In vivo characterization of clinical anaesthesia and its components J.F. Antognini, E Carstens  British Journal of Anaesthesia  Volume 89, Issue 1, Pages 156-166 (July 2002) DOI: 10.1093/bja/aef156 Copyright © 2002 British Journal of Anaesthesia Terms and Conditions

Fig 1 Guedel's signs for ether anaesthesia included muscle tone, breathing pattern and eye movements. Stage 1 was marked by analgesia and consciousness. In Stage 2, the patient became unconscious, breathing was erratic but delirium could occur, leading to an excitement phase. In Stage 3, surgical anaesthesia occurred, with four planes or levels describing increasing depth until breathing became weak. Stage 4 was marked by respiratory paralysis and death. Other signs included pupil size. Newer anaesthetics and ‘balanced’ anaesthesia have rendered some of these signs less reliable. (Based on reference 46.) British Journal of Anaesthesia 2002 89, 156-166DOI: (10.1093/bja/aef156) Copyright © 2002 British Journal of Anaesthesia Terms and Conditions

Fig 2 Noxious stimulation results in impulse transmission to the dorsal horn, where second-order neurones might send impulses to ascending tracts (such as the spinothalamic tract) or to motor neurones that innervate muscles that initiate a motor response, such as an escape or withdrawal response. The ascending transmission of these impulses ‘activates’ the brain and results in increased arousal. The location of the spinothalamic tract varies from species to species. British Journal of Anaesthesia 2002 89, 156-166DOI: (10.1093/bja/aef156) Copyright © 2002 British Journal of Anaesthesia Terms and Conditions

Fig 3 These dose–response curves for various end-points were developed from a variety of studies. Note that the curves for memory and consciousness are close to each other. The effective dose that results in 50% of patients having unconsciousness is called ‘MAC-awake’. This value is about 30–40% of MAC, although there are differences among anaesthetics. MAC-awake might be greater during the noxious stimulation of surgery. The anaesthetic concentration that blocks the cardiovascular response is called ‘MAC-BAR’. British Journal of Anaesthesia 2002 89, 156-166DOI: (10.1093/bja/aef156) Copyright © 2002 British Journal of Anaesthesia Terms and Conditions

Fig 4 Effect of fentanyl on sevoflurane requirements. Note that MAC-BAR (the minimum anaesthetic concentration required to block adrenergic responses) is affected the most, suggesting that analgesia is an important tool for the control of haemodynamic responses to noxious stimulation. MAC-awake (the concentration that results in unconsciousness) is affected least and merges with MAC and MAC-BAR. Thus a patient given opiates might not move or have a haemodynamic response to noxious stimulation but might be conscious. This is not unexpected, because there are numerous reports of patients awake during what is primarily an opiate ‘anaesthetic’. Based on the work of Katoh and colleagues.5657 British Journal of Anaesthesia 2002 89, 156-166DOI: (10.1093/bja/aef156) Copyright © 2002 British Journal of Anaesthesia Terms and Conditions

Fig 5 At the top are shown the bifrontal EEGs from a goat anaesthetized with isoflurane at 1.5, 3.5 and 5% (3 min and 10 s samples). Below are peristimulus time histograms (PSTHs) representing the corresponding activity of a midbrain reticular formation (MRF) cell. In the first two PSTHs the arrows represent application of a clamp to the goat's lip for 1 min. This MRF cell is inhibited by the noxious stimulus, but at 3.5% isoflurane the spontaneous activity is increased and the cell is not completely inhibited by the noxious clamp. Note that at 3.5 and 5% isoflurane the EEG is isoelectric (with occasional spikes) but the MRF cell is still active. British Journal of Anaesthesia 2002 89, 156-166DOI: (10.1093/bja/aef156) Copyright © 2002 British Journal of Anaesthesia Terms and Conditions

Fig 6 Differential anaesthetic delivery aids elucidation of how anaesthetic action in the spinal cord affects brain arousal.12 18 In the top panel, the anaesthetic (isoflurane) concentration in the spinal cord is sufficient to effectively block the ascending transmission of nociceptive impulses to the midbrain reticular formation (MRF), thalamus (Thal) and brain; no EEG activation occurs. In one scenario (middle), decreasing the spinal concentration of anaesthesia facilitates the ascending transmission of nociceptive impulses, but the sensitivity of the brain is unchanged compared with the top panel. There is minimal EEG activation, owing to the added nociceptive impulses that are transmitted to the brain. In the scenario in the lower panel, we hypothesize that the brain is more sensitive to the additional nociceptive impulses, and there is marked EEG activation (desynchronization). The enhanced sensitivity might be due to increased ascending afferent activity that ‘resets’ the brain's arousal level. By indirectly diminishing brain arousal, the spinal cord action of anaesthetics could affect memory and unconsciousness. British Journal of Anaesthesia 2002 89, 156-166DOI: (10.1093/bja/aef156) Copyright © 2002 British Journal of Anaesthesia Terms and Conditions