Immediate peri-operative memory.

BACKGROUND: Information about anterograde and retrograde amnesias in the immediate peri-operative period is scarce. During this period, assessment of memory for real-life events is also rare. We hypothesized that there would be both anterograde and retrograde amnesias and memory for peri-operative events would be better than for verbal memory. METHODS: We studied 40 patients who underwent general anesthesia and surgery and 19 control volunteers who were matched to the patients but did not have surgery. Patients completed the state anxiety part of the Spielberger State-Trait Anxiety Inventory in the pre-operative period. They were presented with three word lists in the holding area, the operating room before induction of anesthesia and the recovery room. Memory for the words was tested the next day by recall and recognition tests. Memory for events that happened on the day of surgery was tested by administering a questionnaire. The control subjects were tested similarly but did not complete the events questionnaire. Retrograde amnesia would be demonstrated by a decline in patients' memory from the holding area to the operating room which exceeded any corresponding changes in controls; anterograde amnesia would be demonstrated by memory impairment of the patients in the recovery room, relative to controls. RESULTS: Recall and recognition of words were significantly impaired in the recovery room with a decline from 12% in the holding area to zero% in the recovery room for recall and from 43% to 7% for recognition. The decline in memory from the holding area to the operating room was not significantly greater in patients than in controls, 80% vs. 56% for recall and 27% vs. 14% for recognition. There were no significant differences for recognition of events which happened in the three rooms. CONCLUSIONS: We were unable to detect retrograde amnesia. Patients' memory for neutral stimuli in the recovery room was severely impaired. The events questionnaire proved to be insensitive.

Acute marijuana effects on rCBF and cognition: a PET study.

The effects of smoking marijuana on cognition and brain function were assessed with PET using H2(15)O. Regional cerebral blood flow (rCBF) was measured in five recreational users before and after smoking a marijuana cigarette, as they repeatedly performed an auditory attention task. Blood flow increased following smoking in a number of paralimbic brain regions (e.g. orbital frontal lobes, insula, temporal poles) and in anterior cingulate and cerebellum. Large reductions in rCBF were observed in temporal lobe regions that are sensitive to auditory attention effects. Brain regions showing increased rCBF may mediate the intoxicating and mood-related effects of smoking marijuana, whereas reduction of task-related rCBF in temporal lobe cortices may account for the impaired cognitive functions associated with acute intoxication.

Cerebellar hypoactivity in frequent marijuana users.

It is uncertain whether frequent marijuana use adversely affects human brain function. Using PET, regional cerebral blood flow was compared in frequent marijuana users and comparable, non-using controls after at least 26 h of monitored abstention by all subjects. Marijuana users showed substantially lower brain blood flow than controls in a large region of posterior cerebellum, indicating altered brain function in frequent marijuana users. A cerebellar locus of some chronic and acute effects of marijuana is plausible, e.g. the cerebellum has been linked to an internal timing system, and alterations of time sense are common following marijuana smoking.

Auditory evoked responses and learning and awareness during general anesthesia.

BACKGROUND: There is a major distinction between conscious and unconscious learning. Monitoring the mid-latency auditory evoked responses (AER) has been proposed as a measure to ascertain the adequacy of the hypnotic state during surgery. In the present study, we investigated the presence of explicit and implicit memories after anesthesia and examined the relationships of such memories to the AER. METHODS: We studied 180 patients scheduled for elective surgical procedures. After a thiopental induction, one of four anesthetics were studied: Opioid bolus: 7.5 microg x kg(-1) fentanyl, 70% N2O, with 2.5 microg x kg(-1) supplements as needed (n=100); Opioid infusion: Alfentanil 50 microg x kg(-1) bolus, 1-1.5 microg x kg(-1) x min(-1) infusion, 70% N2O (n=40); Isoflurane 0.3%: Fentanyl 1 microg x kg(-1), 70% N2O, isoflurane 0.3% expired (n=16); Isoflurane 0.7%: Fentanyl 1 microg x kg(-1), 70% N2O, isoflurane 0.7% expired (n=23). AER were recorded before anesthesia, 5 min after surgical incision and then every 30 min until the end of surgery. A tape of either the story of the "Three Little Pigs" or the "Wizard of Oz" was played continuously between the recordings. Explicit memory was assessed postoperatively by tests of recall and recognition, and implicit memory was assessed by the frequency of story-related free associations to target words from the stories, which were solicited twice during a structured interview. RESULTS: Six patients showed explicit recall of intraoperative events: All received the opioid bolus regimen. About 7% of patients reported dreaming during anesthesia. The incidence of picking the correct story that had been presented during anesthesia averaged 49%, i.e., very close to chance level. Overall, priming occurred only at the second association tests for the opioid bolus regimen, for which the frequency of an association to the presented story among those not giving an association to the control story was 26%, which was double the frequency (13%) of an association to the control story among those not giving an association to the presented story. This was significant by McNemar's test, P=0.02. There were significant associations between awareness, priming and AER, e.g., recall was associated with higher Nb amplitudes during anesthesia and priming was associated with shorter wave latencies. CONCLUSIONS: The incidence of awareness in patients anesthetized with nitrous oxide and bolus supplementation was 6%. Thus, this anesthetic technique did not reduce the risk of awareness compared with the use of nitrous oxide alone. Implicit memory occurred during nitrous oxide and bolus supplementation. Recording AER during anesthesia may help to predict awareness and implicit memory, particularly the former. The short contents of most of the dreams which were recalled could hamper future studies in this area.

Effects of frequent marijuana use on brain tissue volume and composition.

To investigate CNS effects of frequent marijuana use, brain tissue volume and composition were measured using magnetic resonance imaging (MRI) in 18 current, frequent, young adult marijuana users and 13 comparable, non-using controls. Automated image analysis techniques were used to measure global and regional brain volumes, including, for most regions, separate measures of gray and white matter. The marijuana users showed no evidence of cerebral atrophy or global or regional changes in tissue volumes. Volumes of ventricular CSF were not higher in marijuana users than controls, but were, in fact, lower. There were no clinically significant abnormalities in any subject's MRI. Sex differences were detected in several global volume measures.

Tape-recorded hypnosis instructions as adjuvant in the care of patients scheduled for third molar surgery.

UNLABELLED: As medical costs continue to escalate, there is willingness to consider the role played by nontraditional factors in health. We investigated the usefulness of tape-recorded hypnosis instruction on perioperative outcome in surgical patients in a prospective, randomized, and partially blinded study. Sixty patients scheduled for third molar surgery were studied. Patients were allocated to either an experimental group (E) or a control group (C). Group E received an audio tape to listen to daily for the immediate preoperative week, which guided the patients through a hypnotic induction and included suggestions on enhancement of perioperative well-being. Group C did not receive any tapes. The same surgeon administered local anesthesia and a standard regimen of sedation and performed the operation for all patients. The following variables were assessed 1 wk before surgery, immediately before and after surgery, and for 3 days after surgery by the indicated measurements: State anxiety by a Spielberger scale; nausea and pain by visual analog scales; number of tablets of the analgesics that were used; number of episodes of vomiting; and complications. In addition, the surgeon's assessment of ease of surgery was recorded. Two variables showed differences between the groups. First, Group C exhibited a mean increase of 11.7 points on the Spielberger scale from the screening to the presurgery period, while Group E showed only a mean increase of 5.5 points during the same period, P = 0.01. Second, the mean number of vomiting episodes was more in Group E, 1.3, than in Group C, 0.3, P = 0.02. In conclusion, anxiety was reduced before surgery by means of an audio tape containing hypnotic instructions; however, for no apparent reason, there was also an increase in the incidence of vomiting. IMPLICATIONS: We administered hypnosis instructions to patients before third molar surgery. Anxiety was reduced, but there was an increase in the incidence of vomiting. Although an easy and cost-effective method, the value of this approach remains to be established.

Classical conditioning during nitrous oxide treatment: influence of varying the interstimulus interval.

Classical conditioning of the rabbit nictitating membrane response (NMR) was accomplished by presenting a 75-ms tone conditioned stimulus (CS) at intervals of 0, 100, 200, 400, and 800 ms before the presentation of a 100-ms shock unconditioned stimulus. Following every four paired trials (tone followed by shock), the occurrence of conditioned responses (CRs) was tested on every fifth trial in which only tone was presented (test trials). Three doses of nitrous oxide in oxygen (0, 33, and 67%) were used during conditioning. Nitrous oxide produced dose-dependent decrements of learning. Conditioned responding was related to the interstimulus interval (ISI) by a concave-down function. The higher dose of nitrous oxide caused more decrements of learning at several ISIs compared to the other two doses, changing the shape of the curve. Trace conditioning, which was examined in the present study, was more impaired under the influence of nitrous oxide than conditioning in a previous study, which used the standard delay paradigm. Thus, the drug impairs explicit memory more than implicit memory.

Interaction of a subanaesthetic concentration of isoflurane with midazolam: effects on responsiveness, learning and memory.

There are situations in which "light" anaesthesia combined with neuromuscular block is the only anaesthetic regimen that can be tolerated safely by the patient. Benzodiazepines have hypnotic and specific amnesic effects. Therefore, we have examined the interaction of midazolam with a subanaesthetic dose of isoflurane (0.2% end-expired concentration) in 28 healthy volunteers. Thereafter, 15 subjects received midazolam 0.03 mg kg-1 i.v. and 13 subjects received midazolam 0.06 mg kg-1 in a random, double-blind manner. Word lists were administered and response to commands was tested before and after administration of midazolam. After 1 h of recovery, memory for word lists was tested by word completion, free recall and forced choice recognition tasks. After administration of midazolam, recall and, to a lesser degree, implicit memory were absent. Recognition was also absent after administration of midazolam 0.06 mg kg-1 and at the 3-min and 15-min assessments after administration of midazolam 0.03 mg kg-1. Responsiveness was more frequent with midazolam 0.03 mg kg-1 than with 0.06 mg kg-1 and increased over time. We conclude that a larger dose of midazolam or isoflurane, or both, may be necessary to abolish responsiveness.

Sedative, stimulant, and other subjective effects of marijuana: relationships to smoking techniques.

A double-blind, placebo-controlled study assessed subjective effects of smoking marijuana with either a long or short breath-holding duration. During eight test sessions, 55 male volunteers made repeated ratings of subjective "high," sedation, and stimulation, as well as rating their perceptions of motivation and performance on cognitive tests. The major finding of the study was that the long, relative to the short, breath-holding duration increased "high" ratings after smoking marijuana, but not placebo. Marijuana smoking increased sedation and a perception of worsened test performance, and decreased motivation with respect to test performance. Paradoxical subjective effects were observed in that subjects reported some stimulation as well as sedation after smoking marijuana, particularly with the long breath-holding duration. Breath-holding duration did not produce any subjective effects that were independent of the drug treatment, i.e.. occurred equally after smoking of marijuana and placebo, such as we previously observed with respect to test performance.

Vasopressin levels in major head and neck surgery.

In an effort to further understand the perioperative intravascular volume status of major head and neck surgery patients, serum antidiuretic hormone (ADH) and osmolality levels were assessed at four perioperative junctures. Thirty-five major head and neck surgical patients were randomly selected for examination with placement of a central venous pressure monitor. Serum osmolality and serum vasopressin levels were obtained at four junctures perioperatively. ADH levels were lower both after patients were anesthetized and five hours into the procedure than at either baseline or 24 hours after the end of the procedure. ADH levels after patients were anesthetized did not differ from those at five hours into the procedure, nor did ADH levels at baseline differ from those 24 hours after the end of the procedure. In addition, osmolality levels did not change over time. Additional analyses examining relationships between preoperative, intraoperative, and postoperative characteristics and ADH levels after patients were anesthetized and five hours into the procedure, as well as changes from baseline at these times and the baseline levels themselves, detected no significant relationships. This study provides information about the perioperative intravascular volume status of major head and neck surgery patients which may be important to intraoperative care, especially to decisions regarding invasive intraoperative fluid monitoring. Specifically, the data provide additional evidence against the need for the routine placement of central venous catheters to guide fluid administration during major head and neck surgery.

Effects of sedation with midazolam or propofol on cognition and psychomotor functions.

PURPOSE: The study compared the effects of midazolam and propofol on explicit and implicit memory, cognition, and psychomotor function in patients undergoing oral surgical procedures with local anesthesia and conscious sedation. METHODS: Twenty-eight patients were tested in a randomized, double-blind study. Patients were randomly allocated to one of two groups. One group received a bolus dose of midazolam, 0.1 mg/kg, followed by a continuous infusion of saline. The other group received a bolus dose of propofol, 1.0 mg/ kg, followed by a continuous infusion of propofol, 65 micrograms/kg/min. Subjective rating questionnaires and tapping, memory, and Digit Symbol Substitution tests were administered. Testing was done at baseline, 10 minutes after the drugs were given, 10 minutes after surgery ended and 10 minutes later. RESULTS: The midazolam and propofol groups did not differ significantly on any demographic variables. Both drugs produced mental and physical sedation, which did not become substantially attenuated during the time studied. Both tranquilization and attitudes or other feelings showed smaller drug effects than mental and physical sedation. Tapping was decreased by both drugs 10 minutes after treatment, but not postsurgery. Performance on the Digit Symbol Substitution test was below baseline levels for both drugs at 10 minutes after treatment, but only for midazolam in the postsurgery assessment; at 10 minutes after treatment, propofol was associated with poorer performance than midazolam. Immediate and delayed explicit recall were impaired by both drugs 10 minutes after treatment. Immediate and delayed recall were lower for midazolam than propofol postsurgery, but only the difference on immediate recall was significant. Implicit memory was spared by both drugs. CONCLUSIONS: Midazolam and propofol generally produced equivalent impairments, but the duration of the effects of propofol was shorter. Unlike explicit memory, implicit memory resisted impairment.

The interaction between nitrous oxide and isoflurane on suppression of learning: a study using classical conditioning in rabbits.

BACKGROUND: Nitrous oxide (N2O) is commonly combined with a volatile agent for administration of general anesthesia. We studied the effects of N2O and isoflurane on learning of the rabbit nictitating membrane responses (NMRs). METHODS: Classical conditioning of the NMR was accomplished by presenting a 400 ms tone conditioned stimulus before the presentation of a 100 ms shock unconditioned stimulus over 6 daily training sessions. The percentages of conditioned responses (CRs) were calculated for animals treated with 0% (n = 10), 33% (n = 11), 67% (n = 11), and 75% (n = 7) N2O and for those treated with 0% (n = 8), 0.2% (n = 7), 0.4%, (n = 13) and 0.8% (n = 9) isoflurane separately. ED-50 for suppression of learning for each drug were calculated. Percentages of CRs were calculated for treatments with combinations of 0.2% isoflurane with either 32 or 48% N2O (n = 14, for each). RESULTS: Isobolographic analysis demonstrated that the combination of the two drugs exerted no greater effect than that seen with either agent administered alone; for well-established CRs (mean of days 5 and 6), the estimated concentrations corresponding to a rate of 70% CRs were 0.31% isoflurane with no N2O, 65.3% N2O with no isoflurane, and 0.2% isoflurane combined with 32.4% N2O. CONCLUSIONS: N2O and isoflurane interact additively on suppression of learning.

Subanesthetic concentrations of desflurane and propofol suppress recall of emotionally charged information.

Whether anesthetized patients register emotionally charged information remains controversial. We tested this possibility using subanesthetic concentrations of propofol or desflurane. Twenty-two volunteers (selected for hypnosis susceptibility) received propofol and desflurane (on separate occasions, and in a random order) at a concentration 1.5-2 times each individual's minimum alveolar anesthetic concentration (MAC)-awake (or equivalent for propofol). We gave vecuronium, intubated the trachea of each volunteer, controlled ventilation, and then presented a neutral (control) drama or a "crisis" drama stating that the oxygen delivery system had failed, assigning crisis and control dramas in a blinded, randomized, and balanced manner. One day later, interviewers blinded to the assigned drama conducted a 2-h structured interview (including hypnosis) to determine whether the contents of the interviews after crisis and control dramas differed. In addition, messages permitting subsequent assessment of learning of matter-of-fact information (Trivial Pursuit-type question task and a behavior task) were presented at the anesthetic concentration just sufficient to prevent response to command in each volunteer. No analyses of the tasks involving matter-of-fact information revealed learning except one which correlated hypnosis susceptibility with behavior task performance. Both propofol and desflurane suppressed memory of the crisis. Consistent with previous findings for isoflurane and nitrous oxide, propofol and desflurane suppressed learning of matter-of-fact information at concentrations just above MAC-awake, except that volunteers' susceptibility to hypnosis correlated with performance of a behavior suggested during anesthesia. Propofol and desflurane suppressed learning of emotionally charged information at anesthetic concentrations 1.5-2 times MAC-awake (less than MAC), a different result from that previously reported for ether.

The efficacy of routine central venous monitoring in major head and neck surgery: a retrospective review.

STUDY OBJECTIVE: To further define the efficacy of routine central venous catheter placement for major head and neck surgery from the standpoint of fluid and blood administration, and various other parameters of perioperative management. DESIGN: Randomized, retrospective chart review. SETTING: University-affiliated medical center. PATIENTS: 104 patients who had undergone major head and neck surgery (defined as surgery lasting longer than 4 hours with a predicted blood loss of 500 ml or greater) at the University of Iowa Hospitals and Clinics between 1985 and 1992. MEASUREMENTS AND MAIN RESULTS: Central venous monitoring was used in 51 of the 104 (49%) procedures. Patients with and without central monitors did not differ in age, weight, preoperative laboratory values [i.e., hemoglobin (Hb), blood urea nitrogen (BUN), creatinine), incidence of significant cardiac or renal disease, or a smoking history exceeding 30 pack years. In addition, these patients did not differ with respect to the following intraoperative characteristics: general type of anesthetic; duration of surgery; estimate of blood loss; Hb values; lowest urine output per hour; development of oliguria; total urine output; amount of replacement of blood, colloid, or crystalloid; development of systolic blood pressure less than 70 mmHg; or use of a myocutaneous flap. Patients also did not differ with respect to the following postoperative characteristics: duration of stay in the surgical intensive care unit or hospital, BUN or creatinine values on days 1 and 2, total urine output or the development of oliguria on days 1 through 3, incidence of reintubation, fever on days 1 through 5, wound dehiscence, death, myocardial infarction, or the development of pneumonia, pulmonary edema, or sepsis. Patients with central monitors had a greater incidence of having a tracheostomy performed and a slightly lower Hb level on the first postoperative day than those without central monitors. CONCLUSIONS: The study raises doubt about the efficacy of routine central venous catheter placement as a necessary guide for fluid and blood administration for these procedures, or as a necessary adjunct for several other parameters of perioperative management. It suggests the need for a randomized, prospective evaluation.

Ketamine: acquisition and retention of classically conditioned responses during treatment with large doses.

Two experiments were conducted in rabbits to examine the effects of ketamine (0, 100, and 200 mg/kg) on the acquisition and retention of the classically conditioned nictitating membrane response (NMR). Classical conditioning of the NMR was accomplished by pairing tone and light conditioned stimuli (CS) with paraorbital shock as the unconditioned stimulus (UCS). Experiment 1 assessed the effects of the drug on acquisition and retention of conditioned responses (CR) and determined the role of previous exposure to the experimental environment. Ketamine blocked the display of CR. However, data from subsequent retention testing under nondrug conditions revealed that rabbits that had previously received 100 mg/kg ketamine learned faster than saline-treated rabbits during the acquisition phases. Rabbits that received 100 mg/kg ketamine and were placed in the experimental chambers, but not presented with stimuli during the acquisition phase, did not learn faster during the retention phase than naive rabbits. Experiment 2 controlled further for the effects of nonassociative, unlearned processes. Control groups were presented with unpaired CS and UCS training after drug administration, and subsequently received conventional acquisition sessions under nondrug conditions. Their data indicated that the ketamine group's rapid acquisition during retention testing could not be attributed to nonassociative factors. We conclude that, although it was impossible directly to observe acquisition in rabbits under the influence of ketamine, it was possible that learning occurred as manifested by "savings" in subsequent learning trials.

The interactions of midazolam and flumazenil on human memory and cognition.

BACKGROUND: Previous research has been unable to show unequivocally whether flumazenil can reverse completely, partially, or not at all the memory effects of benzodiazepines. The effects of midazolam on implicit memory are also unknown. The behavioral effects of flumazenil by itself, and the acute reversal of benzodiazepine effects, are also controversial. The current study was designed to investigate these questions. METHODS: Using a prospective randomized, double-blind crossover study design, memory was assessed using both direct (free recall and recognition) and indirect (word completion) measures. Other cognitive effects were assessed using the digit symbol substitution task. Sedation and other mood effects were assessed using subjective rating scales. Seventy-two healthy subjects were assigned to three equal groups according to the dose of midazolam received (0, 0.05, and 0.1 mg/kg). Each subject received varying doses of flumazenil (0, 1, and 3 mg) in three sessions, at least 1 week apart. After baseline administration of the tasks, midazolam was administered. The assessments were repeated 20 min later, followed by administration of flumazenil. The assessments were repeated 5 and 30 min after administration of flumazenil. After a 2-h recovery period, delayed memory tests were given. RESULTS: Both doses of midazolam decreased all scores in the memory and digit symbol substitution tests and mood ratings. Flumazenil reversed both the sedative and the memory effects of the benzodiazepine. The reversal was as complete with the 1-mg dose of flumazenil as with the 3-mg dose. Flumazenil by itself, and the acute reversal of midazolam effects, caused no significant behavioral reactions. CONCLUSIONS: Midazolam impairs explicit and implicit memory. Flumazenil reverses both the sedative and memory effects of the drug. Flumazenil, in the doses used, has no intrinsic actions.