UPTAKE AND DISTRIBUTION OF VOLATILE ANESTHETICS

DENNIS STEVENS CRNA, MSN, ARNP SEPTEMBER 2006 FLORIDA INTERNATIONAL UNIVERSITY PHARMACOLOGY OF ANESTHESIOLOGY NURSING I NGR 6173

UPTAKE AND DISTRIBUTION OF VOLATILE ANESTHETICS

OBJECTIVES Explain the three phases of general anesthesia. Differentiate between pharmacokinetics and pharmacodynamics. Define MAC associated with inhalational anesthetics. State the goal of general anesthesia. Discuss the three factors that affect anesthetic uptake. Explain the effects of hyperventilation and hypoventilation on alveolar partial pressure. Discuss the factors that affect elimination of volatile anesthetic agents. Explain diffusion hypoxia and its treatment modality.

UPTAKE AND DISTRIBUTION OF VOLATILE ANESTHETICS

INTRODUCTION Nitrous oxide (N2O), chloroform, and ether were the first accepted general anesthetics Chloroform and ether are no longer currently used in the United States Several inhalational agents continue to be used in clinical anesthesia General anesthesia is divided into three phases: Induction Maintenance Emergence

UPTAKE AND DISTRIBUTION OF VOLATILE ANESTHETICS

INTRODUCTION Inhalational anesthetics have useful pharmacologic properties not common to other anesthetic agents due to their unique route of administration Exposure to the pulmonary circulation allows a more rapid appearance of drug in arterial blood Pharmacokinetics: how a body affects a drug; relationship between a drugs dose, tissue concentration, and elapsed time Pharmacodynamics: how a drug affects a body; study of drug action including toxic effects

UPTAKE AND DISTRIBUTION OF VOLATILE ANESTHETICS

INTRODUCTION During general anesthesia a known concentration of anesthetic gas is administered via an anesthetic circuit through ventilation to the patient Anesthetic gas enters the lungs, alveoli, passes through the alveolar membrane into the blood, to the left side of the heart and is distributed to the tissues of the body Initially the brain and vital organs then the muscles, skin, fat, and connective tissues are perfused with this blood/anesthetic gas mixture

UPTAKE AND DISTRIBUTION OF VOLATILE ANESTHETICS

INTRODUCTION The science of uptake and distribution is derived from the full understanding of all the dynamics which affect the flow, transport, and absorption of this anesthetic gas as it makes its way from the vaporizer to the brain and other tissues of the body Goal: To achieve brain concentrations of anesthetic agents that promotes amnesia and analgesia Inhalational anesthetics are standardized by MAC (Minimum Alveolar Concentration)

UPTAKE AND DISTRIBUTION OF VOLATILE ANESTHETICS

UPTAKE AND DISTRIBUTION OF VOLATILE ANESTHETICS

PHARMACOKINETICS Mechanism of action of inhalational anesthetics remains obscure, it is assumed that their ultimate desired effect depends on attainment of a therapeutic tissue concentration in the CNS Factors affecting inspiratory concentration (FI): Fresh gas leaving the anesthesia machine mixes with gases in the breathing circuit prior to being inspired Actual composition of the inspired gas mixture depends mainly on the fresh gas flow rate, volume of the breathing system, and any absorption by the machine or breathing circuit Higher FD and thus higher FI increases rate of rise of FA

UPTAKE AND DISTRIBUTION OF VOLATILE ANESTHETICS

PHARMACOKINETICS Factors affecting alveolar concentration (FA): Alveolar gas concentration (FA) would approach inspired gas concentration (FI) without uptake of anesthetic agent by the body Anesthetic agent is taken up by pulmonary circulation during induction, therefore alveolar concentrations lag behind inspired concentrations (FA/FI < 1.0) Greater the uptake, slower the rate of rise of the alveolar concentration and the lower the FA:FI ratio

UPTAKE AND DISTRIBUTION OF VOLATILE ANESTHETICS

PHARMACOKINETICS Alveolar partial pressure is important because it determines the partial pressure of anesthetic in the blood and ultimately, in the brain Partial pressure of the anesthetic in the brain is directly proportional to its brain tissue concentration, which determines clinical effect Greater the uptake of anesthetic agent...! Three factors that affect anesthetic uptake: Solubility in the blood Alveolar blood flow Partial pressure difference between alveolar gas and venous blood

UPTAKE AND DISTRIBUTION OF INHALATIONAL ANESTHETICS

PHARMACOKINETICS

Solubility: Insoluble agents are taken up by the blood less readily than are soluble agents; as a result the alveolar concentrations rise faster and induction is faster Partition coefficients are the relative solubilities of an anesthetic in air, blood, and tissues The higher the blood/gas coefficient, the greater the anesthetics solubility and the greater its uptake by the pulmonary circulation

UPTAKE AND DISTRIBUTION OF VOLATILE ANESTHETICS

ANESTHETIC SOLUBILITY Rise of alveolar concentration toward inspired concentration most rapid with least blood soluble agent (N2O) and least rapid with most blood soluble agents

FA/FI

UPTAKE AND DISTRIBUTION OF VOLATILE ANESTHETICS

PARTITION COEFFICIENTS OF VOLATILE ANESTHETICS AT 37C

UPTAKE AND DISTRIBUTION OF VOLATILE ANESTHETICS

PHARMACOKINETICS Alveolar blood flow: Alveolar blood flow is essentially equal to CO As CO increases, anesthetic uptake increases, the rise in alveolar pressure slows, and induction is prolonged Low-output states predispose patients to overdosage with soluble agents Higher than anticipated levels of a volatile anesthetic may lower CO even further due to its myocardial depressant effect

UPTAKE AND DISTRIBUTION OF VOLATILE ANESTHETICS

PHARMACOKINETICS Alveolar gas to venous blood partial pressure difference: This gradient depends on tissue uptake Transfer of anesthetic from blood to tissues is determined by: Tissue solubility of agent Tissue blood flow Partial pressure difference between arterial blood and tissue

UPTAKE AND DISTRIBUTION OF VOLATILE ANESTHETICS

PHARMACOKINETICS Tissues are assigned into four groups based on their solubility and blood flow: Vessel-rich group Brain, heart, liver, kidney, and endocrine organs Muscle group Skin and muscle Fat group Vessel-poor group Bone, ligaments, teeth, hair, and cartilage

UPTAKE AND DISTRIBUTION OF VOLATILE ANESTHETICS

PHARMACOKINETICS

Ventilation: Lowering of alveolar partial pressure by uptake can be countered by increasing alveolar ventilation The effect of increasing ventilation will be most obvious in raising the FA/FI for soluble anesthetics For insoluble agents, increasing ventilation has minimal effect Hyperventilation increases rate of rise of FA Hypoventilation decreases rate of rise of FA

UPTAKE AND DISTRIBUTION OF VOLATILE ANESTHETICS

PHARMACOKINETICS

Concentration: Effects of uptake can be lessened by increasing the inspired concentration Higher FD and thus higher FI increases rate of rise of FA Concentration effect: The higher the FI, the more rapidly the FA approaches the FI. The higher FI provides anesthetic molecule input to offset uptake and speeds the rate at which the FA increases A higher inspired concentration results in a disproportionately higher alveolar concentration

UPTAKE AND DISTRIBUTION OF VOLATILE ANESTHETICS

PHARMACOKINETICS Second gas effect: Uptake of large volumes of the first gas (usually N2O) increases the rate of rise of a second gas that is administered concomitantly Factors affecting elimination: Recovery from anesthesia depends on lowering anesthetic concentration in brain tissue Elimination accomplished by: Exhalation Biotransformation Transcutaneous loss

UPTAKE AND DISTRIBUTION OF VOLATILE ANESTHETICS

PHARMACOKINETICS Factors that speed induction also speed recovery: Elimination of rebreathing High fresh gas flows Low anesthetic-circuit volume Low absorption by the anesthetic circuit Decreased solubility High cerebral blood flow Increased ventilation

UPTAKE AND DISTRIBUTION OF VOLATILE ANESTHETICS

PHARMACOKINETICS Factors which slow elimination of inhalational anesthetic agents: High tissue solubility Longer anesthetic times Low gas flows Diffusion hypoxia: N2O elimination is so rapid that it dilutes alveolar oxygen and CO2 Prevented by administering 100% oxygen for 5-10 minutes after discontinuing N2O

UPTAKE AND DISTRIBUTION OF VOLATILE ANESTHETICS

REFERENCES

Morgan, G.E., Mikhail, M.S., and Murray, M.J. (2006). Clinical Anesthesiology. (4th Ed.) New York, NY: McGraw-Hill. Nagelhout, J.J. and Zaglaniczny, K.L. (2005). Nurse Anesthesia. (3rd Ed.). St. Louis, MO: ElsevierSaunders. Stoelting, R.K. (1999). Pharmacology & Physiology in Anesthetic Practice. (3rd Ed.) Philadelphia, PA: J.B. Lippincott Company.