nhalation Anesthetics nhalation Anesthetics

nhalation Anesthetics nhalation Anesthetics

Exposure to the pulmonary circulation allows a Exposure to the pulmonary circulation allows a
more rapid appearance in arterial blood than more rapid appearance in arterial blood than
intravenous administration intravenous administration
Pharmacokinetics (how a body affects a drug) Pharmacokinetics (how a body affects a drug)
dose, tissue concentration, elapsed time dose, tissue concentration, elapsed time
Pharmacodynamics (how a drug affects a Pharmacodynamics (how a drug affects a
body) body) drug action, toxic responses drug action, toxic responses
ontents ontents
Pharmacokinetics of inhalation anesthetics Pharmacokinetics of inhalation anesthetics
Pharmacodynamics of inhalation anesthetics Pharmacodynamics of inhalation anesthetics
linical pharmacology of inhalation anesthetics linical pharmacology of inhalation anesthetics
Nitrous oxide Nitrous oxide
Halothane Halothane
soflurane soflurane
Desflurane Desflurane
Sevoflurane Sevoflurane
Pharmacokinetics Pharmacokinetics
Therapeutic tissue concentration in the Therapeutic tissue concentration in the
central nervous system central nervous system
actors Affecting nspiratory actors Affecting nspiratory
oncentration () oncentration ()
1. resh gas flow rate 1. resh gas flow rate
2. The volume of the breathing circuit 2. The volume of the breathing circuit
3. Any absorption by the machine or breathing circuit 3. Any absorption by the machine or breathing circuit
The higher the fresh gas flow rate The higher the fresh gas flow rate
The smaller the breathing system volume The smaller the breathing system volume
The lower the circuit absorption The lower the circuit absorption
The closer the inspired gas concentration to the fresh The closer the inspired gas concentration to the fresh
gas concentration gas concentration
aster induction and recovery times aster induction and recovery times
actors Affecting Alveolar actors Affecting Alveolar
oncentration (A) oncentration (A)
1. Uptake 1. Uptake
2. Ventilation 2. Ventilation
3. oncentration 3. oncentration
Uptake Uptake
Anesthetic agents are taken up by Anesthetic agents are taken up by
pulmonary circulation during induction pulmonary circulation during induction
A/ < 1 A/ < 1
The greater the uptake The greater the uptake
The greater the difference between A The greater the difference between A
and (the lower the A/ ratio) and (the lower the A/ ratio)
The slower the rate of rise of the alveolar The slower the rate of rise of the alveolar
concentration concentration
The slower of the rate of induction The slower of the rate of induction
actors Affecting Anesthetic actors Affecting Anesthetic
Uptake Uptake
1. Solubility in the blood 1. Solubility in the blood
2. Alveolar blood flow 2. Alveolar blood flow
3. The difference in partial pressure 3. The difference in partial pressure
between alveolar gas and venous blood between alveolar gas and venous blood
Solubility in Blood Solubility in Blood
Partition coefficients: the ratio of the Partition coefficients: the ratio of the
concentration of anesthetic gas in each of two concentration of anesthetic gas in each of two
phases at equilibrium (equal partial pressures) phases at equilibrium (equal partial pressures)
The higher the blood/gas coefficient The higher the blood/gas coefficient
The greater the solubility The greater the solubility
The greater its uptake by pulmonary circulation The greater its uptake by pulmonary circulation
Alveolar partial pressure rises more slowly Alveolar partial pressure rises more slowly
nduction is prolonged nduction is prolonged
Alveolar Blood low Alveolar Blood low
Equal to cardiac output (in the absence of Equal to cardiac output (in the absence of
pulmonary shunting) pulmonary shunting)
ardiac output increases ardiac output increases
Anesthetic uptake increases Anesthetic uptake increases
The rise in alveolar partial pressure slows The rise in alveolar partial pressure slows
nduction is delayed nduction is delayed
Low Low- -output states output states overdosage with soluble overdosage with soluble
agents agents
Myocardial depressant (halothane) Myocardial depressant (halothane) lowering lowering
cardiac output cardiac output positive feedback loop positive feedback loop
The Partial Pressure Difference The Partial Pressure Difference
between Alveolar Gas and Venous between Alveolar Gas and Venous
Blood Blood
Depends on tissue uptake Depends on tissue uptake
actors affecting transfer of anesthetic actors affecting transfer of anesthetic
from blood to tissue: from blood to tissue:
1. Tissue solubility (tissue/blood partition 1. Tissue solubility (tissue/blood partition
coefficient) coefficient)
2. Tissue blood flow 2. Tissue blood flow
3. The difference in partial pressure between 3. The difference in partial pressure between
arterial blood and tissue arterial blood and tissue
Ventilation Ventilation
ncreasing alveolar ventilation ncreasing alveolar ventilation constantly constantly
replacing anesthetic taken up by replacing anesthetic taken up by
bloodstream bloodstream better maintenance of better maintenance of
alveolar concentration alveolar concentration
Ventilation depressant (halothane) Ventilation depressant (halothane)
decrease the rate of rise in alveolar decrease the rate of rise in alveolar
concentration concentration negative feedback loop negative feedback loop
oncentration effect oncentration effect
1. oncentrating effect 1. oncentrating effect
2. Augmented inflow effect 2. Augmented inflow effect
Second gas effect Second gas effect
oncentration oncentration
20
100
80
100
50% uptake
50% uptake
10
40
60
90
20%
80% 67%
11%
X 4 X 6
2
10
32
40
20%
80%
72
100
12
100
12%
72%
actors Affecting Arterial actors Affecting Arterial
oncentration (a) oncentration (a)
Ventilation/perfusion mismatch increase Ventilation/perfusion mismatch increase
the alveolar the alveolar- -arterial difference arterial difference
An increase in alveolar partial pressure An increase in alveolar partial pressure
A decrease in arterial partial pressure A decrease in arterial partial pressure
actors Affecting Elimination actors Affecting Elimination
Elimination Elimination
1. Biotransformation: cytochrome P 1. Biotransformation: cytochrome P- -450 450
2. Transcutaneous loss: insignificant 2. Transcutaneous loss: insignificant
3. Exhalation: most important 3. Exhalation: most important
actors speed recovery actors speed recovery
Elimination of rebreathing, high fresh gas flows, low Elimination of rebreathing, high fresh gas flows, low
anesthetic anesthetic- -circuit volume, low absorption by circuit volume, low absorption by
anesthetic circuit, decreased solubility, high cerebral anesthetic circuit, decreased solubility, high cerebral
blood flow, increased ventilation, length of time blood flow, increased ventilation, length of time
Diffusion hypoxia: elimination of nitrous oxide is Diffusion hypoxia: elimination of nitrous oxide is
so rapid that alveolar O2 and O2 are diluted so rapid that alveolar O2 and O2 are diluted
Pharmacodynamics Pharmacodynamics
General anesthesia: reversible loss of General anesthesia: reversible loss of
consciousness, analgesia, amnesia, some consciousness, analgesia, amnesia, some
degree of muscle relaxation degree of muscle relaxation
All inhalation agents share a common All inhalation agents share a common
machanism of action at molecular level machanism of action at molecular level
The anesthetic potency correlates with The anesthetic potency correlates with
their lipid solubility their lipid solubility
Pharmacodynamics Pharmacodynamics
Anesthetic binding might significantly Anesthetic binding might significantly
modify membrane structure modify membrane structure
Alternations in any one of several cellular Alternations in any one of several cellular
systems: ligand systems: ligand- -gated ion channels, gated ion channels,
second messenger functions, second messenger functions,
neurotransmitter receptors neurotransmitter receptors
GABA receptor, glycine receptor d1 GABA receptor, glycine receptor d1- -
subunit, nicotinic acetylcholine receptors, subunit, nicotinic acetylcholine receptors,
NMDA receptors. NMDA receptors.
Minimum Alveolar oncentration Minimum Alveolar oncentration
MA: the alveolar concentration that MA: the alveolar concentration that
prevents movement in response to a prevents movement in response to a
standardized stimulus in 50% of patients standardized stimulus in 50% of patients
Brain partial pressure Brain partial pressure
1.3 MA prevent movement in 95% of 1.3 MA prevent movement in 95% of
patients patients
0.3 0.3- -0.4 MA is associated with awakening 0.4 MA is associated with awakening
6% decrease in MA per decade of age 6% decrease in MA per decade of age
Nitrous Oxide Nitrous Oxide
The only inorganic anesthetic gas in clinical use The only inorganic anesthetic gas in clinical use
olorless and odorless olorless and odorless
ardiovascular ardiovascular
Depress myocardial contractility Depress myocardial contractility
Arterial BP, O, HR: unchanged or slightly due to Arterial BP, O, HR: unchanged or slightly due to
stimulation of catecholamines stimulation of catecholamines
onstriction of pulmonary vascular smooth muscle onstriction of pulmonary vascular smooth muscle
increase pulmonary vascular resistance increase pulmonary vascular resistance
Peripheral vascular resistance: not altered Peripheral vascular resistance: not altered
Higher incidence of epinephrine Higher incidence of epinephrine- -induced arrhythmia induced arrhythmia
Nitrous Oxide Nitrous Oxide
Respiratory Respiratory
Respiratory rate: Respiratory rate:
Tidal volume: Tidal volume:
Minute ventilation, resting arterial O2: minimal Minute ventilation, resting arterial O2: minimal
change change
Hypoxic drive (ventilatory response to arterial Hypoxic drive (ventilatory response to arterial
hypoxia): depressed hypoxia): depressed
erebral erebral
B, cerebral blood volume, P: B, cerebral blood volume, P:
erebral oxygen consumption (MRO2): erebral oxygen consumption (MRO2):
Nitrous Oxide Nitrous Oxide
Neuromuscular Neuromuscular
Not provide significant muscle relaxation Not provide significant muscle relaxation
Not a triggering agent of malignant hyperthermia Not a triggering agent of malignant hyperthermia
Renal Renal
ncrease renal vascular resistance ncrease renal vascular resistance
Renal blood flow, glomerular filtration rate, U/O: Renal blood flow, glomerular filtration rate, U/O:
Hepatic Hepatic
Hepatic blood flow: Hepatic blood flow:
Gastrointestinal Gastrointestinal
Postoperative nausea and vomiting Postoperative nausea and vomiting
Nitrous Oxide Nitrous Oxide
Biotransformation & toxicity Biotransformation & toxicity
Almost all eliminated by exhalation Almost all eliminated by exhalation
Biotransformation < 0.01% Biotransformation < 0.01%
rreversibly oxidize o in vit.B12 rreversibly oxidize o in vit.B12 inhibit inhibit
vit.B12 vit.B12- -dependent enzymes dependent enzymes interfere myelin interfere myelin
formation, DNA synthesis formation, DNA synthesis
Prolonged exposure Prolonged exposure bone marrow bone marrow
suppression, neurological deficiencies suppression, neurological deficiencies
Avoided in pregnant patients Avoided in pregnant patients
Nitrous Oxide Nitrous Oxide
ontraindications ontraindications
N2O diffuse into the cavity more rapidly than air N2O diffuse into the cavity more rapidly than air
(principally N2) diffuse out (principally N2) diffuse out
Pneumothorax, air embolism, acute intestinal Pneumothorax, air embolism, acute intestinal
obstruction, intracranial air, pulmonary air cysts, obstruction, intracranial air, pulmonary air cysts,
intraocular air bubbles, tympanic membrane grafting intraocular air bubbles, tympanic membrane grafting
Avoided in pulmonary hypertension Avoided in pulmonary hypertension
Drug interactions Drug interactions
Due to high MA, combination with more potent Due to high MA, combination with more potent
agents agents decrease the requirement of other agents decrease the requirement of other agents
Potentiates neuromuscular blockade Potentiates neuromuscular blockade
Halothane Halothane
Halogenated alkane Halogenated alkane
ardiovascular ardiovascular
Direct myocardial depression Direct myocardial depression dose dose- -dependent dependent
reduction of arterial BP reduction of arterial BP
oronary artery vasodilator, but coronary blood flow oronary artery vasodilator, but coronary blood flow
due to systemic BP due to systemic BP
Blunt the reflex: hypotension inhibits baroreceptors in Blunt the reflex: hypotension inhibits baroreceptors in
aortic arch and carotid bifurcation aortic arch and carotid bifurcation vagal vagal
stimulation stimulation compensatory rise in HR compensatory rise in HR
Sensitzes the heart to the arrhythmogenic effects of Sensitzes the heart to the arrhythmogenic effects of
epinephrine (<1.5g/kg) epinephrine (<1.5g/kg)
Systemic vascular resistance: unchanged Systemic vascular resistance: unchanged
Halothane Halothane
Respiratory Respiratory
Rapid, shallow breathing Rapid, shallow breathing
Alveolar ventilation: Alveolar ventilation:
Resting PaO2: Resting PaO2:
Hypoxic drive: severely depressed Hypoxic drive: severely depressed
A potent bronchodilator, reverses asthma A potent bronchodilator, reverses asthma- -
induced bronchospasm induced bronchospasm
Depress clearance of mucus Depress clearance of mucus promoting promoting
postoperative hypoxia and atelectasis postoperative hypoxia and atelectasis
Halothane Halothane
erebral erebral
Dilating cerebral vessels Dilating cerebral vessels cerebral vascular cerebral vascular
resistance resistance B B
Blunt autoregulation (the maintenance of constant Blunt autoregulation (the maintenance of constant
B during changes in arterial BP) B during changes in arterial BP)
P: , prevented by hyperventilation prior to P: , prevented by hyperventilation prior to
administration of halothane administration of halothane
Metabolic oxygen requirement: Metabolic oxygen requirement:
Neuromuscular Neuromuscular
Relaxes skeletal muscle Relaxes skeletal muscle
A triggering agent of malignant hyperthermia A triggering agent of malignant hyperthermia
Halothane Halothane
Renal Renal
Renal blood flow, GR, U/O: Renal blood flow, GR, U/O:
Part of this can be explained by a fall in arterial BP Part of this can be explained by a fall in arterial BP
and O, preoperative hydration limits these changes and O, preoperative hydration limits these changes
Hepatic Hepatic
Hepatic blood flow: Hepatic blood flow:
Biotransformation & toxicity Biotransformation & toxicity
Oxidized in liver by cytochrome P Oxidized in liver by cytochrome P- -450 450
n the absence of O2 n the absence of O2 hepatotoxic end products hepatotoxic end products
Halothane hepatitis is extremely rare (1/35,000) Halothane hepatitis is extremely rare (1/35,000)
Halothane Halothane
ontraindications ontraindications
Unexplained liver dysfunction following previous Unexplained liver dysfunction following previous
exposure exposure
No evidence associating halothane with worsening of No evidence associating halothane with worsening of
preexisting liver disease preexisting liver disease
ntracranial mass lesion, hypovolemic, severe cardiac ntracranial mass lesion, hypovolemic, severe cardiac
disease. disease.
Drug interactions Drug interactions
Myocardial depression is exacerbation by Myocardial depression is exacerbation by - -blockers blockers
and B and B
With aminophylline With aminophylline serious ventricular arrhythmia serious ventricular arrhythmia
soflurane soflurane
Pungent ethereal odor Pungent ethereal odor
A chemical isomer of enflurane A chemical isomer of enflurane
ardiovascular ardiovascular
Minimal cardiac depression Minimal cardiac depression
HR: due to partial preservation of carotid baroreflex HR: due to partial preservation of carotid baroreflex
Systemic vascular resistance: Systemic vascular resistance: BP: BP:
Dilates coronary arteries Dilates coronary arteries coronary steal syndrome coronary steal syndrome
or drop in perfusion pressure or drop in perfusion pressure regional myocardial regional myocardial
ischemia ischemia avoided in patients with AD avoided in patients with AD
soflurane soflurane
Respiratory Respiratory
Respiratory depression, minute ventilation: Respiratory depression, minute ventilation:
Blunt the normal ventilatory response to hypoxia and Blunt the normal ventilatory response to hypoxia and
hypercapnia hypercapnia
rritate upper airway reflex rritate upper airway reflex
A good bronchodilator A good bronchodilator
erebral erebral
B, P: , reversed by hyperventilation B, P: , reversed by hyperventilation
erebral metabolic oxygen requirement: erebral metabolic oxygen requirement:
Neuromuscular Neuromuscular
Relaxes skeletal muscle Relaxes skeletal muscle
soflurane soflurane
Renal Renal
Renal blood flow, GR, U/O: Renal blood flow, GR, U/O:
Hepatic Hepatic
Total hepatic blood flow: Total hepatic blood flow:
Biotransformation & toxicity Biotransformation & toxicity
Limited metabolism Limited metabolism
ontraindications ontraindications
Severe hypovolemia Severe hypovolemia
Drug interactions Drug interactions
Epinephrine (4.5g/kg) Epinephrine (4.5g/kg)
Potentiate nondepolarizing NMBAs Potentiate nondepolarizing NMBAs
Desflurane Desflurane
Structure is similar to isoflurane Structure is similar to isoflurane
High vapor pressure High vapor pressure
Low solubility Low solubility ultrashort duration of action ultrashort duration of action
Moderate potency Moderate potency
ardiovascular ardiovascular
Systemic vascular resistance: Systemic vascular resistance: BP: BP:
O: unchanged or slightly depressed O: unchanged or slightly depressed
Rapid increases in concentration lead to transient Rapid increases in concentration lead to transient
elevation in HR, BP, catecholamine levels elevation in HR, BP, catecholamine levels
Not increase coronary artery blood flow Not increase coronary artery blood flow
Desflurane Desflurane
Respiratory Respiratory
Tidal volume: , respiratory rate: Tidal volume: , respiratory rate:
Alveolar ventilation: , resting PaO2: Alveolar ventilation: , resting PaO2:
Depress the ventilatory response to PaO2 Depress the ventilatory response to PaO2
Pungency and airway irritation Pungency and airway irritation
erebral erebral
Vasodilate cerebral vasculature Vasodilate cerebral vasculature B, P: , B, P: ,
lowered by hyperventilation lowered by hyperventilation
erebral metabolic rate of oxygen: erebral metabolic rate of oxygen:
vasoconstriction vasoconstriction moderate the increase in B moderate the increase in B
Desflurane Desflurane
Neuromuscular Neuromuscular
Dose Dose- -dependent decrease in the response to train dependent decrease in the response to train- -of of- -
four and tetanic peripheral nerve stimulation four and tetanic peripheral nerve stimulation
Renal Renal
No evidence of any nephrotoxic effects No evidence of any nephrotoxic effects
Hepatic Hepatic
No evidence of hepatic injury No evidence of hepatic injury
Biotransformations & toxicity Biotransformations & toxicity
Minimal metabolism Minimal metabolism
Degraded by desiccated O2 absorbent into O Degraded by desiccated O2 absorbent into O
Desflurane Desflurane
ontraindications ontraindications
Severe hypovolemia, malignant hyperthermia, Severe hypovolemia, malignant hyperthermia,
intracranial hypertension intracranial hypertension
Drug interactions Drug interactions
Potentiate nondepolarizing NMBAs Potentiate nondepolarizing NMBAs
Not sensitize myocardium to arrhythmogenic Not sensitize myocardium to arrhythmogenic
effects of epinephrine (4.5g/kg) effects of epinephrine (4.5g/kg)
Emergence associated with delirium in some Emergence associated with delirium in some
pediatric patients pediatric patients
Sevoflurane Sevoflurane
Nonpungency and rapid increase in alveolar Nonpungency and rapid increase in alveolar
anesthetic concentration anesthetic concentration smooth and rapid smooth and rapid
inhalation inductions in pediatric and adult inhalation inductions in pediatric and adult
patients patients
aster emergence associated with greater aster emergence associated with greater
incidence of delirium in pediatric populations incidence of delirium in pediatric populations
ardiovascular ardiovascular
Mildly depress myocardial contractility Mildly depress myocardial contractility
Systemic vascular resistance, arterial BP: Systemic vascular resistance, arterial BP:
O: not maintained well due to little rise in HR O: not maintained well due to little rise in HR
Prolong QT interval Prolong QT interval
Sevoflurane Sevoflurane
Respiratory Respiratory
Depress respiration Depress respiration
Reverse bronchospasm Reverse bronchospasm
erebral erebral
B, P: slight B, P: slight
erebral metabolic oxygen requirement: erebral metabolic oxygen requirement:
Neuromuscular Neuromuscular
Adequate muscle relaxation for intubation of children Adequate muscle relaxation for intubation of children
Renal Renal
Renal blood flow: slightly Renal blood flow: slightly
Associated with impaired renal tubule function Associated with impaired renal tubule function
Sevoflurane Sevoflurane
Hepatic Hepatic
Portal vein blood flow: Portal vein blood flow:
Hepatic artery blood flow: Hepatic artery blood flow:
Biotransformation & toxicity Biotransformation & toxicity
Liver microsomal enzyme P Liver microsomal enzyme P- -450 450
Degraded by alkali (barium hydroxide lime, soda lime), Degraded by alkali (barium hydroxide lime, soda lime),
producing nephrotoxic end products (compound A) producing nephrotoxic end products (compound A)
resh gas flows be at least 2 L/min resh gas flows be at least 2 L/min
Not be used in patients with preexisting renal Not be used in patients with preexisting renal
dysfunction dysfunction
Sevoflurane Sevoflurane
ontraindications ontraindications
Severe hypovolemia, susceptibility to Severe hypovolemia, susceptibility to
malignant hyperthermia, intracranial malignant hyperthermia, intracranial
hypertension hypertension
Drug interactions Drug interactions
Potentiate NMBAs Potentiate NMBAs
Not sensitize the heart to catecholamine Not sensitize the heart to catecholamine- -
induced arrhythmias induced arrhythmias