Science and art in
Inhaled Anesthetic
Delivery Systems
Dr Khushboo Bairwa
Inhalational Anesthetics
Inhalational Anesthetics: Inhalational anesthesia
refers to the delivery of gases or vapors to the
respiratory system to produce anesthesia.
UPTAKE AND DISTRIBUTION
Goal:
To develop and maintain a satisfactory partial pressure or
tension of anesthetic at the site of anesthetic action in brain.
Brain with its high perfusion per gram rapidly equilibrates
with anesthetic partial pressure in blood.
Balance between the delivery of anesthetic and its removal
by uptake or metabolism determines FA/FI ratio at any given
time after administration of inhaled anesthetic.
The rate of rise of alveolar concentration (FA) toward inspired
concentration (FI) or FA/FI ratio determines speed of
induction of anesthesia
UPTAKE AND DISTRIBUTION
OF VOLATILE ANESTHETICS
KEY POINT:
• Alveolar partial pressure (FA) governs the
partial pressure of volatile anaesthetic in all
body tissues: all must approach and ultimately
equal alveolar partial pressure.
• Equilibration occurs rapidly between alveolar
& brain anaesthetic partial pressure.
• Therefore Alveolar concentration is ultimately
the principal factor in determining the onset
of action.
Nitrous oxide
1.0
Desflurane
Sevoflurane
Isoflurane
Halothane
0.5
FA/F1
0
0 10 20 30
Anesthesia administration (min)
Anesthetic Uptake Factors :
Three factors determine anesthetic uptake:
solubility (λ),
cardiac output (Q),
alveolar-to-venous partial pressure difference
(Pa - Pv).
Uptake = λ × Q × (Pa - Pv) /barometric
pressure
Factors affecting Uptake and distribution of inhalational agents
Alveolar ventilation
Cardiac output
MAC
Blood-gas partition co-efficient
Concentration effect
Second gas effect
Diffusion hypoxia
Alveolar Ventilation
Increased alveolar ventilation results in a faster rise
in FA and therefore Fb will also rise more quickly,
reducing the onset of anesthesia time. This rate of
rise is dependent upon minute ventilation and FRC.
The greater the FRC, the slower the rise in FA,
therefore, if minute ventilation is increased, the
tension in alveolar air and arterial blood will rise
more quickly lung wash in.
Alveolar Ventilation
The effects of the rate of respiration, to speed or slow
induction, are transient for gasses such as N2O which are
poorly soluble in blood, and thus equilibrate quickly
The minute volume of ventilation has a significant effect on the
highly soluble agents, such as methoxyflurane or diethyl-ether.
Hyperventilation will decrease CBF, and this tends to offset the
increased rise of FA/FI .
Effect of cardiac output
A higher cardiac output removes more volatile
anaesthetic from the alveoli and hence lowers the
alveolar partial pressure of the gas. It will take longer
for the gas to reach equilibrium between the alveoli
and the brain.
Therefore, a high cardiac output prolongs induction
time.
Minimum Alveolar Concentration
Eger 1969
This is defined as the minimum alveolar
concentration at steady-state that prevents reaction
to a standard surgical stimulus (skin incision) in 50%
of subjects at 1 atmosphere.
MAC awake is the alveolar concentration when 50%
of persons will awake to vocal stimulus.
Anesthetic potency is measured in MAC
Factors affecting MAC
Physiological and metabolic factors
Infancy and childhood ↑
Neonatal period and old age ↓
Pregnancy ↓
Hyperthermia ↑
Hypothermia ↓↓
Hyperthyroidism ↑
Hypothyroidism ↓
Hypernatraemia ↑
Pharmacological factors
Catecholamines and sympathomimetics ↑
α2 agonists ↓
Sedatives ↓↓
Opioid analgesics : acute use ↓ chronic use ↑
Alcohol : acute intake ↓ chronic intake ↑
Amphetamines acute dosage ↑↑↑ chronic dosage ↓
Lithium ↓
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
Or it can be defined as the relative
concentrations of anesthetic for two
phases when the partial pressure of two
phases is equal.
oil : gas partition co-efficient :
It indicates the amount of gas that is soluble in oil
phase. It is a measure of lipid solubility of anaesthetic.
Meyer-Overton hypothesis :which demonstrated that
the potency (expressed as, MAC) of an anaesthetic
agent increased in direct proportion to its oil: gas
partition coefficient .
This led to the interpretation that the site of action of
general anesthetics was the lipid bilayer of nerve
membranes.
Blood – gas partition co-efficient:
The solubility of a gas in liquid is given by its Ostwald
solubility coefficient. This represents the ratio of the
concentration in blood to the concentration in the
gas phase .
It is a measure of solubility in the blood.
Lower the blood: gas co-efficient faster the induction
and recovery – Nitrous oxide.
Higher the blood: gas co-efficient slower induction
and recovery – Halothane.
BLOOD GAS PARTITION CO-EFFICIENT
Blood – gas partition co-efficient:
Isoflurane for example has a blood/gas partition
coefficient of 1.36. Thus if the gas is in equilibrium
the concentration in blood will be 1.36 times higher
than the concentration in the alveoli.
SUMMARY
(1) Inspired gas (Fi): (2) Alveolar gas (FA):
1- FGF rate.
DELIVERY:
2- Absorption by breathing
circuit. 1- Concentration.
3- Volume of breathing circuit. 2- Minute Ventilation.
UPTAKE:
(3) Arterial concentration 1- Blood gas solubility.
(Fa): 2- Alveolar blood flow.
V/Q mismatching. 3- Tissue uptake.
Blood – gas partition co-efficient:
Lower B:G coefficients are seen with
Haemodilution
Obesity
Hypoalbuminaemia
starvation
Higher coefficients are seen in:
Adults versus children
Hypothermia
Postprandial
concentration effect
The concentration effect states that with higher
inspired concentrations of an anaesthetic, the rate of
rise in arterial tension is greater it reduces the onset
time.
N2O has a low blood: gas partition coefficient and
therefore a rapid onset and offset of action.
N2O is about 20 times more soluble than O2 and N2.
The second gas effect
The second gas effect usually refers to nitrous oxide
combined with an inhalational agent. Because
nitrous oxide is not soluble in blood, its' rapid
absorption from alveoli causes an abrupt rise in the
alveolar concentration of the other inhalational
anaesthetic agent.
Diffusion hypoxia
First described by Fink in 1955.
The elimination of a poorly soluble gas, such as N2O, from
the alveoli may proceed at as greater rate as its uptake,
(The volume of N2O entering the alveolus is greater than
the volume of N2 entering the pulmonary capillary blood.),
there by adding as much as 1 l/min to alveolar air. This gas
effectively dilutes alveolar air, and available oxygen, so
that when room air is inspired hypoxia may result.
UPTAKE AND DISTRIBUTION
Alveolar to venous anesthetic gradient depends on
tissue uptake.
Tissue uptake:
1. Tissue solubility (tissue/blood partition coefficient)
2. Tissue blood flow
3. Arterial to tissue anesthetic partial pressure
difference
UPTAKE AND DISTRIBUTION
Tissue Groups: Three tissue groups form depots for anesthetic
within the body.
Vessel rich group (VRG) : Brain, heart, splanchnic bed, liver,
kidney and endocrine
Equilibrates with blood in 4-8 minutes
Muscle group (MG) : Muscle and skin
Equilibrates with blood in 2-4 hours
Fat group (FG) : Equilibration: 70-80 min for N2O
30 hours for sevoflurane
Vessel poor group (VPG)) : Bone , cartilage, ligaments,
tendons-no uptake
RECOVERY FROM ANESTHESIA
Recovery correlates with fall in alveolar concentration
Solubility: Low solubility →Rapid recovery
Desflurane>Sevoflurane>Isoflurane
Duration of anesthesia
MAC awake: Varies with different anesthetics
MAC awake of N2O> Inhaled anesthetics
Lower MAC awake: More amnestic the agent
Metabolism: Alveolar washout of halothane more rapid than
enflurane
Residual gases in the anesthetic circuit.
Mechanism of action
Recent research suggests that inhalational agents may act on specific
membrane proteins and alter ion flux or receptor function.
Interruption of Neuronal Transmission: the action of the inhaled
agents on synaptic transmission may be due to alteration of either,
a. presynaptic transmitter release
b. reuptake of transmitter following release
c. binding to post/pre-synaptic receptor sites
d. membrane conductance following receptor activation
GABA A receptors - potentiation of GABA receptor occurs with
halothane, isoflurane and sevoflurane.
Glycine receptors potentiation
Mechanism of action
Two-pore-domain potassium channels – these are
activated by volatile and gaseous anaesthetics and
may modulate membrane excitability
Other possible targets may include NMDA receptors,
HCN channels and some subtypes of the sodium
channel.
Systemic effects
CENTRAL NERVOUS SYSTEM
↓ EEG wave frequency and ↑ amplitude
Higher conc. (2 MAC): Isoelectric EEG and burst
suppression
Protect against ischemia by ↓ CMRO2
Cerebral vasodilation leading to ↑ ICP
Enflurane and sevoflurane to a lesser extent can
cause convulsions
Dose related ↓ amplitude and ↑ latency of evoked
potentials
PULMONARY EFFECTS
Respiratory depression leading to ↓ MV and ↑pCO2:
: Desflurane>Isoflurane>Sevoflurane
Depress ventilatory responses to hypercarbia and
hypoxia in a dose dependent manner
Sevoflurane agent of choice for inhalation induction.
Halothane probably the most potent bronchodilator
Preferential dilatation of distal airways as compared
to proximal airways.
PULMONARY EFFECTS
Action mediated through several complex
mechanisms leading to ↓ intracellular Ca++
Depress mucociliary clearance and function of type II
alveolar cells.
Attenuate hypoxic pulmonary vasoconstriction (HPV)
in vitro.
Modest inhibitory effects on HPV in vivo leading to
shunting and decreased oxygenation.
CARDIOVASCULAR EFFECTS
Systolic and Diastolic Function:
Dose related negative inotropic effect
Halothane=Enflurane>Isoflurane=Desflurane=Sevoflu
rane
Dose related prolongation of isovolemic relaxation,
early LV filling and filling associated with atrial systole
CARDIOVASCULAR EFFECTS
Systemic Hemodynamics:
Depress baroreceptors.
No change in CI except halothane (↓CI)
Desflurane 1 MAC→1.5 - 2 MAC ↑ HR and BP
Sevoflurane 1 MAC→1.5 - 2 MAC ↓ HR or no
change
Isoflurane –Intermediate effect
All cause concentration related decreases in BP
Sevoflurane, desflurane, isoflurane→↓ SVR
Halothane, enflurane→ Myocardial depression
CARDIOVASCULAR EFFECTS
Epinephrine induced arrhythmias:
Halothane arrythmogenic ,Other agents safer
Coronary Steal:
Coronary vasodilataion with isoflurane may cause
detrimental redistribution of coronary blood flow
away from ischemic myocardium with hypotension
leading to coronary steal
No coronary steal if hypotension avoided
UTERINE AND FETAL EFFECTS
Dose dependent relaxation of uterus
Increased blood loss during Caesarean Delivary.
Lower concentrations (=0.5MAC safer)
Inhaled anesthetics cross placenta
Higher concentration: Fetal cardiovascular
depression
Reduction of CBF and O2 delivery to brain
NEUROMUSCULAR SYSTEM
Dose dependent muscle relaxation
Can cause sufficient relaxation to permit
endotracheal intubation and facilitate intra
abdominal procedures
Potentiate the action of muscle relaxants
Non depolarizers > Depolarizers
All trigger MH; Halothane worse
Inhaled Anesthetic Delivery Systems
• Anesthesia machine
• Vaporizers
• Anesthetic breathing circuit
• Ventilator
• Scavenging system
Anesthesia Machine
Generic Anesthetic Machine
• The pressures within the anesthesia machine
can be divided into three circuits
– High-pressure
– Intermediate-pressure
– Low-pressure circuit
Gas supply
Pipeline Cylinder
Vaporizers
A vaporizer is a device
that changes a liquid
anaesthetic agent into its
vapor and adds a
controlled amount of
that vapor to the fresh
gas flow or the breathing
system.
VAPORIZERS
• Vapor Pressure :The pressure of the vapor resulting from
evaporation of a liquid in a closed container.
• Latent Heat of Vaporization
– calories required to change 1 g of liquid into vapor without a
temperature change
• Specific Heat
– calories required to increase the temperature of 1 g of a substance by
1°C.
• Thermal Conductivity a measure of how fast a substance
transmits heat. High thermal conductivity is desirable in
vaporizer construction.
Vapor Pressure and Boiling Point
All inhaled anesthetics liquid at 20 0C
Vapor Pressure: Pressure exerted by the molecules
of the vapor phase at equilibrium of molecules
moving in and out of liquid phase
Vapor Pressure dependent on temperature and
physical characteristics of liquid, independent of
atmospheric pressure
↑ Temperature→↑ Vapor Pressure
Boiling Point: Temperature at which vapor pressure
equals atmospheric pressure
Vapor pressure versus temperature curves
for desflurane, isoflurane, halothane,
enflurane, and sevoflurane
The vapor pressure curve for desflurane is steeper and shifted to higher vapor
pressures compared with the curves for other contemporary inhaled anesthetics.
Physiochemical properties of inhaled
anaesthetics
MAC BP(0C) VP (200C)
Halothane 0.77 50.2 241 mmHg
Enflurane 1.7 56.2 175 mmHg
Isoflurane 1.15 48.5 238 mmHg
Sevoflurane 2.0 58.5 160 mmHg
Desflurane 6.0 23 664 mmHg
N2O 104
Xenon 71
Historical vaporizers
Historically, ether (the first volatile agent) was first
used by John Snow's inhaler (1847) . Ether then
slowly made a revival (1862–1872) with regular use
via Curt Schimmelbusch's "mask", a narcosis mask for
dripping liquid ether.
Modern vaporisers:There are generally two types of
vaporisers:
Plenum
Drawover.
The plenum vaporizer
is driven by positive pressure from the anaesthetic machine, and is
usually mounted on the machine.
The performance of the vaporizer does not change regardless of
whether the patient is breathing spontaneously or is mechanically
ventilated.
The plenum vaporiser works by accurately splitting the incoming gas
into two streams.
One of these streams passes straight through the vaporizer in
the bypass channel.
The other is diverted into the vaporising chamber. Gas in the
vaporising chamber becomes fully saturated with volatile anaesthetic
vapour. This gas is then mixed with the gas in the bypass channel
before leaving the vaporizer.
Variable-bypass vaporizer
The plenum vaporiser
The performance of the plenum vaporiser depends extensively
on the saturated vapour pressure of the volatile agent.
Saturated vapour pressure for any one agent varies with
temperature, and plenum vaporizers are designed to operate
within a specific temperature range.
They often have a metal jacket weighing about 5 kg, which
equilibrates with the temperature in the room and provides a
source of heat.
In addition, the entrance to the vaporising chamber is controlled
by a bimetallic strip, which admits more gas to the chamber as it
cools, to compensate for the loss of efficiency of evaporation
Ohmeda Tec-type vaporizer. At high temperatures, the vapor pressure inside
the vaporizing chamber is high. To compensate for the increased vapor
pressure, the bimetallic strip of the temperature-compensating valve leans to
the right, allowing more flow through the bypass chamber and less flow
through the vaporizing chamber. The net effect is a constant vaporizer output.
In a cold operating room environment, the vapor pressure inside the
vaporizing chamber decreases. To compensate for the decreased vapor
pressure, the bimetallic strip swings to the left, causing more flow through the
vaporizing chamber and less through the bypass chamber. The net effect is a
constant vaporizer output
Drawover vaporizers
The drawover vaporiser is driven by
negative pressure developed by the patient, and
must therefore have a low resistance to gas flow.
Its performance depends on the minute volume of
the patient: its output drops with increasing minute
ventilation.
The drawover vaporiser may be mounted either way
round, and may be used in circuits where
re-breathing takes place, or inside
the circle breathing attachment.
Drawover vaporisers
Drawover vaporisers typically have no temperature
compensating features.
The output concentration from a drawover vaporiser
may greatly exceed that produced by a plenum
vaporiser, especially at low flows..
Despite its drawbacks, the drawover vaporiser is
cheap to manufacture and easy to use.
Dual-circuit gas–vapour blender
It was created specifically for the agent desflurane. Desflurane
boils at 23.5 ºC, which is very close to room temperature. This
means that at normal operating temperatures, the saturated
vapour pressure of desflurane changes greatly with only small
fluctuations in temperature.
A desflurane vaporiser (e.g. the TEC 6 produced by
Datex-Ohmeda) is heated to 39C and pressurised to 200kPa (and
therefore requires electrical power).
It evaporates a chamber containing desflurane using heat, and
injects small amounts of pure desflurane vapour into the fresh
gas flow. A transducer senses the fresh gas flow.
ANESTHETIC CIRCUITS
• Deliver oxygen and anesthetic gases to the
patient
• Eliminate carbon dioxide
– adequate inflow of fresh gas
– carbon dioxide absorbent
Mapleson Systems
Mapleson Systems
Factors influence carbon dioxide rebreathing
(1) the fresh gas inflow rate
(2) the minute ventilation
(3) the mode of ventilation (spontaneous or controlled),
(4) the tidal volume
(5) the respiratory rate
(6) the inspiratory to expiratory ratio
(7) the duration of the expiratory pause
(8) the peak inspiratory flow rate
(9) the volume of the reservoir tube
(10)the volume of the breathing bag
(11)ventilation by mask
(12)ventilation through an endotracheal tube
(13)the carbon dioxide sampling site.
The Bain circuit
• a modification of the Mapleson D system
• spontaneous and controlled ventilation.
The Bain circuit
• Exhaled gases in the outer reservoir tubing
add warmth to inspired fresh gases
• unrecognized disconnection or kinking of the
inner fresh gas hose
• The fresh gas inflow rate necessary to prevent
rebreathing is 2.5 times the minute ventilation
Components of the Circle system
APL, adjustable pressure limiting; B, reservoir bag; V, ventilator
Circle Breathing System
• A circle system can be semiopen, semiclosed,
or closed, depending on the amount of fresh
gas inflow
– Semiopen system has no rebreathing and requires
a very high flow of fresh gas
– Semiclosed system is associated with rebreathing
of gases
– Closed system is one in which the inflow gas
exactly matches that being consumed by the
patient
Circle Breathing System
• Rules to prevent rebreathing of carbon
dioxide in a traditional circle system
– Unidirectional valves must be located between
the patient and the reservoir bag on the
inspiratory and expiratory limbs of the circuit.
– The fresh gas inflow cannot enter the circuit
between the expiratory valve and the patient.
– The overflow (pop-off) valve cannot be located
between the patient and the inspiratory valve.
Circle Breathing System
• Advantages
– stability of inspired gas concentrations,
– conservation of respiratory moisture and
heat,
– prevention of operating room pollution
• Disadvantage
– complex design
SCAVENGING SYSTEMS
• The collection and the subsequent removal of
vented gases from the operating room
• Components
(1) the gas-collecting assembly
(2) the transfer means
(3) the scavenging interface
(4) the gas-disposal assembly tubing
(5) an active or passive gas-disposal assembly
Components of a scavenging system. APL valve, adjustable
pressure limiting valve
Anesthesia Gas Monitoring
Side stream Infrared Multi-gas Analyzer :
Principles Respiratory gases can be potentially analyzed
according to different measuring principles.
Dispersive infrared (DIR) method: uses a single optical
filter and either a prism or a diffraction grating to separate
the component wavelengths for each agent
Non-dispersive infrared (NDIR) method :the non-dispersive
technique incorporates multiple narrow-band optical filters
through which the infrared emission is passed to determine
which gas is present in the mixture.
Non-dispersive infrared (NDIR) method
This measuring principle is based on the fact that many gases
absorb infrared energy at a wavelength specific to the gas being
analyzed.
In modern analyzers, the gas sampling rate from the breathing
circuit is in the range of 50 mL/min to 250 mL/min.
The sample gas flow is directed, using a cuvette, or sample cell,
between the infrared emitter, an optical filter, and the infrared
detector, which outputs a signal proportional to the remaining
infrared energy not absorbed by the gas.
eg. Datex TPX gas analyzer (GE Healthcare, Helsinki, Finland):
Andros/LumaSense 4800 anesthesia gas analyzer
Artema AION anesthesia gas analyzer
Dräger ILCA2 infrared anesthesia gas analyzer
TPX Analyzer Schematic
Functional and usability limitations.
First issue is the relatively high sample flow rate (which can
exceed 200 mL/min) required to achieve an acceptable response
time of less than 300ms.
The high sample flow rate impedes the use of these analyzers
with infants
The second issue :It is essential that water vapor, liquid water,
and patient secretions be controlled and prevented from reaching
and damaging the measuring instrument, or influencing the
accuracy of the measurements.
This task is usually accomplished in the specific design of the
sample line and/or with use of a water trap on the instrument side.
State-of-the-art Sidestream Respiratory Gas
Analysis
(Infrared Side stream Analyzer) family of sensors developed by
PHASEIN AB,
The ISA sidestream multi-gas analyzer is a 9-channel NDIR type gas
analyzer measuring at 4–10 μm spectra with compensation for
pressure, temperature and the broadening effects on CO2.
It is very compact (23 x 64 x 39 mm), weighs only 70 g, features
low gas sample flow (50 mL/min) and integrates a sampling pump, a
zeroing valve and a flow controller.
PHASEIN ISA multi-gas
analyzer
Sidestream Respiratory Gas Analysis
This analyzer is complemented by a sample line design that
totally eliminates the need for a traditional water trap by
removing both water and water vapor from the line .
Micro-Optical Rotor Technology:
spectrometer incorporating a rotating filter wheel offers
the potential to be reduced in size and weight if the filter
elements could be made smaller and be spaced closer
together.
PHASEIN facilitates the use of a miniature micro-optical
rotor integrating a six pole magnet and a number of
circumferentially arranged infrared narrow-band optical
filters.
The rotor is driven by a software controlled stator coil .
Micro-Optical Rotor Technology
This arrangement facilitates full software control of the
micro-optical rotor and its synchronization with the
signal processing elements of the photospectrometer.
The Micro-Optical
Rotor
SIMULATION
OF INHALATIONAL ANAESTHESIA
Simulation is the imitation of the operation of a real-world
process or system over time.
Simulations are very important in the aircraft industry
where they have been used for many years to train pilots on
the ground, thus preventing damage to aeroplanes and loss
of life.
The simulation allows the disaster to be repeated many
times for the anesthetist to develop skills under optimum
interactive learning conditions, without endangering
patients
The act of simulating something first requires that a model
be developed; this model represents the key characteristics
or behaviors of the selected physical or abstract system or
process.
SIMULATION
OF INHALATIONAL ANAESTHESIA
The model represents the system itself, whereas the
simulation represents the operation of the system over time.
In recent years suitable computers and software tools become
available to make simulation in anesthesia feasible and more
widely available . Gas Man® is a unique computer tool for
teaching, simulating and experimenting with anesthesia uptake
and distribution.
Inhaled Kinetic Model
Measurements confirm model and control care
Setting Inhaled Gas Exhaled Gas Anest het ic Dept h
m
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a
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s
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Compartment s Tissues Venous
Breat hing Lungs Art e ria l
and Vaporizer ( Br a in )
Circ uit Blood Blood
Pat hs
FGF = Fresh Gas Flow CO = Cardiac Out put
VA = Alveolar Ventilat ion
o
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ta
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s
The Model - Compartments and Flows
Vaporizer ------Tissues------
Breathing Brain Fat
Circuit Lungs Mus Venous
VRG
Blood Blood
FGF Alv Cardiac
Fresh (Lung) Output
Gas Vent
Flow
The Model - Return Flows
Breathing
Circuit Lungs Venous
Blood
Measurements they make
Vaporizer Brain
Breathing EEG,
Circuit Lungs BIS, PSI?
HR,BP
Setting Inspired Expired
Gas Man Comparison - September
1 MAC brain Iso, Sevo, Des for 1.5 hours
Use the same FGF, VA and CO for all drugs
Start with higher flows for the first few
minutes
Perform a Wake up comparison
Measure time for VRG to reach 0.33 MAC
Measure time for VRG to reach 0.2 MAC
Time zero
After 1.5 hrs
At 0.33 MAC
At 0.2 MAC
GASMAN
Gas Man is an extremely well-written program... [it] permits
unlimited simulations in which the user can alter a wide variety
of parameters to illustrate the different principles of anesthetic
gas uptake...“
The Gas Man computer model graphically simulates the
pharmacokinetics of anesthesia administration.
It shows the time course of anesthesia uptake in each
compartment of the body - lungs, heart, brain - as well as the
breathing circuit and vaporizer.
Gas Man is the answer for teaching, experimenting and planning
anesthesia administration on the computer before trying it in the
operating room