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

Abstract

Early life exposure to general anesthesia in preclinical studies has consistently led to permanent cognitive deficits later in life. However, the extent to which this finding is translatable to humans is the subject of much debate as the results from clinical studies have been mixed. Recently two well-designed clinical trials have attempted to add clarity to our murky understanding. The General Anesthesia compared to Spinal anesthesia (GAS) trial, was an international, prospective, randomized, multicenter, equivalence trial comparing infants undergoing herniorrhaphy receiving general anesthesia vs. neuraxial anesthesia. The results released are from a pre-determined secondary outcome of a behavioral/developmental assessment of 2 years old that found equivalence between the two groups. The Pediatric Anesthesia NeuroDevelopment Assessment (PANDA) trial was an ambi-directional cohort trial, comparing patients receiving general anesthesia for hernia repair before 3 years old vs. sibling-matched controls. The neuropsychological battery performed showed no difference between siblings. Taken together, there is cautious optimism that short anesthesia exposure may not lead to significant cognitive decline in humans, but one should also consider that the GAS trial has yet to release the primary endpoint, IQ testing at age 5, and the PANDA trial may not represent the general population given the high socioeconomic status and high control IQ scores. Furthermore, as seen in preclinical studies, the cognitive deficit might not be significant until later in life, and longer exposures to anesthesia may have a more deleterious effect on cognitive function. While these new studies greatly increase our understanding in humans, there are many more questions that need to be addressed.

Keywords: Early anesthesia; RCT; cognitive impairment; neurotoxicity; pediatric anesthesia.