A Practical Approach to the use of Inhalational Anesthetics
James H. Philip, M.E.(E.), M.D. Anesthesiologist and
Director of Bioengineering, Department of Anesthesia, Brigham and Women's Hospital
Medical Liaison for Anesthesia, Department of Biomedical Engineering Partners HealthCare System Professor of Anaesthesia Harvard Medical School
For BWH employees, the CE number for this lecture is 322799 © 1995 - 2014, James H Philip, all rights reserved
A Practical Approach to the use of Inhalational Anesthetics
James H. Philip, M.E.(E.), M.D. Anesthesiologist and
Director of Bioengineering, Department of Anesthesia, Brigham and Women's Hospital
Medical Liaison for Anesthesia, Department of Biomedical Engineering Partners HealthCare System
Associate Professor of Anaesthesia Harvard Medical School
Conflicts of interest: Financial - None Non-financial - 1) Author of Gas Man® computer simulation of inhaled anesthetics, distributed by Educational
Charitable Organization, Med Man Simulations, Inc. (MMSI) 2) President without financial compensation of MMSI. www.medmansimulations.org
Anyone can download the program and textbook from from the web site, free.
General Anesthesia Techniques
TIVA = Total Intravenous Anesthesia IV drugs only
VIMA = Volatile Induction and Maintenance Anesthesia
Balanced = Inhaled and IV drugs Induction (beginning) = IV Maintenance = IV opioid + IV muscle relaxant + Inhaled sleep and amnesia drug
Components of General Anesthesia
1. Sleep – sedation -> unconsciousness 2. Amnesia - loss of recall 3. Analgesia - loss of pain sensation 4. Paralysis - muscles relaxed or soft 5. Autonomic block - no body response
End of IV Anesthesia
We usually want all effects to go away Except analgesia to block the perception and response to noxious stimuli that remain after the surgery is over, AKA postoperative pain
Prevent or treat postoperative pain with Opioids Non-opioid analgesics of many classes Local anesthesia, Regional anesthesia
Intravenous Anesthesia Drugs and Purpose
Sleep - Sedative/Hypnotic – e.g., propofol Amnesia - e.g., midazolam, propofol Analgesia – opioid plus adjunct Paralysis – Neuro-Muscular junction Blocker-NMB Autonomic block – Beta blocker, side effect of other
drugs
What causes end of IV Anesthesia? Plasma level falls Effect site follows plasma level with 3 – 5 min delay Sedative/Hypnotic drug redistributes fast Hypnotic drugs redistribute slowly; rarely reversed Pain drugs other than remifentanil redistribute slowly NMB drugs we reverse with antagonist physostigmine
and block side effects with glycopyrolate Sympathetic blockade follows sedative/hypnotic drug
Inhalation Anesthesia
One drug does most of everything 1. Sleep – sedation -> unconsciousness 2. Amnesia – no recall 3. Analgesia – no pain sensation 4. Paralysis - muscles relaxed or soft 5. Autonomic block - no sympathetic response
What causes end of Inhalation Anesthesia? Drug is exhaled and removed from blood Plasma level falls rapidly Effect site follows plasma level
3 – 5 min time constant Pain is prevented or treated the same as after IV
anesthesia I give drugs to cover post-op and not intra-op pain
Volatile Induction and Maintenance Anesthesia VIMA No Propofol No NMB
Volatile Induction and Maintenance Anesthesia VIMA No Propofol No NMB No use No waste if prepared properly
BWH Pharmacy robotically-filled Propofol syringes
Inhalation Anesthetic History - William TG Morton
1846 Ether for General Anesthesia demonstrated, published, patented
Ether was made and delivered at the point of use
Oct 16, 1846 Surgery @ MGH Oct 22, 1846 US Patent 4,848
Sep 30, 1846 Tooth extraction
History
1846 Morton found Ethyl Ether to be a vapor that anesthetizes 1950 Kety explained Kinetics from Vaporizer to Brain 1963 Eger normalized drug concentrations to
MAC = Minimum Alveolar Concentration to anesthetize 1 MAC is the ED50 for “no movement from incision”
1963 Eger established End-Tidal = Expired ~ Alveolar conc. Recent
understanding 1.3 MAC ~ ED95 0.7 MAC provides amnesia 0.33 MAC patients respond to command These levels are all in the Brain which is delayed from ET
Inhaled Anesthetic Choices Ether is long gone – Flammable and very slow wake up Halothane was used in pediatric anesthesia until ~ 2005 Nitrous Oxide (N2O) old, rarely used USA
environmental harm, MAC = 110% atm thus not potent Todays agents Name MAC (%atm) Isoflurane 1.1 Sevoflurane 2.1 Desflurane 6.0
2014 Inhaled Agents Isoflurane –
inexpensive, slow return to normal Sevoflurane –
tolerated for mask induction and LMA FDA limits FGF > 1 or 2 LPM. $5 – $10 / hr pretty fast return to normal
Desflurane – very fast return to normal expensive at high FGF FDA approved for very low FGF; cost < $3 / hour
Each delivered with an Anesthesia Delivery Systems
Anesthesia Delivery Systems GE Aisys Draeger Apollo
We could use a manual resuscitator for easy delivery
Gases breathed in, breathed out, thrown away
We could use a manual resuscitator for easy delivery
Gases breathed in, breathed out, thrown away But, much wasted drug and potential environmental harm.
Lets explore rebreathing of anesthetic agents.
CO2
Ab- sorb- ant
Fresh
Normal flow in the breathing circuit - Inspiration
Inspired
Exhaust
CO2
Ab- sorb- ant
Fresh
Normal flow in the breathing circuit - Expiration
1
2 Expired
This is “Circle-Absorber System”
Exhaust Expired
CO2
Ab- sorb- ant
Inspired Fresh
VE
Gas is sampled from circuit near patient to measure I and E
Sampled
Exhaust Expired
CO2
Ab- sorb- ant
200 mL/min
Inspired Fresh
VE
Gas Monitor screen
Agent wave – continuous display
Sevoflurane concentration
6 sec
CO2 wave, also. This shows patient is alive
Sevoflurane concentration
CO2 concentration 6 sec
Inspired and Expired (End-Tidal) timing
I E
Inspired and End-Tidal (ET) numeric display
I E
Graphic Trend of Agent – insp, exp
1 hour
I
E
Graphic Trend of Sevoflurane VIMA Two anesthetics in an 8 hour day
Graphic Trend of Agent
Desflurane 5 minutes
66/18/08 Robot-assisted myomectomy
JHP photo of JHP case 6/18/08
6 hr Robotic Myomectomy w Desflurane
GE Aisys 2007
6 hr Robot Hyx
JHP photo of JHP case 6/18/08
GE Aisys 2007
6 hr Robot Hyx
JHP photo of JHP case 6/18/08
41 mL / 6 hr = 7 mL/hr @$.50/mL =
$3.50 / hr = $21.00 / case
GE Aisys 2007
6 hr Robot Hyx
41 mL / 6 hr = 7 mL/hr @$.50/mL =
$3.50 / hr = $21.00 / case
276 L / 6 hr = 0.7 LPM
JHP photo of JHP case 6/18/08
02/27/07 BWH OR Boston 6 hour Robot-assisted, Radical hysterectomy, w lymph node dissection
6 hr Robotic Hysterectomy w Desflurane
JHP photo of JHP case 2/27/2007
02/27/07 BWH OR Boston 6 hour Robot-assisted, Radical hysterectomy, w lymph node dissection
Emergence - Observe 1 hr trend graph
2 3
JHP photo of JHP case 2/27/2007
Inhalation Agent Theory (Kety 1950)
Anesthetic Path from Vaporizer to Brain: Del (D) -> CKT (I) -> Alv (A, E) -> art (a) -> Brain (VRG)
MAC in brain 1 MAC: 50 % of patients don’t move with incision
100 % are amnestic We use the term Anesthetic Tension rather than Anesthetic Concentration because
Tension equalizes while Concentration equilibrates with a ratio of concentrations in the two compartments that equilibrate.
Thus, anesthetic tension shows the Del -> Brain process
6 sec
Inhalation Agent Practice – Gas Monitor
Anesthetic Path from Vaporizer to Brain: Del (D) -> CKT (I) -> Alv (A, E) -> art (a) -> Brain (VRG)
MAC in brain 1 MAC: 50 % of patients don’t move with incision
100 % are amnestic
6 sec
Set Vaporizer
Inspired Expired = End-Tidal
Vital signs Brain Monitor
Alveolar Tension Curve
We explore kinetics by viewing the
Alveolar response to an Inspired Step
Alveolar Tension Curve
The time course of alveolar tension = PA in response to a step change in
inspired tension = PI
=
PI PA
Path of Anesthetic Tension from Vaporizer to Brain
I Br VRG
A a D
Philip JH, Gas Man®, www.medmansimulations.org, 1984 - 2014
Flows facilitate or impede the passage
I Br A a D
Open (Non-Rebreathing) Circuit provides controlled Inspired Step
I Br A a I D
Good for theory, expensive for practice
0 1 2 0.0
1.0 A / I
3 minutes (time)
Axes and Labels
0 1 2 0.0
1.0 A / I
3 minutes (time)
Inspired Step
Alveolar response to a step change in inspired agent
Inspired Tension
Alveolar Tension
exponential curve
0 1 2 0.0
1.0 A / I
3 minutes (time)
Pure Lung wash-in Without Uptake into Blood
0.63
0.5 min τ =
Alveolar Tension
Inspired Tension
Time constant, tau ( τ ) is the time required to achieve
63% of the final value*
0 1 2 0.0
1.0 A / I
3 minutes (time) * Derive in long course
Time Constant
0.63
0.5 min τ =
Alveolar Tension
Inspired Tension
Time constant, tau ( τ ) time required to fill the compartment
if there were no mixing
0 1 2 0.0
1.0 A / I
3 minutes (time) * Derive in long course
Time Constant
Alveolar Tension
Inspired Tension
0 1 2 0.0
1.0 A / I
3 minutes (time) * Derive in long course
Pure Lung wash-in Without Uptake into Blood
is the same for: Cardiac Output = zero ( CO = 0) or Zerothane, Drug with solubility = zero (λ = 0) Xe, which has a very low solubility ~ 0 This is mixing a new gas into a container with
old gas
Now, add uptake into blood
Uptake into blood produces an Alveolar Tension Plateau
The plateau is formed by the equilibrium between
ventilation in and cardiac output out
0 1 2 0.0
1.0 A / I
3 minutes (time)
Alveolar Tension
Inspired Tension
Pure Lung wash-in Without Uptake into Blood
Plateau
0 1 2 0.0
1.0 A / I
3 minutes (time)
Inspired
Alveolar
Plateau is produced by Anesthetic Removal by Blood
Alveolar Tension Plateau
Tail
Plateau
0 1 2 0.0
1.0 A / I
3 minutes (time)
Inspired
Alveolar
Delivery
Removal
Alveolar Tension Plateau
Tail
Plateau
0 1 2 0.0
1.0 A / I
3 minutes (time)
Inspired
Alveolar
Delivery = VA
Removal = CO • λ
Alveolar Tension Plateau
Hal Enf
Iso
Sevo N O 2
Des
Xe or Zerothane
Infinithane 0 1 2
0.0
1.0 A / I
3 minutes (time)
Alveolar Plateaus
Several Drug Plateaus
Ether
Alveolar Plateau Heights
.38
.54
.66
Ht 1
.24
.06
Hal Enf
Iso
Sevo N O 2
Des
Zerothane
0 1 2 0.0
1.0 A / I
3 minutes (time)
Plateau Heights
Ether
Alveolar Plateau Heights and solubilities
.38
.54
.66
Ht 1
.24
.00
Hal Enf
Iso
Sevo N O 2
Des
Zerothane
0 1 2 0.0
1.0 A / I
3 minutes (time)
1.3 2.4
λ
.67
.42
0
Inf.
Height and Solubility
Ether .06 12.1
Venous Return brings anesthetic back to alveoli
I Br A a V
Tail of the Alveolar Tension Curve
Tail
Plateau
0 1 2 0.0
1.0 A / I
3 minutes (time)
Inspired
Alveolar
Plateau produced by Removal by Blood
Venous Return converts Plateau
0 1 2 0.0
1.0 A / I
3 minutes (time)
Plateau
Tail Alveolar
Inspired
Alveolar
Venous Return converts Plateau into Tail
0 1 2 0.0
1.0 A / I
3 minutes (time)
Inspired
Arterial ~ Alveolar (ignore shunt)
Arterial = Alveolar
0 1 2 0.0
1.0 A / I
3 minutes (time)
Inspired
Tail
VRG = Brain, etc.
VRG follows arterial blood with τ = 3 – 5 min
τ = time constant, time for 63% response
Real drugs and real curves Next,
Des
Sev
Iso
Hal
30 0 Minutes of administration 30 0
P I
P A
1.0
Yasuda & Eger, 1991
Real drugs and real curves
A / I
Des
Sev
Iso
Hal
30 0 Minutes of administration 30 0
1.0 Zero A / I
Plateau height is determined by λ
Des Sev
Iso
Hal
λ
1.3
.67
.42
0
2.4
inf.
.38
.54
.66
1
.24
.00
Ht
Inf
Blood / Gas Solubility Dominates Inhalation Kinetics Determines how closely Expired Tension
approaches Inspired Tension in the first few minutes after you
change inspired
Wake Up !
0
.2
.4
.6
.8
Des
Sev
Iso
Hal
P A
0
0.62
0.34
0.76 Knee
Initial Fall = 0.5 min
0.46
0.00
E = all tissues
0.12
0.29
0.44
0.17
Tail
30 Minutes of emergence
10 20
Emergence from a long 1 MAC anesthetic MAC
1
P MAC
Yasuda & Eger, 1991. Analysis by JHP.
0
.2
.4
.6
.8
Des
Sev
Iso
Hal
P A
0
Initial Fall = 0.5 min
0.00
E = all tissues
0.12
0.29
0.44
0.17
Tail
30 Minutes of emergence
10 20
Emergence from a long 1 MAC anesthetic MAC
1
P MAC
Yasuda & Eger, 1991. Analysis by JHP.
Eger EI, Shafer SL. Tutorial: Context-Sensitive Decrement Times for Inhaled Anesthetics. Anesth Analg 2005 101: 688-696
Eger published this, Sept 2005 80% 88%
90% 92%
95%
The time required to reduce drug level further is termed the Context-sensitive decrement time. These times differentiate these drugs even more
Clinical Care – precise control of anesthetic depth Every time I make a change, up or down, the same thing happens - Initial change, plateau Good clinicians use the shape of this curve to contour the course of inspired, expired, and brain tension to produce the anesthetic they desire It is the tail of the curve that lets the patient drift too deep or too light after the plateau turns into a knee and ongoing tail
IV vs Inhaled agent kinetics
Context-Sensitive Half Time: Opioids and Hypnotics
50 min
Remifentanil
Shafer SL. Varvel JR: Pharmacokinetics. Pharmacodynamics, and rational opioid selection. Anesthesiol. 74:53-63,1991
Context-Sensitive Half Time: Opioids and Hypnotics
H Z D S
and Inhalants
Remifentanil
50 min
Shafer SL. Varvel JR: Pharmacokinetics. Pharmacodynamics, and rational opioid selection. Anesthesiol. 74:53-63,1991
Philip, Gas Man 2008
Computer simulation can explain what we observe
during clinical anesthesia and can help us to plan and create
effective clinical techniques
Simulation Example - Desflurane
FGF Comparison High FGF
5 L/min O2 Progressively increase vaporizer setting
Low FGF 1 L O2 /min Air + O2 Set vaporizer to 18% Watch, wait, Readjust when circumstances merit
Both techniques are after IV induction and secure airway
$7.80 for $0.75 in body
$2.90 for $0.75 in body
Economic advantage of low solubility If expired is close to inspired, then when we lower FGF the expired gas that the patient breaths contains enough anesthetic to not lower the inspired concentration much. Thus, low solubility promotes low FGF Low FGF promotes cost saving
Calculating cost of anesthesia
Fresh Gas Flow, Vaporizer Setting, cost per mL of anesthetic liquid, liquid/vapor volume ratio, and anesthetic administration duration together determine cost of anesthetic administered.
Cost = product of all these
Sevoflurane VIMA1 with VCI2 1 VIMA = Volatile induction and Maintenance Anesthesia
2 VCI = Vital Capacity (single, deep breath) Induction This requires that you supply very high (~ 8%) inspired concentration throughout each inspiration for the first few breaths. Gas Man shows how and why this works.
Philip BK, Lombard LL, Roaf ER, Drager LR, Calalang I, Philip JH. Comparison of Vital Capacity Induction with Sevoflurane to Intravenous Induction with Propofol for Adult Ambulatory Anesthesia. Anes Analg 1999; 89:623-627.
Agent Monitor Graph
Gas Man
Graph
Superimpose
Inhaled anesthetics have a special place in anesthesia care
Sometimes they can be used by themselves with nothing else
As long as we keep FGF low they are very inexpensive
$0
$10
$20
$30
0 1 2 3 4 5 6
Hourly Cost US
FGF L/min
Isoflurane
Desflurane
Sevoflurane
Gas Man 2008 Analysis
Thank you [email protected]
For BWH employees, the CE number for this lecture is 322799
End