Henry L. Bennett

Effects of Isoflurane and Nitrous Oxide in Subanesthetic Concentrations on Memory and Responsiveness in Volunteers

Awareness, defined as conscious memory during anesthesia, has been a problem in anesthesia practice. To determine the effect of isoflurane and nitrous oxide (N2O) on memory, 17 healthy adult volunteers were randomly assigned to receive isoflurane or N2O and received the alternate agent 1-2 weeks later. Each volunteer was studied at four end-tidal concentrations of each agent, consecutively 0.15, 0.3, 0.45, and 0.15 times the minimum alveolar concentration (MAC) for isoflurane or 0.3, 0.45, 0.6, and 0.3 times MAC for N2O. After 15-min equilibration at each end-tidal concentration, volunteers were tested for voluntary response to command and were presented with verbal information to be recalled after anesthesia. Volunteers were interviewed on the day after the study and tested for conscious and unconscious memory of the information presented during anesthetic administration. MAC-awake (the end-tidal concentration preventing voluntary response in 50% of volunteers) was 0.38 (0.35-0.42) times MAC for isoflurane and 0.64 (0.61-0.68) MAC for N2O (means, 95% confidence limits), indicating isoflurane to be more potent than N2O in suppressing voluntary response (P = .0001). Memory data were analyzed in 12 volunteers who completed the study and in whom the allocation of information to be recalled was counterbalanced among agents and concentrations of agents. Memory was decreased by increasing concentrations of both agents. Conscious memory of the information presented during anesthetic administration was prevented by 0.45 MAC isoflurane but not completely prevented by 0.6 MAC N2O. Unconscious memory (defined as memory of information without conscious recognition) occurred during administration of both agents and was prevented by 0.45 MAC isoflurane but not by 0.6 MAC N2O. Isoflurane was more potent in suppressing memory than MAC-equivalent concentrations of N2O. Using models of the relationship between dose of agent and suppression of memory, a dose of both agents was estimated that suppressed memory by 50% (ED50). The ED50 was 0.20 MAC for isoflurane (95% confidence intervals, 0.15-0.25), and 0.50 MAC for N2O (95% confidence intervals 0.43-0.55). We conclude that isoflurane and N2O suppress memory in a dose-dependent manner, and that isoflurane is more potent in preventing memory and voluntary response to command than MAC-equivalent concentrations of N2O.

Distraction with a hand-held video game reduces pediatric preoperative anxiety

Background : Video games have received widespread application in health care for distraction and behavior modification therapy. Studies on the effect of cognitive distraction during the preoperative period are lacking. We evaluated the efficacy of an interactive distraction, a hand‐held video game (VG) in reducing preoperative anxiety in children.

The Electroencephalogram Does Not Predict Depth of Isoflurane Anesthesia

BackgroundThe power spectrum of the electroencephalogram (EEG) may be analyzed to provide quantitative measures of EEG activity (e.g., spectral edge, which defines the highest EEG frequency at which significant activity is found). The current study tested the hypothesis that spectral edge and similar measures distinguish different functional depths of anesthesia in humans. MethodsThree groups were studied. Group 1 consisted of 34 surgical patients (ASA physical status 1 or 2) who received 0.6, 1.0 and 1.4 MAC isoflurane anesthesia. A subgroup (group 2) of group 1 was tested during 1.0 MAC isoflurane anesthesia at surgical incision. Group 3 consisted of 16 volunteers who listened to an audiotape while receiving 0.15, 0.3, and 0.45 MAC isoflurane or 0.3, 0.45, and 0.6 MAC nitrous oxide in oxygen. The audiotape contained information designed to test implicit and explicit memory formation. We tested the ability of six EEG parameters (spectral-edge, 95th percentile power frequency, median power, and zero crossing frequencies and total power in the α- [8–13 Hz] and δ- [<4 Hz] power ranges) to predict movement after surgical incision, purposeful response to command, or memory of information presented during anesthetic administration. ResultsIsoflurane decreased EEG activity in group 1 in a dose-related fashion. The 55% of group 2 who made purposeful movements in response to incision did not differ in their EEG from nonresponders (e.g., spectral edge 19.8 ± 3.1 vs. 19.3 ± 2.6 Hz, mean ± SD). In group 3, memory of the information presented did not correlate with values of any EEG parameter. Response to verbal command was associated with lower anesthetic concentrations and with smaller α- and δ-band power (298 ± 66 vs. 401 ± 80 watts; and 75 ± 20 vs. 121 ± 49 watts, mean ± SD), but there was no difference in values for other parameters. ConclusionsWe conclude that our EEG measures do not predict depth of anesthesia as defined by the response to surgical incision, the response to verbal command or the development of memory.

Subanesthetic Concentrations of Isoflurane Suppress Learning as Defined by the Category-Example Task

BackgroundPreviously, we found unconscious (implicit) learning in subjects given subanesthetic, but not anesthetic, concentrations of isoflurane. Other investigators, using different learning tasks, have reported implicit learning at anesthetic concentrations. We investigated whether one of these tasks might provide a more sensitive test of implicit learning. In addition, to determine whether suppression of explicit or implicit learning is dose-dependent, we studied one of the tasks at three subanesthetic concentrations. MethodsWe applied a category-example task at 0.15, 0.28, and 0.4 minimum alveolar concentration (MAC) of isoflurane, and a behavior task only at 0.4 MAC. After anesthesia, we determined whether volunteers more frequently listed an example of a category (e.g., flute as an example of musical instrument) presented during anesthesia and/or demonstrated a behavior (touching ear, chin, or knee) suggested to them at 0.4 MAC. ResultsResults from the category task indicated implicit learning only at 0.15 MAC, a concentration that also permitted significant explicit learning. Explicit learning was demonstrated at 0.28 but not at 0.4 MAC (ED50 of 0.20 MAC and ED95 of 0.4 MAC). Results from the behavior task revealed neither implicit nor explicit learning. ConclusionsThe ED50 that suppressed explicit learning in our volunteers equaled that previously reported (0.2 MAC) for implicit learning in volunteers measured using a different task. Combined, these results suggest that less than 0.45 MAC isoflurane suppresses learning in volunteers.

Does nitrous oxide antagonize isoflurane-induced suppression of learning ?

BackgroundA greater MAC fraction of nitrous oxide than isoflurane is required to prevent response to verbal commands and suppress the capacity to learn. Speculating that this difference between these agents may be caused by nitrous oxides capacity to increase sympathetic activity, we tested the hypothesis that nitrous oxide may antagonize the suppression of learning found with isoflurane. MethodsWe administered a combination of isoflurane and nitrous oxide at three subanesthetic test concentrations (0.43, 0.56, and 0.68 MAC) to 24 healthy male volunteers. Assuming additivity of the anesthetics, the first test concentration was selected to suppress learning of new Information by 50% (ED50 for suppression of learning); the second concentration, to suppress the ability to respond appropriately to verbal command by 50% (MAC-awake); and the third, to provide 1.4 times MAC-awake. Three tests of learning were applied. At each test concentration, we provided 7 answers to “trivial pursuit”-type questions, resulting in a set of 21 answered questions for each volunteer; an additional 7 unanswered questions served as controls. At the highest test concentration, each volunteer also heard two examples from each of two categories (4 words) repeated 30 times (the category-example task), and a message instructing them to touch either their nose or their ear during a specified interval in the postanesthetic interview (the behavior task). ResultsThe MAC-awake value for the combination of isoflurane and nitrous oxide was 118 ± 4% of the expected value (i.e., the two anesthetics were antagonistic for this effect). Consistent with antagonism, the anesthetic concentration predicted to suppress learning by 30% permitted significantly more learning, and the ED50 was 105 ± 2% of that predicted. Neither the category task nor the behavior task demonstrated evidence of learning at 1.4 times MAC-awake. ConclusionsOur results are consistent with an antagonism between nitrous oxide and isoflurane; however, the degree of antagonism is small.

Subanesthetic concentrations of desflurane and isoflurane suppress explicit and implicit learning.

The capacity of desflurane to suppress learning is unknown.We investigated whether a subanesthetic concentration of desflurane (0.6 minimum alevolar anesthetic concentration [MAC]) suppressed learning as much as the same concentration of isoflurane, and whether such suppression differed with increasing duration of anesthesia and intervening changes in anesthetic concentration. Using a cross-over-design study in 18-30 yr-old human volunteers, we supplied answers to Trivial Pursuit Registered Trademark (Selchow & Righter Co., Bay Shore, NY)-like questions at 0.6 MAC desflurane and isoflurane before and after imposing a half-hour period at 1.7 MAC of each anesthetic, and behavioral directions and a category-example task at 0.6 MAC after the period at 1.7 MAC. These volunteers had a third anesthesia in which no information was supplied (control). After anesthesia, we tested whether the provision of answers during anesthesia increased the number of correct answers to Trivial Pursuit Registered Trademark questions. We tested for the number of correct answers for information presented before versus after the 1.7-MAC period, for increased evocation of examples of categories presented during anesthesia, and for exhibition of a behavior suggested during anesthesia. We found that 0.6 MAC of both anesthetics prevented explicit and implicit learning before and after the period at 1.7 MAC. (Anesth Analg 1995;80:568-72)

Effects of Prone and Reverse Trendelenburg Positioning on Ocular Parameters

Background:In a pilot study of awake volunteers, intraocular pressure (IOP), choroid layer thickness, and optic nerve diameter were shown to increase in the prone position over 5 h with a nonsignificant trend of attenuation using a 4-degree increase of table inclination. These effects have previously not been isolated from anesthetic and fluid administration over a prolonged period, using an adequate sample size. Methods:After institutional review board approval, 10 healthy volunteers underwent IOP measurement (Tono-Pen XL, Medtronic Solan, Jacksonville, FL) as well as choroidal thickness and optic nerve diameter assessment (Sonomed B-1000, Sonomed, Inc., Lake Success, NY, or the I3 System-ABD, Innovative Imaging, Inc., Sacramento, CA) on a Jackson table (Orthopedic Systems, Inc., Union City, CA), during 5 h horizontal prone and 5 h 4-degree reverse Trendelenburg positioning. Measurements were assessed as initial supine, initial prone, and hourly thereafter. Vital signs were recorded at each position and time point. Results:IOP, choroidal thickness, and optic nerve diameter were observed to increase with time in the prone position. A small degree of reverse Trendelenburg attenuated the increase in choroidal thickness but not IOP or optic nerve diameter. Conclusions:Prolonged prone positioning increases IOP, choroid layer thickness, and optic nerve diameter independent of anesthetics and intravenous fluid infusion and 4 degrees of table inclination (15 cm of head to foot vertical disparity) may not attenuate these effects.

Comparison of halothane and isoflurane for rapid anesthetic induction

To study the hypothesis that isoflurane will induce anesthesia faster than halothane when given by a single vital capacity breath technique, we studied 20 ASA I and II adults who breathed approximately 4.5 MAC equivalents of either vapor. The patients, randomly assigned to receive either agent, were fully preoxygenated and monitored for cardiovascular, respiratory, and EEG parameters. All subjects were premedicated with 5 μg/kg fentanyl IV 5 min before induction. Time to loss of consciousness was significantly longer with halothane than with isoflurane (86 ± 4 vs 38 ± 2 sec, respectively) although there were no clinically remarkable differences in cardiovascular or respiratory variables. Patients given halothane had a greater excitatory phase on EEG, whereas those given isoflurane had low frequency predominance. Overall rapid inhalation induction was well-received by all patients and was significantly faster with isoflurane.

Geographic Regional Differences in Rocuronium Bromide Dose-Response Relation and Time Course of Action An Overlooked Factor in Determining Recommended Dosage

Background:Geographic location is not acknowledged as a stratifying factor that can directly affect drug potency, because drugs are still licensed with the same recommended dose for different geographic regions. The aim of the current study was to compare the potency and duration of action of rocuronium bromide in 54 patients in three countries with different life habits, diet, and ambient conditions, namely white Austrians, white North Americans, and Han Chinese in China. Methods:Neuromuscular block of six consecutive 50-&mgr;g/kg rocuronium incremental doses followed by 300 &mgr;g/kg was evaluated using the Relaxometer mechanomyograph (Groningen University, Groningen, Holland). Dose–response curves were created using log-dose-probit transformation. The authors compared rocuronium bromide ED50, ED90, and ED95 (effective doses required for 50%, 90%, and 95% first twitch depression, respectively) as well as Dur25 and Dur0.8 (times from last incremental dose administration until 25% first twitch and 0.8 train-of-four ratio recovery, respectively) in patients of the three countries. Results:Rocuronium ED50, ED90, and ED95 were significantly higher in Austrian patients (258 ± 68, 530 ± 159, and 598 ± 189 &mgr;g/kg) and Chinese patients (201 ± 59, 413 ± 107, and 475 ± 155 &mgr;g/kg) compared with American patients (148 ± 48, 316 ± 116, and 362 ± 149 &mgr;g/kg, respectively). Dur25 and Dur0.8 were significantly shorter in Austrian patients (22.3 ± 5.5 and 36.9 ± 12.8 min) and Chinese patients (30.4 ± 7.5 and 45.7 ± 15.9 min) compared with American patients (36.7 ± 8.5 and 56.2 ± 16.7 min, respectively). Conclusions:The authors demonstrated a significant difference in rocuronium potency and duration of action among patients in the three countries. Larger studies are required for determining dosage recommendations for different geographic regions.

A Low Approach to Interscalene Brachial Plexus Block Results in More Distal Spread of Sensory-Motor Coverage Compared to the Conventional Approach

A low approach to the interscalene block (LISB) deposits local anesthetic farther caudad on the brachial plexus compared with the conventional interscalene block (ISB). We compared the efficacy of LISB and ISB in achieving anesthesia of the distal extremity in 254 patients having upper extremity surgery. The most frequent elicited motor response was the deltoid for ISB and wrist for LISB. There was significantly greater sensory-motor block of regions below the elbow with the LISB compared with ISB (P < 0.001 for both sensory and motor coverage). Our data indicate that LISB results in a higher incidence of distal elicited motor response and greater sensory-motor blockage of the wrist and hand.