Minimum alveolar concentration: Difference between revisions

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{{Short description|Measurement of the potency of anaesthetic gasses}}

The '''minimum alveolar concentration''' at steady state that prevents the reaction to a standard surgical stimulus (traditionally measured as a response to a set depth and width of skin incisions) in 50% of subjects and measured as a percentage at 1 atmosphere (i.e the partial pressure effects of a gas are proportional to the concentration in the brain, assuming a constant alveolar concentration after 15 minutes has occured, allowing for a equlibration between the gasses in the alveoli = blood = brain, and thus the partial pressure in the alveolar (lungs) are said to be equivalent to the partial pressure in the brain).

'''Minimum alveolar concentration''' ('''MAC''') is the concentration, often expressed as a percentage by volume, of a vapour in the alveoli of the [[lung]]s that is needed to prevent movement in 50% of patients in response to pain. MAC is used to compare the [[Potency (pharmacology)|potency]] (dose required to induce a specific effect) of [[Volatile anaesthetic|anaesthetic vapours]].<ref name="urlPolicy: Ban on Use of Ether | Guidelines and Policies | Laboratory Animal Science Center | Laboratory Animal Care and Use Facility | Office of Research Compliance">{{cite web|url=http://www.bu.edu/research/compliance/lacu/lasc/guidelines-policies/appendix21.shtml |title=Policy: Ban on Use of Ether |publisher=Laboratory Animal Science Center |access-date=2008-11-10 |archive-url=https://web.archive.org/web/20080609202527/http://www.bu.edu/research/compliance/lacu/lasc/guidelines-policies/appendix21.shtml |archive-date=2008-06-09 |url-status=dead }}</ref> The concept of MAC was first introduced in 1965.<ref>{{cite journal |vauthors=Eger EI, Saidman LJ, Brandstater B |title=Minimum alveolar anesthetic concentration: a standard of anesthetic potency |journal=Anesthesiology |volume=26 |issue=6 |pages=756–63 |year=1965 |pmid=5844267 |doi= 10.1097/00000542-196511000-00010|doi-access=free }}</ref>

When measured in comparison to the lipid solubility of a volatile agent (oil:gas coefficient) using logarithmic scales, the relationship generated is linear. This relationship is described as the Meyer overton hypothesis (unfortunately, there is still no specific and satisfactory method that explains how volatile agents cause anaesthesia or how anaesthesia works) which explains some of the general physio-chemical properties of volatile agents.

"Minimum alveolar concentration" is a [[misnomer]], as MAC is representative of a ''[[median]]'' value. The original paper proposed MAC as the '''''minimal'' alveolar concentration''',<ref>{{Cite journal|last1=Merkel|first1=Giles|last2=Eger|first2=Edmond I.|date=1963-05-01|title=A Comparative Study of Halothane and Halopropane AnesthesiaIncluding Method for Determining Equipotency|url=http://anesthesiology.pubs.asahq.org/article.aspx?articleid=1967104|journal=The Journal of the American Society of Anesthesiologists|volume=24|issue=3|pages=346–357|issn=0003-3022|doi=10.1097/00000542-196305000-00016|pmid=13935000|s2cid=35750587 |doi-access=free}}</ref> which was shortly thereafter revised to '''''minimum'' alveolar concentration'''.<ref name=":0">{{Cite journal|last1=Eger|first1=Edmond I.|last2=Saidman|first2=Lawrence J.|last3=Brandstater|first3=Bernard|date=1965-11-01|title=Minimum Alveolar Anesthetic ConcentrationA Standard of Anesthetic Potency|url=http://anesthesiology.pubs.asahq.org/article.aspx?articleid=1965701|journal=The Journal of the American Society of Anesthesiologists|volume=26|issue=6|pages=756–763|issn=0003-3022|doi=10.1097/00000542-196511000-00010|pmid=5844267|doi-access=free}}</ref> A lower MAC value represents a more potent volatile anesthetic.

The Meyer-Overton hypothesis correlates lipid solubility of an anaesthetic agent with the MAC and suggests that onset of anaesthesia occurs when sufficient molecules of the anaesthetic agent have dissolved in the lipd membrane resulting in anaesthesia. Exceptions to the Meyer-Overton hypothesis vary depending on:

Other uses of MAC include MAC-BAR (1.7–2.0 MAC), which is the concentration required to block [[Autonomic nervous system|autonomic]] reflexes to [[Nociception|nociceptive stimuli]], and MAC-awake (0.3–0.5 MAC), the concentration required to block voluntary reflexes and control perceptive awareness.

* convulsant property of an agent

* specific receptor (variosu agents may exhibit an additional effect through specific receptors)

==Formal definition==

* Alpha 2 agonist effects decreases the MAC

* Mullin's critical volume hypothesis

The MAC is the concentration of the vapour (measured as a percentage at 1 atmosphere, i.e. the [[partial pressure]]) that prevents patient ''movement'' in response to a supramaximal stimulus (traditionally a set depth and width of skin incisions) in 50% of subjects.<ref>Miller ANESTHESIOLOGY</ref> This measurement is done at steady state (assuming a constant alveolar concentration for 15 minutes), under the assumption that this allows for an equilibration between the gasses in the [[Pulmonary alveolus|alveoli]], the [[blood]] and the [[brain]]. MAC is accepted as a valid measure of potency of inhalational general anaesthetics because it remains fairly constant for a given species even under varying conditions.{{cn|date=February 2022}}

* activation of GABA

==Meyer-Overton hypothesis==<!-- This section is linked from [[Nitrogen narcosis]] -->

{{see also|Theories of general anaesthetic action}}

The MAC of a volatile substance is inversely proportional to its [[lipid]] solubility (oil:gas coefficient), in most cases. This is the '''Meyer-Overton hypothesis''' put forward in 1899–1901 by [[Hans Horst Meyer]] and [[Charles Ernest Overton]]. MAC is inversely related to potency, i.e. a higher MAC equals a lower potency, as a greater concentration of the anaesthetic is required to suppress movement.

The Meyer-Overton hypothesis correlates lipid solubility of an anaesthetic agent with thepotency (1/MAC) and suggests that onset of anaesthesia occurs when sufficient molecules of the anaesthetic agent have dissolved in the lipdcell's lipid membranemembranes, resulting in anaesthesia. Exceptions to the Meyer-Overton hypothesis varycan dependingresult onfrom:

* convulsant property of an agent

* specific receptor (variosuvarious agents may exhibit an additional effect through specific receptors)

* co-administration of α₂ agonists (such as [[dexmedetomidine]]) or opioid receptor agonists ([[morphine]]/[[fentanyl]]) can decrease the MAC<ref>{{cite journal |vauthors=Daniel M, Weiskopf RB, Noorani M, Eger EI |title=Fentanyl augments the blockade of the sympathetic response to incision (MAC-BAR) produced by desflurane and isoflurane: desflurane and isoflurane MAC-BAR without and with fentanyl |journal=Anesthesiology |volume=88 |issue=1 |pages=43–9 |date=January 1998 |pmid=9447854 |doi= 10.1097/00000542-199801000-00009|s2cid=19866907 |doi-access=free }}</ref><ref>{{cite journal |vauthors=Katoh T, Kobayashi S, Suzuki A, Iwamoto T, Bito H, Ikeda K |title=The effect of fentanyl on sevoflurane requirements for somatic and sympathetic responses to surgical incision |journal=Anesthesiology |volume=90 |issue=2 |pages=398–405 |date=February 1999 |pmid=9952144 |doi= 10.1097/00000542-199902000-00012|doi-access=free }}</ref>

* Mullin's critical volume hypothesis

* Positive modulation of [[GABA]] at GABA_A receptors by barbiturates or benzodiazepines

==Factors affecting MAC==

Certain physiological and pathological states may alter MAC. For example, MAC increases with hyperthermia and hypernatremia. Conversely, anemia, hypercarbia, hypoxia, hypothermia, hypotension ([[Mean arterial pressure|MAP]] less than 40mmHg), and pregnancy seem to decrease MAC. Duration of anesthesia and biological sex seem to have little effect on MAC.<ref name = stat974>{{cite web | url=https://www.ncbi.nlm.nih.gov/books/NBK532974/ | pmid=30422569 | year=2022 | last1=Lobo | first1=S. A. | last2=Ojeda | first2=J. | last3=Dua | first3=A. | last4=Singh | first4=K. | last5=Lopez | first5=J. | title=Minimum Alveolar Concentration | publisher=StatPearls }}</ref>

Age has been shown to affect MAC. MAC begins to rise at one month of age with a peak at approximately 6 months of age (i.e., greater anaesthetic concentration is required to reach the effective anaesthetic dose). There is a subsequent steady decline in MAC with increasing age, with the exception of another peak during puberty.<ref name=":0" /> There is a linear model that describes the change in MAC of approximately 6% per decade of age.<ref name = stat974/>

Medications, illicit drugs, and prior substance use history have also been found to affect MAC. For example, acute use of amphetamines, cocaine, ephedrine, and chronic use of alcohol increase MAC. Whereas, administration of propofol, etomidate, barbiturates, benzodiazepines, ketamine, opiates, local anesthetics, lithium, verapamil, and alpha 2-agonists (dexmedetomidine, clonidine) decrease MAC. Acute alcohol intoxication and chronic amphetamine use have also been found to decrease MAC.<ref name = stat974/>

MAC values are additive. For instance, when applying 0.3 MAC of drug X and 1 MAC of drug Y the total MAC achieved is 1.3 MAC. In this way nitrous oxide is often used as a "carrier" gas to decrease the anesthetic requirement of other drugs.<ref>{{cite journal | pmid=11574362 | year=2001 | last1=Eger Ei | first1=2nd | title=Age, minimum alveolar anesthetic concentration, and minimum alveolar anesthetic concentration-awake | journal=Anesthesia and Analgesia | volume=93 | issue=4 | pages=947–953 | doi=10.1097/00000539-200110000-00029 | s2cid=31218667 | doi-access=free }}</ref>

==Common MAC values==

Values are known to decrease with age and the following are given based on a 40-year-old (MAC₄₀):<ref name="MAC">{{cite journal |author=Nickalls, R. W. D., & Mapleson, W. W. |title=Age-related iso-MAC charts for isoflurane, sevoflurane, and desflurane in man |journal=British Journal of Anaesthesia |volume=91 |issue=2 |pages=170–4 |date=August 2003 |pmid=12878613 |doi=10.1093/bja/aeg132|doi-access=free }}</ref>

* [[Nitrous oxide]] – 104{{Efn|Nitrous oxide (N{{Sub|2}}O) is the least potent inhaled anaesthetic agent. With a MAC of over 100, less than 50% of patients would theoretically become anaesthetised if receiving the maximum possible 100% nitrous oxide. While a minority of patients would be anaesthetised at 100% nitrous oxide, the resultant lack of oxygen would be fatal. For this reason, nitrous oxide can be used in practice for pain control, but not as the sole anaesthetic agent.}}<ref name="MAC" /><ref>{{Citation |last=Knuf |first=Kayla |title=Nitrous Oxide |date=2025 |work=StatPearls |url=http://www.ncbi.nlm.nih.gov/books/NBK532922/ |access-date=2025-08-03 |place=Treasure Island (FL) |publisher=StatPearls Publishing |pmid=30422517 |last2=Maani |first2=Christopher V.}}</ref>

* [[Xenon]] – 72<ref name="MAC" />

* [[Desflurane]] – 6.6<ref name="MAC" />

* [[Ethyl ether]] – 3.2

* [[Sevoflurane]] – 1.8<ref name="MAC" />

* [[Enflurane]] – 1.63<ref name="MAC" />

* [[Isoflurane]] – 1.17<ref name="MAC" />

* [[Halothane]] – 0.75<ref name="MAC" />

* [[Chloroform]] – 0.5

* [[Methoxyflurane]] – 0.16

== Notes ==

{{Notelist}}

==References==

{{Reflist}}

{{Anesthesia}}

[[Category:Anesthesia]]