DOES REPEATED GENERAL ANESTHESIA HARM THE BRAINS OF INFANTS AND YOUNG CHILDREN?

Recent scholarly publications have raised the question whether repeated exposure to general anesthesia is harmful to the developing brain in infants and young children.  Millions of children have surgery under general anesthesia each year.

Is repeated exposure to general anesthesia safe for the developing brain of your child? Let’s look at the evidence.

In 2011, a retrospective Mayo Clinic study looked at the incidence of learning disabilities (LDs) in a cohort of children born in Olmsted County, Minnesota, from 1976 to 1982.  Among the 8,548 children analyzed, 350 of the children received general anesthesia before the age of 2.  A single exposure to general anesthesia was not associated with an increase in LDs, but children who had two or more anesthetics were at increased risk for LDs.  The study concluded that repeated exposure to anesthesia and surgery before the age of 2 was a significant independent risk factor for the later development of LDs.  The authors could not exclude the possibility that multiple exposures to anesthesia and surgery at an early age adversely affected human neurodevelopment with lasting consequences. (Flick RP et al. Pediatrics 2011 Nov;128(5):e1053-61. Cognitive and behavioral outcomes after early exposure to anesthesia and surgery.)

The same group of Mayo Clinic researchers looked at the incidence of attention-deficit/hyperactivity disorder (ADHD) in children born from 1976 to 1982 in Rochester, Minnesota.  Among the 5,357 children analyzed, 341 ADHD cases were identified.  For children with no exposure anesthesia before the age of 2 years, the cumulative incidence of ADHD at age 19 years was 7.3%  Exposure to multiple procedures requiring general anesthesia was associated with an increased cumulative incidence of ADHD of 17.9%. The authors concluded that children repeatedly exposed to procedures requiring general anesthesia before age 2 years were at increased risk for the later development of ADHD. (Sprung J, Flick RP et al, Mayo Clin Proc 2012 Feb;87(2):120-9. Attention-deficit/hyperactivity disorder after early exposure to procedures requiring general anesthesia.)

Anesthesia scientists decided to study this problem in mice.  In March 2013, researchers at Harvard and other hospitals exposed 6- and 60-day-old mice to various anesthetic regimens. The authors then determined the effects of the anesthesia on learning and memory function, and on the levels of proinflammatory chemicals such as cytokine interleukin-6 in the animals’ brains. The authors showed that anesthesia with 3% sevoflurane for 2 hours daily for 3 days induced cognitive impairment (i.e., unusually poor mental function) and neuroinflammation (i.e., elevated levels of brain inflammatory chemicals such as interleukin-6) in young but not in adult mice. Anesthesia with 3% sevoflurane for 2 hours daily for 1 day or 9% desflurane for 2 hours daily for 3 days caused neither cognitive impairment nor neuroinflammation. Treatment with the non-steroidal anti-inflammatory (NSAID) drug ketorolac caused improvement in the sevoflurane-induced cognitive impairment. The authors concluded that anesthesia-induced cognitive impairment may depend on age, the specific anesthetic agent, and the number of exposures. The findings also suggested that cellular inflammation in the brain may be the basis for the problem of anesthesia-induced cognitive impairment, and that potential prevention and treatment strategies with NSAIDs may ultimately lead to safer anesthesia care and better postoperative outcomes for children. (Shen X, Dong Y,et al, Anesthesiology 2013 Mar;118(3):502-515.  Selective Anesthesia-induced Neuroinflammation in Developing Mouse Brain and Cognitive Impairment.)

The same Harvard research group assessed the effects of sevoflurane on brain function in pregnant mice, and on learning and memory in fetal and offspring mice. Pregnant mice were treated with 2.5% sevoflurane for 2 hours and 4.1% sevoflurane for 6 hours. Brain tissues of both fetal and offspring mice were harvested and immunohistochemistry tests were done to assess interleukin-6 and other brain inflammatory levels.  Learning and memory functions in the offspring mice was determined by using a water maze. The results showed that sevoflurane anesthesia in pregnant mice induced brain inflammation, evidenced by increased interleukin-6 levels in fetal and offspring mice.  Sevoflurane anesthesia also impaired learning and memory in offspring mice. The authors concluded that sevoflurane may induce detrimental effects in fetal and offspring mice, and that these findings should promote more studies to determine the neurotoxicity of anesthesia in the developing brain.

What does all this mean to you if your children need anesthesia and surgery?  Although further studies and further data will be forthcoming, the current information suggests that:  (1) if your child has one exposure to anesthesia, this may constitute no increased risk to their developing brain, and (2) repeated surgery and anesthetic exposure to sevoflurane may be harmful to the development of the brain of children under 2 years of age.  It would seem a wise choice to delay surgery until your child is older if at all possible.

What does all this mean to anesthesiologists?  We’ll be watching the literature for new publications on this topic, but in the meantime it seems prudent to avoid exposing newborns and young children to repeated anesthetics with sevoflurane.  Currently, sevoflurane is the anesthetic of choice when we put children to sleep with a mask induction, because sevoflurane smells pleasant and it works fast.  Children become unconscious within a minute or two.  After a child is asleep, it may be advisable to switch from sevoflurane to the alternative gas anesthetic desflurane, since the Harvard study on mice showed anesthesia with 9% desflurane for 2 hours daily for 3 days caused neither cognitive impairment nor neuroinflammation.  A second alternative is to switch from sevoflurane to intravenous anesthetics alone, e.g., to utilize propofol and remifentanil infusions instead of sevoflurane.

The concept of pediatric anesthesia harming the developing brain was reviewed in the lay press in Time magazine in 2009 (Eben Harrell, Anesthesia: Could Early Use Affect the Brain Later, Time, Nov 3, 2009).  The four articles I summarized above represent the most recent and detailed advances on this topic.  Stay tuned.  The issue of anesthetic risk to the developing brain will be closely scrutinized for years to come.

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Introducing …,  THE DOCTOR AND MR. DYLAN, Dr. Novak’s debut novel, a legal mystery. Publication date September 9, 2014 by Pegasus Books.

The first four chapters are available for free at Amazon. Read them and you’ll be hooked! To reach the Amazon webpage, click on the book image below:

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Stanford professor Dr. Nico Antone leaves the wife he hates and the job he loves to return to Hibbing, Minnesota where he spent his childhood. He believes his son’s best chance to get accepted into a prestigious college is to graduate at the top of his class in this remote Midwestern town. His son becomes a small town hero and academic star, while Dr. Antone befriends Bobby Dylan, a deranged anesthetist who renamed and reinvented himself as a younger version of the iconic rock legend who grew up in Hibbing. An operating room death rocks their world, and Dr. Antone’s family and his relationship to Mr. Dylan are forever changed.

Equal parts legal thriller and medical thriller, The Doctor and Mr. Dylan examines the dark side of relationships between a doctor and his wife, a father and his son, and a man and his best friend. Set in a rural Northern Minnesota world reminiscent of the Coen brothers’ Fargo, The Doctor and Mr. Dylan details scenes of family crises, operating room mishaps, and courtroom confrontation, and concludes in a final twist that will leave readers questioning what is of value in the world we live in.

REVIEWS:

5.0 out of 5 stars The Doctor and Mr Dylan, March 3, 2015
By
prabha venugopal (chicago, il USA) – See all my reviews
Verified Purchase(What’s this?)
Gripping from the beginning to the end. Very well written, bringing to the forefront all the human emotions seen in an operating room spill over into real life. I cannot wait for Dr. Novak to wrote another book! As another physician in the same profession, my admiration for his book knows no limits.

Bang-Up Debut Novel, November 16, 2014

By Norm Goldman “Publisher & Editor of Bookpleasures”

This part legal and medical thriller is structured with a mixed bag of situations involving relationships, jealousy, evil, lies, courtroom drama, operating room mishaps as well as moments that engender conflicting and unexpected outcomes. Noteworthy is that as the suspense builds readers will become eager to uncover the truth involving a mishap concerning Nico and a surgical procedure that has unanticipated ramifications.

This is a bang-up debut from a writer who understands timing and is able to deliver hairpin turns, particularly involving the courtroom drama,that you would expect from a book of this genre.

TwinCities.com PIONEER PRESS Entertainment

by Mary Ann Grossman, Entertainment Editor, St. Paul Pioneer Press mgrossman@pioneerpress.com, January 4, 2015

“The Doctor & Mr. Dylan” by Rick Novak (Pegasus Books, $17.50)

Dr. Nico Antone doesn’t hide the fact he hates his wife, but he says he didn’t kill her during an operation. The authorities think otherwise and his trial is the riveting suspense in this novel that is part medical thriller, part legal thriller, part exploration of family relationships.

Nico is an anesthesiologist (as is the author) who leaves his wife, their plush life in California and his job at Stanford to move to his hometown of Hibbing so their son, Johnny, has a better chance of getting into a prestigious college. Johnny hates the idea of moving to a small, cold town, but he’s popular from the first day in school. Nico doesn’t do so well. He’s envied by Bobby, an anesthetist who’s jealous of the better-educated Nico. But it’s hard to take Bobby seriously, since he thinks he’s the young Bob Dylan and lives in the house where Bobby Zimmerman grew up. To complicate matters, Nico is attracted to the mother of the young woman his son is dating. When the two teens get in trouble, Nico’s furious, rich wife comes to Minnesota and needs an emergency operation that puts her on Nico’s operating table.

Novak grew up in Hibbing, where he worked in the iron ore mines and played on the U.S. Junior Men’s Curling championship teams of 1974 and ’75. After graduating from Carleton College, he earned a medical degree at the University of Chicago and spent 30-plus years at Stanford Hospital, where he was an associate professor of anesthesia and Deputy Chief of the Anesthesia Department. His courtroom scenes are based on his experiences as an expert witness.

The Physician’s Late-Night Reading List

Two Pritzker alums pen captivating tales

By Brooke E. O’Neill, University of Chicago Pritzker School of Medicine, editir, Medicine on the Midway Magazine

For most physicians, writing — patient notes, case histories, perhaps journal articles — is part of the job. But for anesthesiologist-novelist Rick Novak, MD’80, and neurosurgeon-memoirist Moris Senegor, MD’82, it’s a second career that consumes early morning hours long before they step into the OR.

Fans of John Grisham will find a kindred spirit in Novak, whose fast-paced medical thriller, The Doctor & Mr. Dylan (Pegasus Books, 2014), transports readers to rural Northern Minnesota, where an accomplished physician and a deranged anesthetist who thinks he’s rock legend Bob Dylan see their worlds collide in the most unexpected ways.

Delivering real-life twists and turns — and a love letter to the Bay Area — is Senegor’s Dogmeat: A Memoir of Love and Neurosurgery in San Francisco (Xlibris, 2014), a coming-of-age tale chronicling the author’s away rotation with renowned neurosurgeon Charles Wilson, MD, at the University of California, San Francisco. Brutally honest, it spares no details of a time Senegor, who also served as a resident under the University of Chicago’s famed neurosurgery chair Sean Mullan, MD, describes as “one of the biggest failures of my life.”

One a vividly imagined nail-biter, the other an intimate peek into the surgical suite, both books deliver an ample dose of intensity and drama.

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The Doctor and Mr. Dylan (Pegasus Books, 2014) by Rick Novak, MD’80

“I thought it was a novel way of killing someone,” said Rick Novak, deputy chief of anesthesiology at Stanford University, describing the imagined hospital death that was the genesis of his dark thriller The Doctor & Mr. Dylan. A huge Bob Dylan fan — the rock icon was born in Novak’s hometown of Hibbing, Minnesota, where the story takes place — he then dreamed up a possible culprit: a psychotic anesthetist who thinks he’s Dylan.

From there, the words flowed. “I would write whenever I was with my laptop and had a free moment: in mornings, in evenings, in gaps between cases,” said Novak, who also blogs about anesthesia topics. “I don’t sleep much.”

After finishing the manuscript — one year to write, another to edit — came the challenge of finding a publisher. “In anesthesia, I’m an expert,” Novak said. “In the literary world, I’m an unknown.” After 207 responses of “no, thanks” or no answer at all, he landed an agent. Two months later, she informed him that Pegasus Books had bought his debut novel.

“I started crying,” Novak admits. “I have a third grader and at the time the big word the class was learning was ‘perseverance.’ That was it exactly.”

Dr. Joseph Andresen, Editor, Santa Clara County Medical Association Medical Bulletin, from the January/February 2015 issue:

BOOK REVIEW “THE DOCTOR AND MR. DYLAN”

This past month, Dr. Rick Novak handed me a hardbound copy of his debut novel The Doctor and Mr. Dylan. Rick and I go way back. It was my first week of residency at Stanford when we first met. A newcomer to the operating room, all the smells and sounds were foreign to me despite my previous three years in the hospital as an internal medicine resident. Rick, a soft spoken Minnesotan at heart, in his second year of residency, took me under his wing and guided me through those first few bewildering months, sharing his experience and wisdom freely.

Fast-forward 30 years later. Dr. Rick Novak, a novel and mystery author? This was new to me as I sat down and opened the first page of The Doctor and Mr. Dylan. I have to admit that I didn’t know what to expect. Few books highlight a physician/anesthesiologist as a protagonist, and few books feature a SCCMA member as a physician/author. However, a medical-mystery theme novel wasn’t at the top of my must read list. With my 50-hour workweek, living and breathing medicine, imagining more emotional stress and drama was the furthest thing from my mind. However, three days later, as I turned the last page, and read the last few words. “life is a series of choices. I stuck my forefinger into the crook of the steering wheel, spun it hard to the left and …” This completed my 72-hour journey of and free moments I had, completely immersed in this story of life’s disappointments, human imperfections, and simple joys.

Rick, I can’t wait for your next book. Bravo!

Hibbingite writes twisted medical tale

HIBBING — Readers who are looking for a whodunit that will keep them up all night are in for a treat.

Hibbing native Rick Novak recently released his first book “The Doctor and Mr. Dylan,” a fiction set in Hibbing that merges anesthesia complications, a tumultuous marriage and the legend of Bob Dylan.

“The dialogue is sometimes funny, and there are lots of plot twists,” he said.

Novak said the book will not only entertain readers, but teach them about anesthesiology, Dylanology, the stressful race for elite college admission, and life on the Iron Range.

“The book is very conversational and streamlined,” he said. “I try to write as one would tell a story out loud.”

Novak said “The Doctor and Mr. Dylan” took him three years to perfect. He is currently working on his second book.

5.0 out of 5 stars I Sense We Have Another F.Scott Fitzgerald Emerging on the Literary Scene, December 1, 2014
By
Deann Brady (Sunnyvale, CA USA) – See all my reviews
(REAL NAME)
I found Rick Novak’s first novel, “The Doctor and Mr. Dylan,” a most exciting combination of biting sarcasm, mystery and daily activity spun with fresh new phrases that made me turn my ear back to listen to the literary cadence of his words again and again even though, on the other hand, I was anxious to turn the pages to see what would happen next. His brilliant handling of scenes is reminiscent of The Great Gatsby by F. Scott Fitzgerald. A compelling read!Deany Brady, author of “An Appalachian Childhood”

By

allan mishra

This review is from: The Doctor and Mr. Dylan (Kindle Edition)

Just finished Dr. Novak’s delightful novel. I sincerely enjoyed his honest take about the pressures and values that exist within California’s Silicon Valley. He also brought the North Country of Minnesota to life with memorable characters and a twisting, addictive plot. Buried beneath the fun and funny story is a deeper message about how to best care for your kids, your relationships and yourself. Very well written and highly recommended.

Learn more about Rick Novak’s fiction writing at rick novak.com by clicking on the picture below:

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3 thoughts on “DOES REPEATED GENERAL ANESTHESIA HARM THE BRAINS OF INFANTS AND YOUNG CHILDREN?

  1. Dear Dr. Richard,

    My Name is Yuristian, I am from Indonesia. I Really need your advice about repeated general anesthesia for young children.

    I have situation, my 9 months baby have cataract in left eye, she has surgery when she was 3 months with general anesthesia (as her doctor suggestion). now, my daughter has artificial lens in her left eye. But, because of inflammation in her eye and it makes her left eye still did not function properly, her doctor suggest to re-surgery and it will do under general anesthesia.

    But, based on some literature that I have read before and also your blog, repeated exposure of general anesthesia will increase Learning Disabilities risk. But, her doctor said that with her left eye did not function properly it also impact to her learning ability.

    Now, I am really confused and need advice, please give me your advice for this situation.

    Thank You & Best Regards,
    Yuristian

    Like

    1. Of course I do not know all the medical details for your child, but . . .

      In America, if a 9-month old baby needs a second surgery that is definitely indicated, the anesthesia and surgery will go forward. The risk of Learning Disabilities may not be zero, but if the surgery is necessary, that urgency trumps any theoretical risk of Learning Disabilities. If the surgery can be delayed, the surgeons may very well advise waiting. If surgery can not wait, it will proceed.

      Like

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