Inhaled Anesthetic Pharmacokinetics

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Inhaled Anesthetic Pharmacokinetics

• Steven L. Shafer, M.D.
• Professor of Anesthesia, Stanford University
• Adjunct Professor of Biopharmaceutical Science,
  UCSF
• Editor in Chief, Anesthesia Analgesia

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Key Pharmacokinetic Principles

• The drug goes in via the lungs
• The drug concentration everywhere rises
  asymptotically to the inspired partial pressure
• The partial pressure at equilibrium is the same
  in all tissues, provided the drug enters and
  leaves via the lungs
• The fastest rate of rise is in the alveolus. This
  is rate limiting for all other tissues

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Acknowledgement

• Most of these graphs are taken from Uptake and
  Distribution by Ted Eger in the 5th Edition of
  Anesthesia, edited by Ron Miller
• Ted Eger is also responsible for working out
  nearly all of the concepts presented!

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Washin Of Oxygen
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Washin Of Inhaled Anesthetics
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Nitrous Oxide Uptake

• Concentration Effect
• Effect of nitrous oxide uptake on its own
  pharmacokinetics
• Second Gas Effect
• Effect of nitrous oxide uptake on the uptake of a
  second gas

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Nitrous Oxide Uptake

• Both the Concentration Effect and the Second Gas
  Effect have two components
• The Concentrating Effect as nitrous oxide is
  taken up, the remaining gas in the lungs is
  concentrated (because the uptake occurs from both
  the numerator and the denominator).
• The Ventilation Effect as nitrous oxide is taken
  up, more gas is brought in through an open
  airway, increasing ventilation.

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The Concentrating Effect
75 N2O
50 N2O
50 O2
25 O2
2 liters
4 liters
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The Ventilation Effect
75 N2O
62.5 N2O
50 N2O

75 N2O
50 O2
25 O2
50 O2
2 liters
37.5 O2
2 liters
25 O2
4 liters
4 liters
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Mask Induction

• Start with inhaled anesthetic
• Use your voice to talk the patient to sleep
• Keep carbon dioxide as high as possible
• Get the inhaled gas as high as possible before
  starting nitrous oxide

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Effects of Nitrous Uptake
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Transfer of Nitrous Oxide into a Pneumothorax
Breathing N2O
Breathing 100 Oxygen
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LD50 of Air Embolus
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Transfer of Nitrous Oxide

• The partial pressure will equalize with trapped
  air in the body
• If the structure can expand, then it will
  increase in size, not pressure.
• Vnew Vold 1/(1-FiN20)
• If the structure cannot expand, then it will
  increase the pressure only.
• PnewPold PN20

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Ventilation is Rate Limiting for Soluble
Anesthetics
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High Cardiac Output Slows Onset of Drug Effect
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Ventilation vs. Cardiac Output Effects on Onset
/ Offset
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Myocardial Depression Accelerates Rate of Onset
of Halothane
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Effect of Pulmonary Shunt

• When part of the lung is perfused, but not
  ventilated
• Little change for soluble anesthetics, because
  the ventilated lung can take up twice as much
  anesthetic to compensate
• Rate of rise for insoluble anesthetics is slowed,
  because the giving twice as much anesthetic does
  not double the amount of drug taken up

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Effect of 50 Pulmonary Shunt
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Offset as a function of solubility and anesthesia
duration
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Offset as a function of solubility and anesthesia
duration
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Offset as a function of solubility and anesthesia
duration
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Offset as a function of solubility and anesthesia
duration