Isoflurane Anesthesia Has Long-term Consequences on Motor and Behavioral Development in Infant Rhesus Macaques

Abstract

Background-Experimental evidence correlates anesthetic exposure during early development with neuronal and glial injury and death as well as behavioral and cognitive impairments in young animals. Several, although not all, retrospective human studies of neurocognitive and behavioral disorders following childhood exposure to anesthesia suggest a similar association. Few studies have specifically investigated the effects of infant anesthesia exposure on subsequent

Effect of Anesthesia on the Developing Brain: Infant and Fetus

“…The animal models have extended to non-human primates, determining that exposure to ketamine and volatile anesthetics result in long-term learning problems [4] . A recent study by Coleman et al [18] exposed neonatal rhesus macaques to 5 h of isoflurane anesthesia either once or 3 times to test dose-response to multiple exposures. When compared to control animals, neonatal monkeys exposed to isoflurane 3 times had motor reflex deficits at 1 month of age, and increased anxiety behaviors.…”

Monkey in the Middle

“…It has also sparked parallel retrospective and prospective studies in humans that suggest that pediatric anesthesia might be associated with increased risk for adverse neurocognitive outcomes when exposure is repeated or prolonged 2–9 . The recent investigation by Coleman and colleagues 10 joins a growing number of studies investigating the impact of exposure to general anesthesia in infancy on neurobehavioral development in nonhuman primates. This highly translationally-relevant model makes unique contributions to understanding the phenomena and potential mechanisms of long-term cognitive and behavioral changes after general anesthesia early in life.…”

“…Single anesthesia exposures in infants that have been investigated recently 8,9 are of short duration relative to those in the studies to date with monkeys. It is worth noting that prolonged anesthesia exposure is certainly not unknown in pediatric surgery; Coleman et al 10 cite 30% of infant anesthesia exposures being longer than 3 hours at their institution, and prolonged sedation in the neonatal intensive care unit may last for weeks 17 . However, repeated exposures to anesthesia appear rare in these populations; for example, 7.4% of cases (44/593) in the study by Wilder et al 4 received 3 or more anesthetic exposures, so three long exposures to anesthesia, especially within a week, would be extremely unusual in a clinical context.…”

“…Two studies in monkeys 10,22 have independently reported increased anxiety-related behaviors in monkeys that were repeatedly exposed to general anesthesia as infants, despite using different anesthetic agents and different schedules and durations of exposure. The finding that repeated exposure is associated with adverse neurocognitive outcomes is consistent with some human epidemiological studies 4,23 .…”

“…The finding that repeated exposure is associated with adverse neurocognitive outcomes is consistent with some human epidemiological studies 4,23 . Recent prospective studies in humans have emphasized the safety of single, relatively brief exposures to general anesthesia in the context of pediatric surgery 8,9 ; Coleman et al 10 also find limited effects of single exposures to general anesthesia in monkeys. These observations reinforce one another and suggest that concerns about repeated or prolonged exposure of children to general anesthesia remain significant.…”