Inhalation Agents 2 Flashcards
What factors influence absorption
Uptake
What factors influence distribution
Biotransformation
Lipid Solubility, Tissue Factors, Metabolism (Small) CO
What factors influence excretion
Elimination
Depth of Anesthesia is measure by
Pbrain
How is Fresh Gas Flow determined
vaporizer and flowmeter settings
Fi Is and determined by
inspired gas concentration
it is determined by: FGF rate, breathing circuit volume and circuit/machine absorption
FA is
alveolar gas concentration
FA is determined by
uptake
ventilation
concentration effect and second gas effect
Fa is
arterial gas concentration
Fa is affected by
ventilation/perfusion mismatching
3 A’s of anesthesia
Amnesia- Brain
Analgesia- Thalamus
Areflexia- Spinal Cord
FA- factors affecting Alveolar Concentration
Blood Solubility of the agent
Alveolar Blood Flow
Partial Pressure between alveoli and venous blood
Fa- Factors affecting Arterial Concentration
Alveolar and arterial anesthetic partial pressure are considered equal
Fa is less than the end tidel level will predict. Due to venous admixture, alveolar dead space and non-uniform distribution
Ventilation/Perfusion MisMatch is due to
Right Bronchial Intubation or PFO
V/Q mismatch effect is
to increase the alveolar partial pressure (highly soluble agents) and decrease in arterial partial pressure (low solubility agents)
Stage 1 of Anesthesia
Amnesia & Anesthesia
Initiation of Anesthesia, LOC, patient able to follow simple commands, protective reflexes remain intact, eyelid reflex intact
Stage 2 of Anesthesia
Delirium & Excitation LOC and eyelid reflex Irregular Breathing pattern Dilated pupils Neurons that inhibit excitation are not functional and can lead to vomiting, laryngospasm, cardiac arrest and emergence delirium. More exaggerated in pediatrics
Stage 3 of Anesthesia
Surgical Anesthesia
Initial cessation of spontaneous respirations, absence of eyelash response and swallowing reflexes
Stage IV of Anesthesia
Anesthetic Overdose
Cardiovascular collapse requiring provider intervention (yes, thats you)
MOA of Inhalation Agents
Unknown, but thought to work on these targets: NMDA Receptors tandem pore potassium channels Voltage-gated sodium channels Glycine Receptors GABA Receptors
CNS Effects of Inhalation Agents
CMRO2 is decreased
Cerebral BF is increased (dose dependent)
This effect is called uncoupling.
Greater with Sevo
What does N2O do to CMRO and CBF?
Increases CMRO2 and CBF
When does burst suppression occur?
1.5 MAC of Des
2 MAC w/ Iso and Sevo
What effect do inhalation agents have on evoked potentials
decrease amplitude and increase latency
Developmental Neurotoxicity
Evidence that in rodents and non-human primates that anesthetic agents are toxic to human brain
Three major studies look at it, and found no evidence to support claims. Take aways where: keep surgery as short as possible and use short acting medications and multimodal approaches
Post-Operative Cognitive Dysfunction
POCD
Greater concern in Elderly
No clinical significant association b/t major surgery and anesthesia w/ long term POCD
Emergence Delirium in Children
common with SEvo and Des
Medication adjunct: Precedex
In a dose dependent fashion, all inhalation agents reduce
cardiac output and cardiac index. They reduce the free intracellular Ca2+ contractile state.
As MAC increases, slight increase in Cl and HR
With inhalation agent administration, you can witness reduce MAP secondary to
SVR reduction. N2O in combination with anesthetic will reduce this phenomenon
Volatile agents and N2O induce
HR changes via the sinoatrial node antagonism
Modulation of baroreflex activity
Sympathetic nervous system activity
All inhalation agents produce some
vasodilation (SVR)
Isoflurane can induce
reverse Robin-Hood syndrome in hypotensive patients
Preconditioning
phenomenon in which the heart is exposed to a cascade of intracellular events that protect it from ischemic and re-perfusion insult
Sensitization
volatile agents reduce the quantity of catecholamines necessary to evoke arrhythmias
Safe Epinephrine Dosing
10 ml in 1:100,000 epi in a 10 min period or up to 30ml/hour
Nitrous Oxide causes a slight decrease in
PVR
Worsens pulmHTN
Volatile agents decrease
pulmonary artery pressure
Hypoxic Pulmonary vasoconstriction is
mildly depressed.
Iso has the greatest effect
Cardiovascular Effects of Iso
decreases CO
Decreases SVR
Decreases MAP
increases HR
Cardiovascular effects of Des
no change CO
decrease SVR
Decrease MAP
increase HR
Cardiovascular Effects of Sevo
No change CO
Decrease SVR
Decrease MAP
No change HR
Cardiovascular Effects of N2O
Decrease CO
Increase SVR
No change MAP
Increase HR
Cardiovascular Effects of Xenon
No Change CO
No change SVR
No change MAP
Decrease HR
Volatile agents cause dose dependent decreases in
Tidal volume
Responsiveness in CO2
- increase apneic threshold
- exacerbated by co-administration of an opioid
Halothane Hepatitis
Occurs in b/t 6k-35,000 cases
mostly like from the trifluoracetyl-contained metabolites binding to proteins and forming anti-trifluroacetyl protein antibodies
Re-exposure of the patient to halothane these antibodies will mediate massive hepatic necrosis that can result in death
Transient increase in ALTs will occur with what inhalation agent
Des
What inhalation agent is most associated with risk in patients with renal compromised
Sevo
What inhalation agents has the LEAST impact on renal function
Des
Sevoflurane has the greatest metabolism where and how much
liver
5-8%
All volatile agents produce a dose-dependent relaxation on what muscle
Skeletal muscle
Additive effect with NMBDs
Can be reduced 25-50% of dose when compared to TIVA
Delay recovery from nondeplorizing NMBD
The IDEAL anesthetic Agent
non-irritating to respiratory tract rapid induction and emergence Chemical stable (non flammable) produce amnesia, analgesia and areflexia potent not metabolized and excreted by respiratory tract free of toxicity and allergic reactions minimal systemic changes uses a standardized vaporizer affordable
Four Properties of how agents work
Vapor Pressure
Boiling Point
Partial Pressure
Solubility
Vapor Pressure
Pressure exerted inside a container between liquid and vapor
at Room temp, most volatile agents have a VP below atm pressure
As long as liquid is present, VP is independent of volume
Directly proportional with temperature
Boiling Point
Temperature at which VP exceeds Atm Pressure in an open container
Partial Pressure
fraction of pressure within a mixture (Dalton’s Laws)
Solubility
tendency of gas to equilibrate with a solution (Henry’s Law)
Anesthetic gases administered to the lungs diffuse into the blood until their partial pressures to the alveoli and blood are equal
equalizing of blood and target tissues occurs simultaneously, however there is not gas phase
The concentration of an anesthetic in the tissues is depenedent on (2)
partial pressure and solubility
inspired concentrations or fractional volumes are typically used instead of partial pressures
MAC
Minimun Alveolar Concentration
The definition of MAC is the minimum alveolar concentration (%) required to produce anesthesia (lack of movement) in 50% of the population (ED50)
MAC Awake
50% of the population opens their eyes to command
Mac BAR
MAC necessary to block adrenergeric response to stimulation
Usually 1.3 of MAC value
Can be reduced by administering a narcotic prior to incision
MAC’s additive Effect
0.5 MAC of N2O + 0.5 MAC of iso= 1 MAC Sevo
Factors that increase MAC
hyperthermia
drug induced increases in CNS activity
Hypernatremia
Chronic Alcohol Abuse
Factors that Decrease MAC
hypothermia increasing age alpha 2 agonist acute alcohol ingestion pregnancy hyponatremia
Vaporizers
the delivery device for volatile agents
Facilitate the movement of anesthetic from the machine to the patient through
-Fresh gas flows
-pressure
-temperature
Vaporizers are calibrated for specific agents
Isoflurane
Halogenated Methyl Ethyl Ether
Most POTENET
Slower onset and recovery from anesthesia
Isoflurane’s Cardiovascular Effects
minimal cardiac depression, preserves carotid baroreceptors
dilated coronary arteries, concerns for reverse robin hood
Iso Respiratory Effects
Pungent NOT used for inhalation induction
tachypnea less pronounced
Desflurane
Least Potent
Quicker induction and emergency
Potential to boil at Room temperature
Desflurane Cardiovascular Effects
Rapid increase in Des = increase in HR and BO
Attenuated with fentanyl, Esmolol, and clonidine
Desflurane Respiratory Effects
VERY PUNGENT
cause cause airway irritation
increased salivation, breath holding coughing and laryngospasm
avoid in patient with airway disease
Sevoflurane
Moderate Potency
Rapid induction and emergence
Sevo Cardiovascular Effects
May prolong QT interval
Cardiac Output is less maintained than other agents
HR NOT increased
Sevo Respiratory Effects
Non pungent
preferred for inhalation
Sevo Metabolism and Renal Effects
Metabolized in CYP 450 2E1
- increases inorganic fluoride ions, but has not resulted in nephrotoxicity
Soda Lime can degrade Sevo into Compound A
For safety, calcium hydroxide absorbent, flows 2 lpm, avoid in patients with renal dysfunction
Nitrous Oxide
Not a volatile Anesthetic colorless odorless gas at room temp nonexplosive and nonflammable (but can contribute to combustion) NMDA receptor antagonist
N20 Systemic Effects
Cardiovascular- stimulates Sympathetic nervous system (BP HR CO unchanged or slightly elevated)
RR- increases Respiratory Rate; decreases hypoxic drive
Cerebral- increases CMRO2 and CBF
GI- increases risk of PONV
absolute Contraindications of N20
methionine synthase pathway deficiency
expansion of gas-filled space
Relative N20 Contraindications
PONV First Trimester of Pregnancy Increased ICP Pulm HTN Prolonged surgery (>6hr)
Xenon
Noble gas with known anesthetic properties
odorless colorless nonexplosive naturally occurring
inert, dose not form chemical bonds
Actions via NMDA and glycine receptor binding sites
minimal cardiovascular, hepatic and renal effects
no effect to ozone layer
cost and limited availability have prevented widespread use
Malignant Hyperthermia
Pharmacogentic disordered triggered by volatile agents succinylcholine and stress
Ryanodine receptor gene mutation
MH signs and symptoms
Increase in Co2 production muscle rigidity metabolic acidosis high temperature (late sign) urine color darkness tachycardia, tachypnea
MH is caused by what gases
all inhalation agents except N20
MH treatment
Dantrolene Sodium- muscle relaxant
1mg/kg administer til symtpoms subside, up to 10mg/kg
Ryanodex- new IV formulation of dantrolene for prevention and treatment of MH
- requires fewer vials and less reconstitution
-shorter half-life
-requires supplementation of mannitol
Anesthesia in Pregnancy
0.2-0.75% of pregnant patients require general anesthesia (appendectomy, cholecystectomy, ovarian, trauma)
some clinicians avoid N2O due to teratogenic effects
-elective surgery should be delayed until after delivery
- non-urgent surgery should be performed in 2nd trimester
