3. Old stuff
          3.1. Old pharm stuff (pre 2009)
              3.1.3. Pharmacology
                  3.1.3.2. Inhalational anaesthetic agents
                      3.1.3.2.2. Pharmacodynamics of inhalational anaesthetics
 3.1.3.2.2.1. Minimal alveolar concentration 

Minimal alveolar concentration (MAC)

[Ref: SH4:p33]

Definition of MAC

  • MAC of an AA is the concentration at equilibrium at 1 atmospheric pressure that prevents purposeful skeletal muscle movement in response to a supramaximal painful stimulus (surgical skin incision) in 50% of patients
    * ie. the ED50 of AA
  • A measure of anaesthetic potency

Consistency

  • MAC is relatively consistent between individuals
    * Varying 10 to 15% among individuals

Site of action

  • Immobility produced by AA is mediated principally by effects on spinal cord
    * Also some minor cerebral effect

NB:

  • Decerebration does not change MAC

Comparativity

  • Different AA at similar MAC
    --> Equivalent depression of the spinal cord
    * But different effects on other organs

Dose-response curve

  • MAC is only ONE point on the dose-response curve
  • The dose-response curves for different AA are NOT parallel
  • All dose-response curves are steep
    * 1 MAC prevents movement in 50%
    * 1.3 MAC prevents movement in at least 95%

Additive

  • MAC values for AA are additive

For example,

  • 0.5 MAC of N2O plus 0.5 MAC iso would have the same effect at brain as does a 1 MAC of either AA alone.

 

MAC values for different AAs

[SH4:p33, table 1-8]

  • N2O = 104%
  • Halothane = 0.75%
  • Enflurane = 1.63%
  • Isoflurane = 1.17%
  • Desflurane = 6.6%
  • Sevoflurane = 1.80%
  • Xenon = 63-71%

Conditions at which MAC is measured

(except for N2O)

  • 30 to 55 years old
  • 37 degrees
  • PB = 760mmHg

For N2O

  • 21 to 55 years old
  • Hyperbaric chamber used

Factors influencing MAC

Main factors

  • Age
  • Body temperature

Factors that INCREASE MAC

  • Alcoholism [BH1:p50]
    * Different from SH4
  • Hyperthermia
  • Natural red hair women, due to
    * Increased pheomelanin concentration
    * Mutation of melanocortin-1 receptor gene
  • Cyclosporine
  • Hypernatremia
  • Drug-induced increase in CNS catecholamine level
  • Increased catecholamine stores

Factors that DECREASE MAC

  • Increasing age
    --> Decrease in MAC of 6% per decade after 30 y.o.
    * Also decreased in <6-8 months old
  • Hypothermia
  • Preoperative medication
    * e.g. Opioids
  • Acute alcohol ingestion
  • Alpha-2 agonists
    * e.g. clonidine
  • Pregnancy
    * Due to progesterone [EEW1:p26]
  • Postpartum
    * Returns to normal in 24-72 hours
  • Lithium
  • Lidocaine
  • Cardiopulmonary bypass
  • Hyponatremia
  • Drug-induced decrease in CNS catecholamine level
  • Severe hypoxia (pO2 < 38mmHg )
  • Severe hypotension (BP <40 mmHg )
  • Decreased catecholamine stores
Factors that does NOT affect MAC
  • Gender
  • Duration of anaesthetics
    * However, MAC for isoflurane might decrease with duration
  • Chronic alcohol abuse
    * Different from BH1
  • Anaesthetic metabolism
  • Thyroid dysfunction
  • K+ derangement
  • BP >40mmHg
  • PaO2 >38mmHg
  • PaCO2 15-95mmHg

Different kind of MAC

  • MAC bar = 1.5 MAC
    * MAC required to block autonomic (sympathetic) response to a surgical stimulus in 50% of patients
  • MAC awake = MAC that prevents appropriate response to command in 50% of subjects
    * [EEW1:p39]
  • MAC-hr
    = The integral of MAC by time for exposure of an individual patient to an inhalational anaesthetic agent

MAC awake

Ratio (MAC awake / MAC) varies between anaesthetic agents
--> i.e. MAC awake expressed as a fraction of MAC

[EEW1:p27]

  • Halothane = 0.55 MAC
  • Isoflurane = 0.38 MAC
  • Desflurane = 0.34 MAC
  • Sevoflurane = 0.34 MAC
  • Nitrous oxide = 0.64 MAC
  • Propofol = 0.19 MAC (or 2.69 microgram/L)