Anesthesiology. 2009 Apr

[Valeriy]

Вот такими новостями "радует" Медскейп.
[Ссылки доступны только зарегистрированным пользователям ]

Repeated Early Anesthesia Exposure Linked to Learning Disabilities

Pauline Anderson
March 26, 2009 — Repeated exposure to anesthesia prior to the age of 4 years is associated with almost double the risk of developing a learning disability (LD) later on, according to a new study.

But although the research showed a clear association between multiple episodes of anesthesia and learning disabilities, it cannot yet be concluded that anesthesia causes the disability, said Randall P. Flick, MD, chair of the division of pediatric anesthesiology and an assistant professor of anesthesiology and pediatrics at the Mayo Clinic in Rochester, Minnesota.

"The information has not reached a level that we can make recommendations about change in practice," Dr. Flick told Medscape Psychiatry. "The data are preliminary, it's concerning, it has the attention of the Food and Drug Administration [FDA] and others, and we'll continue to do the necessary research that will help us to better define the problem, if one really exists."

The study is published in the April issue of the journal Anesthesiology.

Dr. Flick and his colleagues analyzed outcomes in a cohort of children born in and around Rochester, Minnesota between January 1, 1976 and December 31, 1982. They tapped into resources from the Rochester Epidemiology Project to identify children from this cohort who underwent surgical or diagnostic procedures that necessitated general anesthesia. The data index included information on the type and duration of surgery, number of anesthetic exposures, age at exposure, type of anesthetic agent, and mode of delivery (inhaled, intravenous, sedative), as well as information on comorbidities.

From the original cohort, 5357 children were included in this current study. Of these, 593 underwent procedures requiring general anesthesia before the age of 4 years. These 593 children underwent 875 procedures.

Most anesthetics included halothane (88%) and nitrous oxide (91%). Dr. Flick said this was typical practice at the time of the study, although halothane is no longer used in the United States, having been replaced by a similar agent.

Assessing Disabilities

The researchers also accessed educational records from all area schools for every child in the birth cohort as well as resources of the privately owned Reading Center/Dyslexia Institute of Minnesota. To test for LD, they used standard formulas, IQ scores, and academic-achievement results to detect the presence of reading, writing, language, or mathematics disabilities.

A total of 932 children developed an LD before the age of 19 years. Compared with children not exposed to anesthesia, the risk for developing an LD was not increased for the 449 children exposed to a single anesthetic. However, the risk was significantly increased for children exposed to 2 or more doses of anesthesia.

Risk for Learning Disabilities Associated With Exposure to Anesthetics
Number of Anesthetics Adjusted Hazard Ratio 95% CI
Single exposure (n = 449) 1.00 0.79 – 1.27
2 anesthetics (n = 100) 1.59 1.06 – 2.37
3 or more anesthetics (n = 44) 2.60 1.60 – 4.24
The estimated incidence of LD by the age of 19 years was 20.0% (95% CI, 18.8% – 21.3%) in those with no exposure to anesthesia; 20.4% (95% CI, 16.3% – 24.3%) in those with a single exposure; and 35.1% (95% CI, 26.2% – 42.9%) in those with multiple exposures.


In addition, the risk for LD was increased with longer duration of anesthesia exposure; it reached statistical significance at a cumulative duration of 120 minutes or more.

The researchers were able to control for potential confounding factors known to affect the frequency of LD such as sex, gestational age, Apgar score, and birth weight.

Risks for Sicker Children

The researchers looked at whether sicker children with multiple exposures to anesthesia are more likely than healthier ones to develop an LD. They compared children who were categorized as American Society of Anesthesiologists Physical Status (ASA PS) III and IV, which signifies significant comorbidity, with patients classed as ASA PS I and II, with fewer comorbidities. In the study, 144 children received multiple doses of anesthesia.

The numbers were too small to come to any definitive conclusions, according to Dr. Flick. "One would expect that the sickest kids in our cohort who were exposed to anesthesia would be the most likely group to have learning disability, but that is not what the data showed," he said. "However, we need a much bigger cohort to be able to answer the question" of whether sicker kids develop more LDs.

Similarly, the numbers were too small to determine whether exposure to anesthesia early in life is associated with any particular type of learning disability. The researchers are collaborating with the FDA to carry out a study to try to answer this and other outstanding questions, said Dr. Flick.

Exposure Before the Age of 2 Years

Although the study included surgeries up to the age of 4 years, the authors repeated their analysis restricting exposure to anesthesia to before the age of 2 years and found the risk for LD to be similar. In fact, "the analysis showed that the effect seemed most pronounced among children whose initial exposure to anesthesia occurred between their first and second birthday," said Dr. Flick.

This study was the next step following extensive animal research that had similar results. "We have a large and growing body of animal evidence that not only is there pathologic brain injury but there are also learning deficits, memory deficits, and behavioral deficits in animals" exposed to anesthesia at an early stage, said Dr. Flick. "These findings have been repeated in various labs with various species and using different tests, so the animal data is pretty strong. The question was, does this translate to humans or not?"

Among the study's limitations is its inability to distinguish the effects of anesthesia from that of other factors such as the stress response to surgical injury. As well, the authors said they could not exclude the possibility that requiring anesthesia is a marker for something other than LD. Because of its superior healthcare, the population under study may overrepresent children with medical needs. The study population is also predominantly white and middle class, so these findings may not apply to other populations.

Best Learning Opportunities

Asked to comment on this study, Scott Benson, MD, a child and adolescent psychiatrist in private practice in Pensacola, Florida, noted that the vast majority of school-aged children who have a diagnosis of LD have never had any major surgery. A child who requires 3 and 4 surgeries before his fourth birthday "is in a group that is going to have a lot of medical problems," he said.

"If there's anything about anesthesia that's causing these kinds of defects, then we should avoid it," said Dr. Benson. "But obviously there are children who have such desperate health problems that they're going to be exposed to repeated anesthesia, and for them, like all children, we have to pay close attention to their education and make sure they get the best learning opportunities."

The message, he said, is that parents should be cautious about any surgery their child undergoes and make sure the intervention is necessary. He pointed out that once it was common for children to routinely have their tonsils removed and be treated with antibiotics for any ear infection, practices now judged unnecessary.


Support was provided by the department of anesthesiology at the College of Medicine, Mayo Clinic, and from research grants from the National Institutes of Health.

Anesthesiology. 2009;110:796-804.

А я говорил ..

Дизайн не безупречен, но дыма без огня, наверное не бывает.

[Valeriy]

Сообщение от zubarew

А я говорил...

Да-да, помню.
Остается надеяться, что результаты хотя бы частично объясняются "общей болезненностью" детей, не зря ж они нуждаются в повторных анестезиях.

[Vlad34]

Ну как-то муторно все это. "Трудности с обучением" - весьма общая фраза. Как с конкретикой - когнитивные, мнестические нарушения. Какой выраженности. По срокам после вмешательства. Извините, но к примеру поведение 12-14 летнего оболтуса, которому на улице интереснее чем в школе, объяснять перенесенным в 2 года вмешательством? Или двумя - тремя? Не зря же комментарии:

Scott Benson, MD, a child and adolescent psychiatrist in private practice in Pensacola, Florida, noted that the vast majority of school-aged children who have a diagnosis of LD have never had any major surgery.

А что теперь? Джина выпустили. Начнется массовый отказ от ургентной хирургии? Или что? Или спишут все на "ядовитый галотан", заодно с закисью?
А так при желании можно найти связь между лунным затмением и появлением двухголовых цыплят...

Да ладно, Влад, просто дополнительный аргумент против галотана у детей и еще раз в пользу потенциально менее токсичных анестетиков. А чтобы получить из этого какие-то конкретные выводы, необходимо иметь контрольную группу больных детей, которым при прочих равных не проводили операцию/анестезию или проводили под местной анестезией и прводить проспективное исследование.

Сомневаюсь что это возможно и будет пропущено этическим комитетом.

[plexus456]

Совсем не понятен акцент на галотан. Какая интересна статистика в штатах галатановых анестезий? Тоже 88% или это прицельная выборка? Снова фармфирмы?

[Valeriy]

Галотан уже не используется в США, широко применялся у детей в 70-е и 80-е гг. См. выше.

Почему не используется. Мне кажется, используется. В Британии точно используется.

[Valeriy]

although halothane is no longer used in the United States, having been replaced by a similar agent.

Я что-то не так понял?

Ну вот, например из темы на параллельном форуме: http://rusanesth.com/forum/index.php...indpost&p=7178

Новорожденный со стридором. Ингаляционная индукция. Агент выбора - галотан. Хотя, речь идет не о США, а об UK.

[Vlad34]

Самое смешное, что и в USA есть. Только под брэндом FLUOTHANE [Ссылки доступны только зарегистрированным пользователям ]. Вот отсюда [Ссылки доступны только зарегистрированным пользователям ]

Complete List Of FDA Approved Drugs As Of 7/31/2006
FLUOTHANE

Не рекомендован в акушерстве [Ссылки доступны только зарегистрированным пользователям ]
И периодически уточняется "побочное действие" [Ссылки доступны только зарегистрированным пользователям ]

[Valeriy]

Спасибо, стало ясно насчет similar agent
Тем не менее, видимо, используется достаточно редко.

Я, кстати, тоже предпочитал (когда трудился в детском ЛОР), фторотан в некоторых ситуациях севофлюрану. Например при операции по поводу аденоматоза гортани, когда нужен достаточно продолжительный эффект ингаляционного анестетика.

[Valeriy]

Теперь наш брат виноват в проблемах с психикой у выписавшихся из реанимации после тяжелого повреждения легких: [Ссылки доступны только зарегистрированным пользователям ] Не тем седируем. Что выжили, никто спасибо не скажет
А ингаляционный анестетик в данном контексте вроде лучше.

[Vlad34]

По моему скромному мнению ,сия заметка из серии "...ах было б только с кем поговорить". В первом указанном исследовании авторы связывают депрессивные расстройства прежде всего с самим фактом нахождения в ОРиТ, и тяжестью состояния, и потом с седатиками. Ничего из этого новостью не является. Признают сами авторы

Previous studies have suggested that post-ICU depression is associated with pre-ICU functional status (8) and duration of ICU stay or sedative administration (27). In univariable analyses, we found similar associations of all three variables with mean HAD score.

А про седатики, где та грань между use и abuse? Но ведь даже abuse происходит не по злому умыслу, а по необходимости. А синдром отмены бензодиазепинов и депрессия... Стоит ли обсуждать? Интересно только, что вначале указывается доза в 75 мг/день мидазолама, как ассоциирующаяся с большей степенью/частотой депрессии, а в тексте

Although we did find a significant association between depressive symptoms and mean benzodiazepine dose, this relationship may not be causal;

То есть предполагается. А по альтернативам, ИМХО предлагается оригинально. Изофлуран. Ню-ню. "У вас есть изофлуран? Тогда мы идем к вам!" Кстати по оригинальному тексту исследования

Memories of hallucinations or delusions from the ICU were less common in the isoflurane group than in the midazolam group, although
differences did not reach statistical significance (p = .06).

There was no significant difference in long-term psychological morbidity as measured by HADS and IES; six of ten isoflurane-sedated and two of six midazolam-sedated full questionnaire responders had moderate or high HADS (>11 in subscale) scores and/or moderate or high IES scores (total score >25) (p = .6).

И наконец

There was, however, no evidence in our patient sample that the trend toward lower incidence of hallucinations or delusions after isoflurane sedation led to a better long-term outcome.

То есть сравнимо с бензодиазепинами, но не более.
Интересующимся - [Ссылки доступны только зарегистрированным пользователям ] и [Ссылки доступны только зарегистрированным пользователям ]