INHALATIONAL ANESTHETICS
Nitrous Oxide (N2O)
physical properties:
-low molecular weight, clear, odorless, inert, inorganic gas
-non-flammable but does support combustion
-gas at room temperature, kept as liquid under pressure
pharmacokinetics:
-low blood solubility (B:G partition coefficient 0.47) "=> rapid
induction
-low tissue solubility (tissue gas solubility coefficient 1.22) "=> rapid emergence
-oil:gas partition coefficient 1.4
-weak anesthetic (MAC 104%)—most commonly used in conjunction
with a volatile anesthetic or moderate dose narcotic technique
-MAC awake approximately 60%
-prominent analgesic effects
-minimal skeletal muscle relaxation
-may play a role in the development of PONV but studies remain
inconclusive (E. Eger states that there is no difference in the
occurrence of PONV in cases which used N2O 50% vs. those which
used none)
respiratory effects:
-minimal at [ ] of 50% or less
-does not increase PaCO2
-produces little ventilatory depression
-profoundly depresses the ventilatory response to arterial
hypoxemia
-*is the only inhalational anesthetic to increase pulmonary vascular
resistance, especially in patients with preexisting pulmonary
hypertension
CV effects:
-produces either no change or modest increases in BP, SVR and CO
from activation of the SNS
-depresses the carotid sinus
-produces mild sympathetic stimulation as evidenced by:
-increase in plasma catecholamines
-mydriasis
-increase in body temperature
-diaphoresis
-increase in RAP
-vasoconstriction of the pulmonary and systemic circulations,
including cutaneous beds
-causes profound circulatory depression in the presence of opioids as
evidenced by:
-decrease in BP, CO
-increases LVEDP and SVR
***lt is possible that opioids inhibit the sympathomimetic effects of N2O
thereby unmasking a cardiac depressant effect
excretion:
-eliminated primarily as an expired gas
-approximately 0.004%—undergoes reductive metabolism to nitrogen
from activity of anaerobic bacteria in the Gl tract
miscellaneous:
-does not potentiate the effects of non-depolarizing muscle relaxants
-does not trigger MH
***because it is 34X more soluble than nitrogen in the blood, it diffuses into air
containing body cavities and can increase the pressure or expand the volume
of gas in these cavities resulting in:
-distention of the bowel
-expansion or rupture of pulmonary cysts
-expansion or rupture of the tympanic membrane in an
occluded middle ear
-pneumoencephalus
-expansion of air emboli in the bloodstream
-expansion of pneumothorax
-expansion of cuffs of ETT or LMA
-causes a negative Ames test but has been implicated in causing an increased
incidence of SAB in OR and PACU personnel -irreversibly oxidizes the cobalt
atom of vitamin B12 thereby inactivating it and interfering with the synthesis of
these enzymes:
-methionine synthase (important in the formation of
myelin)
-thymidylate synthase (important in the formation of
DMA)
-may cause megaloblastic changes and agranulocytosis in bone marrow which
is directly related to the interference of DMA synthesis-has a deleterious
effect on hematopoiesis
***contraindicated for use in pregnancy, the immunosuppressed, and pts with
pernicious anemia -overexposure may lead to peripheral neuropathies
isoflurane (Forane)
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physical properties:
-a halogenated hydrocarbon (methyl ethyl ether); an isomer of
enflurane
-clear, non-flammable liquid at room temperature
-pungent, ethereal odor
-extremely stable—not degraded by soda lime or light
-vapor pressure 240 mm Hg
-molecular weight 184
pharmacokinetics:
-since it is an isomer of enflurane, it exhibits similar pharmacologic
properties
-devoid of seizure activity, hepatic, or renal damage
-intermediate blood solubility (B:G partition coefficient 1.4)
-tissue gas solubility 110
-MAC 1.15% (intermediate potency)
-MAC awake approximately 173rd of MAC
-oikgas solubility 91
respiratory effects:
-produces significant respiratory depression (dose dependent)
CV effects:
-cardiac output may increase from SNS response to hypercapnia
from hypoventilation
-may possess some intrinsic sympathomimetic properties
-*most potent vasodilator of the volatile agents; decreases SVR
-causes coronary steal in steal-prone pts
-does not sensitize the myocardium to catecholamines
CNS effects:
-same as the other volatiles with regard to CMRO2) CBF, and ICP
renal/hepatic effects:
-least deleterious effect on both systems—actually best of all the volatiles
at preserving hepatic blood flow
muscular:
-provides profound skeletal muscle relaxation—greatest of all of the
volatile agents
-potentiates the effects of the NDMBs
-relaxes uterine smooth muscle
-triggers MH
excretion:
-primarily excreted unchanged as expired gas
-undergoes minimal hepatic degradation (approximately 0.2%)
desflurane (Suprane)
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physical properties:
-a fluorinated methyl ethyl ether structurally similar to isoflurane with
substitution of a fluorine atom on the alpha ethyl carbon
-vapor pressure 664 mm Hg—must be vaporized through a heater
-molecular weight 168
-stable in soda lime
-pungent odor; may irritate airways especially at [ ] > than 1 MAC
pharmacokinetics:
-MAC 4.58% to 6.3% (not extremely potent)
-MAC awake approximately I/3"1 of MAC
-insoluble in blood (B:G coefficient 0.42)c>rapid induction/emergence
expected
-low oil:gas partition coefficient—18.7
-low tissue:gas partition coefficient (35); surrendered quickly as agent
dissipates
CV, respiratory, CMS, hepatic, renal, muscular effects:
-thought to be similar in effects on all systems to isoflurane; may have
a slightly greater effect in decreasing SVR
-newer studies report that cardiac stimulation (i.e. tachycardia) is
noted with rapid increases in [ ]
-does not cause coronary steal in canine model; human studies
pending
-does not sensitize the myocardium to catecholamines
-may provide cardiac protection in the face of ischemia
-does not bronchodilate—may actually cause bronchoconstriction and
respiratory irritation (6% or greater) especially in smokers
-may impair cerebral autoregulation at [ ] > 0.5 MAC
-reports of greater incidence of PONV
-recently reported to cause less post-operative delirium in the pedi population
-**may cause CO toxicity if administered through desiccated soda lime
metabolism:
-undergoes minimal biotransformation in the liver (approximately 0.02%)
sevoflurane (Ultane)
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physical properties:
-a fluorinated methyl ethyl ether
-vapor pressure 160 mm Hg
-molecular weight 200
-unstable in soda lime—leads to formation of Compound A which is
nephrotoxic (occurrence primarily in Baralyme)
***fresh gas flows of <2l/min not recommended
-odor less pungent; well accepted for inhalation induction
-may react with glass; H2O added as a preservative; unnecessary in plastic or
aluminum containers
pharmacokinetics:
-insoluble in blood (B:G coefficient 0.69)
-tissue:gas solubility 99
-MAC 1.71 (intermediate potency)
-MAC awake approximately l/3rd of MAC
-poor lipid solubility (oil:gas partition coefficient 55)
CV effects:
-similar effects as other volatiles, particularly desflurane
-does not cause SNS stimulation with rapid increases in [ ]
-does not cause coronary steal
-does not sensitize the heart to catecholamines
-mildly depresses myocardial contractility
CNS effects:
-preserves cerebral autoregulation at [ ] up to 1.5 MAC -increase
in CBF parallels ICP
-recent reports of seizure activity with high [ j in a non-epileptic pt
respiratory effects:
-depresses respiration like other volatiles
-non-irritating to the airways; may reverse bronchospasm, status asthmaticus
hepatic, muscular effects:
-similar to those of desflurane
-triggers MH
metabolism:
-deflourination exceeds that of enflurane; still only 1/3rd of potential
renal toxic dose
-undergoes minimal hepatic degradation (2-3%)