Inhaled Anesthetics- General Flashcards
Meyer-Overton Correlation
Dependent upon affinity for water or affinity for fat (fat/water partition coefficient). States anesthetics are soluble in fat
Unitary Theory
Cell membranes mostly lipid therefore majority of anesthetic effects come from effects on cell membranes
Concept of MAC
Analogous to plasma EC50 - 50% of nonparalyzed do not move with surgical stimulus. Universal measurement for inhaled anesthetic potency
Protein Centered Theory
Signaling proteins (ion channels/receptors) are the molecular site of action
Effects of Inhaled anesthetics on ligand gated ion channels
Potentiate GABA & Glycine, Inhibit Acetylcholine & glutamate
Effects of inhaled anesthetics on voltage gated ion channels
Nervous system - reduction in amplitude through sodium channels, CV system - reduction in amplitude and duration through calcium & potassium channels
Intracellular signaling mechanisms that inhaled anesthetics work on
G-protein coupled receptors, protein phosphorylation, gene expression
Cellular mechanisms of inhaled anesthetics
Hyperpolarize neurons - decrease neuronal excitability (determined by resting membrane potential, threshold potential & input resistance. Alter transmitter release presynaptic & neurotransmitter responses postsynaptic
How do volatile anesthetics enhance inhibitory synaptic transmission postsynaptically?
Potentiating ligand-gated ion channels activated by GABA & glycine, extrasynaptically by enhancing GABA receptors & leak currents, & presynaptically by enhancing basal GABA release
How do volatile anesthetics suppress excitatory synaptic transmission?
Presynaptically by reducing glutamate release (volatile agents) and postsynaptically by inhibiting excitatory ionotropic receptors activated by glutamate (gaseous agents)
Desired effects of inhalation agents
Immobility, unconsciousness, no learning/memory, sedation, neuroprotection, CV & respiratory protectants
How immobility is mediated
Probably by spinal cord NMDA receptors, requires 2.5-4X MAC needed for amnesia & unconsciousness
How unconsciousness is mediated
Hyperpolarization of thalamic sites, dimmer, not on/off, depends on interrupting synchronicity between multiple neural networks
How learning & memory is mediated
Possibly hippocampal & amygdala dependent (usually 0.3-0.4 MAC is enough)
How sedation is mediated in potent agents vs gases?
Potent agents probably stimulate GABA, gases (N2O & Xenon) possibly antagonize NMDA
How neuroprotection is mediated
All potent agents prevent apoptosis, decrease CMRO2 (by increasing inhibitory and decreasing excitatory transmission).
What is a neurological risk of inhaled anesthetics
Neurotoxicity- irreversible cell damage by N2O & less by potent agents
CV Effects of gases - general
Dose dependent myocardial depression, hypotension, SVR, direct negative chronotropic effects, sensitized to arrhythmogenicity, direct coronary artery vasodilation in vitron, coronary vasoconstriction in vivo
Pulmonary Effects of gases - general
Significant respiratory depression via central depression
Why are volatile anesthetics fluorinated?
Reduce or eliminate toxicity via metabolism, reduce/eliminate flammability, allow increased speed of induction and recovery from anesthesia
Basic hydrocarbon structures useful as fluorinated anesthetics include what?
ethane, methyl ethyl ether & propyl methyl ether
Most to least pungent anesthetic
Desflurane, isoflurane, halothane, sevoflurane
Potent inhaled anesthetics pulmonary effects- specifics
Decrease tidal volume in dose dependent manner (get less than adequate increase in RR & increased resting end tidal CO2). Decrease FRC, bronchodilation, increase activity of laryngeal irritant receptors and decrease activity of pulmonary irritant receptors, can adversely effect hypoxic pulmonary vasoconstriction. Effects on PVR are relatively small
Why does FRC decrease
Loss of intercostals, altered respiratory pattern, cephalad movement of diaphragm, altered thoracic blood volume
How are potent inhaled anesthetics bronchodilators
Decreases intracellular calcium concentration & reduces calcium sensitivity- Relaxes airway smooth muscle by directly depressing smooth muscle contractility- it directly effects bronchial epithelium and airway smooth muscle cells through phosphorylated myosin light chain, and indirectly inhibits reflex neural pathways.
What does an increase in pulmonary vascular resistance cause
Corresponding increase in pulmonary arterial pressure which promotes interstitial fluid transudation
When is pulmonary vascular resistance lowest
At lung volume equivalent to FRC
How do inhaled anesthetics effects hypoxic pulmonary vasoconstriction
Through vasodilation of pulmonary vascular bed and dose dependent myocardial depression, blood flow will get to the area that was restricted (such as in the case of a tumor)
Inhaled anesthetics protein binding site, effect & target
Amphiphilic site, effect: conformational flexibility/ligand binding, target: ion channels/receptors and signaling proteins
Inhaled anesthetics action potential site, effect & target
Site: Nervous system Effect: small reduction in amplitude, target: sodium channels. Site: CV system Effect: reduced amplitude & duration Target: Calcium & Potassium channels
Inhaled anesthetic inhibitory site, effect & target
Site: Presynaptic terminal Effect: enhanced transmitter release Target: unknown Site: Postsynaptic terminal Effect: enhanced transmitter effect Target: Glycine & GABAa receptors
Inhaled anesthetic excitatory site, effect & target
Site: Presynaptic terminal Effect: reduced transmitter release Target: sodium & K2P (2 pore potassium) channels Site: Postsynaptic receptors Effect: reduced transmitter effects Target: NMDA, nicotinic and acetycholine receptors
Inhaled anesthetic site, effect & target in neuronal networks
Site: neuronal circuit & integration Effect: Altered long term potential/depression, rhythmicity & coherence Target: synaptic plasticity HCN (non-selective ligand gated) channels, K2P (2 pore potassium) channels, extrasynaptic GABAa receptors
Inhaled anesthetic site of action, effect & target in CNS
Site: Neocortex/hippocampus/amygdala Effect: sedation & amnesia Target: delta & gamma rhythms, synchrony
Site: Diencephalon (thalamus) & brainstem (reticular formation) Effect: unconsciousness Target: ?gamma band
Site: Spinal cord Effect: immobility Target: nocifensive reflex, ?thalamic deafferentation
Inhaled anesthetic site of action, effect & target in CV system
Site: Myocardium Effect: negative inotropy Target: excitation-contraction coupling
Site: Conduction system Effect: dysrhythmias Target: action potential
Site: Vasodilation Effect: vasodilation Target: direct/indirect vasoregulation
CO2 response curves with inhaled anesthetics
Expected to shift right, will get higher end tidal CO2 (secondary to medullary depression) and suppressed ventilatory response to hypercapnia in dose-dependent fashion (<0.2 MAC depress peripheral chemoreflex loop)
Central & peripheral chemoreceptors & pulmonary effect with inhaled anesthetics
Respiratory controller in pontine (pneumotaxic center & apneustic center) & medullary (dorsal & ventral respiratory group) signal with GABAergic to inhibit drive of inspiratory and expiratory premotor neurons- sends inhibitory message to spinal cord/phrenic nerve to go to muscles of inspiration & expiration
Central chemical control of respiration
Located near ventrolateral medulla, respond to changes in hydrogen ion concentration in CSF– NOT altered by arterial CO2 or pH. More profoundly affected by respiratory than by metabolic alterations in arterial carbon dioxide tension
Peripheral chemical control of respiration
located in carotid bodies, sensitive to changes in arterial CO2 tension, pH & arterial oxygen tension
Hypoxemia response to volatile anesthetics
All volatile anesthetics & N2O decrease ventilatory response to hypoxia in dose-dependent manner as low as 0.1 MAC
What does the cephalad shifting of the diaphragm cause?
Decrease lung volumes FRC, increases V/Q mismatching in bases of lungs. As FRC decreases, closing volume increases & eventually overtakes the FRC so some alveoli never open = atelactesis
About how much is the apneic threshold during spontaneous return of respiration for CO2
2-5 mmHg less than PaCO2 (if you give a big breath, CO2 will drop and patient will become apneic quickly)
How inhaled anesthetics cause dose dependent depression of myocardial contractility
Alterations in intracellular Calcium homeostasis, inhibition of NaCa exchange, LV afterload reduction, LA myocardial depression & possibly LV diastolic dysfunction
How inhaled anesthetics cause dose dependent hypotension
Decrease myocardial contractility & cardiac output. LV afterload reduction by iso, des & sevo
How inhaled anesthetics cause direct negative chronotropic effects
Depression of SA node via direct & indirect effects on SA node automaticity (may produce bradycardia & AV conduction abnormalities) & baroreceptor reflex activity
How inhaled anesthetics cause arrhythmogenicity
Sensitize myocardium to effects of epinephrine. *Halothane & iso have been shown to be cardioprotective against VFib from occlusion/reperfusion.. des/iso/sevo do not sensitize heart to PVCs
How inhaled anesthetics cause coronary vasodilation
Reduced MVO2 and simultaneous decreased O2 extraction are indicative of coronary vasodilation
Inhaled anesthetic neurologic effects
All increase CBF by decreasing cerebrovascular resistance = increased ICP (Halothane > Iso = Des = Sevo).
All decrease CMROs (iso slight cerebral protection)
Halothane blunts autoregulatory response of cerebral vasculature, sevo uncouples this by dilating cerebral vessels
Burst suppression effects
All depress SSEP & MEP - use TIVA
Inhaled anesthetic neuromuscular effects
All have centrally mediated muscle relaxant properties. Iso=Des=Sevo>Halothane
Inhaled anesthetic MH triggering properties
Halothane> Iso=Des=Sevo (N2O does not trigger!)
Inhaled anesthetic hepatic effects
Decreased hepatic blood flow (as liver receives its blood supply from hepatic artery & portal vein): halothane>iso>des=sevo
Affected by age/gender/disease/genetics
Hepatic metabolism of inhalation agents
Halothane>Iso>Des=Sevo .. iso/des/hal all metabolize to a trifluoroacetylated protein that may produce liver injury in susceptible patients (usually if they are hypoxic at same time). Iso & Des preserve hepatic artery blood flow better – probably maintain hepatic oxygen supply better than halothane. N2O not metabolized
How inhalation agents are metabolized?
Catalyzed by phase 1 (CYP450) or phase 2 (uridine 5’ diphosphate transferase) enzymes
Inhalation agents renal effects
Similar decreases in renal blood flow, glomerular filtration rate & urine output.
Inhalation agents obstetrical effects
Decrease in uterine blood flow & contractility (don’t give postpartum = bleeding). Halothane>Iso=Des=Sevo
Time Constant defined
A way of describing the amount of change that is occurring in a dynamic system
Time Constant equation
capacity of the system (about 7 L) divided by flow into the system (in L/Min)
How much is 1 TC, 2 TC, 3 TC & 4 TC
1- 63%
2- 85%
3- 95%
4- 98%
How to calculate oxygen percentage of flow into the system
Say you have 3 L of oxygen (that is 100% oxygen), and 2 L air (21% oxygen, 79% nitrogen)… you will take 3 multiplied by 100 percent = 3, and 2 multiplied by 21% = 0.42..
3+ 0.42 = 3.42 then divide that by 7 (3.42/7)= 0.488 = 49% oxygen flowing into the system
MAC awake
1/3-1/4 MAC
MAC intubation
higher than classic MAC, this is more stimulating than incision
MAC Incision
regular MAC
MAC BAR
“blunt autonomic responses” 30-40% greater than MAC
Factors that decrease MAC
advanced age, opioids, ketamine, IV local anesthetics, alpha2 agonists
Factors that increase MAC
young age (up to 9 months, then drops over time)
Awareness defined
postoperative recall of events occurring during general anesthesia
Amnesic wakefulness defined
responsiveness during general anesthesia without postoperative recall
Dreaming defined
any experience (excluding awareness) that patients are able to recall postoperatively that they think occurred during general anesthesia and that they believe is dreaming
Explicit memory defined
Conscious recollection of previous experiences (“awareness” is evidence of explicit memory)
Implicit memory defined
changes in performance or behavior that are produced by previous experiences but without any conscious recollection of those experiences (“unconscious memory formation” during general anesthesia)
Uptake is related to (equation)
Q * lamda * [(Pa-Pv)/barometric pressure]
Q = cardiac output
lamda = blood/gas solubility
(pa-Pv) = alveolar to venous partial pressure gradient in mm Hg (%gas)
– low numbers decrease uptake, high increase uptake. No cardiac output = no uptake, no tissue gradient = no uptake
Henry’s law
Amount of gas that dissolves in a liquid is directly proportional to the partial pressure of the gas over the liquid
How to figure out partial pressure of gas
Barometric pressure multiplied by vol% of gas (6% des = 0.06 x 760 = 46 mmHg des)
High Pa agent
High Fi = higher delivered concentration = greater uptake
High Pv agent
High Fe = high tissue concentration = less uptake
VRG (body weight & CO)
10% body weight, 75% cardiac output
Muscle Group (body weight & CO)
50% body weight, 19% cardiac output
Fat Group (body weight & CO)
20% body weight, 6% cardiac output
FA/Fi ratio and difference between soluble & insoluble agents
insoluble agents reach higher FA/Fi, soluble are lower. A higher concentration of agent will cause ratio to be higher.
Cardiac output and rate of rise of FA/Fi
Lower cardiac output increases rapidity of rise because less is taken up by blood and by tissues - leaves more in the alveoli
Minute ventilation and rate of rise of FA/Fi
Greater minute ventilation increases rise more rapidly because more agent going to the lungs and tissues (no different in insoluble agents)
What if CO & minute ventilation rise together - what happens to FA/Fi ratio
Rises faster
Children Fa/Fi ratio
Have a larger VRG so proportion of CO to VRG is higher- faster induction in kids
Deadspace and uptake of agents
Minimal effects
R to L intrapulmonary shunts such as with R mainstem ETT what happens with uptake?
Over ventilated = more uptake, under ventilated = less uptake, evens out - less effect with soluble agents
If 2/3 of inhaled anesthetic is taken up, how soluble is it and what is the Fa/Fi ratio?
Highly soluble, 33%
If 1/4 of inhaled anesthetic is taken up, how soluble is it and what is the Fa/Fi ratio?
low solubility, 75%
