UPTAKE AND DISTRIBUTIONOF VOLATILE ANESTHETICS

8/3/2019 UPTAKE AND DISTRIBUTIONOF VOLATILE ANESTHETICS

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UPTAKE AND DISTRIBUTION

OF VOLATILE ANESTHETICS

DENNIS STEVENS CRNA, MSN, ARNP

SEPTEMBER 2006FLORIDA INTERNATIONAL UNIVERSITY

PHARMACOLOGY OF ANESTHESIOLOGY NURSING I

NGR 6173


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OF VOLATILE ANESTHETICSOBJECTIVES

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 hypoventilationon alveolar partial pressure.

Discuss the factors that affect elimination of volatileanesthetic agents.

Explain diffusion hypoxia and its treatment modality.


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OF VOLATILE ANESTHETICSINTRODUCTION

Nitrous oxide (N2O), chloroform, and ether were thefirst accepted general anesthetics

Chloroform and ether are no longer currently used inthe United States

Several inhalational agents continue to be used inclinical anesthesia

General anesthesia is divided into three phases:

Induction

Maintenance

Emergence


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INTRODUCTION

Inhalational anesthetics have useful pharmacologic

properties not common to other anesthetic agents due totheir unique route of administration

Exposure to the pulmonary circulation allows a more rapidappearance of drug in arterial blood

Pharmacokinetics: how a body affects a drug; relationshipbetween a drugs dose, tissue concentration, and elapsedtime

Pharmacodynamics: how a drug affects a body; study ofdrug action including toxic effects


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INTRODUCTION

During general anesthesia a known concentration of

anesthetic gas is administered via an anesthetic circuitthrough ventilation to the patient

Anesthetic gas enters the lungs, alveoli, passes throughthe alveolar membrane into the blood, to the left side ofthe 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 thisblood/anesthetic gas mixture


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OF VOLATILE ANESTHETICSINTRODUCTION

The science of uptake and distribution is derived from thefull understanding of all the dynamics which affect the

flow, transport, and absorption of this anesthetic gas as itmakes its way from the vaporizer to the brain and othertissues of the body

Goal:

To achieve brain concentrations of anesthetic agentsthat promotes amnesia and analgesia

Inhalational anesthetics are standardized by MAC

(Minimum Alveolar Concentration)


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OF VOLATILE ANESTHETICSPHARMACOKINETICS

Mechanism of action of inhalational anesthetics remainsobscure, it is assumed that their ultimate desired effect

depends on attainment of a therapeutic tissue concentrationin the CNS

Factors affecting inspiratory concentration (FI):

Fresh gas leaving the anesthesia machine mixes withgases in the breathing circuit prior to being inspired

Actual composition of the inspired gas mixture dependsmainly on the fresh gas flow rate, volume of thebreathing system, and any absorption by the machine orbreathing circuit

Higher FD and thus higher FI increases rate of rise of FA


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PHARMACOKINETICS

Factors affecting alveolar concentration (FA):

Alveolar gas concentration (FA) would approach inspiredgas concentration (FI) without uptake of anestheticagent by the body

Anesthetic agent is taken up by pulmonary circulation

during induction, therefore alveolar concentrations lagbehind inspired concentrations (FA/FI < 1.0)

Greater the uptake, slower the rate of rise of the alveolarconcentration and the lower the FA:FI ratio


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Alveolar partial pressure is important because itdetermines 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


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OF INHALATIONAL ANESTHETICS

PHARMACOKINETICS

Solubility:

Insoluble agents are taken up by the blood less readilythan are soluble agents; as a result the alveolarconcentrations 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 thepulmonary circulation


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OF VOLATILE ANESTHETICSANESTHETIC SOLUBILITY

Rise of alveolar concentration toward inspiredconcentration most rapid with least blood soluble agent

(N2O) and least rapid with most blood soluble agents

FA/FI


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PARTITION COEFFICIENTS OF VOLATILEANESTHETICS AT 37C


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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 myocardialdepressant effect


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PHARMACOKINETICS

Alveolar gas to venous blood partial pressuredifference:

This gradient depends on tissue uptake

Transfer of anesthetic from blood to tissues isdetermined by:

Tissue solubility of agent

Tissue blood flow Partial pressure difference between arterial blood

and tissue


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Tissues are assigned into four groups based on theirsolubility 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


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PHARMACOKINETICS

Ventilation:

Lowering of alveolar partial pressure by uptakecan be countered by increasing alveolar ventilation

The effect of increasing ventilation will be mostobvious in raising the FA/FI for soluble anesthetics

For insoluble agents, increasing ventilation hasminimal effect

Hyperventilation increases rate of rise of FA Hypoventilation decreases rate of rise of FA


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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 FAapproaches

the FI. The higher FI provides anesthetic moleculeinput to offset uptake and speeds the rate at whichthe FA increases

A higher inspired concentration results in adisproportionately higher alveolar concentration


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Second gas effect:

Uptake of large volumes of the first gas (usually N2O)

increases the rate of rise of a second gas that isadministered concomitantly

Factors affecting elimination:

Recovery from anesthesia depends on loweringanesthetic concentration in brain tissue

Elimination accomplished by:

Exhalation

Biotransformation

Transcutaneous loss


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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


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PHARMACOKINETICS

Factors which slow elimination of inhalationalanesthetic agents:

High tissue solubility

Longer anesthetic times

Low gas flows

Diffusion hypoxia:

N2O elimination is so rapid that it dilutes alveolaroxygen and CO2

Prevented by administering 100% oxygen for 5-10minutes after discontinuing N2O


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OF VOLATILE ANESTHETICSREFERENCES

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). NurseAnesthesia. (3rd Ed.). St. Louis, MO: Elsevier-Saunders.

Stoelting, R.K. (1999). Pharmacology & Physiology inAnesthetic Practice. (3rd Ed.) Philadelphia, PA:

J.B. Lippincott Company.

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UPTAKE AND DISTRIBUTIONOF VOLATILE ANESTHETICS