Inhalational anesthestics

Historical Facts - Several accounts of various forms of anesthesia in the BCE era using everything from cannabis and other herbs to carotid compression. - Modern anesthesia - 1842 – Dr. Crawford Long had been using ether for fun with its exhilarating effects on what were known as ether frolics. - Dr. Long used ether to anesthetize a friend to excise some neck tumors (not reported until 1849) - 1845 – Dentist Horace Wells successfully uses nitrous oxide for dental extractions; however, public demonstration fails. - 1846 – First public demonstration of ether at MGH in what is now called the ether dome by Dr. Morton. - Dr. Warren (famous surgeon) was skeptical of Dr. Morton’s offer to keep the patient from pain after Dr. Well’s failed demonstration with nitrous. Dr. Warren called it “Humbug”. - Dr. Morton stayed up all night with Dr. Gould (instrument maker) to construct a device to deliver ether that was more sophisticated than a rag. They arrived for the schedule vascular tumor removal on Mr. Abbot 15 minutes late. Dr. Warren remarked “Well, Sir, your patient is ready”. After inducing anesthesia Dr. Morton fired back “Sir, your patient is ready!”. - After the surgery Dr. Warren commented, “Gentlemen, this is no humbug”

Pharmacokinetics • Pharmacokinetics of inhalational agents divided into four phases - Uptake - Metabolism (minimal) - Distribution (to CNS = site of action) - Elimination • Goal: to produce partial pressure of gas in the alveolus that will equilibrate with CNS to render anesthesia • PARTIAL PRESSURE yields effect, not concentration • At higher altitudes where Patm < 760 mmHg, the same concentration of inhalation agent will exert a lower partial pressure within alveolus and therefore a REDUCED anesthetic effect • At equilibrium the following applies PCNS=Parterial blood=Palveoli

PK: FI, FA, and Uptake • FI (inspired concentration) • Determined by fresh gas flows, volume of breathing system, and absorption by machine/circuit • ↑ fresh gas flow, ↓ circuit, and ↓ circuit absorption allow actual Fi to be close to delivered Fi • FA (alveolar concentration) • Determined by uptake, alveolar ventilation, and concentration/second gas effects • PA (alveolar partial pressure) is determined by input (delivery) minus uptake (loss) » Uptake: gas taken up by the pulmonary circulation. – Affected by blood solubility, alveolar blood flow (i.e. cardiac output), alveolar-to-venous partial pressure difference • ↓ blood solubility, ↓ CO, ↓ alveolar-venous partial pressure difference → ↓ uptake – ↓ uptake → ↑ FA/FI → faster induction • Highly soluble gases = more gas required to saturate blood before it is taken up by CNS • High CO = equivalent to a larger tank; have to fill the tank before taken up by CNS » Rate of rise in FA/FI ratio is a marker of anesthetic uptake by the blood. – More uptake means slower rise of FA/FI – Gases with the lowest solubilities in blood (eg. Desflurane) will have fastest rise in FA/FI

PK: More on Uptake Alveolar Blood Flow: - In the absence of any shunt, alveolar blood flow = cardiac output - Poorly soluble gases are less affected by CO (so little is taken up into blood) - Low cardiac output states predispose patients to overdose of inhalational agents as Fa/Fi will be faster (esp. for soluble gases) ** Shunt States ** Right to Left Shunt (intracardiac or transpulmonary, i.e. mainstem intubation) - increases alveolar partial pressure, decreases arteriolar partial pressure; dilution from nonventilated alveoli → slows onset of induction - will have more significant delay in onset of poorly soluble agents - IV anesthetics = faster onset (if bypassing lungs, quicker to CNS) Left to Right Shunt - little effect on speed of induction for IV or inhalation anesthetics Concentration effect: • ↑ FI not only ↑ FA , but also ↑ rate at which FA approaches FI (see following graph) Second Gas Effect: - concentration effect of one gas augments another gas (questionably clinically relevant with nitrous both during induction and emergence) - rapid intake of nitrous into blood → ↑ relative concentration of second gas