1Wessex Institute for Health Research and Development, University of Southampton, Bassett Crescent East, Southampton SO16 7PX, UK. 2Department of Psychology, University of Portsmouth, King Henry I Street, Portsmouth PO1 2DY, UK. 3Department of Anaesthesia, Southampton General Hospital, Tremona Road, Southampton SO16 6YD, UK*Corresponding author
Accepted for publication: November 14, 2000
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Abstract |
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Br J Anaesth 2001; 86: 5138
Keywords: brain, auditory evoked response; anaesthetics i.v., propofol; measurement techniques, isolated forearm technique; anaesthesia, depth; memory, implicit
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Introduction |
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Patients and methods |
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Pilot studies in spontaneously breathing patients showed that it was impossible to record a meaningful AER when the patients were awake or lightly sedated because of interference from muscle artefact. We therefore used response to command with the IFT as our indicator of awareness. To eliminate the confounding effect of surgical stimulation, the entire procedure was undertaken in the anaesthetic room before surgery. After pre-medication with oral diazepam 10 mg, i.m. morphine 10 mg and prochlorperazine 12.5 mg patients were taken to the anaesthetic room approximately 1 h before the scheduled time for surgery.
In the anaesthetic room full invasive monitoring with continuous recording, including automated ST segment analysis, was started according to standard practice in our unit. The patients free left upper arm was wrapped with soft surgical padding (Soffban; Smith and Nephew) and a padded orthopaedic tourniquet was placed over this. The AER was monitored using the Northwick Park system, as described previously.13 Briefly, the EEG was recorded with a prototype amplifier, digital signal processor system (Loughborough Sound Instruments, Loughborough, UK) and bespoke software running on a 386SX personal computer. Disposable silver/silver chloride electrodes (MSB) were placed on Fpz and the two mastoids as in the International 10:20 system.14 Closely fitting binaural ear pieces were used for delivery of both words and the auditory stimuli (clicks) for evoking the AER. The AER was generated by averaging 512 EEG epochs of 125 ms duration beginning at the click stimuli.
Sixteen words with comparable occurrence frequencies were divided into four lists. The words were selected from a previous implicit memory study in non-anaesthetized volunteers, in which they were found to have similar priming rates (Loveman, van Hooff and Gale, submitted for publication). Each list of four words was recorded onto a compact disc and copied five times. For the post-operative implicit memory tests the same female voice was used for the recording. A compact-disc player presented the first list of words (five times) before induction of anaesthesia with fentanyl 100 µg and propofol 1 mg kg1, followed by an infusion of propofol at 2 mg kg1 h1. As soon as consciousness was lost (absence of eyelash reflex) the tourniquet was inflated to 300 mm Hg and vecuronium 0.1 mg kg1 was administered. After tracheal intubation, mechanical ventilation of the lungs was commenced and adjusted to an end-tidal carbon dioxide tension of 4.55.0 kPa. When the AER was considered stable, the propofol infusion was turned off. At 1 min intervals the patient was called by their name and asked to squeeze the experimenters hand. The request for response to command was made individually to each patient by the same experimenter. If patients had not responded after 20 min the tourniquet was deflated for 10 min and then re-inflated for a further 20-min period. Thus, the maximum inflation time for any patient was 40 min and all patients responded within this period.
When the first unequivocal response was made, the patient was reassured and informed that they were now going to hear another word list. This word list was again played five times. To enable clear hearing, the commands to squeeze the experimenters arm were stopped during presentation of the word list. After presentation of the word lists, the propofol infusion was started again at a rate of 6 mg kg1 h1 for 10 min, reducing to 4 mg kg1 h1 for a further 10 min and then 3 mg kg1 h1 until the response to command was lost. All patients remained responsive to command after presentation of the word list. Testing for response continued each minute and when the response to command had been lost for 3 consecutive min the patient was then played the third word list (five times). All patients were unresponsive to command after the presentation of the third word list. A fourth and final word list was not presented to serve as a baseline measure and the order of the four word lists was rotated between patients. In six patients there was sufficient time to stop the propofol infusion again and repeat the above procedure without the word lists. The patients were then prepared for surgery.
Within 36 h of surgery, after having been transferred to the main ward, patients were assessed for both explicit and implicit memory. To establish any explicit recall of intra-anaesthetic events patients were asked the following four questions:15
What is the last thing that you remember before you were put to sleep for your operation?
What is the first thing that you remember on waking from your operation?
Do you remember hearing anything during the operation?
Did you dream of anything during the operation?
To assess implicit memory (defined as memory without conscious recollection16) patients were presented with 18 pre-recorded spoken word stems, corresponding to the first syllables of the 16 stimulus words of the four lists (e.g. PIC from PICNIC or MEL from MELLOW), plus two practice stems. They were asked to verbally complete each stem with the first word that sprang to mind (e.g. PIC can become PICNIC but also the more typical words such as PICTURE or PICKLE). The word stem completion test has been used successfully in previous anaesthetic studies17 and is a commonly used method for assessing implicit memory in psychological investigations (for a review see Schacter16). Furthermore, the current word stem completion test, including the specific stimuli, the auditory presentation mode and the verbal response format, was previously validated in a study using healthy volunteers (Loveman, van Hooff and Gale, submitted for publication). In addition to this, a forced choice recognition task was undertaken. Patients were played a list of 28 words (the 16 words from the four lists plus 12 fillers) and asked to respond if they felt they remembered hearing any, or if any seemed familiar. This technique has also been used in anaesthetic studies.17 18 Finally, explicit memory was reassessed with the question, do you remember squeezing the experimenters hand at any time during the anaesthetic period?
Measurement of the latency of the Nb wave was undertaken off line by each author independently. Repeatability between us was significant, (r=0.93, P<0.05) and analysis was therefore continued with the scoring of one rater.
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Results |
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AER
The mean latency of Nb was 48.4 (SD 4.3) ms at first response to command and 54.6 (6.7) ms at loss of response to command. A paired samples t-test revealed that this difference in Nb latency was statistically significant (t=5.11, df 13, P<0.001). The individual Nb latencies for each of the patients are shown in Figure 2. In all but two patients (patients 9 and 10) the Nb latencies were longer at loss of response than at response. However, the range of Nb latencies were quite large which illustrates the problem of specifying a general cut-off point. For example, a cut-off point of 60 ms, as suggested by Schwender and colleagues,19 would in our study lead to a sensitivity of 100% (percentage of patients for which the presence of a response to command could be correctly predicted) but also to a very low specificity of 29% (percentage of patients for which the absence of a response to command could be correctly predicted). Similarly, a cut-off point of 51 ms20 would result in a sensitivity of 79% and a specificity of 71%, and a cut-off point of 44.5 ms8 would results in a sensitivity of 21% and a specificity of 93%.
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Discussion |
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High correlations were found between Nb latencies for the first and second measurements in all six patients who repeated the transition from response to no-response. This means that there is minimal hysteresis in the AER, with Nb latency at both periods of response to command and at both periods of loss of response to command being largely similar. This finding, although based on a small number of patients, adds further weight to the possibility of providing individual rather than general cut-off points for awareness during anaesthesia. However, the practical implications need to be the focus of further investigation.
Measurements of arterial pressure at response to command were significantly different from baseline (pre-anaesthesia), and at loss of response to command. It should be noted, however, that arterial pressure was not monitored throughout the experimental procedure, and that changes were measured at two single points in time, for example, response and no response of the isolated forearm. Thus, we cannot comment on what the arterial pressure was at other times.
Measures of memory
We found no evidence of implicit or explicit memory during anaesthesia. In the word stem completion task, manifestations of implicit memory would be a tendency to complete the word stems with the words recently encountered (i.e. before and during anaesthesia), but this was not found. Similarly, in the forced choice recognition task, implicit memory would be if patients recognized at least some of the presented words based upon feelings of familiarity, but this was not found. These results suggest that there is no memory, explicit or implicit, during anaesthesia. However, this does not account for the lack of priming effects for the word list presented in the pre-medicated state before anaesthesia induction, or for the word list presented during the anaesthesia period while patients were responsive to command, using the IFT. This finding is comparable to Russells investigations with the IFT.21
Some studies using the word stem completion test17 have demonstrated memory effects during general anaesthesia, and others have provided no evidence for implicit memory.22 23 Similarly, a number of studies using sub-anaesthetic doses of anaesthesia in volunteers have found an inconsistent relationship between responsiveness during sedation and later recall, as measured by implicit or explicit measures of memory.24 One difficulty with all these studies is that the depth of anaesthesia has not been assessed at the time of presentation. This means that it cannot be ruled out whether the memory effects demonstrated were because of period of inadequate or light anaesthesia.
Perhaps the implicit memory test may not be a reliable enough measure over such a period of time. Roediger and colleagues,25 however, reported that implicit memory, as demonstrated by a word stem completion test, could persist for up to 1 week in normal populations. The lack of implicit memory in our study may reflect an effect on memory from prolonged anaesthesia and sedation (as patients are all sedated up to and during their stay on the intensive care unit).
In summary, we found a correlation between changes in wave Nb of the AER with changes in awareness as measured by the IFT. With the exception of two patients, individual latencies changed in the same direction with increasing depth of anaesthesia, although the variation between individuals was wide. This means that some patients were responding where others had stopped responding and as such reduces the application of the AER for anaesthetic monitoring. No evidence of memory for inter-anaesthetic events was demonstrated.
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References |
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