RCoA report there is currently much debate on the approach anaesthetists and the wider medical team should take in response to publications about the potential of general anaesthetic agents to cause changes in the developing brain. The debate centres on initial observations in immature animals that a variety of anaesthetic agents including volatile anaesthetic agents, propofol, ketamine and benzodiazepines can induce both cytological, biochemical and behavioural changes after anaesthesia. There are a number of published studies looking at the potential relevance in the human infant and additional ongoing studies will provide information in the near future.
The studies have concentrated on the potential harms of anaesthesia on cognitive development in the young after exposure to anaesthetic agents through different approaches: retrospective epidemiological data, prospective cohorts, and randomised controlled trials. The data continues to emerge and therefore any guidance needs to be time sensitive. However there have already been many statements published on this topic with wide spectra of opinion and advice. These include (to date) SmartTots, Safetots, an FDA advisory statement, a European working party statement and editorials in Pediatric Anesthesia and The New England Journal of Medicine (1). These are referenced in the text below. Several of the documents offer conflicting advice on the “at risk” population, the interpretation of potential harm and advice for anaesthetists on what to discuss with parents and carers before surgery.
In response to requests from the anaesthesia community in UK and Ireland, the Royal College of Anaesthetists have provided a brief summary of key points that are clear and provide a safe and sensible response to the current knowledge. This does not take the place of a systematic review on the topic and is not intended to present a prescriptive view on anaesthesia in the very young. The guidance has been prepared to help clarify current knowledge and provide a balanced approach to the data.
RCoA have provided suggestions on how to discuss the subject when it has been brought up by parents. There is also a “Frequently Asked Questions” section with suggested responses, and an up to date reference list. Other data may emerge that will help to clarify the issue, and we will continue to review this guidance document in the light of new knowledge. Advisory statements from the MHRA may emerge on this topic, which will also need monitoring. This Guidance must therefore be seen within the context of a broad approach to this potential (but as yet unproven) problem and adjusted as new information emerges.
Current State of Knowledge
Laboratory studies have shown dose-dependent alterations in brain morphology following exposure of neonatal and infant animals to anaesthesia. [2; 8; 11] Dose-dependent acute tissue effects have been reported with many anaesthetic drugs (volatile agents, propofol, thiopental, ketamine, benzodiazepines). Effects vary with the age of the animal, but it is difficult to directly translate ages across mammalian species. Maturation varies in different brain regions, and structural changes may not reflect significant alterations in function. Some studies have shown long-term adverse effects on memory tests in rodents and cognitive tests in primates following prolonged initial exposures. However, monitoring and maintaining physiological stability is difficult in small animals, and the impact of anaesthesia alone, versus anaesthesia and surgical injury, and potential preventive strategies require further evaluation. As a result, it is difficult to directly extrapolate from the laboratory results to current clinical practice.
Human clinical studies evaluating the potential adverse effects of anaesthesia on behavioural and cognitive outcomes in children have been undertaken through prospective randomised trials and epidemiological methods. Importantly, recent prospective studies have shown no difference in outcome 2 years following hernia repair in infants [4] or at 8-15 years of age following a single anaesthetic before 3 years of age. [10] Evidence from epidemiological cohort studies is mixed, as exposures and outcomes vary, but several recent studies have shown no major adverse effects following single anaesthetics. [3; 5-7; 9] The lack of adverse effect following a single anaesthetic exposure of approximately one hour is reassuring.
The recent FDA Drug Safety Communication for General Anaesthetic and Sedation Drugs
(www.fda.gov/Drugs/DrugSafety/ucm532356.htm) has raised concern and led to responses from anaesthesia bodies. This communication includes recommendations for health care professionals on balancing the benefits and potential risks of prolonged anaesthesia (greater than 3 hours) or repeated anaesthesia in children under 3 years. It also provides recommendations to parents/caregivers on discussing potential risks and benefits with their child’s health care professional. The FDA Safety Communication specifically refers to prolonged or repeated exposure, which is a clinical group where there is limited evidence and it is difficult to attribute effects specifically to anaesthetic drugs. There are many confounde