Transcript Quick Course in Inhalant Kinetics ACPS 06/02/98

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.
Ready
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
Focus on the
Alveolar
Tension
Curve
Alveolar Tension Curve
Alveolar response to an Inspired Step
=
The time course of alveolar tension = PA
in response to a step change in
inspired tension = PI
PI
PA
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
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
Gas Man® Picture shows path of anesthetic tension
I
A a Br
V
Axes and Labels
1.0
A/I
0.0
0
1
2
3 minutes (time)
Alveolar response to a step
change in inspired agent
1.0
A/I
0.0
0
1
2
3 minutes (time)
Inspired Step
1.0
A/I
0.0
0
1
2
3 minutes (time)
1.0
Pure Lung wash-in
Without Uptake into Blood
A/I
is the same as
Cardiac Output = zero ( CO = 0) or
Drug solubility in blood = zero ( = 0)
Call this Zerothane
0.0
0
1
2
3 minutes (time)
Inspired Tension
1.0
A/I
Alveolar Tension
Alveolar response to a step
change in inspired Zerothane
is an
exponential curve
0.0
0
1
2
3 minutes (time)
Inspired Tension
1.0
A/I
Alveolar Tension
0.63
Time constant, tau ( t )
is the time required to achieve
63% of the final value*
t = 0.5 min
0.0
0
1
2
3 minutes (time)
* Derive in long course
Now, add uptake into blood
Uptake into blood
produces
an Alveolar Tension
Plateau
Inspired Tension
1.0
A/I
Pure Lung wash-in
Without Uptake into Blood
0.0
0
1
2
3 minutes (time)
Alveolar Tension Plateau
1.0
A/I
Inspired
Plateau is produced by
Removal by Blood
Alveolar
Plateau
0.0
0
1
2
3 minutes (time)
Alveolar Tension Plateau
1.0
A/I
Inspired
Delivery
Tail
Alveolar
Plateau
Removal
0.0
0
1
2
3 minutes (time)
Alveolar Tension Plateau
1.0
A/I
Inspired
Delivery = VA
Tail
Alveolar
Plateau
Removal = CO • 
0.0
0
1
2
3 minutes (time)
1.0
Zerothane
A/I
Alveolar Plateaus
Des
N2O
Sevo
Iso
Hal
Enf
Infinithane
0.0
0
1
2
3 minutes (time)
Ht
1
1.0
Zerothane
A/I
Alveolar Plateau Heights
.66
Des
N2O
.54
Sevo
.38
Iso
Hal
Enf
.24
Infinithane
0.0
0
1
2
.00
3 minutes (time)
1.0
Ht

1
0
Zerothane
A/I
Alveolar Plateau Heights and solubilities
.66 .42
Des
N2O
.54 .67
Sevo
.38 1.3
Iso
Hal
Enf
.24 2.4
Infinithane
0.0
0
1
2
.00 Inf.
3 minutes (time)
1.0
Ht

1
0
Zerothane
A/I
Alveolar Plateau Height Equation
.66 .42
Des
N2O
.54 .67
Sevo
.38 1.3
Iso
Hal
Enf
Plateau Ratio =
.24 2.4
A
I
0.0
0
1
2
=
1
. 
1 + COV
A
.00 Inf.
3 minutes (time)
Venous Return converts Plateau
1.0
A/I
Inspired
Plateau produced
Tail by
Removal by Blood
Alveolar
Plateau
0.0
0
1
2
3 minutes (time)
Venous Return converts Plateau into Tail
1.0
A/I
Inspired
Alveolar
Tail
Alveolar
Plateau
0.0
0
1
2
3 minutes (time)
Alveolar Tension Curve sections named
1.0
A/I
Inspired
Tail
Knee
Plateau
Initial Rise
0.0
0
1
2
3 minutes (time)
Next,
Real drugs and real curves
Real drugs and real curves
1.0
A/I
Des
Sev
Iso
Hal
PA
Yasuda & Eger, 1991
0
Minutes of administration
PI
30
What is the similarity among these curves?
1.0
A/I
Des
Sev
Iso
Hal
PA
PI
0
Minutes of administration
30
Initial rise follows the same Zerothane curve
1.0
Zero
A/I
Des
Sev
Iso
Hal
PA
PI
0
Minutes of administration
30
What is the difference between these curves?
1.0
Zero
A/I
Des
Sev
Iso
Hal
0
Minutes of administration
30
Plateau Height is the only kinetic difference !
1.0
Zero
A/I
Des
Sev
Des
Sev
Iso
Hal
Iso
Hal
0
Minutes of administration
30
Ht 
1
0
And, plateau height is determined by 
1.0
Zero
A/I
Des
Sev
.66 .42
.54 .67
.38 1.3
.24 2.4
.00 inf.
Des
Sev
Iso
Hal
Iso
Hal
Inf
0
Minutes of administration
30
Blood / Gas Solubility
Dominates Inhalation Kinetics
Determines
how closely
Expired Tension
approaches
Inspired Tension
in the first few minutes
of anesthesia
The end
of
The Alveolar Tension Curve
in its first few minutes