Month: November 2022

Quick look: cognitive damage from well-administered anesthesia 

Recently a client commissioned me to look at the potential cognitive impacts of general anesthesia. I was surprised to find out that it’s not obvious general anesthesia does more damage than spinal or local anesthesia, and my guess is most but not all of the damage is done by the illness or surgery themselves. 

Caveats and difficulties

I’m not a doctor. The following represents something like 5 hours of work, which obviously is not enough time to process even a fraction of the literature. I was focused on the dangers of median uses of anesthesia, where nothing goes obviously wrong and the anesthesiologist considers it a success; I didn’t even attempt to look at the rate of accidents, which can be pretty severe. My friend’s dad’s life was ruined by a fungal contaminant in a spinal injection. And of course, people die from excess general anesthesia. But for this post I only looked at damage done by routine anesthetic usage.

Like all client research, this was tailored to a particular person’s needs and budget, and shouldn’t be considered a general-purpose survey.

It’s pretty hard to tease out the difference between damage done by anesthesia, damage done by whatever necessitated the surgery, and damage done by having your body ripped open and bits moved around. Bodies hate that sort of thing. The few RCTs that exist by necessity focus on a narrow range of minimally invasive surgeries for which there exists a choice in type of anesthesia, and animal studies tended to focus on developing animals rather than adults. Even for procedures where multiple types are possible, patients tend to be pretty opinionated about what they want; one paper even announced they’d given up on reaching their sample size goal because recruiting was too hard.

Studies also often focused on cognition within a few hours of surgery (when people are still at the hospital to test). I think that’s less likely to be “damage” and more likely to be “it’s still wearing off” or “I’m sorry, I just had minor surgery and you want me to take an IQ test?”. This made me throw out a lot of studies.

Few if any of the papers attempted to control for post-operative condition or pain med usage, which seems like an enormous oversight to me.

Tl;dr

My overall take home is that:

  • Little or nothing that necessitates surgery is good for cognition and that needs to be factored into assessments.
  • Surgery itself is enormously stressful, physically and emotionally, and that stress impairs cognition, sometimes in lasting ways. This includes procedures that are not cutting new holes in you, like kidney stone treatments, although presumably it’s worse for open heart surgery.
  • Probably there are additional effects from anesthesia. At least general and spinal, maybe including local. On priors I still believe general and spinal are worse on a purely physical level.
  • Probably a lot of whatever damage there is heals in most people, although people who need surgery are already under heavy load and will be the worst at healing. 
  • There may be treatments that can prevent damage but they’re still in rodent trials right now.
  • I also believe that being awake and aware during surgery can be emotionally traumatic, and trauma is also bad for cognition, so include that in your math. 
    • But I’m not trustworthy on this, seeing as I was terrorized by a series of dentists and now can’t get myself through simple teeth cleaning without some sort of bribe, a human to guard me from the bad dentist monster, and a sedative. 

Papers

I didn’t rigorously track correlational studies, but my sense was they tended to show faster recovery from local and spinal anesthetic, relative to general, presumably because milder cases get milder anesthesia even when the procedures use the same billing code. Additionally a lot of studies were given too soon after surgery, which I don’t expect to predict long term damage

In the few studies that randomly assigned patients to spinal, local, or general anesthesia, and surveyed at least 7 days out, it’s really hard to pick a winner. 

Incidence of postoperative cognitive dysfunction after general or spinal anaesthesia for extracorporeal shock wave lithotripsy tries really hard to claim that spinal and general anesthetic are equally damaging to cognition, despite finding a 3x higher rate of cognitive issues after general anesthestic. I showed this paper to my statistician father and he gave a rant I wish I had recorded because it would make me famous in the right corner of Twitter. Hell hath no fury like a statistician forced to read a medical paper. He agreed with me that 19.6% (the rate of complications in the spinal group) was much larger than 6.8% (rate of complications in the general group), but dismissed that as merely a felony next to the war crimes against statistics they committed by using the wrong test for statistical significance.

Two meta-analyses both find a small difference in favor of spinal over general, with confidence intervals that overlap no-difference. One found spinal to be ~5% better (26 studies), the other 50% (but only 5 studies, so still overlapping with 0). The latter analysis is tiny in part because it is restricted to tests within a week of surgery. The analysis that looked also failed to find improvements from using local anesthetic.

On the other hand, animal studies of anesthesia without surgery regularly show impairment, although they can’t agree if post-anesthesia animals start off worse but catch up, or start off the same but fall behind. Also they found other medications could mediate the effects. I summarize the animal results in this spreadsheet. These are effect sizes we would clearly notice in humans so I assume they’re using much more anesthetic (although they claim it’s proportionate) or the animals, primarily rodents, are much more sensitive. Also the studies tended to be within days of anesthesia application, removing a chance to heal.

Tangent: UpToDate.com

The original commission was to investigate kidney stone treatments, and what I can say there is that the general medical site UpToDate is pretty good. Every claim I investigated checked out and I didn’t find anything at all established that they didn’t.

Thank you to Claire Zabel for commissioning the research and encouraging me to share the findings, and to my Patreon patrons for supporting the public write-up.

Follow up to medical miracle

The response to my medical miracle post has been really gratifying. Before I published I was quite afraid to talk about my emotional response to the problem, and worried that people would strong arm in the comments. The former didn’t happen and the latter did but was overwhelmed by the number of people writing to share their stories, or how the post helped them, or just to tell me I was a good writer. Some of my friends hadn’t heard about the magic pills or realized what a big deal it was, so I got some very nice messages about how happy they were for me.

However, it also became clear I missed a few things in the original post.

Conditions to make luck-based medicine work

In trying to convey the concept of luck-based medicine at all, I lost sight of traits I have that made my slot machine pulls relatively safe. Here is a non-exhaustive list of traits I’ve since recognized are prerequisites for luck based medicine:

  • I can reliably identify which things carry noticeable risks and need to be assessed more carefully. I feel like I’m YOLOing supplements, but that’s because it’s a free action to me to avoid combining respiratory depressants, and I know to monitor CYP3A4 enzyme effects. A comment on LessWrong that casually suggested throwing activated charcoal into the toolkit reminded me that not everyone does this as a free action, and the failure modes of not doing so are very bad (activated charcoal is typically given to treat poison consumption. Evidence about its efficacy is surprisingly equivocal, but to the extent it works, it’s not capable of distinguishing poison, nutrients, and medications).
    • This suggests to me that an easy lever might be a guide to obvious failure modes of supplements and medications, to lower the barrier to supplement roulette. I am not likely to have the time to do a thorough job of this myself, but if you would like to collaborate please e-mail me (elizabeth@acesounderglass.com).
  • A functioning liver. A lot of substances that would otherwise be terribly dangerous are rendered harmless by the human liver. It is a marvel. But if your liver is impaired by alcohol abuse or medical issues, this stops being true. And even a healthy liver will get overwhelmed if you pile the load high enough, so you need to incorporate liver capacity into your plans.
  • A sufficiently friendly epistemic environment. If it becomes common and known that everyone will take anything once, the bar for what gets released will become very low. I’m not convinced this can get much worse than it already has, but it is nonetheless the major reason I don’t buy the random health crap facebook advertises to me. The expected value of whatever it is probably is high enough to justify the purchase price, but I don’t want to further corrupt the system. 
  • Ability to weather small bumps. I’m self-employed and have already arranged my work to trade money for flexibility so this is not a big concern for me, but a few days off your game can be a big deal if your life is inflexible enough. Somehow I feel obliged to say this even though I’ve lost work due to side effects exactly once from a supplement (not even one I picked out; a doctor prescribed it) and at least three times from prescription medications.
  • A system for recognizing when things are helping and hurting, and phasing treatments out if they don’t justify the mental load. It’s good to get in the habit of asking what benefits you should see when, and pinning your doctor down on when they will give a medication up as useless.
    • Although again, I’ve had a bigger problem with insidious side effects from doctor-initiated prescription meds than I ever have with self-chosen supplements.
    • Probably there are other things I do without realizing how critical they are, and you should keep that in mind when deciding how to relate to my advice. 

Feel free to add your own conditions in the comments and I’ll add my favorites to this list.

Ketone Esters

Multiple people have asked for details on the ketone esters thing, and I sure hope that’s because I convinced them to try stuff rather than somehow sold ketone esters in particular as good. Answers to the common questions:

  • I use KE4, but I haven’t tried any others. I think when I originally looked it was the only one available without caffeine, but I could be wrong, or that could have changed.
  • When I first started and was doing longer intermittent fasting I’d do 10-15ml at night, 5-10 in the morning, and 5-15 before workouts (all on an empty stomach). I currently only do 5ml, before bed, to smooth out blood sugar issues whle sleeping.
    • The change is partially because I’m recovering from an injury and that does not mix with intermittent fasting, and partially because KE seems to have caused durable changes so there’s less point. I went from 3-4 sodas a day to none a few days after starting KE4 and it’s never reverted. The only caffeine I’ve had is incidentally in chocolate, and after the Bospro I’ve barely even had that.

Minimal Potato Diet

Again I am not recommending this, but if you would like to know what I’m doing:

  1. I use small potatoes- ideally the really tiny ones, but half-a-fist size at most. And I aim for a variety of color potatoes. These are out of a not particularly verified belief that skin has more vitamins than the core and that color means vitamins, or at least antioxidants. I also prefer the way the small ones cook.
  2. I cook the potatoes as soon as I receive them. If that’s not possible they might spend a few days in the fridge. When I let them age enough to get eyes they upset my stomach.
    1. A lot of people on the potato diet had to skin their potatoes to prevent feeling ill. I am curious if that would have been required if they’d used very new potatoes.
  3. I cook the potatoes by throwing them onto a cookie sheet and roasting at 350F for 45 minutes. I do this because it’s really quick and I prefer the dry texture.
    1. I cook 3 pounds a time because that is both the size of the bag they come in and about what my cookie sheet can hold.
    2. I tried gnocchi, but the additional flavor made me get tired of it faster. Also maybe my weight loss slowed around then but the potato weight loss has been weirdly punctuated so I dunno.
    3. I wish I could share a graph of just how weird the weight loss has been – same weight for 1-2 weeks, then 3 pounds in 4 days. Unfortunately, I keep changing my creatine dosage which ruins the aesthetics with a lot of water weight changes.
  4. The cooked potatoes spend at least a day in the fridge before eating, and ideally several. This is out of a slightly verified belief that the post-cooking cold converts some of the starches from digestible to indigestible, which lowers calories while doing something vaguely good for my digestive tract. But since I’m cooking much less often than eating they inevitably log a lot of fridge time anyway.
  5. Originally I ate about 100g/day, mostly in the morning but if I woke up craving something I’d start with that. For a few days now I’ve been experimenting with eating smaller amounts of potato more times per day and that’s maybe driven calorie consumption further down, but far too early to say for certain, and it’s not totally clear that would be desirable.
    1. This is based on my hypothesis that potatoes reduce calorie consumption in me by being a relatively bland food with (small amounts of) lots of different micronutrients, plus some help from the fiber. 
    2. Slime Mold Time Mold thinks it’s potassium and is testing that now. 
  6. I originally described myself as making no other changes. That was 100% true in the beginning, I will admit I now check in with my food diary calorie total and adjust a bit (including upwards, although not sure about the relative frequency). The point of the food diary is micronutrient tracking but it’s hard to avoid reacting to the calorie number once it’s there. I’m not sure that’s actually affecting things much – on days I happen to have a high count I eat much less the next few days without thinking about it. 
  7. My food diary is very clear I am not reliably hitting the RDA for most vitamins. I think you can do it on my calorie count but it would be a lot of effort and planning and I’m on vitamins anyway. Hopefully I get nutrition test results in the next month, although that will be much more a referendum on the Bospro than the potatoes. 
average nutritional intake for the last two weeks

A male friend lost 4 pounds on a 50% potato diet and then plateaued (but that could be from an injury). A female friend tried my minimal potato diet and experienced no change.  I think if that worked reliably we would already know about it.

Bonus

Shout to reader George who connected me with an offline friend who had similar symptoms with the same cure, who has done a ton of research into mechanisms and suggested some follow-ups. They’re not guaranteed to work but this feels like a rich vein to me. Thanks George and offline friend!