Showing posts sorted by relevance for query ketamine. Sort by date Show all posts
Showing posts sorted by relevance for query ketamine. Sort by date Show all posts

Friday, August 27, 2010

club drug as antidepressant


Good morning. I would like to expose myself. No, wait, there's more!

I would like to expose myself as a person who knows and understands things scientific in a very limited and prejudicial manner. It's just the truth --my capacity is in the realm of the pseudo-, of pretense.

Of course, this being my blog, and this blog representing my real interests, when I present medical information pertaining to CRPS/RSD, I try to educate myself enough that I am not, at the least, being irresponsible.

Okay, okay, except perhaps as pertains to Jose Ochoa, who is clearly a turd but I don't see passing that fact on to my few readers as even remotely irresponsible. It's more like a Public Service Announcement.

I am trying to say that I am more humble than you might think when I set about to read and digest medical studies/announcements.

Even so, sometimes I just want to scream, and possibly shake someone silly.

On the off chance that some CRPS-related information is listed under the search term ketamine, one of my medical feeds checks for daily references to the drug. Most studies relate either to abuse of ketamine, its deleterious side effects, or to proposals of novel uses for the anesthetic.

Today? Well, there is something on the harmful effects of ketamine on the urinary tract ("a new radiological challenge"!), a bit about partial tripolar cochlear implant stimulation in ketamine/xylazine anesthetized guinea pigs, a veterinary medicine label update for KETAMINE HYDROCHLORIDE injection,/solution ("for Intramuscular Use in Cats and Subhuman Primates Only"!), and something about how ketamine can reverse "the expression of tolerance to the anticonvulsant effects of morphine."

Not stuff terribly applicable to CRPS;  Not stuff terribly accessible to a non-medico such as myself.

But then there was this -- An article in Nature, titled Neuroscience: Quick mood lift, with this come-hither statement serving as tantalizing abstract:  Patients taking traditional antidepressants have to wait several weeks for the drugs to kick in. However, a few severely depressed patients taking ketamine, an anaesthetic and recreational drug, have shown improvement within hours.

Okay, so I don't have a subscription to Nature... and cannot access the current edition without forking over $32.  By a search of the terms ketamine and antidepressants, limited to the past week, I feel pretty confident that I understand the claims of the Yale researchers.

A quick search of the journal finds this Nature article -- from 2006, about another study (at the National Institute of Mental Health) that revealed the exact same results and engendered the same excitement:

Club drug finds use as antidepressant:  Psychedelic ketamine hits the blues surprisingly fast

The 'club drug' ketamine may be the fastest-acting antidepressant ever tested, researchers report today.

A team based at the US National Institute of Mental Health (NIMH) in Bethesda, Maryland, studied ketamine in 17 people with major depression. All the subjects had failed to respond to treatment with standard antidepressant drugs or more drastic methods, such as electroshock therapy. But 71% felt better the day after taking ketamine, and 35% still felt better a week later. None improved when dosed with a placebo.

Most striking, the scientists say, was that some patients felt better less than 2 hours after taking ketamine. Currently approved drugs can take weeks to remedy depression. The work is published in the Archives of General Psychiatry.

"It's almost like there's a sound barrier for those us who do depression research, and we have not been able to break it," says Carlos Zarate, chief of the mood and anxiety disorders research unit at the NIMH, and first author of the study. "That's the exciting part of this — now there is evidence that we can."

Zarate and his colleagues are not advocating that doctors start giving depressed patients ketamine right away. Large doses of the drug can cause brain damage in rodents, and its long-term health effects have not been studied in people.

"We don't want to give anyone the message to run out on the street and use ketamine," says Nuri Farber, a psychiatrist at Washington University in St Louis, who was not involved with the work. "It makes you crazy — that's why it's a banned drug."

Scientists are currently testing a wide range of recreationally used-and-abused drugs, including ecstasy (MDMA; see 'The ups and downs of ecstasy') and psilocybin, the active ingredient of magic mushrooms, as potential therapeutics.

Ketamine, invented in 1962 as an anaesthetic, is chemically related to phencyclidine (PCP), also known as angel dust. Both induce hallucinations and out-of-body experiences, hence their use as illegal psychedelics.

Ketamine has milder psychotic effects than PCP and is therefore also used as a legal anesthetic and horse tranquillizer. Scientists are studying whether it can be used to treat alcoholism and chronic pain, as well as depression.

Ketamine targets a brain protein called the N-methyl-D-aspartate (NMDA) receptor. Existing antidepressants target brain chemicals such as serotonin, but there is growing evidence that these drugs eventually affect NMDA receptors. Ketamine may work so quickly because it takes a short-cut straight to this part of the brain.

The psychotic effects of ketamine, such as euphoria, wore off before the antidepressant effects kicked in, Zarate's team found, suggesting that the drug's psychotic and antidepressant effects are separate. One surprising aspect is that other drugs that induce euphoria, such as cocaine, usually lead to a depressive crash once the high wears off.

Zarate's group is looking for substances with some of the chemical properties of ketamine, such as the ability to target NMDA, without the psychedelic effects.

Oh, well, good.

Worried about, ummm, side effects?  No sweat!

Other scientists, including Farber, have developed drugs that can be taken with ketamine to damp its side effects. Giving these drugs together might help patients feel better without getting high.

Of course, in the same issue, there's an article about "what it means to be an ant."

"It's like a magic drug — one dose can work rapidly and last for seven to 10 days," said Dr. Ronald Duman, professor of psychiatry and pharmacology at Yale University, who led the study.

Oh, dear Lord.

One final admonition -- to myself. Keep an open mind. The Ketamine Coma protocol for intractable CRPS has actually allowed some people to mumble the C-word -- cure.

Remember, too, though, that there have been deaths and other bad outcomes in both the Mexican and German research sites.

That ought to attest to the horrors of this disease, that people are willing to be injected with ketamine in an amount sufficient to maintain a coma for 5-7 days, risking their lives to have a chance at lessening the pain of CRPS.

Hmmm.  Here's a thought:  Maybe I should try putting myself in the place of someone so depressed, clinically, that they, too, would choose ketamine...

But I would still find this research more bother than boon.

I still want to shake someone silly.

Sunday, January 30, 2011

Premonition of Civil War

Salvador Dali, Soft Construction with Boiled Beans (Premonition of Civil War)

Okay.  This is where things stand:  After considerable confusion about names, addresses, phone numbers, and staffing... I was able to call the interventional pain center that is reportedly doing low dose ketamine infusions for CRPS/RSD.  That was about 3 on Friday afternoon.  The office was open until 4:30 pm but my call went to voice mail and I left a message. 

Then, of course, I started cooking something fantastically difficult.  I was also in serious pain, thanks to being over-emotional and moving around more than normal.  I don't know if I have mentioned that my right hip replacement, soon to have its 10-year anniversary, is, well, messed up and very painful -- the belief is that there's a post-replacement BooBoo.  Very painful.  Making sitting a nightmare.  It's called a periprosthetic femoral fracture.  (Turns out I did mention it.  What are the odds?)

The point being that I have to limit my time in the wheelchair and maximize my time with legs [carefully] elevated. 

So going full-speed ahead for four hours in the kitchen is kind of contraindicated.  If you've ever wondered why I cook so many things in stages, that's why!  I can rest while a dough rises.  I can rest while a protein marinates.  While something bakes, I'm in bed.

Not this past Friday.  In lieu of doing what I should have, I made ridiculous side dishes, each preceded by an intricate mise en place.  I made a sauce for everything on my menu, damn the calories, damn the weirdness.  I washed, dried, and put away every dish.  I washed things that weren't dirty. 

I even started a "kitchen" load of laundry, because God loves a clean oven mitt.

The phone rang twice.  Neither call was from the interventional pain center, confirming that they do subanesthetic ketamine treatments, that these treatments were custom-made for me, that we could start first thing Saturday morning, and that I'd be walking, dancing, twirling by Sunday evening.  Instead, I spoke with a flooring company and we agreed to a Monday morning delivery of 60 boxes of flooring, with installation scheduled for this upcoming Friday.  I told Fred that next Friday was *perfect* for me, as I would be cured of CRPS by then.  Unfortunately, I added, the installation schedule was going to interfere with my plan to win the Australian Open.  I was going to have to let Na Li take my place in challenging Kim Clijsters and allow the tournament to finish up a week early.

Luckily, changing my plans for swimming the English Channel (scheduled for the 7 - 8:30 Saturday morning activity block) didn't inconvenience anyone beyond the captains and stewards of Captain Haddock's private jet.  Clearly, I need to schedule more individual sporting championships -- out of simple courtesy to family, friends, fans, and support personnel.

So they didn't call.  So I served a many-coursed, complicated dinner that no one really wanted.  So I became terminally crabby, as well as, it sometimes seems, eternally depressed.  So Fred seemed not to be able to reference ketamine without also saying "horse tranquillizer." The first time he neighs, his ass is grass...

My go-to guy of MDVIP fame finally answered my middle-of-the-night email from Thursday.  Do you wonder why I trust this man as much as I do (never mind that he has saved my life a couple o'times)?

No worries. I agree with you about making the consultation visit and really seeing for yourself what it is all about. You are well read and educated on much of this stuff and you are very astute and I believe you will get a feeling one way ot the other whether this is right for you or not. I do know that group and I do have a few patients that I've shared with them and I personally have never had an issue. Give it a try...

That went a long way toward helping me to calm down.

I'm a stute!

In addition to being freaked out over the prospect of entering ketamine treatment, I failed to anticipate one of the more interesting things that happen when I am on the antibiotic regimen... my blood sugars, high from the impact of infection, DROP dramatically.  That's one of the reasons we're doing it, in fact.

An intelligent person, someone who was really A Stute, would have refrained from injecting herself with her usual 70/30 insulin.

It's just that the first two times on the antibiotic, the change in blood sugars happened on the second or third day. My numbers, this time, did not plummet so soon... it took a week. Still, I should have switched over to regular insulin only, and stayed away from the long acting stuff. Live and learn. And learn again. Then, in my case, relearn.

I have spent many hours reading... reading about the original protocols from Dr. Harbut, reading Dr. Schwartzman's studies, reading patient stories. Every so often, I make myself read something from the anti-ketamine crowd, a crowd that is not unsubstantial.

I can't ignore those who think it is too dangerous, too untested, too much of a question mark... because, though he doesn't press the point right now, that's Fred's opinion. {whinny::whinny::neigh::neigh}  Also, it turns out, the opinion of my half-sister, though she knows little about the technical, medical side of things. She said she did not want to have to come here to hurt someone. I'm still not sure whether she was referencing moi, The Stute, or the ketamine-wielding doctor in question.

I cannot seem to rein in [sorry] my wild hopes, though. What if my new insurance coverage won't recognize it as a valid treatment? What if my mind goes on a hike during the infusion, and doesn't come back? What if I am one of those who does not respond? What if I respond, but the pain comes back within a few days?

There is one poor man who worked hard to raise the $30,000+ for a trip to Germany and the ketamine coma treatment.  It was difficult and he had a slow recovery, but he was pain free for the first time in a decade.  He and his family travelled a bit around Europe afterward, and life was suddenly, amazingly, full of promise.  They boarded a plane a few weeks post-treatment and flew into JFK in New York.  He collected his luggage, a simple thing that he couldn't have done before ketamine, and headed out to find a van for the trip home.

He stubbed his toe.

Within minutes, his CRPS/RSD was active again, his foot and leg already changing color, becoming cold, the burning, burning, burning was back.  The stabs, the shooting pain.

True story.  A story I am trying to sit with for a few minutes each day.  Something has to keep me grounded.

American RSDHope, a website/organization that I have never much liked, has an entire section online dedicated to Patient Stories about ketamine treatment -- both the coma therapy and the subanesthetic version.  I think that I may have mellowed since the last time I visited American RSDHope, or they have become more responsibly cautious.  Whatever -- if you are looking for experiential reports, go there.

Below is a list of what I have read so far, the content of which is often redundant -- a redundancy that is both reassuring and frustrating.  Virtually all of it is available over at RSDSA, the site that remains, in my opinion, the most trustworthy of CRPS organizations. Excuse me for not giving the full citations.

Overview of Ketamine Infusion Therapy

Multiday Low Dose Ketamine Infusion for Treatment of CRPS

Use of  oral ketamine in chronic pain management

Ketamine in Chronic Pain Management:  An Evidence Based Review

The neurocognitive effects of 5 day anesthetic ketamine for treatment of refractory CRPS

Safety and Efficacy of Prolonged Outpatient Ketamine Infusions for Neuropathic Pain

Two Approaches to Ketamine Move Forward for Complex Regional Pain

Ketamine Treatment for Intractable Pain in a Patient with Severe Refractory Complex Regional Pain Syndrome:  A Case Report

Ketamine Provides Effective and Long Term Pain Relief in Patients with CRPS Type I

Efficacy of Ketamine in Anesthetic Dosage for the Treatment of Refractory CRPS: An Open Label Phase II Study

Ketamine:  Does Life Begin at 40?

Gambling on experimental treatment for pain

Glutamate and the Neural Basis of the Subjective Effects of Ketamine

Intravenous Ketamine for CRPS: Making Too Much of Too Little?

Outpatient Intravenous Ketamine for the Treatment of CRPS: A Double Blind Placebo Controlled Study

Effect of low dose intranasal (s)-ketamine in patients with neuropathic pain

Trapped in a Medical Nightmare: NJ woman travels to Germany for banned medical treatment, ends up fighting for her life

Update on CRPS (Johns Hopkins 2004 Annual Pain Meeting)

Update on low dose ketamine infusions
 
CASE REPORT:  Complete Recovery From Intractable CRPS Type I Following Anesthetic Ketamine and Midazolam
 
Relief for Worst RSD May Lie With Ketamine Coma


What if I get the call tomorrow, and what if they say they aren't doing ketamine infusions?  What if I get turned away because of co-morbidities?  What if it is inaccessible due to cost?
 
I can't allow myself to entertain this not happening.  I deserve a shot, a chance.  Oh, please, please, please... let this happen, let me try, let me at least try.
 
In the meantime, The Manor needs cleaning and straightening.  Fred is defrosting a couple of Wild Beast Loins.  It is a beautiful sunny day, and if the yeast will proof, I see deliciously fragrant homemade bread in our near future. 

Thursday, January 27, 2011

ketamineketamineketamine

i'm too tired to go into it at the moment, but it looks like i may have a chance to get ketamine infusion treatments (the "awake" version) for crps. 

the problem? 

(and you know there has to be a problem.)

the two docs doing it are... less than pristine, far from stellar, not exactly objects of admiration. 

as the referring health practitioner put it, they are "cowboys."

one had his license revoked for a few years and has multiple medmal settlements.

the other is a D.O. not well liked by his patients, and is really into the ka-ching-side of pain management -- procedures, procedures, procedures. costly intervention!

 however, on the plus side?  the referring health practitioner reports that he "used to be cute."
(well, that settles it.)

additional problems?

(and you know there have to be additional problems.)

getting anyone in my life on board to be supportive about ketamine infusions.  i will need support -- logistically, physically, emotionally.  also a problem?  pitching this to my "go-to" group of doctors, all of whom are less than keen about ketamine anything, much less intravenous infusions of it done on purpose, repeatedly!  i expect resistance based on the unresolved osteomyelitis/infected prostheses and a couple of other persnickety comorbidities.

should i start a petition?  a write-in campaign? 

if i want this treatment, if i can get insurance coverage for it (oh, yeah, i forgot to mention that as a potential problem... mwa ha ha), what does it matter what my "team" thinks?  or my life partner? 

or even la bonne et belle bianca castafiore

i remember when the prospect of "only" receiving temporary and incomplete pain relief was a prospect not deemed worthy of pursuing.  now that i have a good dozen viable suicide plans, "temporary and incomplete" sounds downright enticing.

fred's only comment thus far relates to the probability of hallucinations during treatment... i keep trying to tell him that i doubt he'll be able to notice much of a change.

i'm grateful to the kind practitioner who told me about this today.  she risks putting herself in the middle of an uncomfortable and unsupported referral.  i am enormously grateful that she took the risk. 

i don't quite understand why the availability of "awake" ketamine infusions for crps/rsd in this region of tête de hergé isn't being shouted from our elevated medieval slate rooftops... but if it works out for me, i'll be yodelling the news throughout hill and dale.

from the Holy Wikipedia entry on CRPS:
Ketamine, a potent anesthetic, is being used as an experimental and controversial treatment for Complex Regional Pain Syndrome. The theory of ketamine use in CRPS/RSD is primarily advanced by neurologist Dr Robert J. Schwartzman of Drexel University College of Medicine in Philadelphia, and researchers at the University of Tübingen in Germany, but was first introduced in the United States by Doctor Ronald Harbut of Little Rock Arkansas. Doctor Harbut and Doctor Graeme Correll (of Queensland, Australia) first began studying the use of ketamine in the treatment of CRPS patients. Dr Harbut's first CRPS patients in the USA were successfully treated in 2002 with the low-dose ketamine infusion; also called the "Awake Technique" and he soon began work with FDA on an approved protocol. In early 2003 Dr Harbut began sharing his treatment methods with the Doctors at Drexel University College of Medicine, including Doctor Schwartzman. The hypothesis is that ketamine manipulates NMDA receptors which might reboot aberrant brain activity.


A 2004 article discussing ketamine infusion therapy states, "Although ketamine may have more than one mechanism of action, the basis for using it to treat CRPS may reside in its strong ability to block NMDA receptors. Experimental evidence suggests that a sufficiently intense or prolonged painful stimulus causes an extraordinary release of glutamate from peripheral nociceptive afferents onto dorsal horn neurons within the spinal cord. The glutamate released, in turn, stimulates NMDA receptors on second-order neurons that produce the phenomena of windup and central sensitization. It is reasonable to consider that, by blocking NMDA receptors, one might also be able to block cellular mechanisms supporting windup and central sensitization [4–7,15]. Ketamine is the only potent NMDA-blocking drug currently available for clinical use. Our interpretation is that an appropriately prolonged infusion of ketamine appears to maintain a level of ketamine in the central nervous system long enough to reverse the effects of the sensitization process and associated pain."[41]


There are two treatment modalities; the first consist of a low dose subanesethesia Ketamine infusion of between 10–90 mg per hour over several treatment days, this can be delivered in hospital or as an outpatient in some cases. This is called the awake or subanesethesia technique.

Monday, April 6, 2009

P R U R I E N T ::: I N T E R E S T


I did not lie.

But my interest was prurient.

If I were to want a rhyme, The Oxford Dictionary of Rhymes provides me guidance:

prurient • abeyant , mayn't • ambient , circumambient • gradient , irradiant, radiant • expedient...recreant • variant • miscreant •Orient • nutrient • esurient , luxuriant, parturient, prurient • nescient , prescient •omniscient •

The meaning of "prurient interest" brings out the big guns, too, less interested in rhyming. From The Oxford Companion to the Supreme Court of the United States (2005):

Miller v. California, 413 U.S. 15 (1973), argued 18–19 Jan. and 7 Nov. 1972; PARIS ADULT THEATRE v. SLATON, 413 U.S. 49 (1973), argued 19 Oct. 1972, both decided 21 June 1973 by vote of 5 to 4; Burger for the Court, Douglas, Brennan, Stewart, and Marshall in dissent. Miller v. California articulates the test for obscenity that resolved the dilemma of First Amendment protection for allegedly obscene materials first identified in Roth v. United States (1957). Chief Justice Warren Burger's majority opinion stated that material could be obscene only if “(a) the average person, applying contemporary community standards, would find that the work, taken as a whole, appeals to the prurient interest; [and] (b) the work depicts or describes, in a patently offensive way, sexual conduct specifically defined by the applicable state law; and (c) the work, taken as a whole, lacks serious literary, artistic, political, or scientific value” (p. 25).

I did not lie. I did not tell the truth. My interest was prurient. And I don't want to make a poem with "prurient" as my major rhyming scheme.

Okay, I will tell *you* the truth.

On March 16, I sent the following email:

hello,

you don't know me -- i just saw the message you left on andrea's myspace page. i have crps, too, and had just discovered her fighting4us site when she died down in mexico. you surely don't have to answer this, and perhaps you don't even know yourself -- but what happened? i have been looking into the ketamine coma treatment -- but now that someone has died in connection with it, i don't know anymore.
can you shed any light on whether or not it was the treatment that harmed her or was this just CRPS/RSD doing its dirty work?

sincerely,
the retired educator


How dare I intrude on the death of this lovely girl? Why can't I leave it -- her -- alone, in peace? In part, it is because of the evident lack.

There is nothing but silence around this death, hardly anything beyond the barest of acknowledgements.

Or the most private of them. The nearest and the dearest. And to them, I apologize -- no, rather I beg pardon, for this prurient interest -- not in Andrea, but in what happened *to* Andrea.

The ketamine coma trials... that is what we are made to say, you know -- "the trials."

How many other legitimate "trials" cost well over $50-60,000? How many other legitimate trials cost ANYTHING?


How many other legitimate "trials" suffer a death and allow it to pass into silence, unexplained?
There has also been a high incidence of infection, particularly respiratory -- aspiration pneumonias.

Oh, and how many "trials" make way for someone to repeat the treatment, the benefits of the first time around apparently not having lasted? How was that expressed in the data collection of the second coma? Was the first treatment before the days of the "trials"? You know, back when a person basically only had to produce the money, and be sufficiently young and healthy (beyond having CRPS)? Wait... am I getting it all confused? Because it sure seems like today's requirements are eerily... no, *exactly* the same -- young, otherwise healthy, cash in hand.

My prurient interest has its roots in anger and envy -- as well as in a more legitimate need for information that was not forthcoming from those running the programs. Andrea was getting a second shot at curing or, at least, pushing into remission, her CRPS -- and at a point in time where there is a 2-year waiting list.


Anyway.

I read everything that Andrea ever published on the internet concerning CRPS. She was dedicated but had bought into the demonization of the disease -- it was an actual evil entity to her. This happens in people with CRPS -- because of deleterious effects to the limbic system of the brain? Because of simple human frustration? What can you trust when your own body systems do nothing but lie to you? She cared, and was ferocious in her caring. And she was naive. Childlike.

Her friend wrote me back just this morning.

hi, sorry it took me some time to get back to u ,, i dont check this email offten,.. ok what happend with her was,, from birth she had a bad heart, when she was younger she had surgery to fix it, but with any heart problem eovn if u fix the prob u still have to watch it,, this was her second time getting the ketamine comma treatment done... the first time was great, no probs or issues,,, this last time though, after menay years of fighting, she was 12 when she got the rsd, and died at the age of 24/25 , and all those years of fighgting and medications and the rsd itself, her heart jsut couldnt handle any more and gave out on her... so it wasnt exsactly the ketamine that killed her, it was a combo of evry thing and honestly we all belive evon if she hadnt done the ketamine, she would have died shortly ,,, most people dont realize 1, cause its sugar coated and not spoke about much, 2 doc really dont have any clue when it comes to rsd, unless u haev one that specializes in it, 3 alot of people dont want to belive it and rather live in denighel... rsd can and for the most part the longer u have had it for the more likely it is to happen... effect your internal organs. ive had my rsd for about 3 years now.,.. and its effecting my heart. ive seen the same doc she was seeing.. and he jsut said i haev very agressive and advanced rsd.. and that most likely the ketamine coma wouldnt work for me, but dosnt mean i shouldnt at lest try it.. i have 2 other friends who have done the ketamine infussions. 1 it did nothing for the other it did help almost 90% at getting ride of the pain.. but about 9 months later shes back to as if she never had the infussion... pls dont let the idea of death scare u away form any ketamine treatment...
jsut like the meds we take evryday to help treat our rsd. theres no garentee ur not gonna die form it.. jsut like rsd itself,. in the end it attacts ur own immune system form it and at that point well, its up to u and god... so pls dont let a death scare u/.. rsd isnt easy its scary and not fair and evry miss understood.. the ketamine treatments should not be taken lightly, but nore ignored becuse there have been a problem here or there. rember there were other outside sercomstance that played a role in her dying...
what i tell people who are wanting to do the ketamine treatments but are scared is
u have to stop and ask urself. r u to the point of death as far as taking ur own life in your hands, becuse u have tried evrything ealse possible and nothing has worked, and the ketamine treatments r the last thing, u have left to try.. and if ur answer is yes.. well then u have to make peace with the idea that, this may help it may not, its not 100% safe, but yet u could get hit by a car infornt of ur house in the moring.. also.. if ur about to take ur life becuse the pain is that bad and nothing has worked, really what other option do u have.. than trying ketamine treatments and hopeing for the best, knowing theres a possible risk, or jsut saying nope im giveign up not doing anything more, go into a big depression and kill ur self

2, if u have answerd no to the question., dont do the ketamine treatments, 1 there not coverd by insurance, cost a lot of money, its like a last resuslt thing. evon though it has had the best results, its still a last result. do each and evry other treatment recomende for rsd first evon more than once before trying the ketamine,, sometheing less shocking to the system is always best.. when u have done all the treatments and nothings worked, then that is when u go for the ketamine treatments,,,
i hope this has been helpfull, i dont know how long u have had ur rsd, were it is and how old u are,,, along with what u have tryed and havent for treatments, ive in a way become like a master at knowing rsd and what it dose and and wht can be fdone for it, seeing as my rsd in only almost 3 years is now infected over 50% of my body.. ( liek doc says i have very agressive rsd, apprently its more rare thann rsd, i dont know i jsut know its bad and suckslol) maybe i may beable to help u, with advice things to try, or simply just some one to talk too


this last time though, after menay years of fighting, she was 12 when she got the rsd, and died at the age of 24/25 , and all those years of fighgting and medications and the rsd itself, her heart jsut couldnt handle any more and gave out on her... so it wasnt exsactly the ketamine that killed her

Mercy. Oh, mercy me.

I wrote and thanked her, my prurient interest gone absolutely cold dead.

Tuesday, August 31, 2010

Poststroke CRPS and Even More Ketamine

Good evening. I just watched President Obama clench his jaw and look like his head was going to explode, as he "turned the page" from the War-That-George-Started, which prompted neglect-and-wreck of our financial, health care, and educational systems... all of which he inherited.

All together now: Thanks, yes, thanks a lot, George W.!

All together now: Please, oh please, President Obama, don't have a stroke over George W.! Turn that dang page, dang it!

Why, speaking of strokes... the first of today's CRPS installments deals with Poststroke CRPS. Feeling much like Sergeant Schultz -- "I know nothing!" -- I did a little background reading. I recommend:

Complex regional pain syndrome underdiagnosed: CRPS type 1 is an under-recognized problem in limbs recovering from fracture or immobilized post-stroke
Journal of Family Practice, June 2005

From thalamic syndrome to central poststroke pain
G D Schott
Journal of Neurology, Neurosurgery & Psychiatry 1996 61: 560-564
(You can register at jnnp.bmj.com and have free access to articles before 2006)

If you aren't already confused about terminology, one web site I scoped out informed me that CPSP (Central Post Stroke Pain) is a type of CRPS... that used to be called Thalamic Pain Syndrome (also known as Dejerine-Roussy disease, of course!).  If Wikipedia's description of Thalamic Pain Syndrome is accurate, I am not sure that it so, despite a similarity of symptoms.  If *you* can clarify this for me, please leave me an elucidating comment!


Thalamic syndrome (or thalamic pain syndrome) is a condition that can be associated with inadequate blood supply from the posterior cerebral artery. It is a rare neurological disorder in which the body becomes hypersensitive to pain as a result of damage to the thalamus, a part of the brain that affects sensation. The thalamus has been described as the brain’s sensory relay station. Primary symptoms are pain and loss of sensation, usually in the face, arms, and/or legs.

Pain or discomfort may be felt after being mildly touched or even in the absence of a stimulus. The pain associated with thalamic syndrome may be made worse by exposure to heat or cold and by emotional distress. Sometimes, this may include even such emotions as those brought on by listening to music.
In all of the hour's worth of reading about Post-stroke CRPS, there was a disturbing reiteration of things like "sympathetic blockade" -- about which I have raled before.  Progress in understanding the etiology and processes of CRPS is now directing the treatment response away from a focus on sympathetically-mediated pain.

Anyway... here is the abstract for this latest contribution to the topic:
From Topics in Stroke Rehabilitation. 2010 May-Jun;17(3):151-62.


Poststroke complex regional pain syndrome


Chae J.
Department of Physical Medicine and Rehabilitation, Case Western Reserve University, Cleveland, Ohio MetroHealth Rehabilitation Institute of Ohio, MetroHealth System, Cleveland, Ohio.


Abstract
Poststroke Complex Regional Pain Syndrome (CRPS) affects a significant number of moderate to severely impaired stroke survivors. Until recently, advances in the assessment and management of CRPS have been limited due to the lack of a consensus on diagnostic criteria; however, with the development of the International Association for the Study of Pain diagnostic criteria, the medical and scientific communities are poised to make significant strides. Biomechanical factors and microtrauma to the hemiparetic shoulder may have a significant role in the genesis of CPRS, although the exact pathophysiology that links these triggers to the observed disease manifestation remains uncertain. Sympathetic dysfunction has historical importance in the CRPS literature. However, this appears to be only one of several possible pathophysiologic mechanisms; somatic nervous system dysfunction, inflammation, hypoxia, and psychological factors are also likely contributors to the disease process. There is no definitive treatment for CRPS, and most patients are treated empirically. Nevertheless, there is consensus that the treatment approach should be interdisciplinary with the goals of edema and pain control, maintenance of joint and muscle biomechanics, and functional restoration. As more rigorous clinical trials emerge, the treatment approach will become more rational with selection of interventions based on a specific mechanism or a combination of mechanisms responsible for a given individual's disease manifestation.


The second of today's articles is exciting, in that Dr. Schwartzman and ketamine research are in play. The journal, like most things these days, is beyond me -- Chirality. These are the aims and purposes of the journal:

The main aim of the journal is to publish scientific work on the role of molecular asymmetry in both biologically active and non-biologically active molecules in respect to their pharmacological, biological, and chemical properties. Drugs, pesticides, and other xenobiotics will be a major interest.

Papers on the chemistry (physiochemical, preparative synthetic, and analytical), pharmacology, clinical pharmacology, toxicology, and other biological aspects of chiral molecules will be published.

Among the topics to be covered are stereospecific synthesis, stereoselective analysis, preparative separation of chiral molecules, the influence of chirality on pharmacokinetics (absorption, distribution, protein binding, biotransformation, etc.), the influence of chirality on pharmacodynamics (drug-receptor interactions, pharmacological and toxicological activity), and the influence of chirality on clinical pharmacology (therapeutic index and response, bioavailability, adverse drug reactions, drug-drug interactions). Papers will also be published on regulatory and legal aspects in the development, testing, and marketing of chiral compounds.

Okay, I will 'fess up. I haven't a clue what a chiral compound is, and I am not in touch with the chirality that I was born with... although I think they might worship it off the western shores of Estonia, on a small island in the Gulf of Riga.

Hmmm? What? Oh. Right!  On to the Reference Works!

It turns out that chirality is a fascinating concept/thing/compound/word, derived from the greek for hand.  Of course, yes, I got lost in the term, but just for about twenty minutes.  Have you ever wondered whether it is eye or hand chirality involved when leaning your head aside to drink water straight from the tap?

A chiral molecule is a type of molecule that lacks an internal plane of symmetry and has a non-superimposable mirror image. The feature that is most often the cause of chirality in molecules is the presence of an asymmetric carbon atom.[1][2]

The term chiral (pronounced /ˈkaɪrəl/) in general is used to describe an object that is non-superposable on its mirror image. Achiral (not chiral) objects are objects that are identical to their mirror image. Human hands are perhaps the most universally recognized example of chirality: The left hand is a non-superposable mirror image of the right hand; no matter how the two hands are oriented, it is impossible for all the major features of both hands to coincide. This difference in symmetry becomes obvious if someone attempts to shake the right hand of a person using his left hand, or if a left-handed glove is placed on a right hand. The term chirality is derived from the Greek word for hand, χειρ (cheir). It is a mathematical approach to the concept of "handedness".

In chemistry, chirality usually refers to molecules. Two mirror images of a chiral molecule are called enantiomers or optical isomers. Pairs of enantiomers are often designated as "right-" and "left-handed."

Molecular chirality is of interest because of its application to stereochemistry in inorganic chemistry, organic chemistry, physical chemistry, biochemistry, and supramolecular chemistry.
And here you were thinking that I was gonna stay on topic, regaling you with yet another surge forward in CRPS research!  Ahem...

As I said, Dr. Schwartzman is involved, so you know ketamine cannot be far behind!  (That's unfair... but I am tired.)




From the journal Chirality. 2010 Aug 27


Enantioselective pharmacokinetics of (R)- and (S)-ketamine after a 5-day infusion in patients with complex regional pain syndrome.
Goldberg ME, Torjman MC, Schwartzman RJ, Mager DE, Wainer IW.


Cooper University Hospital, Department of Anesthesiology, UMDNJ-Robert Wood Johnson Medical School, Camden, New Jersey.


Abstract
Introduction: This study determined the pharmacokinetics and pharmacodynamics of (R)- and (S)-ketamine and (R)- and (S)-norketamine following a 5-day moderate dose, as a continuous (R,S)-ketamine infusion in complex regional pain syndrome (CRPS) patients.
Materials and methods: Ketamine was titrated to 10-40 mg/h and maintained for 5 days. (R)- and (S)-Ketamine and (R)- and (S)-norketamine pharmacokinetic and pharmacodynamic studies were performed. Blood samples were obtained on Day 1 preinfusion, and at 60-90, 120-150, 180-210, and 240-300 min after the start of the infusion, on Days 2, 3, 4, 5, and on Day 5 at 60 min after the end of infusion. The plasma concentrations of (R)- and (S)-ketamine and (R)- and (S)-norketamine were determined using enantioselective liquid chromatography-mass spectrometry.
Results: Ketamine and norketamine levels stabilized 5 h after the start of the infusion. (R)-Ketamine clearance was significantly lower resulting in higher steady-state plasma concentrations than (S)-ketamine. The first-order elimination for (S)-norketamine was significantly greater than that of (R)-enantiomer. When comparing the pharmacokinetic parameters of the patients who responded to ketamine treatment with those who did not, no differences were observed in ketamine clearance and the first-order elimination of norketamine.
Conclusion: The results indicate that (R)- and (S)-ketamine and (R)- and (S)-norketamine plasma concentrations do not explain the antinociceptive* activity of the drug in patients suffering from CRPS.
*reducing sensitivity to painful stimuli.

Ah, well.  That's science, that's the way the cookie crumbles, and c'est la vie. So the antinociceptive activity of ketamine remains elusive! It is good that they are working hard to tease out the mechanisms of its effectiveness, so that, one day, we can follow the bread crumbs back home...

I have a number of posts near completion, but keep losing my energy in the penultimate paragraph.  I promise to try and do better, or to trick myself, somehow, into finishing them.

And President Obama?  Good job, and thank you. 

By the way, I don't know if you've heard -- it may not have been included in your daily briefings -- but my Pre-Existing Condition Insurance Plan kicks in at midnight and tomorrow I go for my first battery of tests since they put the left prosthesis back in last year.  Gotta feed that high deductible (because you were willing to take on my high risk)!  So... yes, from the bottom of my heart: good job!

Monday, September 6, 2010

Combining Ketamine With Astrocytic Inhibitor

Astrocytes
Well, I know how hard it is for me to go without news about ketamine.  It's been a few days since I last spoke of this panacea, this club drug gone antidepressant, this animal tranquilizer deemed curative for CRPS/RSD.

It's going to take a lot of research, duplicated, peer-reviewed, and sanctified, thrice, by a Comprehensive and Integral Ad Hoc Committee Assembled by the Creator of the Universe, for me to get on the Ketamine Bandwagon. 

It could happen.

Today's offering comes from a group of scientists from the K. K. Leung Brain Research Centre of the Fourth Military Medical University in Xi’an, China, and is published in Molecular Pain.  The authors come from the Departments of Anesthesiology and Anatomy. 

The folks hailing from Anesthesiology are further specialized as "stomatologists." "Ewww!" was my first thought, closely followed by curiosity about CRPS of one's stoma... but it turns out that stomatology is the study of the mouth and its diseases:  dentistry, in other words!  I guess an anesthesiologist/stomatologist represents -- in Western formulations -- someone with a DDS who has done post-graduate work in anesthesiology.  What it means in the Chinese context, I dunno.  Perhaps it includes acupuncture.

That there is a décalage between Western Dentistry and Chinese Stomatology is clear:  For instance, like the American Dental Association, the Chinese Stomalogical Association declared that fluoride toothpaste helps prevent tooth decay... but C.S.A. did it in 2007.  I guess the actual availability of fluoridation plays a big part in that evolution, and further realize that the issue of fluoridation is not as clear cut to some as it is to me.  If you believe that fluoride causes cancer, then the topic of fluoride in your communal water supply is not a lighthearted topic.  [Okay, moving right along... don't wanna get lost... too late?  Is it too late?]

Rather quickly, I am wondering about the quality of translation in this work.  The current PDF version at Molecular Pain is provisional, with a promise of a fully formatted/full text version to be available soon.  I hope that can include scrutiny of translation from Chinese to English.  For instance, I am sure this sentence can be improved upon:

However, the present clinical therapeutics is still just concerning about neuronal participation.

And just because, I would like one of the authors to expound upon this:

Combined administration obviously relieved mechanical allodynia in a quick and stable manner.  [How?!  How did they know?!  I mean, my assumption is that we're talking lab rats here...  Was it that deep sigh of relief?  The fading furrows on the brow?  That certain sassy swish to the tail?]


Hmmm?  The claim?  The object of the study?  Jeez, but You Readers are demanding.  Is that a Burgeoning Sense of Entitlement rearing its ugly little head? 

Combining ketamine with astrocytic inhibitor as a potential analgesic strategy for neuropathic pain

Molecular Pain 2010, 6:50   doi:10.1186/1744-8069-6-50

Published: 6 September 2010



ABSTRACT
Background: Neuropathic pain is an intractable clinical problem. Intrathecal ketamine, a
noncompetitive N-methyl-D-aspartate receptor (NMDAR) antagonist, is reported to be useful for
treating neuropathic pain in clinic by inhibiting the activity of spinal neurons. Nevertheless,
emerging studies have disclosed that spinal astrocytes played a critical role in the initiation and
maintenance of neuropathic pain. However, the present clinical therapeutics is still just concerning
about neuronal participation. Therefore, the present study is to validate the coadministration
effects of a neuronal noncompetitive N-methyl-D-aspartate receptor (NMDAR) antagonist
ketamine and astrocytic cytotoxin L-α-aminoadipate (LAA) on spinal nerve ligation
(SNL)-induced neuropathic pain.

Results: Intrathecal ketamine (10, 100, 1000 μg/kg) or LAA (10, 50, 100 nmol) alleviated
SNL-induced mechanical allodynia in a dose-dependent manner respectively. Phosphorylated NR1
(pNR1) or glial fibrillary acidic protein (GFAP) expression was down-regulated by intrathecal
ketamine (100, 1000 μg/kg) or LAA (50, 100 nmol) respectively. The combination of ketamine
(100 μg/kg) with LAA (50 nmol) showed superadditive effects on neuropathic pain compared with
that of intrathecal administration of either ketamine or LAA alone. Combined administration
obviously relieved mechanical allodynia in a quick and stable manner. Moreover, down-regulation
of pNR1 and GFAP expression were also enhanced by drugs coadministration.

Conclusions: These results suggest that combining NMDAR antagonist ketamine with an
astrocytic inhibitor or cytotoxin, which is suitable for clinical use once synthesized, might be a
potential strategy for clinical management of neuropathic pain.

Direct Correspondance to:

Dr. Li-Xian Xu at
Department of Anesthesiology, School of Stomatology
Fourth Military Medical University, Xi’an, 710032, China
Tel: 86-29-84776115 Fax: 86-29-84776115 E-mail: kqmzk@126.com

Dr. Sheng-Xi Wu at
Department of Anatomy, Histology and embryology; K.K. Leung Brain Research Centre, Fourth
Military Medical University, Xi’an 710032, China
Tel: 86-29-84773074 E-mail: shengxi@fmmu.edu.cn

Dr. Yun-Qing Li at
Department of Anatomy, histology and embryology, K. K. Leung Brain Research Centre, Fourth
Military Medical University, Xi’an, 710032, China
Tel: 86-29-84774501 E-mail: deptanat@fmmu.edu.cn

ABOUT MOLECULAR PAIN:

Molecular Pain is an open access, peer-reviewed, online journal that encompasses pain research at the cellular, subcellular and molecularlevels.

Molecular pain is a growing research field that represents an advanced step from conventional pain research, addressing physiological and pathological pain at the cellular, subcellular and molecular levels.

Molecular pain research integrates pain research with molecular biology, genomics, proteomics, modern electrophysiology and neurobiology. The field of molecular pain research has great promise for the identification of highly specific and effective targets for the treatment of intractable pain.

Monday, January 26, 2009

Laura Beckett

[family photo of Laura Beckett and daughter]
Roughly two years ago, I was ready to fight.

I was looking into going to Germany for the ketamine coma treatment that has had such great -- but poorly understood -- results in people with refractory CRPS. I have CRPS/RSD in all of my limbs and now, in my face. Blah blah and yadda yadda!

At the same time, recognizing some tough financial realities and the not-so-minor detail that I have a lot of what is charmingly designated by the medicos as "co-morbidities," my neurologist was urging me to look into getting a pain pump. I had wanted a spinal cord stimulator earlier on but the spread of the disease made that a not so effective option and he was having a hard time handling my pain.


Isn't that a riot?


My doctors have a hard time handling my pain. There are days, though this is not one of them, that I resent that. With my neurologist, I try to walk a fine line. There is significant dissonance in his urgings that I get one implant or the other -- because he would always preface this desire with this slightly jarring statement: "Of course, with you? If you got an infection, you would be dead before you could get to the Emergency Room." [Given what ER-based blogs reveal, I think the ER/ED might be a waste of time, anyway.]


When I first investigated the ketamine coma protocol, it cost around $20,000. The cost has at least tripled -- probably due to inflation and the increased complexity of the care as the program has evolved. But, in my opinion (and I very much respect those on the other side of the argument), the ketamine coma is the best thing, indeed, the only thing, out there that comes close to a cure. It is not permitted in the states, not because of the drug but because of the length of time patients spend in coma. Indeed, "awake" ketamine infusion therapy is gaining in popularity as a treatment.


So why are my hopes in the past tense? I began to feel ill in ways that did not make sense -- although I did, for the longest time, attribute every symptom to CRPS and just thought that this freakishly weird disease was just getting weirder. Anyway -- eventually, we discovered that I have infected joint prostheses, as well as osteomyelitis. I have had three major surgeries since August 2008, and am facing another in the coming weeks. I have had my artificial shoulders removed and am not promised new ones. My left hip and my lower spine are suspicious for infection, too. The pathogen(s) involved have not grown in the lab -- although there is no doubt that there is massive infection (According to my surgeon, when he bored into the left humerus, it suddenly "exploded," spewing pus all over the place, even sending some up into my neck. Yummy details!).


All of my plans and hopes for either the ketamine coma (I thought my investment portfolio was sitting pretty!) or the pain pump are over. No one is going to put me under for any period of time (Did I not mention ending up on a ventilator for 5 days after one of the recent surgeries?) or put another foreign body into this body.


Oh, and I have MRSA.


Today I have a major appointment with the doctor I respect the most, whose opinion I highly value. In essence, when I am unsure but he is not? I will substitute his assurance for my waffling will. He has somehow pretty much predicted the outcome of each leg of the journey thus far. "I don't think we are looking at a positive outcome."


When I face a week like this one -- The Boutiqueur today, Infectious Disease tomorrow and Wednesday, Dr. PainDude Thursday -- I get fairly antsy. I know it will be physically hard and very painful but more than that, I have to prepare for getting emotionally jerked around.


So I clean my house like a rabid woman, I cook at 4 am, I attend to a myriad of details because, all of a sudden, details alone matter.


This morning -- after finally getting my Baked Cayenne Cheese Grits to set -- I log on to find that the most recent visitor to elle est belle la seine la seine elle est belle arrived via a search for "karl beckett crps." It is not surprising that this happened -- I mean, I may mention Karl Marx from time to time, Samuel Beckett is one of my literary heroes, and CRPS? Well, I might speak of it occasionally!


My heart sank when I followed this person's lead and read the story about the very real Karl Beckett, the ketamine coma, and CRPS.


His wife went to Germany for the treatment, but on the second day of the coma, developed a terrible staph infection -- MRSA -- and is now on a vent and has lost the use of her legs and arms. Their money has run out and he has lost his job.


Just to get her home via air ambulance, he needs at least $71,000.


Please read their story and, if you are so led, a trust fund has been set up:
c/o TD Bank NS, 129 S.Blackhorse Pike Runnemede, NJ 08078

Here's another article about the situation: N.J. woman trapped in German hospital.

*Edit: Reading the sometimes ridiculous comments that follow the articles can be upsetting to those of us with CRPS. Dr. Schwartzman is wrongly being smeared -- everything I know of the man tells me that he is a selfless, tireless worker on behalf of those with this stupid disease. Laura Beckett's family is, of course, upset and highly emotional but it is unfortunate that Dr. S has become the sacrificial lamb to their tragedy.

As for the ketamine coma therapy itself? The main reason it is not approved for use in the United States is the *length* of the coma, not the use of ketamine. I believe that the FDA will not approve coma treatments that last more than two days. Ketamine is being used as an accepted treatment in the U.S. for CRPS, but only as a short "infusion" while the patient is awake.

About the fur flying over the issue of ketamine being a "street drug," well, get a grip, people! Ketamine is used as anesthesia for humans in ERs and ORs every day just as, yes, it is used illicitly as Special K [on scuzzy street corners and in dank, dark, evil bars] every day, too. It often happens that there is a lag time in the general understanding of how a drug that is abused on the street can have an extant legitimate medical use -- I encountered this when I began using methadone as my long-acting pain reliever. Folks who weren't aware of its profile as a cheap and effective pain reliever preferred to conclude that I was a heroin addict. Luckily, I have long experience in, as put by my darling brother, the Grader Boob, "making like a duck, and letting it roll off my back."

In their present circumstances, the Becketts can hardly be as forgiving. The overarching issue of whether the German doctors screened Laura for MRSA is something of a non-issue. She may have acquired it there; She may have been a carrier -- whatever, MRSA, like "stuff," HAPPENS. There is no relief to be had by playing the blame game.

This poor family is surely at wits' end. If you can, consider donating or bringing heat to their legislators, or publicizing Laura's plight. Word is spreading and I am optimistic that help is on the way -- but from Laura's vantage point, it must feel like forever.

Oh, the statement by the German doctors that this is the first complication in the ketamine coma treatments? Ridiculous. It is well known that pneumonia is not at all uncommon in the course of the week spent on a ventilator -- in fact, it happens fairly frequently, but my understanding is that the ICU nurses are good at respiratory hygiene, keep the patients turned and well-suctioned, etc. The most frequent consistent negative that I've read about is the one anticipated -- the difficult transition from ketamine coma to a normal awakened state (generalized weakness, hallucinations, trouble eating, etc.). All in all, considering the extreme nature of the treatment, I think things have gone remarkably well. Do I think it is risky? Of course, it is risky. Who has ever said otherwise?

Considering how few treatments there are for CRPS, I hope that the community of "sufferers" can refrain from being inflammatory while working to help the Becketts. Let's keep them the focus and not make this specific set of circumstances (which we really do not know, anyway) a referendum on the coma protocol.

Friday, July 31, 2009

More On Ketamine (Courtesy of the StudMuffin)

Courtesy of Jim Broatch, the StudMuffin of RSDSA (Reflex Sympathetic Dystrophy Syndrome Association -- an organization in need of a new name, if ever there was one...). Jim and His Fellow StudMuffins at RSDSA do phenomenal work for those mired in suffering now, all the while keeping their heads above water, their eyes on the prize of future therapies and happenin' research.

In fact, kiddos, the real "read" here is not this pitiful little article from People magazine (I mean, the magazine's editors *would* look at the most extreme and ill-afforded "therapy" out there -- forget the hundreds of thousands who have no access to it, or who don't believe in its claims, or who are just too far gone into misery... and co-morbidity. I rhymed!) -- no, the real read is in this link that Jim Broatch also provides, which is to legitimate information to help you make up your mind about the ketamine angle based on solid stuff.

To read up on my illegitimate posting on ketamine, much of it having to do with Laura Beckett and her sad odyssey, take a gander here. I promise it is all uninformed opinion. You're welcome.


All of that said, here's the gist of the People article, and best wishes to John Roach, its subject.

I love the title!

*** *** *** *** *** *** *** ***

This Man CHOSE to be in a Coma


After years of excruciating pain that drove him to thoughts of suicide, John Roach decided to gamble on a controversial new treatment-a ketamine-induced coma.

August 10, 2009
By Alicia Dennis
PEOPLE Magazine

John Roach looks up at wife Rosemary from his bed in room 133 at the Hospital San Jose in Monterrey, Mexico. "Don’t say goodbye," he pleads as doctors prepare to send the burly grandfather form Allentown, Pa., into unconsciousness. "It’s okay," Rosemary says. "Pleasant dreams."

Soon, deep in a coma, John descends into a frightening, topsy-turvy world. Scene: He’s in a strange house with paintings on the ceiling. Scene: He’s watching as his cat rushes into the path of an oncoming car. Scene: He’s a World War II soldier fighting on a blood-soaked battlefield. "It was weird and frightening," John recalls of his voluntary, five-day ordeal in late May. "But I needed to do something."

Suffering from a debilitating neuromuscular disorder called reflex sympathetic dystrophy (RSD) , John, 50, is one of about 100 chronic-pain patients resorting to a radical new treatment in search of relief-medically induced coma using ketamine, a surgical anesthetic and hallucinogen sold illegally as "Special K." advocates say ketamine comas can be a godsend for some. "We're giving people in excruciating pain a normal life," says Dr. Robert J. Schwartzman, neurology chairman at Philadelphia's Drexel University College of Medicine; since coma therapy isn't FDA approved, he's sent more than 60 patients to Germany and Mexico. But other experts say the treatment, which costs as much as $ 50,000 with travel, is too risky. "Vulnerable people are getting something expensive and potentially dangerous," says Dr. Norman Harden of the Rehabilitation Institute of Chicago.

Some 200,000 people suffer from RSD, in which ordinary pain escalates to crippling levels. "Think of holding a blowtorch to your skin," says John, whose entire left side was affected after he fell down rotted stairs and tore his rotator cuff in 2002. Because ketamine blocks pain receptors, Schwartzman says, very high doses can restart the nervous system, "like rebooting a computer."

Brandy Sachs, 23, of Christianburg, Va., had spent seven years in a wheelchair after a finger injury and ankle sprain spiraled into all-over agony. "I was giving her pain meds in doses that would have killed a horse," says her family doctor, Jeremy Freeman. Last fall, after undergoing a five-day coma in Germany, Brandy needed months of therapy to relearn how to walk, talk and eat. But now, she says, she's pain-free and plans to start her master's degree: "It's a miracle."

Not always. In October 2008, RSD patient and mother of three Laura Beckett, 47, of Magnolia, N.J., developed pneumonia while in a coma in Germany and was kept under for three weeks as doctors fought to save her. She woke up paralyzed from the neck down and now lives at a rehabilitation center. "It's an understatement to say things went wrong," says husband Karl, though he adds his wife's pain was so unbearable they would likely choose the coma again. Says Schwartzman: 'We've had tragic outcomes. But this is only attempted after every other treatment has been tried."

John, a jovial retired phone-company worker, had tried surgery, physical therapy and heavy doses of pain medication, including OxyContin, codeine and fentanyl. When nothing worked, he thought of ending it all. "I couldn't be touched," he says. "I couldn't hold my wife's hand or sleep next to her. It wasn't the life I wanted."

Back home now, John is amazed that he's been virtually pain-free. Getting regular ketamine booster injections (at non-coma levels) from his physicians, Schwartzman and Dr. Anthony Kirkpatrick, he has removed a protective compression sleeve he wore for years and can once again wear his watch and wedding ring. Best of all, he can walk hand in hand with Rosemary and scoop up his granddaughters for hugs. "I have been missing all the little joys in life," he says. "Now I want to live every one of them."

RSDSA: Information on Ketamine Treatment

Friday, October 23, 2009

Voice of Frustration

This is the text of an email from Anthony F. Kirkpatrick MD PhD (via Tony Tobin):

FDA approval of ketamine coma therapy
From: Anthony Kirkpatrick MD, PhD
Sent: 13 October 2009 14:37:54
To:

Today, a physician in Australia wrote the following:

"I hope the FDA sees the light and approves the Ketamine coma therapy in the U.S before too long...good luck and keep up the great work."

My reply:

"In my opinion, the FDA will never approve a disease specific indication for ketamine such as CRPS because there is no patent protection and, therefore, no money to be made by a drug company in going through the FDA approval process for a specific disease state / diagnosis.

There is little financial incentive for the FDA to approve ketamine for a specific pain diagnosis without a drug company supporting the New Drug Application (NDA). More than 60% of FDA's budget comes from drug companies. Check this site out:

http://www.rsdfoundation.org/en/research.html

Thirty years ago, the FDA approved ketamine for a specific route of administration (IV) and dosage range up to and including general anesthesia to treat breakthrough pain regardless of the underlying disease state / diagnosis.

Forget about the FDA ----- it is not the solution. Third party payers (e.g., Australian, US Governments) are likely to reimburse patients for ketamine treatments with the publication control studies like those found here:

http://rsdhealthcare.org/PatientInfo/outpatient_ketamine.htm

It is unlikely that a study with an active placebo control (e.g. midazolam, fentanyl) conducted in the ICU will ever take place from an ethical standpoint given that ketamine has already been proven effective at a low dose for treating CRPS on an outpatient basis. Under this circumstance, how many patients with CRPS would volunteer to be intubated and mechanically ventilated for 5 days in the ICU with an active placebo instead of ketamine?"

A. Kirkpatrick, MD, PhD

www.rsdfoundation.org
www.rsdhealthcare.org

Thursday, April 12, 2012

A Year Ago: Bed 5, Round 4

first published on 4/12/2011

I had my first opportunity to serve as Ambassador of Ketamine yesterday, a duty that I discharged with vigor, if not honesty.

About a half hour before being escorted to the treatment area, ketamine patients are instructed to stop by the outpatient pharmacy, sidle nonchalantly on up to the counter and hit the pharmacist up for 10 mg of Valium.

I think nonchalant sidling is akin to the skedaddle of the detritus loving Fiddler Crab.

You ask for your Valium out of the side of your mouth;  You cover your purchase with a bag of sour Skittles and maybe some Milk Duds;  You pay your dollar, pop your pill, and go wait to be called for treatment.

So I'm in line, humming, fondling the candy.  There is a guy in a wheelchair taking up a lot of time -- like, they tell him it will be a few minutes before his medication is ready, and he says okay, I'll just wait *here*... but, like, I can't get to the counter because he is entrenched, waiting *there*... 

Jeez, people in wheelchairs think they own the world.

Fred does his clear-the-throat routine.  That doesn't work because, heck, we're in the middle of a hospital where half the population has tubes running down their throats and the sound of raspy retching is the sound of normal.

I finally just call out over the guy's shoulder -- "Yo!  I'm here to get my one-buckValium and to pay for these Skittles and maybe some Milk Duds before I go fall in my K-hole, yo, y'all."

At which point the guy in front of me practically does a wheelie.

"You, too, huh?  This is my first time.  I'm really nervous.  Does it really work?  What are you getting it for?"

Aw, fudge.

I'm nervous, myself, and this is my fourth treatment.  And I am not feeling chatty, or excited, or even vaguely benevolent.

Nonetheless, I proceed to be a fine ambassador of subanesthetic ketamine infusion therapy for intractable pain.  My routine is peppered (and salted) with plenty of "it varies from patient to patient..."

"Is it working for you?  How long does it take before it works?  Is it scary?" And so on, and so forth.  I meet his Blessed Mother, who has blue helmet hair and clearly thinks I might be one of them "drug atticks."  He rolls up his pants to show me his red lobster legs, trying to convince me that his pain is horrible, that he cannot sleep, that he's tried everything.  I tell him he is obviously a cry baby, signal the money-grubbing pharmacist tech, peel off wide, and catch my neatly packaged diazepam on the fly.  Fred tucks the candy into his backpack, I leave an IOU tucked in the Bowel Program For High Quadriplegia aisle (next to the cards and magazine rack), promise to settle accounts "next time," and we leave that big old cry baby and his helmet-headed mama with mouths hanging open, sucking in our dust.

When I am assigned an area back in the treatment room -- Bed 5 -- guess who is put in Bed 4?  You guessed it!  And his mama, too.

Big fat paralyzed cry baby seems to know every doctor and nurse who strolls by... and for some reason, people seemed to be taking their lunch-break power promenades down Ketamine Alley, peeking in at us weirdos and our wheelchairs, canes, catheters, ports, and world-weary loved ones valiantly trying to stay awake as lights and sounds dim, then mute. Fred and I listen to my neighbor bitch and moan as a namby pamby, softspoken, I-think-I-can-help-you type doctor attempts to tweek his spinal cord stimulator so that the cry baby can sleep long enough to have a wet dream. The doctor leaves him with several programs to try and some inspirational thoughts by Jack Handey.

I am the last person to be hooked up, even though I have the largest dose to be given.  As usual, when I start the infusion, ketamine greets me with one of its more dependable effects -- a kind of sepia treatment, a brownish, sometimes greenish, tint or wash that rubs out details and crosses soft edges.  That, and hearing so acute that I perceive Fred thinking of ducking out to grab a sandwich -- and his loud, booming hope for a kosher dill on the side.

Big fat paralyzed red-legged mama's boy cry baby, like many of us, has brought music to listen to in the form of an MP3 player.  In fact, I had spent a fair amount of time during the night making a playlist specifically for the Ketamine Experience, hoping to avoid Jimi Hendrix and the Banner, "Knockin' On Heaven's Door" and stuff like the giggle-inspiring "Illegal Smile."  Me and my 54 songs were ready for Round 4, all negativity purged, insipid pop privileged over mind-bending instrumentals, rock classics, and Mozart.

But now, in the cozy environs of Bed 5, there was this competing roar that I couldn't at first locate and never managed to silence.  That's right -- the cry baby's music (if it can be called that! sniff:sniff) vibrated all over the damned place, bleeding from his earbuds.  His taste in songs seemed to be limited to groups formed by cousins.

I apparently don't rise above a whisper during ketamine infusions.  Fred has to lean in close to hear me and says that I perpetually inquire as to whether or not I am being too loud, and seek reassurances that I am not, in fact, shouting. 

So there was that to contend with -- supersensitive hearing and leaky earbuds.

And yes, once again, I became hyperconcerned about a little old lady who was stashed in the last bed on Ketamine Row.  She was moaning so, and weeping.  Would these people never shut the hell up?

Part of the reason I was late getting started was that they accessed my portacath for the first time. Thankfully, that went fine, despite the nurse's contention that it was still too "infected" to use.  The problem is now relegated to one tiny area of the incision, through which pokes this recalcitrant little stitch that refuses to "dissolve" and be absorbed by my body.  Every few days or so, I clip the ends, and to keep things free of pus, crusty critters, and squishy maggots, first thing every morning and last thing at night, I douse the area with cognac and smear bacon grease over the wound, concentrating on that problematic corner.

Sorry.  That's what I felt like telling the nurse every time she inquired whether or not I was applying neomycin, keeping it clean and covered, etcetera.  It seemed she asked a hundred times and that was before the pharmacy even delivered the right dose of ketamine -- they had prepared a bag of 50 mg when I had graduated to 125, and the time required to correct the error was sufficient for her to worry enough about my site to page the doctor for "clearance" to use the port.

Clearly peeved at having been pulled from his clinic patients, he glared at me (not her, mind you, but me), poked at it meaningfully with an ungloved index finger, and declared it "perfect."  Before dashing back to the crowded exam rooms and stacks of charts, he gave me a short pep talk, even using the word "miraculous" to describe the relief that would be coming my way any day now.  Fred had a sneezing fit in the middle of the doctor's testimony, and I thought I saw the word bullshit fly out of his delicate aquiline nose and dance in the air before diving into his fine linen handkerchief.

If you are dying to know whether I got any pain relief from Round 4 of subanesthetic ketamine, you're not alone.  So am I.

At 4:10 pm, I had no pain in my feet, no pain below my knees.  I laughed, I smiled.  I announced it.  And then it was gone.  No one reacted to my news, so I am not sure whether I actually said it out loud.  Even when I retold the tale on the ride home, Fred didn't think I was serious.

When people describe how heartbreaking it is to have pain relieved only to have it return?  There is no melodrama there.  It really does tear the heart asunder -- bundles of ischemic cardiac muscle fall apart, shred, and twitch in extremis.

To answer the question, then, I don't know.  I might have dreamed it, I might have hallucinated it, but at 4:10 pm, I had no pain in my feet, no pain below my knees.

All I can conclude is that maybe we are nearing the right dose of ketamine... I heard the nurse and the doctor discussing something about adjusting the rate but not the dose, but I am not sure they were talking about me.

 The big fat paralyzed red-legged mama's boy cry baby next to me?  When they inquired about his pain level following the infusion, he crowed -- "Zero!  Zero, man, zero!"

His little blue-haired mama looked confused, but pleased, and announced that they were gonna go get them some Taco Bell.

My next treatment is set for next Wednesday at which time the dose will be 150 mg.




"cocorosie K-hole {independent} music video" uploaded to YouTube by ensnyggflicka on Dec 4, 2006




Tiny spirit in a k-hole
Bloated like soggy cereal
God will come and wash away
Our tattoos and all the cocaine
And all of the aborted babies
Will turn into little bambies

Wounded river push along
Searching for that desert song
And mozart's requiem will play
On tiny spearkers made of clay
Tell my mother that i love her
Martin luther you're an angel

Charming monkey saunter swagger
Drunken donkey limbs disjointed
Your chest is a petting zoo
Mexican pony fucked up shoes
I dreamt one thousand basketball courts
Nothing holier than sports

Dragonfly kiss your tail
Precious robot built so frail
Universe of milk and ember
Your hot kiss in mid december
What's god name i can't remember
Trough the crack eye lovely weather

Tuesday, July 12, 2011

Recent CRPS Research

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I'm not feeling much like blogging these days, being about as busy as a body can be hosting Tête de Hergé's most anticipated Pity Party of the 2011 season.  Nonetheless, having run across some interesting newly published research, I did some wicked-fast copying and pasting, cogitating and perusing, and hope that you will find some of this CRPS work helpful and interesting.  I confess to having focused on aspects of this Sucky Disorder that are posing a challenge and raising questions in my life at present:  sensory dysfunction, disorder of body schema, hemilateral sensory disturbances, dystonia, and -- what the heck! -- ketamine induced liver injury!

There is some comfort in noting the many articles and topics being published and discussed -- just not enough comfort to warrant ending the Pity Party.  Maybe come August.  (Actually, ManorFest is about a week away, at which time my rabid navel-gazing will no longer be tolerated around here.  Already, people are strumming their fingers and rolling their eyes at my wailing and cultivated introspection.  I saw a preliminary ManorFest schedule in which I am relegated to working night shifts, exclusively, far from the public eye.  Harrumph.)

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Title
Comparable disorder of the body schema in patients with complex regional pain syndrome (CRPS) and phantom pain.

Author(s)
Reinersmann A, Haarmeyer GS, Blankenburg M, Frettlöh J, Krumova EK, Ocklenburg S, Maier C

Institution
Abteilung für Schmerztherapie, Berufsgenossenschaftliches Universitätsklinikum Bergmannsheil GmbH Bochum, Ruhr-Universität Bochum, Bochum, Deutschland, annika.reinersmann@rub.de.

Source
Schmerz 2011 Jul 9.

Abstract
In patients with complex regional pain syndrome (CRPS) a disruption of the body schema has been shown in an altered cortical representation of the hand and in delayed reaction times (RT) in the hand laterality recognition task. However, the role of attentional processes or the effect of isolated limb laterality training has not yet been clarified.The performance of healthy subjects (n=38), CRPS patients (n=12) and phantom limb pain (PLP) patients (n=12) in a test battery of attentional performance (TAP) and in a limb laterality recognition task was compared and the effect of limb laterality training in CRPS patients and healthy subjects evaluated.The RTs of both CRPS and PLP patients were significantly slower than those of healthy subjects despite normal TAP values. The CRPS and PLP patients showed bilaterally delayed RTs. Through training RTs improved significantly but the RTs of CRPS patients remained slower than those of healthy subjects. In this study an equal disruption of the body schema was found in both CRPS and PLP patients which cannot be accounted for by attentional processes. For CRPS patients this disorder cannot be fully reversed by isolated limb laterality recognition training.

Language
GER

PubMed ID
21739258


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Title
Impaired Hand Size Estimation in CRPS.

Author(s)
Peltz E, Seifert F, Lanz S, Müller R, Maihöfner C

Institution
Department of Neurology, University of Erlangen-Nuremberg, Erlangen, Germany.

Source
J Pain 2011 Jul 7.

Abstract
A triad of clinical symptoms, ie, autonomic, motor and sensory dysfunctions, characterizes complex regional pain syndromes (CRPS). Sensory dysfunction comprises sensory loss or spontaneous and stimulus-evoked pain. Furthermore, a disturbance in the body schema may occur. In the present study, patients with CRPS of the upper extremity and healthy controls estimated their hand sizes on the basis of expanded or compressed schematic drawings of hands. In patients with CRPS we found an impairment in accurate hand size estimation; patients estimated their own CRPS-affected hand to be larger than it actually was when measured objectively. Moreover, overestimation correlated significantly with disease duration, neglect score, and increase of two-point-discrimination-thresholds (TPDT) compared to the unaffected hand and to control subjects' estimations. In line with previous functional imaging studies in CRPS patients demonstrating changes in central somatotopic maps, we suggest an involvement of the central nervous system in this disruption of the body schema. Potential cortical areas may be the primary somatosensory and posterior parietal cortices, which have been proposed to play a critical role in integrating visuospatial information. PERSPECTIVE: CRPS patients perceive their affected hand to be bigger than it is. The magnitude of this overestimation correlates with disease duration, decreased tactile thresholds, and neglect-score. Suggesting a disrupted body schema as the source of this impairment, our findings corroborate the current assumption of a CNS involvement in CRPS.

PubMed ID
21741321

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Title
The Specificity and Mechanisms of Hemilateral Sensory Disturbances in Complex Regional Pain Syndrome.

Author(s)
Knudsen L, Finch PM, Drummond PD

Institution
School of Psychology, Murdoch University, Perth, Western Australia.

Source
J Pain 2011 Jun 22.

Abstract
Hyperalgesia often extends from the affected limb to the ipsilateral forehead in patients with complex regional pain syndrome (CRPS). To investigate whether this is more common in CRPS than other chronic pain conditions, pressure-pain thresholds and sharpness to a firm bristle were assessed on each side of the forehead, at the pain site, and at an equivalent site on the contralateral side in 32 patients with chronic pain other than CRPS (neuropathic or nociceptive limb pain, radicular pain with referral to a lower limb or postherpetic neuralgia), and in 34 patients with CRPS. Ipsilateral forehead hyperalgesia to pressure pain was detected in 59% of CRPS patients compared with only 13% of patients with other forms of chronic pain. Immersion of the CRPS-affected limb in painfully cold water increased forehead sensitivity to pressure, especially ipsilaterally, whereas painful stimulation of the healthy limb reduced forehead sensitivity to pressure pain (albeit less efficiently than in healthy controls). In addition, auditory discomfort and increases in pain in the CRPS-affected limb were greater after acoustic startle to the ear on the affected than unaffected side. These findings indicate that generalized and hemilateral pain control mechanisms are disrupted in CRPS, and that multisensory integrative processes may be compromised. PERSPECTIVE: The findings suggest that hemilateral hyperalgesia is specific to CRPS, which could be diagnostically important. Disruptions in pain-control mechanisms were associated with the development of hyperalgesia at sites remote from the CRPS limb. Addressing these mechanisms could potentially deter widespread hyperalgesia in CRPS.

PubMed ID
21703937

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Title
Fixed Dystonia in Complex Regional Pain Syndrome: a Descriptive and Computational Modeling Approach.

Author(s)
Munts AG, Mugge W, Meurs TS, Schouten AC, Marinus J, Moseley GL, van der Helm FC, van Hilten JJ

Source
BMC Neurol 2011 May 24; 11(1):53.

ABSTRACT:
BACKGROUND: Complex regional pain syndrome (CRPS) may occur after trauma, usually to one limb, and is characterized by pain and disturbed blood flow, temperature regulation and motor control. Approximately 25% of cases develop fixed dystonia. Involvement of dysfunctional GABAergic interneurons has been suggested, however the mechanisms that underpin fixed dystonia are still unknown. We hypothesized that dystonia could be the result of aberrant proprioceptive reflex strengths of position, velocity or force feedback.
METHODS: We systematically characterized the pattern of dystonia in 85 CRPS-patients with dystonia according to the posture held at each joint of the affected limb. We compared the patterns with a neuromuscular computer model simulating aberrations of proprioceptive reflexes. The computer model consists of an antagonistic muscle pair with explicit contributions of the musculotendinous system and reflex pathways originating from muscle spindles and Golgi tendon organs, with time delays reflective of neural latencies. Three scenarios were simulated with the model: (i) increased reflex sensitivity (increased sensitivity of the agonistic and antagonistic reflex loops); (ii) imbalanced reflex sensitivity (increased sensitivity of the agonistic reflex loop); (iii) imbalanced reflex offset (an offset to the reflex output of the agonistic proprioceptors).
RESULTS: For the arm, fixed postures were present in 123 arms of 77 patients. The dominant pattern involved flexion of the fingers (116/123), the wrists (41/123) and elbows (38/123). For the leg, fixed postures were present in 114 legs of 77 patients. The dominant pattern was plantar flexion of the toes (55/114 legs), plantar flexion and inversion of the ankle (73/114) and flexion of the knee (55/114). Only the computer simulations of imbalanced reflex sensitivity to muscle force from Golgi tendon organs caused patterns that closely resembled the observed patient characteristics. In parallel experiments using robot manipulators we have shown that patients with dystonia were less able to adapt their force feedback strength.
CONCLUSIONS: Findings derived from a neuromuscular model suggest that aberrant force feedback regulation from Golgi tendon organs involving an inhibitory interneuron may underpin the typical fixed flexion postures in CRPS patients with dystonia.

PubMed ID
21609429

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Title
Drug-induced liver injury following a repeated course of ketamine treatment for chronic pain in CRPS type 1 patients: A report of 3 cases.

Author(s)
Noppers IM, Niesters M, Aarts LP, Bauer MC, Drewes AM, Dahan A, Sarton EY

Institution
Department of Anesthesiology, Leiden University Medical Center, Leiden, The Netherlands.

Source
Pain 2011 May 3.

Abstract
Studies on the efficacy of ketamine in the treatment of chronic pain indicate that prolonged or repetitive infusions are required to ensure prolonged pain relief. Few studies address ketamine-induced toxicity. Here we present data on the occurrence of ketamine-induced liver injury during repeated administrations of S(+)-ketamine for treatment of chronic pain in patients with complex regional pain syndrome type 1 as part of a larger study exploring possible time frames for ketamine re-administration. Six patients were scheduled to receive 2 continuous intravenous 100-hour S(+)-ketamine infusions (infusion rate 10-20mg/h) separated by 16days. Three of these patients developed hepatotoxicity. Patient A, a 65-year-old woman, developed an itching rash and fever during her second exposure. Blood tests revealed elevated liver enzymes (alanine transaminase, alkaline phosphatase, aspartate transaminase, and γ-glutamyl transferase, all⩾3 times the upper limit of normal) and modestly increased eosinophilic leukocytes. Patient E, a 48-year-old woman, developed elevated liver enzymes of similar pattern as Patient A during her second ketamine administration and a weakly positive response to antinuclear antibodies. In a third patient, Patient F, a 46-year-old man, elevated liver enzymes (alanine transaminase and γ-glutamyl transferase) were detected on the first day of his second exposure. In all patients, the ketamine infusion was promptly terminated and the liver enzymes slowly returned to reference values within 2months. Our data suggest an increased risk for development of ketamine-induced liver injury when the infusion is prolonged and/or repeated within a short time frame. Regular measurements of liver function are therefore required during such treatments. During repeated ketamine infusion for treatment of CRPS1, three patients developed liver injury probably allergic in nature.

PubMed ID
21546160