To creat anesthesia, inhalants must go from the vaporizer to _____
________, not concentration, of anesthetic in the _____ produces anesthesia
Partial pressure; brain
Brain partial pressure equilibrates quickly or slowly with alveolar partial pressure?
Quickly -cardiac output to brain is high -brain partial pressure ALWAYS moves towards alveolar partial pressure
Alveolar partial pressure is a balance between what two things?
1. input to the alveoli - Delivery
2. Loss from the alveoli - Uptake
Factors that affect delivery
- inspired anesthetic concentration
- Vaporizer setting
- Fresh gas flow
- Volume of breathing circuit
- alveolar ventilation
Inhalants are removed from alveoli by _____
Pulmonary blood (this is uptake)
Factors that influence uptake
- solubility of anesthetic
- patient's cardiac output
- alveolar-venous anesthetic partial pressure difference
How can we make an animal anesthetize quickly?
1. Fast rise in alveolar concentration
2. Increase delivery
- turn up vaporizer output
- turn up carrier gas flow rate
- minimize volume of breathing circuit
- increase ventilation
3. Slow down uptake
- inhalant w/ low solubility
- slow down cardiac output
- minimize partial pressure gradient
What are the effects of solubility on the uptake and distribution of inhalants?
Less soluble = readily leaves blood to reach equilibrium with gas and tissues More soluble = greater tendency to stay in the blood
A low blood:gas partition coefficient will have what 3 effects on uptake and distribution?
1. Rapid induction 2. Precise control of anesthetic depth 3. Rapid elimination and recovery
Why does decreased solubility result in rapid rise of anesthesia?
Decr solubility > faster alveolar rate of rise > faster brain rate of rise > rapid anesthesia
How does the amount of cardiac output affect uptake and distribution?
Amount of blood flow to lungs and tissues influences uptake
- high CO = greater amount of blood carrying inhalant away from alveoli to tissue
- low CO = less blood flow through lungs with less anesthetic removed
With lower cardiac output states, such as colic or sepsis, it is easier/harder to overdose on inhalants?
What is the effect of arterial to venous partial pressure gradient on uptake and distribution?
- venous blood returning to the lungs for re-oxygenation will retain some inhalant
- Pa - Pv gradient must exist fro uptake to occur
- as anesthetic duration progresses, alveolar rate of rise slows due to narrowing of the Pa-Pv gradient
What is uptake into muscle and fat slower than the brain?
Due to lower tissue perfusion and higher tissue:blood partition coefficients
Recovery from anesthesia is due to _____
Removal of inhalants from the CNS - Gradient: CNS > blood > alveoli > outside - decr partial pressure in alveoli & anesthesia circuit
4 factors that affect elimination of inhalants
1. Alveolar ventilation 2. Inhalant solubility 3. Cardiac output 4. Duration of anesthesia
If a drug has a lower solubility, it will have a faster/slower recovery?
Other factors affecting inhalant recovery include:
- decr inhalant delivery > faster elimination - incr alveolar ventilation > faster elimination - incr CO > faster elimination -body temperature Decr temp > incr solubility > longer recovery -metabolism of inhalants (minimal)
Describe the role of inhalant metabolism on removal from the body?
-minimal role in removal - toxic metabolites can be produces E.g. Sevo > Compound A Iso, desflurane, enflurane > carbon monoxide
Which of these is incorrect? A. MAC is a measure of potency B. MAC is a measure of speed of induction C. MAC is additive among multiple inhalants
Name some desirable effects of inhalants
- reversible, dose-dependent general anesthesia -non-addictive -decrease cerebral metabolic rate -elimination not dependent on hepatic and renal function
What effects do inhalants have on the cardiovascular system?
-Major effect -all REDUCE cardiac output - decreased myocardial contractility Decr stroke volume and CO -decrease peripheral vascular resistance Hypotension -dose-dependent effects
What effects do inhalants have on the pulmonary system?
As inhalant dose is increased:
- decr spontaneous ventilation
- depressed tidal volume & resp frequency
- incr arterial CO2
- medically stimulation of respiration due to hypercapnia is reduced
- respiratory arrest occurs at 1.5-3 MAC
How the dose-related decrease in ventilation and blunting the response to increased CO2 act as a safety mechanism?
Incr partial pressure in brain > decr ventilation > decr uptake > decrease partial pressure of brain
What are the effects of inhalants on the CNS?
1. Immobility and unconsciousness
2. increase cerebral blood flow
- Cerebral vasodilation
- Hypoventilation > incr CO2 > vasodilation
- Leads to an incr in ICP (dose related)
3. high doses of inhalants (>1 MAC) > loss of cerebral blood flow autoregulation
- these are often avoided with increased intracranial pressure b/c brain is within a fixed space and contains CSF, blood/vasculature, brain tissue
What are the effects of inhalants on the liver?
1. Minimal hepatic metabolism of inhalants
2. Possible prolongation of drug metabolism
- decr CO > decr hepatic blood flow
- decr hepatic metabolism co-administered drugs
3. Isoflurane most likely to maintain hepatic blood flow
What are the effects of inhalants on the kidneys?
1. Mild, reversible, dose-related decrease in renal blood flow & GFR - Related to overall decr CO 2. Nephrotoxicity - Rarely documented in domestic spp. - Breakdown of sevoflurane > free fluoride ions & Compound A
What is malignant hyperthermia?
1. Reported in horses, dogs, pigs
2. Myopathy secondary to inhalant exposure
- Genetic mutation of ryanodine receptor (in mm cells, important in mm contraction)
- massive incr in cytosolic Ca2+
- incr sk mm oxidative metabolism
- decr O2 supply and incr CO2
- eventually causes cric collapse & death
- discontinue inhalant administration
- Dantrolene sodium - muscle relaxant
High potency -MAC = 1.2-1.6% Intermediate solubility -Blood:gas partition coefficient = 1.4 Minimal liver metabolism -Best at maintaining liver perfusion Most common modern inhalant used (cheap)
Intermediate potency - MAC = 2.2-3% Low solubility - Blood:gas partition coefficient Small amount of liver metabolism (-5%) Compound A production - no real clinical significance