Withdrawing life support after severe brain injury (complicated post)


Is Life Support Being Withdrawn Too Soon After ICH?
Medscape Medical News, 2013-02-13

Claude Hemphill et al have written about this concept for years.  Claude’s enormous heart is in the right place. He and everyone else for that matter desires to do the right thing in terms of maximizing treatment to get the best outcome possible.  However, the author here is preaching to the wrong choir. This is not an article per se, but a review of a concept by “Medscape”, the “People Magazine” of medical information.  The information therein is just vague enough to potentially suggest to family practitioners and patient surrogates that read Medscape that the “more is better” theory is synonymous with “if more is better than more than that might be better yet.”

The issue of prospective living wills and powers of attorney for health care delivery is not mentioned, so one might get the impression that a good course might be to suggest that an incompetent patient who has previously opted out for extended ICU care on “life support” might have made a “better” decision on the basis of this data. If that’s the case, then as the French say: “Ze worm….. it is out of ze can” as it pertains to other prospective wish issues.

This article opines:  “Those outcomes in these patients may not still be true today with our sophisticated medical care”.  There is no convincing data to suggest this is true in many, many ICU treatments, many of which convert death to life-in-death ensconced in skilled nursing facilities. The “we can do so much more than we used to” argument is directly responsible for many surrogate demands for open-ended ICU care. The mortality and morbidity statistics for ICU care have changed little in the past 20 years, and recent evidence of an intensive four year study by Levy and Chalfin et al rather convincingly suggest that the odds of hospital mortality were higher for patients managed by ICU physicians than not *.

3.  The article does not mention any limits as to how much longer an ICU admission will take to generate how much improvement in a patient to break the threshold of “acceptable quality of life”.  So, which scenario do you believe according to the ongoing clinical evidence, not the prospective optimism:

A. Each additional day of ICU care has
increasing potential to generate a viable
patient and each additional treatment
has more potential to improve outcome?

B.  Each additional day of ICU care
Does not show any improvement and each additional
therapeutic treatment has more potential
to prolong length of stay?

If you take the position that each additional day of ICU care has diminishing potential to generate a viable patient, but each additional therapeutic treatment has more potential to increase length of stay based on “hope”, then you have elevated “hope” to a self fulfilling prophesy. Your responsibility to your resource allocation system is to give up.  It isn’t a “right thing to do” anymore. It becomes practical economics. There IS a limit and you’ve reached it.

If, however, you take the position that each additional day of ICU care has increasing potential to generate a viable patient, and each additional treatment has more potential to improve quality of life than the one before it, then you will be asked to support that position not as the “right thing to do” in a perfect world but in terms of cost/benefit. When is it a straight up money issue.

In 2009, the USA spent (all told) twenty five trillion dollars on health care. That’s US$8,000 per person, 17.3% of the GDP and increasing about 6% annually. But we only fully indemnify about ~ 60% of our population and the USA ranks below Portugal in preventable mortality. California increased its cost of health insurance 20% this year and there is no end in sight. As the price of health care goes up, fewer businesses can afford health care for their employees. 62% of all personal bankruptcies involve medical bills in 2010. The whole system is swirling around the bowl and the advent of the AHCA of 2008 (fully implemented in early 2014), will radically change the whole concept of health care indemnification.

There are several fixation options available, two of which will painful prescriptions for providers.

1.      Allocate resources toward health care and away from other previous priorities such as entitlement programs, military security, and bureaucratic priorities.

2.      Pay providers less for the same (or increased) workload.

3.      Reorganize health care spending so that more money is spent on some services and less or nothing is spent on others; essentially, say no more often.

History suggests that it is unlikely any modern society can or will decrease support of entitlements such as social welfare, unemployment insurance, social security benefits, or retirement benefits that citizens depend on and have paid into during their working careers. Cutting military security funding is equally unlikely. Most if not all national budgets include little else that can be reallocated in any meaningful amount. That leaves options 2 and 3. It is virtually certain that providers will have to reorganize their priorities one way or the other, and accept less remuneration in the process.’’

That said, if the patient is not better in a week, then how long are you wiling to wait on hope-based criteria?  Two weeks?  Six weeks? Indefinitely?   UPMC bills NICU care (full support) at around US$12,000 per day of which it collects about a third from most indemnifiers. I figure the real cost of an ICU day to the hospital is about break even, maybe slightly below. When will the moneymen find a break point instead of you? None of them have arrived in your (or my) office yet, but that day is coming, and when it does, defense of your resource allocation decisions will not be credible if it’s anecdotal. Providers will squeal like pigs in hot oil to be greeted by the stone faces of suits

“All the voyeurs and the lawyers
who can pull a fountain pen,
And put you where they choose,
With the language that they use,
And enslave you till you
work your youth away”

Don McLean (Bronco Bill’s Lament, 1970)

*  http://www.biomedcentral.com/content/pdf/cc8910.pdf

(Sorry- Typos are routine for me. I never proofread. Write it once and never read it again)

Dr. Crippen gets an EMG (almost)


EMG Doctor (Thick Eastern European Accent, one eye patched): “Yas…yas….my lovely…..ve vill INTERRIGATE ze nerves and ve vill find ze TRUTH….you and I…… ze truth will try to hide, but we VILL find it……you and me…..together…..(slurp)”

(Cut to routine meeting with maximum administrative leader and pillar of wisdom, Dr. X

Dr. X: “So…..how’s Guillian and Barre. I see you’re walking”

Moi: (Idly) “Yeah, getting better…..scheduled for an EMG at two”

Dr. X: “WHAT!!!! What do you need that for? You said you’re getting better!”

Moi: (suspiciously) “Dunno, Max said I needed it for completeness”

Dr. X: (Sneers)” Yeah? Well, you tell Max you’ll get one right after he gets one, if he can still walk. Do you know those things hurt like a BITCH. It’s medieval. They stick needles in you and then run electricity through them. If it doesn’t seem like it hurts enough they turn the juice up. You can hear the screams all over the 8th floor!”

Moi: (sharply clinical interest developing) “HUH…..I didn’t sign up for that! He didn’t say anything about HURTING!!

Dr. X: (Smirks) “Well unless you want to squeal like a pig in hot oil and be carried out of there covered in cheap Walmart band-aids, you better call Max up and re-negotiate!”

Moi: (Cheerfully) “Hi Max……(imitating Monty Python) “I’m getting better”

Max: (jovially) “No you’re not, you’ll be stone dead in a minute”.

Moi: (whines hopefully) “Um…(explains situation)……do I really need this EMG if I’m getting better……?

Max (whispers to companion): “Damned doctor patients…biggest pussies in the universe”.

Of cash cows and cookie jars


In the Sunday Pittsburgh Tribune-Review.  The sad story of a physician gone very, very bad,

Oliver Herndon, MD. 40 year old guy, trained at some of the most prestigious institutions in the country. UCLA, Stanford. Specialized in pain management, Board certified in Internal Medicine and Palliative Medicine. Said by many to be a regular guy, worked hard, did a good job. Internet patient ratings three stars out of four (for what that’s worth). Married, five kids, living in an upscale community.

Pleaded guilty last Monday to defrauding insurers and drug trafficking. Finally busted by a DEA undercover plant who made an appointment and received a prescription for Oxycontin for a trivial complaint after a brief interview and no physical exam.


How can this be?  Here’s a hard working guy with a family, trained in the big leagues with impeccable credentials, committed specifically to helping those with pain and suffering.

It’s the old, old story. Herndon entered the world of expensive interests that turned into obsessions exceeding his ability to finance them.  Multiple expensive homes. Big game hunting junkets to Africa. Once he tasted them, it was impossible to go back. He found it only too easy to finance them by alternate means. His waiting room was packed with dirt balls urinating on the walls. His office is said to have taken in US$60,000 cash in one week. Average time interviewing a patient was under three minutes. “Investigators described him as the largest source of illegally obtained oxycodone and oxymorphone in Western Pennsylvania and said his March arrest cut supplies so much that the street value of oxycodone doubled to $40 a pill”.

More importantly, how did he get away with for as long as he did. It was all there, local pharmacists refused to fill his prescriptions for weeks. Herndon told his patients the further they got from Pittsburgh, the easier it would be to get them filled. His patients when squeezed by the police, turned him in as their source. Like Bernie Maddoff, he surely must have known he had a limited time to make this work and presumably tried to enjoy it to the inevitable end.

It’s a scary prophesy with the potential to plague us all. Applicants to medical school are said to be carefully screened for honesty and an authentic  service orientation? Not necessarily. They’re screened for grades, book learning and community service they all commit to because they know admissions panels desire it. They can be all those things but they don’t have to. They know what’s expected and they know how to play the game.  The reality is there is no way to screen out potential Herndons. We just hope for the best.

Physicians have the potential to live the dream, and common sense would dictate a desire and ability to do so within the limits of their better-than-average income and social status. But the cookie jar is always there and it’s always open. Once the taste for La Dolce Vita occurs, it’s a vice that can be hard to regulate.

Herndon will appropriately go to jail and the DEA will continue to ferret out the many similar physicians still out there, some more successfully than others. Some physicians will continue to commit fraud in their billing and dispense anything that brings in cash.  If there is any way to fix this situation, I don’t know what it might be. The rest of us will live the dream also, knowing that the hazards are always present and those hazards don’t necessarily select for the weakest of us. We are all at risk and that bears some recognition.

Career advice from me


Dr. Crippen:

“I am curious as to whether I should pursue medical school, or graduate and post-graduate studies.  I would not be applying to either sort of programs for another two years. I am intending to take the pre-medical course load regardless, however, any insight to the medical field, research, and the realm of neuro-psychology would be greatly appreciated”.

Thank you very much,


I am not currently recommending a career in medicine for a number of reasons.

1.  The amount of money needed to finance a four-year medical education is simply prohibitive.  Most of the kids I know are in for somewhere in the range now of $150,000 or more in loans, all of which come with interest and will take most of their career to pay back. That’s not including four years of college or university.

2.  There is no question at all that the financing of health care is destined to include decreasing resources for providers. The current health care reform plan, if it gets implemented, will instantly inject at least 31 million people into a system already overloaded. There is only one way to finance this increase, pay providers less and have them work more.

The only physicians making big bucks are specialty surgeons doing complex procedures. Neurosurgeons and cardiac surgeons.  The residency programs for these programs are seven and eight years after medical school and they are brutal. They make a lot of money when they get out and they break their asses doing it.

“Most” non-surgical physicians (including neurologists) spend at least three to four years after medical school making yeoman wages and doing a lot of “service” (scut) work for the hospital to justify them getting paid for medical education. Then they don’t make enough money (and will probably less in the future) to comfortably pay off the huge debts incurred.

It’s a radically different world and I have lived and functioned in both. When I was your age, there was no liability in going to college. It was cheap and many kids had little other option other than the military, which wasn’t very popular or getting an entry-level job in some industry that would probably be a dead end. College was cheap, available and socially popular. Everyone that could did.  And when they got out, they entered a job market amenable to “college graduates”.  Didn’t matter what it was, if you had a diploma, you here hire-able because you had the price of admission.

Some time in the late 90s I think, It was found that having a degree in something unrelated to a specific job skill was non-contributory even as a price of admission. So, it slowly evolved that a college degree in functionally inconsequential things like history, English, biology and art appreciation became a very expensive diversion following which one then had to be trained for increasingly skilled employment.

Advanced college degrees are even more iffy. BS or BA degrees, especially in the pure humanities or science are worthless. The amount of money it takes to get an advanced degree with no guarantee of employment is off the screen, and is soon to change the entire spectrum of education if it hasn’t already. Masters Degree isn’t much better unless in the realm of teaching. It takes at least 6 years to get a PhD and can cost $130,000 educational debt. I know some that went a year without getting a job and finally landed one at a private college teaching with a salary of $48,000 a year.  The paybacks for educational loans are $600.00 per month for a LONG time.

If a kid gets out of high school and takes a two-year tech course in auto mechanics, he can get a job immediately and make a reasonable wage to support a family that’s pretty cost/benefit effective.  If a kid goes straight to college and ends up with a Masters 6 years later, he might get a job in a tight market as a high school teacher and make about the same as the mechanic.  But he can discuss Chaucer with his friends at parties and wear a sport jacket out to dinner.  Pay your nickel and take your choice.
That said, there is and always will be a place for higher education.  There will always be those that will rise to the top in any endeavor, but it cannot be counted on. The bad news is its connection to gainful employment is capricious and unreliable.

The reality” – your interest in higher education must eventually be directed toward getting someone to pay you for that knowledge.  That requires some hard scrutiny.  Do you have the resources required to simply make yourself more well read as a matter of personal desire and thirst for knowledge as an end in itself? Are you willing to pay a lot of money to become an interesting conversationalist at cocktail parties?  To rub shoulder with a higher class of friends? If you have the resources, that’s a perfectly OK goal. The issue of making an issue is separate. Or do you want to proceed toward a livelihood that will pay you a living wage?  If so, that requires a separate path, also becoming quite expensive.

In the end, you must work and you must make a living wage to put a roof over your head and food in your mouth. That’s the human condition. And you don’t have an unlimited time frame to get it done. The clock ticks, and the longer you’re out there figuring out what you want to do without actually doing it and getting paid for it, the harder it will be to get moving to it. Trust me on this. I have been there and done all of it.

On The Affordable Health Care Act of 2008



Here is the website for Dr. Levin’s highly biased personal  opinion.



Dr. Levin is a conservative pundit that interprets and spins political issues according to his personal opinion, not accepted as mainstream by many other physicians.


Here is an alternative opinion:  I have read “Obama care” from stem to stern as it will directly affect everyone when fully implemented. Technically it’s formal name is the  “Affordable Heath Care Act of 2008” (AHCA 2008).  The cold reality: there is absolutely nothing in it (except in the mind of Dr. Levin and other wing-nuts) that proscribes treatment for needy patients of any age. What the law does include is an end-of-life facet, commonly misinterpreted, usually intentionally.


The law allows payment for physicians to include discussions of end-life care preferences and what’s available to them, not what they are mandated to do. That means that a discussion of whether such aggressive measures as CPR, endotracheal intubation and mechanical ventilation, dialysis, vasoactive medications to stabilize blood pressure, IV medications for cardiac arrhythmias and other similar measures are desired under the circumstances of admission or if the patient suddenly or unexpectedly deteriorates.


That means that if I land in the trauma bay at age 68, and I’m all other factors equal in pretty good baseline health and I have good family support systems, and I get operated on and I land in an ICU for a while, the discussion of my care would be what modalities were available, what could be effectively applied and what my expected outcome would be. The discussion of  “end-of-life” would ONLY occur to determine my  (prospective) wishes should I suddenly and unexpectedly have a cardiac standstill, or major full hemispheric stroke, or big intracranial bleed…….something that dramatically changed my potential for an  outcome I or anyone else would want. I would have an opportunity to determine what my wishes might be in such circumstances BEFORE I became incompetent to speak for myself. Then that discussion would revolve around goals of care, what it’s surmised that I might want for myself, what my wife would want for me.  Does that sound reasonable?


Would I want to be fully maintained with a tracheostomy, feeding tube  and skilled nursing home admission on the long shot chance I might  unexpectedly get better? Or would I or my wife want to opt for “comfort  measures”, letting nature take it’s course as it will anyway.  It’s all about choice, not demands of arrogant surgeons that some politician is mandating something or nothing.


The “Death Panel” ploy was originated in 2008 by the impeccably ruthless, self-promoting political opportunist Sarah Palin who knows nothing about any health care formulation. Palin took the above and bastardized it to a tortured interpretation.  That discussions of  end-of-life care necessarily allowed the Federal Government to use those  discussions as a foot-in-door, then inform the patient or their family  that the physician would deny care unilaterally by some structured  mandate. She then famously told audiences that Obama would have let her kid with Downs Syndrome die, which should give you a pretty good view of what she’s capable of.  There is not a single syllable in the AHCA of 2008 that even remotely suggests that ANY needy patient will be denied care on the basis of their age or any other objective factor.


And thereby hangs a dilemma.


The United States is the ONLY country in the global village that allows patients and their family’s wishes to drive the health care industry.  That’s good news and bad news. The good news is you can pretty much name your poison.  The bad news is that in allowing this, the cost of health care is unbelievably expensive and increasing arithmetically every year, actually every month.  What that means as a practical matter is that someone somewhere is eventually going to have to start making decisions about the appropriateness of flying 95 year old Hunt & Hess grade 5  (unresponsive) intracranial bleeds to hospitals like mine in helicopters so they can run up a big bill before we stop the nonsense. We have the ability now to pretty accurately access outcome for virtually any disease process. That means that sooner or later, patients and their families desiring extremely long shot cures for vanishingly small outcome potential are going to have to back off or pony up the cash.  Who will make those decisions?


Unlikely I will, nor should I.  Traditionally my role is as a patient advocate. I am expected to defend my patient against the vicissitudes of any bureaucratic body tending to use them as isolated cost-savers. That means that it’s a conflict of interest for me to have anything to do with conservation of resources at the macro level. My job is to do the best I can with what I have to work with. In a perverse way, Palin is right. Death Panels will probably eventually arrive, but it won’t be for the purposes of saving the government money. It will be because it’s medically inappropriate to spend money on patients without a meaningful potential to survive with a quality of life any normal hominid would desire. That day is coming, but it wasn’t Palin that accurately predicted it.


You want to be scared?  I’ll give you a good scare. A family of four,  Mama, Papa both work to make ends meet, two kids both in grade school  making a combined income of under US$50,000/Year. They make ends meet as long as there are no unforeseen emergencies, but it’s tight. In this kind of job market, it’s highly unlikely either of them receive any meaningful health care indemnification from their jobs. Jobs that pay these kinds of wages rarely offer affordable medical insurance. If it is offered, it’s extremely expensive and increasing in price anywhere from 9% to 15% a year. They probably don’t opt for it in order to afford kids clothes and school expenses.  Then the patriarch has a car accident, lands in a trauma bay, ends up in the operating room.  Worse, they look up and and see ME. Neurological injuries are particularly devastating and expensive. A three hour neurosurgical procedure later, they land in  a Neuro-ICU intubated and it takes three days to get them extubated,  then another week treating other disasters, transfer to the ward for  another three days and home but unable to work for a while due to  residual deficits. Then expensive physical rehab.


Now this family is running on ONE income, less than half the funds available before the accident just about what it takes to pay the  mortgage on their modest home. Now they are in a DEEP financial bind, and since the patriarch is not in a union and there is no right to work  law, they give his job to the next in line and he’s out of work. THEN the hospital presents them with a total bill for about US$100,000 and demands a payment schedule be set up about the same as purchasing a  Mercedes. The hospital then issues a legal claim and gets a judgment allowing them to garnish the wages of the one remaining worker.


This scenario happens every day and it breaks my heart. I never send anyone a bill for anything. I am an employee of the medical center and I deal with everyone and everyone that comes my way. I don’t know nor do I care what their financial status is which one of the reasons I’m here. It’s the hospital that acts as the bad guy and they have no problem with it.  It’s cold, impersonal business.


The reason I support the AHCA of 2008 is not because it’s perfect. It isn’t. I support it because it does SOMETHING to rectify the outrageous inequity of people getting sick and ruining the rest of their lives. The AHCA of 2008 adds 31 million hard working needy persons to the roles of an indemnification plan that literally saves their lives in the event of   medical emergency. It forces greedy and heartless insurance companies to quit cherry picking only healthy clients, ignoring those most likely to need medical care, and it also forces them to stop arbitrarily and capriciously refusing to pay for care after it’s already been rendered.  It’s a start and it’s better than what we have now.  You don’t see any members of the aforementioned family out in Tea Party lines carrying  “repeal Obamacare” signs. You see idealists that don’t understand the situation, or don’t care about their fellow Americans.

Because of Clark’s Law, there is a whole contingent out there dedicated to opposing everything and anything the current sitting President does,  including anything that might be beneficial. A lot depends on if he is re-elected, which as a practical matter is likely when the smoke from the Republican circular firing squad clears. If the AHCA clears the Supreme Court, which its likely to all other factors being equal, I think it will be beneficial for the public. If not, the current stockholder driven health care insurance companies will continue to drive the price (profit) to unaffordability for all.


Worried about the cost of the AHCA/2008?  Worry more about the cost without it.  Something like the AHCA of 2008 is necessary to protect the public from exorbitant costs of health care in the USA. The rates are exorbitant because they’re geared to the insurance trade, which pays ten cents on the dollar, so if they bill ten times more than they expect to get, they break even. But for the uninsured, they pay the ten times rate. Access to health care is DIRECTLY related to indemnification.  Paying up front for them is cheaper than paying MORE for them once they put off medical care and get sicker. Because of HIPPA and COBRA, EVERYONE must be treated when they show up.  As soon as they land in an ER, they must be treated, admitted and kept till they can be put back on the street. Taxpayers are going to pay for them in any event. If the health care services get them earlier, the taxpayers pay lass for them.

A Flicker of Consciousness (Review)



A healthy 45 y. man falls from a 3 foot stepladder striking his head, spends some time in a hospital unresponsive, ultimately progresses to unresponsive wakefulness (“persistent Vegetative State”), and is transferred to a skilled nursing facility. The family told not to expect much for the rest of his life, such as it is.  Then after a while, the persistent family gets a second opinion from a group in Belgium specializing in “coma”, and it’s found that the patient exhibits some sympatico with his wife. Emotional responses on command, and interestingly, following his reflection in a mirror (nothing else).

Somewhere Pete Townshend is smiling.

“You don’t answer my call
With even a nod or a twitch
But you gaze at your own reflection!
You don’t seem to see me
But I think you can see yourself.
How can the mirror affect you?”

From “Tommy” (1969)

Nobel laureate Francis Crick took a reductionist view of consciousness, postulating that the ghost in the machine is simply grounded in brain tissue somewhere and when that tissue is damaged, the effect on consciousness disappears commensurately.  Hawking likens the brain to a computer. When the power switch is flicked off, the screen goes black. Mike Darwin says the essence of personality can be cryopreserved and retreived at a much later date.

But the diagnosis of Persistent vegetative State (PVS) seems to be expanding as relatives continue the search for understanding this difficult diagnosis. “Time” says that as many as 40% of patients previously diagnoses as PVS may actually have more interaction of their environment than previously thought, including some understanding of commands but inability to interact with them in traditional manners.

Of particular interest is the occasional patient that improves their alertness following the administration of zolpidem (Ambien), a popular sleeping medication. Ambien is a very effective  omega 1 specific indirect GABA agonist that has been reported to show some effect, but never for long periods and never promoting a regain of functional consciousness. Other studies show no effect.  My personal opinion FWIW is that zolpidem may suppress sub-clinical seizures in some brain injured patients. Just to see what might happen, we have occasionally given an occasional PVS patient that crosses our border a dose, and we’ve never noticed any change at all.

Of course, “Time” then hastens to add that after much study, the subject of this discussion has shown no further improvement and is unlikely to do so.  So their rhetorical question is “have we opened up a big mess identifying an marginal expansion of consciousness that doesn’t mean anything as a practical matter. None of these patients will ever be self sufficient again. What has it gained them or their families that we think they now have some form of nonfunctional cognition?”

Of course, this invariably means that families of all PVS patients will develop a strong interest in having their patients evaluated by lots of expensive tests to see if they might be better than thought, then requesting lots of long term expensive rehabilitation therapy in the hope that in time the patient might have some communicative ability.

This dovetails with the current thrust of neurologists that we are writing off some extensively damaged patients too soon, and if we continue to be aggressive with them longer, we might convert some outright deaths to skilled nursing home admissions.

As I sit here, a Hunt & Hess Grade V patient resides in the NICU, intubated and unresponsive except for a flicker for a week. NS told the family they “might get better in time” if aggressive care was continued. Then the social worker is left to drop the bad news that they have no resources for any of that rehabilitation, and if the patient lands in a skilled nursing facility, they will not even get much basic medical care, much less rehab care and the State will take all the family’s resources to finance it.

My question is and continues to be, who will be willing to pay for this enhanced care of non-functional patients in an economy, and I mean a GLOBAL economy that is quickly circling the drain. As I sit here, reimbursement to reverse active disease processes in potentially viable patients is dwindling and promises to continue.  The issue is not the continuance of aggressive care on the off chance that an unexpected outlier might appear.  the issue is is open ended optimism that in order to select out one true miracle, 99 unfortunates will be condemned to life-in-death of a skilled nursing facility, and who is going to pay for that. Where is the balance?

Xigris pulled from market

  • Let me give you a little history.I go all the way back to CENTOXIN, which must have been mid 90s, wasn’t it?  Centoxin too was a magic bullet that supposedly got between some of the flow products of sepsis and scotched it.  At the time I had a friend who was a Roche (Pharma) Rep and he was always around (back in the day they could actually come into the hospital).  He got all excited about the new company that was making Centoxin (Centocor biotech) who had offered him a big financial package to come to them.  He asked my opinion and my opinion was that he had a good reliable job and this Centocor thing might turn out to be a flash in the pan. And that the magic bullet was being heavily marketed as a magic cure for sepsis, which given the fact that sepsis is a very multi-factoral disorder was highly unlikely. But the lure of was too much and the next time I saw him he was honchoing lots of Centoxin in the unit on a “Compassionate” protocol (giving the stuff away to get doctors used to using it). LOTS of hospital people pulled out their life savings and put it into Centocor stock.

    Then as time progressed, there came an article/editorial in the New England Journal of Medicine stating flatly that Centoxin didn’t work, and was prohibitively expensive even if it did. When the NEJM nails your coffin shut, it stays shut. Within a couple of weeks, Centocor died miserably and everything it touched along with it, including my friend who, having burned his Roche bridge, went back to being a retail pharmacist. I know nurses that lost their life savings.

    Then enter Activated Protein C (Xigris), said to be a higher grade version of Centoxin.  As far as I could see, Xigris was essentially the same as Centoxin only with an infinitely more massive marketing push behind it. Now, at this point I must divulge that I am not a sepsis guy, have only rarely taken care of sepsis patients and I am absolutely not anything close to an expert in the field.  But I started seeing the approaching battle strategy.

    Lilly figured out early that this had the potential to put them into the upper ionosphere of Big Pharma and to get there they were going to have to spend a bundle in marketing.  Mike Hansen will remember that the then Lilly Rep (the lovely and affable Rose) literally walked around the unit and pointed out patients she thought Xigris would be of value. Xigris was expensive enough to support several third world drug lords. The way to circumvent that was to pay a lot of doctors a LOT of money to advertise the drug on speaking circuits and in print. Like many of the articles in Crit Care, thinly veiled advertisements for favorite-son drugs.  And have their Reps assure providers that the effectiveness of the drug was a foregone conclusion because it was desired. The cash flowed and soon the prevailing opinion was exactly that. The drug was a miracle cure because a lot of experts said so in print and in word.  Lilly paid a LOT of doctors to publish and lecture on a LOT of anecdotal evidence that if used early and aggressively enough, Xigris was a strong positive.  They blew off the expense by stating the fact that everything in an ICU was expensive and an extra US$8,000 a day or so was a drop in the bucket, especially if you get a survivor.

    However, it quickly became clear that If every family practitioner or Internist used the drug for all their nursing home victims with UTIs (which is exactly where this was headed), it could easily break the drug budget in a few weeks. So the hospital (SFMC) started ratcheting down who could use Xigris and under what circumstances. The intent was to discourage use by inconvenience, and it worked. By the time any potential user jumped through all the mandatory hoops the patient would be long dead.  So it actually wasn’t used much where I was for that reason. The relatively few times it was used, I was not terribly impressed that I saw any radical turn-arounds.  Any turn-arounds that did occur were, of course, attributed to Xigris.  And there were some bleeding problems that turned up. Then some articles by objective researchers………

    Finally, when a lot of experience with the compound developed, the luster started to wear off (kind of like some of the Republican presidential candidates).  Few in the other parts of the global medical village used it because of the expense and the sparse outcome numbers. Stephen Streat of New Zealand gave some interesting numbers on how many patients it would take to get one survivor, and the money spent to do so would break their bank quickly.  They never used any of it. Then some studies started to show that outcomes weren’t exactly as everyone had been assured, and there were some problems that had been expertly glossed over. But the handwriting appeared on the wall. It only needed to be clarified.

    Then the crash.


    In the end, Lilly spent a LOT of money on this high stakes gamble to get to the top of the heap. How much they recouped will never be known. Those doctors that made careers on this compound inevitably will go on to other miracle cures, What’s the next highly touted medical miracle that doctors are now making careers on?

    >>On 10/25/11 9:52 PM, Timothy G. Buchman, Ph.D., M.D. wrote:
    >>I go back to HA-1A as well. And I was a participant in the study.
    >>And there were a couple of patients who seemed to respond, Lazarus-like.

    I think there was an article a while back on one of the journals, maybe not even mainstream, the thesis of which was that if researchers wanted to believe something intensely enough, they can subjectively prove it in their studies, even if they’re trying to be objective. I tend to believe in the ability of humans to prove what they believe. I do it all the time .

    There was an article in Neurocritical Care recently in which the authors actually did a review f the literature suggesting a bunch of anecdotal evidence that a hematocrit of 30 or above improved outcome in subarachnoid bleeds. Even enhancing hematocrit with 30 day old banked blood that doesn’t carry oxygen, which is of course nonsense.  They then announced that their future research efforts  would prove this thesis!!! Of course it will!

    I’m by nature very jaded about fads. I’ve seen ’em come and I’ve seen ’em go. Again, I hasten to add that I am not an expert in sepsis and I am not a researcher, although years ago I did some bench research on rats with Peter Safar and wrote two papers with him in Resuscitaton that others built on later.  BTW, did you know that the lowly Ratus ratus is God’s favored creature?  Anyone hurting a rat is in big trouble with God. Lots of additional purgatory time per rat. That was in one of the Dead Sea Scrolls a while back. I don’t expect to do well postmortem.

    I’m old enough to have seen fads come and go, and I’m jaded enough not to believe much of the latest iterations thereof at face value. I remember “small bowel bypasses” for obesity that was the supposed cure for obesity and the death and disability that followed. Then came the balloons-in-the-stomach fad that my dad bought into, followed thereafter by the perforations. Now comes the staples and other high tech manipulations via endoscopy for obese patients looking for a miracle cure.  Others see the weight loss. I see the perforations, leaks, systemic sepsis, renal failure, weeks in an ICU and end-stage co-morbidities.  Maybe a few such patients lose weight, are happy and lose their diabetes. I see the ones with perpetual diarrhea, constant abdominal cramps, dietary nightmares and reversals when they’ve had enough. Sorry, surgery guys. despite glowing journal articles, I’m just not impressed.

    I don’t deal with sepsis often, but when I do, I’m impressed that there are a LOT of multi-factorial issues.

    I have had two memorable such patients, both accidental tourists in my unit. One was a big, 300 pound plus biker that trashed his Harley drunk, had multi-system trauma and landed in my unit because there was not a bed available in the Trauma ICU.  Over two months I (and a bunch of other people) got that guy over respiratory failure (I trached him), renal failure (dialysis) and multiple other disasters. He comes back twice since and his wife keeps in touch with me on Facebook. I’m encouraging him to get a three-wheeler and get back on the road (but you knew that).

    The second was a young guy in his 30s from South America here looking for a job as a lawyer who had a AV fistula blow, went down, aspirated and ended up with ARDS, renal failure and all that. The on-call intensivist told the patient’s wife at one point there was little chance the patient would get through the night alive.  I (and a lot of other people) got his ass through the night and he comes to visit me every so often.


    Now the new fad is hypothermia for all ills.  I take heat all the time for this from guys like Kuiper and Darwin. Some of my own colleagues here too. I say again I am less than impressed. I was with Safar when after years of intense study he came to the conclusion that hypothermia was only of value if instituted immediately after a brain insult.  In my bench research with rats, I showed that hypothermia was not protective against hypoxic brain insult.  Look up the cite. It’s in Resuscitation somewhere near the end of the 80s. I’m the first author.

    FWIW, here’s my take on hypothermia.  There were a couple of articles a while back that seemed to show benefit. Some researchers wanted so badly to believe it that they jumped on it with the intent to prove it was true, invoking the Rule of the True Believer. In fact, there is probably a very small group of brain injured patients that might marginally benefit from hypothermia but in 2011 the True Believers are in charge, and their initial research is as optimistic as the PROWESS was initially. One of my colleagues is trying to prove it is beneficial in myocardial infarction.  After a while when more data inevitably comes in, the current belief that hypothermia is a cure all for everything from hangnails to belly button lint will do pretty much the same thing the date for Activated Protein C did. Dwindle. then they will all find something else to hang a career on.

    I know I will get a three page harassment from Darwin no later than tomorrow calling me ten varieties of a philistine and heathen.  But FWIW, hat’ my honest take on it.

Sir Paul McCartney and brain fade


I was struck by an earlier post by Mike about Sir Paul McCartney’s deteriorating prowess as a songwriter and performer.

>Sir Paul McCartney is still writing and performing music.

>Some of his compositions are creditable, and occasionally

>slightly interesting. But they are no longer either fresh or vital.

>This is true of almost all composing musicians and mathematicians

>who enjoy a long career. The raw processing power of youth,

>coupled with preternatural insight, is the basis for almost

>all of the blockbuster, paradigm shifting advances in physics

>and maths. Newtwon was in his early 20s when his

>fundamental insights were made.

Mike seems to say that the McCartney genius faded as he got older. The fresh exciting material of the 60s and 70s was replaced (with age) by reasonable but not stellar material, and Mike seemed to blame this on cognitive deterioration with age.  That’s an interesting concept and I see it in myself.  But I think it’s much more complex than simply isolated brain fade.

If you read Malcolm Gladwell’s “Outliers” *, his thesis is that most of the stars that made it to the top built that success on a platform not visible to the public, and a lot was not directly controlled by the individuals involved, or necessarily a direct result of their brain power. There are interesting accidents of nature that contribute to high levels of success.

For example, a disproportionate number of elite Canadian hockey players born in the first few months of the calendar year go on to hockey stardom. Since youth hockey leagues determine eligibility by calendar year, children born on January 1 play in the same league as those born on December 31 in the same year. Because children born earlier in the year are bigger and maturer than their younger competitors, they are often identified as better athletes, leading to extra coaching and a higher likelihood of being selected for elite hockey leagues.

J. Robert Oppenheimer grew up in one of the wealthiest neighborhoods in Manhattan, the son of a successful businessman, attended the best schools in the City and was afforded a childhood of unusual acculturation and cultivation. Gladwell argues that these opportunities gave Oppenheimer the chance to develop the practical intelligence necessary for success.  When Oppenheimer was a student at University of Cambridge, he made an unsuccessful attempt to poison one of his tutors. When he was about to be expelled from the school, he was able to compromise with the school’s administrators to allow him to continue his studies at the university, using skills that he gained during his cultivated upbringing.

The Beatles performed live in Hamburg, Germany over 1,200 times from 1960 to 1964, amassing more than 10,000 hours of playing time. Gladwell asserts that all of the time The Beatles spent performing shaped their talent, “so by the time they returned to England from Hamburg, Germany, ‘they sounded like no one else. It was the making of them.'”  Bill Gates gained almost unlimited access to a high school computer in 1968 at the age of 13, and spent over 10,000 hours programming on it, bringing him to the point where creating practical software was effortless. Raw talent was not a serious factor in any of these people. It was the path they trod and their ability to persevere.

So I suspect the genius of Paul McCartney was not so much his innate brain power as a youth, but rather an amalgam of his environment and those who contributed, all of which came together by chance.  Most of his greatest work was written in tandem with John Lennon and many uncredited contributions from others including George Martin, without whom the Beatles’ body of work would have been radically different. As the times changed, so did Paul’s potential to create, not necessarily because his brain power faded. Similarly, Lennon didn’t do much in succeeding years. They both inevitably evolved to different styles more mediated by their decreasing energy level and widening awareness of other life issues with age, not so much brain fade.

I think I see it in myself. In my glory days, I think I came up with some very original thought about things I was interested in. Sedation and analgesic issues in the ICU, delirium, and especially ethanol withdrawal. I wrote prolifically and instituted a lot of clinical treatment that I think still works today. Then I got old and I don’t have the same energy level and my ability to learn and retain new things diminished as well. But other facets of my brain function were enhanced with age.

My clinical Fellows are quick, they know all the latest research and medical acumen. They are spry and with boundless curiosity and energy. But there is a lot more to clinical medicine than a knowledge base.   I have spent 30 years at the bedside and there isn’t much I haven’t seen at one time or another. I walk into a patient area and I intuitively know many, many things about a patient I’ve never seen before that the Fellows have yet to learn by experience.  I sense trouble long before it starts. I sense when to hang black crepe with families regarding outcome and when to be more optimistic because I’ve been burned so many times in the past. I sense what will work and what will not, and when to act early and when to hang back.

Judgement. I think this is the value of the aging brain. The experiences of the past congeal to form teachable moments to those coming up the line who MUST achieve that seasoning to survive in clinical medicine. Trial and error doesn’t work well in clinical medicine. The only way to get it is to absorb the decision making processes of those who have been there and see the cause/effect.  Maybe that’s the way the aging brain is supposed to evolve.  The bright flame of youth cannot be sustained because the energy required to maintain it’s intensity isn’t endlessly available, so it’s prolonged at a lower temperature to  extend whatever benefit may be available.

* http://www.gladwell.com/

Variations on an End-of-Life Theme


Really fascinating comments by Mike Darwin about what amounts to variations on end-of-life themes.

I think it’s a reality that the human body is programmed to deteriorate in time, probably led by brain function, anatomically and physiologically. It’s been said that this deterioration is universal and expected and so it’s incumbent on us to do what we can in the limited time we have. I have patients in their 60s that suffer dementia outside of the usual etiology of diabetes, hypertension and multiple stroke.  I routinely see 50 year old guys that look and act like they’re 80. I have had guys stroke big time in their 30s. Some have multi-organ disease, some don’t.  I knew guys that were old men in high school.

But the variation in brain function as the body deteriorates is very remarkable. My mother is 93 years and her body has just about hit the terminal skids. She’s deaf as a post, now wheelchair bound from generalized osteoarthritis. She weighs about 70 pounds now.  But she instantly recognizes me, asks about my family, knows all their names, remembers fine points of the past and I bring her big print books and crossword puzzles that she devours using a big magnifying glass.  My father died at age 90, the day before he had a mild stroke he was wandering around town in a sport jacket shopping for books to read. He was not hypertensive and never took a single medicine in his entire life. He died of anesthesia complications after an emergency operation for strangulated hernia (I suspect).  My paternal grandmother was dating much younger men in her late 60’s, advising them she was 50 and getting away with it. My German professor in college was 93.

Mike and I differ in that I look at life span very fatalistically. I’m acutely aware that I have been graciously given a finite amount of time on this earth and there will be limits to want to get done. And there is little in anything I can do about that. As I age, I find that I can do less and less of what I was able to do when I was 20 or even 40.  It just is what it is, and the benchmark is how much you can do in the time allotted.

Most of my friends who work with the brain are “scientists” who ponder about how the brain “works”. They poke and prod and measure things trying to find out what it means when an impulse moves from one place to another through various neurotransmitters.  Personally, I don’t think any of this matters because it won’t lead to an understanding of what and why we are.  Where the rubber meets the road is what makes us cognitive humans, not collections of neuron circuits. I think the ultimate explanation, if there is one, lies in the realm of philosophy. I try to understand it using a common sense filter.

I suspect there are aspects of the brain that are very computer-like.  Hawking said there is no after-life because when the computer is shut off, it’s function totally vanishes in a volatile fashion. But I’m not so sure.  The human soul is what differs us from dogs and cats, and does not necessarily depend on computer function to exist.  Whether the seat of the soul will be the ghost in the computer is a much more interesting and elusive concept.  It could be argued that person-hood probably has some storage area. Maybe not, but let’s argue that it is unlikely to exist in the ethereal mist. Everything that makes David Crippen or Mike Darwin a “person” is possibly contained in the transfer-RNA of those parts of his brain reserved for memory and storage of experience.  The technology for unlocking this resource and transferring the information to a super-computer does not currently exist but it will in the future, as the development curve for computer power is almost vertical. It’s only a matter of time. As far as that goes, it’s only a matter of time before computers become “self aware” as in the “Terminator” sense, but I digress.

If this information can be uploaded, there is no technical reason why it cannot be downloaded back into another storage area (super-computer?) or (why not?) another brain wiped clean of information. There are people that think this is possible, or will be in the future.  But, does that make David Crippen the same guy that now tutors doctors, drives exotic sports cars, ogles gorgeous blondes, plays in a rock band and tours the world on two wheels?  Technically, it’s possible but I suspect not. The information held in the portion of the brain that serves as the repository of the person of David Crippen is not all there is. I suspect the person-hood of David Crippen is more than the sum of his parts. It is the interaction of the sum of the parts that would not necessarily occur outside the delicate balance in its original setting, even though all the parts were present. Like cutting up a camel and then putting him back together. All the parts would fit but they would not necessarily work the way they did before.

Mike wants a chance to come back and live another lifetime, maybe an infinite number of lifetimes. The potential to do that is unlikely but possible. I’m not sure at all that I would want to do that as the same person that I am now. I have managed to pack a lot into my life and plan to pack in a lot more before age incapacitates me. But I think I will be happy with what I can do in a “lifetime”, for a lot of reasons.

I think if my brain were reconstituted from it’s current iteration by transferring all my t-RNA (constituting my memories) into a super-computer and then downloading it into a wiped clean brain, there is no guarantee that I would emerge as me.  My memories are not necessarily my soul, and there is no guarantee that my soul can be localized, accessed and reproduced. I am a creature of my present, an integral part of my present. There is no guarantee that I would not find a future to be like an LSD experience, an untenable psychosis in which I would not be able to participate. It has been my experience that many people I have known welcome death at an advanced age. They did what they did and the time came.

On the basis of my family history, I suspect I will live to my 90s.  I’ll probably dance on Darwin’s grave. If I do, I think I will accept the inevitable deterioration in my persona and do what I can with what I have to work with. It isn’t out of the question that someday I may reside in a personal care home for no other reason that I won’t be able to take care of myself. I’ll hang photos of glory days on the wall and hope my vision and hearing will allow a laptop that I can keep an eye on what’s happening in a world I can no longer participate in. I think I would be happy with that deal, all things considered. I don’t think I would be capable of starting over. I had my shot at it, I took it and when the time comes, it must be given up gracefully, ever thankful for the opportunity.

On the nature of death and personhood


Most of my friends who work with the brain are “scientists” who ponder about how the brain “works”. They poke and prod and measure things trying to find out what it means when an impulse moves from one place to another through various neurotransmitters. I don’t think any of this matters because it won’t lead to an understanding of what and why we are. I’m interested in where the rubber meets the road, especially what makes us people, not a collection of neuron circuits. Hammaroff is trying to explain philosophical concepts using physics. I didn’t think that was possible the first time I heard it, and I still don’t. I think the ultimate explanation, if there is one, lies in the realm of philosophy. But I’m not smart enough to understand much really involuted philosophy, and certainly not physics since I can’t add two and two three times and come up with the same number. I try to understand it using a common sense filter.

Having said that, I suspect there are aspects of the brain that are very computer-like, and those secrets will be unlocked in the future. Whether the seat of the soul will be the ghost in the computer is a much more interesting and elusive concept. Person-hood probably has some storage area. Maybe not, but let’s argue that it is unlikely to exist in the ethereal mist. Everything that makes a “person” is possibly contained in the transfer-RNA of those parts of his brain reserved for memory and storage of experience. The technology for unlocking this resource and transferring the information to a super-computer does not currently exist but it will in the future, as the development curve for computer power is almost vertical. It’s only a matter of time. As far as that goes, it’s only a matter of time before computers become “self aware” as in the “Terminator” sense, but I digress.

If this information can be uploaded, there is no technical reason why it cannot be downloaded back into a storage area (super-computer?) or (why not?) another brain wiped clean of information. There are people that think this is possible, or will be in the future. Cryonicists are involved in the practical aspects of this, and currently there are about 150 severed heads reposing in liquid nitrogen awaiting the day. (Am am not a Cryonicist myself but I understand the theory because I have friends that are passionately involved).

In so doing, all memory and experience would be restored in a different brain. Does that make the same individual that now tutors brainiac graduate students in physics? Technically, it’s probable but I suspect not. The information held in the portion of the brain that serves as the repository of the person is not all there is. I suspect the person-hood is more than the sum of his parts. It is the interaction of the sum of the parts that would not necessarily occur outside the delicate balance in it’s original setting, even though all the parts were present. Like cutting up a camel and then putting him back together. All the parts would fit but they would not necessarily function the way they did before.

We have very issues in deep in clinical medicine that blend into philosophy and even morality. The issue of organ donation for transplantation is quickly heading in this direction. For the moment I will simplify it for you. Traditionally organs are only donated after brain death, which is defined as clinical death by law and by current social agreement. Recently, another way of defining death has become popular, that of “cardiac death”, when the heart dies, the brain eventually dies, and so it’s death once removed. Again this is complicated, so trust me on this for a while.

The maxim is that when the heart dies, brain death is inevitable so the patient is “dead enough” to offer up organs for donation. But the key to brain death is “irreversibility”. By statute, the brain must be irreversibly dead become clinical death occurs. But with cardiac death, the brain may or may not be irreversibly dead. We don’t know because we don’t try to resuscitate the patient after cardiac death occurs. This brings up an interesting philosophical question involving cryonics.

Consider this interesting thought experiment.

The drill that occurs in the initiation of cryopreservation is interesting. The dying process is monitored and observed and then the patient is officially pronounced dead by a physician. At that point the patient is very legally dead. Once that pronouncement is made, the patient becomes a cadaver, and the rules for dealing with cadavers are quite different than with live humans. The concept of “consent” changes (a patient cannot consent to be dead at a finite point, but once dead, the family can order up just about anything). The consent for the cryopreservation kicks in (illegal before death). The cryopreservation team springs into action and “resuscitates” as much as they can to insure the best possible tissue condition for the procedure of preserving enough brain function to someday retrieve t-RNA and other goodies from the brain. This involves restoring blood flow to the brain ASAP. A mechanical CPR device is quickly brought to bear and “effective” CPR is initiated, creating forward flow of circulation. Inotropes and vasopressors are brought into play. The cadaver is intubated and placed on mechanical ventilation.

Now it gets interesting. In many instances, the cadaver “wakes up” following this treatment. Pupils respond again and spontaneous motion occurs. In many cases they use the potent sedative 5-hydroxy GABA (brought in from Mexico) to stop moving them around. Then the major artery and vein are cannulated and the preservation brew is circulated through the tissues to protect it from ice crystals during the freezing process with liquid nitrogen.

Was this patient really “dead”? Sure he was. He was officially pronounced dead by a licensed physician. A patient is dead when his doctor says he’s dead. The morgue and the Conqueror Worm await. Is the person Is morally, ethically spiritually, physically, positively, absolutely, undeniably, reliably and most sincerely dead? That’s a lot more arguable.