Understanding Rebreathing Kinetics James H Philip, ME(E), MD, CCE Anesthesiologist and Director Bioengineering, Brigham and Women's Hospital Professor of Anaesthesia, Harvard Medical School Boston Massachusetts USA
Understanding Rebreathing Kinetics James H Philip, ME(E), MD, CCE Anesthesiologist and Director Bioengineering, Brigham and Women's Hospital Professor of Anaesthesia, Harvard Medical School Creator of Gas Man anesthesia kinetics simulation DISCLOSURE Gas Man and Med Man Simulations Inc. (MMSI) are a nonprofit charitable organization I receive no financial benefit from it
Optimal Volatile Agent Delivery Accurate Control of the Anesthetic State Anesthetize the Brain and Spinal Cord Get the Anesthetic Agent to the Effect Site Produce the correct anesthetic level Quickly Precisely Accurately Persistently And reverse this process rapidly
Electrical model explains inhalation kinetics P! DEL! P! =! P! P! I! A! E! P! VRG! F! MUS! F! FAT! P! DEL! F! FGF! F! VA! C! CKT! F! VRG! C! FRC! C! VRG! C! MUS! C! FAT! P = Partial Pressure or Tension (electrical V or E) F = Gas Flow = Conductance (electrical G = 1/R) C = Capacitance (electrical C) = Anesthetic flow (electrical current = I)
Electrical model explains inhalation kinetics P! DEL! P! =! P! P! I! A! E! P! VRG! F! FAT! This audience F! MUS! F! FGF! F! VA! F! VRG! P! DEL! probably C! C! CKT! FRC! could use this P = Partial Pressure or Tension (electrical V or E) F = Gas Flow = Conductance (electrical G = 1/R) C = Capacitance (electrical C) = Anesthetic flow (electrical current = I) C! VRG! C! MUS! C! FAT!
Our industrial colleagues used feedback control to overcome this complexity for users. Possible for USA soon,, as discussed at AAMI-FDA Summit 17 Sept 2014!
GE Aisys ET Control Agent, O 2 Draeger Zeus ET Agent, Insp O 2, TCI IV 2014 World Anesthesia Machines
A structure-behavior model shows this We and clinical colleagues might use Gas Man to understand what we do
GAS MAN physiologically-based model for inhalation kinetics Model was described by Kety in 1950 1 and is routinely used by Eger 2 and several in this room. Accurately predicts expired concentrations during induction and emergence 3. Flow-limited 4-compartment mammillary model plus breathing circuit 4. Each compartment has linear one-compartment mixing with anesthetic brought to it 4. Concentration effect makes the model no stationary and thereby nonlinear 4. Blood & tissue solubilities, gas & blood flows, compartment volumes are from literature 4. User selects patient size and can adjust Vaporizer, FGF, Ventilation, Cardiac Output 4. User can change body habitus adjusting Volumes and Flows of compartments like Fat and Muscle.4. The modified Euler Integration stabilizes model behavior under extreme settings like CO or VA = 100 5. Learners can use and learn from Gas Man effectively without supervision 6. Researchers can explore subtle aspects of clinical anesthesia 7,8. 1 Kety, SS. Anesthesiology. 1950, 11, p. 517 2 Eger EI, Shafer SL Anesth Analg 2005, 101: 688-696 (Tutorial). 3 Bouillon T, Shafer SL. Br J Anaesth 2000; 84:429 31 4 Philip JH Int J Clin Monit Comp 1986;3:165 73. 5 Ji XB, Philip HM, Philip JH. Proc. STA Ann. Mtg 1997 6 Garfield JM, Paskin S, Philip JH. Med Educ 1989;23:457 62. 7 Leeson S, Roberson R, Philip JH. Anesth Analg 2014 8 Hendrickx, DeWolf, Feldman, others in this room.
Mathematics Gas Man solves the simultaneous differential equations for multiple gases Used Euler s method of integration (Ver 1 & 2) New value = Old value + dp/dt * Δt Δt should be < 1/10 tau minimum Stiff integration problem adds complexity Several very different time constants (Lung = 0.5 minutes, Fat = 6 hours) Large Δt is OK late Small Δt is required early Ver 3 replaced Euler Integration with Exponential Integration 1 Some parameters change as a function of the the variables, thus nonlinear Any parameter can be changed during simulation, thus time-variant Gas Man is a nonlinear time-varying model 1. Ji XB, Philip HM, Philip JH. Gas Man overcomes stiff-integration oscillation using Exponential Integration. Proc. STA Ann. Mtg 1997.
(A) Wash-in 360 minutes = 6 hr. "15 minutes" (B) Wash-out "after breathing 1 MAC for 1 hr. " (C) Wash-out "after breathing 1 MAC for 2 h. " Gas Man model and math appear to be correct for induction and emergence" (D) Wash-out "after breathing 1 MAC for 4 h. " (E) Washout "after breathing 1 MAC for 12 h." Bouillon T, Shafer S. Editorial Hot air or full steam ahead? An empirical pharmacokinetic model of potent inhaled agents. Brit J. Anaes. 84:429-431 2000."
A structure-behavior model shows this Agent Level (Partial Pressure) Flow of carrier and agent
Compartments and Flows Tension = Partial Pressure D I Delivered Inspired A a Br arterial Alveolar Brain V Veins
Return Flows I A Inspired Alveolar V Veins Then agent returns
Flows link locations Flows link locations
Time, Uptake, and Delivered Quantity are shown Timing (L)! (L)! Uptake Delivered
The Model helps you Control Anesthetic Depth. Goal is VRG (Brain) = 1.0 MAC or some fraction or multiple JHP inference from Philip, Gas Man, 2008
A graph traces the behavior over time Alveolar response to step change in Delivered Concentration from a on-rebreathing circuit! Xe" " Des" " Sevo" " Iso" Alveolar Tension Curve" Show Alveolar over Delivered!
Alveolar and other tissue response to a step change in Delivered Concentration with high and low fresh gas flow!
8 L/min vs L/min Desflurane simulation!
Inspired response to a step change in Delivered!
Alveolar response to a step change in Delivered!
VRG response to a step change in Delivered "
Alveolar / Inspired for high flow and low fresh gas flow "
VRG / Alveolar for high flow and low fresh gas flow"
Low FGF " makes Inspired track Delivered poorly. But, if Inspired is well controlled despite the low FGF, other compartments be well controlled.!!! These curves are not identical because we are plotting the ratio of two responses.! If we had plotted the system transfer function or step response of the brain, they would have been identical!
Some of today s and most of tomorrow s! Anesthesia machines achieve agent control while using low fresh gas flow.! They do this using feedback control of measured expired agent.!
Case 1! Two recent examples where our clinical skills and low fresh gas flow failed us! Patient well-anesthetized on Desflurane-Air Oxygen! Drifted a little too deep over time! We tried negative bolus plus decreased infusion! Vaporizer off until ET reached desired! Vaporizer set to 1% less than before the negative bolus! Here is what it looked like!!
FGF 1 L/min limits ability to lighten anesthesua! GE Remote View"
FGF 1 L/min limits ability to lighten anesthesua! Zoom"
Computer Simulation shows and explains this!
ET control can avert some anesthetic overdoses" US Hospital! FGF 1 LPM! Des set to 10! I/E = 7% / 6%! Perfect case!!!
ET control can avert some anesthetic overdoses" US Hospital! FGF 1 LPM! Des set to 10! I/E = 7% / 6%! Perfect case!! Tubing caught and cut in CT Scan"!
Inadvertent overdose requiring pressors! Des I/E" 7/6" 15/9"
Computer Simulation shows this, and much of what we observe!
Wake Up!"
Inverted Alveolar Tension Curves (Emergence after infinite time anesthetic)! Iso" " Sevo" " Des" " Xe"
Brain Delay after ET Agent change! 2 6 minutes, for all agents in most patients! This is the Effect Site delay! Agent monitor and a timer let you see this! Use monitor s trend graph of ET Agent! ET three minutes ago is Brain level now! Compare this analysis to processed EEG Usually very close!
Brain delay from expired, on Gas Monitor and EEG Monitor" 0:00" 0:03" JHP Case"
Sevo brain delay 3 minutes!
Sevo Brain Close-up"
Simulate Sevoflurane VIMA and compare with ET monitor Agent Monitor! Gas Man"
Understanding Rebreathing Kinetics" Anyone can download Gas Man Student Edition free www.gasmanweb.com, www.medmansimulations.org NAVAt attendees may download a 2 month Gas Man Professional Edition license from the meeting web site or get it from Gas Man table
Understanding Rebreathing Kinetics" Thank you" Anyone can download Gas Man Student Edition free www.gasmanweb.com, www.medmansimulations.org NAVAt attendees may download a 2 month Gas Man Professional Edition license from the meeting web site
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