The notion that natural redheads need “more anesthesia” and/or are resistant to certain medications has been spread by the media (ie, Time Magazine and The New York Times), the scientific literature, and even seasoned anesthesiologists who (anecdotally) claim this to be true.

The “basic science” behind this stems from the high prevalence of allele mutations in redheads in the melanocortin-1-receptor (MC1R) gene. Normally this receptor stimulates eumelanin production in melanocytes. These mutations favor the production of pheomelanin which is responsible for the red hair, lighter skin, etc. Interestingly, subtypes in this receptor family are also expressed in the central nervous system and may antagonize opioid pathways leading to variations in the experience of pain. We still don’t know all the details!

Surgical general anesthesia (GA) must address four primary components: unconsciousness, memory, pain, and movement. These are better known as hypnosis, amnesia, analgesia, and immobility, respectively. I use a combination of volatile gas anesthetics with intravenous medications to confer the aforementioned state. As with anything else in medicine, every patient is different based on their age, comorbidities, etc… but does red hair actually make a difference? Let’s look at the literature.

In 2004, Liem et al. showed that in a head-to-head comparison of 20 healthy women, the redhead phenotype required a higher alveolar concentration of desflurane to not “feel” an electrical stimulus (a surrogate for minimal alveolar concentration, or MAC). However, almost a decade later, the same institution found that specifically with propofol, the most common IV hypnotic I use, redheads exhibit similar pharmacokinetics/dynamics to dark haired individuals.

Myles et al. performed a prospective, matched cohort study with a larger sample size (468 healthy adults) receiving inhaled GA with subsequent multivariate analysis showing that there was no significant difference in recovery times/pain scores in redheads accounting for what drugs/doses were used.

Remember that anecdotes are not data. Enough said.

We are still early in understanding how inhaled anesthetics actually work at the lipid bilayer, membrane protein level. Perhaps future research will examine if specific redhead-associated allele mutations do indeed affect the functional mechanism of anesthetics. Until then, this “myth” is just that. I do NOT change my anesthetic plan just because someone is a redhead.

Drop me a comment with your thoughts and questions!

19 Comments

  1. Well, as a redhead, I mostly agree with you. If anything, there may be more extremes in metabolic rates — the slow metabolizer described above, vs a fast metabolizer (me). But as a blanket statement about needing “more” anesthetic, it’s just not accurate.

  2. Andy Jenkins Reply

    On the subject of myths, we should remember that inhaled agents do not act on the lipid bilayer to generate anesthesia. Even your Harvard professors who strongly proposed such mechanisms abandoned these notions decades ago.

    A handful of ion channel proteins are the primary targets for Des-, Sevo- and Isoflurane.

    ;o)

  3. I’m well retired but the Reds are well established anywhere.
    My most remembered Red was a big beauty at 6 centimeters and waiting for an epidural.
    I asked if she or the family had and difficult with anesthesias in the past.
    Her dad needed 3 dental injections and 45 min to set in.
    The good epidural was as slow as her dads and she had the same outcome.

    I was a cardiothoracic guy in the 90s. And as I saw you and your travels we have a lot in common.
    Good luck bud, though I don’t think you need much.
    All the best,
    John J. Wilson MD

  4. Agreed. I am newly retired and have spent most of my career in a pediatric practice where this sort of anecdote is raised often by both patients and practitioners. My response to these stories is the same as yours; “anecdotes are not data”. Redheads are relatively unusual in the population and so are more memorable when there are variances from the usual clinical response. This makes people often convinced of their conclusion. Our biases, explicit and implicit, are why we invented statistics and the scientific method.

    • Couldn’t agree more, Eileen! What worries me is that this mentality spreads not only among the patient population but among healthcare providers as well.

    • Rafael Achecar Reply

      I have heard the same about redheads, during training and practice.
      I also have heard that patients of Asian heritage need “less anesthesia”, I do not change my plan based on ethnicity but I keep it in mind
      Thanks

  5. It’s funny because in residency it was pointed out early on the red hair individual last likely needed more MAC, and the list in Morgan and Mikail was shown all the time in discussions. I personally have noticed sometimes requiring a a little more initial anesthetic to reach steady state but not maintenance.

  6. In training, I was constantly told by patients and nurses (no physicians) that this is the case, but have not really seen any significant increase in anesthetic concentration beyond the usual adjustment for alcohol/drug use. Maybe redheads (Irish ancestry) tend to self-medicate more? I notice the patients who are more anxious pre-op/baseline tend to need more general anesthetics but not local anesthetics (after sedation). The majority of my patients that get PONV (and I aggressively give meds to prevent PONV) tend to be those nauseated preop due to anxiety (I usually ask in they’re nauseated in preop for elective surgeries). When patients tell me they’re “very resistant to local anesthetics,” they seem to be more anxious at baseline, so maybe their dentists tell them they’re more resistant to make them feel better in the moment. I’m still trying to figure it out.

    • Thanks for taking the time to share your insight and experiences, Eric! You touch on several important points! In my opinion, the idea of being “very resistant” to something based on an INDIVIDUAL’S past experience has some merit, but for people to extrapolate that to an entire population based on a visible phenotype like red hair WITHOUT going through the scientific method to isolate that variable and account for confounders is just bad science.

  7. Yep. We titrate anesthetic meds to all patients anyway. There’s no doubt that some patients require more anesthetic than others. Younger patients often need more, but we titrate.

    The word data is plural. Each anecdote could be considered a datum, but of little use. If they are collected systematically it’s data. But then, they’re not anecdotes anymore. The best data is randomized and prospective.

    • Not sure about local anesthetics specifically. And I’m not sure how the trend/pattern observations by a single individual should be extrapolated to everyone as “data” or “evidence” without appropriately designed studies (randomized, controlling for likely confounders, adequately powered, etc.) Guess we’ll agree to disagree.

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