Test 3: Pharmacodynamics of INH Agents

Question 1

What are the factors that can influence the side effects of INH agents?

Answer 1

-Anesthetic Concentration (dese-dependent)
-Patient Age (elderly decreases requirements. If you give normal dose to elderly, will have inc SEs)
-Coexisting Diseases
-Intravascular Fluid Volume (hypotension)
-Preoperative Medication (Benzos, Precedex can exaggerate hypotension)
-Additional IV Anesthetics
-Variations from Normocapnia
-Concomitant Drug Therapy
-Alterations in Body Temperature (cold blood = more soluble drug = delayed wake up)

Question 2

Which INH agents produce cerebral vasodilation (blue box)?

Answer 2

ALL Inhalation Agents produce cerebral vasodilation.

Question 3

Autoregulation is maintained Except with which INH agent (blue box)?

Answer 3

Halothane

Question 4

_____ can produce epileptiform changes on EEG during induction and emergence (blue box)?

Answer 4

Sevoflurane
-Maybe avoid use if known seizure issues

Question 5

What are the effects of INH agents on the Central Nervous System?

Answer 5

🡻CMRO2
🡹 or 🡻 or no effect on CBF depending on concentration of drug

-Decreased cerebral vascular resistance = increase in CBF, cerebral blood volume and cerebral spinal fluid pressure.
-Effects are dependent on: Dose of volatile, Admin of other drugs (propofol, nitrous, narcs), MV – rate of change in CO2

Question 6

What is Uncoupling?

Answer 6

-Normally, decreases in O2 lead to vasodilation to get more O2 to the brain.
-With volatile agents, Dec in CMRO2 are accompanied by increases in CBF (mismatch - demand is down but supply is up).
-🡻CMRO2 + 🡹CBF
-Magnitude of change is variable and dose-dependent, meaning that some flow-metabolism coupling mechanism is preserved.
-Oxygen utilization and glucose metabolism (what does this mean?)

Question 7

What can you do to minimize increases in ICP with the use of volatile agents?

Answer 7

-Avoid inc ICP in patients with brain tumor, intracranial hemorrhage, head injury
-Hyperventilation can decrease the PaCO2, causing cerebral vasoconstriction
-If patient is hyperventilated before the volatile agent is started, the inc in ICP can be minimized.

Question 8

What is the effect of N2O on CRMO2 and ICP?

Answer 8

-Increases CMRO2
-Increases ICP
Likely due to activation of the SNS
-Can be combined with other agents (IV anesthetics) or with hyperventilation to reduce CBF in patients with inc ICP.

Question 9

What is the normal cerebral vascular response to CO2?

Answer 9

Normally, hypocapnia or rapid ventilation causes vasoconstriction (can lower ICP). Hypercapnia causes vasodilation.
-Volatiles vary in interruption of this effect.

Question 10

How do volatile agents effect the cerebral vascular response to CO2?

Answer 10

-Different among the agents in their ability to interfere with the cerebral vasculature’s response to CO2.
-Variables that affect it include type of surgical procedure, associated pathophysiology, and the presence of underlying coexisting diseases.
-In general, the concentrations of Iso, Sevo, and Des that are used preserve the reactivity to changes in carbon dioxide and flow metabolism coupling. This is why you can prevent increases in ICP by mild hyperventilation and by using concentrations less than 1.5 MAC.

Question 11

What are the effects of volatiles on Evoked Potentials?

Answer 11

-Brainstem (most resistant)
-Visual (most sensitive)
-↑Latency or ↓Amplitude
All volatiles effect Latency equally.
-Dose dependent inhibitory effects on evoked potentials.

Question 12

What is Latency?

Answer 12

The time between the the initiation of a peripheral stimulus and the onset of the evoked potential as recorded by scalp electrodes.

Question 13

What are the effects of Volatiles on EEG activity?

Answer 13

-Dose-related suppression of EEG activity (an initial increase and a later decline in amplitude and decreased frequency)
-High concentrations produce electrical quiescence (inactivity).
-Burst suppression can occur at deeper levels of anesthesia

Question 14

Which agents are the best to use in neuromonitoring cases?

Answer 14

-Can use 0.5 MAC of Des or Sevo
-Can use TIVA

Question 15

How do volatile agents effect emergence?

Answer 15

-Residual agent can delay neuro assessment (can lead to unnecessary diagnostic tests or predispose patient to respiratory complications)
-Agitation & delirium in pediatrics (tx with reducing pain/anxiety, unite with parents)

Question 16

What is important to know regarding Sevo and seizures?

Answer 16

-Incidence doubles in the presence of hypocapnia
-Can augment epileptic activity
-Avoid in children with hx of epileptic activity

Question 17

What is the effect of volatile agents on the Cardiovascular System?

Answer 17

Dose-dependent depression of cardiac activity.
-↓ MAP, ↓ CO, and ↓ CI due to ↓ SVR

Question 18

Which agent decreases MAP by directly depressing myocardial tissue?

Answer 18

Halothane.

Other agents work by decreasing SVR.

Question 19

How do volatile agents reduce intracellular free Calcium?

Answer 19

Iso, Sevo, & Des reduce intracellular free Ca 2+ concentrations in cardiac and vascular smooth muscle.
-Reduction in Ca2+ influx through the sarcolemma
-Depression of depolarization-activated Ca2+ release from the sarcoplasmic reticulum
-Results in depression of the contractile state of the myocardium and dilation of the peripheral vasculature

Question 20

How do volatile agents modify the Heart Rate?

Answer 20

1) Antagonism of the SA node (will initially see some bradycardia before peripheral vasodilation causes baroreceptor reflex to kick in - increasing HR)
2) Modulation of baroreceptor reflex
3) SNS activation

Question 21

How do different volatile agents affect the baroreceptor reflex?

Answer 21

In general, decreases in arterial blood pressure lead to activation of ANS reflexes and trigger an increased HR.
-Halothane & Sevo have little effect on HR, because they attenuate baroreceptor input into the ANS
-Des & Iso significantly increase HR, because they cause less depression of the baroreceptor reflex (cause SNS activation due to an irritant effect)

Question 22

What is unique about Desflurane and HR?

Answer 22

Des can trigger transient SNS activation, with elevated catecholamine levels, and cause marked increases in HR and BP during administration of high Des concentrations or when Des concentrations are changed rapidly.
-Caution with CAD patients. Decreases diastole.
-Can modulate with fentanyl 5 min prior to increase in Des concentration (1.5-4.5 mcg/kg will do as much as 70% modulation)
-Esmolol will block the HR, but not the MAP (because it’s selective and quick - will only have time to block HR before it’s out of your system)

Question 23

How does N2O affect the Cardiovascular System?

Answer 23

N2O activates the SNS, leading to an ↑ SVR, which causes ↑ MAP and ↑ CVP.
-N2O helps to support arterial blood pressure

Question 24

Can you always use tachycardia as signs of anesthetic depth?

Answer 24

Inc in HR due to volatile agent is NOT associated with increases in plasma catecholamines, blood pressure, or CO2 production; therefore mydriasis and tachycardia as signs of anesthetic depth could be misleading at times.

Question 25

T/F: Volatiles produce vasodilation.

Answer 25

True; Sevo produces the least.

Question 26

What is Coronary Steal Syndrome?

Answer 26

-Worse with multi-vessel disease
-a reduction in the perfusion of ischemic myocardium with simultaneous improvement of blood flow to non-ischemic tissue.
-When you have diseases tissue, there is a pathologic process occurring.
-Maximal dilation has already occurred in diseased tissue (was doing everything it could to bring in more O2).
-When volatile comes through, diseased tissue doesn’t get bigger.
-Normal functioning vessels get even bigger, stealing from the diseased tissue.
-Reverse robin hood. Stealing from the poor (diseased tissue) and giving to rich (healthy tissue).
-

Question 27

When does Coronary Steal Syndrome occur the most?

Answer 27

With the use of Iso & Des in the setting of hypotension.
-Reduce risk by keeping them normotensive and maintaining perfusion pressure.

Question 28

Which agents can be used in patients with a history of ischemic heart disease?

Answer 28

Iso, Devo, and Des can all be used.
-If ST changes occur in the absence of abnormal hemodynamics a change in agent may be necessary

Question 29

Which agents have the greatest risk for arrhthmias?

Answer 29

-Potential for bradycardias & AV conduction abnormalities
-Greatest risk with Sevo and Halothane
-The mechanism for this is their ability to depress slow-response (SA and AV nodal tissue) and fast-response (atrial or ventricular musculature, Purkinje fibers) action potentials.

Question 30

What is Sensitization?

Answer 30

A reduce in the catecholamine threshold necessary to produce an arrhythmia.
-An adverse drug rxn that occurs with volatiles.
-Patient becomes more arrhythmo-genic (easier to create an arrhythmia)
-The ability of the inhalation agents to reduce the quantity of catecholamines necessary to evoke arrhythmias is commonly, but inaccurately, called sensitization. It is more accurate to describe this phenomenon as an adverse drug interaction.

Question 31

___% N2O may protect the myocardium from steal.

Answer 31

50% N2O.

Question 32

What are the effects of INH agents on the Respiratory System?

Answer 32

Dose-dependent depressant effect on the medullary ventilatory center.
-Decrease Tidal Volume leads to an increase in RR as compensation (minimal change to minute ventilation)
-Blunt CNS response to ↑PaCO2 & ↓PaO2
-Effects may be counteracted by surgical stimulation
-Depress mucociliary function, leading to mucus pooling and inc risk of atelectasis and postop respiratory complications (hypoxemia & respiratory infections)

Net Effect: ↑ PaCO2 & ↓MV

Question 33

Which two agents are the standard Inhalational Induction agents and why? (Blue Box)

Answer 33

-Sevo & N2O
-due to their low incidence of breath holding (other agents smell bad), coughing, secretions and laryngospasm.
-Sevo is the least irritating to the airway.

Question 34

T/F: Volatiles are Bronchoconstrictors.

Answer 34

False; INH agents are Bronchodilators.
-Relax airway smooth muscle
-Tx of refractory status asthmaticus

Question 35

What do you need to know regarding the respiratory system and emergence?

Answer 35

-Be mindful of hypercarbia (trying to get them to breathe by increasing CO2, but then also not breathing off gases)
-Some patients may be hypoxic driven (not hypercarbia driven) to breathe. (Ex: COPD)
-End tidal of volatiles may persist, especially if recent narcotic administration. Concentration gradients become less steep and it’s harder for gas to flow out.
-Even as little as 0.1 MAC (except with Des) can inhibit response to hypoxia in early postop period

Question 36

What is Hypoxic Pulmonary Vasoconstriction (HPV)?

Answer 36

A natural compensatory mechanism that occurs in response to hypoxia or atelectasis.
-Helps to match ventilation and perfusion.
-Pulmonary arterioles constrict in alveolar hypoxia (PaO2 < 70 mmHg), diverting blood flow away from poorly ventilated alveoli (decreasing the shunt).
-Important for maintaining oxygenation in patients with lung pathology and one-lung ventilation.
-Marginally affected by inhalational agents (decrease the HPV response, maintaining the shunt, increasing the V/Q Mismatch).

Question 37

What is the range for Renal Autoregulation?

Answer 37

80-180 mmHg. (can shift with chronic HTN).
-Keep BP in range to avoid renal issues.

Question 38

What are the effects of INH agents on the Renal system?

Answer 38

-Autoregulation remains intact.
-↓SBP = ↓Renal vascular resistance
-↓GFR = ↓Intraoperative urine output (UO)

Remember: Acceptable UOP is 0.5 mL/kg/hour.

Question 39

Which agent alters renal integrity the least?

Answer 39

Desflurane.
-Can be used in renal diseased states.

Question 40

What lab values are used to determine the extent of renal damage?

Answer 40

-Creatinine
-BUN
-Serum inorganic fluoride concentrations

Question 41

What is important to know regarding Sevo and the Renal System?

Answer 41

-Older soda lime formulations (K & Na hydroxide) degrade Sevo to Compound A (nephrotoxic). Sevo + Dessicated soda lime = anesthesia machine fire.
-No clinical evidence of Compound A in humans.
-FDA cautions use if Creatinine is > 1.5.
-Newer absorbents use Calcium or Lithium Hydroxide and avoid this problem.

If using older soda lime, FDA recommends that sevo exposure not exceed 2 MAC hours at flow rates of 1-2 L/min (FGF rates <1 are not recommended).

Question 42

What is important to know regarding volatile anesthetics and the Liver (blue box)?

Answer 42

All volatile anesthetics:
-🡻 total hepatic blood flow
-🡹 or maintain hepatic artery blood flow ~ EXCEPT Halothane
-Thereby limiting any accompanying attenuation in portal vein flow.

Question 43

Volatiles have the potential to ___ drug clearance due to decreased total hepatic blood flow.

Answer 43

Volatiles have the potential to decrease drug clearance due to decreased total hepatic blood flow.
-But, all volatiles (except Halo) increase or maintain hepatic artery blood flow (balances out).

Question 44

What causes Volatile induced Hepatotoxicity?

Answer 44

-Due to inadequate hepatocyte oxygenation
-Decreased hepatic blood flow
-Increased O2 demand of enzyme induction
-Possible with all volatiles, especially Halothane (But rarely caused by iso, sevo, or des).
-Possible immunologic mechanism
-Can take days to appear.

Question 45

Why is it rare for Iso, Sevo, or Des to cause Hepatotoxicity?

Answer 45

-Minimally metabolized
-Increased fluorination resists hepatic degradation.
-Cause minimal changes in hepatic blood flow

Question 46

Prior exposure to Halothane can cause what with a current exposure to another volatile agent?

Answer 46

-Can cause hepatitis because the body was sensitized by the prior exposure to Halothane.
-Immunologic memory

Question 47

The Hepatic artery receives ___% of blood flow and ___% of O2 supply.

Answer 47

Hepatic artery: 25% of blood flow, 50% of O2 supply

Question 48

The portal vein receives ___% of blood flow and ___% of O2 supply.

Answer 48

Portal vein: 75% of blood flow, 50% of O2 supply

Question 49

All volatile agents produce a _____-____ _____ of skeletal muscle (blue box).

Answer 49

All volatile anesthetics produce a dose-dependent relaxation of Skeletal Muscle

Question 50

All volatile anesthetics potentiate the effects of ____ and ____. (blue box)

Answer 50

All volatile anesthetics potentiate the effects of DMR and NDMR.
-Decrease MAC requirements with the use of MRs.

Question 51

How do volatile agents affect the Neuromuscular system?

Answer 51

-↓ Neural activity within the CNS
↓ Effect at the NMJ (Predominantly post-synaptic membrane)
-Creates muscle weakness.

Question 52

In general, nondepolarizing muscle relaxant dosages are decreased by approximately ___% to ___ % of that required with TIVA when they are used in combination with an inhalation agent.

Answer 52

In general, nondepolarizing muscle relaxant dosages are decreased by approximately 25% to 50% of that required with TIVA when they are used in combination with an inhalation agent.

Question 53

T/F: Nitrous Oxide causes skeletal muscle relaxation.

Answer 53

False; N2O can cause skeletal muscle rigidity.

Question 54

Explain how volatiles cause a time-dependent potentiation of NDMR & Delay of recovery?

Answer 54

The inhalation agents have also been shown to delay recovery from the nondepolarizing muscle relaxants.
-Ex: after 30 minutes of exposure to sevoflurane, recovery from vecuronium to 25% of baseline neuromuscular function is prolonged by 89%, and after 60 minutes, prolongation exceeds 100%.
-Take this into account when timing wakeup.
-Inhalation agents are also implicated in impairing reversal of NDMR blocks.