Desflurane Flashcards
What is the ONLY inorganic IA?
Nitrous (means it does NOT contain carbon)
When did IV inductions begin (approximately)
Just before WWII.
Dr Lundy first used thiopental as induction agent? (LM)
1850-1930 Diethyl ether - used for what?
Inhalation inductions - historically took a LONG time to induce. This is where the PLANE or STAGE of anesthesia came from.
(was the Queen of anesthesia)
Stage I
Analgesia or disorientation - from the beginning of induction of GA to loss of conciousness
Stage II
Excitement or delirium
from loss of conciousness to onset of automatic breathing. Eyelash reflex disappears. Coughing, vomitting & struggling may occur; respiration irregular with breath-holding.
(Almost skipped with current IV induction agents, could last 5 minutes with Diethyl ether!)
Stage III
Stage of SURGICAL anesthesia
-from onset of automatic respiration to respiratory paralysis, divided into four planes:
(THIS IS WHERE IV INDUCTION PUTS PATIENTS VERY QUICKLY)
Stage III - PLANE 1
onset of automatic respiration to cessation of eyeball movements. Eyelid reflex lost, swallowing reflexes disappears, marked eyeball movement may occur, conjunctival reflex is lost at the bottom of the plane.
Stage III - PLANE 2
cessation of eyeball movements to beginning paralysis of intercostal muscles. Laryngeal reflex lost, corneal reflex disappears, secretion of tears increases (a good sign of LIGHT anesthesia), respiration automatic and regular, movement & deep breathing as response to skin stimulation disappears.
Stage III - PLANE 3
Beginning to completion of intercostal muscle paralysis. Diaphragmatic respiration persists, progressive intercostal paralysis, pupils dilated & light reflex abolished.
- desired plane when muscle relaxants were not used. ** Typically try to avoid now-a-days**
Stage III - PLANE 4
Complete intercostal paralysis to diaphragmatic paralysis
(usually occurs around MAC of 2)
Stage IV
Stopping of respiration to death.
- Anesthesia overdose
- Medullary paralysis with respiratory arrest and vasomotor collapse
- Pupils widely dilated and profound muscle relaxation.
MEET BART DURHAM!
-big problem in the 1930’s, as there were no ETTs!
Desflurane was introduced when?
1992 (2 years before sevo)
Can be described as LIGHTSWITCH anesthesia…. (by des reps :)
still need to turn up gas flows at the end of a case however to help blow the gas off.
Getting rid of all halogens except for fluorine results in an anesthesitc with??
- Poor lipid solubility
- Extremely resistant to metabolsim
Insolubility Advantages are what?
- rapid induction
- Precise control of anesthetic concentrations (can make very quick changes)
- Prompt recovery independent of length of anesthesia
Disadvantages of Des
- Airway irritation (not suitable for inhalation induction)
- SNS stimulation (if you increase levels too quickly)
- CO production (carbon monoxide)
- Requires New vaporizer technology (can fill des vaporizer while in use)
Vaporizer is warm while in use (like a little campfire in the OR! )
Pharmacoeconomics
Des has a high bottle pricetag.
HOWEVER - more than just the pricetag should be a factor.
- factor in the cost savings of rapid induction and early wake-ups? - could save getting patients out of OR and home sooner.
- can use lower flow rates
**Could be argued that DES might actually be the cheapest way to go. **
What is the Vapor pressure of Des?
669
(close to atmospheric pressure! Ball-spring that pushes ball back and lets vapor out… )
Is why new technology was required…
For every cc you would get into a REGULAR vaporizer, 20 cc would get into the atmosphere…
What is the Odor of Des?
Etheral or monkey perfume (but goes away VERY quickly)…. but LM said he doesn’t think he has smelled it..
Which is more insoluble, Des or Nitrous?
Des
What is the preservative in Des?
There is none!
What is the Blood gas partition of Des?
0.42
What is the typical MAC of Des (37 C, 40yo, sea level, 100% 02, blah blah blah)
6.6%
Desflurane is Isoflurance with what chemical difference?
Clorine atom replaced witha fluorine atom.
Properties of DES
Is a Fluorinated methyl ethyl ether
- Substitution of flourine for chlorine on the ethyl component of the methy-ethyl ether
- Enhanced molecular STABILITY
- 3 X Greater vapor pressure than ISO
5 X LESS potent than ISO
Is there a correlation between between anesthetic potency and blood gas partition coefficient?
NO
What is the only measurable metabolite in Desflurane?
tri-fluoroacetate
Airway properties of Des
Airway Irritant (especially if inspired concentrations are increased rapidly - avoided by incremental increases of inspired concentrations 2% every 2-3 breaths. )
Salivation
Breath holding
Coughing
Laryngospasm
Occurs mainly @ concentrations greater than 6% (NOT THE MAC, but the %)
Not for inhilation induction
May be used for LMAs
The FI quickly approximates WHAT?
FA
-Rapid achievement of alveolar partial pressures necessary for anesthesia
Des patients usually wake up quickly or slowly (assuming sufficient gas flows)
quickly
(Lower blood gas solubility)
Will Desflurane impair the mental function of OR personnel via inhaling trace gases?
NO
DES will provide retrograde amnesia. True of False?
False (it will not).
Des does what to CMRO2 and cerebral activity?
Decreases them.
Des decreases cerebral blood flow. True of False?
False!
- It increases cerebral blood flow (was a typo on his slides)
In regards to EEG, < 0.4 MAC = what?
Increased frequency and voltage
EEG - 0.4 MAC ?
Begins to reduce CMRO2
EEG - 1 MAC?
Decrease in EEG frequency, maximal voltage occurs
EEG - 1.5 MAC ?
Suppression of BURST activity
EEG - 1.5 - 2 MAC
Electrical Silence
No S/S of seizure activity
Evoked Potential Monitoring
- Causes dose-depedent large decreases in amplitude.
- Causes does-dependent moderate increases in the latency of CORTICAL components.
- Decreases amplitude are greater than decreases in latency.
- Use of nitrous with desflurane does not abolish these characteristics.
- Starting at 0.5 MAC, des INCREASINGLY depresses EVOKE POTENTIALS
How would you DECREASE Cerebral blood flow under Des?
Hyperventolate to 30 ETCo2.
Desflurane produces dose-dependent ____ in Cerebral blood flow?
Increases
@ Greater than 0.6 MAC, with normocapnia, desflurane produces what??
Cerebral vasolidation
reduced cerebral vascular resistance
increased CBF
lowered CMRO2.
These changes occur within MINUTES of des administration.
Cerebral Blood flow changes occur independent of ___ and increases in CBF last up to ___ hours.
Independent
4
Does desflurane abolish cerebral blood flow auto-regulation?
No consesus at this time.
DES Impact on CMR02
- Desflurane produces dose depedent decreases in CMRO2
- When EEG becomes isoelectric, no further reductions in CMRO2
- Desflurane reduces CMRO2 less than iso, but COMPARABLE to sevo.
DES and Intracranial pressures?
Raise or lower ICP?
Patients with space occupying intracranial lesions are at ____ risk?
Hyperventilation to what opposes this phenomenon?
What dose is required to increase ICPs?
Raise
Increased
30mmHg
0.8-1.1 MAC
Circulatory changes of DES? (6)
- Lower systemic BP
- Increased HR
- Alterations in CO, SV, and RAP
- Reduction of SVR
- Alterations in heart rythm
- Alterations in coronary blood flow
What can be substituted for an equal MAC portion of DES to decrease magnitude of BP drop?
Nitrous
DES and MAP
Dose dependent decreases in MAP
Decreases in BP is due to reduction of systemic vasular resistance, unlike halothane
Des and HR
Increases HR
(effect is blunted by giving opioids or beta blockers)
Doesn’t alter carotid sinus/SA
HR increases seen LESS with the elderly
Does not cause dysrhythmias
Does NOT alter QT interval
DES and Cardiac Output
LV SV is dropped by how much?
30%
(dissipates within 5 hours of des anesthesia)
Increases in HR offset decreases in SV
vasodilatory effects of des makes observation of myocardial depressant effects LESS aparent - Yet enough DES can cause stage 4 - Circulatory Collapse!
DES and RAP (right atrial pressure)
DES raises RAP similar to ISO/SEVO despite vasodilatory effects.
Reduces SVR (due to increased (up to x4) skeletal muscle perfusion)
DOES NOT appreciably alter pulmonary vascular resistance
DES and Neurocirculation
Abrupt increases in desflurane concentrations INCREASES SNS & renin-angiotensin activities
Transiet Increases in HR & BP
Maximal response is reached at 8% des or higher
Sites mediating this response?
upper airway and lungs
Abated by Fentanyl and Betablockers
DES has what myocardial depressant effects? (4)
- Inhibition of CNS outflow
- Autonomic ganglionic blockade
- Decreases catecholamine release
- Decreased influx of Calcium Ions
Coronary Steal and Des..
Robs from the Poor and Gives to the Rich! Robin Hood would be pissed!
Coronary Steal is NOT clinically significant with DES.
-Des induces coronary vasodilation - acts on vessels of 20-50 um.
What MAC does des produce increases in RR?
Up to 1 MAC
-also produces reductions in Vt, (lizard on a hot rock)
NET Effect:
lower MV, higher PaCO2
What is the breathing pattern of DES up to 1 MAC?
Rythmic and regular - no sighs
(lizard on a hot rock)
Decreased Ventilatory response to CO2
Apnea occurs at what MAC?
1.5-2 MAC
Increases in PaCO2 more profound in patients that have what?
Lung disease
Increases in PaCO2 begin to dissipate after how many hours of SPONTANEOUSLY breathing Des anesthesia?
5 hours
Surgical stimulation under des increases MVV. True or False?
True
Breathing
Mechanism or action?
Inteferance with intercostal muscle function causes what?
Mechanism - direct depressant effects on MEDULLARY VENTILATORY CENTER
Chest wall de-stabilization
Assisted ventilation is very effective in significantly reducing PaCO2 under des. True or False?
False
it is NOT effective…
What is the best way to manage Des mediated ventilatory depression?
Controlled Ventilation
(assisted ventilation will only lower PaCO2 3-5 mmHg)
DES depresses the ventilatory response to ___?
Hypoxemia
DES may induce bronchoconstriction in __.
Smokers
(not contraindicated in smokers, but you must be sure to use it correctly…
In HIGH enough concentrations DES can actually break status asthmaticus
DES and the Liver
- Hepatic blood flow is maintained similar to Iso/Sevo (completely maintained)
Portal vein blood flow may be INCREASED.
There can be transient increases in LFTs following DES administration
Hepatotoxicity….
Post-op liver dysfunction may occur…
Hepatocyte hypoexmia.
Pre-existing liver disease increases the risk.
Desflurane oxidative metabolized by cytochrome P450 to form acetylated liver protein adducts by mechanisms similar to halothane.
Incidence with desflurane will be markedly lower due to less metabolism.
DES produces dose dependent decreases in Renal blood flow, GFR, and U/O. True of False?
True
Mechanism is reduced SVR & CO
(preop hydradation helps prevent this)
DES produces Compound A.. true or false?
FALSE
No compound A or free flouride ion problems
(can used in a closed circuit)
Neuromuscular junctions
Desflurane relaxes skeletal muscle 2x > than halothane
DES provides dose-dependent enhancement of NM blockers
DES can trigger MH, but less potent than halothane- still avoid DES with pt. hx or family hx of MH.
DES produces dose depedent ____ in uterine smooth muscle contractility.
Decreases
-also reductions in uterine blood flow.
Modest changes @ 0.5 MAC, significant at 1 MAC
Desflurane is both mutagenic and carcinogenic. True or false?
False
It is NEITHER.
DES is unlikely to decrease resistance to bacterial infection and does not alter leukocyte phagocytotic function.
Overall total body 02 requirements are ___.
Why?
reduced
(heart more so than other organs)
Due to metabolic depressant effects and overall decreased functional needs.
Where does metabolism of DES occur?
What drug is the metabolic pathway of DES similar to?
What are the results of DES metabolism
ether or ether-halogen bonds
Iso
(0.02% undergoes oxidative metaboism via cytochrome P-450)
Results are inorganic fluorides, trifluoroacetic acid, C02, & water
Carbon Monoxide - What causes this?
More or less than ISO?
Occurs with dry CO2 absorbents, High absorbent temps, prolonged HIGH gas flow rates…
HIGHER Carbon monoxide levels than iso
DES requires ___ for production.
ISO (will always be more expensive because of this)
Boiling point and Vapor pressure (at 20C)
23.5 and 664
Major Characteristics of DES
(4)
- DECREASED solubility
- DECREASED potency
- INCREASED stability
- INCREASED vapor pressure
Human Tissue: Blood Particion Coefficients
Fat
Brain
Heart
Liver
Kidney
Muscle
Fat - 27
Brain 1.3
Heart 1.3
Liver 1.3
Kidney 1.0
Muscle 2.0
What are the major implications of LOW solubility?
- More rapid wash-in
- Greater anesthetic control and precision
- More rapid emergence
- POTENTIAL greater economy
- May eliminate N20 without kinetic disadvantage
Which is faster for inspired and alveolar concentration equilibration, DES or Nitrous?
Nitrous, but a close second id DES…
then sevo, iso, then halothane
Metabolic pathway results of both DES and ISO are?
Both end up with triflurocetic acid
METABOLISM OF INHALED AGENTS
% Uptake recovered as Urinary Metabolites?
DES 0.02
ISO 0.2
SEVO 5
Halo 15-20
(the less metabolized = the less metabolites produced! No metabolism would be the best!)
Effect of Age on MAC?
Younger = Increased MAC %
Age - 100% 02 - 60% N20
<1 - 9.2-10 - 7.5
1-12 - 8.1-9.1 - 6.4
18-30 - 7.3 - 4
31-60 - 6 - 2.8
>60 - 5.2 - 1.7
Can a patient have “DES” breath in PACU?
Unlikely
MAC, make awake, MAC - BAR
MAC - 6.0%
MAC-awake 2.42%
MAC-BAR 1.45%
MAC with 60-70% nitrous - 2.83%
