Inhaled Agents Part 2 Flashcards
When is Ether day?
October 16, 1846
WTG Morton successfully demonstrates the use of ether in the removal of a jaw tumor at Mass Gen
Fresh gas flow is determined by
the vaporizer and flowmeter settings
Fractional inspired gas concentration is determined by
FGF rate, breathing-circuit volume and machine absorption
Fractional arterial gas concentration is affected by
ventilation/perfusion mismatching
Fractional alveolar gas concentration is determined by
uptake, ventilation, and the concentration effect and second gas effect
The Fi/FA ratio is a
gas to gas ratio
Factors that affect inspiratory concentration include
fresh gas flow, breathing system volume, & machine absorption
Factors affecting alveolar concentration include
blood solubility of the agent, alveolar blood flow, partial pressure between alveoli and venous blood
If Fa is less than the end-tidal level it is possible that
venous admixture, alveolar dead space, or non-uniform distribution exists
Ventilation/perfusion mismatch can occur in a situation such as
right bronchial intubation
The overall effect for V/Q mismatch is
increase in alveolar partial pressure (highly soluble agents) and decrease in arterial partial pressure (low solubility agents)
What is the mechanism of action of inhaled gases?
unknown
possible targets may include: NMDA receptors, Tandem pore potassium channels, voltage-gated sodium channels, glycine receptors, & GABA receptors
What is the Meyer Overton Theory?
liphophilicity equates to potency
this is not absolute though
What are the CNS effects of inhaled gases?
CMRO2 is decreased
cerebral blood flow is increased (dose-dependent)
What does “uncoupling” mean?
describes the phenomenon of a decrease in CMRO2 but an increase in cerebral blood flow
greater with sevoflurane
What does nitrous oxide do to the brain?
increases both CMRO2 and CBF
mild hyperventilation helps attenuate increases in
CBF
Clinically relevant doses of inhalational agents preserve this when ICP is a concern, mild hyperventilation 30-35 mmHg
cerebral vascular responsiveness to CO2
What is the effect of inhalational agents on evoked potentials?
inhalational agents decrease amplitude and increase latency
EEG and evoked potentials
inhalational agents produce a dose-related suppression
burst suppression occurs at: 1.5 MAC of desflurane & 2 MAC with isoflurane and sevoflurane
For neonates having surgery,
there is a concern for developmental neurotoxicity
it was demonstrated in rodents and non-human primates that they cause activation of extrinsic and intrinsic apoptotic cell death pathways
When giving gas to neonates it is recommended that
keep surgery as short as possible
use short acting medications and multimodal approaches
All volatile inhalation agents reduce
cardiac output and index in a dose-dependent fashion
Volatile agents and nitrous oxide induce HR changes via
SA node antagonism
modulation of baroreflex activity
sympathetic nervous system activity
Reduced MAP secondary to
SVR reduction
nitrous oxide used in combination with anesthetics reduces this
Reduced cardiac output is caused by
reduction in free intracellular Ca2+ contractil state
As MAC hours increase, there is slight increase of CI and HR
Emergence delirium in children
is more common with sevoflurane and desflurane
& can cause injury & delay discharge
Emergence delirium in children can be prevented by
having a quiet, stress-free environment and giving medication adjuncts
Postoperative cognitive dysfunction is of
great concern in the elderly
there is no clinically significant association between major surgery and anesthesia with long-term POCD
Nitrous oxide causes a slight increase in
PVR and it worsens in patients with pulmonary hypertension
The volatile agents affect pulmonary circulation
by decreasing pulmonary artery pressure
Gases are able to affect the pulmonary circulation by
mildly depressing hypoxic pulmonary vasoconstriction
isoflurane has the greatest effect
All inhalational agents produce some
vasodilation (SVR)
in hypotensive patients this can result in a ‘reverse-Robin Hood’ syndrome (isoflurane)
Preconditioning is
a phenomenon in which the heart is exposed to a cascade of intracellular events that protect it from ischemic and reperfusion insult
Sensitization is
when volatile agents reduce the quantity of catecholamines necessary to evoke arrhythmias
Less common in ASA I & II classifications
The CO, SVR, MAP, and HR in isoflurane:
CO: decreased
SVR: decreased
MAP: decreased
HR: increased
The CO, SVR, MAP and HR in desflurane:
CO: —
SVR: decreased
MAP: decreased
HR: increased
The CO, SVR, MAP, and HR in sevoflurane:
CO: –
SVR decreased
MAP: decreased
HR: no change
The CO, SVR, MAP, and HR in nitrous oxide:
CO: decreased
SVR: increased
MAP: no change
HR: increased
The CO, SVR, MAP, and HR in xenon is:
CO: no change
SVR: no change
MAP: no change
HR: decreased
The gases do what to the airways?
relax airway muscle and produce bronchodilation
Volatile agents cause dose-dependent decreases in (respiratory related)
tidal volume- compensated by increase in RR (but not sufficient to offset TV)
Responsiveness to carbon dioxide
-increases apneic threshold
-exacerbated by co-administration of an opioid
What volatile agent has the potential to impair hepatic function?
Halothane
halothane hepatitis (rare)
caused by trifluoracetyl-containing metabolites binding to proteins and forming antibodies
re-exposure of the patient to halothane cause massive hepatic necrosis
What gas was historically associated with increased production of haloalkene, compound A?
sevoflurane
This occurs with the use of older absorbents (CaOH or lithium OH)
newer agents (NaOH and KOH do not have this issue
should not exceed 2 MAC hours at flows <2L per minute
Fresh gas flow <1 L per minute not recommended
Autoregulation of renal circulation remains relatively intact
decrease in renal SVR leads to decline in GFR
ultimately a decrease in urine output
desflurane has least impact on renal function
Action of volatile agents on hepatic function
possible impairment although extremely rare
sevoflurane undergoes the greatest metabolism (5-8%)
however it does not cause hepatic toxicity
Neuromuscular effects of volatile agents include
dose-dependent relaxation on skeletal muscle
additive effect on non-depolarizing NMBDs
delays recovery from non-depolarizing NMBDs
The ideal anesthetic agent properties:
non-irritating to the respiratory tract, rapid induction and emergence, chemically stable (non-flammable), produce amnesia analgesia and areflexia, potent, not metabolized and excreted by respiratory tract, free of toxicity and allergic reactions, minimal systemic changes, uses a standardized vaporizer, affordable
The four properties that affect how agents work include
vapor pressure, boiling point, partial pressure, and solubility
Boiling point is
the temperature at which vapor pressure exceeds atmospheric pressure in an open container
Vapor pressure is
the pressure exerted inside a container between liquid and vapor
at room temperature, most volatile agents have a
vapor pressure below atmospheric pressure
it is directly proportional with temperature
The partial pressure is
fraction of pressure within a mixture (Dalton’s Law)
Solubility is
the tendency of a gas to equilibrate with a solution (Henry’s Law)
anesthetic gases administered to the lungs diffuse into the blood until the partial pressures of the alveoli and blood are equal
The concentration of anesthetic in tissue is dependent on
the partial pressure and solubility
For most drugs, concentration is measured as
mass (mg/mL) but it can be expressed in percent by weight or volume
Gas is expressed as
a fractional concentration
fractional volume= Panesthetic/Patmospheric
MAC awake is
the MAC in which 50% of the populations opens eyes to command
MAC ‘BAR’
the MAC necessary to block adrenergic response to stimulation
usually 1.3 of MAC value
can be reduced by administering a narcotic prior to incision
MAC requirements decrease with age
age
6% decline (of a normal MAC) each decade after the age of 40
MAC relatively unaffected by gender, duration of anesthesia, comorbidities
The additive effect
0.5 MAC of nitrous oxide + 0.5 MAC of isoflurane= 1 MAC sevoflurane
the idea that giving nitrous can decrease the MAC requirement of another gas but make it as effective as 1 MAC of another agent
Vaporizers are
calibrated for specific agents
The vaporizer facilitates the movement of anesthetic from the machine to the patient through
fresh gas flow, pressure, and temperature
What is the chemical structure of isoflurane?
halogenated methyl ethyl ether
Isoflurane is the most ____ of the volatile agents
potent
slower onset and recovery from anesthesia
Isoflurane affects CV by
minimal cardiac depression, preserves carotid baroreceptors
dilates coronary arteries; concern for ‘reverse-Robin-Hood’
Isoflurane respiratory effects
pungent, not used for inhalational induction
tachypnea less pronounced
Desflurane is the ____ _____ of the volatile agents
least potent
quicker induction and emergence
potential to boil at room temperature
The cardiovascular effects of desflurane are
rapid increases in desflurane lead to increases in HR & BP
attenuated with fentanyl, esmolol, clonidine
The respiratory effects of desflurane are
very pungent; can cause airway irritation, increased salivation, breath holding, coughing, laryngospasm
avoid in patients with reactive airway disease
The chemical structure of sevoflurane
fluorinated methyl isopropyl ether
Sevoflurane has moderate
potency and has rapid induction and emergence
Sevoflurane is the preferred volatile for
inhalational induction because it is non-pungent
Sevoflurane has the following CV effects:
may prolong QT interval
CO is less maintained than other volatile agents- HR not increased
Sevoflurane is metabolized
in the liver
increases in inorganic fluoride ions but never shown to result in nephrotoxicity
Soda lime can degrade sevoflurane
into Compound A
increased gas temperature, low flow anesthesia,
high sevoflurane concentrations and prolonged
surgeries (nephrotoxic in rats, not humans)
For safety: calcium hydroxide absorbent, flows 2 lpm, avoid in patients with renal dysfunction
Nitrous oxide is
not a volatile anesthetic
it is colorless and odorless
Nitrous oxide acts on
NMDA receptor antagonist which may lower risk for chronic pain after surgery
A safety consideration of nitrous oxide is
it is nonexplosive and nonflammable however it does support combustion like oxygen
Nitrous oxide has decreased in popularity because
chronic exposure can lead to inactivation of vitamin B12 cofactor for enzyme synthesis, disrupting DNA synthesis leading to teratogenic bone marrow and immunosuppression effects (don’t use on pregnant women in first two trimesters)
Nitrous oxide has effects on the respiratory system including
increasing respiratory rate
decreasing hypoxic drive
Nitrous oxide has effects on the cerebral system including
increases CMRO2 and CBF
Nitrous oxide increases the risk of
PONV
Nitrous oxide stimulates the
SNS, BP, HR, CO unchanged or slightly elevated
Absolute contraindications to using nitrous oxide include
expansion of gas-filled space
methionine synthase pathway deficiency
Relative contraindications of nitrous oxide include
PONV, first trimester of pregnancy, increased ICP, pulmonary HTN, prolonged surgery >6 hours
Xenon is a
noble gas with known anesthetic properties
Xenon works
through NMDA and glycine receptor binding sites
Xenon has minimal
CV, hepatic, or renal effects and has no effect on the ozone layer
Xenon violates the principle of ideal gases because
it is expensive and has limited availability (hard to extract)
The BP, VP, blood:gas, oil:gas, MAC for sevoflurane
BP: 59, VP: 157, Blood gas: 0.65, Oil:gas 47, MAC 2.0
The BP, VP, blood:gas, oil:gas, MAC for desflurane
BP: 24, VP: 669, Blood gas: 0.42, Oil:gas 19, MAC: 6.0
The BP, VP, blood:gas, oil:gas, MAC for isoflurane
BP: 49, VP: 238, Blood:gas 1.46, Oil:gas 91, MAC 1.2
The BP, VP, blood: gas, oil:gas, MAC for nitrous oxide
BP: -88, VP: 38,770, Blood gas: 0.42, oil:gas 1.4, MAC 104
Malignant hyperthermia can be triggered by
volatile anesthetics, succinylcholine, and stress
Malignant hyperthermia is due to
ryanodine receptor gene mutation (chromosome 19)
Signs and symptoms of malignant hyperthermia include
increase in CO2 production, muscle rigidity, metabolic acidosis, high temperature (late sign)
also may see dark urine color, tachycardia, tachypnea
The treatment for malignant hyperthermia is
dantrolene sodium- muscle relaxant
1 mg/kg (supplied in 70 mL vials containing 20 mg of Dantrolene, 3000 mg of Mannitol and sodium hydroxide)
administer until symptoms subside
up to 10 mg/kg
Ryanodex is
a new IV formulation of dantrolene for the prevention and treatment of MH
shorter half-life
requires supplementation of mannitol
requires fewer dials and less reconstitution
Anesthesia in pregnant patients
most common appendectomy, cholecystectomy, ovarian, or trauma
For pregnant patients
elective surgery should be delayed until after delivery
Nonurgent surgery should be performed in the second trimester
