The origin of the magic MAC number

Eger EI, Saidman LJ & Brandstater B. Minimum alveolar anesthetic concentration: a standard of anesthetic potency. Anesthesiology 1965; 26:756-763.

RHH Journal Club. July 4th, 2013. Dr Niv Jena

Full-text article (if available)

This seminal body of work performed by Eger and his team in the 1960’s provides the basis for much of how we practice anaesthesia today. It continues to be referenced nearly 50 years later because of its importance. They introduced the concept of MAC and using it as a standard and comparison of potency of inhalational agents.

Study design

  • Observational animal (dogs) crossover study (San Francisco) 1963 onwards



n=3 dogs initially, then 7 in further tests…

Intervention/ Control

Once anesthetised for 15 mins, various (9) test stimuli were applied to each of the 3 dogs (thereby acting as their own control.)

  • Gas induction (halothane)
  • Alveolar concentration was held constant for 15 min before stimulation
  • Various stimuli applied 1 min- eg tail & paw clamping, electrical, 20cm incision


  • Positive response was a gross purposeful muscular movement
  • MAC was defined as the concentration midway between the highest concentration allowing and the lowest concentration preventing a response


  • Single centre
  • Study in dogs – reproducible in humans?
  • Small sample number
  • Alveolar gas analyses carried it out in a fairly basic way – still ingenious for it’s time
  • Unclear as to whether same study sample used over and over again, as may have affected results
  • Tests applied to each dog so acting as own controls


  • Most striking finding was the stability of MAC values
  • MAC was the same at the beginning, end and during intervening times of anaesthesia
  • It did not vary two weeks later when the dogs were again anaesthetised
  • Highlighted the individual variation between each subject
  • MAC varied depending on the type of stimulus
  • Highest when the tail was clamped and was lowest when the paw rather than the tail was clamped
  • Increasing the stimulus beyond a certain point did not increase MAC
  • MAC decreased after the dogs were given ammonium chloride, making them acidaemic
  • Respiratory acidosis and alkalosis had little effect on MAC.
  • MAC also changed little during hypoxia until the PO2 was allowed to dip below 4 kPa
  • MAC was additionally shown to decrease when the dogs were allowed to haemorrhage.

Take home message

Recognition that measuring alveolar concentration of an agent would most likely be a good estimate of the concentration in the brain.

Recognition that subjects needed a relatively constant concentration of anaesthetic agent so as not to respond to a painful stimulus. This has since been extrapolated and proven in humans, which is a fundamental concept of inhalational anaesthesia now.



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