general anaesthesia

see also:

• anaesthetics
• history of anaesthesia
• induction agents for anaesthesia
• neuro-muscular blockers

1. stage of analgesia
   • no amnesia until late in stage.
2. stage of excitement
   • delirium, excited, amnesic, irregular respiration, vomiting, incontinence.
3. stage of surgical anaesthesia
   • recurrence of regular respiration;
   • 4 planes described according to pupil size, eye reflexes & ocular movements
   • 4 EEG phases of maintenance anaesthesia:
     • phase 1: light anaesthesia - decrease in EEG beta activity (13-30Hz), increase in alpha activity (8-12Hz) and delta activity (0-4Hz)
     • phase 2: intermediate state - an increase in alpha and delta activity in the anterior leads compared to posterior leads “anteriorization”, and EEG resembles stage 3 non-REM (slow-wave) sleep
     • phase 3: deep anaesthesia - EEG characterised by flat periods interspersed with periods of alpha and delta activity
     • phase 4: profound anaesthesia - EEG is flat, isoelectric and this phase induced by barbiturates or propofol is often used as a neuroprotective function in neurosurgery, or in Mx of status epilepticus.
   • approximates brain-stem death as patients are:
     • unconscious, have depressed brain stem reflexes, do not respond to nociceptive stimuli, have no apnoeic drive
     • require cardiorespiratory and thermoregulatory support
4. stage of medullary depression
   • severe depression of vasomotor & respiratory centres
   • ⇒ death without full circulatory & resp. support

• failure of patient to track movement of your finger with their eyes +/- onset of nystagmus
• blinking increases
• oculocephalic, eyelash and corneal reflexes are lost but pupillary light reflex remains
• heart rate typically increases unless opiates or benzodiapines have been administered prior to or during induction
• while BP may rise or fall

• heart rate and/or BP may rise dramatically
• perspiration
• tearing
• changes in pupil size
• return of muscle tone and movement if not paralysed by muscle relaxants
• changes in EEG measures of brain activity

• NB. we still do not understand the mechanism of consciousness
• actual mechanisms are complex
• primary mechanism appears to be suppression of excitatory neurons
• it appears many agents act by suppressing neuronal activity in the brain stem arousal centres - the lateral dorsal tegmental areas of the pons and the midbrain paramedian region.
• apnoea is partly due to actions on GABA[sub]A[/sub] interneurons in the respiratory control network in the ventral medulla and pons.
• the rapid atonia following a propofol bolus is thought to be due to actions on the spinal cord as well as the pontine and medullary reticular nuclei that control antigravity muscles
• microtubule quantum effect hypothesis of consciousness
  • 1st proposed by Penrose
  • neurons consists of many microtubules which are mainly composed of tryptophan which is capable of fluorescence and UV and in 2024 were shown to potentially produce quantum superradiant states ^{1) 2)} although this needs further studies to confirm
  • these microtubules are affected by inert gases such as xenon which do have anaesthetic effects
• isoflurane and other inhalational anesthetics activate type 1 ryanodine receptors (RyR1) which may be their functional action, and this stimulates calcium release from the endoplasmic reticulum ³⁾
  • patients with abnormal type 1 ryanodine receptors (RyR1) (RyR1 mutations) have been known to be at higher risk of malignant hyperthermia

• depth of anaesthesia determined by concentration in CNS.

• Concentration of a gas is proportional to its partial pressure (tension).
• Rate at which a given concentration of anaesthetic is achieved in CNS depends upon:

• blood:gas partition coefficient = relative affinity for blood cw air
• poorly soluble gases (ie. low blood:gas partition coefficient) (eg. N₂O):
  • relatively few molecules are needed to diffuse to raise arterial tension
    • ⇒ perfusion limited
    • ⇒ high arterial tensions develop rapidly
    • ⇒ faster induction of anaesthesia
    • ⇒ at equilibrium, arterial tension closer to alveolar tension
    • eg. N₂O reaches ~90% of its alveolar tension but methoxyflurane only 20%

• proportional to alveolar tension achieved
  • ⇒ higher concentrations increase rate of rise of arterial tension
  • ⇒ increase rate of induction of GA
  • THUS, use 3-4% halothane initially then maintenance of 1-2%

• proportional to rate of rise of arterial tension achieved effect greatest on high soluble gases (eg. methoxyflurane, halothane) eg. 4x minute ventilation ⇒ doubles arterial tension of halothane in 1st 10'

• increased cardiac output SLOWS rate of rise of arterial tension less time of blood in contact with alveolus larger volume of blood exposed to gas
  • ⇒ shock increases rate of induction esp. for high-soluble drugs

• the greater the difference, the longer the time required for equilibration gradient depends on degree of uptake in tissues which depends upon:
  • tissue perfusion (brain,heart,liver,kidneys > muscle > adipose)
  • solubility in that tissue

• rate of recovery from GA depends on redistribution away from brain & elimination.

• depend on factors as for uptake BUT:
  • while uptake can be increased by increasing inspired concentration, the reverse process cannot be enhanced as cannot reduce conc. below zero.
  • tension in various tissues is variable (ie. not zero as at start of GA) & depends on:
    • solubility in tissues, perfusion of tissues
    • duration of GA - longer duration ⇒ higher tissue tensions ⇒ slower recovery
    • poorly soluble gases are “washed out” faster ⇒ rapid recovery

• esp. methoxyflurane (→ release of fluoride ions) & halothane (15-20% metabolised).

• partial pressure of alveolar gas as a % of 760mmHg that results in immobility in 50% pts when exposed to noxious stimuli such as surgical incision ie. represents the ED50 on a conventional quantal dose-response curve
• THUS is a measure of relative anaesthetic potency
• it gives NO information about the slope of this curve, but in general, it is steep ie. >95% pts may fail to respond to surgical incision @ 1.1MAC !!
• individual pts require between 0.5 - 1.5 MAC for GA
• MAC values decrease with age but NOT affected by sex, height or weight.
• MAC values may decrease substantially when adjuvant drugs used (eg. opiates).

• halothane, enflurane
  • ⇒ decreased cardiac output but no effect on total peripheral resistance (TPR) ⇒ decreased BP
  • myocardial depressant effect ⇒ reduced myocardial oxygen needs
• isoflurane ⇒ marked decrease in TPR but little effect on cardiac output ⇒ decreased BP
• all GA's tend to increase right atrial pressure (RAP)si
• GA's alter heart rate via direct effect on no-atrial (SA) node &/or via autonomic effects
• halothane sensitises myocardium to catecholamines ⇒ risk of ventricular fibrillation (VF)

• all GA's except N₂O decrease tidal volume & increase resp. rate → decreased minute ventilation
• all GA's
  • ⇒ increase resting PaCO₂
  • ⇒ increase apnoeic threshold
  • ⇒ decreased ventilatory response to hypoxia - important in recovery phase where this response needed
  • ⇒ depress mucociliary function → pooling of mucus
  • ⇒ tend to cause bronchodilation

• all GA's ⇒ decrease metabolic rate of brain
• most GA's
  • ⇒ increase cerebral blood flow via decreased cerebral vascular resistance
  • ⇒ raised intracranial pressure (least with N₂O)
• NB. although N₂O has low GA potency, it has marked analgesic & amnesic effects

• all GA's
  • ⇒ decreased effective renal blood flow (RBF) & glomerular filtration rate (GFR)
  • ⇒ increased filtration fraction
  • ⇒ increased renal vascular resistance ⇒ impaired autoregulation
• methoxyflurane ⇒ flouride ions and other metabolites ⇒ irreversible polyuric renal failure

• all GA's ⇒ decreased hepatic blood flow (15-45% of pre-GA flow)
• halothane ⇒ possible hepatotoxicity

• most (not N₂O) ⇒ potent uterine muscle relaxation
  • ⇒ helpful in manipulations of fetus during delivery
  • ⇒ risk of haemorrhage in D&C's, etc.

• N₂O ⇒ prolonged exposure causes megaloblastic anaemia

• GA's esp. with volatile gases or suxamethonium in susceptible pts ⇒ malignant hyperthermia
  • ⇒ tachycardia, hypertension
  • ⇒ acidosis, hyperkalaemia, muscle rigidity, hyperthermia
  • Rx: IV dantrolene, lower temperature & restore electrolyte & acid-base balance