Anesthetic‐induced neurotoxicity of the neonate: time for clinical guidelines?

By now most pediatric anesthetists will be aware of the issue of possible neurotoxic effects of general anesthetics on the developing brain. The subject is regularly discussed in editorials, reviews, and conference meetings. It is also being raised in the lay press. Parents are understandably concerned about the effects of any drugs on their newborn or unborn child. Is it time to go further and develop clinical guidelines based on the available evidence? Some recommendations have indeed already been made. In 2007, the Federal Drug Administration (FDA) anesthetic and Life Support Drugs Advisory Committee released minutes suggesting that surgery that was truly elective should be postponed until after 6 months of age. This was based on concerns about the neurotoxic effects of anesthetics on neonatal animals (1). An editorial in 2008 built on these remarks stated: Until the risk of neurocognitive injury is understood, pediatric surgical specialties, in conjunction with anesthesiologists and pediatricians, should identify surgical procedures that can be delayed until older ages without incurring additional risk (2). Are these recommendations sufficient, or should more concrete clinical guidelines be developed? The above recommendations suggest surgery be delayed provided it is either elective, or the delay incurs no added risk. A key question in implementing this recommendation is how long should surgery be delayed. Also, it only applies to the relatively uncommon scenario of the truly elective case that can be postponed indefinitely. It is already recognized that anesthesia in the neonate is technically challenging, and that neonatal anesthesia poses greater risk than anesthesia in older children. This is for many reasons apart from neurotoxicity (3,4). In consequence, truly elective surgery tends not to be performed in infants; infants have surgery or anesthesia because they need it, and therefore, any delay usually incurs some risk. For clinical guidelines to have any practical value, they must address the scenarios where delay is unavoidable or delay has some risk. To develop guidelines for these cases, additional questions must be answered: what is the actual risk of general anesthetic exposure, which infants are most at risk, and which anesthetic techniques have least risk? Additionally, are there any safe and effective protective agents that can be used? If these questions can be answered, the degree of risk of exposure in a particular infant can be balanced with the risk of delay, and alternate anesthetic techniques or protective strategies can be suggested. Thus, the five key questions that must be answered to develop practically useful clinical guidelines are: 1. What is the degree of risk in terms of likelihood and magnitude? 2. At what age does the risk of exposure become negligible? 3. Apart from age, what other patient factors influence risk? 4. To what extent can different anesthetic techniques, agents, and dose influence risk? 5. Are there protective agents that can be used? Correspondence to: Dr. Robert D. Sanders, Department of Anaesthetics, Imperial College London, Magill Department of Anaesthetics, Pain and Intensive Care Medicine, Chelsea & Westminster Hospital, Fulham Rd, London SW10 9NH, UK (email: robert. sanders@imperial.ac.uk). Pediatric Anesthesia 2009 19: 1141–1146 doi:10.1111/j.1460-9592.2009.03141.x