Absence of implicit and explicit memory during propofol/remifentanil anaesthesia

BACKGROUND AND OBJECTIVE: High doses of opioid associated with low doses of hypnotic is a popular anaesthetic technique since the use of remifentanil has become widespread. This type of anaesthesia could result in a higher incidence of implicit memory. METHODS: Ten patients were anaesthetised with a target-controlled infusion of remifentanil (target concentration of 8 ng mL(-1)) combined with a target-controlled infusion of propofol with progressive stepwise increases until loss of consciousness was reached. A tape containing 20 words was then played to the patients. Bispectral index (BIS, Aspect Medical Systems, Newton, MA, USA) was continuously monitored during the whole study period. Implicit and explicit memories were tested between 2 and 4 h after recovery. RESULTS: Loss of consciousness was obtained with a mean calculated propofol plasma concentration of 1.3 +/- 0.4 microg mL(-1). At this low hypnotic concentration no implicit or explicit memory was found in the three postoperative memory tests. Median (range) BIS value during word presentation was 93 (80-98). CONCLUSIONS: In our group of young American Society of Anesthesiologists (ASA) I/II patients, no explicit or implicit memory was found when the calculated concentration of propofol combined with a high concentration of remifentanil was maintained at the level associated with loss of consciousness with high BIS values.     

Target-controlled infusion of propofol induction with or without plasma concentration constraint in high-risk adult patients undergoing cardiac surgery

BACKGROUND: Calculated plasma (Cp) and calculated effect site concentrations (Ce) of propofol associated with loss of consciousness (LOC) have been studied in young healthy patients. The aim of the study was to evaluate the calculated propofol concentrations required to induce LOC in ASA III adult patients undergoing cardiac surgery using a smooth target controlled infusion of propofol. METHODS: After informed consent, 44 patients were premedicated with 0.5 mg alprazolam orally. Propofol TCI using the pharmacokinetic set of Marsh et al. incorporated in the Diprifusor (ThalfKeo of 2.6 min) was used. Propofol Ce was progressively increased by 0.5 micro g/ml until LOC was obtained. The constraint on the maximum gradient between Cp and Ce was either 1 micro g/ml in group 1 or not limited in group 2. Hemodynamic variations were assessed. RESULTS: Mean preoperative left ventricular ejection fractions were 44 +/- 15.4% and 56 +/- 11.4% in groups 1 and 2, respectively (P < 0.01). At LOC, mean Cp was 1.9 micro g/ml in both groups but mean Ce was 1.08 +/- 0.31 and 1.43 +/- 0.42 micro g/ml in groups 1 and 2, respectively (P < 0.01). The mean induction time was 12.8 +/- 7.1 min in group 1 and 8.5 +/- 2.7 min in group 2 (P < 0.05). No episode of hypotension has been observed in either group. CONCLUSION: In ASA III patients undergoing cardiac surgery, smooth propofol TCI induction, using the pharmacokinetic set of Marsh et al. incorporated in the Diprifusor, is associated with LOC at a low mean calculated plasma concentration of 1.9 micro g/ml and good hemodynamic stability.     

Gender differences between predicted and measured propofol C(P50) for loss of consciousness

OBJECTIVE: To investigate gender differences in the effective dose of 50% for loss of consciousness (C(P50LOC)) for propofol using Diprifusor, the most commonly used target-controlled infusion system. DESIGN: Prospective, randomized, comparative study. SETTING: University-affiliated hospital. PATIENTS: 50 ASA physical status I and II patients, aged 20 to 50 years, scheduled for minor surgery. INTERVENTIONS: Patients were randomized into two groups of 25 patients each. A target-controlled infusion of propofol (Diprifusor) was maintained at a predetermined target concentration. After a 10-minute steady state, blinded investigators evaluated patients' consciousness using verbal commands. The propofol test concentration was predetermined using a modified version of Dixon's up-and-down method (starting at 2.5 mug/mL; step size of 0.1 microg/mL). MEASUREMENT: Predicted and measured C(P50LOC) values and bispectral index (BIS) were obtained by averaging the crossover midpoint (ie, consciousness to unconsciousness). Those values were analyzed by unpaired t test: P < 0.05 was considered significant. RESULTS: The predicted C(P50LOC) for men was 2.14 +/- 0.10 microg/mL, which was lower than that for women, 2.55 +/- 0.11 microg/mL (P < 0.0001). No significant difference was found for measured C(P50LOC) in men (2.37 +/- 0.41 microg/mL) and in women (2.30 +/- 0.28 microg/mL) or for BIS measurements. CONCLUSION: Predicted C(P50LOC) by Diprifusor for men tended to be underestimated; that for women tended to be overestimated. Our data support a review of Diprifusor (Astra Zeneca, Osaka, Japan) pharmacokinetic parameters to avoid awareness during operation, particularly for women.     

Postoperative reading speed does not indicate implicit memory in elderly cardiac patients after propofol and remifentanyl anaesthesia

BACKGROUND: A recent study in young patients undergoing propofol-alfentanil-nitrous oxide anaesthesia demonstrated implicit memory for stories presented during operation using a postoperative reading speed task. In this study we investigated whether patients who tolerate only small amounts of anaesthetics are prone to develop implicit and explicit memories about intraoperative events. METHODS: Thirty patients with poor physical status (ASA III-IV) undergoing cardioverter defibrillator implantation were included in the study. Patients were premedicated with intravenous midazolam and anaesthesia was maintained using propofol and remifentanil infusions. During surgery one of two audio-tapes containing two short stories was played to the patients. Reading speed for the stories played during surgery and two similar stories from the other tape was tested 4 h later. Explicit memory was tested at 4 h and 24 h after audiotape presentation using a structured interview and a forced-choice recognition test pertaining to the story content. Thirty additional awake subjects served as controls. RESULTS: Although half of the patients seemed to be awake one or more times during the operation, no explicit memories of intraoperative events were reported. The forced-choice recognition of the stories was at chance level. No effect on reading speed was found in either the patients or the control subjects. CONCLUSIONS: The possible reasons for reduced explicit and implicit memory performance in elderly patients are age and poor physical status of the patients and the modality change between study and test phases. A non-anaesthetised control group of the same age and physical status should therefore be included in all studies of implicit memory.     

LEARNING DURING GENERAL ANAESTHESIA: IMPLICIT RECALL AFTER METHOHEXITONE OR PROPOFOL INFUSION

Forty-four patients undergoing coronary artery surgery wereallocated randomly to receive an infusion of propofol or methohexitoneas a hypnotic supplement to a fentanyl-based anaesthetic technique.A taped message was played to the patients, consisting of 10words associated with prompt sentences and a suggestion fora specific postoperative behavioural response. Twenty patients(10 propofol and 10 methohexitone) (perioperative group) wereexposed to the taped message during surgery and in the immediatepostoperative period and the other 24 patients (postoperativegroup) were exposed to the tape only in the postoperative period,after return to the intensive care unit (ICU). No patient hadexplicit recall of any events during the period when the tapewas played. The patients in the propofol group who heard thetape during surgery had significant implicit recall of the wordassociations compared with the equivalent 10 methohexitone patients(P = 0.004), when tested 48 h after surgery. The patients whowee played the tape whilst receiving identical infusion regimensfor sedation in the ICU did not demonstrate implicit recallof the word associations in either the propofol or the methohexitonegroups. There was no evidence of a response to the specificbehavioural suggestion during the postoperative interview. Theresults confirm that auditory perception can occur during clinicallyadequate anaesthesia, and that suppression of auditory awarenessor learning is a function of both the pharmacological degreeof sedation and the degree of surgical stimulation.     

Target-controlled infusion of propofol and remifentanil in cardiac anaesthesia: influence of age on predicted effect-site concentrations

Background. Propofol-anaesthesia administrated via target-controlledinfusion (TCI) has been proposed for cardiac surgery. Age-relatedchanges in pharmacology explain why propofol dose requirementis reduced in elderly patients. However, the Marsh pharmacokineticmodel incorporated in the Diprifusor propofol device does nottake age into account as a covariable. In the absence of depthof anaesthesia monitoring, this limitation could cause adversecardiovascular effects resulting from propofol overdose in olderpatients. We assessed the influence of age on effect-site propofolconcentrations predicted by the Diprifusor and titrated to thebispectral index score (BIS) during cardiac anaesthesia. Methods. Forty-five patients received propofol by Diprifusorand remifentanil by software including Minto model. Propofoland remifentanil effect-site concentrations were adapted toBIS (40–60) and haemodynamic profile, respectively. Theinfluence of age on effect-site concentrations was assessedby dividing patients into two groups: young (<65 yr) andelderly (     

新辅助化疗对乳腺癌患者靶控输注异丙酚意识消失时半数有效效应室靶浓度的影响

目的 探讨新辅助化疗对乳腺癌患者靶控输注异丙酚意识消失时半数有效效应室靶浓度(EC50)的影响.方法 择期拟行乳腺癌切除术患者90例,女性,ASAⅠ或Ⅱ级,年龄30～60岁,体重指数<30kg/m2,根据术前是否接受新辅助化疗及其化疗方案分为3组(n=30),未化疗组(Ⅰ组)术前不使用任何化疗药物;紫杉醇化疗组(Ⅱ组)及环磷酰胺+阿霉素+5-氟尿嘧啶联合化疗组(Ⅲ组)均进行4个疗程化疗,并于第4个疗程结束后10～15d时行乳腺癌切除术.麻醉诱导:靶控输注异丙酚,按序贯法确定异丙酚的效应室靶浓度,第1例患者异丙酚效应室靶浓度为2.07μg/ml,各相邻靶浓度之比为1.09.以睫毛反射消失及对言语指令无反应作为判断意识消失的标志.若患者意识消失,则持续靶控输注该浓度异丙酚,并静脉注射芬太尼3μg/kg及罗库溴铵0.6 mg/kg后气管插管;若患者意识未消失,则停止靶控输注,静脉注射异丙酚2mg/kg、芬太尼3μg/kg及罗库溴铵0.6 mg/kg后气管插管.计算靶控输注异丙酚意识消失时的EC50.结果 与Ⅰ组比较,Ⅱ组及Ⅲ组患者靶控输注异丙酚意识消失时的EC50.均降低(P<0.05),Ⅱ组和Ⅲ组间上述指标差异无统计学意义(P>0.05).结论 新辅助化疗可降低乳腺癌患者靶控输注异丙酚意识消失时的EC50.     

Target controlled infusion (TCI): applications of the "TCI visual" program in anesthesia and sedation with propofol

BACKGROUND: Systems for Target Controlled Infusion accepting not only patient' data, like Diprifusor, but also a pharmacokinetic model have not been available in Italy in the last years. Therefore a program which controls a Pilot Anesthesia Vial pump and accepts any pharmacokinetic model was developed and applied to propofol infusion for anaesthesia and sedation. METHODS: Two versions of the Visual TCI program have been developed. The first, at intervals, supplies the anaesthetist with the values for the pump; the second directly interacts with the pump. The program also supplies the anaesthetist with the current amount of drug in each compartment and with the estimated awakening time. DESIGN: preliminary prospective study. SETTING: operatory theatre and Intensive Care Unit in a University Hospital. Patients: 6 patients undergoing total intravenous anaesthesia with propofol and fentanyl for abdominal surgery; 6 patients undergoing sedation with propofol in an Intensive Care Unit (the first 4-hour period was taken into account). Interventions: propofol infusion was regulated by the Visual TCI program. The first version was employed in three patients of each group and the second one in the others. Hypo- and hypertensive episodes (systolic pressure less than 80 mmHg or higher than basal value plus 25%) were recorded during anaesthesia and sedation. Propofol concentration was measured in plasma three times at defined intervals and per cent differences between measured and computer-calculated values (Predictive error, PE) were calculated. RESULTS: No hypo- or hypertensive episodes were recorded. PE was 27.4 +/- 17.9%. CONCLUSIONS: The program was easily employed, caused no inconvenience, and its use was associated with a remarkable cardiovascular stability. PE distribution was acceptable on the ground of the criteria reported in the literature. The program can be applied to drugs other than propofol, with both two and three compartment pharmacokinetic models and the anaesthetist can choose the most suitable model for the patient.     

妊娠早期丙泊酚麻醉诱导和苏醒时的预测效应室靶浓度

背景妊娠时孕妇对镇静药的需要量减少，据称与孕酮有关。然而，妊娠和孕酮对丙泊酚的需要量产生怎样的影响，至今没有人彻底的研究过。本研究的目的是确定在妊娠早期，麻醉诱导意识消失期间和麻醉苏醒睁眼时所用丙泊酚的剂量和预测效应室靶浓度是否减低。同时观察血孕酮的含量与使意识消失时丙泊酚剂量和效应室靶浓度有无相关性。方法我们研究了57例ASA1-2级拟行终止妊娠的患者和55例行经阴道卵泡穿刺体外受精的对照患者。浓度为1％的丙泊酚以200ml／min的输注速度实施麻醉。记录在诱导时意识丧失过程中所用丙泊酚的剂量和预测效应室靶浓度（Schnider模型）。同时预测在麻醉苏醒睁眼时的效应室靶浓度。血孕酮的量在手术结束时测定。结果在意识消失时，妊娠患者较非妊娠患者所用丙泊酚剂量的平均值（±1个标准差）显著减少（分别为108．57±20．04mg和117．59±17．98mg，P=0．014）。与之相似，意识消失时预计的丙泊酚效应室靶浓度在妊娠患者有显著的降低。在麻醉苏醒睁眼时丙泊酚的预计靶浓度没有差别。没有观察到血孕酮水平与意识消失时丙泊酚的剂量和效应室靶浓度的相关性。结论早期妊娠时使意识消失的丙泊酚的剂量和预计的效应室靶浓度减低。孕酮并不能解释这一结果。     

A-line autoregression index monitoring to titrate inhalational anaesthesia: effects on sevoflurane consumption, emergence time and memory

BACKGROUND: A-line autoregression index (AAI) is a parameter derived from auditory evoked potentials proposed as depth of anaesthesia monitor. We evaluated the effects of AAI guidance on sevoflurane consumption, emergence time, explicit and implicit memory. METHODS: One hundred patients submitted to major abdominal surgery were randomized into two groups. In group A (n = 50), sevoflurane was titrated according to AAI (target = 20 +/- 5), in group B (n = 50) according to clinical signs. Anaesthesia was induced with fentanyl, propofol, atracurium and maintained with sevoflurane. The mean value of sevoflurane consumption (g/min) and emergence time has been assessed in both groups. After emergence, A test of explicit memory was administered. We assessed implicit memory using a category generation test. RESULTS: In group A, mean sevoflurane consumption was significantly (P = 0.0001) reduced by 20.4% and mean emergence time was significantly (P = 0.00012) shorter by 2 min with respect to group B. No patients experienced explicit memory while the difference between the two groups in implicit memory results was not significant (P = 0107). CONCLUSIONS: AAI titration of anaesthesia allows a significant reduction in sevoflurane consumption and emergence time without significant effects on the incidence of explicit and implicit memory. Nevertheless the relationship between AAI and memory requires studies in larger groups of patients.     

Patient-controlled sedation using remifentanil for third molar extraction

The purpose for this study was to examine the efficacy of patient-controlled sedation (PCS) with remifentanil as an intravenous adjunct to local anaesthesia for treating pain associated with dental extraction during monitored anaesthetic care. Forty ASA 1-2 and aged 18 or older Chinese patients presenting for third molar extraction on an outpatient basis were randomly assigned to either remifentanil (RG; n =20) or saline groups (CG; n =20). All patients completed the study. Patients in the RG and CG were comparable in terms of demographic variables, PCS demands and PCS boluses. There was high variability of PCS among patients in both groups in terms of demands (range for RG 0-62; CG 0-41) and consumption (range for RG 0-26; CG 0-13). Neither group required any rescue local anaesthetic injection for pain or midazolam for anxiety. There was no clinically relevant differences in outcome measures (pain scores, anxiety scores, systolic and diastolic blood pressures, heart rate, and SpO2) between the two groups. There were no other major complications such as apnoea, desaturation, bradycardia, or chest wall rigidity in either group. We conclude that, although it appeared to be safe, the addition of patient-controlled remifentanil was not a useful adjunct to local anaesthesia for pain associated with third molar dental extraction.     

Target-controlled infusion of propofol for intraoperative sedation: determination of effect-site concentration and assessment of bispectral index

OBJECTIVES: To determine the effect-site concentration (Ce) of propofol, required to achieving adequate sedation. To assess the efficacy and safety of a target-controlled infusion system during monitored anaesthesia care and to evaluate the ability of bispectral index (BIS) to predict sedation level. Study design. - Prospective clinical study. PATIENTS: Women scheduled for insertion of tension-free vaginal tape under local anaesthetic infiltration. METHODS: After premedication with hydroxyzine, 1% propofol was infused using the Diprifusor system at an initial target plasma concentration (Cc) of 1 microg/ml and then adjusted by steps of 0.2 microg/ml at 5 min intervals. The level of sedation was assessed using the observer's assessment of alertness/sedation (OAA/S) scale; the objective was to obtain an OAA/S level at 4 or 3 (response to verbal stimulation). Ce of propofol and BIS were noted every 5 min. Relation between Ce or BIS and OAA/S scale was analysed by linear regression and probability of prediction (P(K)). RESULTS: Fifty patients aged 62 +/- 12 years were studied. Sedation at level 4 or 3 was observed in all patients. Ce of propofol and BIS to maintain this OAA/S score were, respectively, 1.0 +/- 0.2 microg/ml and 87 +/- 7. There was a linear relation between OAA/S scale and BIS or Ce; however, individual values demonstrate wide variability. The average of P(K) values computed for each patient for the BIS and Ce was 0.84 and 0.83, respectively. CONCLUSIONS: Target-controlled infusion of propofol provides easy and safe management of intraoperative sedation, allowing a fast and precise adjustment of the propofol concentration to the clinical response of the patient.     

Is there implicit memory after propofol sedation?

Recent evidence indicates that implicit memory may be preserved during general anaesthesia. We tested for the presence of explicit and implicit memory in patients undergoing surgical procedures with local or regional anaesthesia and sedation with propofol. Initial i.v. boluses of propofol 0.5 mg kg-1 and fentanyl 1 microgram kg-1 were administered, followed by an infusion of propofol 50 micrograms kg-1 min-1. Administration of one or more doses of propofol 30 mg i.v. during operation was controlled either by the patient or the anaesthetist. At the start of the last skin stitch, patients were presented with a list of 15 stimulus words and the most frequently associated response. The infusion was then discontinued. After 1 h in the recovery area, all patients were tested for free recall, free association, cued recall and recognition on the list presented during surgery (critical list) and a matched list not presented (neutral list). Data of all patients without free recall (explicit memory) were analysed with repeated-measures analysis of variance. Of 36 patients, five demonstrated free recall. For the remaining 31 patients, cued recall and recognition showed no evidence of explicit memory. However, the free association tests demonstrated significant priming. The mean number of critical free associations was 6.6 (SEM 0.4) compared with 5.5 (0.4) neutral free association (P < 0.05). In the absence of explicit memory, implicit memory persists after intraoperative sedation with propofol.      

An Investigation of Learning during Propofol Sedation and Anesthesia Using the Process Dissociation Procedure

Background: Many studies have shown that patients may remember words learned during apparently adequate anesthesia. Performance on memory tests may be influenced by explicit and implicit memory. We used the process dissociation procedure to estimate implicit and explicit memory for words presented during sedation or anesthesia.

Methods: We investigated intraoperative learning in 72 women undergoing pervaginal oocyte collection during propofol and alfentanil infusion. One word list was played once before infusion, another was played 10 times during surgery. Venous blood was taken for propofol assay at the end of the intraoperative list. Behavioral measures of anesthetic depth (eyelash reflex, hand squeeze response to command) were recorded and used to adjust the dose of anesthetic where clinically appropriate. On recovery, memory was assessed using an auditory word stem completion test with inclusion and exclusion instructions.

Results: The mean blood propofol concentration was 2.5 [mu]g/ml (median, 2.3 [mu]g/ml; range, 0.7-6.1 [mu]g/ml). Mean alfentanil dose was 2.1 mg (median, 2.0 mg; range, 1.2-3.4 mg). Comparison of target and distractor hits in the inclusion condition showed memory for preoperative words only. However, the process dissociation procedure estimates showed explicit (mean, 0.18;P < 0.001) and implicit (mean, 0.05;P < 0.05) memory for the preoperative words, and a small amount of explicit memory for the intraoperative words (mean, 0.06; 95% confidence interval, 0.01-0.10). Memory performance did not differ between the 17 patients who consistently responded to command and eyelash reflex and the 32 patients who remained unresponsive. Blood propofol concentration and alfentanil dose did not correlate with memory for the intraoperative list.     

Propofol effective concentration 50 and its relationship to bispectral index

Sixty unpremedicated healthy adult patients were studied during induction of anaesthesia with intravenous propofol delivered by a 'Diprifusor' target-controlled infusion. Bispectral index (BIS) and spectral edge frequency (SEF95) were measured concurrently with the predicted blood and effect site propofol concentrations. Logistic regression was used to calculate the predicted propofol blood and effect site concentrations required to produce unconsciousness and no response to a noxious stimulus in 50% and 95% of patients and to correlate BIS with these end-points. The Diprifusor TCI software produces anaesthesia at consistent target concentrations. Bispectral index correlates well with clinical end-points and may be useful during propofol anaesthesia.     

Safety and efficacy of target controlled infusion (Diprifusor) vs manually controlled infusion of propofol for anaesthesia.

In this multi-centre, randomized trial, we compared the safety and efficacy of Diprifusor TCI with manually controlled infusion (MCI) of propofol for anaesthesia. With approval, 123 adult male and female patients were studied. Firstly, each investigator anaesthetized five patients to familiarize themselves with Diprifusor TCI. In Stage 2, 98 patients were randomized to receive propofol-based anaesthesia via TCI or MCI. Adjuvant drugs, airway management and monitoring were managed at the discretion of the anaesthetist. Results are presented as mean (SD). Induction times were significantly longer [67 (32) vs 54 (17)s] and induction doses were significantly lower [14 (5) vs 16 (4) ml] in the TCI vs the MCI group. Recovery times and total doses were not significantly different. There were statistically but not clinically significant differences in mean arterial blood pressure and heart rate. Quality of anaesthesia and ease of control of anaesthesia were similar. We conclude that Diprifusor TCI and MCI are similar in terms of safety and efficacy.     

Implicit memory for words played during isoflurane- or propofol-based anesthesia: the lexical decision task

BACKGROUND: Unconscious processing of words during general anesthesia has been suggested after surgery with several tests of implicit memory. Patients can neither recall those words nor do they have explicit memories of other intraoperative events. It is unclear to what degree information is processed during general anesthesia and which tests are best suited to detect implicit memory. In the current study, a lexical decision paradigm not previously used to demonstrate implicit memory during anesthesia was used. METHODS: Sixty patients undergoing lumbar disc surgery were assigned to receive isoflurane infusion- or propofol infusion-based anesthesia combined with alfentanil infusions and a nitrous oxide-oxygen mixture. A control group of 10 medical students listened to tapes without receiving anesthesia. Two tapes, each containing a list of 30 low-frequency German nouns repeated for 15 min, were prepared, with half of the patients listening to tape A and the other half listening to tape B during the operation. Exposure time was 15 min from the time of skin incision onward. In the test phase, approximately 7 h later, words from lists A and B plus 60 nonwords were presented in random order by a computer program. Subjects were asked to indicate, by pressing one of two response buttons, whether the spoken word was or was not a legal German word (lexical decision). RESULTS: A recognition test revealed chance recognition for words presented during anesthesia. Lexical decision responses, however, were slightly faster to primed (previously presented) words than to unprimed (not previously presented) words when the entire group of patients was tested, suggesting a small implicit memory effect, which barely failed to reach the significance level. When the two medication groups were tested separately, no significant implicit memory effect could be ascertained statistically. The effects of previous exposure were much more pronounced in the control group. CONCLUSIONS: Balanced anesthesia techniques with isoflurane or propofol lead to only a minimal, statistically borderline implicit memory effect in the lexical decision paradigm.     

An investigation of learning during propofol sedation and anesthesia using the process dissociation procedure

BACKGROUND: Many studies have shown that patients may remember words learned during apparently adequate anesthesia. Performance on memory tests may be influenced by explicit and implicit memory. We used the process dissociation procedure to estimate implicit and explicit memory for words presented during sedation or anesthesia. METHODS: We investigated intraoperative learning in 72 women undergoing pervaginal oocyte collection during propofol and alfentanil infusion. One word list was played once before infusion, another was played 10 times during surgery. Venous blood was taken for propofol assay at the end of the intraoperative list. Behavioral measures of anesthetic depth (eyelash reflex, hand squeeze response to command) were recorded and used to adjust the dose of anesthetic where clinically appropriate. On recovery, memory was assessed using an auditory word stem completion test with inclusion and exclusion instructions. RESULTS: The mean blood propofol concentration was 2.5 microg/ml (median, 2.3 microg/ml; range, 0.7-6.1 microg/ml). Mean alfentanil dose was 2.1 mg (median, 2.0 mg; range, 1.2-3.4 mg). Comparison of target and distractor hits in the inclusion condition showed memory for preoperative words only. However, the process dissociation procedure estimates showed explicit (mean, 0.18; P < 0.001) and implicit (mean, 0.05; P < 0.05) memory for the preoperative words, and a small amount of explicit memory for the intraoperative words (mean, 0.06; 95% confidence interval, 0.01-0.10). Memory performance did not differ between the 17 patients who consistently responded to command and eyelash reflex and the 32 patients who remained unresponsive. Blood propofol concentration and alfentanil dose did not correlate with memory for the intraoperative list. CONCLUSIONS: There was no unprompted recall of surgery, but the process dissociation procedure showed memory for words presented during surgery. This memory was apparently explicit but did not correlate with the measures of depth of anesthesia used.     

Comparing the effects of stimulation and propofol infusion rate on implicit and explicit memory formation

Doubt remains about the conditions under which learning persistsdespite anaesthesia. This study investigated the relative importanceof dose of anaesthetic and stimulation for learning during propofolinfusion before surgery. Thirty-six patients were randomly assignedto three groups. Group 1 received two word lists (category examplesand nonsense words) during infusion of propofol to a targetconcentration of 2 µg ml^–1. Groups 2 and3 received the word lists during infusion of propofol 5 µg ml^–1.Group 2 received nonsense words before tracheal intubation andcategory examples during intubation; Group 3 heard categoryexamples before and nonsense words during intubation. Bispectralindex was recorded as a measure of depth of sedation/anaesthesia.We assessed explicit memory on recovery using a structured interviewand a recognition test. We assessed implicit memory using acategory generation test and a preference rating task. To establishbaseline, a control group of 12 patients completed the categorygeneration test without receiving the category examples duringanaesthesia. Overall, there was no evidence for learning duringpropofol infusion, though the category generation task showeda trend towards more implicit memory for words presented duringintubation than during anaesthesia. We conclude that learningdoes not occur during anaesthesia without surgery. Br J Anaesth 2001; 86: 189–95     

Effects of fentanyl, alfentanil, remifentanil and sufentanil on loss of consciousness and bispectral index during propofol induction of anaesthesia

The bispectral index (BIS) and a sedation score were used todetermine and compare the effect of propofol in the presenceof fentanyl, alfentanil, remifentanil and sufentanil. Seventy-fivenon-premedicated patients were assigned randomly into five groups(15 in each) to receive fentanyl, alfentanil, remifentanil,sufentanil or placebo. Opioids were administered using a target-controlledinfusion device, to obtain the following predicted effect-siteconcentrations: fentanyl, 1.5 ng ml^–1; alfentanil, 100ng ml^–1; remifentanil, 6 ng ml^–1; and sufentanil,0.2 ng ml^–1. After this, a target-controlled infusionof propofol (Diprifusor) was started to increase concentrationgradually, to achieve predicted effect-site concentrations of1, 2, and 4 µg ml^–1. At baseline and at each successivetarget effect-site concentration of propofol, the BIS, sedationscore and haemodynamic variables were recorded. At the momentof loss of consciousness (LOC), the BIS and the effect-siteconcentration of propofol were noted. The relationship betweenpropofol effect-site concentration and BIS was preserved withor without opioids. In the presence of an opioid, LOC occurredat a lower effect-site concentration of propofol and at a higherBIS₅₀ (i.e. the BIS value associated with 50% probability ofLOC), compared with placebo. Although clinically the hypnoticeffect of propofol is enhanced by analgesic concentrations ofµ-agonist opioids, the BIS does not show this increasedhypnotic effect. Br J Anaesth 2001; 86: 523–7