Investigation of implicit memory during isoflurane anesthesia for elective surgery using the process dissociation procedure

BACKGROUND: This prospective study evaluated memory function during general anesthesia for elective surgery and its relation to depth of hypnotic state. The authors also compared memory function in anesthetized and nonanesthetized subjects. METHODS: Words were played for 70 min via headphones to 48 patients (aged 18-70 yr) after induction of general anesthesia for elective surgery. Patients were unpremedicated, and the anesthetic regimen was free. The Bispectral Index (BIS) was recorded throughout the study. Within 36 h after the word presentation, memory was assessed using an auditory word stem completion test with inclusion and exclusion instructions. Memory performance and the contribution of explicit and implicit memory were calculated using the process dissociation procedure. The authors applied the same memory task to a control group of nonanesthetized subjects. RESULTS: Forty-seven patients received isoflurane, and one patient received propofol for anesthesia. The mean (+/- SD) BIS was 49 +/- 9. There was evidence of memory for words presented during light (BIS 61-80) and adequate anesthesia (BIS 41-60) but not during deep anesthesia (BIS 21-40). The process dissociation procedure showed a significant implicit memory contribution but not reliable explicit memory contribution (mean explicit memory scores 0.05 +/- 0.14, 0.04 +/- 0.09, and 0.05 +/- 0.14; mean automatic influence scores 0.14 +/- 0.12, 0.17 +/- 0.17, and 0.18 +/- 0.21 at BIS 21-40, 41-60, and 61-80, respectively). Compared with anesthetized patients, the memory performance of nonanesthetized subjects was better, with a higher contribution by explicit memory and a comparable contribution by implicit memory. CONCLUSION: During general anesthesia for elective surgery, implicit memory persists even in adequate hypnotic states, to a comparable degree as in nonanesthetized subjects.     

Changes in the Auditory Evoked Potentials and the Bispectral Index following Propofol or Propofol and Alfentanil

Background: Midlatency auditory evoked potentials (MLAEP) show graded changes with increasing doses of hypnotics but little change with opioids. The effect of their combination on the MLAEP was evaluated. Also, the bispectral index (BIS) was compared with the ability of MLAEP to correlate with sedation and predict loss of consciousness.

Methods: Twenty healthy volunteers were randomly assigned to receive stepped increases in propofol concentration (10 subjects) or propofol plus alfentanil 100 ng/ml (10 subjects). At baseline and at each targeted effect site concentration the mean MLAEP, BIS, measures of sedation, and drug concentration were obtained. The relation among MLAEP, BIS, and sedation score was determined. The prediction probability (Pk) was calculated and compared for BIS and MLAEP.

Results: The BIS and MLAEP patterns showed significant changes (Pa and Nb decreased in amplitude and increased in latency) with increasing level of sedation (P < 0.0001). The BIS correlated better with sedation scores (0.884) than did the MLAEP (P < 0.05). Pa and Nb latencies showed the best correlation with sedation levels (0.685 and 0.658, respectively). The addition of alfentanil did not affect the relation between MLAEP and loss of consciousness (P > 0.15). The BIS (Pk = 0.952) was a better predictor of loss of consciousness than were Pa and Nb amplitude (P < 0.05) but were comparable to Pa and Nb latency (Pk = 0.869 and 0.873, respectively).     

Intra-operative awareness in children and post-traumatic stress disorder

Adults who experience intra-operative awareness can develop disturbing long-lasting after-effects, such as daytime anxiety, sleep disturbances, nightmares, flashbacks and, in the worst case, a post-traumatic stress disorder (PTSD). It is unknown whether intra-operative awareness has a similar psychological impact in children. We designed the present study in order to evaluate the incidence of psychological symptoms in children who had either confirmed or possible intra-operative awareness. Attempts were made to locate 11 children who had been identified in a previous study, approximately 1 year following their experience. A PTSD questionnaire was administered to the children and their parents in order to detect any long-term or short-term psychological symptoms (the 1-month postoperative data were evaluated retrospectively). Factors believed to be associated with PTSD, such as intra-operative perceptions, the children's temperament and cognitive strategies, and the parents' coping strategies, were also analysed. Seven children were successfully located and interviewed and no short or long-term psychological symptoms were identified. None of them offered negative appraisals of the traumatic event and none had displayed dysfunctional behaviour or cognitive strategies. Thus, none of them had developed a PTSD syndrome. In contrast with what has been reported in adults, these children claimed not to have experienced major pain, terror or helplessness during their surgery. Despite the small sample size, the results of the present study suggest that children suffer less psychological sequelae than adults following intra-operative awareness. This may be due to the fact that the children reported less frightening intra-operative sensations as compared with the adults, and had less understanding of the anaesthesia procedure, and this may have influenced their appraisal of their awareness and protected them from the full impact of this potentially traumatic experience.     

Determination of the Potency of Remifentanil Compared with Alfentanil Using Ventilatory Depression as the Measure of Opioid Effect

Background: Remifentanil is a new opioid with properties similar to other mu-specific agonists. To establish its pharmacologic profile relative to other known opioids, it is important to determine its potency. This study investigated the relative potency of remifentanil compared with alfentanil.

Methods: Thirty young healthy males were administered double-blind remifentanil or alfentanil intravenously for 180 min using a computer-assisted continuous infusion device. Depression of ventilation was assessed by the minute ventilatory response to 7.5% CO2 administered via a "bag in the box" system. The target concentration of the study drug was adjusted to obtain 40-70% depression of baseline minute ventilation. Multiple blood samples were obtained during and following the infusion. The concentration-effect relationship of each drug was modeled, and the concentration needed to provide a 50% depression of ventilation (EC50) was determined.

Results: Only 11 subjects in each drug group completed the study; however, there were sufficient data in 28 volunteers to model their EC50 values. The EC50 (mean and 95% confidence interval) for depression of minute ventilation with remifentanil was 1.17 (0.85-1.49) ng/ml and the EC (50) for alfentanil was 49.4 (32.4-66.5) ng/ml.     

Investigation of Implicit Memory during Isoflurane Anesthesia for Elective Surgery Using the Process Dissociation Procedure

Background: This prospective study evaluated memory function during general anesthesia for elective surgery and its relation to depth of hypnotic state. The authors also compared memory function in anesthetized and nonanesthetized subjects.

Methods: Words were played for 70 min via headphones to 48 patients (aged 18-70 yr) after induction of general anesthesia for elective surgery. Patients were unpremedicated, and the anesthetic regimen was free. The Bispectral Index (BIS) was recorded throughout the study. Within 36 h after the word presentation, memory was assessed using an auditory word stem completion test with inclusion and exclusion instructions. Memory performance and the contribution of explicit and implicit memory were calculated using the process dissociation procedure. The authors applied the same memory task to a control group of nonanesthetized subjects.

Results: Forty-seven patients received isoflurane, and one patient received propofol for anesthesia. The mean (+/- SD) BIS was 49 +/- 9. There was evidence of memory for words presented during light (BIS 61-80) and adequate anesthesia (BIS 41-60) but not during deep anesthesia (BIS 21-40). The process dissociation procedure showed a significant implicit memory contribution but not reliable explicit memory contribution (mean explicit memory scores 0.05 +/- 0.14, 0.04 +/- 0.09, and 0.05 +/- 0.14; mean automatic influence scores 0.14 +/- 0.12, 0.17 +/- 0.17, and 0.18 +/- 0.21 at BIS 21-40, 41-60, and 61-80, respectively). Compared with anesthetized patients, the memory performance of nonanesthetized subjects was better, with a higher contribution by explicit memory and a comparable contribution by implicit memory.     

Near-death experience in a boy undergoing uneventful elective surgery under general anesthesia

Near-death experience (NDE) is a complex subjective experience, which may include affective elements such as a sense of peacefulness, paranormal components such as a sensation of floating out of the body, and a perception of being in a dark tunnel and seeing a brilliant light. It is usually reported to occur in association with a wide range of life-threatening situations, as for instance, cardiopulmonary resuscitation. We report on an episode of NDE that occurred in a 12-year-old boy who underwent a general anesthesia for an elective uncomplicated surgery. To our knowledge, this is the first case of NDE in a child that has been reported in this context.     

Changes in the auditory evoked potentials and the bispectral index following propofol or propofol and alfentanil

BACKGROUND: Midlatency auditory evoked potentials (MLAEP) show graded changes with increasing doses of hypnotics but little change with opioids. The effect of their combination on the MLAEP was evaluated. Also, the bispectral index (BIS) was compared with the ability of MLAEP to correlate with sedation and predict loss of consciousness. METHODS: Twenty healthy volunteers were randomly assigned to receive stepped increases in propofol concentration (10 subjects) or propofol plus alfentanil 100 ng/ml (10 subjects). At baseline and at each targeted effect site concentration the mean MLAEP, BIS, measures of sedation, and drug concentration were obtained. The relation among MLAEP, BIS, and sedation score was determined. The prediction probability (Pk) was calculated and compared for BIS and MLAEP. RESULTS: The BIS and MLAEP patterns showed significant changes (Pa and Nb decreased in amplitude and increased in latency) with increasing level of sedation (P < 0.0001). The BIS correlated better with sedation scores (0.884) than did the MLAEP (P < 0.05). Pa and Nb latencies showed the best correlation with sedation levels (0.685 and 0.658, respectively). The addition of alfentanil did not affect the relation between MLAEP and loss of consciousness (P > 0.15). The BIS (Pk = 0.952) was a better predictor of loss of consciousness than were Pa and Nb amplitude (P < 0.05) but were comparable to Pa and Nb latency (Pk = 0.869 and 0. 873, respectively). CONCLUSION: MLAEP changes, like the BIS, correlate well with increasing sedation produced by propofol, and these changes in the MLAEP are independent of the presence of an opioid. Among all the MLAEP parameters, Pa and Nb latencies are the best predictors of increasing sedation and loss of consciousness.     

Naloxone-responsive acute dystonia and parkinsonism following general anaesthesia

Various movement disorders such as dystonia may acutely develop during or at emergence from general anaesthesia in patients with or without pre-existing Parkinson disease. These movements are triggered by a variety of drugs including propofol, sevoflurane, anti-emetics, antipsychotics and opioids. The postulated mechanism involves an imbalance between dopaminergic and cholinergic neurotransmitters in the basal ganglia. We report an acute, severe and generalised dystonic reaction in an otherwise healthy woman at emergence from general anaesthesia, dramatically reversed by the administration of naloxone, pointing to a potential role of the fentanyl and morphine that the patient had received. Recent literature on the mechanisms of abnormal movements induced by opioids are discussed. The severity of the reaction with usual doses of opioids, in a patient with no prior history of parkinsonism, led to further investigation that demonstrated the possibility of an enhanced susceptibility to opioids, involving a genetically determined abnormal function of glycoproteine-P and catechol-O-methyltransferase.     

Determination of the potency of remifentanil compared with alfentanil using ventilatory depression as the measure of opioid effect.

BACKGROUND: Remifentanil is a new opioid with properties similar to other mu-specific agonists. To establish its pharmacologic profile relative to other known opioids, it is important to determine its potency. This study investigated the relative potency of remifentanil compared with alfentanil. METHODS: Thirty young healthy males were administered double-blind remifentanil or alfentanil intravenously for 180 min using a computer-assisted continuous infusion device. Depression of ventilation was assessed by the minute ventilatory response to 7.5% CO2 administered via a "bag in the box" system. The target concentration of the study drug was adjusted to obtain 40-70% depression of baseline minute ventilation. Multiple blood samples were obtained during and following the infusion. The concentration-effect relationship of each drug was modeled, and the concentration needed to provide a 50% depression of ventilation (EC50) was determined. RESULTS: Only 11 subjects in each drug group completed the study; however, there were sufficient data in 28 volunteers to model their EC50 values. The EC50 (mean and 95% confidence interval) for depression of minute ventilation with remifentanil was 1.17 (0.85-1.49) ng/ml and the EC50 for alfentanil was 49.4 (32.4-66.5) ng/ml. CONCLUSION: Based on depression of the minute ventilatory response to 7.5% CO2, remifentanil is approximately 40 (26-65) times more potent than alfentanil when remifentanil and alfentanil whole-blood concentrations are compared. As alfentanil is usually measured as a plasma concentration, remifentanil is approximately 70 (41-104) times more potent than alfentanil when remifentanil whole-blood concentration is compared with alfentanil plasma concentration. This information should be used when performing comparative studies between remifentanil and other opioids.