Physics and Pharmacology of Volatile Anesthetic Agents
Physical Properties of Volatile Anesthetics
What is the relationship between boiling point and atmospheric pressure?
Boiling point depends on the atmospheric pressure. Vaporizers are constructed and calibrated at one atmosphere.
Therefore, you cannot take these vaporizers to a high altitude area and use them without recalibration because the boiling point changes.
What is the difference between boiling point and critical temperature regarding atmospheric pressure?
Critical temperature does not alter with the atmospheric pressure. It has nothing to do with atmospheric pressure, unlike the boiling point.
What is vapor pressure and saturated vapor pressure?
When a liquid anesthetic is kept in a closed container, molecules at the surface gain kinetic energy from the latent heat of vaporization and convert into a vapor state, bombarding against the container walls to produce a pressure called vapor pressure.
When the number of particles entering the vapor phase equals the number returning to the liquid phase at a particular temperature, the pressure exerted is called saturated vapor pressure.
What does saturated vapor pressure depend on?
Saturated vapor pressure depends only on the temperature. It has nothing to do with atmospheric pressure.
If you increase the temperature, more particles enter the vapor state and exert more pressure. When mentioned without a temperature, it is always at 20° centigrade.
Why is saturated vapor pressure important in anesthesia?
It is crucial for the construction of vaporizers. The output of anesthetic agent from the vaporizer depends on the saturated vapor pressure and atmospheric pressure.
For example, if sevoflurane has a saturated vapor pressure of 157 mm Hg, the percentage of vapor coming out of the vaporizing chamber is (157/760) x 100 = 21%.
How does saturated vapor pressure determine vaporizer output?
If 79 ml of oxygen is passed through a vaporizing chamber containing sevoflurane, it will pick up 21 ml of sevoflurane vapor, resulting in 100 ml of output containing 21% sevoflurane.
This high concentration must be diluted with bypass gases before administration to the patient.
What is the splitting ratio in a vaporizer?
The splitting ratio is the ratio between the bypass flow and the gas flow entering the vaporizing chamber.
For 1% sevoflurane with 2000 ml bypass flow and 79 ml entering the chamber, the splitting ratio is approximately 25:1.
To achieve 2% sevoflurane, 158 ml must enter the chamber, changing the splitting ratio to approximately 13:1.
Can you use halothane in an isoflurane vaporizer and vice versa?
Halothane and isoflurane have nearly similar saturated vapor pressures (244 and 237 mm Hg respectively).
If you keep 1% concentration output, using halothane in an isoflurane vaporizer will still deliver 1% concentration.
However, this is dangerous because their MAC values differ significantly.
Isoflurane MAC is 1.2 while halothane MAC is 0.75, so using the wrong agent can lead to overdosage or underdosage.
Why can't desflurane be used in a conventional variable bypass vaporizer?
Desflurane has a saturated vapor pressure of 660 mm Hg.
If 100 ml of oxygen passes through a conventional vaporizer containing desflurane, it would pick up approximately 85-90% desflurane (about 900 ml), producing nearly 1000 ml output with 900 ml desflurane.
To dilute this to 1%, 70-80 liters of bypass gases would be required, which is impossible, making it potentially fatal.
Desflurane requires a specially designed vaporizer like the Tec 6.
Partial Pressure and Minimum Alveolar Concentration (MAC)
What is partial pressure and how does it relate to volume percent?
When administering vapor through a vaporizer, the output concentration is always volume percent.
If using 1% isoflurane at one atmosphere (760 mm Hg), the partial pressure is 1% of 760 mm Hg = 7.6 mm Hg.
Gases move from one space to another based on their partial pressure gradient, not concentration gradient.
What is MAC and who introduced this concept?
MAC (Minimum Alveolar Concentration) is the concentration of an anesthetic agent in oxygen at one atmosphere, at 37° centigrade, in patients between 30-60 years, that prevents movement in 50% of patients in response to a noxious stimulus.
The concept was introduced by Eger in 1972.
Why are temperature, age, and atmospheric pressure specified in the MAC definition?
- Temperature: MAC value changes with body temperature. In hypothermia, MAC value decreases.
- Age: After 40 years, MAC value decreases by 6% every decade. In younger individuals, MAC value is higher.
- Atmospheric pressure: MAC is specified at one atmosphere because partial pressure determines anesthetic effect, not concentration. At high altitude, the same concentration produces lower partial pressure.
What is the importance of MAC?
- Determines potency: Lower the MAC, higher the potency of the agent. Desflurane MAC is 6, isoflurane MAC is 1.2, making isoflurane much more potent than desflurane.
- Compares agents: MAC allows comparison of different agents for their pharmacodynamic effects at equipotent concentrations.
- MAC depends on lipid solubility - higher the oil:gas partition coefficient, lower the MAC.
What is MAP (Minimum Alveolar Partial Pressure)?
MAP is the minimum partial pressure of an anesthetic agent required to prevent movement in 50% of patients.
For halothane, MAP is 5.7 mm Hg.
Partial pressure is more important than concentration because as long as 5.7 mm Hg partial pressure of halothane is achieved anywhere (hyperbaric chamber or high altitude), it will produce the same effect.
MAP is now preferred over MAC as it doesn't require specification of atmospheric pressure.
What are the different types of MAC values?
- MAC 95: Minimum alveolar concentration that prevents movement in 95% of patients. It is 1.2-1.3 times MAC.
- MAC int: Minimum alveolar concentration required for intubation without patient response. It is 1.4 times MAC.
- MAC bar: MAC that blocks the adrenergic response (sympathetic response) to laryngoscopy and intubation. It is 1.5 times MAC.
- MAC awake: Minimum alveolar concentration where awareness is lost and patients can open their eyes. It is 0.15-0.3 times MAC.
What factors increase MAC?
- Hyperthermia
- Chronic alcoholics
- Increased CNS stimulation
- CNS stimulants like amphetamines and cocaine
What factors decrease MAC?
- Increasing age (6% decrease per decade after 40 years)
- Hypothermia
- Pregnancy
- Anemia
- Reduced cardiac output
- Hypoxia
- Hypercarbia (respiratory acidosis)
- Metabolic acidosis
- Acute alcohol intake
- Hyponatremia
Pharmacokinetics: Uptake and Distribution of Volatile Anesthetics
What factors influence equilibration from vaporizer to the patient's airway (FI)?
- Inspired concentration: Higher vaporizer concentration leads to faster equilibration with FI.
- Circuit volume: Higher volume increases equilibration time.
- Fresh gas flow: Higher fresh gas flow decreases equilibration time.
What is the time constant in anesthesia circuits?
Time constant is the time required to complete a process if it were linear.
If fresh gas flow is 8 L and circuit volume is 8 L, one time constant is 1 minute.
However, processes are exponential - with one time constant, only 67% of the process is completed.
Four time constants are required for 95% completion.
With 2 L fresh gas flow and 8 L volume, one time constant is 4 minutes, requiring 16 minutes for equilibration.
How can you hasten the equilibration process?
- Increase fresh gas flow (use higher flows initially)
- Collapse the reservoir bag to reduce circuit volume
- These techniques are used at the start of anesthesia, later switching to low-flow techniques
What factors influence equilibration from FI to FA (alveolar concentration)?
- Minute ventilation: Higher minute ventilation leads to rapid equilibration between FI and FA.
- Functional Residual Capacity (FRC): Lower FRC leads to rapid equilibration.
Which patient groups show faster induction with inhalational agents?
- Pediatric patients: Have reduced FRC and minute ventilation almost double that of adults, leading to rapid induction.
- Pregnant patients: FRC reduced by 20%, minute ventilation increased by 50%, leading to rapid induction.
- Geriatric patients: Though FRC is high and minute ventilation low, decreased MAC leads to faster induction.
What factors influence equilibration at the alveolar level?
- Concentration effect: Higher the concentration, more rapidly alveolar concentration increases.
- Second gas effect: Nitrous oxide (rapidly diffusible, 7 times more than nitrogen) creates a void in alveoli, allowing more gases from the circuit to enter, bringing the anesthetic agent with them.
What factors influence uptake from alveoli into blood?
Three factors delay FI-FA equilibration:
- Blood:gas solubility coefficient: Higher solubility means more agent dissolves in blood, delaying equilibration.
- Cardiac output (pulmonary blood flow): Higher blood flow removes more agent from alveoli, delaying equilibration.
- Concentration gradient: Higher gradient between alveoli and pulmonary arterial blood increases uptake, delaying equilibration.
Why is blood:gas solubility coefficient clinically important?
It affects both induction and recovery:
- Induction: Lower blood:gas solubility coefficient = faster induction (desflurane 0.42, sevoflurane 0.6, isoflurane 1.4, halothane 2.4)
- Recovery: Lower blood:gas solubility coefficient = faster recovery as agent is rapidly excreted via respiratory tract
- Halothane and isoflurane are not irritants and can be used for induction despite higher solubility
Historical Development of Anesthesia
When and where was anesthesia introduced to the world?
Anesthesia was introduced on October 16, 1846.
William Thomas Green Morton introduced anesthesia to the world at Massachusetts General Hospital.
The patient was Gilbert Abbott, and the surgeons were Warren and Bigelow.
A vascular tumor was removed using ether anesthesia.
October 16th is celebrated as World Anesthesia Day (until 2002, it was celebrated as Ether Day).
Why are anesthetists called "gasmen" in the UK?
For a long time, anesthesia meant only inhalation anesthetic agents.
Many people do not know anesthetists are doctors and think they only give gas.
This perception existed because anesthesia was born due to volatile anesthetic agents.
Who introduced chloroform and why?
James Simpson, an obstetrician, introduced chloroform.
He wanted to find an alternative to ether because:
- Ether was very pungent
- Ether had high blood:gas solubility coefficient (12.1), causing delayed induction and recovery
- He wanted a smooth, rapidly acting anesthetic for cesarean sections and labor analgesia
How was chloroform discovered?
Chemist friends gave Simpson various chemicals to try.
One evening, Simpson and his friends inhaled chloroform and lost consciousness, found everywhere in the hall the next morning.
Simpson realized it could be an ideal anesthetic agent for cesarean sections and used it on pregnant women.
Who popularized chloroform and how?
John Snow popularized chloroform by providing labor analgesia to Queen Victoria for her eighth and ninth children.
He used a handkerchief placed over her face, dropping chloroform onto it.
This made chloroform very popular, though many deaths occurred in India due to its cardiac and liver toxicity.
What was the Hyderabad Commission on Chloroform?
The Hyderabad Commission investigated deaths occurring due to chloroform:
- First commission: 1888, inconclusive
- Second commission: 1889, financed by the Nizam of Hyderabad
- Principal investigator: Edward Lawrie, a surgeon
- Research: Nearly 558 dogs were anesthetized with high chloroform concentrations and autopsied
- Publication: Findings published in The Lancet in 1893
- Recommendations: Advised on chloroform administration, problems, and emphasized continuous pulse monitoring
- Chloroform was found to produce respiratory arrest and dysrhythmias
Who introduced nitrous oxide to anesthesia?
Horace Wells received credit for introducing nitrous oxide to anesthesia in 1842, four years before ether.
Gardner Quincy Colton, a chemist, used to bring nitrous oxide to cities for parties where people inhaled it and danced in a state of delirium (laughing gas).
How did Wells discover nitrous oxide's anesthetic properties?
At one of Colton's parties, Wells observed a person fall, injure their shin, and bleed, yet continue dancing with laughter.
When asked about the injury, the person felt no pain.
Wells, a dentist, realized this could be used for tooth extraction.
Why did Wells' public demonstration of nitrous oxide fail?
Wells attempted to demonstrate nitrous oxide at Massachusetts General Hospital on a medical student for tooth extraction.
Nitrous oxide has a very low blood:gas solubility coefficient (0.42-0.44), causing very fast recovery.
The surgeons came slightly late, and by the time they tried to hold the tooth, the medical student cried with pain and ran away.
Wells later quarreled with his friend and was imprisoned.