Volatiles - test 3 Flashcards
What four things does pharmacokinetics describe in inhaled anesthetics?
- Uptake from the alveoli into the pulmonary capillary blood,
- Distribution,
- Metabolism,
- Elimination via Lungs.
The pharmacokinetics of inhaled anesthetics are influenced by ________.
Aging.
What factors does aging contribute to the pharmacokinetics of inhaled anesthetics?
- Decreased body mass,
- Increase fat mass (increase Vd for lipid-soluble drugs),
- Decrease clearance if pulmonary exchange is impaired (COPD, atelectasis),
- Increase time constraints due to lower cardiac output.
Boyle’s Law states that at a constant temperature, pressure and volume of a gas are __________ ___________.
Inversely proportional.
As positive pressure ventilation begins, the bellows contract. This will cause pressure to increase within the ventilator and circuit resulting in anesthetic gases flowing from high pressure to low pressure (lungs).
What is Fick’s law of diffusion?
It describes the rate at which molecules move from an area of high concentration to an area of low concentration.
Once the molecules get to the alveoli, they move around randomly and begin to diffuse into the pulmonary capillary.
What three things does diffusion depend on?
- Partial pressure gradient of the gas (high to low),
- Solubility of the gas (diffusion),
- Thickness of the membrane.
According to Graham’s Law of Effusion, smaller molecules effuse faster dependent on ________.
Solubility (Not just based on size alone).
Carbon dioxide, molecular wt 44 g; Oxygen, molecular wt 32 g; Carbon dioxide is 20x more diffusible because it is more soluble than O2.
An inhaled anesthetic will travel from the alveolus to the pulmonary artery and to the ___________ in one or two circulation times to exert its effect.
brain.
What is alveolar pressure an indicator of?
How is alveolar pressure measured?
Depth of anesthesia (“Is patient asleep enough?”),
Recovery of anesthesia (“Is the patient waking up?”).
Pulmonary alveolar pressure can be measured through end-tidal gas.
If the amount of anesthetic gas is greater in the alveolus (PA) than in the brain (PBr) what does that mean?
The patient is still awake, there is still room in the brain for anesthetic gas.
If the amount of anesthetic gas is greater in the PBr than in PA, what does that mean?
Gas is leaving from the brain (vessel-rich) to the alveolus where the patient will eventually wake up.
What are the 3 partial pressure gradients that affect the induction process?
- Anesthetic machine to alveoli,
- Alveoli to blood,
- Arterial blood to the brain.
What is a partition coefficient?
The partition coefficient refers to the relative solubility of the anesthetic gas between two compartments.
What four factors will affect the input of the volatile anesthetic from the anesthetic machine to the alveoli?
- Inspired partial pressure,
- Alveolar ventilation,
- FRC,
- Anesthetic breathing system (Is there a lot of breathing?).
What 3 factors will affect the uptake of volatile anesthetics from the alveoli to the blood?
- Blood: gas partition coefficient,
- Cardiac output,
- Alveolar-to-Venous partial pressure differences.
What 3 factors will affect the uptake of volatile anesthetics from the arterial blood to the brain?
- Brain: blood partition coefficient,
- Cerebral blood flow (dependent on CO),
- Arterial-to-Venous partial pressure difference.
What factor contributes to how rapidly PA (pressure of the alveolus) approaches PI (Pressure of Inspired Volatile)?
Concentration Effect (concentration gradient).
6% desflurane will get a patient sedated faster than 1% desflurane.
How would you offset a slow induction from highly soluble volatiles?
Over pressurization, a large increase in inspired pressure (PI).
Get the patient asleep in a couple of breaths, but sustained delivery will result in an overdose.
1 _________ breath of high concentration of Sevoflurane (7%) will result in loss of eyelash reflex (stage 2).
vital capacity.
The second gas effect is the use of high-volume gas (________) concurrently with a volatile (sevoflurane, isoflurane, desflurane).
Nitrous (N2O).
Why is Nitrous always used in the second gas effect?
Nitrous creates a concentration effect.
The high volume of N2O uptake into the pulmonary capillary (very diffusable) will increase the concentration of the 2nd gas (ie: desflurane). This will increase the uptake of 2nd gas due to the gradient.
Nitrous oxide likes to diffuse into ___________ cavities.
air-filled cavities (lungs, bowels, ear canals).
What are some procedures where you want to avoid using nitrous oxide?
- Open belly (compliant space),
- Ear Cases (non-compliant space),
- Eye Cases (non-compliant space).
What happens if you give N2O to patients with a pneumothorax?
It will increase the size of the pneumothorax by 250% when compared to giving supplemental oxygen.
If nitrous oxide was administered during intraocular retinal repair, what will happen?
The patient will have retinal artery vision loss within one hour.
By ________ alveolar ventilation, you can increase the speed of induction.
increasing.
Increasing respiration rate from 10 bpm to 20 bpm). This will work to an extent.
Hyperventilation will cause a decrease in __________ which will decrease cerebral blood flow (vasoconstriction) and limit the speed of induction.
PaCO2.
Differentiate between spontaneous ventilation and mechanical ventilation.
Spontaneous ventilation has a dose-dependent depressant effect on alveolar ventilation (negative feedback loop). As input decreases due to decreased ventilation, the volatile redistributes from tissue with high concentration (brain) to tissues with low concentration (fat). As brain concentration decreases, ventilation increases.
When mechanical ventilation, the body is not able to provide a negative feedback loop. The ventilator will continue to administer molecules at a set rate.
Solubility is defined as a ________ of how the inhaled anesthetic distributes between 2 compartments at _________ when partial pressures are equal.
Solubility is defined as a ratio of how the inhaled anesthetic distributes between 2 compartments at equilibrium when partial pressures are equal.
Solubility is temperature dependent. If the temperature of the blood increases, solubility _________.
Decreases.
The volatile anesthetic agent does not want to stay in the blood, it will want to go into the brain. Faster induction.
If blood solubility is high, a large amount of volatile anesthetics must be dissolved. How will this affect induction?
The anesthetic agent wants to stay in the blood and induction is prolonged.
Which one has the lowest solubility?
A. Desflurane
B. Sevoflurane
C. Isoflurane
Desflurane will have the lowest solubility followed by Sevo and then Iso.
This means that people will go to sleep and wake up faster from desflurane.
Halothane has a Blood: Gas Partition Coefficient of 2.54. What does that mean?
When the relative ratio is the same (when solubility equals out). There is 2.54 times more Halothane in the blood than in the gas compartment. This means that halothane is VERY soluble, it likes to stay in the blood. The blood will hold a lot of halothane. Slow induction and slow emergence.
What is the Blood: Gas Partition Coefficient of Desflurane?
0.42
This means that desflurane is not very soluble and does not want to stay in the blood. Fast induction, fast emergence.
What is the Blood: Gas Partition Coefficient of Halothane?
2.54
What is the Blood: Gas Partition Coefficient of Enflurane?
1.90
What is the Blood: Gas Partition Coefficient of Isoflurane?
1.46
What is the Blood: Gas Partition Coefficient of Nitrous Oxide?
0.46
What is the Blood: Gas Partition Coefficient of Sevoflurane?
0.69
Emergence depends on the rate of decrease in ______.
This process begins when the inspired partial pressure of volatile gas is _____.
Pbr.
0 mmHg
How _________ the gas is determines how soon the gas will be turned off for emergence.
soluble.
Less soluble turn gas (desflurane) will be turned off toward the end of surgery. More soluble gas (isoflurane) will be turned off sooner.
What are the colors associated with the following volatile gasses? Isoflurane: Sevoflurane: Desflurane:
Isoflurane: Purple,
Sevoflurane: Yellow,
Desflurane: Blue.
What is the definition of MAC?
The minimum alveolar concentration (MAC) is the concentration at 1 atm that prevents skeletal muscle movement in response to supramaximal, painful stimulation in 50% of patients.
What is the MAC required to prevent skeletal muscle movement in response to supramaximal, painful stimulation in 99% of patients?
1.3 MAC
What is the value for MACawake?
0.3 - 0.5 MAC
Patient will be able to respond to touch and sound, there will be protective airway reflexes.
What is the value for MACbar?
1.7 - 2.0 MAC
BAR- Blunt Autonomic (Adrenergic) Responses.
At MACbar there will be no SNS response to intubation.
What is the MAC value of Nitrous based on 30-55 y/o average, 37 degrees, C; 760 mmHg (1 atm)?
104%
Unable to give a MAC of nitrous unless you are in a hyperbaric chamber. Nitrous is never given alone as a general anesthetic. Nitrous is used as a supplement (second gas effect).
What is the MAC value of Halothane based on 30-55 y/o average, 37 degrees, C; 760 mmHg (1 atm)?
0.75%
What is the MAC value of Enflurane based on 30-55 y/o average, 37 degrees, C; 760 mmHg (1 atm)?
1.63%
What is the MAC value of Isoflurane based on 30-55 y/o average, 37 degrees, C; 760 mmHg (1 atm)?
1.17%
What is the MAC value of Desflurane based on 30-55 y/o average, 37 degrees, C; 760 mmHg (1 atm)?
6.6%
What is the MAC value of Sevoflurane based on 30-55 y/o average, 37 degrees, C; 760 mmHg (1 atm)?
1.8%
What are the two biggest factors that alter MAC?
Body Temperature
Age- 6% per decade (under 30, above 50)
What factors increase MAC?
- Hyperthermia
- Excess pheomelanin production (red-heads)
- Drug-induced increase in catecholamine levels
- Hypernatremia
What factors decrease MAC?
- Hypothermia
- Pre-op Meds (BZD), intraop opioids
- Alpha-2 agonist (precedex, clonidine)
- Acute EtOH ingestion
- Pregnancy
- Post partum (12-72 hours)
- Lidocaine
- PaO2 < 38 mmHg
- Mean BP < 40 mmHg
- Cardiopulmonary Bypass
- Hyponatremia
What factors do not affect MAC?
- Chronic EtOH abuse
- Gender
- Duration of anesthesia
- PaCO2 15-95 mmHg
- PaO2 > 38 mmHg
- Hyper/hypokalemia
- Thyroid gland dysfunction
How does anesthesia affect spinal immobility?
Spinal immobility is also affected by enhancing inhibitory ________ and acts on sodium channels to block the release of __________.
By depressing excitatory AMPA and NMDA receptors.
Glycine; Glutamate
There will be a loss of consciousness by the inhibitory transmission of GABA in the _________ and especially the _______.
Brain and RAS
There will be potentiation of glycine activation in the brainstem.
What is the pressure that would be exerted by one of the gases in a mixture if it occupied the same volume on its own?
Partial Pressure
Sum of the partial pressures will equal total pressure (Dalton’s Law).
What is the pressure at which the vapor and liquid are at equilibrium?
Vapor Pressure
What is Henry’s Law?
The amount of dissolved gas in a liquid is proportional to its partial pressure above the liquid.
The more dissolved gas that is in the liquid, the more partial pressure in the vaporizer. -This is how over-pressurizing works.
What increases vapor pressure and what decreases vapor pressure?
Heat increases vapor pressure.
Cold decreases vapor pressure.
What is the relationship between vapor pressure and volatility?
The greater the vapor pressure the more likely to evaporate and be considered more volatile.
Ie: Desflurane.
What is the vapor pressure of Halothane?
243 torr
What is the vapor pressure of Enflurane?
175 torr
What is the vapor pressure of Isoflurane?
238 torr
What is the vapor pressure of Desflurane?
669 torr
What is the vapor pressure of Sevoflurane?
157 torr
What is the ratio of by-pass gas/gas through the vaporizer compartment?
Splitting Ratio
What kind of vaporizer increases the gas-liquid interface and improves the efficiency of vaporization?
Flow-over vaporizer
Four functions of the anesthesia circuit:
- Deliver oxygen
- Deliver inhaled drugs
- Maintains temperature/humidity
- Removes carbon dioxide and exhaled drugs
Three types of anesthesia circuits:
- Rebreathing (bain)
- Non-breathing (self-inflating)
- Circle systems
Components of circle systems:
- Fresh gas inlet
- Inspiratory and expiratory limbs
- Reservoir bag
- CO2 absorbent
- One way valves
- Y piece
What is high flow anesthesia?
Fresh gas flow (FGF) exceeds minute ventilation (Vm)
What are some downsides to high flow anesthesia?
Wasteful and cools/dries delivered volume
What are some good things about using high flow anesthesia?
- Allows rapid changes in anesthetic
- Prevents rebreathing
What is low flow anesthesia?
Fresh gas flow is less than minute ventilation
What are some good things about low flow anesthesia?
Low cost and less cooling/drying
What are some downsides to low flow anesthesia?
- Very slow changes in anesthetic
- Concern with compound A production
Factors that contribute to the price of anesthetics:
- Cost of liquid/ml
- Volume percent of anesthetic delivered (potency)
- FGF rate
How do volatiles cause bronchodilation?
Relax airway smooth muscle by:
- Blocking voltage gated Ca++
- Deplete Ca++ in SR
- Require intact epithelium
Bronchodilation WITHOUT bronchospasm:
- Baseline pulmonary resistance unchanged by 1-2 MAC
- Need histamine release or vagal afferent stimulation
Risk factors for bronchospasm with volatiles:
- Cough response with ETT,
- age <10,
- URI
_____ > isoflurane at causing bronchodilation
Sevoflurane
Which volatile may worsen bronchospasm in smokers due to pungency/irritation?
Desflurane
Respiratory Resistance Comparison:
What are the 3 best gasses to use if you do not want respiratory resistance?
- Sevoflurane
- Halothane
- Isoflurane
Neuromuscular effects of volatiles:
Dose dependent skeletal muscle relaxation
- nitrous oxide has no relaxant effect on skeletal muscles
- Potentiate depolarizing and non-depolarizing NMBDs (nAch receptors at NMJ, enhance glycine at spinal cord)
What is ischemic preconditioning?
If the heart recognizes brief periods of ischemia before being subjected to longer periods of ischemia, the heart is able to prepare itself for the longer period of ischemia.
What effects do volatiles have on CNS activity?
Dose dependent
- Decrease CMRO2 and cerebral activity
- Begins approx at 0.4 MAC as wakefulness changes to unconsciousness
- 1.5 MAC = burst suppression
- 2 MAC = electrical silence
How would you choose which volatile to use based on CNS activity?
Isoflurane = sevoflurane = desflurane
- choice of volatile for CNS activity doesn’t matter
Which volatiles have anticonvulsant activity?
Desflurane, isoflurane, sevoflurane
*at high concentrations and with hypocarbia
Which volatiles have proconvulsant activity?
Enflurane
*especially above 2 MAC or PaCO2 <30 mmHg
Ischemic preconditioning is mediated by _____
Adenosine
- Increases protein kinase C activity
- Phosphorylates ATP sensitive K+ channels
- Production of reactive oxygen species
- Better regulate vascular tone
At what MAC can ischemic preconditioning occur?
As low as 0.25 MAC
Why is ischemic preconditioning useful?
Prevents “reperfusion injury”
- Cardiac dysrhythmias
- Contractile dysfunction
- Clinically apparent in delaying MI for PTCA, CABG
What is SSEP?
Stimulation to periphery, it registers and is measured in the brain to ensure adequate neurotransmission to the spinal cord
What are MEPs?
There is stimulation in the brain and it is sent down the spinal cord and there is a measured response in the periphery
How do volatiles effect evoked potentials?
*Dose related - dercease amplitude and increased latency
- 0.5-1.5 MAC
- there won’t be enough impulses sent to measure if the spinal cord is getting damaged
What combination of volatiles is adequate for monitoring evoked potentials?
Nitrous 60% and 0.5 MAC volatile
How do volatiles effect cerebral blood flow?
*Dose dependent
- Increased CBF due to decreased cerebral vascular resistance
- may increase ICP
- Onset >0.6 MAC
- Occurs within minutes despite lack of BP change
Which volatile has the least vasodilatory effect?
Sevoflurane
- Isoflurane = Desflurane
- Nitrous is a potent vasodilator
- Halothane is the worst
At what MAC of halothane is autoregulation lost?
0.5 MAC
At what MAC of sevo is autoregulation lost?
Sevo preserves to 1 MAC
At what MAC of Iso and Des is autoregulation lost?
0.5-1.5 MAC
What is the volatile of choice for neuro anesthetics?
Sevoflurane - preserves autoregulation up to 1 MAC
Autoregulation graph
Which patients are most at risk of increased ICP from volatiles?
Patients with space-occupying lesions most at risk
At what MAC will there be an increase in ICP?
Onset >0.8 MAC
- ICP increases by 7 mmHg
How do volatiles effect respiration?
*Dose dependent↑ rate, ↓ Vt
- direct depression of medullary ventillatory centers
- interfere with intercostal muscles
- Rate change insufficient to maintain Vm or PaCO2
At what MAC does apnea occur?
1.5-2.0 MAC
How do volatiles effect hypoxic response?
Blunts hypoxic response - normally mediated by carotid
- At 0.1 MAC (50-70% depression) and 1.1 MAC (100% depression)
How do volatiles effect hypercarbic response?
Blunts hypercarbic response - dose dependent
- Nitrous does not increase PaCO2 - substitution for part of MAC: less depression
Carbon dioxide response curve:
What is hypoxic pulmonary vasoconstriction?
Normal contraction of pulmonary artery smooth muscle to divert blood to better oxygenated areas
When is HPV most concerning?
1 lung ventilation
After how long does HPV kick in and decrease regional blood flow in half?
5 mintutes
How long does the maximal HPV response last?
2-4 hours
How do volatiles effect HPV?
*Dose dependent decrease in response
- 50% depression at 2 MAC - only at the beginning
How do volatiles effect MAP?
Direct myocardial depression - alters Ca++ entry and SR function
- Dose dependent = ↓ contractility, SV and CO
-↓MAP primarily due to ↓SVR
- Greater significance in diseased hearts with already altered contractility
Which volatile has no cardiac depression?
Nitrous
How do volatiles effect heart rate?
*Dose dependent increases
- Sevoflurane only >1.5 MAC
- Iso and Des at lower concentrations
How do volatiles affect cardiac output?
*Dose dependent decrease in CO - offset by mild increase in heart rate for modern volatiles
What effect does nitrous have on cardiac output?
Sympathomimetic = mild increase in CO
Volatiles and Cardiac index graph
Immune effects from volatiles:
Neuroendocrine stress response
- ANS and HPA activated
- Perioperative surge in catecholamines, ACTH, cortisol
- Suppression of monocytes, macrophages and T cells
How is hepatic blood flow effected by volatiles?
Total hepatic blood flow = maintained
Hepatic artery flow = maintained
Portal vein flow = increased - volatiles vasodilate at 1-1.5 MAC
Which volatile decreases hepatic blood flow?
Halothane = hepatitis
What causes hepatotoxicity?
Inadequate oxygenation of hepatocytes - decreases blood flow and enzyme induction - increased oxygen demand
Type 1 hepatotoxicity:
- 20% of patients
- 1-2 weeks after exposure
- Direct toxic effect or free radical effect?
- Nausea, lethargy, fever
Type 2 hepatotoxicity:
- Less common
- Immune-mediated response against hepatocytes: eosinophilia, fever
- Prior exposure
- 1 month after exposure
- High mortality: acute hepatitis, hepatic necrosis
Volatile anesthetics are metabolized through P450 to ___________ metabolites
Acetyl Halide
Enflurane > Isoflurane > Desflurane
When volatiles are oxidized by P450, the metabolites can cause ____ ____.
antibody reaction
*most likely in patients sensitized by Halothane or Enflurane
What does sevo metabolize into?
Vinyl halide - not capable of stimulating antibody formation
What renal effects do volatiles have?
*Dose dependent decrease in RBF, GFR and urine output
- not related to vasopressin
- preoperatively hydrate
What causes nephrotoxicity with volatiles?
Fluoride toxicity
What 3 things does fluoride toxicity cause?
- Hyperosmolarity
- Hypernatremia
- Increased creatinine
Which volatile has the highest risk of nephrotoxicity?
Methoxyflurane
- 70% metabolized
- 1st noticed
- Removed from market
Why do newer volatiles not cause nephrotoxicity?
They have lower solubility and are exhaled prior to being metabolized and eliminated renally
How can sevo spontaneously combust?
Reacts chemically with desiccated absorbent
- Produces methanol and formaldehyde
How do you prevent combustion from sevo?
Add additional water to the sevo
How is MH diagnosed?
Caffeine contracture test
What are triggers for MH?
all volatile agents and succinylcholine
Pathophys of MH:
Hypermetabolic state of skeletal muscle
- excessive release of Ca++
- muscle rigidity
- Rhabdo
Symptoms of MH:
- increased body temp, CO2 production, O2 consumption
- 80% mortality untreated
How does dantrolene work?
- Blocks intracellular Ca++ release
- Supportive care of rhabdo
Which volatiles are emetogenic?
All of them
If general anesthetics are given with 2 triggering agents, what percentage of patients will have PONV?
25-30%
What metabolic deficiency can be caused by nitrous?
B12 deficiency
- Oxidizes cobalt ion in B12 - inhibits methionine synthase - inhibits DNA synthesis
*developing fetus at risk (use scavenging system)
Metabolic effects: What does nitrous oxide suppress?
Megaloblastic bone marrow suppression
- after 24 hours of exposure
- Repeated exposures <3 day intervals cumulative
Metabolic effects: What does nitrous oxide increase?
Plasma homocysteine levels
- associated with low B vitamins and > levels of atherosclerosis
- increase perioperative myocardial events
What obstetric effects do volatiles have?
*Dose dependent (0.5-1.0 MAC)
- decrease uterine smooth muscle contractility
Useful with retained placenta
- Worsen blood loss in uterine atony
What obstetric effects does nitrous have?
- No effect on contractility
- Increases analgesia without opioid/BZD depression
Halothane is a halogenated ________.
Halthothane is compatible with ____________.
Smells _______and ________.
________ potency and _______ solubility.
Alkane
Inhalation Induction
Sweet and non-pungent
High potency and intermediate solubility
Concerns for halothane:
- Catecholamine-induced arrhythmias
- occasional hepatic necrosis
- pediatric brady-arrhythmias
- Decomposition to HCL acid - thymol preservatives added
Pros of halothane:
- Lower risk of N/V
- non-flammable
Isoflurane is an isomer of _______.
Isoflurane is highly _______ and highly _____.
Isoflurane is not good for __________
Enflurane
Highly pungent and highly potent
Inhalation induction
Pros of Isoflurane:
- Resistance to metabolism
- Unlikely organ toxicity
- Stable - no deterioration after 5 years
Cons of Isoflurane:
Expensive to purify (distillation is complex and expensive)
Solubility of isoflurane:
Intermediate
Desflurane (Suprane) is a fluorinated _______.
Identical to __________ except that F is substituted for Cl-.
Desflurane has decrease _______ and ________
Desflurane has high ________.
methyl ethyl ether;
Identical to isoflurane;
decrease solubility and decrease potency;
high vapor pressure
Why does desflurane need to be heated?
Needs special vaporizer to heat it because it’s closer to atmospheric pressure
Why are you least likely to do induction with desflurane?
Desflurane
Causes coughing, salivation, breath holding, laryngospasm (with >6% FI)
What can happen if you over pressurize desflurane?
SNS stimulation - very tachycardia
What happens to desflurane is absorbent is dehydrated?
It will degrade to Carbon monoxide
Desflurane > Enflurane > Isoflurane > Sevoflurane (trivial)
Sevoflurane (Ultane) is a fluorinated _________.
_______ Solubility
Smells _______
Least ________ of modern volatiles
Methyl Isopropyl Ether;
Low Solubility;
Smells sweet and non-pungent;
Least airway irritation
Sevoflurane is metabolized to __________
Sevoflurane is least likely to form ________
Inorganic fluoride;
Carbon monoxide
________ is not usually used as a sole anesthetic.
Nitrous oxide
N2O has ________ solubility and _______potency.
N2O does not produce __________ relaxation.
N2O smells ________.
Low and low;
skeletal muscle relaxation;
Sweet-smelling/odorless
Pros of nitrous:
- Good analgesia
- 2nd gas effect
Cons of nitrous:
- Can’t deliver 1 MAC (MAC is 104%)
- N/V >50% of patients
- Increase Pulmonary Vascular Resistance
- Neonates may increase right to left shunt
- Jeopardize arterial oxygenation
Contraindicated in Bowel, Globes, Ear, Lung procedures
