Awareness, dreaming and unconscious memory formation during anaesthesia in children

Best Practice & Research Clinical Anaesthesiology Vol. 21, No. 3, pp. 415–429, 2007 doi:10.1016/j.bpa.2007.05.001 available online at http://www.sciencedirect.com

10 Awareness, dreaming and unconscious memory formation during anaesthesia in children Andrew J Davidson *

MBBS, MD, FANZCA

a

Staff Anaesthetist Head of Anaesthesia Research Groupb Clinical Associate Professorc a

Department of Anaesthesia, Royal Children’s Hospital, Melbourne, Australia Anaesthesia Research Group, Murdoch Childrens Research Institute, Melbourne, Australia c Department of Pharmacology, University of Melbourne, Melbourne, Australia b

Recent studies have reported an incidence of awareness in children of around 1%, while older studies reported incidences varying from 0% to 5%. Measuring awareness in children requires techniques specifically adapted to a child’s cognitive development and variations in incidence may be partly explained by the measures used. The causes and consequences of awareness in children remain poorly defined, though a consistent finding is that many children do not seem distressed by their memories. There are, however, some published reports of persistent psychological symptoms after episodes of childhood awareness. Compared to explicit memory, implicit memory is more robust in young children; however there is no evidence yet for implicit memory formation during anaesthesia in children. Children less than 3 years of age do not form explicit memory, although toddlers, infants and even neonates have signs of consciousness and implicit memory formation. In these very young children the relevance of awareness remains largely unknown. Key words: awareness; memory; consciousness; children.

AWARENESS IN CHILDREN Compared to adults, there is considerably less known about awareness in children.1 Until recently there were few formal awareness studies in children. Awareness was * Department of Anaesthesia, Royal Children’s Hospital, Flemington Road, Parkville 3052, Victoria, Australia. Tel.: þ61 3 9345 5233; Fax: þ61 3 9345 6003. E-mail address: [email protected] 1521-6896/$ - see front matter ª 2007 Elsevier Ltd. All rights reserved.

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rarely mentioned in paediatric anaesthesia texts and children were rarely mentioned in awareness reviews. The reasons for this are unclear. Researchers may have been deterred by the generally greater difficulty of performing studies in children, or concerned that a child’s self-reporting may be unreliable. The lack of any litigation and the general reluctance of children to report adverse events may have added to a perception that awareness occurs rarely in children, or it may be that awareness in children was thought to be no different to awareness in adults and hence required no particular attention. There are however several reasons to suspect that awareness may be different in children. Differing surgical procedures, different anaesthesia techniques and age related changes in the pharmacology may influence cause and incidence, while the emotional and cognitive development may influence the way a child responds to awareness. Several studies have now confirmed that awareness does occur in children and evidence for the differing causes and consequences of awareness in children is beginning to emerge. The opinions of paediatric anaesthetists may also be changing. In a recent survey of paediatric anaesthetists through the British and French Paediatric Anaesthesia Societies, 60% of responders indicated that awareness was a problem in children, and 27% reported at least one case of awareness in their paediatric practice.2 The majority indicated that the incidence was about 1:1000 however more than 86% still do not discuss awareness as a potential risk. Definition problems in children The definition of awareness is a core concept in any discussion of the subject. Different studies have defined awareness in different ways and used different measures. Often assessments use interview techniques based on that originally described by Brice et al3, though the modifications to the original description have become so varied that quoting Brice is perhaps becoming increasingly meaningless. The exact choice of definition and the method of measure have great importance in children as there are substantial changes in memory, cognition and consciousness during development. Awareness is usually defined as the explicit recall of an event that occurred during anaesthesia. Explicit recall requires explicit memory. Children begin to develop some form of explicit memory at around 3 years of age. Between this age and adulthood, explicit memory continues to be refined and developed. Clearly explicit recall cannot be used as a measure of awareness in very young children, while in older children the developmental changes in explicit memory need to be considered when measuring or defining an episode of explicit recall. Incidence of awareness in children The reported incidence of awareness in children varies widely. There are five studies which were designed to specifically determine the incidence of awareness in children.4–8 Several more studies were primarily designed to test for wakefulness or implicit memory formation.9–14 Some of these also made some measure of explicit memory.9–12,14 Finally three reports studying the consequences of awareness included some adults who were children when the awareness occurred.15–17 In 1973, McKie and Thorpe from The Royal Children’s Hospital, Melbourne, published a prospective study of awareness and dreaming in children having a variety of surgical procedures.4 Two hundred and two children aged between 7 and 14 years

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were interviewed. They used a structured interview based on that described previously by Brice.3 The interview was worked into a more general conversation ‘‘without being too direct’’. The children were assessed by interview in hospital within 72 hours and later by questionnaire completed by the parents at 1 month. Awareness was judged by the investigators on two criteria: a) an obvious correlation with events occurring or words spoken and b) how definite the children were in their recollection. There were ten cases of definite awareness (5%). Twelve children (6%) reported dreaming with no awareness. In 1988, O’Sullivan et al from Alder Hey Children’s Hospital, Liverpool, reported the effect of pre-treatment with tubocurarine on the incidence of dreaming in children receiving suxamethonium.7 They enrolled 144 children aged between 5 and 14 years. The children were randomised to receive either pre-treatment with tubocurarine or no pre-treatment. The incidence of dreaming in the pre-treatment group was 2.8% compared to 16.7% in the control group. There is no convincing physiological explanation for this odd result. There were no cases of explicit recall. Also in 1988, the same investigators from Alder Hey published a prospective study of dreaming and awareness in 120 day-case children aged between 5 and 17 years.6 The children received a ‘‘Liverpool technique’’ (nitrous oxide, neuromuscular blocker and oxygen). The children were interviewed once before discharge. Nineteen percent reported dreaming but again there were no cases of awareness. In 1992, Bonke et al from Rotterdam published a study seeking evidence for memory of stimuli presented during anaesthesia in 80 children aged between 4 and 11 years having eye surgery.12 The memory tests were administered once on the morning after surgery. They were unable to detect any implicit or explicit memory formation. In 1995, Kalff et al from Leiden reported a study similar to Bonke et al, but without benzodiazepine premedication.11 Thirty-six children aged between 3 and 12 years were enrolled. Once again, no implicit or explicit memory formation was detected. In a third study, Rich et al played word pairs to 20 children aged 8–15 years during propofol anaesthesia for gastroscopy. They found no evidence of explicit or implicit memory formation.10 The isolated forearm technique may be used to detect wakefulness during anaesthesia. Byers et al used this technique with 41 children aged 5–16 years during 2% halothane and nitrous oxide anaesthesia.9 They found evidence for wakefulness in eight children but no explicit recall. In a similar study by Deeprose et al, the isolated forearm technique was also used to detect periods of wakefulness14 (and personal communication from Dr Andrade April 2nd 2007). Children were instructed to move their fingers at a designated point. Two of the 186 children that completed all tests in the study moved their fingers as commanded though neither had any explicit recall of the event. In 2005, we published a large audit of awareness in 864 children aged from five to 12 years of age having surgery at the Royal Children’s Hospital, Melbourne.5 The children were randomly selected and anaesthetists were unaware which children had been enrolled. The cohort did not include children expected to go to intensive care postoperatively, children with significant developmental delay or out-of-hours emergency cases. Post-operatively the children were interviewed three times with screening questions. The first interview was conducted in hospital by trained researchers. The second and third were conducted on days 3 and 30 by the parents. The screening interview was similar to the Brice interview but with more questions designed to help orient the child in time. If the child answered ‘‘no’’ to ‘‘did you have any dreams or feel or hear anything while you were having the operation’’ then they were asked no further awareness specific questions. If they answered ‘‘yes’’ then they were interviewed

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by the principal investigator. This follow-up interview sought to identify the nature of the awareness and the degree of distress, but avoided leading questions wherever possible. The child’s verbatim responses were then sent to four independent paediatric anaesthetists who judged each report as ‘‘no awareness’’, ‘‘possible’’ or ‘‘awareness’’. Twenty eight reports were generated and of these 7 cases were judged as awareness by all four adjudicators (0.8%). Recently Lopez et al from Geneva reported an audit of awareness in 410 children aged from 6 to 16 years of age.8 The anaesthetic technique was at the discretion of the anaesthetist and both elective and emergency cases were included. Children undergoing neurosurgery or those with cognitive impairment were excluded. The children were interviewed by trained psychologists within 36 hours and 1 month after the procedure. The interview was carefully constructed with introductory questions to orient the child chronologically before general open ended questions, and then increasingly specific questions. The reports were recorded and then reviewed by three independent adjudicators who classified the transcript as ‘‘awareness’’, ‘‘possible awareness’’ or ‘‘not awareness’’. Thirty-two reports were sent to the adjudicators of which 11 children (2.7%) had at least one adjudicator classify the event as awareness. Five children were classified as awareness by two adjudicators and possible awareness by the other adjudicator, and another six children were classified as awareness by one adjudicator and possible awareness by the other two. When considering the incidence of awareness in children there are two salient points: firstly the variation between studies, and secondly the high rate reported in some studies compared to awareness in adults. The studies span over 30 years of paediatric anaesthesia. Anaesthetic agents and techniques have changed significantly over that time. In the study by McKie et al, some of the aware cases received no volatile anaesthesia. Four of the ten aware children received nitrous oxide, but no volatile anaesthetic, for maintenance. The other four received either halothane or methoxyflurane. This may partly explain the high incidence in this study, however all the children in the studies by Hobbs et al and O’Sullivan et al also had no volatile anaesthesia and they found no evidence for explicit recall. The studies by Kallf, Rich and Byers all had small numbers of participants and therefore it is not surprising that they did not detect awareness. The numbers enrolled by Hobbs, O’Sullivan and Bonke were greater but still insufficient to confidently exclude a relatively rare phenomenon. A distinction should also be drawn between the very specific physiological studies by Kallf, Bonke, Rich and Byers and the other studies that were audits of more general practice. The physiological studies looked for awareness at particular moments during prescribed anaesthesia regimens and therefore have limited generalisability to the general population. Studies conducted in adults have found awareness reporting may be delayed, and repeated interviews are recommended. Only McKie, Davidson and Lopez used an additional delayed interview. The lack of delayed interviews may partly explain the low incidence in the studies by Hobbs and O’Sullivan. The differences in incidence (both between child studies and between children and adults) may be due to differences in the underlying causes in awareness or due to differences in the measure used to detect or define awareness. Awareness is usually defined as having occurred if the subject can freely recall an event which is very likely to have occurred during the anaesthesia. How likely or not it occurred is sometimes obvious (such as remembering specific conversation) but more often it is less than obvious. The recalled event may have occurred in recovery, it may be confused with a dream, the memory may be implanted or the memory may be invented for secondary gain. It is not always clear cut to which category the event belongs. To overcome

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any investigator bias in these subjective decisions, researchers may use independent adjudicators and then pool or average their opinion. The subjective and somewhat arbitrary nature of this process will result in some inaccuracy in detecting the true incidence. Davidson used four adjudicators that all had to agree, Lopez required one (or two) of three to agree and McKie et al used no independent adjudicators. It is not surprising that the reported incidence is inversely proportional to the number of adjudicators! Perhaps the best definition of awareness is the simplest: if the patient thinks they were aware, then they were aware. Using this definition there is less discordance between the Lopez, Davidson and McKie studies with about 5% of children reporting a memory between going to sleep and waking up that they did not think was a dream. Unfortunately this definition is not very useful if we are seeking to understand awareness which is due to intra-operative anaesthesia failure. Interviewing children for awareness Eliciting an accurate recall of an event requires careful questioning.18 This is true for both adults and children. In children questions about awareness must be designed to match their cognitive and emotional level. Suboptimal questioning may lead to an overestimate of awareness due to implanted memory, or conversely an underestimate of awareness if children fail to understand the question or lack the motivation to answer. When comparing incidence of awareness in children to awareness in adults, the reliability of the child’s report is a contentious issue.19,20 Both adults and children are suggestible, but children are more suggestible. In children the degree of suggestibility steadily increases as age decreases. There has been considerable interest in the suggestibility of children due to the importance of a child’s testimony in legal proceedings. The optimal way to reduce implanted memory is to ask the question in a neutral tone that provides no incentives, no indication of which answers the questioner wants and does not presuppose an answer. Questions should not be repeated and should be open ended rather than specific.21,22 Questions with only two responses are particularly likely to lead to guessing or suggested answers. This technique may be optimal in reducing implanted memory but for several reasons will increase the chance of a child not reporting a memory (high specificity for awareness with reduced sensitivity). To increase the chance of a child recalling a memory, the question must have contextual meaning for the child and the child must be motivated to answer the question. Children are also more likely to encode and retrieve memories that have meaning or importance for them. Between the ages of 4 and 8 years, children become better at encoding and retrieving memory. This is due to several factors including steadily increasing myelination and speed of processing, the adoption of better mechanisms of memory management and finally greater overall knowledge. Knowledge allows faster encoding and retrieval as children have a better understanding of the context of the event or memory. They can remember things better if the event has meaning or they can be related easily to other events. Facts or events that fit into a logical context are easier to remember than a series of what appear to the child to be unrelated events or facts. Therefore when asking a child if they remembered an event it is important to build the context around the event. It is possible that children may not report awareness memories if the questions are too open-ended and they cannot locate the memory without any

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context. In practice, when interviewing children for awareness, it is important to orient the child to the time period in question. Recall will be greater if the interviewer uses simple language that can be understood by the child. The child’s interest and motivation must also be maintained. This can be achieved by repeating back some of the child’s comments, and providing praise for the child’s efforts, without rewarding particular answers. Children are reluctant to say ‘‘don’t know’’ so they should be informed that if they do not know the answer then it is okay to say so. In the postoperative period awareness interviews are often conducted on more than one occasion. The child may assume the repeated questioning is due to them providing the wrong answers so it is important to tell the child that the repeated questions are because they may still be affected by the anaesthetic. The optimal interview in children starts with free narrative. In this phase simple language should be used, there should be no coercive techniques and no questions about specific details, the interviewee should be allowed flexibility and encouraged to provide elaborate answers.23–25 After this, open-ended questions should be used and finally more specific questions can be asked to clarify the memories recalled in earlier responses. The child’s motivation should be maintained with judicious encouragement, care should be taken so that the child understands the temporal context, questions with dual answers should be avoided and the child given specific permission to declare they do not know the answers. In conclusion, interviewing children for awareness is a specialised skill which will inevitably involve some inaccuracy. Specific and repeated questioning may overestimate awareness by implanting memory. In contrast, questioning may underestimate awareness if the child is unmotivated, does not understand the question, or is unable to temporally locate the memory. Open-ended questions will be more specific and less sensitive while directed questions may be more sensitive but less specific. Before understanding the incidence, consequences, causes and prevention of awareness in children, a clearer agreed measure is needed. Nature of awareness in children In adults awareness is more common in paralysed patients or in patients where haemodynamic responses cannot be assessed.26 It is often auditory and may be accompanied by pain. Patients are often terrified and feel unable to move. Awareness is usually associated with tachycardia or hypertension though these signs are often present without awareness.26,27 In my experience and in published reports17, some unfortunate children do experience awareness very similar to that described in the adult literature (i.e. paralysed, distressing, auditory and painful). From the published cohort studies, however, there is some suggestion that for a substantial proportion of childhood awareness experiences may be significantly different to that typically described by adults. Here a note of caution is warranted: even when considering all relevant studies the total number of aware children is still small. This significantly limits any conclusions that can be drawn about the nature, causes or consequences of awareness in children. While there is some evidence emerging to suggest awareness in children is usually (but not always) a different phenomenon to awareness in adults, the exact incidence, causes, consequences and best strategies for prevention remain largely conjectural. In our recent cohort study, the aware children described auditory and tactile experiences, and four of the seven children described mild pain.5 The anaesthetists were informed of any awareness cases. For one case the anaesthetist commented that the

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child had moved while for the others the anaesthetists could recall no obvious signs of light anaesthesia (though this data is difficult to interpret as it was retrospective, incomplete, unblinded and possibly biased). Two children described trying to talk but being unable to. When compared to the non-aware population there was no difference between groups in use of sedative premedication. The children reporting awareness in the study by McKie et al described auditory, tactile and visual experiences.4 Some described minor pain. There were no obvious associations between anaesthesia technique and awareness though actual comparative data was not presented. Awareness occurred in children with and without neuromuscular blocking agents (two of the ten aware children did not receive neuromuscular blocking agents) and 60% of those who were aware moved at some stage during the anaesthesia. Lopez et al also found no obvious associations between awareness and anaesthesia technique. All the children in this study had tactile sensation while 64% described auditory and 27% described visual sensations. Some children tried to move and one felt paralysed. Causes of awareness in children Awareness in adults is usually due to:  Inadvertent light anaesthesia after mishap or misjudgment  Unintentional light anaesthesia where signs of light anaesthesia cannot be seen or are masked (for example paralysed patients or cardiopulmonary bypass)  Intentional light anaesthesia where the patient could not tolerate larger doses of anaesthesia (for example trauma or caesarian section). In the studies by McKie et al, Davidson et al, and Lopez et al most awareness cases occurred in what would be considered as low risk groups. Lopez et al found some evidence for an association between awareness and multiple airway manipulations but no other associations were found. Specifically we found use of neuromuscular blocking agents did not increase risk of awareness. There are three possible explanations for the high incidence found in children:  The finding is spurious due to inaccuracy of recall  Paediatric anaesthetists use techniques that increase the risk of awareness  There are fundamental differences in the pharmacology of anaesthetics in children. The first possibility has been discussed above. The second possibility was voiced in an editorial by Davis.19 Davis suggests that the use of induction rooms increases the risk of awareness. Use of induction rooms is widespread in Europe and Australia, as it allows the child to be anaesthetised in a quieter friendlier environment and parents can accompany the child without having to enter the main operating room itself. If induction rooms are used the patient is usually disconnected from the circuit for transfer and lightening may occur even though the transfer usually takes only a matter of seconds. Lightening of anaesthetic depth is particularly likely if the second circuit is not primed. However, in adults, the use of induction rooms is also widespread in many countries and does not seem to be an obvious cause for awareness. The incidence of awareness in European studies where induction rooms were used was no

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greater than that in American studies where they were not used.28,29 Also the events described by children are not always consistent with events that occurred immediately after transfer. An alternate possibility is that paediatric anaesthetists may accept periods of lighter anaesthesia because awareness had been infrequently described in children. This may be possible but there is no evidence to support such a supposition. The third possibility is the most intriguing. There is indeed some evidence emerging to suggest that the pharmacodynamics of anaesthesia agents are different in children compared to adults. The minimum alveolar concentration of volatile anaesthetic preventing movement following skin incision in 50% of subjects (MAC) peaks in infancy then declines with increasing age. For some agents such as sevoflurane there is little change in MAC between the age of one year and 10 years.30 In adults (and children down to about the age of 12 months), the electroencephalograph (EEG) shows characteristic changes with increasing doses of anaesthesia.31,32 In contrast to MAC, the dose of sevoflurane required to achieve a specified processed EEG index such as the bispectral index (BIS; Aspect Medical Systems Inc., Norwood, MA, USA) and state and response entropy (GE Healthcare, Helsinki, Finland) falls significantly between infancy and adolescence.31 Similarly the BIS at the age adjusted MAC concentrations of sevoflurane, desflurane and isoflurane falls with increasing age during childhood.33,34 In other words younger children have a more active EEG at the dose of anaesthesia that prevents movement. If the activity of the EEG correlates with consciousness or memory processing, then the margin between remembering and moving is less in children. Could children be more likely to hear before they move? There are a number of assumptions that limit this theoretical explanation for increased awareness in children – firstly that EEG correlates with awareness and secondly that the MAC data itself is accurate. Consequences of awareness in children In adults the consequences of awareness vary from bored indifference to post traumatic stress disorder. The small numbers, variable follow-up and often unrepresentative sampling limit accurate data but most adults do not like the awareness experience35 and about a third develop some significant psychological symptoms (which may be delayed).36–38 The studies by McKie, Davidson and Lopez were remarkably similar in the finding that most children reported the memories eagerly without any signs of distress or concern while only a few showed signs of anxiety or developed psychological symptoms. McKie et al reported that no child who was classified as having awareness appeared disturbed by the memories, but two children who had reported dreams experienced disturbing dreams (one of whom showed persistent behaviour change).4 In our cohort study, there was one child who gave a particularly convincing awareness recollection who was not obviously distressed by the awareness per se. However, later, this child developed a phobia requiring brief psychological intervention.5 In our study, we also assessed behaviour change in the entire cohort of aware and non-aware children using the Vernon Post Hospitalisation Questionnaire. Five of the seven aware children completed the questionnaire (the child with the phobia was one who did not complete the questionnaire). One of these five aware children developed negative behaviour changes. This rate of behaviour change was not significantly different to rate of behaviour change in the non-aware children (16%). In this study few of the aware children were paralysed and hence the lack of distress is consistent with the observation previously made in adults that awareness is less likely to be distressing if it is experienced

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without paralysis. Lopez et al reported that four aware children (36%) felt some anxiety during their awareness. A little under half realised that they were aware and of these only one had negative thoughts. Later follow-up found little evidence for psychological problems.20 In studies of awareness in adults, late onset psychological symptoms may occur. The McKie and Davidson studies have not reported the long term follow up of awareness. Three studies interviewing adults about their experiences of awareness included adults who suffered the awareness experience when they were children. In a recent study Samuelsson et al interviewed 2681 patients who had undergone previous anaesthesia identifying 46 cases of awareness.15 Of these, five were children at the time of the previous surgery (aged 7–12 years). Of the 46 cases, 15 had late mental symptoms but none were children when they were aware. Earlier, Schwender et al interviewed 45 people who responded to advertisements about awareness or were referred by colleagues.16 Of these, eight would have been under the age of 18 years at the time of awareness. Only one of these eight children developed sequelae compared to 12 of the 37 adults. Osterman et al also interviewed adults who responded to advertisements or were referred by colleagues.17 Of the 16 interviewed, three would have been children at the time of awareness aged 8, 12 and 14 years of age. All these had diagnostic criteria for post traumatic stress disorder. Such studies are difficult to generalise to the wider population as they rely on self reporting to advertisements, but the study by Osterman et al demonstrates that although awareness may be more common in children, and it may appear to be usually less distressing, there are still some children who can have significantly disturbing awareness. It is not clear why children reporting awareness usually report less anxiety. One important factor is that many of these children report events that do not include paralysis. It is also possible that children have a range of fears and anxieties when confronted with hospitalisation and surgery. An awareness event, especially if it is not associated with paralysis, may not make a substantial difference to an already distressed child. It is also possible that children have less understanding of the concept of anaesthesia. They may equate anaesthesia with sleep and hence not be surprised if they awaken when surgery starts. In contrast an adult has a better understanding of anaesthesia; knowing that something is definitely wrong if they were conscious during surgery or remembered being awake. Children also have different ways of coping with distressing or traumatic events. If a child reports awareness, they should be listened to sympathetically and their account should not be dismissed. The degree of distress should be gauged and if the child does appear distressed the family should be referred to a psychologist familiar with counseling children. In all cases of suspected awareness the parents should be given contact details for help if the child develops later signs of behavioural change. Adult-like and paediatric forms of awareness From the published studies it appears that two types of awareness may be described: an adult-like awareness and ‘‘paediatric’’ awareness. Children can experience either type. Children can experience awareness very similar to that described in the adult population with the same causes as adults, and perhaps the same incidence and consequences. There is no reason to think that the common causes of awareness in adults are not applicable to children. This uncommon and adult-like awareness would be

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expected to occur mostly in children undergoing cardiac surgery, bronchoscopy and surgery for major trauma. Similarly children having major surgery with neuromuscular blocking agents may be at greater risk. However compared to adults, the use of neuromuscular blocking agents is less common in paediatric anaesthesia, and therefore across the general population this ‘‘adult-like’’ form awareness is less common in children having anaesthesia. In contrast there is some evidence that the majority of children who describe awareness describe a different type of awareness. This paediatric form of awareness is not associated with paralysis, is less likely to be distressing and not obviously associated with signs of light anaesthesia, mishap or intentional under dosing. We do not know why this paediatric awareness occurs and it can be legitimately argued that some of it may indeed be spurious. It must be highlighted that this distinction between adult-like and paediatric awareness is based on small studies with incomplete data, and with further study may yet prove to be erroneous or an oversimplification. Preventing awareness in children Effective strategies to prevent awareness require an understanding of why awareness occurs. In adults there is good evidence that BIS monitoring reduces awareness in high risk groups such as cardiac surgery and trauma patients.39 There is also some weaker evidence to suggest BIS may prevent awareness in paralysed adults.40 The performance of BIS and other processed EEG devices is probably as good in older children as it is adults.32 Therefore there is no reason to believe that children at risk of adult-like awareness (such as those undergoing cardiac surgery, bronchoscopy or trauma) would not benefit from EEG monitoring such as BIS. For children not at high risk, it is less clear that EEG monitoring would prevent awareness. The nature of ‘‘paediatric’’ awareness is sufficiently different that it cannot be assumed that adult based trials can be extrapolated to children. Separate trials of awareness prevention strategies (including BIS) are needed in children before these monitors can be advocated widely in children. Such trials will be difficult without a more robust and universal measure of awareness in children. UNCONSCIOUS OR IMPLICIT MEMORY FORMATION DURING ANAESTHESIA IN CHILDREN Implicit memory refers to memory which cannot be consciously or intentionally recalled but which will result in changed behaviour or performance. Unconscious memory is memory that is formed when the subject is not conscious. There is very little evidence to suggest (at least in adults) that unconscious memory ever leads to explicit memory formation. Similarly there is no evidence that adults can have awareness without episodes of wakefulness. In contrast, for adult subjects, there is some evidence that implicit memory may occur when information is presented during apparently adequate anaesthesia. In other words there may be unconscious implicit memory. Of course implicit memory can also be formed during periods of wakefulness or consciousness. The study of implicit memory formation during anaesthesia is difficult and there are few studies in children. One problem in interpreting these studies has been the omission of recording whether or not the subject was conscious or unconscious during presentation of the information. Another issue is the variable affect of anaesthesia

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on the different types of implicit memory. Nevertheless the study of implicit memory formation may have particular relevance to children. Developmentally, children form implicit memory far earlier than explicit memory and during later childhood their capacity for implicit memory changes less than explicit memory. Children also have a high incidence of post anaesthesia behaviour disturbance.41 It has been suggested that some of this may be due to implicit memory formation. In 1987, Standen et al from Queens Medical Centre, Nottingham, studied cued recall in children anaesthetised with a regional block and two different concentrations of halothane (0.5% and 1.5%).13 The authors enrolled 41 children aged between 5 and 13 years. Cued recall was compared between groups and with a control group. There was no strong evidence of auditory registration in this small study. Bonke et al and Kalff et al also tested for implicit memory formation.11,12 A taped recording of phrases including naming colors was played during anaesthesia and children were subsequently presented with various colors after the surgery. They found no preference for the colors that were named on the tapes during anaesthesia. Rich et al played word pairs to 20 children aged 8–15 years during propofol anaesthesia for gastroscopy. They also found no evidence of explicit or implicit memory formation.10 Finally, in an abstract recently presented, Deeprose, Andrade and Barker reported preliminary data suggesting no evidence for implicit memory formation during anaesthesia in children14 (and personal communication from Dr Andrade April 2nd 2007). Although these studies have all failed to detect implicit memory formation during anaesthesia in children, the difficulties in reliably detecting implicit memory formation in children make it premature to conclude that children do not form implicit or unconscious memory during anaesthesia. The study by Deeprose et al also used the isolated forearm technique to detect periods of wakefulness. Children were instructed to move their fingers at a designated point. Two of the 186 children that completed all tests in the study moved their fingers as commanded though neither had any explicit recall of the event14 (and personal communication from Dr Andrade April 2nd 2007). In contrast an earlier study by Byers and Muir using the isolated forearm technique found movement in 19.5% of 41 children anaesthetised with 1.5–2.5% halothane and nitrous oxide.9 These two studies have shown, that as for adults, periods of wakefulness may occur without explicit recall in children. DREAMING DURING ANAESTHESIA IN CHILDREN Four of the studies investigating awareness in children also reported the incidence of dreaming.4,6,7,42 McKie et al reported dreaming in 11% of children.4 No associations were found between dreaming and use of premedication, anaesthetic agents or type of surgery. The content of the dreams was varied. There were both vivid and vague dreams, and some of dreams were associated with hospitalisation. Hobbs et al reported that 19% of children dreamt under anaesthesia.6 Like McKie et al, dreaming was not associated with use of pre-medication or type of surgery. However, dreaming was more frequent in those that received suxamethonium compared to atracurium. Children who dreamt were also more likely to have been calm prior to anaesthesia (independent to use of pre-medication). In a follow-up study O’Sullivan et al assessed the affect on dreaming incidence of non-depolarising muscle relaxant pretreatment before suxamthonium administration.7 The incidence of dreaming in non-pretreated children was 16.7% compared to just 2.8% in those pretreated

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with tubocurarine. The mechanism for this effect remains unclear. The nature of the dreams was not reported by Hobbs or O’Sullivan. The largest cohort was reported by Huang et al.42 In a cohort of 864 children aged 5–12 having anaesthesia, 90 children (10.4%) reported dreaming. The content of the dream was mostly pleasant and only a few were related to hospitalisation. The content of the dreams was usually related to animals, self representation or other characters. Only 9 children (10% of dreamers) had dreams that could be described as scary or frightening. Dreaming was more common in younger children but there was no association between anaesthesia agent or use of pre-medication and dreaming. Dreaming in children during anaesthesia was not associated with an increased risk of posthospitalization negative behaviour change. While Huang et al, described more dreaming during anaesthesia in younger children, during normal sleep younger children dream less than older children.43,44 In other respects dreams during normal sleep were similar to dreams during anaesthesia. In normal sleep younger children tend to have brief dreams, lacking in vivid emotion, without self characterisation and dominated by animal themes. Older children have longer dreams with more self characterisation and fewer animals. These trends were also noted in anaesthesia dreams. In both adults and children, dreaming is more common in those that also report awareness.4,5,45 In the study by McKie et al three of the aware children also reported dreaming separate to their awareness memories4 while Davidson et al reported dreams in four of the seven awareness cases.5 The reason for the association between dreams and awareness is unclear but it may indicate that awareness and dreaming are both more likely to occur in those that experience light or inadequate anaesthesia. AWARENESS IN YOUNG CHILDREN AND INFANTS None of the studies mentioned so far include children less than five years of age. As mentioned earlier there is little evidence for explicit recall in children younger than three years of age. Therefore there is little relevance in discussing awareness in infants and toddlers if we only consider explicit recall. There are two more relevant areas to consider in these younger children: implicit memory formation and consciousness without explicit recall. Discussing these leads to a series of fascinating questions which are hotly debated by parents, doctors, psychologists, physiologists, philosophers, theologians and even politicians.46 When do children start to from implicit memory? Is implicit memory formation during anaesthesia important in toddlers, infants, neonates or even the foetus? When do humans become conscious? At what stage of development do humans feel pain? The development of consciousness and memory Definitions of consciousness vary. From an internal perspective consciousness can be described in terms of a sense of self. This involves awareness of our own sensory perceptions and, being able to link the perceptions both temporally and across senses. However, when looking for consciousness in infants the internal perspective is only of limited value as we cannot remember much, or anything, before the age of three or four years. To investigate consciousness below that age we need to seek external signs of consciousness, such as evidence for cognition or evidence of self.

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There is evidence of cognition from early infancy. Infants plunged into darkness will search for hidden objects which they saw previously, and they will look longer at events that are inconsistent with previous experience (for example a ball that appears to fall upwards and not downwards). Evidence for self is harder to define, however, infants demonstrate that they can learn what is under their control and what is not, and certainly by the age of two they can recognise themselves in pictures and mirrors. In the neonatal period evidence for consciousness is less obvious. However, while a neurophysiologist or philosopher would suggest we cannot assume consciousness is there unless it is proven, an anaesthetist (and parent) would take the opposite stance: we should assume neonates are conscious (and hence need anaesthesia for distressing procedures) unless it can be proven beyond doubt that they are not conscious. A relatively new idea is that consciousness is not an all or none phenomenon, but it develops as a continuum throughout fetal and infant life. However even with this argument there is a point where it must start. From a practical perspective, there is good evidence that neonates do better if they have adequate analgesia for major procedures. There is also some indication that premature babies that are shielded from excessive handling, noise and lighting also do better. Whether neonates are conscious or not, preventing exposure to noxious stimuli and providing analgesia improves outcome. As mentioned above implicit memory is formed earlier than explicit memory. There is increasing evidence that neonates, preterm babies and perhaps even the fetus can form some types of implicit memory. The relevance of these memories is unclear; though evidence is emerging that implicit memory of nociceptive stimuli may adversely influence subsequent behaviour and response to similar stimuli. There is absolutely no information to guide us with how much anaesthesia is needed to prevent these memories in toddlers, infants and neonates. CONCLUSION Awareness in children is a difficult area to study and adult paradigms and measures are not always appropriate. However interest and knowledge about awareness in children is steadily increasing. The incidence is hard to judge but is probably at least as high as that in adults. Although paralysed, distressing adult-like awareness can certainly occur in children it appears that milder forms of awareness are more common. The reasons for awareness in children, the consequences or even whether it is just a spurious finding are still largely unknown. While in high risk adult-like cases EEG monitoring should have role in reducing awareness, their role in the majority of paediatric cases still needs to be determined from randomised trials done specifically in children. In children less than five years of age we know very little indeed about the frequency or impact of consciousness and memory formation during anaesthesia.

Practice points  Awareness can occur in children.  Awareness can occur in non high risk children.  Many children may not be distressed by their memories though in some there can be an adverse psychological impact.

428 A. J. Davidson

Research agenda  The first priority is to develop a robust, developmentally appropriate measure of awareness specifically for children.  The long term consequences of awareness in children need to be better defined.  Before assessing or planning prevention the causes of awareness in children must be identified.

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