Effect of General Anesthesia in Infancy on Long-Term Recognition Memory in Humans and Rats

Abstract

Anesthesia in infancy impairs performance in recognition memory tasks in mammalian animals, but it is unknown if this occurs in humans. Successful recognition can be based on stimulus familiarity or recollection of event details. Several brain structures involved in recollection are affected by anesthesia-induced neurodegeneration in animals. Therefore, we hypothesized that anesthesia in infancy impairs recollection later in life in humans and rats. Twenty eight children ages 6-11 who had undergone a procedure requiring general anesthesia before age 1 were compared with 28 age-and gender-matched children who had not undergone anesthesia. Recollection and familiarity were assessed in an object recognition memory test using receiver operator characteristic analysis. In addition, IQ and Child Behavior Checklist scores were assessed. In parallel, thirty three 7-day-old rats were randomized to receive anesthesia or sham anesthesia. Over 10 months, recollection and familiarity were assessed using an odor recognition test. We found that anesthetized children had significantly lower recollection scores and were impaired at recollecting associative information compared with controls. Familiarity, IQ, and Child Behavior Checklist scores were not different between groups. In rats, anesthetized subjects had significantly lower recollection scores than controls while familiarity was unaffected. Rats that had undergone tissue injury during anesthesia had similar recollection indices as rats that had been anesthetized without tissue injury. These findings suggest that general anesthesia in infancy impairs recollection later in life in humans and rats. In rats, this effect is independent of underlying disease or tissue injury.

Early‐life single‐episode sevoflurane exposure impairs social behavior and cognition later in life

“…2012; Stratmann et al. 2014). However, rats in both groups were treated for 4 h with sevo ranging from 2.1% to 5.3%.…”

“…2016), while another group found cognitive impairment in children ages 6–11 years (Stratmann et al. 2014). …”

Long-term Fate Mapping to Assess the Impact of Postnatal Isoflurane Exposure on Hippocampal Progenitor Cell Productivity

“…Consistent with this idea, experimental manipulations that transiently deplete adult-generated granule cells have been shown to produce a variety of behavioral deficits, including disruption of hippocampal dependent memory, 50-52 impaired responses to anti-depressant medications [53][54][55] and altered responses to convulsant drugs. 56,57 Deficiencies in recollection memory have recently been observed five to ten years following anesthesia and surgery in infancy, 58 possibly reflecting long-term consequences of transient hippocampal disruption. Animal and human studies designed to detect such transient deficits should be carefully timed with regard to the exposure period to optimize the chances of observing an effect.…”

Is a short anesthetic exposure in children safe? Time will tell: a focused commentary of the GAS and PANDA trials

“…Infant rats were given an anesthetic of isoflurane, nitrous oxide and midazolam and were subsequently found to have significant neuronal cell death and lasting memory impairment (10). Since then there have been many animal studies demonstrating this effect in different species (5,11), with different anesthetic agents (12)(13)(14)(15), and affecting different domains of cognition (16)(17)(18). Early studies focused on anesthesia-induced apoptosis (10,19), however the developing brain possesses neurons in excess and normal apoptosis is present during development (20,21).…”

“…Anesthesia exposure at later ages in development results in a less significant insult, underscoring a time-sensitive period of vulnerability and further complicating our understanding of the mechanism of injury (14,22). Similarly, the duration of anesthesia is a critical determinant of the extent of the deficit, with shorter, lower concentrations leading to less or undetectable insults (18,23,24). A number of retrospective observational human studies have been done, with varied results.…”