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Concepts and Mechanisms of General Anaesthesia

LEARNING OBJECTIVES

• To be able to define general anaesthesia.
• To be able to discuss general anaesthesia in terms of its component parts, i.e. the triad of general anaesthesia.
• To be able to define balanced anaesthesia.

1.1 Definitions

Anaesthesia literally means 'lack of sensation/feeling' (from an meaning 'without' and aesthesia pertaining to 'feeling'). Therefore, general anaesthesia means global/total lack of sensations, whereas local anaesthesia relates to lack of sensation in a localised part of the body.

General anaesthesia can be defined as a state of unconsciousness produced by a process of controlled, reversible, intoxication of the central nervous system (CNS), whereby the patient neither perceives nor recalls noxious (or other) stimuli.

General anaesthesia is, however, often referred to as the state of the patient when the three criteria in the triad of general anaesthesia have been met.

1.1.1 The Triad of General Anaesthesia

1. Unconsciousness: no perception or memory (therefore including amnesia), of any sensory, or indeed motor, event.
2. Analgesia (or, more correctly in an unconscious patient, antinociception): can also be thought of as suppressed responses/reflexes to nociceptive sensory inputs.
3. Suppressed reflexes: autonomic (e.g. haemodynamic, respiratory and thermoregulatory) and somatic (e.g. proprioceptive reflexes such as the righting reflex).
   • Suppression of somatic reflexes can be useful, e.g. it can provide a degree of muscular weakness/relaxation.
   • Suppression of autonomic reflexes can be a nuisance (see Chapter 18 on Monitoring), but autonomic stability can be a desirable component of anaesthesia and is often listed as a fourth component.

All these components could potentially be achieved in a patient following administration of a single 'anaesthetic' drug but, e.g. if that drug did not have very good analgesic properties, then large doses would be required to produce sufficiently 'deep' unconsciousness to reduce the response to noxious stimuli. Such deep anaesthesia is often associated with extreme depression of the CNS and homeostatic reflexes (Table 1.1).

An alternative approach, therefore, would be to produce each component (of the 'triad') separately by administering several drugs, each of which targets one component more specifically. This latter approach is theoretically advantageous because, by 'titrating to specific effect', relatively smaller doses of each individual drug tend to be sufficient, thereby minimising both each individual drug's, and the overall, side effects. This 'polypharmacy' approach is often referred to as balanced anaesthesia.

1.1.2 Balanced Anaesthesia

The administration of a number of different drugs, each with different actions, given during the immediate peri-operative period, to produce an overall state of general anaesthesia, which fulfils the criteria of unconsciousness, analgesia, and muscle relaxation.

Table 1.1 Summary of effects of general anaesthesia.

Central Nervous System Depression

• Loss of consciousness
• Damping of reflexes
  
  • Cardiovascular Hypotension
    
  • Respiratory Hypoventilation
    
  • Thermoregulatory Hypothermia
    
  • Postural Reduced muscle tone
    
• Central modulation of nociception (hopefully providing analgesia/antinociception)

Cardiovascular System Depression ( Hypotension)

• Reflex (e.g. baroreflex) suppression (centrally and peripherally)
• Changes in autonomic balance
• Changes in vasomotor tone (drug effects, centrally and peripherally)
• Myocardial depression
  
  • Direct (drugs)
    
  • Indirect (e.g. hypoxaemia, hypercapnia [acidosis])
    

Respiratory Depression ( Hypoventilation; resulting in hypercapnia/hypoxaemia)

• Reflex suppression (ventilatory response to PCO2 [pH], and PO2)
• Reduced respiratory muscle activity ( sighing and yawning)
• Alveolar collapse/small airway closure (atelectasis)
• Reduced functional residual capacity
• Ventilation/perfusion mismatch

1.1.2.1 Components of the Peri-operative Period

• Pre-operative assessment: patient stabilisation; provision of (pre-emptive) analgesia.
• Premedication: anxiolysis/sedation and initiation/continuation of analgesia provision if not already provided.
• Induction of anaesthesia.
• Maintenance of anaesthesia; provision of muscle relaxation; continuation of analgesia/antinociception provision.
• Recovery from anaesthesia (sometimes referred to as 'reanimation'): aftercare; continuation of ('preventive') analgesia provision.

1.2 The Depth of General Anaesthesia

Some texts refer to various stages and planes of anaesthesia that try to mark the progression of the continuum between consciousness and death. When ether was used as the sole anaesthetic agent, five 'degrees' of progression through ever 'deeper' stages of anaesthesia in people, from consciousness to deep coma, were described by John Snow; Overton did similar for chloroform. Guedel developed Snow's ideas further and, in 1937, produced a chart outlining the patient's responses at each of four successive stages of diethyl ether anaesthesia. This was developed still further by Artusio in 1954, who divided Guedel's stage 1 into three planes.

Table 1.2, included purely for historical interest, describes the features of diethyl ether anaesthesia in the dog, after Guedel. The features of these stages and planes, however, do not necessarily apply similarly to other inhalant agents, and apply even less to injectable agents, to say nothing of the combination of inhalational and injectable agents that can be administered when balanced anaesthesia is practised. Furthermore, the chart is not necessarily transferrable to other species.

So, when we do not want to use ether, when we need to consider species other than dogs, when we prefer to practise 'polypharmacy' to achieve the desired state/depth of general anaesthesia, and when we add surgical stimulation to the anaesthetised patient (because depth of anaesthesia is not only related to the 'dose' of drug/s administered, but is also dependent upon the degree of stimulation [usually surgery] at the time), we should still monitor the patient's physiological responses to, and status during, anaesthesia, which are considered in more detail in Chapter 18.

Although Table 1.2 is included purely for interest, it is important to note that during induction of anaesthesia, stage II (involuntary excitement/movement) may be witnessed; and during recovery from anaesthesia, all the stages are traversed in the reverse order, such that emergence excitement/delirium (stage II) may be observed.

1.3 Mechanisms of Action of General Anaesthetic Drugs

Compounds that exert general anaesthetic effects exhibit a wide diversity of chemical structure and can be administered by injection (usually intravenously), or by inhalation. Although a unifying target for their action has been sought, the diversity in their structure makes a single target site unlikely.

Nevertheless, Meyer (1899) and Overton (1901), independently, reported that anaesthetic potency was strongly correlated with lipid solubility which sparked interest in lipid membranes as the site of action. It was variously hypothesised that anaesthetic agents may exert a non-selective physical perturbation of a lipid site within the membrane or possibly perturb the volume or fluidity of the membrane itself. That physical dissolution of lipid-soluble agents within plasma membranes caused their expansion, sparked the 'critical volume' and 'membrane expansion' hypotheses, with some demonstration of pressure-reversal. The lipid theory, however, had several problems, including the fact that some isomers with identical lipid solubilities had different anaesthetic potencies, not all anaesthetic effects were reversible with applied pressure, and small temperature changes could also change membrane volume but without anaesthetic effects.

Table 1.2 Stages of ether anaesthesia in the dog, after Guedel.

Stage of anaesthesia Depression of CNS MM colour Pupil size Eyeball activity Breathing Stage I: stage of voluntary movement/excitement ?Sensory cortex N / flushed Small Voluntary Rapid/irregular Stage II: stage of involuntary movement/excitement 'delirium' Motor cortex
Decerebrate rigidity...