There is concern that sedatives and anaesthetic agents may have harmful effects on the developing brain
MECHANISMS OF NEUROTOXICTY
NMDA antagonists and GABA agonists both trigger neuronal apoptosis in experimental infant animals via both:
- receptor upregulation following blockade resulting in overexcitation
- decreased trophic stimulation
- dose and time dependent
- shown for all sedative/anaesthetic agents in animal studies
- worse with agents or combinations that work via both NMDA and GABA receptor
- maximal at the time of peak synaptogenesis (in humans this is 20-26 weeks gestation)
It is unclear whether these agents speed up normal apoptosis or trigger new events
- Direct evidence in humans lacking but some evidence that early exposure to anaesthesia may result in learning problems later in life
- There is also evidence that pain may promote neuronal apoptosis at least as severe as anaesthetic agents
- paradoxically, ketamine has also been found to have neuroprotective effects in some studies
- No current guidelines on what to do in light of the above findings
- direct evidence based on animal studies (mainly rat pups at high doses) and may not be applicable in the clinical setting
- Limiting exposure seems sensible
- consider limiting the use of combinations of NMDA antagonists and GABA agonists
- overall the benefits of using these agents currently outweighs the risks
References and Links
- Sun, L. Early childhood general anaesthesia exposure and neurocognitive development. Br. J. Anaesth. (2010) 105 (suppl 1): i61-i68. [Free Full Text]
- Rappaport B, Mellon RD, Simone A, Woodcock J. Defining safe use of anesthesia in children. N Engl J Med. 2011 Apr 14;364(15):1387-90. PMID: 21388302. [Free Full Text]
- Green SM, Coté CJ. Ketamine and neurotoxicity: clinical perspectives and implications for emergency medicine. Ann Emerg Med. 2009 Aug;54(2):181-90. PMID: 18990467.
Chris is an Intensivist and ECMO specialist at the Alfred ICU in Melbourne. He is also a Clinical Adjunct Associate Professor at Monash University. He is a co-founder of the Australia and New Zealand Clinician Educator Network (ANZCEN) and is the Lead for the ANZCEN Clinician Educator Incubator programme. He is on the Board of Directors for the Intensive Care Foundation and is a First Part Examiner for the College of Intensive Care Medicine. He is an internationally recognised Clinician Educator with a passion for helping clinicians learn and for improving the clinical performance of individuals and collectives.
After finishing his medical degree at the University of Auckland, he continued post-graduate training in New Zealand as well as Australia’s Northern Territory, Perth and Melbourne. He has completed fellowship training in both intensive care medicine and emergency medicine, as well as post-graduate training in biochemistry, clinical toxicology, clinical epidemiology, and health professional education.
He is actively involved in in using translational simulation to improve patient care and the design of processes and systems at Alfred Health. He coordinates the Alfred ICU’s education and simulation programmes and runs the unit’s education website, INTENSIVE. He created the ‘Critically Ill Airway’ course and teaches on numerous courses around the world. He is one of the founders of the FOAM movement (Free Open-Access Medical education) and is co-creator of litfl.com, the RAGE podcast, the Resuscitology course, and the SMACC conference.
His one great achievement is being the father of three amazing children.
On Twitter, he is @precordialthump.