1. Quick Course in Inhalant Kinetics The Alveolar Tension Curve Written for BWH Anesthesia Sunrise Lecture Series 2008 - 2009 © Copyright 1995 - 2008, James H Philip, all rights reserved. Dr. James Philip has performed funded research on Isoflurane, Sevoflurane, and Desflurane and is often supported by the manufacturers of these drugs to teach about these drugs.

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3. Quick Course in Inhalant Kinetics The Alveolar Tension Curve James H. Philip ME(E) MD Anesthesiologist and Director of Bioengineering Department of Anesthesia Brigham and Women’s Hospital Associate Professor of Anaesthesia, Harvard Medical School President, Med Man Simulations, a nonprofit organization that distributes Gas Man ®, worldwide

4. Alveolar Tension Curve Focus on the

5. Alveolar response to an Inspired Step Alveolar Tension Curve The time course of alveolar tension = P A in response to a step change in inspired tension = P I = P I P A

6. Alveolar Tension is important Tension = Partial Pressure Tension equalizes when Concentration equilibrates Concentration does not drive molecular motion Tension drives molecular motion Inspired Tension drives Alveolar Tension Alveolar Tension drives Arterial Tension Arterial Tension drives Tissue Tension Brain it the important tissue for Anesthesia Brain Tension drives depth of anesthesia

7. Alveolar Tension is important Tension = Partial Pressure Tension equalizes when Concentration equilibrates Concentration does not drive molecular motion Tension drives molecular motion Inspired Tension drives Alveolar Tension w loss + delay Alveolar Tension drives Arterial Tension = approx Arterial Tension drives Tissue Tension w delay Brain it the important tissue for Anesthesia Brain Tension drives depth of anesthesia If we know Alveolar Tension, we know the hard part

8. Gas Man ® Picture shows path of anesthetic tension IBrAa V

9. Axes and Labels 012 0.0 1.0 A / I 3 minutes (time)

10. 012 0.0 1.0 A / I 3 minutes (time) Alveolar response to a step change in inspired agent

11. Inspired Step 012 0.0 1.0 A / I 3 minutes (time) Inspired Step

12. 012 0.0 1.0 A / I 3 minutes (time) Pure Lung wash-in Without Uptake into Blood is the same as Cardiac Output = zero ( CO = 0) or Drug solubility in blood = zero ( = 0) Call this Zerothane

13. Inspired Tension Alveolar Tension Alveolar response to a step change in inspired Zerothane is an exponential curve 012 0.0 1.0 A / I 3 minutes (time)

14. 0.63 0.5 min  = Alveolar Tension Inspired Tension Time constant, tau (  ) is the time required to achieve 63% of the final value * 012 0.0 1.0 A / I 3 minutes (time) * Derive in long course

15. Now, add uptake into blood Uptake into blood produces an Alveolar Tension Plateau

16. Inspired Tension 012 0.0 1.0 A / I 3 minutes (time) Pure Lung wash-in Without Uptake into Blood

17. Alveolar Tension Plateau Plateau 012 0.0 1.0 A / I 3 minutes (time) Inspired Alveolar Plateau is produced by Removal by Blood

18. Tail Alveolar Tension Plateau Plateau 012 0.0 1.0 A / I 3 minutes (time) Inspired Alveolar Delivery Removal

19. Tail Alveolar Tension Plateau Plateau 012 0.0 1.0 A / I 3 minutes (time) Inspired Alveolar Delivery = V A Removal = CO

20. Hal Enf Iso Sevo N O 2 Des Zerothane Infinithane 012 0.0 1.0 A / I 3 minutes (time) Alveolar Plateaus

21. Alveolar Plateau Heights.38.54.66 Ht 1.24.00 Hal Enf Iso Sevo N O 2 Des Zerothane Infinithane 012 0.0 1.0 A / I 3 minutes (time)

22. Alveolar Plateau Heights and solubilities.38.54.66 Ht 1.24.00 Hal Enf Iso Sevo N O 2 Des Zerothane Infinithane 012 0.0 1.0 A / I 3 minutes (time) 1.3.67.42 0 2.4 Inf.

23. Alveolar Plateau Height Equation.38.54.66 Ht 1.24.00 Hal Enf Iso Sevo N O 2 Des Zerothane 012 0.0 1.0 A / I 3 minutes (time) 1.3.67.42 0 2.4 Inf. V I. O A 1 1 + C Plateau Ratio = A =

24. Tail Venous Return converts Plateau Plateau 012 0.0 1.0 A / I 3 minutes (time) Inspired Alveolar Plateau produced by Removal by Blood

25. 012 0.0 1.0 A / I 3 minutes (time) Venous Return converts Plateau into Tail Plateau Tail Alveolar Inspired Alveolar

26. 012 0.0 1.0 A / I 3 minutes (time) Alveolar Tension Curve sections named Inspired Initial Rise Knee Tail Plateau

27. Real drugs and real curves Next,

28. Des Sev Iso Hal 300 Minutes of administration 300 P I P A 1.0 Yasuda & Eger, 1991 Real drugs and real curves A / I

29. Des Sev Iso Hal 300 Minutes of administration 300 P I P A 1.0 What is the similarity among these curves? A / I

30. Des Sev Iso Hal 300 Minutes of administration 300 P I P A 1.0 Initial rise follows the same Zerothane curve Zero A / I

31. Des Sev Iso Hal 300 Minutes of administration 300 1.0 What is the difference between these curves? Zero A / I

32. Des Sev Iso Hal 300 Minutes of administration 300 1.0 Zero A / I Plateau Height is the only kinetic difference ! Des Sev Iso Hal

33. Des Sev Iso Hal 300 Minutes of administration 300 1.0 Zero A / I And, plateau height is determined by Des Sev Iso Hal 1.3.67.42 0 2.4 inf..38.54.66 1.24.00 Ht Inf

34. Blood / Gas Solubility Dominates Inhalation Kinetics Determines how closely Expired Tension approaches Inspired Tension in the first few minutes of anesthesia

35. The end of The Alveolar Tension Curve in its first few minutes