Absence of explicit and implicit memory in unconscious patients using a TCI of propofol

BACKGROUND: Episodes of implicit memory have been described during propofol anaesthesia. It remains unclear whether implicit memory is caused by short periods of awareness or occurs in an unconscious subject. METHODS: Sixty patients were randomized in an experimental group (EG), a control group (CG) and a reference group (RG). Loss of consciousness (LOC) was obtained by progressive stepwise increases of propofol using a target-controlled infusion device (Diprifusor, Alaris Medical Systems, San Diego, CA). A tape containing 20 words was played to the patients in the CG before the start of anaesthesia and to the patients in the EG at a constant calculated concentration of propofol associated with LOC. The tape was not played to the patients in the RG. Three memory tests were performed postoperatively. RESULTS: Explicit and implicit memories were evidenced in the CG but not in the EG. CONCLUSION: In our group of young ASA I/II patients, in the absence of any noxious stimulus, no implicit or explicit memory was found when the calculated concentration of propofol using a Diprifusor was maintained at the level associated with LOC.     

Predictive performance of computer-controlled infusion of remifentanil during propofol/remifentanil anaesthesia

Background. The predictive performance of the available pharmacokineticparameter sets for remifentanil, when used for target-controlledinfusion (TCI) during total i.v. anaesthesia, has not been determinedin a clinical setting. We studied the predictive performanceof five parameter sets of remifentanil when used for TCI ofremifentanil during propofol anaesthesia in surgical patients. Methods. Remifentanil concentration–time data that hadbeen collected during a previous pharmacodynamic interactionstudy in 30 female patients (ASA physical status I, aged 20–65 yr)who received a TCI of remifentanil and propofol during lowerabdominal surgery were used in this evaluation. The remifentanilconcentrations predicted by the five parameter sets were calculatedon the basis of the TCI device record of the infusion rate–timeprofile that had actually been administered to each individual.The individual and pooled bias [median performance error (MDPE)],inaccuracy [median absolute performance error (MDAPE)], divergenceand wobble of the remifentanil TCI device were determined fromthe pooled and intrasubject performance errors. Results. A total of 444 remifentanil blood samples were analysed.Blood propofol and remifentanil concentrations ranged from 0.5to 11 µg ml^–1 and 0.1 to 19.6 ng ml^–1respectively. Pooled MDPE and MDAPE of the remifentanil TCIdevice were –15 and 20% for the parameter set of Mintoand colleagues (Anesthesiology 1997; 86: 10–23), 1 and21%, –6 and 21%, and –6 and 19% for the three parametersets described by Egan and colleagues (Anesthesiology 1996;84: 821–33, Anesthesiology 1993; 79: 881–92, Anesthesiology1998; 89: 562–73), and –24 and 30% for the parameterset described by Drover and Lemmens (Anesthesiology 1998; 89:869–77). Conclusions. Remifentanil can be administered by TCI with acceptablebias and inaccuracy. The three pharmacokinetic parameter setsdescribed by Egan and colleagues resulted in the least biasand best accuracy. Br J Anaesth 2003; 90: 132–41     

Psychomotor dysfunction after remifentanil/propofol anaesthesia

BACKGROUND AND OBJECTIVES: Early recovery after anaesthesia is gaining importance in fast track management. The aim of this study was to quantify psychomotor recovery within the first 24 h after propofol/remifentanil anaesthesia using the Short Performance Test (Syndrom Kurztest (SKT)), consisting of nine subtests. The hypothesis was that psychomotor performance remains reduced 24 h after anaesthesia. METHODS: Thirty-seven patients scheduled for elective surgery took part in the study. The SKT was performed on the day before general anaesthesia (T0), 10, 30, 90 min and 24 h after extubation (T1). Parallel versions were used to minimize learning effects. Anaesthesia was introduced and maintained with remifentanil/propofol as a target controlled infusion. Propofol plasma concentration was measured 10 and 90 min after extubation. Perioperative pain management included novaminsulfon and piritramide. RESULTS: Up till 90 min after surgery and anaesthesia, psychomotor performances were significantly reduced as the lower test results in all SKT subtests indicated (P < or = 0.007 vs. baseline T0). In the three memory subtests (ST 2, ST 8 and ST 9), psychomotor performance was still reduced on the first postoperative day (P < or = 0.005; T1 vs. T0). There was no correlation between propofol plasma concentration and the psychometric test results. CONCLUSIONS: Propofol/remifentanil-based target controlled general anaesthesia for surgery is associated with a reduced psychomotor function up to the first postoperative day. Further studies are needed to confirm the usefulness of the SKT in the perioperative period and to clarify which components in the perioperative period are responsible for a lower performance in the SKT.     

Analysis of implicit memory during propofol anesthesia

OBJECTIVE: Consensus has not been achieved on the presence of unconscious memory of messages in general anesthesia for methodological reasons. Our objective was to apply a model of anesthesia that allows for clinical control of the level of hypnosis in order to evaluate the presence and characteristics of implicit memory in deep sedation with propofol. PATIENTS AND METHODS: We randomly assigned 48 consecutive patients undergoing lower limb surgery to two groups. In both groups subarachnoid anesthesia was with varying doses of propofol to maintain a level of hypnosis marked by inability to respond to orders, absence of movements and spontaneous ventilation. The experimental group listened to a recording of the words "banana" and "melon" for the semantic category of fruits and "white" and "black" for colors. The control group listened to a recording of environmental operating room noise. We recorded, among other variables, anxiety and age. Upon awakening, after the presence of conscious memory had been ruled out, we investigated implicit memory by comparing the percentage of correct answers in the two groups. RESULTS: The experimental group had a higher percentage of correct fruit names (p = 0.03). No differences were detected for colors. The youngest patients in the experimental group were correct more often about the fruits than were older members (p = 0.04) and those with greater anxiety were more often correct (p = 0.002). CONCLUSIONS: Implicit memory is preserved under hypnosis with propofol and is more likely to be present among those who are younger or experience greater anxiety. Concrete words with object references are more easily remembered than abstract words referring to perception. The semantic load of messages is relevant.     

SNAP index and Bispectral index during different states of propofol/remifentanil anaesthesia

The accuracy of the new SNAP index with the Bispectral index (BIS) to distinguish different states of propofol/remifentanil anaesthesia was compared in 19 female patients who were undergoing minor gynaecological surgery. Comparisons of the SNAP index, BIS, spectral edge frequency, mean arterial blood pressure and heart rate were performed. The ability of all parameters to distinguish between the steps of anaesthesia -awake vs. loss of response, awake vs. anaesthesia, anaesthesia vs. first reaction and anaesthesia vs. extubation - were analysed with the prediction probability. The prediction probability to differentiate between two interesting nuances of anaesthetic states -loss of response vs. first reaction - was calculated. Only the BIS showed no overlap between the investigated steps of anaesthesia. Both the SNAP index and BIS failed to differentiate the nuances of anaesthesia. The SNAP index and BIS were superior to mean arterial blood pressure and heart rate and spectral edge frequency in distinguishing between different steps of anaesthesia with propofol and remifentanil and provided useful additional information.     

Absence of explicit or implicit memory in patients anesthetized with sufentanil/nitrous oxide.

Verbal paired associates were presented to 25 surgical patients from initial incision to closure of the incision during general anesthesia. Sufentanil with nitrous oxide and oxygen was administered; intravenous morphine (0.05 mg/kg) was administered when the skin suturing was completed; no volatile anesthetic agents or benzodiazepines were administered. When ready for discharge from the postanesthesia care unit, and again 2 weeks later by telephone, patients were tested for free recall, cued recall, recognition, and free association. No evidence of explicit memory for the word list was demonstrated by patients on tests of free recall, cued recall, or recognition, nor did a free-association test of implicit memory demonstrate a significant priming effect, in contrast to previous results obtained with isoflurane. The precise conditions under which surgical events can be processed, and retained in the form of implicit memory outside of conscious awareness, remain to be determined.     

Narcotrend-assisted propofol/remifentanil anaesthesia for prevention of awareness

Editor—I read with interest about the comparison of theuse of Narcotrend and clinical assessment in judging the depthof anaesthesia while using total i.v. anaesthesia (TIVA).¹ Ifully agree with the authors that the use of clinical assessmentalone would lead to a greater deviation from a defined targetwhile     

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.     

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     

Comparison of propofol/remifentanil and sevoflurane/remifentanil for maintenance of anaesthesia for elective intracranial surgery

Background. Propofol and sevoflurane are suitable agents formaintenance of anaesthesia during neurosurgical procedures.We have prospectively compared these agents in combination withthe short-acting opioid, remifentanil. Methods. Fifty unpremedicated patients undergoing elective craniotomyreceived remifentanil 1 µg kg^–1 followed by an infusioncommencing at 0.5 µg kg^–1 min^–1 reducing to0.25 µg kg^–1 min^–1 after craniotomy. Anaesthesiawas induced with propofol, and maintained with either a target-controlledinfusion of propofol, minimum target 2 µg ml^–1 orsevoflurane, initial concentration 2%_ET. Episodes of mean arterialpressure (MAP) more than 100 mm Hg or less than 60 mm Hg formore than 1 min were defined as hypertensive or hypotensiveevents, respectively. A surgical assessment of operating conditionsand times to spontaneous respiration, extubation, obey commandsand eye opening were recorded. Drug acquisition costs were calculated. Results. Twenty-four and twenty-six patients were assigned topropofol (Group P) and sevoflurane anaesthesia (Group S), respectively.The number of hypertensive events was comparable, whilst morehypotensive events were observed in Group S than in Group P(P=0.053, chi-squared test). As rescue therapy, more labetolol[45 (33) vs 76 (58) mg, P=0.073] and ephedrine [4.80 (2.21)vs 9.78 (5.59) mg, P=0.020] were used in Group S. Between groupdifferences in recovery times were small and clinically unimportant.The combined hourly acquisition costs of hypnotic, analgesic,and vasoactive drugs appeared to be lower in patients maintainedwith sevoflurane than with propofol. Conclusion. Propofol/remifentanil and sevoflurane/remifentanilboth provided satisfactory anaesthesia for intracranial surgery.     

Recovery from propofol anaesthesia supplemented with remifentanil

We have examined the effects on recovery end-points of supplementationof a propofol-based anaesthetic with remifentanil. After inductionof anaesthesia with propofol and remifentanil 1.0 µg kg^–1,15 patients each were randomly allocated to target plasma propofolconcentrations of 2, 3, 4 or 5 µg ml^–1for maintenance of anaesthesia. Remifentanil was administeredby infusion for supplementation in doses required for maintenanceof adequate anaesthesia. All patients received 50% nitrous oxidein oxygen and ventilation was controlled. The total amount ofdrugs used and times to different recovery end-points were recorded.Cognitive function was also assessed using a Mini-Mental Statequestionnaire. The median dose of remifentanil for maintenanceof adequate anaesthesia (excluding the initial bolus dose) inthe four groups was 0.21, 0.15, 0.11 and 0.13 µg kg^–1 min^–1respectively (P=0.0026). The median times to eye opening andorientation were shortest in the 2 µg ml^–1group [6.0 and 6.5 min, 8.5 and 10.8 min, 13.4 and15.8 min, and 14.2 and 19.5 min respectively in thepropofol 2, 3, 4, and 5 µg ml^–1 groups respectively(P<0.001)]. The times to discharge from the recovery wardand the Mini-Mental State scores were not significantly different. Br J Anaesth 2001; 86: 361–5     

Effect of tramadol on Bispectral Index during intravenous anaesthesia with propofol and remifentanil

The aim of this study was to investigate the effects of tramadol on the Bispectral Index (BIS) during total intravenous propofol-remifentanil anaesthesia. Forty-four adult ASA Physical status I-II patients, scheduled for elective general surgical procedures were included in a prospective observational randomized study. Doses for anaesthetics and opioids were adjusted to keep the BIS value at 50 +/- 5. After 20 minutes of stable anaesthesia, the subjects were randomly allocated to receive intravenous saline (control group) or tramadol 1.5 mg/kg (tramadol group). BIS values, mean arterial pressure, and heart rate were recorded every five minutes for 20 minutes. Mean BIS values after tramadol administration were not significantly different from those following saline, throughout the observation period (P > 0.05). There were no patients in whom BIS values were more than 60 or who presented explicit recall of events under anaesthesia. There were no significant changes in mean arterial pressure, SpO2, or heart rate (P > 0.05). The results indicate that the administration of tramadol during stable total intravenous anaesthesia with propofol-remifentanil does not affect BIS values. The clinical relevance is that tramadol can be safely administered pre- and intraoperatively as pre-emptive or preventive analgesia without modification of the depth of anaesthesia.     

Comparison of the antitussive effect of remifentanil during recovery from propofol and sevoflurane anaesthesia

This prospective randomised study compared the antitussive effect of remifentanil during recovery from either propofol or sevoflurane anaesthesia. Seventy‐four female patients undergoing thyroidectomy were anaesthetised with either propofol and remifentanil or sevoflurane and remifentanil. During recovery, remifentanil was maintained at an effect‐site concentration of 2 ng.ml^?1 until extubation and the occurrence of coughing, haemodynamic parameters and recovery profiles were compared between the two groups. During recovery, neither the incidence nor the severity of cough (incidence 20% with propofol; 24% with sevoflurane, p = 0.77), nor the haemodynamic parameters were different between the two groups. Time to awakening and time to extubation were significantly shorter in the propofol group (4.7 min, 6.1 min min, respectively) compared with the sevoflurane group (7.9 min and 8.9 min respectively) (p < 0.001 and p = 0.002, respectively). An effect‐site concentration of 2 ng.ml^?1 of remifentanil was associated with smooth emergence from both propofol and sevoflurane anaesthesia.     

Less postoperative nausea and vomiting after propofol + remifentanil versus propofol + fentanyl anaesthesia during plastic surgery

BACKGROUND: The effect of different opioids on postoperative nausea and vomiting (PONV) has not been conclusively determined yet, thus the aim of this study was to compare the incidence of PONV in propofol-anaesthetized patients receiving either fentanyl or remifentanil as opioid supplement. METHODS: Sixty ASA physical status I and II patients scheduled for plastic surgery gave their written informed consent for this prospective, randomized, double-blind study. Anaesthesia was induced with propofol, rocuronium and fentanyl (n = 30; 2 microg kg(-1)) or remifentanil (n = 30; 1 microg kg(-1)). After tracheal intubation, anaesthesia was maintained with propofol, oxygen in air and an infusion of the opioid studied, which was modified according to clinical criteria. Baseline postoperative analgesia was achieved with intravenous propacetamol + metamizol. Intravenous morphine was given if visual analogic scale (VAS) for pain was > or = 4 (scale 0-10) and metoclopramide was administered if a patient presented > or = 2 PONV episodes (nausea or vomiting) in less than 30 min. Postoperatively (2, 12 and 24 h), we registered VAS, rescue morphine consumption, number of patients with episodes of PONV and number of patients requiring metoclopramide. P < 0.05 was considered significant. RESULTS: There were no significant differences between groups in the demographic parameters, ASA physical status, propofol dose, VAS, and rescue morphine requirements. Fourteen patients in the fentanyl group and four in the remifentanil group presented PONV episodes 2-12 h postoperative hours' interval; (P < 0.05). Ten patients in the fentanyl group and four in the remifentanil group presented vomiting episodes in the same period (P < 0.05); and eight patients in the fentanyl group and one in the remifentanil group required metoclopramide; (P < 0.05). The number of postoperative PONV episodes were low, both in the 0-2-h period (n = 2 vs. n = 1, fentanyl and remifentanil, respectively) and in the 12-24-h period (n = 3 vs. n = 1). CONCLUSION: Propofol + fentanyl anaesthesia resulted in a higher incidence of PONV and requirements of antiemetic drugs in the period between 2 and 12 postoperative hours compared with propofol + remifentanil, in patients undergoing plastic surgery.     

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.     

麻醉剂量的丙泊酚对内隐记忆的影响

目的观察麻醉剂量下丙泊酚对内隐记忆及其脑电双频谱指数(BIS)的影响.方法选择42例子宫全切术的病人,随机分为三组.Ⅰ组,Ⅱ组为试验组,各11例.Ⅲ组为对照组20例.三组病人均施予腰麻硬膜外联合麻醉.试验组加用丙泊酚2mg@kg-1,维库溴铵8mg诱导行气管内插管,静脉持续泵入丙泊酚110μg@kg-1@min-1维持麻醉.采用HXD-1型多功能脑电监测仪监测BIS.BIS＞60的病人为I组,BIS＜60的病人为Ⅱ组,关腹后给予内隐记忆听刺激.术后6h测试其模糊辨听率,同时对术中的记忆情况进行调查.结果Ⅰ、Ⅱ组间脑电BIS有显著差异,分别为71.93±10.51和56.04±11.86(P＜0.05).模糊辨听率三组间无差异(P＞0.05).试验组病人无一例存在有外显记忆.结论临床剂量的丙泊酚无论BIS大于或小于60,内隐记忆不能被消除.     

Category generation testing in the search for implicit memory during general anaesthesia

We gave auditory examples of two semantic categories through headphones to 100 surgical patients anaesthetized with propofol and enflurane. This presentation was made during certain stages of the procedure, potentially associated with arousal, and during steady-state anaesthesia. Postoperative review using category generation tests showed successful priming in a pre-induction group but no evidence of implicit memory in the anaesthetized groups. These results suggest that timing an auditory input to coincide with surgical stimulation does not increase the probability of retrieval of information by this type of testing.