Inhaled Anesthetics Flashcards
Meyer-Overton Correlation
- chemically indifferent substances that are soluble in fat are anesthetics
- their relative potency depends on their affinity for water and their affinity for fat— their fat/water partition coefficient
- potency of an anesthetic agent is proportional to lipid solubility as measured by its oil-gas partition coefficient
Unitary Theory
-cell membranes were mostly lipid therefore the majority of anesthetic effects must come from the effects on the cell membranes
The Concept of MAC
- MAC is analogous to plasma EC50
- universal measure for inhaled anesthetic potency
- the product of an anesthetics oil gas partition coefficient and MAC is a CONSTANT
Protein Centered Theory
- signaling proteins (ion channels and receptors) are the molecular site of action
- do anesthetics interact with lipids in the vicinity of these membrane proteins and alter their function properties?
Sites of desired actions in the nervous system:
Unconsciousness
- Cortex, Thalamus, Brainstem
- Glutamate blockade
- Na+ channel blockade
Sites of desired actions in the nervous system:
Analgesia
- Spinothalamic Tract
- NMDA blocked, K2P blocked and AMPA blocked
Sites of desired actions in the nervous system:
Amnesia
- Amygdala, hippocampus
- GABA potentiated
- nACHr may cause hyperalgesia?
Sites of desired actions in the nervous system:
Immobility
- Spinal cord and central pattern generators
- Glycine receptor potentiated
Molecular Targets of Inhaled Anesthetics:
Ligand gated Ion Channels (4)
- Potentiation of GABA and Glycine
2. Inhibition of Acetylcholine and Glutamate
Molecular Targets of Inhaled Anesthetics:
Voltage Gated Ion Channels
- Na Channels
- Ca Channels
- K channels
Molecular Targets of Inhaled Anesthetics:
Intracellular Signaling Mechanisms
- G-protein coupled receptors
- Protein Phosphorylation
- Gene expression
Cellular Mechanisms: Neuronal Excitability
- Determined by resting membrane potential, threshold potential, and input resistance
- Inhalation agents hyperpolarize neurons
Cellular Mechanisms: Presynatpic effects
-Inhalation agents alter transmitter release
Cellular Mechanisms: postsynaptic effects
-inhalation agents alter NTM release
Glycine and Gaba are ______
Inhibitory
Na+ Channels, K2P channels, NMDA, Nicotinic and Acetylcholine are __________
Excitatory
Sedation
- potent agents probably stimulate GABA
- N2O and Xenon possibly antagonize NMDA
Learning and Memory
- possibly hippocampal and amygdala dependent
Unconsciousness
- probably hyper polarization of thalamic sites
- probably more dimmer switch
- also dependents on interrupting synchronicity between multiple neural networks
Neuroprotection
- prevents apoptosis, decreases CMRO2
- neurotoxicty: possible irreversible cell damage by N2O and less so by potent agents
CV and Respiratory
- dose dependent myocardial depression and hypotension (decreased Ca++ availability and sensitivity)
- significant respiratory depression via central depression (increases inhibitory and decreases excitatory)
Immobility
- probably mediated by spinal cord NMDA receptors
- requires 2.5-4 X MAC needed to produce amnesia and unconsciousness
At Clinically Relevant concentrations volatile anesthetics __________ modulate inhibitory GABA receptors
-positively modulate
At Clinically Relevant concentrations volatile anesthetics __________ modulate inhibitory Glycine receptors
-positively modulate
At Clinically Relevant concentrations volatile anesthetics __________ excitatory NMDA type glutamate receptors
-inhibit
At Clinically Relevant concentrations volatile anesthetics __________ neuronal nACH receptors
-inhibit
At Clinically Relevant concentrations volatile anesthetics __________ K2P and K+ leak channels
-activate
At Clinically Relevant concentrations volatile anesthetics __________ multiple voltage gated Na+ channels
-inhibit
Why are VA fluorinated?
- reduce or eliminate toxicity
- reduce of eliminate flammability
- allow increased speed of induction and recovery from anesthesia
Halothane is a _________
alkane
Iso, Sevo, Des and En-Flurane are fluorinated __________
methyl ethyl ethers
All potent inhaled anesthetics- pulmonary effects
- Decrease Vt in a dose dependent manner
-less than adequate increase in RR
-increased resting ETCO2
enflurane > des = iso > sevo= halothane > N2O - Increase activity of laryngeal irritant receptors and decrease the activity of pulmonary irritant receptors
- Decrease FRC
-loss of intercostals
-altered respiratory pattern
-cephalad movement of diaphragm
-altered thoracic blood volume
VA cause bronchoconstriction or bronchodilation?
- Bronchodilation
-relax airway smooth muscle by pressing smooth muscle contractility, direct effects on bronchial epithelium and airway smooth muscle, indirect inhibition of reflex neural pathways
-blocks voltage gated Ca++ channels
-depletion of ca++ stores in SR, potentiates GABA
-will not notice under normal respiratory conditions, i.e.;
great bronchodilator under BRONCHOSPASTIC conditions (less evident with DES)
Can you bronchodilate a laryngospasm?
NO- must apply positive pressure and possibly give succs
PVR
- lowest at a lung volume equivalent to FRC
- an increase in PVR causes a corresponding increase in pulmonary arterial pressure that promotes interstitial fluid transaction
- pvr also increased by PEEP, alveolar hypoxia, hypercapnia, and CCP
- inhaled VA tend to reduce lung volume
Hypoxic Pulmonary Vasoconstriction
- is unique to the pulmonary circulation in that other vascular beds dilate in response to hypoxia
- anesthetics that interfere with HPV may adverses affect gas exchange
- all VA vasodilator the pulmonary vascular bed
- all VA cause dose dependent myocardial depression
Chemical Control of Respirations: Central
- located near ventrolateral medulla and other brainstem sites
- respond to changes in the H+ concentration in CSF
- NOT arterial CO2 tension or pH
- more profoundly affected by respiratory than by metabolic alterations in arterial CO2 tension
Chemical Control of Respirations: Peripheral
- located in carotid bodies
- sensitive to changes in arterial CO2 tension, pH
- and arterial oxygen tension
Post Operative effects on breathing: CO2 response curves
-all VA depress ventilatory response to hypercapnia in a dose-dependent fashion
-<1 MAC of VA markedly attenuate or entirely eliminate hypercapnia-induced increases in ventilatory rate
-
Post Operative effects on breathing: Hypoxemia Response
- VA and N2O attenuate the ventilatory responses to hypoxia in a dose-dependent manner
- at concentrations as low as 0.1 MAC
- can remain depressed for hours after GA
REMEMBER: all inhalation agents decrease the patients response to hypoxia and hypercarbia and there affect ________________ respiratory drives
BOTH= central and peripheral respiratory drives
How can you assist bronchdilation in the reactive airway?
-deepend the anesthetic
ISO pulmonary effects
- respiratory depression
- less tachypnea than with HAL
- Most depression of the ventilatory response to hypoxemia and hypercapnia
- similar impairment of the hypoxic pulmonary vasoconstriction response
Des pulmonary effects
- extremely noxious pulmonary irritant
- NOT recommended for inhalation induction and probably poor choice for patients with reactive airway disease
- respiratory depression
SEVO pulmonary effects
- respiratory depression with slight tachypnea
- decreased VT causes decreased minute ventilation and CO2 retention
- bronchodilation
- great for inhalation induction- least irritating
Halothane pulmonary effects
- respiratory depression
- alveolar hypoventialtion- arterial hypercapnia (rapid and shallow resps)
- blunts ventilatory response to high CO2
- important to administer O2 to patients after extubation= sub anesthetic doses abolish ventilatory response to hypoxemia
CV effects: ALL inhaled anesthetics cause:
- dose dependent depression of myocardial contractility
- alterations in intracellular Ca++ and entry into SR
- inhibition of Na+-Ca2+ exchange
- LV diastolic function
- LV after load effects
- LA myocardial depression - Dose dependent decrease in SBP
- halothane and enflurane reduce myocardial contractility and cardiac output
- iso, des, sevo decrease arterial blood pressure primarily as a result of reductions in LV after load - Dose dependent decrease in SVR
- Direct negative chronotropic effects: depress SA node, baroreceptor reflex activity
VA effects on SA node
- slow the rate of SA discharge via direct and indirect effects on SA node automaticity
- potential to product bradycardia and AV conduction abnormalities - arrhythmogenicity
- halothane, enflurane, iso can be cardioprotective against v fib produced by coronary artery occlusion and reperfusion
- halothane and other VA sensitize myocardium to arrhythmogenic effects of epic
- des, iso, and sevo do NOT sensitize the heart to ventricular extrasystoles
ISO CV effects
- decrease in BP due to decrease in peripheral vascular resistance
- mild myocardial depressant (enhanced in patients taking Ca+ blockers such as Verapamil)
- mild direct negative chronotropic effect on SA node
- junctional rhythms**
- However, ISO can result in increased HR d/t indirect activation of SNS, ANS, and baroreceptor
- coronary vasodilation and decrease CVR
- does NOT increase risk of MI in patients at risk
- does NOT cause coronary steal
DES CV Effects
- myocardial depression and arterial vasodilation
- greater tachycardia than ISO
- autonomic ton is more important in DES
- abrupt increase in des can lead to increased SBP 30 mmHg and increased HR of 30 BPM, increasing plasma epi
- does NOT cause coronary steal
SEVO CV Effects
- decrease in myocardial contractility, CO and SVR
- less arterial vasodilation and less decrease in SVR than ISO
- does not increase SNS like Des does
- NOT cause coronary steal
- NOT increase incidence of ventricular arrhythmia like hAL
Halothane CV Effects
- most prominent CV effect= arterial hypotension
- SVR stable even with deep halothane
- decrease BP and increased CVP
- greatest negative inotropic effect in all agents except enflurane (alterations in Ca+ influx)
- does NOT activate SNS
- decreases coronary blood flow
- directly depresses SA node and conduction
- Slow AV junctional rhythm and AV dissociation during halothane anesthesia (treat with atropine)
- decreases threshold at which catecholamines will cause ventricular ectopy= no more than 100 mcg of epi be injected in less than 10 minutes and no more than 5 mcg/kg during injection process. (Worse with hypercapnia) ******
Neurological effects
- All inhalation agents increase CBF by direct cerebrovascular vasodilation which leads to increased ICP
- all decrease CMRO2
- halothane blunts auto regulatory response of cerebral vasculature
- ISO causes EEG burst suppression at 1.5 MAC
- Enflurane causes seizure like activity on EEG at 2 MAC
Neuromuscular effects
-All inhalation agents have centrally mediated, dose dependent relaxant properties
-decrease depolarizing current as NMJ in response to ACH d/t direct inhibition of nACHr
-potentiate both depolarizing and non-depolarizing muscle relaxants
-elimination of volatile agent will facilitate recovery from blockade
-when using IV muscle relaxants:
iso=des=sevo > enflurane > halothane
MAC fraction to cause effects:
- Amnesia
- Unconsciouness
- Immobility
- 0.25 MAC
- 0.5 MAC
- 1.0 MAC
Hepatic effects of inhalation agents
-liver receives blood from hepatic artery and portal vein
-all inhalation agents decrease hepatic blood flow:
halothane > enflurane> iso> des/sevo
-most drug catalyzed by phase 1 or phase 2 enzymes
-affected by age, gender, disease, genetics
-iso, des, hal, enf all metabolize to trifluoroacetylated protein that may produce liver injury in susceptible patients
-halothane hepatitis- hepatocyte hypoxia
-iso and des preserve hepatic artery blood flow
-N2O is not metabolized in humans
Renal effects
- all inhalation agents cause decrease in renal blood flow, GFR and urine output
- do not use sevo in renal failure
OB effects
- all inhalation agents decrease uterine blood flow and uterine contractility
- N2O decrease the activity of methionine syntheses and thymidylate syntheses which is important in RNA/DNA replication patterns
Immune system effects
- immunocompromise in surgical patients is related to neuroendocrine stress response
- immune effects of surgery are greater than anesthesia
- VA: inhibit inflammatory cytokines, reversibly inhibit VGCa++ channels, inhibit neutrophil bacterial killing
N2O
-Mac= 105%
additive
-concentration effect: as N2O is taken up it leaves spaces in the FRC for fresh gas inflow to occur. As fresh gas is saturated with anesthetic flows in, the concentration of anesthesia in the FRC increases faster
-second gas effect: second gas (potent anesthetic) also rises to a higher concentration more quickly because of the above principles
Diffusion hypoxia
- N2O washes out fast
- as N2O rushes into lungs, it drags other gases with it an displaces O2 which can result in diffusion anoxia or diffusion hypoxia
N2O CV Effects and Respiratory Effects
- increase SNS which counteracts hypotension of inhaled
- increases circulating norepi in humans
- increases arterial vasomotor tone
- slight reduction in cardiac output- probably balanced by above
respiratory: decrease TV and increase RR - reduces response to hypoxia and hypercapnia
- respiratory depressants are additive
N2O CNS and Renal effects
- increase CBF and ICP and CMRO2
- decreases seizure activity
renal: decreases renal blood flow, GFR, UO
Complications with N2O:
- N2O is 30 X more soluble in blood than nitrogen and will rapidly move into air spaces filled with nitrogen before it can move out
- contraindicated in closed air spaces: tympanic membrane and ear surgeries, pneumothoraces, double in size in 10 minutes- small bowel obstruction, pneumocephalus, air emboli
- impairs DNA synthesis in pregnant women
NIOSH standards state less than _______ ppm N2O in ambient OR air
25
Time constant
capacity of the system (L)/ flow into the system (L/min)
1 TC
2 TC
3 TC
4 TC
63% change
85 %
95 %
98 %
anesthesia circuit capacity?
normally 7 L
induction and emergence flows?
maintenance flow rate?
8-10 L/min
.5-1L/min
