Steps Between the Administrations of Inhaled Anesthetics to Deposition in the Brain

Steps Between the Administrations of Inhaled Anesthetics to Deposition in the Brain

There are many steps between the administration of an anesthetic from a vaporizer and its deposition in the brain. By controlling the inspired partial pressure (PI) of an inhaled anesthetic, a gradient is created such that the anesthetic is delivered from the anesthetic machine to its site of action, the brain. The primary objective of inhalation anesthesia is to achieve a constant and optimal brain partial pressure (Pbr) of the anesthetic (Fig1:1). The brain and all other tissues equilibrate with the partial pressure of the inhaled anesthetic delivered to them by the arterial blood (Pa). Likewise, the blood equilibrates with the alveolar partial pressure (PA) of the anesthetic: PA (alveolar partial pressure) ↔ Pa ↔ Pbr (brain partial pressure)

Maintaining a constant and optimal PA becomes an indirect but useful method for controlling the Pbr. The PA of an inhaled anesthetic mirrors its Pbr and is the reason the PA is used as an index of anesthetic depth, a reflection of the rate of induction and recovery from anesthesia, and a measure of equal potency.

Factors that determine alveolar partial pressure: The PA and ultimately the Pbr of an inhaled anesthetic are determined by input (delivery) into the alveoli minus uptake (loss) of the drug from the alveoli into the pulmonary arterial blood. Input of the inhaled anesthetic depends on the inspired partial pressure (PI), alveolar ventilation (VA.), and characteristics of the anesthetic breathing system. Uptake of the inhaled anesthetic depends on the solubility, cardiac output (CO), and alveolar-to-venous partial pressure difference (PA _ Pv). These six factors act simultaneously to determine the PA.

Input of Inhaled Anesthetics

Inspired anesthetic partial pressure: A high PI is necessary during initial administration of an inhaled anesthetic. This initial high PI (i.e., input) offsets the impact of uptake into the blood and accelerates induction of anesthesia as reflected by the rate of increase in the PA. This effect of the PI is known as the concentration effect (Table1:1).

Alveolar Ventilation (VA)

It is a part of tidal volume (the volume of air inspired or expired per breath) which take part in gas exchange. Increased VA, like PI, promotes input of inhaled anesthetics to offset uptake into the blood. The net effect is a more rapid rate of increase in the PA and induction of anesthesia. Predictably, hypoventilation has the opposite effect, acting to slow the induction of anesthesia. Controlled ventilation of the lungs that results in hyperventilation accelerates the rate of increase of the PA by virtue of increased input (i.e., increased VA).

Characteristics of the anesthetic breathing system that influence the rate of increase of the PA include the volume of the system, solubility of inhaled anesthetics in the rubber or plastic components of the system, and gas inflow from the anesthetic machine. The higher the fresh gas flow rate, the smaller the breathing system volume, and the lower the circuit absorption, the closer the inspired gas concentration will be to the fresh gas concentration. Clinically, these attributes translate into faster induction and recovery times.

Uptake of Inhaled Anesthetics

If there were no uptake of anesthetic agent by the body, the alveolar gas concentration (FA) would rapidly approach the inspired gas concentration (FI). Because anesthetic agents are taken up by the pulmonary circulation during induction, alveolar concentrations lag behind inspired concentrations. The greater the uptake, the slower the rate of rise of the alveolar concentration and the lower the FA: FI ratio. Because the concentration of a gas is directly proportional to its partial pressure, the alveolar partial pressure will also be slow to rise. The alveolar partial pressure is important because it determines the partial pressure of anesthetic in the blood and, ultimately, in the brain. Similarly, the partial pressure of the anesthetic in the brain is directly proportional to its brain tissue concentration, which determines clinical effect.

Therefore, the greater the uptake of anesthetic agent is the greater the difference between inspired and alveolar concentrations, and the slower the rate of induction. Three factors affect anesthetic uptake: solubility in the blood (blood gas partition coefficient), alveolar blood flow, and the difference in partial pressure between alveolar gas and venous blood.

The Blood Gas Partition Coefficient

This is defined as the ratio of the amount of anaesthetic in the blood to the amount in the gaseous phase when the phases are in equilibrium (i.e. the pressures are the same). It is really a measure of the solubility of the anaesthetic in blood. High blood solubility means that a large amount of inhaled anesthetic must be dissolved (i.e., undergo uptake) in the blood before equilibrium with the gas phase is reached. When the blood-gas partition coefficient is high, a large amount of anesthetic must be dissolved in the blood before the Pa equilibrates with the PA. The higher the blood gas solubility, the slower the induction and the slower the recovery from anesthesia. Ether has high blood gas solubility and is therefore a slow induction agent. Nitrous oxide has a low blood gas partition coefficient, so both induction and recovery are fast. Halothane has a coefficient in between nitrous oxide and ether.

Alveolar Blood Flow

As cardiac output (CO) increases, anesthetic uptake increases, the rise in alveolar partial pressure slows, and induction is delayed. A high CO (e.g., fear) results in more rapid uptake, such that the rate of increase in the PA and the induction of anesthesia are slowed. A low CO (e.g., shock) speeds the rate of increase of the PA because there are fewer uptakes into the blood to oppose input. A common clinical impression is that induction of anesthesia in patients in shock is rapid.


Table 1.1 Factors Determining the Speed of Induction of Inhalation Drugs

Factors Increasing the Speed of Induction Factors Slowing Down the Speed of Induction
  • The inhaled concentration.
  • Hyperventilation with both spontaneous and controlled ventilation.
  • A poor peripheral blood flow, e.g. in patients who are shocked.
  • Decrease in the inhaled concentration.
  • Respiratory obstruction.
  • Hypoventilation from any cause.
  • Increase in the circulation to non-vital organs.

Alveolar (PA)-to-venous (Pv) partial pressure differences: The PA - Pv reflects tissue uptake of inhaled anesthetics. Highly perfused tissues (i.e., brain, heart, kidneys, and liver) account for less than 10% of body mass but receive about 75% of the CO. As a result, these highly perfused tissues equilibrate rapidly with the Pa. After 6 to 12 minutes, about 75% of the returning venous blood is at the same partial pressure as the PA (i.e., narrow PA _ Pv). For this reason, uptake of volatile anesthetics from the alveoli is greatly decreased, as reflected by a narrowing of the PI _ PA difference.

Recovery From Anesthesia

After discontinuation of anesthetic administration, elimination of anesthetic occurs by ventilation of the lungs. As the alveolar partial pressure decreases, anesthetic is subsequently transferred from the tissues (including the brain) into the alveoli.

Hypoventilation or use of low fresh gas flows that permit rebreathing of anesthetic will lead to transfer of anesthetic back into the tissues (including the brain), delaying patient recovery.

Last modified: Wednesday, 16 November 2016, 12:48 PM