General anesthesia may cause unintended side effects in some infants, studies have found. Regional anesthesia may therefore be the better option.
In a study published in Pediatrics (2015;136:e1-e12, doi:10.1542/peds.2014-3526), researchers found that children who received general anesthesia before 4 years of age had a lower IQ, decreased brain matter density and slower language comprehension than a comparator group of children who did not receive anesthesia. In other studies, published in Anesthesiology, researchers found that regional anesthesia may be preferable to general anesthesia for infants during their first year of life.
Because most children don’t have elective surgeries—and some may require multiple surgeries to correct serious health problems, such as cardiac issues—it is critical to determine the effects of anesthesia on young patients, said Andreas W. Loepke, MD, PhD, professor of clinical anesthesia and pediatrics at the University of Cincinnati College of Medicine. Dr. Loepke and other researchers from Cincinnati Children’s Hospital Medical Center looked at developmental delays potentially related to early surgery.
Yin and Yang
Anesthetics can be protective in certain settings, but may be harmful in others. It’s a “yin and yang” relationship, Dr. Loepke said. “We started our animal research trying to find ways for anesthesiologists to alleviate some of the developmental delays seen following major surgeries, such as for congenital heart disease,” he said. “We felt that some of these delays could be due to problems in the operating room during cardiopulmonary bypass and that anesthetics may protect in this situation. More recently, we have looked into how anesthetics themselves may negatively affect brain development.”
The retrospective study compared the scores on the Oral and Written Language Scales and the Wechsler Intelligence Scale between 53 participants aged 5 to 18 years who had no history of surgery and the scores of 53 children in the same age range who had surgery before 4 years of age. The average test scores for all 106 students were within population norms, regardless of surgical history. However, when the researchers matched the children on age, sex, handedness and socioeconomic status, those exposed to anesthesia scored significantly lower for listening comprehension and performance IQ. In addition, the decreased language and IQ scores were associated with lower gray matter density in the occipital cortex and cerebellum, as seen on MRI scans.
“Compared to the overall population, we did not see a decrease,” Dr. Loepke said. “However, I was very surprised that previously exposed patients did not score higher on any of the tests and, in fact, did significantly worse on two tests—listening comprehension and performance IQ.”
Other recent studies have indicated that language could be one way to study development more specifically than “academic performance,” particularly if a validated test is used. In addition, the structural findings on the children’s MRI scans matched study results published by Dr. Loepke’s group in the British Journal of Anaesthesia last year (2014;113:443-451) that showed cell death in the posterior region of the brain as well.
“All of the animal studies suggest that general anesthesia may be detrimental to the developing brain,” Dr. Loepke said. “The problem is that all human studies are retrospective, and we can’t isolate the cause of the impairment.”
Another aspect of the study is that the researchers estimated a social cost of their findings. Research from 2008 estimated that a 1-point reduction in IQ could decrease a person’s lifetime earnings by $18,000. For a loss of 5 points in IQ in this study, the researchers said the 6 million children who undergo surgery in the United States each year could lose potential lifetime earnings totaling $540 billion.
“We don’t know if a 5-point decrease means the difference between being accepted to an Ivy League school or a community college in terms of a measurable impact for the individual,” Dr. Loepke said. “However, our finding could represent a big societal problem.”
No Problem Anecdotally?
The study has received mixed reactions. Some have indicated that this idea isn’t new, while some clinicians say they have treated patients for decades without noticing a problem anecdotally.
“If we simply say ‘none of my kids come out dumb,’ we are making it too easy for ourselves,” Dr. Loepke said. “Our No. 1 concern is the safety of kids during surgery, and we owe it to our young patients to continue research to eliminate threats to their development.” Because researchers still aren’t sure exactly what happens to the developing brain during anesthesia or how to mitigate potential problems, more research needs to be done.
Several researchers at Cincinnati Children’s Medical Center are investigating alternative anesthetic techniques in ongoing studies and are participating in an international clinical trial to test an alternative regimen in young children undergoing urologic procedures. Unfortunately, studies in children will be slow to produce results, Dr. Loepke said. Adults can undergo a neurocognitive test before and after surgery, whereas children may be most susceptible to adverse effects at an age when validated neurocognitive tests are not available. Dr. Loepke and others want to look more closely at patient age at exposure and specific phenotypes.
Despite these findings, Dr. Loepke wants parents, surgeons and anesthesiologists alike to remember that surgeries and anesthesia are safe for children. In fact, survival rates for premature neonates undergoing complex procedures are at an all-time high, Dr. Loepke noted, and many surgeries that treat chronic ear infections, sleep apnea or enlarged tonsils can alleviate health problems and improve school performance.
“We all need to take on a bigger role in the discussion of risks, benefits and side effects,” he said. “Actually, delaying or not performing needed surgery may be more harmful for children than undergoing the surgery. It’s ‘yin and yang’ again.”
Is Regional the Answer?
A potential solution is suggested by two studies published in Anesthesiology: choosing regional over general anesthesia. In the studies (2015;7:38-54 and 55-65), an international group of researchers measured the presence of apnea following hernia surgery in 722 infants who underwent anesthesia during their first year of life. Regional anesthesia reduced the risk for significant apnea in the first 30 minutes after surgery.
“As an anesthesiologist, you worry about how to help the baby after surgery,” said Andrew J. Davidson, MD, associate professor and medical director of the Melbourne Children’s Trials Centre. “Do you send the baby home? Stay overnight? Go to the NICU [neonatal ICU] for a few days?”
Of the 722 infants, Dr. Davidson’s colleague Geoff Frawley, MBBS, a physician-anesthesiologist and clinical associate professor in the Department of Anaesthesia and Pain Management, The Royal Children’s Hospital, in Melbourne, Australia, examined 339 patients who had spinal anesthesia and searched for factors affecting failure or success of the technique. He found that nearly 17% of cases required an additional form of anesthesia, and sometimes the failure included the provider’s relative inexperience in administering spinal anesthesia.
“We aimed to establish which factors are associated with better outcomes when infant spinal anesthesia is used,” Dr. Frawley said. “We found that there is a steep learning curve among anesthesia providers for infant spinal anesthesia, but learning the technique could have a far-reaching impact.”
The study was the largest of its kind to date looking at apnea. Drs. Davidson and Frawley plan to publish results focusing on neurodevelopmental outcomes in the coming months. Their research is part of a larger initiative to examine the effects of anesthesia on brain development, which is being led by SmartTots, a public–private partnership between the FDA and the International Anesthesia Research Society.
“This collaboration is a huge step forward in pediatric anesthesia,” Dr. Davidson said. “Adult trials started with a similar one, which led to one study after another.”
For now, Dr. Davidson advised that anesthesiologists consider training in regional anesthesia in infants. Although the technique has been well known and well described for decades, many clinicians are still nervous about holding the baby motionless and finding the right spot for the anesthetic, he said.
“If you haven’t done it before, it can be a steep learning curve and disheartening when you do it incorrectly,” he said. “But the good news is once you’ve done it a few times, it becomes facile and a fantastic technique.” Spinal anesthesia proved successful in 86.9% of cases and a combined caudal spinal anesthetic approach was successful in 76.1%.
Furthermore, this may make for a better experience for the child, parent, surgeon and anesthesiologist alike. The baby tends to fall asleep, the operation is peaceful, and it’s easy to wake up the infant after surgery, he said.
“Like a lot of regional anesthesia, once you become good at it, you get hooked,” he said. “And it may be better for children in the end.”