Paradox of age: older patients receive higher age-adjusted minimum alveolar concentration fractions of volatile anaesthetics yet display higher bispectral index values

Br J Anaesth. 2019 Sep;123(3):288-297. doi: 10.1016/j.bja.2019.05.040. Epub 2019 Jul 3.


Background: Minimum alveolar concentration (MAC) and MAC-awake decrease with age. We hypothesised that, in clinical practice, (i) end-tidal MAC fraction in older patients would decline by less than the predicted age-dependent MAC decrease (i.e. older patients would receive relatively excessive anaesthetic concentrations), and (ii) bispectral index (BIS) values would therefore be lower in older patients.

Methods: We examined the relationship between end-tidal MAC fraction, BIS values, and age in 4699 patients > 30 yr in age at a single centre using unadjusted local regression (locally estimated scatterplot smoothing), Spearman's correlation, stratification, and robust univariable and multivariable linear regression.

Results: The end-tidal MAC fraction in older patients declined by 3.01% per decade (95% confidence interval [CI]: 2.56-3.45; P<0.001), less than the 6.47% MAC decrease per decade that we found in a meta-regression analysis of published studies of age-dependent changes in MAC (P<0.001), and less than the age-dependent decrease in MAC-awake. The BIS values correlated positively with age (ρ=0.15; 95% CI: 0.12-0.17; P<0.001), and inversely with the age-adjusted end-tidal MAC (aaMAC) fraction (ρ= -0.13; 95% CI: -0.16, -0.11; P<0.001).

Conclusions: The age-dependent decline in end-tidal MAC fraction delivered in clinical practice at our institution was less than the age-dependent percentage decrease in MAC and MAC-awake determined from published studies. Despite receiving higher aaMAC fractions, older patients paradoxically showed higher BIS values. This most likely suggests that the BIS algorithm is inaccurate in older adults.

Keywords: age factors; anaesthesia; dose–response relationship; electroencephalography; monitoring.

MeSH terms

  • Adult
  • Age Factors
  • Aged
  • Aging / metabolism
  • Aging / physiology*
  • Anesthetics, Inhalation / administration & dosage
  • Anesthetics, Inhalation / pharmacology*
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Electroencephalography / drug effects*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Monitoring, Intraoperative / methods
  • Pulmonary Alveoli / metabolism
  • Retrospective Studies


  • Anesthetics, Inhalation