Sea of Tranquility

by DrKSSMDPhD | September 28, 2016 7:28 am

[Ed. Note: Dr. KSS writes about medicine and biotech stocks for the Irregulars. He has agreed to our trading restrictions, chooses his own topics, and his words and opinions are his own. All of his past articles and most recent comments are on his Stock Gumshoe page[1].]

“I live in the light

of the bright summer moon.

I’ll take you all sailing

from midnight til noon.

I’ll show you a Sea of Tranquility….”

—Gordon Lightfoot[2]


As a corntop child, age in the single digits, I knew I was living in fulsome times, in times when there was a class of larger-than-life people routinely capable of doing things I couldn’t. “Did you know,” I said to a seatmate on the schoolbus, “that for those Apollo guys, they make them stick their bare feet in a bucket of icewater for seven minutes? No way I could stand that!” An ullullational “wow” rose from my quarter of the bus. “And not only that,” I went on, “but they test them by putting them on this, this machine that spins them in three directions at once to see if they puke!” Several of us began tossing our heads in rapid multiple circles and giggling.

“You guys all suddenly have group epilepsy?,” the bus driver said, snarling.

The boy in the seat in front of me waggered his head so spiritedly he succeeded in making himself vomit. “Kyle yorked!,” someone shouted.

My father worked in the newsroom of a busy urban TV station. Once a week during the mid-sixties, he brought home to me a reel of fresh 16mm film in a NASA shipping container: news footage about the Apollo missions released for broadcast. I spliced each one onto a growing reel of clips in our downstairs projection room, and whiled away the heat of summer days screening them again and again.

But an eager heart is tough to slake. I needed a map for a situation room so I could be with them in spirit on their missions….one into which I could place a pushpin at each point of LEM touchdown. “Houston, Tranquility Base here…..the Eagle has landed,” squawked Neil Armstrong at 3:18 pm EST on 20 July 1969. Its occurrence on a Sunday juiced up history’s Klieg lights on its epicness. Who wasn’t watching? I recited Armstrong over breakfast the next morning, making a vivid “pssshhhht” squelchy radio noise so my brother and sister would snicker. I reached for a box of Cap’n Crunch Peanut Butter Cereal, one my mother had bought the day before. As I poured it, I noticed a cool advert on the back. For only four Cap’n Crunch boxtops, which I could mail in, I’d get by return mail a vinyl blue map of the moon with the moon’s geographical features printed in glow-in-the-dark ink. “Mom, can we get back to the grocery store this week? We’ve gotta get more extra boxes of Cap’n Crunch.”

August, when the map arrived, seemed an infinite wait. I taped it to the wall above my bed, and sat up most of the first night staring at it like a Tibetan monk gazes at a thangka. All the craters where there. So was Sea of Tranquility and the other designated “waterways.” Down at the extreme southeastern corner, just as the surface curved over into the far side, was a clearly marked portion of a crater. Marinus, the map read.


*      *      *     *      *      *     *     *


“Just the place for a Snark! I have said it twice:
That alone should encourage the crew.
Just the place for a Snark! I have said it thrice:
What I tell you three times is true.

—-Lewis Carroll


Seizures are bad.

In a May 2014 Gumshoe Biotech column[3], we introduced you to a woman I called The Belle of the Everglades, an HCV patient I treated early in my career. Though she lived alone among swamp alligators in south Florida (a place I imagined having a Frogs (great 1972 horror schlock with Sam Elliott[4]) vibe to it), she was robust and hale, and wanted to do her interferon-alfa treatment there.

I had screened her with double-redoubtable thoroughness, noting in particular she’d never had any seizures, something interferon-alfa is capable of rarely provoking. But within a brief time after her first self-injection, she was thrashing on her floor in status epilepticus. As recounted in detail in the earlier column, a botched attempt at intubating her by EMS in the field led to an occipital artery air embolism, which left her cortically blind. I was aghast enough at what had happened that for a week I earnestly considered abandoning medicine.

Seizures are really bad.

Nigisti had no idea what she was facing. A year earlier, when she was 18, she’d moved from Eritrea to the United States with her parents and siblings.  All were refugees of a war at the time with Ethiopia. She’d engrafted poorly in her new home, and her parents, running an ethnic grocery, had fared little better. The area had no Eritrean expatriate community to speak of, and nearly every default assumption about life in America clashed with the family’s social objectives.

Children grow up at different rates: though Nigisti was the eldest, she was very much a child. She still desperately needed parental attention and approval. It wasn’t to be found: they were pre-occupied with their transplant status, with the extreme stress of having moved a world away. They feared Nigisti was associating with teenagers her age who would corrupt her, and said so. Their approval lacking, Nigisti schemed a way to get it back.

She wasn’t in school. She refused to pursue an education. When her parents were nearby but not actually watching, she began having spasmodic fits, flailing, acting confused, collapsing, drooling for heightened effect. Her siblings would fetch her parents, who would find her confused or pretending to be, lying just so in picturesque disorder on the floor. Despite her tumbles, she never injured herself. Neither did she ever lose control of her bladder or bowel.

When they took her to an American doctor, the doctor wasn’t clued in. He lacked insight into the overall upheaval of their lives, the displacement, the fear, the failure to fit in. Many people in the family’s position would have adjudged themselves happily now in a land of freedom and opportunity. Nigisti and her family, however, seemed to need the tight rules of Eritrean society in order to feel grounded. They understood the contentment of caged birds.

The doctor was concrete. She was having fits. He feared she had onset of epilepsy. He’d ordered a brain CT and this had horrified Nigisti: she was now sick enough that someone thought her brain needed scanning. What a terrible new country this was!

He had not obtained an EEG. He did not refer her to a specialist. He decided to treat the presentation at face value, and prescribed Nigisti phenytoin (Dilantin), a seizure drug. That was nearly three weeks ago. But Nigisti was having pseudoseizures. She was faking it in a primitive, regressive, very dysfunctional ploy for attention that while pathetic, was about to prove very dangerous. Indeed, she was about to get the metaphoric cup with which she begged for attention three times filled and running over. But seeing a psychiatrist had either not been suggested or had been vetoed instantly by her parents lest Nigisti fall into what they perceived as the most excrescent clutches of Western medicine.

During the autumn of my first year as an attending physician, Nigisti was admitted to the hepatology inpatient service at our hospital, a household-name prestigious academic medical center. She was admitted via the emergency department. Her parents had brought her there because she had broken out nearly all over in red papules. Worse, her laboratory studies in the ED were in startling disarray, topped off by an ALT (a liver enzyme) in the thousands. A normal ALT is under 50. A couple of more days at this pace and her liver would be facing a kind of China Syndrome.

As a class of medications, seizure drugs are regarded with caution and awe. Their purpose is to dull, ever so slightly, electrical activity in the brain so that storm currents abate into subdued ripples. Sedation isn’t the goal, but is often the consequence. Phenobarbital was an ancestral seizure drug, and with it, primidone, a drug broken down by liver into phenobarbital. The benzodiazepines are wonderful for buffering seizures, but are habit-forming, and when they are stopped, seizure threshold falls: even people regularly taking Ambien for sleep must taper off the drug rather than stopping it abruptly lest they seize. Valproic acid is good at preventing seizures, but irks the liver, often considerably. The clinic will always have room for new anti-seizure drugs that are safe and effective, a sentiment to which we’ll return in some paragraphs.

Phenytoin, which isn’t sedating or habit-forming, is often considered a “safe” place to start treating seizures, though no liver doctor would ever agree that phenytoin is safe, especially among people of African ancestry. About one percent of people metabolize phenytoin through an aberrant liver pathway that sets off a colossal hypersensitivity syndrome. Nigisti’s eosinophil count was sky-high. Phenytoin hypersensitivity is often called pseudolymphoma because, as in her case, every known anatomical group of lymph nodes, from submandibular to epitrochlear to inguinal, wells up, becomes very palpable. The commonest cause of death in this situation isn’t liver failure (the liver has great capacity to right itself) but rather Staphylococcal or Streptococcal infections from skin breakdown.

Among the rare people sickened by phenytoin, most are black. The manifestations have a way of always beginning around 21 days after the first dose.

I started Nigisti on preventive iv antibiotics for her skin, but her liver was our chief and grimmest concern. It was profoundly injured. She was jaundiced. Her liver was soccer-ball-sized and tender. One worry was that her parents insisted Nigisti couldn’t have incurred this on her own: that it was those no-good friends she hung out with. They’d started her on street drugs, the parents were sure. Academic physicians are obsessed with the idea that the hoofbeats you hear may belong to zebras, not horses. Could this be virus hepatitis from illicit drugs starting up acutely? Worse, was her liver headed for fulminant failure? Was it going to shut down on us and require replacing this weekend?

It was a Friday afternoon, and there were four hepatologists. We met and discussed her case. We decided we were all in agreement: we needed to do an urgent biopsy on Nigisti’s liver to assess damage and give a clear clue as to cause. Drug-induced liver injury would appear quite different to virus injury. Using special stains for a matrix protein called reticulin, we could also predict whether her liver was likely to survive the insult. We wanted to do the biopsy ASAP because at the time, she was still able to clot. No guarantees on that during the weekend, however.

It was my weekend on call, thus I drew the short straw. I talked to Nigisti about the biopsy….that I’d numb her up generously, that biopsy was quick and nearly painless, and why we needed to do it. I asked her to read and sign an informed consent document. She balked initially, wanting her parents to handle the task, but I explained that since she was 19, she was legally an adult and needed to sign it herself if she was willing to have the biopsy. I was careful to explain to her that what we needed most was for her to promise to be cool, collected, calm after the biopsy…that she’d need to lie on her right side for two hours at least so as to let the site begin healing and form a solid blood clot.

I asked her to eat just a small portion of supper in order to clamp down her gallbladder and get it out of harm’s way. I asked her to answer any calls of nature, if she had them, so she’d not need to get out of bed soon after the biopsy. She was pleasant. She behaved as if she appreciated being addressed with respect, as if she were a full-grown woman. I began prepping a site with Betadine. As I draped her and established a sterile field, dabbing her right lower chest with orange medical warpaint, she spoke: “Has anyone ever died from this?”

“Well, only very rarely,” I answered. “I’ve never had a patient die from it and never known of a patient to die from it. When that happens it’s usually because the patient didn’t cooperate, didn’t lie calm and still after the biopsy. We’ll not have that problem though, I think.”

When I perform a liver biopsy, I have a singular goal: to proceed in the style of a commando raid. If you dawdle during set-up, or act unsure of yourself, or seem mystified about the precise spot you’ll insert the needle and what azimuth you’ll use, only one thing happens: the patient grows tense. Muscle tone rises. Blood pressure rises. Their fear takes on a dimension such that they are likelier to perceive mere touch as pain. In fact, there’s little reason a biopsy should be painful: the liver has no nerve endings. If you generously instill local anesthetic (I prefer bupivicaine because it lasts for two hours longer than lidocaine) down to the level of the liver, the biopsy should be quick, a painless non-event. The procedure uses an 8-inch 16-gauge needle, one that you NEVER allow the patient to see,  with a sharp beveled cutting edge. Into the needle you aspirate a worm-in-tequila-sized core of liver tissue. You need the confidence and experience to accomplish this in one needle pass, as risk surges with additional needle passes.

Sedation? I never use it. Most hepatologists keep in their minds a large inventory of exceptionally funny jokes (some raunchy, depending upon the patient) to deploy to calm a patient. But a sedated patient cannot cooperate. A patient undergoing biopsy needs to exhale crisply on command to draw the left lung up out of harm’s way. The same patient needs to roll smartly and immediately up onto their right side the instant the biopsy is done to establish pressure on the site.

Nigisti’s biopsy was a slam dunk. I was finished in under 5 minutes, having lolligagged to let the bupivicaine fully take effect. A nice core of liver had plonked into my syringe, and I decanted it into a clean vial of formaldehyde. “Have you ever been in two places at once Nigisti?,” I asked, making magician motions with my hands.

“What do you mean?”

“Well, there you are in bed, and here you are in this bottle!” I showed her the small bit of liver, bloodless, swirling on the bottle bottom.

“That’s all you need?”

“Yes, it’s plenty. You do good work!”

By now I had her up on her right side. She was comfortable. She’d had no pain. I repositioned her bed a few degrees so she’d have a clear view of the wall television, and placed the remote control by her side.

“OK, my dear. See the clock? It’s 6:15 now. I need you to stay STILL just like this til 8:15. Then you can move a little, but I don’t want you out of bed before 10:15.  Can you do that for me?”

I called her nurse to the room, and explained that I now needed vital signs to be recorded every 15 minutes for 2 hours. I gave some parameters….to page me if her blood pressure got below x, if her pulse rose above y. I authorized some small iv doses of Demerol, a strong opioid, for pain if she were to experience any during her rest.

As I left to go home, I wondered where Nigisti’s family were. Because of her history, I still had some worries about how she’d act alone in the room between nurse stop-ins. The nursing staff called their motel room number, got no answer, and left a message.

At 7:20 pm, someone from that hospital ward paged me. Her nurse, a stoic British woman, came on the line. “I went to check on her, and found her sitting on the floor outside her bathroom. She was jerking, twitching……but fully conscious. There was no evidence she’d soiled herself, and she didn’t seem confused. My thought ran to pseudoseizure.”

 “Yes, what we’ve suspected all along. She’s faking these for attention, and the outside doctor blindly put her on phenytoin, which is now wrecking her. Everything for the wrong reason.”

“I got her back into bed and on her side. Her vitals were OK, but she was screaming at me….very emotional, wanting her parents. She hurled the TV remote at me.”

I asked the nurse to send a stat CBC, to enlist the aid of hospital security in finding her family and getting them to her room, and then to give her a milligram of lorazepam, similar to Valium, iv to calm her down, not because she was seizing, but to keep her from provoking internal bleeding. People with pseudoseizures, seizures that they are feigning, flail and contort mightily but are generally unaware that in grand mal generalized tonic-clonic seizures, one is never conscious. Succeeding in duping others into thinking you’re unconscious is nearly impossible, as you remain ticklish and very susceptible to tricks, such as having a sneaky nurse tell you she just found a $1000 bill in your pocket.

“This could be really bad,” I said. “She’s acting out. Protesting her existence. If she can’t stay chilled, she will bleed from her liver. Could you page me back when the CBC is in? Read her the riot act if you have to.” Hospitals often keep discreet rosters of people in the community friendly to the hospital who can be called upon in a pinch to translate for patients speaking uncommon languages. We wondered if we might find someone who spoke Tigrinya, that perhaps talking to such a person would soothe Nigisti. But we had no  luck. I had asked Nigisti if she spoke Arabic, as many Eritreans do. She didn’t.

The nurse paged me back 15 minutes later. Nigisti seemed to have become disinhibited from the lorazepam, and was now refusing to stay in bed. She was standing in her doorway screaming. Her family couldn’t be found and had left no cell phone number with the staff. “Her hemoglobin is 10, down from 12.8. We’ve tried talking her down, reasoning with her. It’s not working.”

“Thanks. Look, please have the blood bank type and screen her now, as we’ll likely need to give her blood tonight. If you would, please give her five mg of iv haloperidol pronto. Repeat that at five-to-10 minute intervals for a maximum of 20 mg til we get her to behave. I am going to work on getting her an ICU bed, as this is more than the floor can deal with reasonably.”

I arranged for the ICU bed, donned my shoes and headed back to hospital. This would be an ugly night. Nigisti was in full cry, inconsolable, angry about not being in Eritrea, about being in a strange land, about being sick, about now having the full repertoire of the medical system aimed at her: she was going to an intensive-care bed. She was still juvenile, a person whose frontal lobes hadn’t matured, and showing no impulse control. She was wailing, and tears were making her cough. She coughed vigorously enough that she vomited from the post-tussive effect. A CT scan showed a belly full of blood. Her systolic blood pressure was now dipping below 90. I started her on dopamine, a blood-pressure supportive drug, and transfused her two units of red cells.

Having gotten her somewhat stabilized, I asked a colleague in vascular radiology to perform an emergency hepatic arteriogram. Possibly we could find a bleeding locus in the liver and embolize that.

Nigisti’s night was one in which medicine desperately played all its aces, to no avail. Her kidney function was ebbing, her skin rash worsening, and she remained critical and unstable. Her liver biopsy specimen had been rush-processed, and showed horrible falling away of reticulin: her liver wouldn’t make it, but in two ways she wasn’t a candidate for surgery. No sane surgeon would have operated on her in her present condition, and likewise no rational liver transplant selection committee would have authorized her for a new organ. There was an ugly reality: she had needlessly brought all of this on herself, and if she lacked the impulse control to cooperate one evening post-biopsy, how could she possibly ever be counted to take her anti-rejection drugs and keep her appointments post-transplant? Livers are allocated not just on acute need, but also on the premise that they are rare and precious, that they must go to those with personal and family circumstances indicating that they could be counted on to take pristine care of their new organ. To a vivid and ugly degree, “deservingness” has to be invoked in allocating organs. Nigisti had to be deemed an inappropriate transplant candidate because she was psychiatrically reckless, and for reasons that might take weeks of therapy to bring under control. The patient awaiting a liver transplant who had the highest priority at our institution was a 42-year-old mother of three dying of cirrhosis caused by HCV she’d gotten as a result of RhoGAM injections.

Nigisti died Monday morning. When deputy sheriffs served all four hepatologists with lawsuit notices a month later, it was a hardly a surprise. A judge dismissed the case without prejudice before depositions were ever taken as, to a reasonable degree of medical certainty, Nigisti’s entire fate was one she had brought upon herself, no matter how tragic. Admittedly I have resorted to some mild rhetorical sleight of hand in using her case to propel my argument that seizures are bad: she never seized. But I think of the Sunday School notion of the graven image, and how rotten things accrue to those who dabble in them. When you fake an illness, doctors can hardly be blamed for trying to help you in spite of yourself. Had we done nothing, she’d have died anyway and we’d still have been sued.

When I was 16, my best friend invited me to go with him to the mall one Saturday. At one juncture we sat sipping Cokes on a bench and he found himself bored. “Watch this!,” he said. He threw himself to the ground in a crowded aisle and began flailing, chomping his teeth and drooling. When sufficient wellwishers had gathered, he stopped the theater, sat up, and said, “Ha ha…fooled all of you!” All of us were livid. But this was many minutes into his stunt, by which time EMS had been called. A policeman cuffed him and took him away, and I bummed a quarter from a bystander to call my dad for a lift home. That was the last day of that friendship.

For the third time: seizures are bad. In William Monahan’s comic rampage Light House: A Trifle, Or,  Actual Modern Fiction, a man beleaguered by his wife shouts, “I divorce thee! I divorce thee! I divorce thee! Three times in the Muslim sense.”

As a middle-aged divorcee, my life seemed to have everything in it except what I wanted most: companionship. Via an unlikely series of coincidences, an English-speaking crackerjack of a woman in a far-off place befriended me, and we began a lively digital exchange. Via texts, Skype and email, a vivid camaraderie grew at a healthy pace. I’d long since accepted her as the best thing in my life, and realized that two years had elapsed. The time had come when I felt I had to meet her in person. I booked passage….a journey via what is probably the longest flight in commercial aviation on earth. At a layover in Texas, I grabbed The Atlantic, Granta, Harper’s, The New Yorker and Vanity Fair from a newstand. I’d make short work of my night over water in an aluminum can.

In “Ballad of a Thin Man,” Bob Dylan sings “Something is happening here/But you don’t know what it is.”

Somewhere over the Aleutian Islands, a sense of feeling oddly ill at ease descended over me. A flight attendant served chicken-or-beef, but I stopped eating after two bites because of the taste, which seemed neither spoiled nor exactly wrong, but metallic and absent. Cocktails were offered but I deferred. Ligaments began diffusely to ache where they inserted into my bones. My head hurt.

When you rise out of an airline seat, your initial motion is one of extending your head forward and ducking slightly. I wanted to stretch my legs, but significant pain in my neck and back when I attempted standing kept me in the seat.  Two seats up and across the aisle from me, I became aware of a woman whose gaze left me ill at ease when she turned her head. She had had profound facial trauma at some point, and had had extensive reconstruction of not just the skin structures of her face, but the bones beneath as well. I was feeling radically unlike myself: I am a physician and normally would regard such a sighting with a detached professional comportment and no emotions except for great empathy for the woman. Now I was frightened of her.

We endured hours of fierce headwinds and lightning, and for long intervals, I found I had to keep my eyes open to avoid vertiginous nausea from a plane that seemed to be seiching importunately. I longed to sound off to the pilot and demand we ascend higher into the tropopause, but kept subdued: I had flown more than a million miles, and what we were experiencing was mere modest turbulence  (nothing even remotely like the horror of a plane I’d flown once in the Serengeti….one that took off by running over a cliff at low speed because the runway was 100 feet of washboard). I felt very afraid. Why?

After what seemed a Canada of cold darkness, an eastern glow sent pink-tipped orange tendrils into the window view. A reprieve, perhaps: in a thick Tagalog accent, the pilot spoke over the intercom. The jet had burned excessive fuel during the night wrestling with exceptional headwinds, and he planned for us an unscheduled ditching well short of our destination so that we could refuel. But the increasing light level—soon it would be broad daylight—caused fright in me.

As we landed, passengers de-sardined themselves. They stretched, fetched overhead belongings and began the crush to the front of the aircraft. I sat in my seat. It seemed to be the thing to do. I wasn’t sure why, as I was deeply confused. My head ached severely now, and so did my back.  At the goading of a flight attendant who told me I had to get off the plane, I tried standing up and saw that I could not. My soul, my innermost level of consciousness, felt like a coin that had fallen deep into a couch. I was sweating inappropriately.

Flight attendants began gathering around me, and locked into my gaze. “I’m fine,” I said. “I am a doctor by the way. And I am NOT having a heart attack, a pulmonary embolism, a stroke or anything like that. I’ve got no DVTs. I flexed my calves religiously. I’ve not taken any drugs, and I had nothing to drink during the flight.”

“We’ve been noticing you during the flight. You’ve been acting rather strange, sir.”

A face mask exuding plastic-smelling O2 was shoved on me.

They kept staring. “Shall I try again to get off the plane?” I asked.

“No, don’t want you going anywhere. Leave the O2 on, sir.”

“You know, I really really really do not feel like myself. I have never felt this way. I am losing control of my brain.”

A wheelchair came down the aisle for me. I overhead flight attendants describing me to what evidently would be a receiving hospital.

“No……..,” I said.

Now, 10,000 miles from home, in the company of no one who knew me, the single biggest medical event of my life was just moments away. And I would never be the same after it.

[To be continued.]

  1. his Stock Gumshoe page:
  3. May 2014 Gumshoe Biotech column:
  4. horror schlock with Sam Elliott:

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