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.
"When in doubt, tell the truth."
– Mark Twain,
Following the Equator
Primum non nocere.
First of all, the ancients advise us, you should do
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
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
She was using applied physiology, I suppose.
Or, to be more accurate, she had become a specialist in applied
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
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
She was agreeable.
It was a brilliant idea. [I was a brilliant doctor.]
I was going to exchange her osmotic diuretic for a
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.
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
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
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
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
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
And what was the outcome of my brilliant intervention to save
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
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.
I had almost destroyed a young woman's kidney function with a
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
Get over it.
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
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,
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
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:
Drugs that are not
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 had been a problem for Elizabeth, there was
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]