Department of Anaesthetics and Intensive Care, University of Auckland, Waikato Clinical School, Hamilton, New Zealand
*Corresponding author. E-mail: vossl@waikatodhb.govt.nz
Accepted for publication: August 7, 2003
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Abstract |
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Methods. Two different methods of memory testing were used; (1) free-association (F-A) word-pair testing (n=33) to test conceptual implicit memory and (2) process dissociation procedure (PDP) (n=26) to detect perceptual implicit and explicit memory. One hour after surgery, whilst sedated, the F-A group received one of two lists of 10 category-exemplar word-pairs through headphones, while the PDP group was presented with one of two lists of 16 five-letter words. When awake and co-operative, the F-A group was tested using F-A testing, and the PDP group was tested using the PDP.
Results. The F-A group had a mean (SD) correct response rate of 7 (9)% for the target list, and 9 (8)% for the distractor list. The PDP group had a mean (SD) correct response rate of 11 (14) and 10 (13)% for the inclusion and exclusion lists, respectively, with mean correct response rates of 13 (14)% for both the corresponding distractor lists. Neither group showed any significant differences between their responses and a list of distractor words (Wilcoxon tests).
Conclusion. We found no evidence for memory formation in post-cardiac surgery patients under moderate to deep propofol sedation.
Br J Anaesth 2003; 91: 81014
Keywords: anaesthetics i.v., propofol; sedation, implicit memory
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Introduction |
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The concept of implicit memory formation whilst unresponsive has been around for decades. Despite many investigations, evidence for the formation of memories whilst unresponsive as a result of sedation or anaesthesia remains unsubstantiated.2 Some studies have reported that adequate anaesthesia is associated with implicit memory formation.3 Conversely, there is evidence that memory formation is abolished at subanaesthetic doses of volatile agents.4 5 Some of these conflicting results may be a result of ambiguities in the definition of general anaesthesia and sedation. For example, adequate anaesthesia is defined by some according to the bispectral index3 and by others in terms of the response to surgical stimulus.4 5 Clarification of this contentious area of research is important from both a clinical and a psychological perspective. There may be therapeutic benefits related to the implicit processing of positive aural stimuli6 7 while equally, awareness or recollection of unpleasant events may contribute to the trauma of surgery or intensive care.
For the purpose of this paper we have categorized the level of sedation in our subjects according to guidelines published by the American Society of Anesthesiologists8 and the Harvard Medical School.9 Thus, moderate sedation is a drug-induced depression of consciousness during which patients respond purposefully to verbal commands8 and deep sedation is a state of depressed consciousness or unconsciousness from which the patient is not easily aroused and is unable to respond purposefully to physical stimulation or verbal command.9 All of the subjects in the current study were either deeply or moderately sedated according to these guidelines, but probably not anaesthetized (see Methods).
We investigated whether moderately to deeply sedated post-cardiac surgery patients can form explicit and/or implicit memories. We chose patients who had had cardiac surgery because they are an at risk group for awareness during surgery and are kept sedated for several hours after surgery.
We used two different methods of memory testing; free-association (F-A) testing and the process dissociation procedure (PDP). The former is commonly used to detect implicit memories, while the latter can, in theory, reveal both implicit and explicit memories. To our knowledge, this is the first study of memory formation in sedated patients after cardiac surgery.
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Methods |
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After undergoing their cardiac operation patients were transferred to the intensive care unit (ICU) to recover. Here, patients were kept sedated (i.v. propofol 100300 mg h1) to allow tolerance of the tracheal tube. This was sufficient for 67% of F-A and 92% of PDP subjects to be classified as deeply sedated (unresponsive to physical stimulation or voice9) and 18% of F-A subjects as moderately sedated (responsive to voice8). The remainder (15% of F-A and 8% of PDP subjects) were responsive to physical stimulation (moderate pressure to thumb nail bed) but not responsive to voice. General anaesthesia is most commonly defined as the alveolar partial pressure of a gas at which 50% of humans will not respond to a surgical incision.10 11 Thus, without doing a surgical incision we were unable to classify any patient as anaesthetized. It is unlikely that any of the deeply sedated subjects were anaesthetized, as a propofol dosage of 170 mg h1 is not normally sufficient to induce a state of general anaesthesia. Accordingly, we refer to the present subject group as being moderately to deeply sedated.
The initial conditioning phase of the study started 1 h after the patients admission to ICU, to allow the effects of isoflurane and neuromuscular blocking agents administered during surgery to wear off. All subjects were intubated and ventilated during the conditioning phase. We recorded each patients age, sex, sedation level (using the Observer Assessment of Alertness and Sedation scale12), bispectral index (BIS) score (F-A group only), the dosage of fentanyl and midazolam received during surgery, and the rate of propofol infusion in ICU. The unavailability of a BIS monitor prevented us recording BIS in the PDP group.
Memory testing
Two well-recognized memory tests were investigated, F-A testing (n=33) and PDP (n=26). Both of these tests have been used extensively to investigate memory in sedated and anaesthetized subjects.3 1316
F-A testing
We tested implicit memory by using category-exemplar word-pairs (e.g. animallion) given while sedated and subsequently comparing recall of the words heard (targets) with a control list of word-pairs not heard (distractors). Any implicit memory of the conditioning phase in ICU should result in a significantly greater frequency of correct responses to target words relative to distractors.
With most (67%) still deeply sedated, patients in the F-A group were presented with one of two different lists (list A or B, Appendix 1) of 10 category-exemplar word-pairs. All words were presented five times using pre-recorded lists from a computer, through headphones. Patients were randomly assigned to either list A or list B.
The memory testing phase of the study began once patients were awake and lucid, on average 1.5 days after surgery. Patients underwent an F-A test, whereby the category word from every word-pair in both lists A and B (i.e. targets and distractors) was played in random order through headphones to the patient, and the patient was asked to respond with the first word which came to mind. Nothing was an acceptable answer. Correct and incorrect responses were manually recorded. The headphones and voice used during the testing phase were identical to those used during the conditioning phase, to give all possible cues to memory.
PDP
The PDP uses word-stem completion tests to measure implicit memory formation, and also to ascertain the existence of any explicit memories that may have been formed.17 The presented words are split into inclusion and exclusion lists, with the patient being given different tasks for each. The inclusion list requires the patient to complete each stem with a five-letter word recalled from ICU, or failing that, the first five-letter word that comes to mind. Both implicit and explicit memory contributes to the patients score here. In contrast, the exclusion word list requires the patient to respond with a different word from that heard in ICU, or else in the absence of recall, with the first word that comes to mind. Therefore, any explicit memory present will result in a lower score on the exclusion stems than on the inclusion stems, while implicit memory will raise both scores above the level of random guessing.
With the majority (92%) still deeply sedated, patients were presented with pre-recorded words from a computer, through headphones. Patients were divided into four sub-groups (groups iiv), and presented with one of two lists (list Y or Z, Appendix 2) of 16 five-letter words. For each of 640 cycles, the computer randomly chose one of the 16 words to present. Thus, each word was presented approximately 40 times.
Once patients were awake and lucid, usually 3 days after surgery, they were tested for implicit and explicit memory of the words heard in ICU. The average time between the conditioning and testing phases was longer amongst the PDP group, because of the more complex nature of the PDP testing, which required patients to be more fully recovered. Patients were played all word-stems from both lists Y and Z, with the words not heard previously acting as distractors. Half of the words from each list were used in the inclusion phase of testing and the other half in the exclusion phase. Counter-balancing was used to eliminate bias, as described by Lubke.3 Responses were recorded as hits if they matched the five-letter word the stem was derived from. Responses in the singular were accepted even if the original word was plural, and patients could choose to pass if they could not think of a word within 5 s.
Data analysis and statistics
The PDP and F-A group responses were analysed using the Wilcoxon test, comparing the number of target hits to the number of distractor hits.14 The equations of Jacoby and colleagues17 were used to quantify any explicit or implicit memory present in the PDP group:
Explicit memory index=inclusion score exclusion score
Implicit memory index=[exclusion score/(1 explicit memory)] distractor score
The Wilcoxon test was used to see if the values generated differed significantly from zero.
Data are presented as mean (SD). In all cases, P<0.05 was considered statistically significant.
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Results |
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Discussion |
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There is some evidence for the formation of implicit memories during general anaesthesia. How then can we explain the ability of the brain to form implicit memories whilst fully anaesthetized, but not when sedated with lower levels of propofol? Some researchers suggested that the stress of surgery might play an important role in the generation of implicit memories under general anaesthesia.14 The stress of surgery causes the release of adrenaline and cortisol, both of which may aid the formation of memory.19 Conflicting results may also be explained in some instances by differences in experimental design. For example, isolated forearm testing (IFT) is recommended in anaesthetized, paralysed subjects to confirm that they are unresponsive to stimulation.16 A number of studies that have demonstrated memory formation during anaesthesia, coupled with neuromuscular block, did not use the IFT technique.15 20 21 The importance of repetition in implicit memory formation has also been emphasized by some22 and investigations exploiting higher repetitions than in the present study have demonstrated implicit memory during general anaesthesia.15 22 Another possible explanation for the failure to detect implicit memory under sedation is that memory function is not proportional to propofol dosage.
A major problem we had carrying out this study was that of patient exhaustion. It is difficult to separate memory function from other aspects of cognitive function. The nature of this particular study involved the recruitment of patients undergoing cardiac surgeryan operation notorious for impairing cognitive function for some time post operation.23 While other studies used subjects whose operations were sufficiently minor as to allow memory testing to proceed within hours of the conditioning phase, no patients in this study were adequately recovered from their surgery to complete the testing phase before 24 h had passed, and many took longer than this. However, a previous study has shown that the length of interval between the conditioning and testing phases does not significantly affect memory performance3 and is therefore unlikely to have confounded the results.
An initial pilot survey was done of six non-patient (non-sedated) volunteers who completed (without prior conditioning) the 32 word-stems used in the PDP. The volunteers guess rate was higher than the patient group, with an average hit rate of about 20%, compared with 13% for distractor lists amongst the patients (because of a higher rate of passing and inappropriate responses). This suggests that cognitive impairment following cardiopulmonary bypass surgery, perhaps as a result of sleep fragmentation, or pain, may have detrimentally affected the patients ability to generate suitable words.
In conclusion, we found that explicit and implicit memory formation is abolished in patients after cardiac surgery who are under moderate to deep propofol sedation.
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Acknowledgements |
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Appendices |
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References |
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