wayne e. ellis, ph.d., crna. effects on renal system decreased renal blood flow decreased glomerular...
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Wayne E. Ellis, Ph.D., CRNA
Decreased renal blood flow
Decreased Glomerular Filtration Rate
Decreased urine output
SVR mostly decreased by Isoflurane/Desflurane
Most Myocardial depression occurs with Halothane/Enflurane
Halothane/sevoflurane mostly depress baroreceptor reflex (no HR increases despite decreased BP)
Isoflurane/Desflurane least depress baroreceptor reflex (HR increases with decreased BP)
Maximum adult dose of Epinephrine with Halothane is 1mcg/kg
-2 to 3mcg/kg with any other agent
Children less sensitive to Epinephrine/Halothane◦ max epinephrine 1.5mcg/kg◦ 3mcg/kg with other agents
Avoid using Aminophylline with Halothane. -Aminophylline triggers the release of norepinephrine.
Halothane sensitizes myocardium to catecholamines.
Limit Epinephrine, norepinephrine, Isoproterenol, and dopamine use.
Dysrhythmias are easily induced.
Avoid Halothane in patients with acute cocaine intoxication.
Cocaine blocks reuptake of norepinephrine.
Isoflurane causes hypothermia by depressing hypothalamus temp regulator
Volatile agents dilate cerebral vasculature Increased cerebral blood flow (mostly with Halothane) Decreased cerebral metabolism Increased ICP (least with Isoflurane) Depressed neuronal function
Dose dependent decrease in ventilatory response to CO2
0.1 MAC completely block ventilatory response to hypoxemia
Enflurane / Desflurane causes the highest symptoms of ventilatory depression
Halothane causes the least symptoms of ventilatory depression
Agents are effective bronchodilators Halothane / Sevo are least pungent and
airway irritant 1-1.5 MAC or more inhibits Hypoxic
Pulmonary Vasoconstriction
Agents metabolized in liver by cytochrome P-450
N2O metabolized to N2 in intestine by anaerobic bacteria
Blood solubility determines the speed of build-up / elimination from blood / brain
Blood:Gas coefficient provides a measure of blood solubility
Shows volatile agents in liquid(blood) compared to gas phase
Isoflurane blood:gas ratio is 14/10 =1.4
Speed of uptake determined by blood/gas ratio More blood solubility = > blood/gas ratio = slower uptake Speed of uptake/elimination from brain is inversely R/T
solubility. Lower blood solubility means faster induction/recovery Higher blood solubility means slower induction/recovery Slower uptake leads to smaller FA/FI ratio FA = Fraction of inhalation agent in alveolar gas FI = Fraction of inhalation agent in inspired gas FA/FI in 30mins is inversely related to blood solubility Halothane with high solubility diffuses more from alveoli to
blood With high solubility alveolar partial pressure (FA/FI) builds up
slowly
Desflurane is poorly blood soluble:
Small quantities diffuse from alveoli to blood
FA/FI increases rapidly
Uptake is slow
Speed of onset is fast
Induction is fast
Isoflurane, Halothane, & Enflurane are highly blood soluble:
Alveolar uptake with high solubility agents is slow
Agents with high blood/gas ratio are highly blood soluble
Uptake by blood is fast/large Speed of onset and FA/FI is slow Great pulmonary circulation uptake Prolonged induction
Agents with highest oil/gas ratio are:
More lipid soluble More potent Have smaller MAC The lower the MAC the greater the
potency
High blood solubility leads to slower brain uptake
Decreased cardiac output increases agents carried to brain
Increased alveolar ventilation speeds brain uptake
Increased inspired concentration speeds brain uptake
Blood flow controls tissue uptake
N2 is 34X less soluble in blood than N2O
N2 is carried very poorly in blood
Gas diffusion is proportional to it's blood solubility (Fick's law)
More N2O diffuse into blood than N2 diffuse out
N2O is 34X more soluble than N2 More N2O leaves the alveoli Alveoli shrink in size Alveolar concentration of N2O remains high Fick's law of diffusion explains the
concentration effect
Increased uptake of volatile agent when given together with N2O
Fick's law also explains second gas effect
When N2O is turned off:
More N2O diffuse from blood to alveoli Less N2 diffuse from alveoli to blood Blood has limited capacity to hold N2(poor
solubility)
Alveoli Expands
CO2/O2 are diluted
Diffusional hypoxia occurs in patients on room air O2 during emergence
N2O increases both SVR/PVR
N2O has a mild sympathomimetic effect
Malignant Hyperthermia
Venous Air Embolism
Middle Ear Surgery
Closed Pneumothorax
Bowel Obstruction
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Very rare risk of renal toxicityRisk of seizures in patient with
seizure history
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Halogenated methyl ethyl etherPungent, ethereal ordor
CoughingBreath holding
Synthesized 1965Clinical Practice 1981
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Clear, nonflammable liquidVolatile at room temperatureVapor pressure 240 torr @ 20
CMolecular weight 184Solubility
Blood/gas = 1.4Oil/gas = 90.8
MAC70% Nitrous Oxide = 0.5100% Oxygen = 1.15
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< blunting of the baroreceptor reflexMaintenance of CO
Increase in heart rate
Epinephrine> halothane< enflurane
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TachycardiaHypotensionExtremely potent vasodilator
Classes of inhaled anesthetics◦ Hydrocarbons
Chloroform - highly toxic◦ Ethers
Cyclopropane, ethylene and ether - explosive
◦ Non- carbon-base gases Nitrous oxide, xenon
Halogenation reduces flammability
Flurination reduces solubility Triflurocarbon groups add
stability
Campagna, JC N Eng J Med 2003;348(21):2110-2124
Partition coefficients◦ Represent the relative affinity of a gas for two different substances
(solubility)◦ Measured at equilibrium so -----
PARTIAL PRESSURES ARE EQUAL BUT
◦ The amounts of gas dissolved in each substance (concentration) are not equal
◦ Most commonly refer to blood:gas partition coefficient◦ The larger the number, the more soluble the gas in blood
Anesthetic Blood:Gas PC
Desflurane 0.42
Nitrous Oxide 0.46
Sevoflurane 0.65
Isoflurane 1.46
Enflurane 1.91
Halothane 2.50
Barash 4th Edition p378
Rate of increase in alveolar anesthetic concentration (FA) toward the concentration inspired (FI) during induction relates inversely to the solubility of the potent agent in the blood
Fluorinated methyl-ethyl ether At room temperature
◦ Vapor pressure (20o C) – 669 mmHg◦ Clear, nonflammable liquid◦ Pungent odor
Least soluble potent anesthetic◦ Blood-gas coefficient 0.42
Boiling point is 22.8o C◦ Vapor pressure of desflurane changes
greatly with small fluctuations in temperature
◦ Accurate gas delivery with normal plenum vaporizer is impossible
Requires a special vaporizer◦ That is heated and pressurized◦ Ensures that desflurane 100%
vaporized◦ Injects small amount of pure
desflurane vapor into fresh gas flow utilizing a transducer
◦ Requires electrical power◦ Requires a warm-up period
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Pharmacodynamicsalmost identical to isofluraneDose related decreases in BP and COGreater than seen with isoflurane
Factor of rapidity of increasing dose
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Volatile at room temperatureStored under pressureBoiling Point 23.5 CVapor Pressure 664 torr @ 20
CSolubility
Blood/gas = 0.42Oil/gas = 18.7
MAC70% Nitrous Oxide = 2.83100% Oxygen = 6
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PharmacokineticsLow blood/gas partition coefficient“Very fast-on, fast-off”
Similar to Nitrous OxideMetabolism
< isoflurane
MAC in 20-60y olds is 6.0 0.09%◦ Decreases with:
Advancing age Decreased body temperature Administration of other CNS depressants
Cardiovascular effects◦ Direct effects similar to isoflurane◦ Sympathetic nervous system activation
Mechanism unclear ? due to rapid stimulation of airway receptors Can result in significant HR and BP Related to rate of rise of desflurane concentration
Respiratory effects◦ Depressant◦ Pungent odor prevents mask inductions
Recovery◦ Emergence rapid◦ May be associated with emergence delirium◦ Discharge to home similar to other agents
Absorbents ◦ Initially calcium hydroxide used alone
abundant, inexpensive and easily handled◦ Slaked lime
Not efficient by itself NaOH added to increase efficiency Mixtures of sodium and calcium hydroxide
developed and referred to as SODA LIME◦ Soda lime
Ineffective unless moisture added to granules
Neutralization increases as moisture content increases
Biodegradation is minimal CO production from absorbents
◦ 1st report by Middleton 1965 Scattered reports in literature Fang et al 1994
Demonstrated CO production with desiccated absorbents
Increases with increase in temperature Highest production with Desflurane
◦ Recommendations Turn off gas flow when machine not in use Change soda lime if dormant > 24 hrs Change absorbent when color change occurs Change all absorbent Change compact canisters more frequently
Moon RE, APSF Newsletter 1994;9:13-16
Fang ZX, APSF Newsletter 1994:9:25-36
Berry PD, Anesth 1999;90(2):613-616
Olympia MA, APSF Newsletter 2005;20(2):25-29
Occurs when Desflurane, Ethrane, Forane degraded by dry soda lime or Baralyme > 600 ppm
Does not occur with fully hydrated absorbentsCommon scenario: * Monday morning case and gas has been left
on over the weekend, drying the absorbentAbsorber temperature rapidly rises
Use fresh absorbentUse soda lime rather than barium
hydroxideUse the new CO2 absorbent called
“Amsorb” Prevents anesthetic breakdown that would lead
to CO formationAbsorbs less CO2 than other absorber
compounds
Turn off gas when case complete
A methyl-isopropyl ether At room temperature
◦ Vapor pressure (20o C) – 170 mmHg◦ Clear, nonflammable liquid◦ Little or no odor
Blood-gas coefficient 0.65
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Clear, volatile liquidVapor pressure 160 torr @ 20CSolubility
Blood/gas = 0.59Oil/gas = 55
MAC70% Nitrous Oxide = 0.66100% Oxygen = 1.71
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Pleasant smellingWell tolerated for inhalation inductionAs temperature increases, degradation
occursCompound (Substance) A
Unstable in soda limeHigh degree of metabolism
MAC varies with age◦ 3.3% -- Neonates◦ 2.03% -- Age 1-9y◦ 2.93% -- Teenagers◦ 1.3% -- Mid-age adults◦ 1.2% -- > 80y
Potent cardiorespiratory depressant◦ Profile is similar to isoflurane and desflurane
Recovery rapid
Clear, volatile liquid
Pleasant smellingWell tolerated for inhalation inductionAs temperature increases, degradation occurs
Compound (Substance) A
Unstable in soda limeHigh degree of metabolismTachycardia seen with > 1.5 MACNo increase in CVP
Molecular Weight 200Boiling Point 58.5 o CVapor pressure 160 torr @ 20COdor Ethereal, PleasantSolubility
Blood/gas 0.59 – 0.69Brain/Gas 1.7Oil/gas 53.4 – 55
MACNitrous Oxide 0.66Oxygen 1.71
Can be used safely for inhalation induction
Quick inductionDoes not initiate coughing, secretions, breath
-holding, laryngospasmCan be used for difficult airway & intubation:
Fiberoptic with spontaneous ventilations
Can maintain spontaneous respirations + anesthesia
Compound A is of most concernUp to 60 ppm in normally operating anesthesia
circuitAverage concentrations 20-25 ppm
1% = 10,000 ppm
Renal toxicity @ 25-60 ppm
Dilutent gas flowTemperatureSodalime moisture contentSevoflurane concentrationTime
From Sevoflurane
Isoflurane, Desflurane & Sevoflurane decrease CMRO2 in a dose-related fashion
Increases CBF in dose-related fashion (Hoffman)4% ET: Minimal vasodilation9% ET: Greater vasodilation
No seizure activity noted with DesfluraneEpileptiform EEG pattern with Sevoflurane during
mask inductionIncreased HR with either spontaneous respirations or
controlled hyperventilation
Methyl Ethyl etherCHCl2CF2OCH3
CH3 metabolically unstableSweet, pungent smellTolerated for inhalation induction
Very slowNot easily managed in adults
Metabolism – highPolyuric dysfunction - High output renal failure
Caused by release of Fluoride ion during metabolism, Plasma fluoride > 50 micromols puts patient at risk
Vapor Pressure 22.5 torr @ 20CBoiling Point 105 o
SolubilityBlood/gas 12
MAC100% Oxygen 0.16 – 0.23
Extremely high lipid solubilityHigh output renal failure
In Vivo ◦ Biotransformation results in organic and inorganic fluoride
metabolites Occurs via cytochrome P-450 catalyzed oxidation producing a
transient intermediate that decomposes into Inorganic fluoride Organic fluoride metabolite hexafluoroisopropanol (HFIP)
Conjugated with glucuronide and excreted in the urine Renal toxicity correlates with peak serum F-
< 40 M -- no clinical effects 50-80 M -- subclinical toxicity 90-120 M -- mild toxicity 80-175 M -- overt toxicity
Duration of exposure may be more important than peak serum levels
Hobbhahn J, ESA Refresher Courses 2000;3 RC 1
In Vitro◦ Reacts with CO2 absorbers
Baralyme > soda lime Low flows Dry absorbent High absorbent temperatures High sevoflurane concentrations
◦ Forms compounds A, B, C, D◦ Only compound A clinically significant
Compound A is a haloalkene (vinyl halide) Formed when sevoflurane reacts with strong bases in absorbents
Animal models demonstrate renal toxicity In rats nephrotoxicity characterized by necrosis of proximal tubular
cells Clinically presents with diuresis, proteinuria, glucosuria and enzymuria Threshold for damage in rats approximately 96-114 ppm for 3 hrs Related to bioactivation of this compound by renal β-lyase pathway
No evidence this is dangerous to humans
2004 reports of ◦ Exothermic reactions◦ Spontaneous ignition◦ Explosions◦ Fires
Fatheree RS, Anesth 2004;101:531-533
Wu J, Anesth 2004;101:534-537
Castro BA, Anesth 2004;101:537-539
Desflurane Sevoflurane Desflurane Sevoflurane
Anesthesia
Duration2 hours 10.9 17.8 12.7 21.2
4 hours 11.3 20.8 14.8 25.3
8 hours 14 28 19 33
Response to Command (min) Orientation (min)
Eger EI, Anesth Analg 1998;86(2):414-421
Joshi D. Anesth Analg 1998;86(2):267-273
P<0.015 vs. sevoflurane
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Halogenated methyl ethyl etherPungent, ethereal odorLess potent than other volatile agentsSynthesized - 1963Clinical Use - 1972Isomer of isoflurane
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Clear, nonflammable liquidVolatile at room temperatureVapor pressure 172 torr @ 20 CMolecular weight 184Solubility
Blood/gas = 224Oil/gas = 98.5
MAC70% Nitrous Oxide = 0.6100% Oxygen = 1.7
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Extremely rare risk of postop liver dysfunction
Increased doses of epinephrine> halothane or isoflurane < dysrhythmias
Muscle relaxantCaution in patients with Myasthenia Gravis
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Very rare risk of renal toxicityRisk of seizures in patient with seizure
history
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Methyl Ethyl etherSweet, pungent smellTolerated for inhalation
inductionVery slowNot easily managed in adults
Metabolism - high
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Vapor Pressure 22.5 torr @ 20CSolubility
Blood/gas = 12
MAC100% Oxygen = 0.16
Extremely high lipid solubilityHigh output renal failure
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