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.

Does implicit memory during anaesthesia persist in children?

BACKGROUND: Recent studies suggest that implicit memory (especially perceptual implicit memory) persists during adequate general anaesthesia in adults. Studies in children, however, have failed to demonstrate implicit memory during general anaesthesia, possibly because of differences in methodological design. We therefore designed a prospective study with the aim of evaluating implicit memory in children undergoing general anaesthesia, using a perceptual memory test based on the mere exposure effect, previously tested in a control group. METHODS: Twelve infrequent neutral words were played 12 times in a random sequence via headphones to 36 children aged 8-12 yr during elective or emergency surgery. The children were not premedicated, and general anaesthesia was maintained with isoflurane. The word presentation started immediately after the surgical incision. Within 36 h after the stimulus presentation, the memory was assessed by using a forced-choice preference judgement task. Time constraint and word deterioration with a low-pass filter were used to prevent the subjects from utilizing intentional retrieval. The implicit memory score was obtained by calculating the proportion of target words preferred, which was compared with the chance level (0.5). RESULTS: The percentage of correct responses given by the children was comparable with the chance level. The memory score was mean (sd) 0.48 (0.16) (95% CI 0.43-0.53). CONCLUSIONS: The use of a perceptual implicit memory test based on the mere exposure procedure in children failed to reveal any evidence of implicit memory under general anaesthesia.

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.

Intra-operative awareness in children: the value of an interview adapted to their cognitive abilities.

Intra-operative awareness in paediatric patients has been little studied for many years because of the difficulties in relying on children's testimony. Earlier questionnaires used to detect this complication were not adapted to children's language and memory capacities. By using a qualitative method, a semi-structured in-depth interview adapted to their cognitive abilities, we have now conducted a prospective evaluation of the incidence and risk factors for intra-operative awareness in children undergoing general anaesthesia. Data were obtained from interviews with 410 children (aged 6-16 years) which were conducted within 36 h of general anaesthesia for elective or emergency surgery. One month after surgery, 293 of these patients were interviewed again. Three independent adjudicators classified each potential case of awareness. We considered awareness to include both the 'confirmed awareness' and the 'possible awareness' cases. The accuracy of the children's recall was calculated. The relationship between their awareness and the anaesthesia management was examined. There were five cases of confirmed awareness, and six cases of possible awareness. The incidence of confirmed awareness was 1.2%, but when the possible cases were also considered, the overall incidence of this complication was as high as 2.7% (95% confidence interval, 1.4-5.0%). The only predictive factor identified was the multiple manoeuvres with which the airways were secured (odds ratio, 8.4; 95% confidence interval, 2.4-29.07%). The present study confirms the existence of intra-operative awareness in the paediatric population. The application of a semi-structured in-depth interview adapted to the cognitive capacities of the children appears to enhance the detection of awareness in this population.

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.

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.

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 effects of solution concentration and epinephrine on lateral distribution of hyperbaric tetracaine spinal anesthesia.

In a search of a differential spinal block between dependent and nondependent sides, we investigated whether the use of a larger concentration of hyperbaric tetracaine (T) and/or the omission of epinephrine (E) would provide differential spread in patients left for 15 min in the lateral decubitus position. Spinal anesthesia was performed in the lateral decubitus position with the operated side dependent in 60 patients scheduled for lower limb surgery. All patients remained lateral for 15 min after spinal injection before being turned supine. They received 12 mg of T in 10% dextrose and E 0.2 mg was added when predicted duration of surgery was more than 90 min. The concentration of T to be used for each patient was randomized. This resulted in four groups of 15 patients: T 0.5% + E (control group), T 1% + E, T 0.5%, and T 1%. A unilateral anesthesia was defined as the presence of an adequate sensory (L-1 or higher) and/or motor (3 degrees) blockade on the dependent side and the absence of one or both modalities on the nondependent side, or as a duration of sensory (regression to L-2) and motor (1 degrees of recovery) blockade 20% longer on the dependent compared to the nondependent side. None of the 60 patients showed unilateral sensory block. A comparable number of patients in all groups showed unilateral motor block: four in T 0.5% + E, two in T 1% + E, four in T 0.5%, and five in T 1%. Likewise, a comparable number of patients in all groups showed a prolonged duration of sensory and motor block, respectively: six and eight in T 0.5% + E, six and nine in T 1% + E, six and eight in T 0.5%, and seven and seven in T 1%. In conclusion, although a preferential distribution of hyperbaric T toward the dependent side in patients of all four groups was noticed, the use of a larger concentration of T, omission of E, or combination of these two factors did not provide a more marked differential spread when compared to the standard solution of T 0.5% + E.