PRIMUM NON NOCERE.

	"When in doubt, tell the truth." – Mark Twain, Following the Equator   K. Patrick Ober, MD   Affiliation with the Medical School: Professor of Internal Medicine (Endocrinology and Metabolism) Place of birth: Ames, Iowa Where you grew up: Ames, Iowa (until age 2) Conrad, Iowa (until age 12) Brandon, Florida (until 18) East Lansing, Michigan (until 21) Gainesville, Florida (until 25) Winston-Salem, NC (Where the growing up continues...I hope.) College & Medical School: Michigan State University, University of Florida College of Medicine Major in College: Biochemistry Goals: Do some good in the world every day. Create some laughter in the world every day. Personal Philosophy on Life and/or Medicine: 1. The journey is more important than the destination. 2. Never take yourself too seriously. Favorite Quote: "When in doubt, tell the truth." – Mark Twain, Following the Equator

Primum non nocere.

First of all, the ancients advise us, you should do no harm.

Whenever I read this most essential guideline and credo for the practice of medicine, I immediately think of Elizabeth.

Primum non nocere.

Is it even necessary to state such an obvious thing? What could be more self-evident? As a physician, my goal is to "do good" [as nebulous and uncertain as that may seem at times]. The details of how to "do good" often seem elusive and evasive, but the fundamental obligation to avoid harm should be flagrantly apparent. Why does it even require commentary?

Even so, the old ones continue to whisper to us from the distant past: First, do no harm.

*******

Elizabeth came to my clinic as a 25-year-old graduate student. She was new in town. She had ten years of type 1 diabetes under her belt, and she wanted to establish contact with a physician to help her manage the disease. Her home was far away. Her graduate studies had been disrupted when her research advisor was recruited to another institution, an event that forced her to dig up her roots and move on in order to keep on track with her thesis and her career. I quickly got the feeling that the relocation had been challenging for Elizabeth, and that there other things going on in her personal life that were troubling her, not yet ready for disclosure to me.

She wasn't going to tell me much about any of that. She was here for her diabetes, and that was all.

Her diabetes, she was quick to admit, was not in very good shape right now. With all of the recent disruptions in her life, she was not paying much attention to it. She was on autopilot, taking the same insulin doses every day as a default, since she had not been monitoring her glucose enough to be able to make data-driven adjustments. She was not having any hypoglycemia, which she saw as a positive result of her "benign neglect." She realized that she was undoubtedly having significant hyperglycemia at times, but that did not worry her so much, as long as her glucose did not plummet.

As we discussed her insulin dosing, it came to light that she did make one adjustment regularly.

Her single and singular insulin adjustment had nothing to do with glucose measurements.

She adjusted her insulin in order to deal with swelling.

Every month, Elizabeth would suffer through several days of fluid retention, predictably correlated with the hormonal fluxes of her menstrual cycle. Those were the days she always felt swollen and bloated, and she became absolutely miserable and dysfunctional. As those days approached so predictably every month, she had figured out a "cure" for her impending malaise: she reduced her insulin dose to 50% of her usual dose [even though her "usual dose" was already inadequate to regulate her glucose satisfactorily]. And cutting her insulin by half would resolve her edema before it ever created misery.

She was using applied physiology, I suppose.

Or, to be more accurate, she had become a specialist in applied pathophysiology.

The concept is simple: glucose in our bloodstream gets filtered through our kidneys, along with just about everything else. For those of us who do not have diabetes, our kidneys "save" all of the glucose and put it back into our bloodstream [along with all of the other things the kidneys know they are supposed to save], and none of the sugar is wasted in our urine. That system works perfectly well, to a point. If the blood glucose goes high enough, though, the kidneys are overwhelmed by the workload and are unable to return all of the glucose back to the bloodstream; the surplus sugar ends up in the urine. It isn't really possible for a person to have a blood sugar high enough for that to occur, unless the person has diabetes.

Elizabeth had diabetes.

And, as the glucose goes into the urine, it drags extra fluid along with it, which is why people with high blood sugar from diabetes can have increased urination. They will eventually also develop an increase in thirst. The loss of fluid from the pull of the glucose is called an "osmotic diuresis" in doctor talk.

Elizabeth knew that letting her blood sugar go high enough to run through her kidneys to create an osmotic diuresis was not a healthy approach to her diabetes, but she did it to prevent herself from feeling terrible from the swelling. The resulting loss of fluid helped her function better on a day to day basis, and that short-term benefit was of more importance to her than long-term considerations about the effects of high glucose on her body.

 She was very honest and straightforward in telling me her methods.

It was not a time for a lecture from me: "Don't do that! It's unhealthy! Stop it!"

She already knew every word I would say in my lecture, without me even giving it, so why should I bother? She weighed the benefit/risk ratio of her actions within her own mind every month, and each month she came to the same conclusion. She needed to function in the world. She had to get through this day. The fluid retention was interfering, and she could make it go away.

First, do no harm, our predecessors remind us. Did I mention that earlier?

When I heard of her methods, I expressed gratitude for her openness with me, and I saw an opportunity to help Elizabeth start to get her diabetes on track.

I saw a chance to solve a problem.

I saw an opportunity to do some good, the kind of "good" that doctors are supposed to do. Elizabeth and I would team up. We would make things better.

"Elizabeth…I have an idea…," I started off, hesitantly. Maybe I could give her a solution, when she was expecting a lecture about her behavior.

She was attentive.

"What if we try this? How about if I give you a prescription for a mild fluid pill -- a diuretic -- for you to take for 4 or 5 days of the month when the fluid retention bothers you? Then you won't need to lower your insulin dose and let your sugar run high. You can take the full insulin dose. We can control your swelling and we can control your blood sugar better, all at the same time!"

She was agreeable.

It was a brilliant idea. [I was a brilliant doctor.]

I was going to exchange her osmotic diuretic for a pharmacological diuretic.

We were going to be fixing things!

I was doctoring with the best of them.

I wrote a prescription for hydrochlorothiazide.

I had a game plan. We would work together, and I would be supportive and gain trust.

We weren't going to fix her diabetes all at once, but our first step was a move in the right direction.

*******

It all turned out to be a step in the wrong direction.

*******

Elizabeth called me a few weeks later. She told me that she was not feeling well. Her symptoms were nonspecific. No pain. No fever. She had been monitoring her glucose periodically, and her blood sugar wasn't too bad. But she felt terrible. Weak. Wiped out.

Nothing on physical examination gave me any clues.

But the laboratory results did.

Her creatinine and blood urea nitrogen, tests of kidney function, had been perfect when I first saw her. Now, a few weeks later, they were significantly and worrisomely elevated. And she just felt bad, sick, weak, nauseated, and horrible. She agreed to coming into the hospital for some IV fluids, to have some monitoring, to get some testing.

As for me, I had no diagnosis.

Nothing fit.

I anticipated things would turn around and get better. Something was definitely going on, though I didn't know what it was. Watching her in the hospital would rule out some possibilities, and give some time to sort out other considerations. It is amazing what you can figure out sometimes, just by watching a patient.

Each day, though, the only thing I watched was her kidney tests getting worse.

Each day, she felt worse.

After the first day, when it became apparent that this was not going to be one of those "let's give you some fluids and make everything normal again" admissions, and that something bad was going on with Elizabeth's kidneys, a nephrology consultant was called in.

And her kidney function got worse and worse.

Elizabeth required dialysis.

[Did I tell you? A month earlier, she was doing fine, and she had normal kidney tests…]

Now, her kidney function had shut down, and she was on dialysis.

Elizabeth hated dialysis.
"Will I have to be on dialysis forever?" she asked. "If I have to be on chronic dialysis, I won't do it. I refuse! I would rather die. Do you think I will have to do this forever?"

"It depends." That was the best answer I could give.

"I hope that your kidney function will come back to normal. Time will tell."

I hope…

[I hope…]

And, day after day, there was NO evidence that her kidney function was coming back.

Did I mention her test results?

When she came into the hospital, she had a lot of eosinophils in her urine. The abrupt decline in her kidney function led to a kidney biopsy to try to find the reason. The biopsy showed an "interstitial nephritis," an inflammation and infiltration of the kidneys with huge numbers of eosinophils.

This kind of inflammation, with all of the eosinophils, can indicate a reaction to a medication. Antibiotics and nonsteroidal drugs are most common. It -- very rarely -- can be a reaction to a thiazide diuretic. [Hydrochlorothiazide, for example.]

First of all, the ancients now shouted at me across the centuries, do no harm.

But how was I to know the stupid medicine would do this???, I wanted to scream back at them.

I had given her hydrochlorothiazide so she could do better with her diabetes, so she could protect her kidneys from damage by diabetes.

And what was the outcome of my brilliant intervention to save her kidneys?

I killed her kidneys.

*******

The good news is that her kidney function eventually returned to normal, as it often does in such cases, once the offending agent is taken away.

Elizabeth was glad to be off dialysis, and she went back to her daily routine. Nothing changed with her, though, as far as her approach to diabetes. She had not found "enlightenment" as a result of her dialysis experience; there was no new-found commitment to a healthy life, no epiphany, no breakthrough.

 Her old habits continued. She eventually moved away, and I cannot tell you the rest of her story.

I can tell you a bit of my story.

I now had a problem of my own to wrestle with.

Hydrochlorothiazide.

I had almost destroyed a young woman's kidney function with a prescription.

I don't know whether Elizabeth or I was the most relieved when her kidney function returned.

What do I do with this experience? How does a doctor process something like that?

The intellectual part of my brain got past it quickly. It was a fluky reaction. Weird things happen in life, and they aren't predictable.

Get over it.

Move on.

Don't change a thing.

Shrug it off.

The emotional part of my brain had more of a problem.

I had almost killed a young woman's kidneys by writing a prescription for hydrochlorothiazide. 

I vowed to never do that again.

And there was only one way to make sure that the experience wasn't repeated

New Rule for Self: Never Prescribe Hydrochlorothiazide.

 I was backed up by one of medicine's most essential precepts. [First of all, do no harm.]

And I didn't prescribe it, for about a decade.

I didn't prescribe it for young women with monthly fluid retention, no matter how miserable they were.

I didn't prescribe it for middle aged men with hypertension, no matter how effective it would have been.

I didn't prescribe it for anyone.

As far as I was concerned, people could tough out their symptoms, or we could use alternative medications, but I vowed I would NEVER do anyone harm with hydrochlorothiazide again, EVER.

And I had my "n of one" experience to back me up.

If you practice internal medicine, or a subspecialty of internal medicine, it is possible to practice for a decade and not prescribe hydrochlorothiazide.

Take my word.

I did it.

But it is not easy.

After a while, it gets wearing on the soul.

And it is probably bad medicine.

I don't know how many times I would see a patient in clinic and think "Before I knew Elizabeth, I would have prescribed hydrochlorothiazide for you…but now, because of Elizabeth, I refuse!"

I cannot even remember the number of patients I saw where a prescription for something was in order, when I even thought that hydrochlorothiazide might well be the patient's best option, but [in my days of post-Elizabethan distress] it could never be an acceptable option for me. My life as a prescriber of medications became a recurrent word search through my mental pharmacopoeia, which I rearranged to contain these categories:

ACE inhibitors

Beta blockers

Corticosteroids

Drugs that are not hydrochlorothiazide

Expectorants…

So, what happened?, you ask.

After a decade, it dawned on me that I was not doing the best that I could do for my patients, who deserved the best therapy available. And sometimes that was going to be hydrochlorothiazide.

Hydrochlorothiazide had been a problem for Elizabeth, there was no doubt.

And I had managed to make it a problem for me.

I did not make it a problem for "Elizabeth and me," which would have been fair.

Instead, I had made it a problem for "all of my patients and me," which was not fair to "all of my patients."

After a decade, I got use again to the idea that it is an effective drug. I accepted the fact that weird and unpredictable reactions can happen with any drug.

I got use to the idea that the practice of medicine involves personal discomfort and worry, daily, if not hourly. [In the final analysis, perhaps that is what the practice of medicine really turns out to be.]

I even figured out something really important: to not use an effective therapy can also be a type of "harm."

And I remember what the ancients had to say.

First, do no harm.

And, now, I can prescribe hydrochlorothiazide with the best of them.

And I do.

But I would be lying if I didn't confess that, to this day, I still have some palpitations and sweaty palms each time I do.

*******

We should be careful to get out of an experience only the wisdom that is in it -- and stop there; lest we be like the cat that sits down on a hot stove-lid. She will never sit down on a hot stove-lid again -- and that is well; but also she will never sit down on a cold one anymore.
[Mark Twain, Following the Equator]