Medical Pharmacology Chapter 14:  Physics and Anesthesiology

Ventilation: Perfusion Concepts

¹³Attribution: color illustrations and design below: from Lecture 8. Lung Dynamics by Dr. M. Ludwig, McGill University  

• ¹⁰Ventilation/Perfusion Anomalies:  Consequences for Anesthesiology

  • The relevance of the presence of ventilation perfusion abnormalities or mismatching relates to the underlying assumptions having to do with our previous analysis.  Previously, alveolar and arterial anesthetic gas partial pressures approximate equilibrium state in normal patients; however, such conditions may not obtain if ventilation perfusion abnormalities are present.

  • Equilibration may not occur in the presence of certain diseases including:

    1. Atelectasis

    2. Pneumonia

    3. Emphysema

    4. Certain congenital cardiac defects.  

  • In these circumstances abnormalities in the ventilation vs. perfusion relationship result in an increase in the alveolar (end tidal) anesthetic partial pressure and a reduction in the arterial anesthetic partial pressure.  The net effect is a non-equilibrium condition with respect  to anesthetic transport.

  • Depending on the  blood: gas solubility of the anesthetic, this circumstance will be more likely that the end-tidal anesthetic concentration is somewhat increased while the arterial partial pressure is substantially reduced (for marginally soluble anesthetic agents) or the opposite condition (for highly soluble anesthetic agents).

    • Marginally soluble anesthetics:

      • Condition A:  increased ventilation relative to perfusion -- consequence: limited, anesthetic transfer is not substantially altered.

      • Condition B: reduced ventilation relative to perfusion--consequence: significant given that the poorly ventilated region of the lung will not allow significant anesthetic transfer to the blood perfusing that region.  

        • Subsequently, blood containing little anesthetic will be mixed with blood from more normally ventilated regions, but the result is that the arterial pressure pressure will be below normal, possibly significantly below normal depending on the extent to inadequate matching of ventilation to alveolar perfusion.

• Highly soluble anesthetics

  • Condition: increased ventilation relative to perfusion -- consequence:  anesthetic partial pressure rises more rapidly into a higher level (more anesthetic molecules transferred) in this case. 

    • The overall partial pressure of anesthetic might be higher, even after mixing, depending on the possible presence of hypoventilated regions that would compensate.

• An example of these types of effects are noted in the figure below in which endobronchial intubation results in only one lung receiving anesthetic. Figure from: Eger II, E.I., "Uptake and Distribution" in Anesthesia 5th edition vol. 1 (Miller, R.D. editor; Cucchiara, R.F., Miller, Jr., E.D., Reves, J.G., Roizen, M.F. and Savarese, J.J., consulting editors) Churchill Livingstone, Philadelphia, 2000, pp 83 (reference 10); original citation: Eiger, E II, Severinghaus. JW:  Effect of uneven pulmonary distribution of blood and gas on induction with inhalation anesthetics.  Anesthesiology 25:  620-626, 1964. (reference 14)

• Normal case:  The continuous (solid) lines in the above graph refer to the case when alveolar and arterial pressure pressures rise in a coordinated way with the limit being the inspired partial pressure.  That is, without ventilation/perfusion abnormalities, the alveolar (P_A or P_{End Tidal}or P_ET and arterial P_a) anesthetic partial pressures increase together (solid lines)

• By contrast, if 50% of cardiac output is shunted to only one lung, the consequent effect depends on blood: gas solubilities of the anesthetics. 

  • Generally, with 50% shunting, the rate of rise of P_ET is increased and the rate of rise of arterial partial pressure (P_a) is reduced

  • An example of a very soluble anesthetic in this analysis is ether whereas a representative of a sparingly soluble anesthetic is cyclopropane. although these anesthetics are not in use clinically, they are helpful in illustrating the influence of the particular agent solubility on the effects of shunting.

• With one lung hyperventilated (secondary to endotracheal intubation for example), some effect will be seen on F_A/F_I for the sparingly soluble agent (cyclopropane).

  • Because of the poor solubility, which is very limiting, the slight increase in F_A/F_I is not sufficient to compensate for the loss of potential anesthetic uptake from the other lung; consequently, the rate of rise in arterial anesthetic tension is significantly slowed.  

  • On the other hand, if one examines a very soluble anesthetic, represented here by ether, a slight increase in F_A/F_I is again observed; however, in this case there is sufficient capacity in the blood to compensate for the loss of uptake by the non-ventilated lung. 

    Therefore, the rate and extent of rise in arterial gas tension are not significantly affected.

    • Cyclopropane; blood:gas partition coefficient = 0.46; MAC = 9.2%

    • Nitrous oxide blood:gas partition coefficient = 0.47; MAC = 110%

    • Diethylether: blood:gas partition coefficient = 12; MAC = 1.92%

    • Halothane blood:gas partition coefficient = 2.5; MAC = 0.75%

• The above graph represents a simulation; however, experimental data comparing the rate of anesthesia tension rise in the presence in absence of endotracheal intubation dogs reveals comparable findings:(see below graph)  [Figure from: Eger II, E.I., "Uptake and Distribution" in Anesthesia 5th edition vol. 1 (Miller, R.D. editor; Cucchiara, R.F., Miller, Jr., E.D., Reves, J.G., Roizen, M.F. and Savarese, J.J., consulting editors) Churchill Livingstone, Philadelphia, 2000, pp 83 (reference 10); ¹⁵original citation:Stoelting,.R.K., Longnecker, D.E. Effects of right-to-left shunt on rate of increase in arterial anesthetic concentration.  Anesthesiology 6: 352-356, 1972.

• As expected, the rate of rise for cyclopropane (Cyclopropane; blood:gas partition coefficient = 0.46,very sparingly soluble), is delayed compared to control; for halothane (Fluothane), C, an effect is also observed, but not as prominent.  And for the soluble agent, methoxyflurane, ; blood:gas partition coefficient = 15, no appreciable effect on the rate of rise was noted. 

• One clinically-relevant conclusion might be that, if ventilation perfusion mismatching exists, a greater delay in anesthesia would be observed for the relatively sparingly soluble agents such as desflurane (Suprane), sevoflurane (Sevorane, Ultane) and nitrous oxide by contrast to other agents such as isoflurane (Forane) or halothane (Fluothane).

Citations

• ¹⁰Eger II, E.I., "Uptake and Distribution" in Anesthesia 5th edition vol. 1 (Miller, R.D. editor; Cucchiara, R.F., Miller, Jr., E.D., Reves, J.G., Roizen, M.F. and Savarese, J.J., consulting editors) Churchill Livingstone, Philadelphia, 2000, pp 74-95.

• ¹¹Eger, II, E.I., "Concentration and Second Gas Effects" in Anesthetic Uptake and Action, The Williams & Wilkins Company, Baltimore, Maryland, Chapter 6, pp 113-121, 1974

• ¹²Eger, II, E.I., "Ventilation, Circulation and Uptake" in Anesthetic Uptake and Action, The Williams & Wilkins Company, Baltimore, Maryland, Chapter 7, p. 131, 1974.

• ¹³Color illustrations and design: from Lecture 8. Lung Dynamics by M. Ludwig, McGill University (http://www.mmi.mcgill.ca/Unit2/Ludwig/lect21ventilationperfusion.htm)

• ¹⁴Eiger, E II, Severinghaus. JW:  Effect of uneven pulmonary distribution o fblood and gas on induction with inhalation anesthetics.  Anesthesiology 25:  620-626, 1964.

• ¹⁵Stoelting,.R.K., Longnecker, D.E. Effects of right-to-left shunt on rate of increase in arterial anesthetic concentration.  Anesthesiology 6: 352-356, 1972.