Week 7 - Anesthesia and Cognitive Development Flashcards
What was included in the FDA warning/labeling changes of 4/27/17 concerning early exposure to anesthesia/sedation drugs?
FDA label changes for anesthetic and sedation drugs in children <3 years old
- exposure for lengthy period or over multiple surgeries/procedures may negatively affect brain development
- describes studies in young/fetal animals showing >3 hours exposure causes wide spread loss of nerve cells (suggest long term negative effects on behavior/learning)
What was the 12/14/16 FDA announcement concerning early exposure to anesthesia/sedation drugs?
Referred more specifically to 3rd trimester exposure to anesthetic and sedation drugs
*less emphasized in 4/27/17 announcement
What have many studies of late fetal or early neonatal GA in animals shown?
Blockage of NMDA glutamate receptors for a few hours results in widespread apoptotic neurodegeneration
Which neurotransmitter is involved in neuronal survival?
The excitatory neurotransmitter Glutamate
Define apoptosis and neuroapoptosis
Apoptosis = programmed cell death
Neuroapoptosis = apoptotic neuronal death
*essential for normal brain development
What percent of brain cells does neuroapoptosis eliminate during normal brain development?
50-70%
How does blockage of NMDA glutamate receptors affect neuroapoptosis?
Blockage of NMDA glutamate receptors produces abnormal increase in neuroapoptosis
*associated with persisting learning deficits during later life in rats
Exposure to which class of drugs during early life are shown to be associated with adverse effects on CNS development?
Blockage of NMDA glutamate receptors
Activation of GABAa receptors
*virtually all common volatile, injectable, and gaseous anesthetics have NMDA antagonist and GABA mimetic effects
Where has neuroapoptosis/ neurodegeneration been found?
Various brain regions (including cortex)
Various anesthetics
Various species
-mice, rats, guinea pigs, swine, rhesus monkeys
Cortical damage has been shown with which drugs (individually or in combo)?
- Ketamine
- Volatile anesthetics (Isoflurane, Desflurane)
- Nitrous Oxide
- Benzodiazepines (Midazolam, Diazepam)
Do anesthetics have analogous CNS/cognitive effects in humans?
- Some drugs do
- Alcohol use during pregnancy – fetal alcohol syndrome
- Some antiepileptic drugs (valproic acid, phenytoin) during pregnancy – fetal malformations, microcephaly, developmental delay
*anesthesia effects on CNS/cognition of otherwise “healthy” human infants has been studied little until recently (2009 on) – no clinically obvious long-lasting effects noted
What are some issues with some of the older clinical studies that examined neurological outcomes of anesthesia and surgery?
- Often lacked specific measures of brain structure/activity
- Sometimes lacked specific measures of cognition
- Outcome measures: heterogeneous, sometimes not well-defined
- Involved patients with significant medical problems that might affect CNS/cognition
- Involved other confounding conditions (prematurity, low birth weight, malformations, genetic syndromes, cardiopulmonary bypass)
- Sometimes, limited follow-up periods (a few months after surgery)
- Temporary behavioral problems don’t imply long-lasting effects
What are some results of the more recent clinical studies of the effects of anesthesia on cognitive development?
- Anesthesia during age 0-3 years found 2+, but not 1, exposure to anesthesia increased learning disabilities during childhood and learning disabilities were related to duration of anesthesia
- Brief anesthesia exposure during Cesarean delivery did NOT increase learning disabilities
- Later developmental and behavioral disorders were more frequent for infants and young children exposed to anesthesia for hernia repair than those who were not
- Later behavioral problems were not significantly higher for younger than older ages of exposure to anesthesia during ages 0-6 years
What are the conclusions of human studies to date on the effects of anesthesia on cognitive development?
- Findings quite mixed
- Some adverse effects of anesthesia found
- Some studies show no effects
- Unclear if effects depend on type of assessment (i.e. cognitive tests, diagnoses, academic achievement, or brain imaging)
- Very few brain imaging studies
- Unclear what factors influence effects (type of surgery/anesthetic, duration of anesthesia, age at time of anesthetic, gender, prematurity, other health issues… etc)
If it is accepted that commonly used anesthetics have adverse CNS effects in young children, what are alternatives?
Don’t do the procedure or delay surgery until after 3rd birthday?
Alternative non-surgical treatments?
Alternative drugs?
-dexmedetomidine: different mechanism… although not sufficient for GA alone
