UPTAKE AND DISTRIBUTION OF VOLATILE ANESTHETICS

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UPTAKE AND DISTRIBUTIONOF VOLATILE ANESTHETICS

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

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UPTAKE AND DISTRIBUTIONOF 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.

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UPTAKE AND DISTRIBUTIONOF 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

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UPTAKE AND DISTRIBUTIONOF 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

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UPTAKE AND DISTRIBUTIONOF 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

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UPTAKE AND DISTRIBUTIONOF 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)

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UPTAKE AND DISTRIBUTIONOF VOLATILE ANESTHETICS
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UPTAKE AND DISTRIBUTIONOF 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

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UPTAKE AND DISTRIBUTIONOF 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 lt 1.0)
• Greater the uptake, slower the rate of rise of
  the alveolar concentration and the lower the
  FAFI ratio

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UPTAKE AND DISTRIBUTIONOF 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

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UPTAKE AND DISTRIBUTIONOF 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

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UPTAKE AND DISTRIBUTIONOF 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
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UPTAKE AND DISTRIBUTIONOF VOLATILE ANESTHETICS

• PARTITION COEFFICIENTS OF VOLATILE ANESTHETICS AT
  37C

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UPTAKE AND DISTRIBUTIONOF 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

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UPTAKE AND DISTRIBUTIONOF 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

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UPTAKE AND DISTRIBUTIONOF 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

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UPTAKE AND DISTRIBUTIONOF 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

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UPTAKE AND DISTRIBUTIONOF 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

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UPTAKE AND DISTRIBUTIONOF 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

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UPTAKE AND DISTRIBUTIONOF 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

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UPTAKE AND DISTRIBUTIONOF 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

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UPTAKE AND DISTRIBUTIONOF 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
  Elsevier- Saunders.
• Stoelting, R.K. (1999). Pharmacology Physiology
  in Anesthetic Practice. (3rd Ed.) Philadelphia,
  PA
• J.B. Lippincott Company.