inhalational agents: history and MAC Flashcards
what was surgery like prior to the invention of anesthetic agents?
- surgery was a last, and desperate, resort
- attempted a wide range of plants (marijuana, belladonna, jimsonweed), hypnosis, and knocking unconscious
- alcohol: levels needed caused N/V, death rather than sleep
- opium: strong analgesic but not enough to completely blunt sympathetic stimulation response
when is anesthesiology considered to have begun?
1842 w/ the discovery of three agents:
- nitrous oxide
- ether
- chloroform
when and by whom was chloroform discovered?
- 1847
- Dr. James Simpson, British obstetrician
who is Dr. John Snow?
first to devote his practice to the administration of anesthetics
-administered chloroform to Queen Victoria during the birth of Prince Leopold
who may have first discovered ether?
- Dr. Crawford W. Long
- from Georgia
- first to conceive the use of ether to alleviate pain of surgery, but did not publish his finding
- not until others took credit for it, claimed he had used since 1841 for minor operations
who first suggested the use of nitrous oxide for anesthesia?
- Horace Wells
- Connecticut Dentist who had used nitrous oxide successfully during tooth extraction
- tried to demonstrate technique to a group of Harvard Medical students, but pt. cried out
- he did not understand the lack of potency of nitrous oxide
- called “humbug” and driven out of Boston; became addicted to chloroform and committed suicide 1848
- 1864 finally credited by American dental assoc. and American medical assoc. w/ discovery
who gained recognition first for use of ether?
William T.G. Morton
- dentist and colleague of Wells (N2O)
- administered ether to Gilbert Abbott at Mass. General, marking first successful public demonstration
- October 16, 1846- “Ether Day”
- he called it letheon but later was forced to reveal it was simply diethyl ether
- able to provide anesthesia during Civil War
what did Morton use to administer the ether?
he made a glass inhaler and placed an ether soaked sponge
describe the event on ether day
- October 16, 1846
- William T.G. Morton, Boston dentist, demonstrated the use of ether during surgery
- used a glass inhaler containing an ether-soaked sponge to administer the anesthetic to Gilbert Abbott
- Abbott had a vascular tumor removed by widely known surgeon, John Collins Warren, MD
- Abbott woke up and denied feeling any pain
- Warren exclaimed of Morton, “gentlemen, this is no humbug!”
- known as the “greatest gift ever made to suffering humanity”
Who was Charles Jackson, MD?
- Boston physician and chemist who advised Morton to use ether and claimed to have a large part in the discovery
- pressed claims for credit all the way to Congress, which upheld Morton as discoverer
- history of making such claims: also claimed Samuel Morse stole his idea for inventing the telegraph
who is known as the first anesthesiologist and what was his first use?
- Dr. John Snow
- first administered chloroform to Queen Victoria on April 7, 1853
who proposed the use of chloroform as an alternative to ether?
James Simpson, MD, an OB in Scotland
why were anesthetics meet religious opposition?
- thought to mock the curse of “primal sin”
- Genesis 3:16 “Unto a woman, He said, I will greatly multiply the sorrow and thy conception; in sorrow thou shalt bring forth children”
- Exodus 22:18 “Thou shalt no suffer a witch to live” thought a witch couldn’t handle pain of labor
who finally endorsed the use of anesthetics, rebuffing the minority of priests and ministers who condemned OB anesthesia?
Archbishop of Centerbury, John Bird Summer (1780-1862)
who coined the term “anaesthesia”?
- Oliver Wendell Holmes, Sr. (1809-1894)
- from the Greek word “anaisthesia”, meaning “lack of sensation” (1846)
what objections to anesthesia took place?
- American Medical Association (1848)
- vice president of AMA, John P. Harrison (1849): “pain is curative, the actions of life are maintained by it…”
- Henry Ward Beecher (famous preacher): “the less pain, the less life capacity; the less pain power, the less life power”
- Pennsylvania Hospital prohibited use until 1853
describe the ideal anesthetic
- non flammable
- easily vaporized at ambient temperature
- potent
- low blood solubility to assure rapid induction and emergence
- minimal metabolism
- compatible w/ epinephrine
- skeletal muscle relaxation
- suppresses excessive SNS activity
- not irritating to airways
- bronchodilation
- absence of excessive myocardial depression
- absence of cerebral vasodilation
- absence of hepatic and renal toxicity
what were the issues w/ ether?
- flammability
- prolonged induction
- delayed emergence
- PONV high incidence
what brought the development of “modern” inhalation agents?
- with the development of the atomic bomb came discoveries in fluorine chemistry
- after 1950, all introduced agents (except ethyl vinyl ether) contains fluorine
- first fluroxene (limited use d/t PONV), then halothane
what were the advantages and disadvantages of halothane?
advantages
- non flammable
- less pungent
- less soluble
- decreased toxicity
disadvantages: decreased CO and increased arrhythmias (hepatotoxicity)
describe halothane structure
- not an ether, no oxygen
- an ethane, 2 carbon chain
- an alkane
after halothane, describe the emergence of newer agents
- Dr. Ross C. Terrell synthesized over 700 fluorinated compounds in an effort to find a better anesthetic than halothane
- enflurane: methyl ethyl ether; chlorine #347
- isoflurane: isomer #469 (1970-1980s)
- desflurane: #653; couldn’t be used in conventional vaporizer d/t its vapor pressure near atmospheric pressure at 669 and low potency making more expensive
who invented Sevoflurane?
- Wallin
- there was no perceived need d/t expensive cost and difficult to synthesize
what encouraged further development of desflurane and sevoflurane?
the advent of outpatient surgery in the 1980s requiring more rapid recovery with a short acting agent
what were the effects of increasing fluorination in the agents?
- nonflammable
- decreased solubility (MAIN advantage)
- decreased potency (increased MAC)
- less toxic d/t resistance to degradation
- decreased percentage metabolized
define MAC
- minimal alveolar concentration (partial pressure) of inhaled agent at 1 atmosphere (760 mmHg) that prevents skeletal muscle movement in response to a noxious stimulus in 50% of pts.
- ED50 or potency
- MAC can be measure, but what really has the effect on the body is partial pressure
how is the ED95 of an agent calculated?
- MAC x 1.3
- 10-30% greater concentration than MAC produces immobility in 90-95% of pts.
what portion of the CNS determines MAC?
- spinal cord excitability is decreased resulting in immobility
- perfusion of the brain alone w/ ordinary circumstances does NOT produce immobility (took up to 3-6x MAC)
- w/ propofol, the brain determines immobility
why use minimal alveolar concentration rather than inspired concentration?
- alveolar reflects the concentration at the cord or the brain most accurately
- must allow for equilibrium (generally about 10-15 min)
- dependent on agent: 2-3 time constants
what are factors that alter MAC?
- age
- temperature
how does age effect MAC?
- *as age increases, MAC decreases about 6% per decade
- use of nitrous oxide usu. decreases MAC about 60%, but even more in elderly
- MAC is greatest in pts. less than 1 yr. of age and decreases by nearly 50% in the elderly
- *greatest to least MAC: infants-children-neonates-adults
how does body temperature effect MAC?
- body temperature reduction causes MAC reduction
- MAC of desflurane decreases almost in half by 10 degree C decrease in temp
- *MAC of nitrous oxide is not as effected
- *MAC decreases 2-5% for every 1 degree C drop in temp
- *consider w/ CABG, use less MAC
what factors decrease MAC?
- pregnancy
- decreased CNS sodium: lethargy (d/t dehydration or absorption of irrigation fluid)
- depressant drugs
- other drugs
- possibly neuraxial opioids
- PaO2 less than 38 mmHg (but we wont allow this low)
- BP less than 40 mmHg systolic (we wont allow)
- cardiopulmonary bypass (decreased temp and metabolic rates)
how does pregnancy decrease MAC?
- increased concentrations of progesterone
- decreases nearly 30% in early postpartum
- normalizes within 12-72 hrs.
- typically, moms don’t go for tubal ligations until 2nd day postpartum, so probably normalized
what are the effects of depressant drugs on MAC?
- decreased MAC
- opioids: *non linear synergistic with a ceiling effect (even small dose like fentanyl 3 mcg/kg, causes big decrease in MAC; almost 50% in des from 6.3 to 3.2%, but w/ double the dose only dropped from 6.3 to 2.2%)
- no amnestic dose of opioids, so w/ ceiling effect, cant totally eliminate MAC needed
- benzodiazepines: *dose dependent decrease
- barbiturates and propofol: decrease but redistribution, so effect on MAC doesn’t last long
- acute ETOH ingestion decreases (but chronic ETOH increases MAC d/t enzyme induction)
- local anesthetics: lidocaine IV decreases MAC on induction and may prolong if used on emergence
- N2O: 0.5 MAC of N2O plus 0.5 MAC of isoflurane are additive to 1 MAC of either drug
what other drugs decrease MAC?
- clonidine and dexmetomidine (Precedex) decrease MAC by decreasing CNS catecholamines and by hyperpolarizing of CNS cell membranes
- some beta blockers
- some calcium channel blockers
- adenosine
what are factors that increase MAC?
- red hair d/t excess pheomelanin production
- drug induced increases in CNS catecholamine levels (cocaine, ketamine, amphetamines)
- hyperthermia
- hypernatremia
- chronic ETOH d/t enzyme induction
what factors do not alter MAC?
- gender
- duration of anesthesia (except for isoflurane, which decreases d/t accumulation b/c of increased solubility)
- body mass
- PaO2 greater than 50 mmHg
- PaCO2 less than 80 mmHg
- hematocrit less than 10%
- SBP greater than 40 mmHg
define MAC awake
the average of the concentrations immediately above and below those permitting voluntary response to command
- usually exceeds MAC amnesia, which is hard to measure, so if at MAC awake, know amnesia is covered also
- gives an idea of how good an amnestic agents is (if wider range between MAC and MAC awake)
what affects MAC awake?
- decreases w/ age (but MAC also decreases, so the ratio of the two doesn’t change)
- inhalation agent
what type of anesthetic use are high incidence of recall and why?
highest types of case for recall is an opioid, N2O case since MAC awake is 68% and cant give any more than 70%
-very smaller range between MAC awake and MAC (larger ratio or percentage of MAC) and can easily not be above MAC awake
what is MAC awake for desflurane, isoflurane, and sevoflurane?
1/3 (34%) of their MACs
what is the MAC awake for halothane?
55% of MAC
what is the MAC awake for N2O?
64% of MAC
- not as good an amnestic
- must supplement for amnesia
what is the importance of the ration of MAC awake / MAC?
- higher the ratio, the faster recovery
- higher the ratio, the poorer the amnestic value
- *low dose opioids (fentanyl 2-3 mcg/kg) minimally affects MAC awake, but does decrease MAC; this increase the ratio, causing quicker awakening, but poorer amnesia (MAC is decreased closer to MAC awake)
does MAC awake ensure ability to protect airway?
NO, MAC awake does not ensure return of esophageal sphincter tone or return of pharyngeal function
**sphincter tone is impaired at very low concentrations
at what MAC ensures patient airway safety?
- *concentrations of inhaled agent may require levels of less than 0.1 MAC for patient safety
- *blow all gas off
define MAC TE
MAC that allows tracheal stimulation
- no coughing or bucking during suctioning of pharynx
- no movement or coughing within 1 minute of extubation
- no breath holding or laryngospasm after extubation
- *equal to or exceeds MAC (Sevo 2.9-3.2%, 50% more than MAC)
- *much greater for children
when does MAC TE matter?
- important for pediatrics where only inhalation agents are used prior to laryngoscopy
- when wanting to extubate deep
- if cuff is deflated, and start to cough, probably in stage II and if extubate, will laryngospasm
- inflate cuff and allow to wake up
define MAC BAR
- minimum alveolar concentration that Blocks Autonomic Response (B-A-R) to surgical stimulus
- exceeds MAC
why should you be careful w/ decreasing MAC and MAC BAR w/ opioids?
- opioids don’t decrease MAC awake
* fentanyl 1.5-3 mcg/kg decreases isoflurane MAC BAR to 0.4 MAC w/ 0.6 MAC of N2O, approaching MAC BAR
with 60% N2O, what is MAC BAR of desflurane and isoflurane?
1.3 MAC (w/ 0.6 MAC N2O, total 1.9 MAC)
with 67% N2O, what is MAC BAR of sevoflurane?
- 45 MAC (w/ .67 MAC N2O, total 2.2 MAC)
* fentanyl of 3 mcg/kg alone decreases it by 83%
why is MAC BAR essential in children?
usu. don’t have agents like opioids to block autonomic responses, so much more MAC is required to achieve MAC BAR
- adults have many other drugs that decrease stimulation (opioids, NMB, beta blockers, etc.)
