Preferential effect of isoflurane on top-down vs. bottom-up pathways in sensory cortex

The mechanism of loss of consciousness (LOC) under anesthesia is unknown. Because consciousness depends on activity in the cortico-thalamic network, anesthetic actions on this network are likely critical for LOC. Competing theories stress the importance of anesthetic actions on bottom-up “core” thalamo-cortical (TC) vs. top-down cortico-cortical (CC) and matrix TC connections. We tested these models using laminar recordings in rat auditory cortex in vivo and murine brain slices. We selectively activated bottom-up vs. top-down afferent pathways using sensory stimuli in vivo and electrical stimulation in brain slices, and compared effects of isoflurane on responses evoked via the two pathways. Auditory stimuli in vivo and core TC afferent stimulation in brain slices evoked short latency current sinks in middle layers, consistent with activation of core TC afferents. By contrast, visual stimuli in vivo and stimulation of CC and matrix TC afferents in brain slices evoked responses mainly in superficial and deep layers, consistent with projection patterns of top-down afferents that carry visual information to auditory cortex. Responses to auditory stimuli in vivo and core TC afferents in brain slices were significantly less affected by isoflurane compared to responses triggered by visual stimuli in vivo and CC/matrix TC afferents in slices. At a just-hypnotic dose in vivo, auditory responses were enhanced by isoflurane, whereas visual responses were dramatically reduced. At a comparable concentration in slices, isoflurane suppressed both core TC and CC/matrix TC responses, but the effect on the latter responses was far greater than on core TC responses, indicating that at least part of the differential effects observed in vivo were due to local actions of isoflurane in auditory cortex. These data support a model in which disruption of top-down connectivity contributes to anesthesia-induced LOC, and have implications for understanding the neural basis of consciousness

Incidence of Connected Consciousness after Tracheal Intubation A Prospective, International, Multicenter Cohort Study of the Isolated Forearm Technique

Background: The isolated forearm technique allows assessment of consciousness of the external world (connected consciousness) through a verbal command to move the hand (of a tourniquet-isolated arm) during intended general anesthesia. Previous isolated forearm technique data suggest that the incidence of connected consciousness may approach 37% after a noxious stimulus. The authors conducted an international, multicenter, pragmatic study to establish the incidence of isolated forearm technique responsiveness after intubation in routine practice. Methods: Two hundred sixty adult patients were recruited at six sites into a prospective cohort study of the isolated forearm technique after intubation. Demographic, anesthetic, and intubation data, plus postoperative questionnaires, were collected. Univariate statistics, followed by bivariate logistic regression models for age plus variable, were conducted. Results: The incidence of isolated forearm technique responsiveness after intubation was 4.6% (12/260); 5 of 12 responders reported pain through a second hand squeeze. Responders were younger than nonresponders (39 +/- 17 vs. 51 +/- 16 yr old; P = 0.01) with more frequent signs of sympathetic activation (50% vs. 2.4%; P = 0.03). No participant had explicit recall of intraoperative events when questioned after surgery (n = 253). Across groups, depth of anesthesia monitoring values showed a wide range; however, values were higher for responders before (54 +/- 20 vs. 42 +/- 14; P = 0.02) and after (52 +/- 16 vs. 43 +/- 16; P = 0.02) intubation. In patients not receiving total intravenous anesthesia, exposure to volatile anesthetics before intubation reduced the odds of responding (odds ratio, 0.2 [0.1 to 0.8]; P = 0.02) after adjustment for age. Conclusions: Intraoperative connected consciousness occurred frequently, although the rate is up to 10-times lower than anticipated. This should be considered a conservative estimate of intraoperative connected consciousness