Guedel’s Signs of Anesthesia
Stage I: Amnesia occurs with induction and LOC, no pain remembrance,
lightest stage, patient still feels pain
Stage II: Delirium with period of excitement, muscle movement, irritability,
and pupils dilated, disconjugate gaze, increased RR and HR, the deliriums are
usually masked, risk of laryngospasm, want room quiet with as little
manipulation of patient as possible
Stage III: Surgical plane (target depth), fixed gaze of eyes, constricted pupils
and no response to pain
StageIV : Overdose, absent or shallow RR, hypotension, profound CV
compromise
Characteristics of General Anesthesia
reversible loss of consciousness
analgesia
amnesia
altered state
muscle relaxation
Definitions
FGF: fresh gas flow is determined by the vaporizer and flowmeter settings
FI: inspired gas concentration is determined by FGF, breathing circuit volume,
and circuit absorption
FA: alveolar gas concentration is determined by uptake, ventilation, the
concentration effect and second gas effect
Fa: arterial gas concentration is affected by ventilation/perfusion mismatch
Meyer-Overton Rule
Anesthetic potency correlates with their lipid solubility
Implies when a specific hydrophobic region is occupied-anesthesia results
Anesthetics act nonselectively on neuronal membranes
Signs of Anesthesia
Anesthesia depth can be assessed by:
lack of movement in non-paralyzed state
respiratory rate and pattern
respiratory depression(ETco2 and VE)
eye signs
BP and Pulse values
BIS analysis
FI/Inspired Gas Concentration
Inspired gas composition depends on :
Fresh gas flow and rate
Volume of breathing system
absorption of machine circuit
FA/Alveolar Concentration
FA is determined by Uptake, Ventilation, Concentration/Second gas effect
Uptake: [(λ)x (Q)x(PA-Pv)]/Barometric Pressure
λ= Solubility
Q= cardiac output
PA-Pv= alveolar venous partial pressure difference
Factors that affect anesthetic uptake
Solubility in the Blood
The more soluble the anesthetic agent is in the blood the more the
drug goes into the body
the more soluble the AA(anesthetic agent) is in the blood the slower
the patient becomes anesthetized
Insoluble agents have a slower uptake by the blood so a faster
induction
Solubility is expressed as Partition Coefficients: ratio that describes the
solubility of gas in blood/brain/liver/kidney/muscle/fat
Anesthetic
BloodGas
BrainBlood
LiverBlood
KidneyBlood
MuscleBlood
FatBlood
Desflurane
0.45
1.3
1.4
1.0
2.0
27
Nitrous Oxide
0.47
1.1
0.8
1.2
2.3
Sevoflurane
0.65
1.7
1.8
1.2
3.2
48
Isoflurane
1.4
1.6
1.8
1.2
2.9
45
Enflurane
1.8
1.4
2.1
1.7
36
Halothane
2.5
1.9
2.1
1.2
3.4
51
Ether
12
2.0
1.9
0.9
1.3
5
Methoxyflurane
15
1.4
2.0
0.9
1.6
38
Solubility Tibidts
Higher the blood/gas partition coefficients(blood solubility of an anesthetic),
increase solubility, increase uptake of gas by the blood, slower uptake by the
brain
Blood solubility determines the speed at which the partial pressure of the
agent builds up in the blood and then the brain. It also determines the speed
at which an agent is eliminated from the blood and brain
POTENCY is directly related to LIPID SOLUBILITY
Cardiac Output(Q)/Alveolar Blood Flow
Decreased blood flow through the lungs, less anesthetic taken up by
the blood therefore the alveolar concentration increases
Highly soluble agents are more affected
Increase in CO, more blood travels through the lungs, thereby
removing more anesthetic from the gas phase, decrease alveolar
concentration and slower FA increase
PA-Pv/Partial Pressure difference in Alveolar gas and Venous blood
Depends on tissue uptake
Transfer of anesthetic from blood to tissue is determined by:
tissue solubility
tissue blood flow
arterial blood/tissue partial pressure difference
Concentration and Second gas effects on FA/Alveolar Concentration
Concentration Effect: increasing the inspired concentration can increase
alveolar concentration
Fick’s law of diffusion explains the concentration effect!
Increasing the concentration will speed the rate of equilibrium of the agent
Uptake declines as tissues become saturated, plateaus in about an hour
Second Gas Effect: Uptake of large volumes of a first or primary gas(usually
N2O) from alveoli increases the rate of increase in alveolar concentration of a
second gas given at the same time
The factors that are responsible for the concentration effect also control the
second gas effect: increasing ventilation and concentration
Fa/Arterial Concentration
Ventilation/Perfusion Mismatch will increase the alveolar-arterial difference
Metabolism/Elimination
Biotransformation: cytochrome P-450(CYP)
Transcutaneous: diffusion through the skin, very insignificant
Exhalation: most important
increasing ventilation and FGF
low anesthetic circuit volume
decreased solubility
increase cerebral blood flow
Physiologic Effects of Inhalational Anesthetics
Respiratory
Most agents are irritants, especially Desflurane, Sevoflurane and
Halothane are nonpungent
Tidal Volume is decreased
Respiratory rate is increased
Minute ventilation is decreased
Chemoreceptor response to CO2 is blunted
Apneic Threshold, the highest PaCO2 at which a patient remains apneic, is
raised
PCO2 raised during spontaneous ventilation, CO2 retention
All are great bronchodilators by direct action on smooth muscle
Good for bronchospasm, Status Asmaticus
Physiologic Effects of Inhalational Anesthetics
CVS
All cause cardiac depression, causes an increased rate of
concentration rise, which can cause even more cardiac depression-Halo=Enfl>Des=Iso=Sevo
Desflurane >Isoflurane can cause initial tachycardia, Halothane
reduces HR, Sevo and Enf are nuetral
Cardiac Output is fairly well preserved--Des and Iso>Sevo
Baroreceptor reflexes are preserved All inhaled agents are smooth
muscle relaxants
All cause vasodilation(decreased SVR) leading to hypotension except
Nitrous Oxide
Physiologic Effects of Inhalational Anesthetics
CVS
Coronary Dilators--Iso>Sevo=Des
Arrhythmias can be induced by the agents, Halothane the
worst>enfl>iso>des
potentiates catecholamine induced arrhythmias, sensitizes the heart
to the arrhythmogenic effects of epinephrine
Physiologic Effects of Inhalational Anesthetics
CNS
Increased Cerebral Blood flow, auto regulation of cerebral blood is
impaired
Increased ICP due to increased blood flow and induced
hypercapnea(prevented by hyperventilation)
Ventilatory responses are blunted due to sleep apnea, narcotics and
benzos
EEG--decreased Amplitude, increased Latency
Physiologic Effects of Inhalational Anesthetics
CNS
Intraoperative Awareness is estimated at 0.15% of all cases--Risk factors
include: age, gender, substance abuse/use, underlying medical conditions,
ALSO
Paralytic use
Type of surgery
Poor Machine maintenance
Physiologic Effects of Inhalational Anesthetics
KIDNEY
renal effects almost always transient and renal function usually
returns to normal after stopping anesthesia
does dependent decreases in renal blood flow, GFR, Urine output
Sevo potentially produces Compound A which is renal toxin but not
really shown in humans
Anesthetized patients are heavily dependent on renin-angiotnesin
system to regulate volume status
Most issues with output caused by inhalational can be abolished with
preoperative hydration
Physiologic Effects of Inhalational Anesthetics
LIVER
Hepatic blood flow decreased, drug metabolism slowed, so agents are
hepatotoxic
Most agents casue a transient increase in LFT’s
Minimum Alveolar Concentration(MAC)
MAC is the alveolar concentration of an inhalational agent at which 50% of
patients do not move in response to skin incision or similar noxious stimuli
Alveolar concentration is used as the measure of anesthetic concentration
because the partial pressure in the aveolus quickly equilibrates with that in the
blood and brain because of the brains high blood flow
MAC is INVERSELY related to POTENCY
The oil:gas partition coefficient correlates most closely with MAC
oil:gas partition coefficient provides a quantitative measure of lipid solubility
ED95= 1.3 MAC of any volatile anesthetic has been found to prevent
movement in 95% of patients
Minimum Alveolar Concentration(MAC)
MAC-awake= MAC of volatile anesthetic at which a patient will open their eyes
(0.3-0.4 MAC)
MACBAR-MAC necessary to block the sympathetic response to noxious
stimuli=1.5
ISOFLURANE(Forane)
Advantages: cheap, very soluble-slow to leave pt, cardio-protective
Disadvantages: Solubility-high residual at end of case, requires more skill to
use(timing), risk of awareness, may slow OR turnover, can’t be used for gas
induction
Blood:Gas coefficient= 1.4
DESFLURANE(Suprane)
Advantages: Insoluble, fast on and off, easy to use, faster turnover in OR, low
residual at end of case, patient more awake afterward/less hangover feel
Disadvantages: pungent smell, cost, SNS stimulation, can’t be used for
induction, careful with irritable airways, asthma, smokers, requires special
vaporizer
Blood:Gas coefficient= 0.45
SEVOFLURANE(Sevo)
Advantages: non-pungent smell, good for induction, less SNS activation,
cardio-protective, can be used with N2O to decrease need of Sevo, quicker
wakeup
Disadvantages: cost, solubility, compound A
Blood:Gas coefficient= .65
Nitrous Oxide (N₂O)
Only inorganic anesthetic gas in clinical use, also called LAUGHING GAS
colorless, pleasant smell, non-explosive, non-flammable
usually used in combination with inhaled gas or with O2
Blood:Gas coefficient= 0.47
No respiratory irritation, good for induction
Cheap
Low solubility
Nitrous Oxide (N₂O)
Minimal CV effects, slight myocardial depression usually offset by the
SNS(increased endogenous catecholamines)
Increased RR, decreased TV, reduced ventilatory response to CO2 and
hypoxia(Hypoxic Drive)
NOT a triggering agent for MH
Major drawback is the diffusion of N2O into closed air spaces
N2O is 30 more soluble than N2, both are insoluble
So nitrous moves more quickly into the space because of the need to supply
high concentrations of N2O
Nitrous Oxide (N₂O)
The space will expand, increasing volume , increasing pressure or both
Avoid N2O use in bowel cases/obstruction, pnuemothorax/blebs, venous air
emboli, middle ear surgery, some eye surgeries,
Careful use in long cases with Endotracheal tubes
CNS: not potent, but great analgesic
35%= maximum analgesia
75%= 50% patients are unaware of surroundings
60% and over= increase CBF and ICP
Nitrous Oxide (N₂O)
TOXICITY: N2O activates methionine synthetase by oxidizing the cobalt in Vit
B12 and can affect DNA, spontaneous abortions in women working in the
OR/dental offices (Unproven)
Malignant Hyperthermia (MH)
Fulminant HYPERMETABOLIC state of skeletal muscle induced by volatile
anesthetics, succinylcholine, and, perhaps by stress and exercise
The release of excessive calcium from the sarcoplasmic reticulum(SR) is
believed to be the primary pathophysiologic event in MH
Ryanodyne receptor (RYR1) is thought to be commonly involved
Increased ETco2, increased heart rate and temperature
Metabolism
Drug
Liver
Enzyme
Kidney
Halothane
25%
CPY2E1
Minimal
Sevoflurane
5%
CPY2E1
<1%
Isoflurane
0.025%
CPY2E1
None
Desflurane
Minimal
CPY2E1
None
Enflurane
<1%
CPY2E1
2%
MAC Values
Agent
MAC %
Vapor Pressure
Nitrous Oxide
105
-
Halothane
0.75
273
Isoflurane
1.2
240
Desflurane
6.0
681
Sevoflurane
2.0
160
Tissue Group Characteristics
Characteristic
Vessel Rich
Muscle
Fat
Vessel Poor
Percent Body
Mass
10
50
20
20
Percent
Cardiac Output
75
19
6
0