Bispectral index-guided administration of anaesthesia: comparison between remifentanil/propofol and remifentanil/isoflurane.

BACKGROUND AND OBJECTIVE: The bispectral index of the electroencephalogram is a measure of the hypnotic component of anaesthesia and can be used to guide the administration of anaesthesia. This study compares bispectral index-guided anaesthesia with remifentanil and either propofol or isoflurane. METHODS: Eighty consenting patients were randomly assigned to two groups. Following induction with propofol and remifentanil, anaesthesia was maintained with remifentanil/propofol or remifentanil/isoflurane. Remifentanil infusion rates were guided by haemodynamic responses--maintaining mean arterial pressure and heart rate within 20% of baseline. Propofol and isoflurane administration was guided using the bispectral index (45-60). Thirty minutes before the end of surgery, morphine was administered (0.15 mg kg(-1) intravenously). Fifteen minutes before end of surgery, propofol and isoflurane were reduced (bispectral index 60-75). At the end of surgery, the anaesthetic agents were discontinued. Groups were compared for recovery, remifentanil doses and signs of inadequate anaesthesia using the chi2-test and ANOVA (P < 0.05). RESULTS: The duration of surgery was longer in the propofol/remifentanil group (121 +/- 53 versus 94 +/- 40 min). Recovery data were not different between groups. The remifentanil infusion rate was significantly lower with additional isoflurane (0.18 +/- 0.06 microg kg(-1) min(-1)) than with additional propofol (0.31 +/- 0.20 microg kg(-1) min(-1)). The propofol infusion rate was 123 +/- 48 microg kg(-1) min(-1); isoflurane concentration was 0.66 +/- 0.13%. CONCLUSIONS: Bispectral index-guided anaesthesia with remifentanil plus propofol or isoflurane results in the absence of postoperative recall and a fast recovery with both drug combinations. In our patients, at comparable bispectral index-levels, haemodynamic control requires higher doses of remifentanil with propofol than with isoflurane.

The effect of bispectral index monitoring on anesthetic use and recovery in children anesthetized with sevoflurane in nitrous oxide.

UNLABELLED: The utility of bispectral index (BIS) monitoring to guide anesthetic administration has been demonstrated in adults. This prospective, randomized observer-blinded study was designed to evaluate the effect of BIS monitoring on anesthetic use and recovery characteristics in pediatric patients. After data collection in 38 historical controls, 202 patients age 0-18 yr were randomized into one of two groups: standard practice (SP) and BIS guided (BIS). Patients age 0-3 yr undergoing inguinal hernia repair (IH) and patients age 3-18 yr undergoing tonsillectomy and/or adenoidectomy (TA) were selected. All patients were anesthetized with sevoflurane in 60% N(2)O/O(2). Hernia patients also received a caudal epidural anesthetic before surgery. In the BIS group, anesthetic delivery was adjusted in an effort to achieve a target BIS of 45-60 during maintenance and 60-70 during the last 15 min of the procedure. BIS was recorded throughout surgery in all patients, but data were unavailable to the anesthesiologist in the SP group. In the TA patients, BIS monitoring was associated with a significant reduction in end-tidal sevoflurane concentration during maintenance (2.4 +/- 0.6%, SP and 1.8 +/- 0.4% BIS, mean +/- SD) and during the last 15 min of the procedure (2.1 +/- 0.7, SP and 1.6 +/- 0.6, BIS). There was a 25%-40% decrease in measured recovery times. In the patients 0-6 mo of age undergoing IH, sevoflurane concentrations during maintenance (2.0 +/- 0.4% SP, 0.9 +/- 0.8 BIS), during the last 15 min (1.6 +/- 0.4% SP, 0.6 +/- 0.6% BIS), and at the end of the procedure (1.1 +/- 0.6% SP, 0.3 +/- 0.3% BIS) were smaller in the BIS group. Emergence and recovery measures were unaffected by BIS titration. In the children 6 mo-3 yr of age, there were no significant differences between the SP and BIS groups in anesthetic use or recovery measures. IMPLICATIONS: Bispectral index monitoring in children results in less anesthetic use and faster recovery than standard practice.

Clinical impact of hypnotic-titration guidelines based on EEG bispectral index (BIS) monitoring during routine anesthetic care.

STUDY OBJECTIVES: To examine the impact on perioperative care of routine Bispectral Index (BIS) monitoring during general anesthesia throughout an entire operating room (OR) suite. DESIGN: Open, observational trial with retrospective analysis of guideline performance. Data were analyzed from 1,552 adult patients receiving general anesthesia with surgical times of at least 1 hour and who were extubated by postanesthesia care unit (PACU) discharge. Staff were trained using a simple decision matrix, which integrated BIS titration goals with anesthetic management. Unmonitored patients were compared to either BIS-monitored patients or to performance subgroups based on BIS measurements recorded during anesthetic maintenance ("deep", BIS < 50; "target", 50-65; "light", >65). SETTING: Large, urban academic/trauma center. MEASUREMENTS AND MAIN RESULTS: Demographic profiles of all groups and subgroups were similar. Anesthetic emergence, recovery times, and volatile drug use were significantly shortened or reduced only when BIS values were maintained between 50 and 65. Extubation time from end of surgery decreased by 2.1 minutes from 5.7+/-7 (37%); OR exit time decreased by 2.2 minutes from 9.3+/-6 (24%); eligibility for phase 1 PACU discharge decreased by 4 minutes from 22+/-42 (23%); and actual PACU discharge decreased by 15 minutes from 130+/-78 (7%). PACU extubation frequency decreased from 6.9% to 2.6%. Modest decreases in total intraoperative drug use were noted with an increase in PACU analgesic administration. CONCLUSIONS: Routine application of BIS monitoring throughout an OR suite impacted clinical outcome only if guideline targets were met. BIS values within the last 30 minutes of surgery were not predictive of emergence or recovery. Hypnotic maintenance at BIS < 50 did not confer any clinical advantage over unmonitored cases. Anesthetic maintenance at BIS values between 50 and 65 was associated with shortened emergence and recovery from general anesthesia.

Memory formation during general anesthesia for emergency cesarean sections.

BACKGROUND: Occurrence of explicit memory (i.e., conscious recall) has been reported especially after surgical procedures in which anesthesia is considered to be "light." In addition, previous research has shown that implicit memory (e.g., improved memory test performance in absence of conscious recall) decreases with increasing hypnotic state. The current study investigated explicit and implicit memory during emergency cesarean sections with consistently light levels of hypnotic state. METHOD: Words were presented via headphones, and the bispectral index was recorded throughout surgery. Memory for the presented words was tested after recovery with a word-stem completion test. Using both parts of the process dissociation procedure allowed separation of explicit and implicit memory. In the "inclusion" part of the process dissociation procedure, patients are asked to complete word stems, if possible, with the corresponding words recalled from the intraoperative presentation. In the "exclusion" part, patients are instructed to avoid the words presented intraoperatively and to use other words instead. In the absence of recall, patients are asked to use the first word that comes to mind. RESULTS: The mean bispectral index during word presentation was 76.3 (+/-3.0). On average, the 24 patients were able to make correct inclusion-exclusion decisions: In the inclusion part, hit rates (i.e., the probability of responding with a word presented during surgery) were higher than base rates (0.37 vs. 0.31), whereas in the exclusion part hit rates were lower (0.23 vs. 0.28). Importantly, the patients made these inclusion-exclusion decisions without being able to consciously recall the words presented during surgery. CONCLUSIONS: This study shows that if words are presented at relatively light levels of anesthesia, patients are able to control their inclusion-exclusion decisions. This weak form of explicit memory can occur in the absence of conscious recall.

Awareness and different forms of memory in trauma anaesthesia.

Awareness during surgery and memory for perioperative events may have substantial psychological consequences for the patient. The risk of awareness during trauma surgery is higher than during most elective procedures due to the fact that administration of adequate concentrations of anaesthetics is not always feasible. As a consequence, the risk of memory formation might be increased. The present review discusses different forms of memory, and the possibilities and limitations of awareness and memory prevention.

Dependence of explicit and implicit memory on hypnotic state in trauma patients.

BACKGROUND: It is still unclear whether memory of intraoperative events results entirely from moments of inadequate anesthesia. The current study was designed to determine whether the probability of memory declines with increasing depth of the hypnotic state. METHOD: A list of words was played via headphones during surgery to patients who had suffered acute trauma. Several commonly used indicators of anesthetic effect, including the bispectral index, were recorded during word presentation. First, these indicators served as predictors of the memory performance in a postoperative word stem completion test. Second, general memory performance observed in the first part was separated into explicit and implicit memory using the process dissociation procedure, and then two models of memory were compared: One model assumed that the probability of explicit and implicit memory decreases with increasing depth of hypnotic state (individual differences model), whereas the other assumed equal memory performance for all patients regardless of their level of hypnotic state. RESULTS: General memory performance declined with decreasing bispectral index values. None of the other indicators of hypnotic state were related to general memory performance. Memory was still significant at bispectral index levels between 60 and 40. A comparison of the two models of memory resulted in a better fit of the individual differences model, thus providing evidence of a dependence of explicit and implicit memory on the hypnotic state. Quantification of explicit and implicit memory revealed a significant implicit but no reliable explicit memory performance. CONCLUSIONS: This study clearly indicates that memory is related to the depth of hypnosis. The observed memory performance should be interpreted in terms of implicit memory. Auditory information processing occurred at bispectral index levels between 60 and 40.

The effect of the interaction of propofol and alfentanil on recall, loss of consciousness, and the Bispectral Index.

UNLABELLED: The Bispectral Index (BIS) correlates well with the level of consciousness with single anesthetic drugs. We studied the effect of the interaction of propofol with alfentanil on propofol concentration and BIS associated with 50% probability of loss of consciousness and lack of recall (Cp50 and BIS50, respectively). We studied 40 consenting volunteers at two institutions who were randomly assigned to receive stepped increases of propofol (10 subjects at each site), propofol plus alfentanil 50 ng/mL (10 subjects at Emory site), or propofol plus alfentanil 100 ng/mL (10 subjects at Duke site) by using a target-controlled infusion device. Measures of sedation, BIS, deltaBIS (absolute change of BIS after a painful stimulus), memory, and drug concentration were obtained at each target drug concentration. The relation among BIS, measured drug concentration, sedation score, and presence or absence of recall was determined by linear and logistic regression for different drug regimens, and the prediction probability (Pk) was calculated. The addition of alfentanil in increasing doses did not significantly affect the BIS50 and propofol Cp50 values for loss of consciousness and lack of recall. DeltaBIS was significantly decreased by both an increase in the concentration of propofol and the presence of alfentanil. The Pk for BIS was >0.93 with all drug regimens, better than those of the target and measured propofol concentrations. We conclude that BIS correlated well with the hypnotic component of anesthesia independent of the presence of an opioid. Moreover, the level of consciousness, and, therefore, the BIS index, is affected by a painful stimulus, and this response is ablated either by opioids or increasing propofol concentration. IMPLICATIONS: In volunteers, the sedation and changes in memory function produced by propofol correlated well with changes in the Bispectral Index. This relationship was not altered by the addition of an analgesic (alfentanil). However, in moderately sedated patients who received a painful stimulus, the Bispectral Index increased, but this response was blocked by the analgesic or increasing propofol concentrations.

The interaction of eltanolone and fentanyl with special reference to logistic regression analysis.

UNLABELLED: We investigated whether fentanyl decreases the serum concentrations of the steroid anesthetic eltanolone effective in producing loss of consciousness in 50% of patients (EC50induction) and in preventing movement at skin incision in 50% of patients (EC50incision). For anesthetic induction, patients received effect-site target concentrations of fentanyl 0.0, 1.5, 3.0, or 4.5 ng/mL and eltanolone 500, 750, 1000, or 1200 ng/mL. Loss of response to verbal command was assessed after 10 min. For incision, patients received effect-site target concentrations of fentanyl 0.5,1.5, 3.0, or 4.5 ng/mL and eltanolone 547-2926 ng/mL. Movement at incision was assessed at least 10 min after new targets were entered. Probability of loss of consciousness and of movement versus arterial serum concentration combinations were analyzed by logistic regression. Dixon up-down analysis was used to estimate ET50incision effective target concentration combinations. In the absence of fentanyl, anesthesia was induced in only 1 of 12 patients, which suggests that the EC50induction is >1500 ng/mL at fentanyl 0.0 ng/mL. With fentanyl (38 patients), eltanolone EC50induction was independent of fentanyl concentration, calculated as 628 ng/mL. For the incision phase (52 patients), logistic regression failed to generate a valid model. Dixon analysis (43 patients) produced an eltanolone ET50incision of 2288 ng/mL at fentanyl targets of 0.5 ng/mL, 754 ng/mL at 1.5 ng/mL, 735 ng/mL at 3.0 ng/mL, and 645 ng/mL at 4.5 ng/mL. Fentanyl reduced the serum concentration of eltanolone required to produce loss of consciousness and the target concentration of eltanolone required to prevent movement to skin incision. IMPLICATIONS: Fentanyl reduced the serum concentration of eltanolone required to produce loss of consciousness and the target concentration of eltanolone required to prevent movement to skin incision. Future interaction studies of this nature using logistic regression should model responses to hypnotic alone separately from responses to hypnotic-analgesic combinations.

Esmolol potentiates reduction of minimum alveolar isoflurane concentration by alfentanil.

UNLABELLED: Esmolol, a short-acting beta1-receptor antagonist, decreases anesthetic requirements during propofol/N2O/morphine anesthesia. This study was designed to determine whether esmolol affects the volatile anesthetic (isoflurane) required to prevent movement to skin incision in 50% patients (minimum alveolar anesthetic concentration [MAC]) with or without an additional opioid (alfentanil). One hundred consenting adult patients were randomly divided into five treatment groups: isoflurane alone (I), I with continuous large-dose (250 microg x kg(-1) x min(-1)) esmolol (E), I with alfentanil (effect site target of 50 ng/mL) via a continuous computer-controlled infusion (A), A plus continuous small-dose (50 microg x kg(-1) x min(-1)) esmolol (A1), or A plus large-dose esmolol (A2). Anesthesia was induced via a face mask, and steady-state target end-tidal isoflurane concentrations were maintained before incision. The MAC of isoflurane alone was 1.28% +/- 0.13%. Large-dose esmolol did not significantly alter the isoflurane MAC (1.23% +/- 0.14%). Alfentanil alone significantly decreased isoflurane MAC by 25% (0.96% +/-0.09%). Adding small-dose esmolol did not further decrease MAC with alfentanil (0.96% +/- 0.13%). However, large-dose esmolol significantly decreased isoflurane MAC with alfentanil (0.74% +/- 0.09%). Esmolol and alfentanil both significantly reduced the increases in heart rate and mean arterial pressure associated with endotracheal intubation and incision. The mechanism of this effect is unknown. IMPLICATIONS: Most anesthetic techniques rely on a balance of several highly selective medications. The current results define a new anesthetic-sparing effect when volatile anesthetic, analgesic, and beta-adrenergic blocking drugs are combined.

Central nervous system monitoring during open heart surgery: an update.

Electroencephalography (EEG) is used to monitor the function of the central nervous system in a variety of surgical procedures. During cardiac surgery with cardiopulmonary bypass, ischemic changes on the EEG as a result of impaired central nervous system blood supply can be noted. The EEG also may be used to monitor the functional state of the brain during and after profound hypothermic circulatory arrest. If a desired goal is to reduce cerebral metabolism using a barbiturate or other such agent, the EEG can be monitored to provide a measurable pharmacodynamic end point (burst suppression). Techniques have been developed to process the EEG signal using a computer and to improve on-line interpretation. These include fast Fourier transformation to develop a three-dimensional plot or compressed spectral array, evoked-potential monitoring, and bispectral analysis to derive a univariate descriptor of the EEG. These techniques have been used to detect awareness and indirect memory function, as well as to assess the adequacy of anesthesia. There is a good correlation between implicit memory and alterations in midlatency auditory-evoked responses. The bispectral index has been used to assess the adequacy of anesthesia as well as to detect awareness. Preliminary studies suggest that titrating the anesthetic to bispectral index levels may be useful during cardiac surgery.

Monitoring depth of anaesthesia.

In clinical practice, indirect and non-specific signs are used for monitoring anaesthetic adequacy. These include haemodynamic, respiratory, muscular and autonomic signs. These measures do not indicate adequacy of anaesthesia in a reliable manner. Many attempts have been made to find a more accurate monitor. Direct monitoring of anaesthetic effect should be possible by EEG measurement. EEG information can be reduced, condensed and simplified, leading to single numbers (spectral edge frequency and median frequency). These methods appear insufficient for assessing anaesthetic adequacy. The bispectral index, derived from bispectral analysis of the EEG, is a very promising tool for measuring adequacy of anaesthesia. An alternative approach is to monitor evoked potentials. Middle latency auditory evoked potentials may be helpful in assessing anaesthetic adequacy. Both techniques need further validation.

A multicenter study of bispectral electroencephalogram analysis for monitoring anesthetic effect.

Bispectral analysis (BIS) of the electroencephalogram (EEG) has been shown in retrospective studies to predict whether patients will move in response to skin incision. This prospective multicenter study was designed to evaluate the real-time utility of BIS in predicting movement response to skin incision using a variety of general anesthetic techniques. Three hundred patients from seven study sites received an anesthetic regimen expected to give an approximately 50% movement response at skin incision. EEG was continuously recorded via an Aspect B-500 monitor and BIS was calculated in real time from bilateral frontocentral channels displayed on the monitor. Half of the patients were randomized to a treatment group in which anesthetic drug doses were increased to produce a lower BIS. In the control group, BIS was recorded, but no action taken on the data displayed. A determination of movement in response to skin incision was made in the 2 min succeeding incision. Retrospective pharmacodynamic modeling was performed using STANPUMP to estimate effect-site concentrations of intravenously administered anesthetics. BIS values were significantly higher in the control group (66 +/- 19) versus the BIS-guided group, in which additional anesthesia was administered to produce a lower BIS (51 +/- 19). The movement response rate was significantly higher in the control group at 43% compared with 13% in the BIS-guided group, but response rates were low at sites which used larger doses of opioids. Logistic regression analysis showed that BIS, estimated opioid effect-site concentrations, and heart rate (in that order) were the best predictors of movement at skin incision. This study demonstrates that dosing anesthetic drugs to lower BIS values achieves a lower probability of movement in response to surgical stimulation. BIS is a significant predictor of patient response to incision, but the utility of the BIS depends on the anesthetic technique being used. When drugs such as propofol or isoflurane are used as the primary anesthetic, changes in BIS correlate with the probability of response to skin incision. When opioid analgesics are used, the correlation to patient movement becomes much less significant, so that patients with apparently "light" EEG profiles may not move or otherwise respond to incision. Therefore, the adjunctive use of opioid analgesics confounds the use of BIS as a measure of anesthetic adequacy when movement response to skin incision is used as the primary end point.

Recovery of consciousness after thiopental or propofol. Bispectral index and isolated forearm technique.

BACKGROUND: Currently, there exists no effective monitor that can predict the probability of a patient being conscious during general anesthesia. The electroencephalogram-derived bispectral index (BIS) is a promising new method to assess anesthetic adequacy. This study used the BIS to predict the probability of recovery of consciousness after a single bolus induction dose of propofol or thiopental. METHODS: Twenty unpremedicated surgical patients were anesthetized with 4 mg/kg thiopental and 20 patients with 2 mg/kg propofol. The BIS was monitored throughout the study. After induction, before administration of neuromuscular blocking agent, a tourniquet was applied to one arm and inflated above the systolic blood pressure. This allowed preservation of the ability to move the hand after neuromuscular blocking agent onset. Patients were then prompted to squeeze the investigator's hand every 30 s, until they responded to the request. At the time of response, anesthesia was reinduced and the study terminated. RESULTS: The BIS at loss of consciousness and recovery of a response was not statistically different between propofol and thiopental. No patient with a BIS less than 58 was conscious. In both groups, a BIS of less than 65 signified a less than 5% probability of return of consciousness within 50 s. CONCLUSION: The BIS can be used to predict probability of recovery of consciousness after a single injection of either thiopental or propofol.

Esmolol reduces anesthetic requirement for skin incision during propofol/nitrous oxide/morphine anesthesia.

BACKGROUND: Although beta blockers have been used primarily to decrease unwanted perioperative hemodynamic responses, the sedative properties of these compounds might decrease anesthetic requirements. This study was designed to determine whether esmolol, a short-acting beta 1-receptor antagonist, could reduce the propofol concentration required to prevent movement at skin incision. METHODS: Sixty consenting patients were premedicated with morphine, and then propofol was delivered by computer-assisted continuous infusion along with 60% nitrous oxide. Patients were randomly divided into three groups, propofol alone, propofol plus low-dose esmolol (bolus of 0.5 mg/kg, then 50 micrograms.kg-1.min-1), and propofol plus high-dose esmolol (bolus of 1 mg/kg, then 250 micrograms.kg-1.min-1). Two venous blood samples were drawn at equilibrium. The serum propofol concentration that prevented movement to incision in 50% of patients (Cp50) was calculated by logistic regression. RESULTS: The propofol Cp50 with nitrous oxide was 3.85 micrograms/ ml. High-dose esmolol infusion was associated with a significant reduction in the Cp50 to 2.80 micrograms/ml (P < 0.04). Propofol computer-assisted continuous infusion produced stable serum concentrations with a slight positive blas. Esmolol did not alter the serum propofol concentration. No intergroup differences in heart rate or blood pressure response to intubation or incision were found. CONCLUSIONS: Esmolol significantly decreased the anesthetic requirement for skin incision. The components and mechanism of this interaction remain unclear. A simple pharmacokinetic interaction between esmolol and propofol does not explain the Cp50 reduction. These results demonstrate an anesthetic-sparing effect of a beta-adrenergic antagonist in humans under clinically relevant conditions.

Reduction of isoflurane minimal alveolar concentration by remifentanil.

BACKGROUND: Remifentanil is a new micro-specific opioid receptor agonist currently under investigation. The interaction between opioids and volatile anesthetics is complex. Defining this interaction provides a basis for more rational dosing schemes when such combinations are used for anesthesia and allows the anesthetic potency of remifentanil relative to other opioids to be determined. METHODS: Two centers enrolled a total of 220 patients. Patients were randomized to receive a target concentration of remifentanil via a computer-assisted continuous infusion device of either 0.0, 0.5, 1.0, 1.5, 2.0, 4.0, 8.0, 16.0, and 32.0 ng/ml initiated before the administration of isoflurane. Patients were also stratified by groups 18-30, 31-55, and 56-65 yr. After induction of anesthesia with isoflurane the initial patient in each dose group was assigned an age-adjusted isoflurane concentration. The isoflurane concentration for each subsequent patient was adjusted according to the up/down technique until a minimum of 12 patients were enrolled in each group. Arterial blood samples for remifentanil whole blood concentrations were obtained. The patient was observed for purposeful movement for up to 1 min after skin incision. The minimum alveolar concentration (MAC) of isoflurane (0 ng/ml remifentanil group) and MAC reduction of isoflurane by remifentanil were determined. RESULTS: The MAC of isoflurane alone was 1.3%. Remifentanil caused an exponential reduction in the MAC of isoflurane with 1.37 ng/ml remifentanil a 77% reduction and 32 ng/ml a 91% reduction of isoflurane MAC. CONCLUSION: The MAC reduction of isoflurane by remifentanil is similar to that produced by other opioids. Although remifentanil was given at extremely high concentrations in the absence of isoflurane, it did not provide adequate anesthesia. A 50% isoflurane MAC reduction is produced by 1.37 ng/ml remifentanil whole blood concentration compared to previously published plasma concentrations of fentanyl of 1.67 ng/ml or sufentanil of 0.14 ng/ml.

Therapeutic suggestion has not effect on postoperative morphine requirements.

This study was designed to confirm the effect of therapeutic intraoperative auditory suggestion on recovery from anesthesia, to establish the effect of preoperative suggestion, and to assess implicit memory for intraoperative information using an indirect memory task. Sixty consenting unpremedicated patients scheduled for elective gynecologic surgery were randomly divided into three equal groups: Group 1 received a tape of therapeutic suggestions preoperatively, and the story of Robinson Crusoe intraoperatively; Group 2 heard the story of Peter Pan preoperatively and therapeutic suggestions intraoperatively; Group 3 heard the Crusoe story preoperatively and the Peter Pan story intraoperatively. A standardized anesthetic technique was used with fentanyl, propofol, isoflurane, and nitrous oxide. After surgery, all patients received patient-controlled analgesia (PCA) with a standardized regimen. In the 24 h postsurgery, morphine use was recorded every 6 h and at 24 h an indirect memory test (free association) was used to test for memory of the stories. Anxiety scores were measured before surgery and at 6 and 24 h postsurgery. There were no significant differences between groups for postoperative morphine use, pain or nausea scores, anxiety scores, or days spent in hospital after surgery. Seven of 20 patients who heard the Pan story intraoperative gave a positive association with the word "Hook," whereas 2 of 20 who did not hear the story gave such an association. Indirect memory for the Pan story was established using confidence interval (CI) analysis. (The 95% CI for difference in proportion did not include zero). No indirect memory for the Crusoe story could be demonstrated. This study did not confirm previous work which suggested that positive therapeutic auditory suggestions, played intraoperatively, reduced PCA morphine requirements. In contrast, a positive implicit memory effect was found for a story presented intraoperatively.