M. M. Ghoneim

The incidence of awareness during anesthesia: a multicenter United States study.

Awareness with recall after general anesthesia is an infrequent, but well described, phenomenon that may result in posttraumatic stress disorder. There are no recent data on the incidence of this complication in the United States. We, therefore, undertook a prospective study to determine the incidence of awareness with recall during general anesthesia in the United States. This is a prospective, nonrandomized descriptive cohort study that was conducted at seven academic medical centers in the United States. Patients scheduled for surgery under general anesthesia were interviewed in the postoperative recovery room and at least a week after anesthesia and surgery by using a structured interview. Data from 19,575 patients are presented. A total of 25 awareness cases were identified (0.13% incidence). These occurred at a rate of 1–2 cases per 1000 patients at each site. Awareness was associated with increased ASA physical status (odds ratio, 2.41; 95% confidence interval, 1.04–5.60 for ASA status III–V compared with ASA status I–II). Age and sex did not influence the incidence of awareness. There were 46 additional cases (0.24%) of possible awareness and 1183 cases (6.04%) of possible intraoperative dreaming. The incidence of awareness during general anesthesia with recall in the United States is comparable to that described in other countries. Assuming that approximately 20 million anesthetics are administered in the United States annually, we can expect approximately 26,000 cases to occur each year.

Effects of diazepam and scopolamine on storage, retrieval and organizational processes in memory.

The effects of intramuscular injections of diazepam (0.3 mg/kg) and scopolamine (8 Μg/kg) on memory processes and subjective moods were studied in 36 volunteers. Subjects (Ss) were tested in groups of four in a double blind procedure with treatments distributed according to a Latin square design. Lists of words were presented to Ss who were then tested with an immediate free recall test prior to drug administration. Following injection delayed free recall and recognition tests were given. Subsequently two sets of lists were presented separately and tested in the same fashion. Two of the lists in the last set were composed of words falling into distinct categories. Memory was additionally analyzed by testing immediate recall of digit sequences and employing a visual recognition test. Subjective moods were evaluated with a rating questionnaire.Both diazepam and scopolamine impaired memory functions although the action of the latter drug was more pronounced and prolonged. The deficit appeared to be in the storage process leaving retrieval processes unaffected. Scopolamine in addition interfered with organizational processes. Subjectively, scopolamine also produced a larger sedative effect than diazepam.

Effects of chronic marijuana use on human cognition

Impairments of human cognition and learning following chronic marijuana use are of serious concern, but have not been clearly demonstrated. To determine whether such impairments occurred, this study compared performance of adult marijuana users and non-users (N=144 andN=72, respectively) matched on intellectual functioning before the onset of drug use, i.e., on scores from standardized tests administered during the fourth grade of grammar school (Iowa Tests of Basic Skills). Subjects were given the twelfth grade versions of these tests (Iowa Tests of Educational Development) and other, computerized cognitive tests in successive test sessions. “Heavy” marijuana use (defined by use seven or more times weekly) was associated with deficits in mathematical skills and verbal expression in the Iowa Tests of Educational Development and selective impairments in memory retrieval processes in Buschkes Test. The retrieval impairments were restricted to words that were easy to visualize. Impairments depended on the frequency of chronic marijuana use, i.e., “light” and “intermediate” marijuana use (defined by use one to four and five to six times weekly, respectively) were not associated with deficits. Intermediate use was associated with superior performance in one condition (“fuzzy” concepts) of a Concept Formation test.

DOSE-RESPONSE ANALYSIS OF THE BEHAVIORAL EFFECTS OF DIAZEPAM: I. LEARNING AND MEMORY

A total of 120 healthy volunteers were randomly assigned to four treatments (placebo, 0.1, 0.2, and 0.3 mg/kg) and three testing times (7 AM, 1 PM and 7 PM). Immediate and delayed free recall of word lists revealed consistent decreases in performance as oral diazepam dose increased from 0.1, 0.2, to 0.3 mg/kg. Paradoxically, as the dose increased, the number of predrug list words recalled also increased. A serial number-learning task displayed a pattern of delayed improvement of acquisition as the dose increased. Response times in a semantic-categories task were prolonged as the dose increased. Parallel recovery functions were observed for all doses and tasks. Full recovery after a single administration of 0.1, 0.2, and 0.3 mg/kg doses was estimated to occur after 3.5, 4.5, and 5.5 h, respectively. Several analyses were consistent with the view that acquisition and not retrieval was impaired by diazepam. There were no circadian interactions with the effects of the drug.

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 subjects MRI. Sex differences were detected in several global volume measures.

Ketamine: behavioral effects of subanesthetic doses

Effects of subanesthetic doses of ketamine (0.25 and 0.5 mg/kg) on memory, cognition, psychomotor function, subjective moods, and incidence of adverse reactions were investigated in 34 healthy young volunteers. The drug caused impairment of immediate and delayed recall. Most of the impairment was du

Awareness During Anesthesia: Risk Factors, Causes and Sequelae: A Review of Reported Cases in the Literature

BACKGROUND: Awareness during anesthesia is uncommon. The number of cases that are found in one single study are insufficient to identify and estimate the risks, causal factors and sequelae. One method of studying a large number of cases is to analyze reports of cases of awareness that have been published in scientific journals. METHODS: We conducted an electronic search of the literature in the National Library of Medicine’s PubMed database for case reports on “Awareness” and “Anesthesia” for the time period between 1950 through August, 2005. We also manually searched references cited in these reports and in other articles on awareness. We used two surgical control groups for comparative purposes. The first group in a study by Sebel et al. consisted of patients who did not experience awareness. The second group, from the 1996 data from the National Survey of Ambulatory Surgery included patients who received general anesthesia. We also used data from the National Center for Health Statistics to compare weight and Body Mass Index. RESULTS: We compared the data of 271 cases of awareness with 19,504 patients who did not suffer it. Aware patients were more likely to be females (P < 0.05), younger (P < 0.001) and to have cardiac and obstetrics operations (P < 0.0001). Only 35% reported the awareness episode during the stay in the recovery room. They received fewer anesthetic drugs (P < 0.0001), and were more likely to exhibit episodes of tachycardia and hypertension during surgery (P < 0.0001). A much larger percentage of these patients (52%, P < 0.0001) voiced postoperative complaints related to awareness. Inability to move and feelings such as helplessness, sensation of weakness, and hearing noises and voices were related to the persistence of complaints such as sleep disturbances and fear about future anesthetics (P < 0.041–0.0003). Twenty-two percent of the patients suffered late psychological symptoms. CONCLUSIONS: Our review suggested light anesthesia and a history of awareness as risk factors. Obesity and avoidance of nitrous oxide use did not seem to increase the risk. Light anesthesia was the most common cause. Our findings suggest preventive procedures that may lead to a decrease in the incidence of awareness.

Pharmacokinetics of Etomidate, a New Intravenous Anesthetic

Etomidate sulfate, 0.3 mg/kg, was administered intravenously to eight patients and venous blood samples were drawn at intervals for the subsequent 10 hours. Plasma etomidate was determined by mass fragmentography. Plasma concentrations were fitted to a triexponential equation consistent with a three-compartment open pharmacokinetic model. Mean (±SD) variables were: initial t1/2, 2.6 ± 1.3 min; intermediate t1/2, 28.7 ± 14.0 min; apparent elimination t1/2, 4.6 ± 2.6 hours; volume of the central compartment, 23.2 ± 11.4 1; total apparent volume of distribution, 4.5 ± 2.2 1/kg; fraction of drug in the central compartment, 7 per cent; total plasma clearance, 860 ± 230 ml/min. Total blood clearance was estimated to be 754 ml/min and hepatic clearance, 739 ml/min. The large apparent volume of distribution indicates considerable tissue uptake. The hepatic clearance, being about 50 per cent of hepatic blood flow, indicates that changes in hepatic blood flow or hepatic metabolism will have only moderate effects on etomidate disposition.

Effects of frequent marijuana use on memory-related regional cerebral blood flow.

It is uncertain whether frequent marijuana use adversely affects human brain function. Using positron emission tomography (PET), memory-related regional cerebral blood flow was compared in frequent marijuana users and nonusing control subjects after 26+ h of monitored abstention. Memory-related blood flow in marijuana users, relative to control subjects, showed decreases in prefrontal cortex, increases in memory-relevant regions of cerebellum, and altered lateralization in hippocampus. Marijuana users differed most in brain activity related to episodic memory encoding. In learning a word list to criterion over multiple trials, marijuana users, relative to control subjects, required means of 2.7 more presentations during initial learning and 3.1 more presentations during subsequent relearning. In single-trial recall, marijuana users appeared to rely more on short-term memory, recalling 23% more than control subjects from the end of a list, but 19% less from the middle. These findings indicate altered memory-related brain function in marijuana users.

Caffeine and diazepam: Separate and combined effects on mood, memory, and psychomotor performance

The effects of caffeine and diazepam on several mood, cognitive, learning, memory, and psychomotor tasks were investigated in a double-blind study of 108 young healthy adults who were randomly assigned to nine treatments; oral administration of caffeine (0, 3 and 6 mg/kg), diazepam (0, 0.15, and 0.30 mg/kg) and their combinations. Subjects completed a battery of tasks once before and twice after administration of the drugs. Caffeine alone showed no effects on cognitive, learning, and memory performance, but impaired fine motor coordination and increased anxiety and tenseness. Diazepam alone produced sedation, lowered other ratings of subjective moods, and impaired cognitive, learning, and memory performance. The two drugs did not antagonize the effects of each other, except in the symbol cancellation task.