| Image may be NSFW. Clik here to view.  |
| Via Wikimedia Commons. This image is a gross misrepresentation of the real disability that is ADHD. But it was public domain, so I used it. |
Having been advised not to make too much of headlines that
First of all, like any parent of a child with ADHD, I clicked on the first headline about this study that I encountered. After reading the opening grafs, I immediately calculated how many general anesthesia procedures my nine-year-old with severe ADHD has had, and it's at least four (I lose track with all the children and all the surgeries). FOUR. When you read further into the news articles, you find (in most of them) that while it's not all anesthesia or any age of exposure, it's multiple general anesthesias before
A nanosecond more math, and I've reduced his exposures that might be relevant here to two. One for ear tubes, one for lacrimal ducts that were blocked with bone. Each procedure was incredibly brief, and he was under general anesthesia for much less than 30 minutes for each.
Having done all of this heavy math, I went looking for the paper itself. It's a study that was done in the Mayo Clinic, and it's published in...Mayo Clinic Proceedings (full text), which recently fell under the Elsevier publication umbrella [PDF]. To keep things reasonably clear, I've bullet pointed the main findings of the study below:
- For children not receiving anesthesia for procedures before age 2, the cumulative incidence of ADHD at age 19 was 7.3% (95% CI, 6.5%-8.1%).
- For single and multiple (≥2) exposures to anesthesia for procedures, the estimates were 10.7% (95% CI, 6.8%-14.4%) and 17.9% (95% CI, 7.2%-27.4%), respectively (Figure).
- In unadjusted analysis, exposure significantly increased ADHD risk (Table 3).
- In analysis adjusted for the covariates of sex, birth weight, and gestational age, multiple (HR, 2.49 [boldface mine]; 95% CI, 1.32-4.71), but not single (HR, 1.35; 95% CI, 0.90-2.02), exposures to anesthetics for procedures increased ADHD risk.
- Similar results were found using stratified proportional hazards regression with strata defined based on the propensity for receiving anesthesia (multiple exposure HR, 1.95; 95% CI, 1.03-3.71; single exposure HR, 1.18; 95% CI, 0.79-1.77).
- When analyzed either as a continuous or a categorical variable, the total duration of anesthesia was also associated with ADHD in unadjusted and covariate-adjusted analysis, but this association did not reach statistical significance in propensity-stratified analysis (Table 3).
Then, the researchers scraped the data for factors that might also influence the presence of ADHD and still found an increased risk of ADHD among children who'd had general anesthesia at least twice before age 2. In fact, their risk was about 2.5 times that of children with one or no exposures. There was a hint that the length of anesthesia was relevant to the outcome in terms of ADHD risk.
Taking a closer look at the paper, I found something that struck me as odd. The children in this paper were all born between January 1976 and December 1982. For them to have had general anesthesia before age 2, they'd've had it somewhere between 1976 and 1984 or so. In other words, the most recent episode of general anesthesia under consideration in this study occurred ~27 years ago, and the earliest occurred 36 years ago.
Naturally, I thought, "Hmm. Wonder if anesthesia has changed at all in the intervening decades."
It has. The general anesthesia protocol used most often in the children in this study involved halothane inhalation (87.1%) combined with nitrous oxide administration (88.1%). Apparently, halothane is in very limited use these days, replaced by sevoflurane, which evidently has advantages that include more rapid induction of anesthesia and more rapid emergence from it. It also is associated with less post-operative nausea and vomiting and appears to be associated with a reduced incident of heart episodes compared to halothane.
According to an anesthesiology newsletter from October 2011 (link may go to paywall), "much has changed in the practice of pediatric anesthesia over the past 25 years," including the development of safer anesthetics. Other newly developed anesthetics may help reduce some of the aftermath of pediatric general anesthesia, including "agitation."
In other words, this paper is about the influence of having 2 or more episodes of general anesthesia before age 2 about 30 years ago. There is no way of knowing what factors associated with anesthesia--if any--are relevant to the findings of this paper, but some of those factors have changed, so there's also no way of knowing how relevant these findings are in the context of current practices.
Then I thought about the length of anesthesia. Luckily, the authors provide an analysis of this. For parents who read that headline and immediately flashed onto the operations for ear tubes their little darlings may have had, I think you can rest easy. Those brief procedures don't seem to be linked to any ADHD-related outcomes. Based on the paper, there's no increased ADHD risk for children who had procedures lasting in total less than 30 minutes, and placement of ear tubes, for example, requires a duration of anesthesia of about 15 minutes. In addition, there doesn't seem to be any significant increase in risk until you get to a total duration of 1.5 hours or more.
That takes me to the observation that a surgical intervention lasting more than 30 or 45 minutes is generally no minimal intervention. These aren't ear tube operations or any of the more seemingly run-of-the-mill surgeries that children seem to have so frequently today; even infant hernia operations require only a "relatively brief" visit to la-la land. The children who had anesthesia in this cohort also had a more frequent rate of other health problems compared to children who didn't and were more likely to have low birth weight and have been born before full term ("lower gestational age"). In other words, the indications for these general-anesthesia-associated surgeries likely outweighed any long-term concerns over risk for ADHD-- 30 years ago.
One news article about the current study cites "animal and human" studies suggesting an influence of anesthesia on "the developing brain," which to me seems likely. But that article links to another story as support...that is from the same research group working with the same retrospective data from the same cohort (study here). In their ADHD/anesthesia paper, the authors cite a study linking the inhibition of certain signals in the brain and ADHD in an animal model, but that study didn't use the same anesthetics or administration route used on the children in their study cohort. They also cite a report they intend to support their assertion of an association between learning disabilities and anesthesia, but the study they cite found no link "between a single, relatively brief anesthetic exposure in infancy...and reduced academic performance" in the teen years.
Not only have things changed in the world of pediatric anesthesia in the last three or four decades, but they've also changed in the world of diagnostic criteria for learning disorders and ADD/ADHD. The current paper used the Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV for exclusion based on other disorders, combing school records for "any indication of concern regarding learning and behavior" and using DMS-IV criteria as one possible confirmation factor for an ADHD diagnosis. But the authors appear to have accepted an ADHD diagnosis from the period combined with a parental questionnaire as another method of confirming the ADHD diagnosis:
Patients were defined as having research-identified “definite” ADHD if their records included a clinical diagnosis of ADHD and at least 1 form of supporting evidence, including documentation of symptoms that met DSM-IV criteria for ADHD (with 6 or more separate entries in the medical or school records that were consistent with DSM-IV criteria) and positive parent or teacher ADHD questionnaire results.The children in the study were all diagnosed with ADHD before age 19, so between the years of about 1980 (for diagnoses starting at about age 4) to about 2001 (for children born in 1982), spanning
Anachronism piles on top of anachronism here, and I can't see how any of this is relevant to, say, my nine-year-old son--or anyone else--in 2012.
The news media stories seemed to largely overlook the issue of how pediatric anesthesia practices may have changed in the decades since the cohort in this study had general anesthesia or the issues of diagnostic variability. Does emerging from anesthesia more rapidly, as children do today with sevoflurane, have an effect? What about the improvements in the surgeries themselves that may make them shorter today? Or amelioration of post-operative vomiting and nausea, or post-operative agitation? Things have changed a lot in the 30 years since the children in this study underwent their surgeries, so that leaves me asking just how relevant these findings are to children born--and having surgery--today.
Image may be NSFW.
Clik here to view.![]()
Image may be NSFW.Clik here to view.
Clik here to view.