"Uptake and distribution of anesthetic gases

1. Dr.J.Edward Johnson M.D.(Anaes),D.C.H. Asst. Professor, Dept. of Anaesthesiology, Kanyakumari Govt. Medical College Hospital. "Uptake and distribution of anesthetic gases

2. "Uptake and distribution of anesthetic gases is virtually incomprehensible" wroteLawson: Gas Man Review, Anesthesia and Analgesia, August 1991

3. "Uptake and distribution of anesthetic gases Goal To develop and maintain a satisfactory partial pressure or tension of anesthetic at the site of anesthetic action in brain. Alveolar concentration of anaesthetic gas is indirectly reflects brain concentration. Pa PB

4. Path of anesthetic tension Vaporizer Breathing Circuit Alveoli (lungs) Arterial Blood Tissues (VRG [brain], MUS,FAT) Venous blood (coming back to lungs) Alveoli (lungs, again) Breathing Circuit (to be rebreathed)

5. Alveolar Tension is important Tension = Partial Pressure Important • Tension equalizes when Concentration equilibrates • Concentration does not drive molecular motion • Tension drives molecular motion

6. If we know Alveolar Tension, we know the hard part Inspired Tension drives Alveolar Tension Alveolar Tension drives Arterial Tension Arterial Tension drives Tissue Tensions Brain is the important Tissue for Anesthesia Brain Tension drives depth of anesthesia

7. Basics of Uptake and Distribution Bird’s eye view 1 2 FD MAC Fi Ventilation λB/G λT/B Fa Equilibrates CO Tissue blood flow Fa/Fi PA - PV [Parterial - PTissue] VRG Time constant Brain Partial pressure drives depth of anesthesia Time constant Concentration and second gas effects

8. I. Alveolar concentration Factors raising the alveolar concentration (Fa/Fi ) • The inspired concentration (Fi)Inspired concentration - Fa/Fi • The alveolar ventilation (Valveolar) - Minute alveolar ventilation - Fa/Fi - larger the FRC - slows raise of alveolar concentration • The time constant • Anesthetic uptake by the blood • The concentration and second gas effects

9. b)The alveolar ventilation (Valveolar) Increase in Minute alveolar ventilation Increases Fa/Fi The change is greatest for more soluble anesthetics Halothane depress Valveolar and limit the raise of alveolar concentration Hyperventilation reduces cerebral blood flow soinduction time is function of solubility Nitrous oxide and Halothane – slows induction Ether – faster induction

10. c) The time constant

11. c) The time constant - example • If 10 liter box is initially filled with oxygen and 5 l/min of nitrogen flow into box then, • TC is volume (capacity)/flow. • TC = 10 / 5 = 2 minutes ( 1 Time Constant) • So, the nitrogen concentration at end of 2 minutes is 63%.  Time Constant at Lungs 8 Mts 2 Mts 4 Mts 6 Mts O2 N2 5 Lt/min 10 Lt 86% 95% 98% 63%

12. d) Anesthetic uptake by the blood Uptake from the lung = Blood solubility x Cardiac Output x [PA-PV] / Barometric pressure Factors that Increase or Decrease the Rate of Rise of FA/FI

13. e) The concentration effect 4Lt 3Lt 4Lt 2Lt 50%O2 Uptake of half of the N2O 66%O2 2Lt 62%O2 2.5Lt 33%N2O 1Lt 1Lt of N2O 2Lt 50%N2O 38%N2O 1.5Lt Ventilation Effect Inspired Gas 1 Lt 50%O2 + 50%N2O

14. e) The second gas effect 4Lt 3Lt 4Lt 40ml 1% Isoflurane 1.3% Isoflurane 40ml 1.25% Isoflurane 50ml 61.25%O2 49%O2 Uptake of half of the N2O 65.3%O2 1.960Lt 1.960Lt 2.450Lt 33.3%N2O 1Lt of N2O 1Lt 2Lt 50%N2O 37.5%N2O 1.5Lt 1Lt Inspired Gas 1 Lt 50%O2 + 49%N2O + 1% Isoflurane 490ml 500ml 10ml

15. Concentration and second gas effect Concentration effect 65% nitrous oxide produces a more rapid rise in the Fa/Fi ratio of nitrous oxide than the administration of 5% Second gas effect Fa/Fi ratio for 4% desflurane rises more rapidly when given with 65% nitrous oxide than when given with 5%

16. I. Alveolar concentration We have Learned Factors raising the alveolar concentration (Fa/Fi ) • The inspired concentration (Fi) • The alveolar ventilation (Valveolar) • The time constant • Anesthetic uptake by the blood • The concentration and second gas effects

17. II. Uptake from lung Factors determining uptake by blood • Solubility in blood • Cardiac Output • The mixed venous anesthetic concentration Tissue uptake of anesthetic Uptake from the lung = Blood solubility x Cardiac Output x [PA-PV] Barometric pressure

18. Solubility / Partition Coefficient • Solubility is defined in terms of the partition coefficient • Partition coefficient is the ratio of the amount of substance present in one phase compared with another, the two phases being of equal volume and in equilibrium [λB/G = CB ] CG

19. Blood: gas partition coefficient λB/G Partition Coefficient = Ratio of Concentration Concentrations Equilibirates CG =CB Gas Halothane λB/G = CB =2.5 =2.5 CG 1 Equal volume Blood PG = PB Partial pressure Equalize

20. Blood: tissue partition coefficient λB/T Concentrations Equilibirates CG =CB = CT Tissue Gas Equal volume Blood PG = PB = PT Partial pressure Equalize

21. A.Solubility in blood Poor solubility Rapid induction 0.47 The more soluble the anesthetic The more drug will be taken up by the blood The slower the rise in alveolar concentration 0.65 1.4 15 High solubility Slow induction

22. B.Cardiac Output Greater the cardiac output The more drug will be taken up by the blood The slower the rise in alveolar concentration Cardiac output is lowered cerebral circulation less maintained (shock) Induction Induction slower rapid

23. C. The Alveolar-to-Venous Anesthetic Gradient The difference between partial pressure in the alveoli and that in venous blood Partial pressure in venous blood depends on tissue uptake of anesthetic At equilibrium, (no tissue uptake) The venous partial pressure = arterial partial pressure = alveolar partial pressure PA – PV = 0 Rate of rise of the mixed venous concentration depends on the tissue uptake of the anesthetic

24. The Alveolar-to-Venous Anesthetic Gradient PA Fa/Fi VRG 4-8mts No tissue uptake AT EQUILIBRIUM MG PA= PV 2-6Hrs PA – PV = 0 FAT 3-4 days PV

25. D.Tissue uptake of anesthetic The tissue uptake equals the uptake from the lungs 1. The tissue/blood partition coefficient (tissue solubility) 2. The tissue blood flow. 3. The tissue anesthetic concentration Tissue Uptake = Tissue solubility x Tissue blood flow x [Parterial - PTissue] Atmospheric pressure

26. III. Distribution to tissues

27. III. Distribution to tissues (Contd...) Equilibration of the VRG complete in 4 to 8 minutes After 8 minutes, the Muscle group (MG) determines most of uptake. Once MG equilibration is complete Fat group (FG) determines the uptake

28. Tissue Time Constant Time Constant = Tissue solubility x Volume Flow λ Fat/Bld: N2O 2.3 Sevo 48 Metho 38 λ Brain/Bld: N2O 1.1 Sevo 1.7 Metho 1.4 3 TC 95%

29. The Alveolar Tension CurveSynthesis of Factors Governing the Rise in Fa/Fi Ratio AB Initial Rise - Alveolar Wash-In BC 8 First knee – Solubility with blood C 8 C B Second knee – Equilibration with VRG 8 mts A Third knee - Equilibration of the MG

30. Mapleson Hydraulic Model Cylinders : represent the inspired reservoir (mouth), the alveolar gas, vessel rich group, the muscle group, and the fat group VRG Anesthetic Gas 75% MG 18% Ventilation Blood Supply FAT MOUTH LUNG 5.5% Cross sectional : surface of each cylinder corresponds to its capacity (λB/T * volume) Diameter of the pipes : correlates to the λB/G * CO to each group Height of the column of fluid : in each cylinder corresponds to the partial pressure of the anesthetic in that cylinder

31. Mapleson Hydraulic Model Low solubility anaesthetic • All compartments are small VRG • Pipes are represented as small because low solubility of anaesthetic is less carried by the given blood flow 75% Anesthetic Gas MG 18% Ventilation Blood Supply FAT MOUTH LUNG 5.5% • To achieve equilibrium for low soluble anaesthetic small quantity of anaesthetic has to go in to the system

32. Mapleson Hydraulic Model High solubility anaesthetic • All compartments are large • Pipes are represented as larger because high solubility of anaesthetic is more carried by the given blood flow VRG Anesthetic Gas 75% MG 18% Ventilation FAT Blood Supply MOUTH LUNG 5.5% • To achieve equilibrium for high soluble anaesthetic large quantity of anaesthetic has to go in to the system

33. Basics of Uptake and Distribution 1 2 FD MAC Fi Ventilation λB/G λT/B Fa Equilibrates CO Tissue blood flow Fa/Fi PA - PV [Parterial - PTissue] VRG Time constant Brain Partial pressure drives depth of anesthesia Time constant Concentration and second gas effects

34. RECOVERY 100% 60% 10% Recovery 0%

35. Recovery from an inhalational anesthetic 1. Increased solubility slows recovery 2. Increasing ventilation may help the recovery from potent agents 3. Prolonged anaesthesia delays recovery 4. There is no concentration effect on emergence

36. Diffusion Hypoxia • The large outpouring of nitrous oxide diluting the inspired oxygen at the conclusion of a case in the first 3-5 minutes after terminating the nitrous oxide • Managed with supplemental oxygen for a few minutes following termination of the nitrous.

37. Further References • Eger's The Pharmacology of Inhaled Anesthetics • Miller's Anesthesia, Seventh Edition • Barash : Handbook of Clinical Anesthesia (6th Ed. 2009) • http://www.anesthesia2000.com/ • www.gasmanweb.com

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