Causes tonic clonic seizures. Exacerbated by?
Enflurane - hypocarbia and repetitive auditory stimuli
Only IA that suppresses seizure activity
Used in neurosurgery at 0.5 MAC
Can compensate for increase in ICP by hyperventilation
Desflurane Isoflurane as well - but at the time the induction agent is given
CANNOT compensate for increased ICP by hyperventilation
Enflurane - Hypocarbia can cause tonic clonic seizures
Highest amount of CO production
Desflurane Then Iso and enflurane Trace with sevo and halo
Safest for CAD with the supplementation of opioids
NO increase in CVP or RAP
Nitrous oxide Transient with desflurane and Isoflurane
Giving opioids with this agent may unmask undiagnosed myocardial depression, CAD and severe hypovolemia
Nitrous oxide - opioids take away the SNS stimulation and these patients get a profound SUDDEN bradycardia and hypotension
Autoregulation to CO2 remains UNCHANGED with these agents up to what MAC?
Sevoflurane up to 1.5 MAC Naglhout also states Desflurane as well.
Which agent offers the greatest cerebral protection from ischemia?
Isoflurane - at >1 MAC it is often used for Neurosurgery but at 0.5 MAC Due to the unchanged CBF at >1 MAC (still increased CBF) and decreased cerebral metabolic oxygen requirements Greatest uncoupling of CMRO2 and CBF
Which agent produces only a mild increase in ICP
Nitrous oxide - likely due to the inability to administer 1 MAC
Isoflurane is and Isomer of Enflurane with these key differences
1. Does not induce seizures, but rather supresses seizure activity 2. It does not increase CSF production and allows CSF outflow 3. Iso has minimal myocardial depression
IA that increases CSF production and increases resistance to CSF outflow
Which agents cause direct myocardial depression
Halothane Nitrous oxide
Which agents decrease BP is a result of the agents ability to primarily decrease SVR and have minimal myocardial depression?
Sevoflurane Isoflurane Desflurane
Gasses that have baroreceptor reflex intact
Ennflurane, Isoflurane, Desflurane
Volatile anesthetic that typically increases HR but in Elderly and Neonates this effect is blunted and Heart rate is decreased
This volatile anesthetic suppresses SA node depolarization (junctional rhythm) and decreases conduction in the bundle of his and purkinge fibers
Increases BP, HR, SVR and CO d/t SNS stimulation
Volatile anesthetic that produces DOSE DEPENDENT decrease in CO
LVSV is decreased __________% for all volatile anesthetics. Our notes say a specific one.
15 - 30% for desflurane Often times increased HR is enough to offset the decrease in stroke volume
This volatile anesthetic has a wider margin of safety between that which anesthetizes the brain and that which produces cardiovascular collapse. This means it has minimal cardiac depressant effects in the doses we use it.
Does Not have an increase in CVP or RAP
Has minimal effects on SVR
Halothane (all other volatile anesthetics decrease SVR)
_____________ increases blood flow to ____________ and ____________ areas. This distribution is similar to a ___________ effect. There is an excess perfusion relative to oxygen needs. It may manifest in the OR as ____________ due to _____________ blood flow. There also may be enhanced _______________ like NM blockers.
Isuflurane skeletal muscles and cutaneous areas ß-agonist loss of heat due to cutaneous delivery of drugs.
What is a possible explanation for the increase in cutaneous blood flow produced by all volatile gasses?
May reflect a central inhibitory action on temperature regulating mechanisms.
should be avoided in the neonate with congenital heart disease
Nitrous - d/t increased PVR which may increase the magnitude of a right to left shunt causing further decrease in arterial oxygenation.
Two volatile gasses that sensitize the heart to Epi
Halothane Enflurane ≥ 4.5 mg/kg
Dilate the small coronaries and cause a redistribution of flow from the ischemic area to that of non ischemic areas, but it is not clinically significant and thus still cardioprotective
Isoflurane - causing coronary steal
An abrupt Increase this volatile gas to cause neurocirculatory response.
Desflurane -irritates airway and will cause a transient increase in BP and HR d/t SNS stimulation - this can be blunted by opioids/esmolol/clonidine prior to increasing MAC Also consider this for Isoflurane - but des has a faster onset
T or F Volatile anesthetics produce the same amount of myocardial depression in the healthy and diseased myocardial muscle?
TRUE - the significance is just greater in the diseased heart because they are starting form a lower baseline (baseline decreased contractility).
Neurocirculatory responses by abruptly increasing Desfluarane want to be avoided in which patient
Causes a myocardial depression in CAD patients that does not occur with healthy individual
As little as 40% of nitrous oxide
What anesthetic may not be good for aortic stenosis but good for mitral or aortic regurgitiation? Why?
Isoflurane - because of the peripheral vasodilation decreasing after load
what may enhance the myocardial depressant effects of volatile anesthetics
Drugs that can influence the magnitude of cardiac depression and circulatory effects
CCB- already decrease contractility and make the heart more vulnerable to myocardial depression antihypertensives and ß-blockers may make patients more vulnerable to the circulatory effects
What is it called when volatile anesthetics activate the K ATP pump causing hyper polarization. Which has negative inotropic effects and relax vascular smooth muscle
Ischemic preconditioning - which is cardiaoprotective
All inhaled anesthethetics except _______________ produce DOSE DEPENDENT increases in respiratory rate. What does this gas do?
Isoflurane Increases RR up to 1 MAC At concentrations >1 MAC it does not further increase the frequency of breathing
What is the net effect of the respiratory changes produced by anesthetic gasses to a patient under anesthesia
Rapid shallow breathing, with decreased minute ventilation and increased PaCo2 (increased RR not enough to offset the decreased TV)
Which anesthetic gas has MINIMAL changes in minute ventilation and MINIMAL changes in resting CO2 levels?
why would adding nitrous to an anesthetic plan of a COPD patient be beneficial?
COPD may attenuate the magnitude of the increase in PaCO2 by volatile anesthetics. Nitrous however does not increase PaCO2 and using it may result in less of a depression of ventilation. This ventilatory-sparing effect is detectable with all volatile anesthetics
How do volatile anesthetics effect minute ventilation and CO2
Dose dependent decrease in minute ventilation and dose dependent increases in PaCO2
What can be used to asses upper airway reactivity
the presence of a cough to ETT cuff inflation
Volatile anesthetic that causes hepatic artery vasoconstriction and decreases hepatic blood flow
Volatile anesthetics that maintain hepatic blood flow.
Sevoflurane, Isoflurane and Desflurane
Why is maintenance of hepatic blood flow important?
Hepatocyte hypoxia is a significant etiology of post-op hepatic dysfunction
Blunts Baroreceptor response, so not increase in HR
Volitile anesthetic NOT metabolized by CYP450 2EI
Sevoflurane - but is metabolized by CYP450
Because of its chemical structure Sevoflurane cannot undergo metabolism to an ______________. Therefore it does not result in the formation of ______________ and cannot stimulate the formation of _______________. However, Halothane, desflurane, and enflurane are metabolized to ___________ and therefore are susceptible to ________________ and _____________.
Acetyl Halide, trifluroacetylated proteins, anti-fluroacetylated protein antibodies. Acetyl Halides, Immune mediated hepatotoxicity and cross sensitivity.
In a patient with preexisting renal failure which VA should be avoided and which are best and why?
Sevoflurane should be avoided. There is potential that it could accentuate pre-existing renal disease. It has no be confirmed, but just to be safe. It is metabloized to inorganic fluoride which MAY cause inability to concentrate urine. Use Desflurane or Isoflurane because they are less likely to aggravate preexisting renal disease
What may be enhanced by opioids in patients who are receiving nitrous oxide?
Skeletal muscle rigidity. Normally rigidity occurs at doses >1 MAC, delivered in a hyperbaric chamber, but ant normal atmospheric pressure and at lower doses, it can occur with the administration of opioids
VA that least potentiates the effects of NMB
Isoflurane Its effects are similar to halothane per Stoelting*
Nitrous oxide irreversibly binds what?
Cobalt atom in B12 leading to a b12 deficiency and deficiency in B12 dependent enymes that facilitate DNA synthesis and myelin formation (pernicious anemia, birth defects, megaloblastic anemia which is bone marrow depression and neuropathies).
0.004% Metabolized in GI tract by reductive metabolism bu anaerobic bacteria such as pseudomonas
15 - 20% metabolized by CYP 2EI oxidation (acetylation of hepatocellular molecules, trifluocedic acid) when enough 02 is present but undergoes reductive metabolism when 02 is insufficient
2.3 - 3% metabolism via CYP450 2EI oxidation, the free fluoride comes from the fluorine on the terminal carbon
0.2 - 2% metabolism via CYP450 2EI oxidation to trifluocedic acid- susceptible to auto antibodies in susceptible patients.
0.02% metabolism via CYP450 2EI oxidation to trifluocedic acid- susceptible to auto antibodies in susceptible patients.
The VA that break down to CO have contain a CHF2 moiety , which anesthetics are these
Desflurane>Enfluane and Isoflurane
5-20% undergoes oxidative metabolism via CYP450 system to for organic and inorganic FLUORIDE metabloites
Sevoflurane - it DOES NOT undergo metabolism to an acetyl halide - like ALL other volatile gasses of
Uptake of a volatile anesthetic into the blood = ____ x _____ x _____
Solubility x CO x A-v Solubility: how anesthetic partitions between blood/reservoir and gas/alveoli (use partition coefficients aka "Oswaldt Solubility Coefficients") A-v is difference in partial pressures in alveolar and venous blood
At normal body temp (37C), list the blood/gas solubility coefficients (Des, N2O, Sevo, Iso, En, Halo)
Des 0.42 (poorly soluble) N2O 0.47 Sevo 0.69 Iso 1.4 En 1.8 Halo 2.4
The lower the solubility (Des), the ____ (faster/slower) induction and emergence
FASTER Solubility determines how fast the concentration in the alveoli (FA) reaches the concentration inspired (FI), the faster these values, the faster uptake to the brain and induction (PA = Pa = Pbr), also the fastest rate of rise on FA/FI curves It is faster bc very little anesthetic must dissolve in the blood before partial pressures equilibrate
An anemic patient will have a ____ (lower/higher) coefficient
Lower Less soluble due to fewer binding sites for anesthetic in the blood, faster uptake of inhalational agent
What does FA and FI represent? What are they determined by?
FA: partial pressure of anesthetic going to the brain. Determined by inhaled partial pressure, alveolar ventilation, breathing circuit (uptake into plastics/rubber), FRC. FI: inspired %, can be controlled by flow rate and vaporizer setting
Change in FA (alveolar concentration) is ____ (faster/slower) with increase RR and decreased TV
FASTER Except N2O bc it already has such a low solubility, inc in ventilation will not shift the curve significantly, especially compared to halothane
What is uptake influence on FA/FI?
Uptake opposes the effect of ventilation (which increases FA), there is uptake at tubing, tissues, it all takes away from alveolar concentration If uptake removes 2/3 of the anesthetic, FA would be 1/3 of FI (Review slide 23)
What is overpressure?
Use of high delivered concentrations For example, halothane B/G of 2.4 would result in a slow induction, but using overpressure, increased concentration will speed up the induction By increasing the PI above that required for maintenance of anesthesia, the high Pa (and slow induction) can be offset to some extent
Increased CO (seen in shock for example), will ____ (inc/dec) speed of induction
DECREASE Increase CO will increase solubility, the higher solubility, the slower the induction
For lean tissue (brain), coefficients are between __ and __ For fat, coefficients (except for N2O) are between ___ and ___
Lean tissue coeffiecients between 1-2 Fat coefficients are high, from 27-67, except N2O is 2.3
Vessel rich group is __% of body mass and ___ % of CO Vessel poor group is __% of body mass and ___% of CO
VRG 9% of body mass and 75% of CO VPG 22% of body mass and 0% of CO
Muscle group is __% of body mass and ___ % of CO Fat group is __% of body mass and ___ % of CO
MG 50% body mass and 18% CO FG 19% body mass and 7% CO
In the FA/FI curve, what does the initial steep rise represent? First knee? Second rise? Second knee?
Initial rise: quick rise if low solubility First knee: uptake by VRG Second rise: uptake by MR group, uptake by VRG slows second knee: uptake by MRG slows
____ influences knee height ____ influences tail
B-G solubility influences knee height Tissue-Gas solubility influences tail
What is MAC
Minimum alveolar concentration, ED50 (effective dose in 50%) The concentration that will produce absence of movement in 50% of patients to noxious stimuli
To keep FA constant, how should FI be adjusted?
High at first, then decrease as VRG is equilibrated, decrease further when MRG is equilibrated.
The greater than alveolar ventilation/FRC ratio, the ___ (faster/slower) the induction
FASTER Neonates have a very fast induction for example
Inc ventilation and inc CO has what effect on FA/FI?
In theory no change, but slightly increases FA/FI 2x the ventilation and 2x the CO for example would double both input and removal
What is the concentration effect?
Results when a large volume of gas in absorbed. The remaining residual gas is concentrated as the volume decreases and the inspired ventilation increases which adds more anesthetic (neg pressure created by uptake draws more gas into the lung), just think: alveoli shrink and agents become concentrated Book definition: The higher the PI, the more rapidly the PA approaches the PI, speeds the rate PA increases
What is the second gas effect?
When N2O is used with another gas, a reduction in volume and replacement of N2O will increase concentration and amount of any gas given with N2O, which was absorbed in large volume The FA of a gas increases more rapidly when N2O is given as a second gas than when given alone
As the duration of anesthesia lengthens, washout will take ___ (longer/shorter)
Longer, more anesthetic is in the reservoirs Least soluble washout first The higher the B/G solubility coefficient, the longer emergence will take In general, emergence depends on length and depth of anesthesia, solubility of the agent, and MAC awake
Which is more soluble, N2O or nitrogen? What is the implication (which surgeries are N2O avoided in)?
N2O is 34x more soluble. Nitrogen=0.014, N2O=0.47 The bottom line with this difference is that when using N2O, increased pressure can build up in a closed space (bowel, pneumo, tympanic graft), and in these instances, N2O should be avoided
What is diffusion hypoxia? How is it avoided?
Diffusion Hypoxia: when rapid transfer from blood and tissue to alveoli decreases arterial tension of oxygen Avoided by washing out with oxygen instead of air for an adequate amount of time
What is the Meyer-Overton Theory? (Critical volume theory)
Correlation between lipid solubility of inhaled anesthetics (oil:gas partition coefficient) and anesthetic potency shows that inhaled anesthetics act by disrupting the structure or dynamic properties of the lipid portions of nerve membranes. Absorption of anesthetic molecules expands hydrophobic region of lipid bilayer which alters membrane function
According to the Meyer-Overton Theory, increased affinity for lipid will ____ (inc/dec) potency A decreased MAC means the inhaled agent is ____ (more/less) potent
Inc affinity for lipids will INCREASE potency Dec MAC is MORE potent
Which inhalational agents are cautioned with epi use?
CNS reflexes are mediated where?
Ventral horn of the spinal cord
Compare stages 1 and 2 of Anesthesia according to Guedel (pupils, HR, BP)
Stage 1: amnesia/analgesia; pupils react normally to light; irregular pulse; normal BP Stage 2: delirium/excitement: pupils pinpoint (reaction to light); irregular, fast HR, high BP, this stage can be disturbing to parents Note: stage 3 "operative" pupils not reactive, stage 4 "danger/OD"
T/F: N2O is safe to use as a sole anesthetic agent
FALSE. Use a balanced technique with other agents MAC is 105%!
As we increase altitude, we ___ barometric pressure
Boiling point occurs when what 2 values become equal?
When vapor pressure = barometric pressure
List factors that decrease MAC
Old age, pregnancy Hypothermia, hyponatremia Hypotension Hypoxemia, anemia Opioids, ketamine, benzos, clonidine, A2 agonists, LAs, ETOH
List factors that increase MAC
Hyperthermia CNS stimulants Youth (under one year old)
Which inhalational agent has the most potent bronchodilator effect?
What are the hepatic effects of halothane?
Oxidized metabolite: trifluroracetic acid Hepatotoxicity Halothane Hepatitis
What are risk factors for volatile agent induced hepatitis?
Fat Female Forty Mexican Prior exposure
Which agent has 0 risk of halothane hepatitis, why?
Sevoflurane, it can't be metabolized to trifluroacetylated liver proteins
Which inhalational agents should you avoid in peds?
Which inhalational agents do not decrease hepatic blood flow?
Isoflurane Desflurane Sevoflurane
Which inhalational agent is delivered through the tec 6 vaporizer?
How can sevoflurane lead to renal toxicity? What is a good preventative measure?
Sevoflurane is not renal toxic, but if compound A is produced (when sevo interacts with soda-lyme) and goes through bioactivation, the conjugates that produce reactive thiol can be renal toxic Prevent using at least 2 L/min FGF
Which inhalational agent blunts the baroreceptor reflex, possibly leading to decreased HR? (All others increase or don't change HR)
Which inhalational agent decreases seizure threshold?
Which inhalational agent produces the highest level of carbon monoxide?
Desflurane Then enflurane and isoflurane