November 8th, 2011

Wrestling with Uncertainty in Clinical Practice

About a week ago I was asked to consult on a patient I’ll call Betty. This delightful 92-year-old woman, who lived alone, was admitted during the night with pain in the upper chest and shoulders. She had been feeling this discomfort off and on for 2 days, and when it woke her from sleep, she came to the ER. She also reported a history of hypertension, hyperlipidemia, and mild diabetes treated with oral medication. She was pain-free when I met her, and her exam was unremarkable. Both her troponin and her CPK levels were borderline elevated, and her EKG showed extensive T-wave inversion in the precordial leads.

So what was I to do with these worrisome clinical findings? Evidence-based medicine provides me with very little, well, “evidence” to apply to this patient. At 92, she was much older than the mean age of patients in trials such as CURE (64 years), FRISC (69 years), and the original trial of heparin in unstable angina (58 years). We know that treatments for acute coronary syndrome are all double-edged swords, with both benefits and risks. What about the dictum “first do no harm?”

I must admit that I didn’t pay much attention to the kind of medical uncertainty that Betty’s case illustrates until I made a transition from academic medicine to private practice years ago. In academia, we focused a lot on what was known. Betty’s case would have presented a bundle of teaching opportunities. If Betty had been discussed on our rounds, we would have made a group decision and moved on to the next patient. But my busy new practice had no teaching rounds, no team. In practice, such decisions made me feel utterly alone, and the uncertainty of medicine hit me like a ton of bricks.

I am pretty sure that no clinical trials apply to Betty. But am I even certain of that? This is the uncertainty that drives us to specialize in narrow fields, hoping to develop some sense of security in our decisions.

I discussed the options with Betty. She was firm that she wanted to pursue medications and avoid any cardiac procedures. Given the extensive EKG changes, I was a little uneasy about her decision, but I was pleased that she resolved my own decisional conflict. Her pain resolved, too, and she was discharged back to her home on a variety of medications, including a beta-blocker, nitrates, a statin, and dual antiplatelet therapy.

Betty returned to the ER yesterday, this time complaining of mild shortness of breath that occurred in the middle of previous night. The ER physician noted that she seemed quite comfortable without any particular treatment. Her exam was normal, labs were unremarkable, chest X-ray was clear, and EKG was unchanged. An echocardiogram showed an ejection fraction of 70% with LV hypertrophy, aortic sclerosis (no stenosis), and moderate mitral annular calcification — all expected findings for a 92-year-old woman.

On her first visit Betty had presented a therapeutic dilemma; on her second the uncertainty I experienced was of a different sort. What was troubling her? Was she simply anxious about being at home alone with a new cardiac diagnosis? What was the true origin of her symptoms?

Often a patient’s true condition is obscure. The human body is infinitely complex, and patients are infinitely variable. We use tests that are imprecise because of resolution constraints and artifacts. Many of those tests are indirect, creating problems with reproducibility, sensitivity, and specificity. Their predictive value is affected by how they are used. All of these factors contribute to diagnostic uncertainty.

Predicting an outcome for an individual patient is even more imprecise. A second order of uncertainty called ambiguity arises. It’s like an error bar around a point estimate. A patient may ask you, “Doc, how long do I have?” We can give a number, but the range of uncertainty around that number can make your answer almost meaningless.

Uncertainty is why we use clinical reasoning, intuition, induction, and inference. Probability is uncertainty quantified, and most probability calculations in clinical medicine are subjective and intuitive. It’s imperative that we apply basic scientific principles, evidence from clinical trials, and hard clinical data as we make decisions, but doing that for an individual patient requires judgment.

Sometimes we wear a mask of certainty, often an arrogant one: “Pay no attention to the man behind the curtain. I am the all powerful Wizard of Oz!” We all know a colleague who is “sometimes wrong but always certain.”

A better approach is to recognize uncertainty and to become familiar with the ways that human decision makers adapt to it, as I’ve discussed in previous posts. In doing so, we replace arrogance with confidence and develop a greater sense of comfort as we struggle to provide the best care for our patients.

Is the optimal treatment for Betty uncertain?

When you are uncertain about something in your care of a patient, do you discuss it with the patient?


9 Responses to “Wrestling with Uncertainty in Clinical Practice”

  1. Dan Hackam, MD PhD says:

    John, any possibility this patient could have a PE? Granted it would be an atypical presentation given her EKG findings and risk factors for CAD (as noted in your synopsis), but PE is the great masquerador, and chest pain syndromes in elderly females are often so difficult to sort out. Without some sort of definitive (non-invasive) imaging technique, for CAD vs VTE, it is not possible to sort this one out beyond the play of probabilities (ie. more likely to be ACS, less likely to PE, etc).

  2. John E Brush, MD says:

    Good point, but I don’t think that PE is the explanation for her original presentation. To keep the blog post brief, I had to leave out some details. The CPK MB and troponin were both slightly but clearly abnormal with a typical rise and fall, consistent with MI and her EKG was strikingly abnormal. Could the second presentation be a PE? Now you have made me feel insecure. I can’t be absolutely certain, but I don’t think so. She looked too comfortable and her oxygen saturations were 100%. She was briefly immobilized the previous week, but she was on full dose heparin at the time. The ER physician, the patient, and I all agreed that it was anxiety about being home alone and the realization that she would soon have to move out of her own home. But PE, like aortic dissection in the previous post, is a diagnosis that causes nagging uncertainty. They are like the Black Swans in Nassim Taleb’s book – catastrophic events that are very hard, if not impossible, to predict. I haven’t heard from her for about a week now and I am waiting to see her soon for her first outpatient follow up visit.

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  3. Antonious Attallah, MD says:

    Hey John,

    Great post. My best approach that I have learned from mentors is to weigh the risk and benefits clearly and be honest with myself and my patient and present the management options as honestly as I can. Eventually, the patient and I (family) come to a mutual decision and are happy with the course of treatment/outcomes whatever it may be. In your case since she is coming back again, I would try to assess her ischemic burden by performing a pharmacologic MPI. That will introduce some objectivity to what you are dealing with here…a low ischemic burden would reassure you and the patient that medical therapy is the way to go…while a moderate to high ischemic burden may lead into having to revisit invasive options with this patient…to me the best approach with these patient is to gauge how functional they really are…a 92 y/o with semiactive lifestyle who performs her ADLs and is somewhat independent is different from an 80 y/o debilitated nursing home resident who depends on others for everything…I take the same approach in my patients at a high bleeding risk or with advanced CKD to objectively assess the risk/benefit ratio of pursuing intervention. If the scan came back grossly abnormal (> 20% ischemic burden) with high risk features, I would sit with her and honestly explain that there are no trials that have looked at her population with this typical situation, but that studying her might be an option if she elects to…again, all of this is guided by your impression of her ECOG status and how functional she is.

    Hope this helps…

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  4. John E Brush, MD says:

    Great suggestions. I like your advice to have an honest discussion to facilitate shared decision making. But what if the patient says “what ever you say, doc.” Then you are right back in the same spot. The real issue that I am wrestling with in this blog post is the uncertainty of clinical practice. What do we do when the patient, because of advanced age, or any number of other factors, is a type of patient that has not been included in clinical trials? What to do when there are no clear rules to follow? How do we know how to proceed? Lacking a relevant guideline or clinical trial, we are left to our intuition. In my view, this is why it is so important to understand intuition – how to set it up to succeed and how to avoid its fallacies.

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  5. Edgar Abovich, MD says:

    I suspect you considered mild CHF. Nocturnal SOB post MI is usually due to CHF. CXR may still be fairly normal. Did she wake up with it? What was BNP?

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    • John E Brush, MD says:

      Yes, CHF was considered when she presented the second time. An echo was ordered, which showed normal systolic function. You could propose diastolic dysfunction, but probably every 92 year old has some degree of diastolic dysfunction and that wouldn’t explain her acute symptoms. She had no rales and her CXR was normal. Her symptoms resolved without any specific treatment. The ER physician reported that she seemed to feel better that night just with a little reassurance.
      You asked about her BNP. Our hospital uses an assay for NT-proBNP. I’m not sure that this test helps us very much because age affects NT-proBNP levels, irrespective of the diagnosis of heart failure. According to Kim and Januzzzi (Circulation 2011;123:2015-19), the optimal cutoff points for NT-proBNP are <450 for age <50, <900 for age 50-75, and <1800 for age greater than 75. What is the cut-off point for a patient who is 92 years old? I am concerned that we are dealing with spectrum bias here, where the test may not apply to my patient because the measures of test performance were defined in a population that didn’t include enough patients like my patient.
      So her NT-proBNP level was 1999. For a 92 year old woman with recent ACS, that test result doesn’t seem to help me very much. It doesn’t rule out CHF, but doesn’t rule it in either. I’m still left wrestling with clinical uncertainty.

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  6. Dan Hackam, MD PhD says:

    Great case (as usual from Dr Brush). Although it’s impossible to know what to do unless actually standing in the attending’s shoes in front of this patient, I agree with the above comment that the chronological age of 92 does not necessarily imply a physiological age of 92. If quality of life is good, complication rates are deemed acceptable, and the gain might be a reduction in angina frequency or severity, I might refer her for coronary angiography. If there is no chance she is going to be offered a cardiac cath, I’m not sure a pharmacological MPI is going to offer any useful information to me – I would simply intensify her medical management instead.

    In truth guidelines and clinical trials are not going to help very much with this situation. It comes down to the oft stated “values, preferences and goals of the patient”. Easy to say this – but if she replies “what ever you say, doc”, I would try to put myself in the patient’s shoes. What does she stand to gain from a heart cath versus what does she stand to lose? Definitely one must consider that the risk of an MI, bleed or stroke in this situation is considerably higher than a 50 year old male with angina or ACS presenting for the same indication. Anyway, the patient has made it very easy. “She was firm that she wanted to pursue medications and avoid any cardiac procedures.” At least, that was her opinion at the first ER presentation. I don’t know if it has changed with her second.

    Last but not least, I often find that very elderly women presenting with ACS often have an aggravating or complicating factor such as a urinary tract infection, cognitive dysfunction or even a fall or series of falls, anxiety or depression, etc. Demand ischemia from infection seems to be so very common in this age group, and ACS can respresent a manifestation of sepsis or other systemic infection (pneumonia, UTI, skin, etc). Something little, even trivial, always tips these little old ladies over, and the ACS is quite simply the straw that breaks the camel’s back. Likely this has already been worked up and ruled out, but the point is worth making.

  7. Lisa Martin, AB, MD says:

    I am honest with patients about a dilemma, but if I really would like to talk to a colleague or do some research, I am not afraid to tell the patient that there situation is not straightforward and I would like to give it some thought, and do some research, discuss with colleagues, explore the options. I have not had a patient unhappy about my decision to want to think about them carefully. I just then follow up and take the action I said I would, and then follow up with the patient.

  8. Edgar Abovich, MD says:

    I agree there is always some uncertainty especially with 92 year olds. I also agree with your frustration with the pro-BNP, doesn’t help as much (I suspect it’s probably less expensive test). I think however that history on presentation should give some clues. If she woke up SOB I doubt it’s anxiety. Uncertainty is extremely common, more so in the office setting than in the ER. Detailed history is always helpful but it is not a guarantee. You just make your best shot and…proceed in the usual manner.

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