commentary from my vastly more experienced colleagues, it is nice to know that I’m not the only one agonizing over these workup and management decisions in this challenging patient population.
    On a final note, cheers to Dr. Sax’s proposed study!

    • Paul Sax says:

      Thanks for your comment. In my first year as an attending (oh, about a hundred years ago), I was complaining to senior colleague (and brilliant clinician) Jamie Maguire how frequently I just couldn’t figure out the source of the fevers in all these hospitalized patients. His response: “Get used to it!”
      Of course another way of looking at it is Dr. Horowitz’ view — there are “too many” sources!

  5. Todd ellerin says:

    We need a bio marker that can reliably distinguish pyogenic inflammation versus aseptic inflammation. I think we’re on the right track with pro calcitonin but not there yet.

  6. Elizabeth Hudson says:

    Thank you for this wonderful commentary! I will be sending this to all my fellow ID docs.

  7. Sumon Chakrabarti says:

    I was so happy when I read Dr. Horowitz’s commentary because I often leave this ICU fever cases feeling like I don’t know what I’m doing. I’m in my third year of practice, and I must say there haven’t been too many of these cases where there was a “silver bullet” explanation that was treated and the fever went away. In fact, when I DO find something, it’s a rarity.

    One of my mentors in fellowship was one of the best clinicians I’ve ever worked with. For the patients who’d been on broad spectrum antibiotics for a long time, were intermittently still febrile, but stable, he would often stop all the antibiotics at once and watch clinically. Once in a while the fever would go away, but often times it made absolutely no difference to the patient’s status….other than the fact we were being good antibiotic stewards.

    Seriously, it’s a good move–especially for someone in the ICU being watched closely.

  8. Sumon Chakrabarti says:

    ….I’m meaning to say that having patient who remains stable but is now OFF of broad-spectrum antibiotics, is a good thing 🙂

  9. Stu Feinstein says:

    Brilliant, wry essay.i had already posted it as a must read at my hospital. I practice alone and it’s reassuring to hear other md’s similar experiences. It’s not what I signed up for when I went into id in the early eighties but times change. Thanks dr. Horowitz.

  10. Jim Greig says:

    Have the courage of your convictions. If you do not know the cause of the fever stop the antibiotic if doing no good, start only if the patient is deteriorating. “Don’t just do something, stand there”

HIV Information: Author Paul Sax, M.D.

Paul E. Sax, MD

Contributing Editor

NEJM Journal Watch
Infectious Diseases

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