Brain Damage From Anesthetics

Say it aint so.....

So far no one has shown a direct effect of anesthetics to produce brain damage in people.  However, there are some disturbing reports about post operative cognitive dysfunction after surgery, especially in the elderly.  The Mayo group published data suggesting a link between age of onset of alzheimers and cumulative lifetime anesthetic exposure.  Moreover, Monk's group has shown an association between depth of anesthesia by BIS and one year mortality.  So what's up?

Pretty much every category of anesthetic has been impugned:

Opioids.

I am pretty sure I (and my colleagues) published the first papers showing histologic injury from a clinically used anesthetic drug (Anesth Analg 75:953‑964, 1992.   see fig).  We showed that high doses of alfentanil in paralyzed ventilated rats produced seizures and limbic system  brain damage in paralyzed ventilated physiogically controlled rats.  The doses were about ten times higher than analgesic, a dose range commonly used in cardiac surgery.  Similar results were produced with sufentanil, fentanyl, and remifentanil.  Given to monkeys in a PET scanner we saw FDG temporal lobe activation with fentanyl.  We gave brief high dose remifentanil to five humans fully paralyzed and ventilated also showing limbic system activation.  I just published another paper reporting limbic system activation at low doses of remifentanil in 29 volunteers with a variation in the activation pattern according to apolipoprotein E genotype.  Kearse and Tempelhoff have shown limbic epileptiform activity from fentanyl in humans.  Sullivan et al and Augoustides et al have shown that the proconvulsant properties of  remifentanil make for easier ECTs.  I had one patient seize from a remi injection before ect (do we shock or not?) and another developed post remi-ect status epilepticus.

     So the evidence seems overwhelming that opioids can produce limbic activation and in the right setting   produce brain damage, but we still don't know about people.(NB: when i suggested to several NIH study sections and the AHA in the early 90's that what we were seeing in rats might be relevant they returned non scored critiques...real visionaries there...)

Gabergic drugs

Drugs like barbiturates and benzodiazepines have been long considered to be protective.  Thus the chagrin from many quarters when todorovic, olney and colleagues showed that neonatal exposure to midazolam and nitrous oxide produced later histologic damage and cognitive dysfunction. 

NMDA antagonists: Nitrous oxide and ketamine

Todorovic's group has also shown that N2O and ketamine both produce cingulate lesions in rodents.  worse with higher age.  I gave N2O to young and middle aged wild type and transgenic amyloid overproducing mice and let them age. The old  N2O exposed WT mice did worse on cognitive testing but no effect was seen on the dumb transgenics (histology pending).   Also, collaborating with Biegon at Stonybrook,  N2O was associated with persistent opening of glutamate channels the day after exposure.

Volatile anesthetics

Eckenhoff and colleagues showed that in vitro halothane produced precipitation of amyloid that on EM looked like alzheimer plaques and was associated with in vitro cytotoxicity of cultured cells.  In later studies his group showed worse cognitive test results in elderly mice given isoflurane with histologic evidence of injury.  Of interest however, is that this effect was only seen in wild type mice...those transgenic mice that overproduced amyloid precursor protein became dumb in old age but the isoflurane did not make them dumber.  Others have also seen this phenomenon.
    Wei etal have shown that isoflurane produces apoptosis and that sevoflurane does not.  something to do with calcium, sarcoplasmic reticulum, and calpain.  Anyone interested  in more details will have to look up work by Hua Fung Wei.  Of interest that sevo produces epileptiform activity on induction of anesthesia.  Now I am really confused.

  So in summary, every major category of anesthetics has been linked both mechanistically and phenomenologically to brain damage in non humans.  Some physiologic congruent effects have been seen in humans and in some humans surgery (and anesthesia) have been linked to post operative cognitive deficits.  Notably the lab findings seem to focus on the limbic system,  where cognition is based.

It is daunting to test an hypothesis of harm in humans.  Moreover, anesthesia is given to millions and millions and no ill effects seem obvious.  This is work in progress and the full answers are not yet in.

Comments

[colleen]

Approximately 5 years I went into surgery to have a spinal fusion. When I came out of surgery I was very grouchy and didn't feel like myself (understandably) BUT when I was released and went home I was told to walk alot. I went outside to walk (which I loved to do before surgery) and as I was walking it was like a wall was slowly coming up in my mind and I didn't feel like walking anymore (which was odd). I have a hard time concentrating on anything. I can't seem to think things through, I get dizzy and sometimes I feel like going to lay down. Everything is a chore for me especially if it consists of thinking hard. If I try to think too hard I get sick on the stomach. Before I left my job for my operation, at work I could not see the computer screen if I would put my reading glasses on (but I needed them to read my paperwork and would have to take them off to look at my pc screen), then when I went back to work after the operation (3mts) I had to wear them to see the screen (which was odd to me)! I lost both my jobs last year and have to make up a resume but I get sick when I try to think of dates and things that need to be included. I cry every morning when I get up because I have soo much to do but can't think to get them done. I have mentioned it to the doctors but they just blew it off and think I'm crazy! How do you get them to listen to you? Could I have suffered a little brain damage from being put under for the operation because I know my thinking is very different and troubling!!

[Lorrie]

I had to have my kidney removed recently due to a cancerous tumor. Versed was used on me. I was not that nervous about the surgery before hand. But, when I woke up from surgery something was very wrong and I have not been the same since. I got no sleep the 4 days I was in the hospital. When my husband got me home I literally could not sit still for more than a count of 20 and I could maybe lay down for 20 minutes. All I could do was pace the house. My husband kept asking why can't you relax. I broke down in tears saying I would if I knew how. I just cannot stop pacing. I went without sleep for about a month. The doctors had no answers for me and told me it was all psychological and that I was just afraid of death. I am now 6 months out from the surgery and I am still a nervous wreck. They have me on Valium and I tried Remeron but hated the side effects and I was still nervous. However, I am getting a full nights sleep now. They are trying to switch me over to Celexa. I have tried to scan a lot of the responses on this site to see if anyone else found something that helped counteract the effects of the Versed. I didn't really see anything. I just want to be able to put my life back together and function normally and not be a nervous wreck all the time. I have tried to talk to my psychiatrist about Versed and my psychologist and they pretty much dismissed me. I just don't know what to do??? ANY SUGGESTIONS WOULD BE GREATLY APPRECIATED. I just want to have some hope!

I did see that Rather_Not_Say stated that Fentanyl has helped them. I was just wondering if you could give more feedback as to how it has helped and if you take it because you had extreme anxiety?

[Sonja]

I feel that many drugs are given when not necessary, just because the doctor likes to work without trouble and the patient is afraid.
Acupuncture is a good alternative, at least for minor procedures, reducing the amount of pain so much that everybody can take it.
It is just the convenience of the doctor and todays common belief in drugs that prevents the widespread application of acupuncture. The doctor doesn't have to live with the damage that he has caused.
So it is up to us to push for alternatives.

[Jimmy]

Hate to get off topic here but, I had knee surgery a year and a half ago, I've been a straight A student for as long as I've been in school, and have always been a hot shot when it comes to school, never been a problem. But I've noticed ever since i went under anesthetics, I havn't been the same person. I have had trouble concentrating, retaining information, and even spelling. This has been bothering me ever since and seems to be getting worse as I get older. I don't see how this could affect me since I'm in my mid teens, I usually here it happening to older people. Does anyone have any idea what's going on here?

[Jeff R.]

I donated a portion of my liver 5 months ago and have trouble with short term memory loss. It seems like my brain is in slow motion. I pray it gets better!

[nadja]

My late mother, had a rotator cuff (shoulder) operation a little over a year ago, aged 69yrs. She did not recover well physically and mentally. It was her 2nd such op. Having had the other shoulder done several years before with no such problems- well obvious problems anyway. In addition to the pain in her shoulder that dragged on for much longer than the previous op, she also had trouble sleeping and more interestingly - complained constantly about a foggy brain. It was only after developing extreme fatigue, forgetting how to turn her car off, and feeling non-emotional that we took her back to the hospital, some 6 weeks after the op. She was diagnosed with a glioblastoma (malignant) brain tumour 5cm in diameter. Two days later she was operated on, had to have 2 anaesthesias due to surgery complications, suffered several strokes in the operation and well go figure - was a mess from then on. The surgeon told us our mother would only live 3 months if not operated on, well she lived 3 months and WAS operated on. Whether the foggy brain and tumour were related to the anaesthesias - we can't be sure. Perhaps and I damm well hope that in years to come more light is shed on the effects of anaesthesia on the brain. And that this information is available to the public NOT just the medicos. Doctors hold too much truthful information back for my liking.

[Susan Engelhard]

I am a 62-year-old licensed professional counselor. I have known for a long time that my brain does not function like other's brains do. I am different from my 3 younger sisters and different from my 2 daughters. Organization and following through with tasks are very difficult for me. When I was 7 years old, I had a tonsillectomy in which ether was used. I have always wondered if that anesthesia induced some brain damage. Add to that, I am sure my mother was drugged during her labor with me. I am angry because I have been persecuted within my family for being this way. I will be trying Chinese medicine to see if I can improve my functioning without taking pharmaceuticals, which carry more problems. --LPC IN FL

[Katherine]

My mother is STRUGGLING after 6 treatments of anesthesia in 3 years. She is now being diagnosed with pre Alzheimers.

How do we get these chemicals out of her head?

Help! :)

[T Smith]

My 6yo son had an operation on his throat in a renowned Private Hospital in Australia nearly a week ago, for which he had a GA (4 drugs). It was routine and apparently nothing went off schedule. He's been recovering awfully. He's got memory problems (can't remember friend's names), balance problems, gross and fine motor problems (can't climb what he used to climb, or play pieces on the piano he used to play easily), he can't keep up with instructions, he doesn't read books all the way through like he used to (I even mean shorter books as we don't expect him to be 100% - he was reading Harry Potter 3 and now he gets bored reading a short picture book and tosses them aside unfinished), he screeches (like a bird) and tantrums like a toddler. He's having what we can only describe as 'autistic episodes', he's become very tactile and rubbing venetian blinds or pieces of paper repetitively. He's got a slight facial droop on one side that only his family can notice. To be honest it looks as though he's 'half baked' on hard drugs. All he wants to do is watch DVDs and/or play computer games - things that never interested him overly before as he was an avid reader. Since he's been home we've made phone calls about advice for his behaviour to- paramedics (000), nurses (Health Direct) and The Anesthetist (twice). We've made a trip to the Emergency at the Hospital and had the paramedics over once. Everybody has been very reassuring, explaining to us, like we're slow, that it will wear off and any blood tests would cause him more unnecessary stress after his operation. I'm not sure how blood tests help, so we had to agree. We'd just like our kid back now, thanks... What has the potential to be the most interesting thing is that he was IQ tested only a month or so before the operation. It won't take much to get him tested in a month or two and see if there's a palpable difference...

[Suzy Frame]

This is pretty intense! I had no clue that there was so much to know about medical aesthetics and how they can help me! I didn't know they could really affect you this much though! thanks for sharing!

[Mac Cooper]

In 1959 I was put under with ether for a tonsillectomy. I was 6 years old. I have pondered that experience all my life. When I returned to school I was asked to give my class a narrative of my experience, I'd like to share that with you... I was on the table with a bright light overhead, there were people beside me, someone put something over my nose and mouth, I was asked to count backwards from a hundred, I can only remeber getting to 96. I was then surrounded by grey balls, they were all around and all spinning in circles by me. I cannot say I was spinning, it was just the balls around me. I had a feeling of loneliness and wanted to get out of the spinning balls. I awoke and was very sick, I could not have any of the icecream they promised me.
As I grew older I've always wondered what the grey balls were all about. A conclusion I have come to is the grey balls around me were cells, stem cells maybe... and maybe they were not spinning, the spin was me. I cannot explain the grey light that was all around. In a sense I believe the ether pushed my soul into a cell in my body. My soul experienced the lonliness that may be death for some, a reality I have no idea.
I would like to talk to some others who experienced the ether trip. I would like to know what they were aware of while being under.
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