Inhaled Anesthetics Flashcards
Nitrous Oxide (chart)
Molecular weight: 44
Odor: sweet
Blood:gas partition coefficient: 0.46
MAC c 100 O2: 104
Halothane (chart)
Molecular Weight: 197 Boiling Point: 50.2 Vapor Pressure: 244 Odor: Organic Not stable in soda lime Requires a preservative Blood: gas partition coefficient - 2.54 (Most soluble in blood) MAC c 100% O2: 0.75 MAC c 60-70% N2O: 0.29
Enflurane (chart)
Molecular Weight: 184 Boiling Point: 56.5 Vapor Pressure: 172 Odor: Ethereal Blood:gas partition coefficient: 1.9 MAC c 100% O2: 1.63 MAC c 60-70% N20: 0.57
Isoflurane (chart)
Molecular weight: 184 Boiling Point: 48.5 Vapor Pressure: 240 Odor: Ethereal Blood:gas partition coefficient - 1.46 MAC c 100% O2: 1.17 MAC c 60-70% Nitrous: 0.5
Desflurane (chart)
Molecular Weight: 168 Boiling Point: 22.8 Vapor Pressure: 669 Odor: Ethereal Blood:gas partition coefficient 0 0.42 MAC c 100% O2: 6.6 MAC c 60-70% N2O: 2.83
Sevoflurane (chart)
Molecular Weight: 200 Boiling Point: 58.5 Vapor Pressure: 170 Odor: Ethereal Not stable in soda lime Blood:gas partition coefficient - 0.69 MAC c 100% O2: 1.8 MAC c 60-70% N2O: 0.66
Partial pressure
Dalton’s Law is the total pressures of a mixture of gases is the sum of the pressures each gas would exert if it were present alone
- We want to get inhaled anesthetics to the brain
Minute Ventilation
Sum of all exhaled gas volume in 1 minute
Minute ventilation =Tidal volume x Breaths/min
= 5 L/min
Alveolar Ventilation
Volume of inspired gases actually taking part in gas exchange in 1 minute
PCO2
(Tidal Volume - Dead Space) x Breaths per min
Dead Space
Basically any volume of inspired breath which dose not enter the gas exchange areas of the lungs is dead space.
Anatomic Dead Space
The breath entering the mouth, pharynx, and tracheobronchial tree but does not enter into the alveoli
Alveolar Dead Space
the portion of a breath that enters alveoli which are ventilated but not perfused
AKA West Zone’s 1
Alveolar Partial Pressure (PA)
determined by input (delivery) of inhaled anesthetic into alveoli minus uptake (loss) of drug from alveoli into arterial blood
Determinants of PA
alveolar ventilation anesthetic breathing system solubility CO Alveolar to Venous Partial Pressure Differences
Concentration Effect
The higher the inspired concentration of anesthetic agent, the more rapid the relative rise in alveolar concentration of the agent
Machine -> alveoli -> blood -> brain
Second Gas Effect
The ability of the large volume uptake of one gas (first gas) to accelerate
We use Nitrous to do this
More applicable to a gas with a higher blood:gas partition coefficient
Partition coefficient
reflects the relative capacity of each phase to accept anesthetic; is temperature dependent
Blood:gas solubility
- states how soluble an anesthetic is in blood
- inversely related to induction time
- less soluble the gas is in blood = quicker induction of anesthesia
Tissue:Blood Partition Coefficient
Determines uptake of anesthetic into tissues and time necessary for equilibration of tissues with Pa
Tissue:Gas
Concerns lean tissues (muscles, vessel rich organs) affinity for a given anesthetic agent
Predicts emergence times from anesthesia
Lower ratios indicate the gas is relatively insoluble in tissues thus emergence will be more rapid
Stage I of Anesthesia
Begins with induction of anesthesia
Ends with loss of consciousness (no eye-lid reflex)
Still can sense pain
Stage II of Anesthesia
Delirium Excitement
Uninhibited excitation
Pupils dilated, divergent gaze
Potentially dangerous response to noxious stimuli: Breath holding Muscular rigidity Vomiting Laryngospasm
Stage III of Anesthesia
Surgical Anesthesia
Centralized gaze with constriction of pupils
Regular respirations
Anesthesia depth is sufficient for noxious stimuli when the noxious stimuli dose not cause increase sympathetic response
Stage IV of Anesthesia
Stay away from this stage. It is TOO DEEP
- Apnea
- Non reactive dilated pupils
- Hypotension resulting in complete CV collapse if not monitored closely
Cardiac Output’s effect on Anesthesia
- carries away either more or less anesthetic from alveoli
Increased: more rapid uptake—slowed induction
Decreased: speeds rate of rise in PA—less uptake—quicker induction
Recovery from Anesthesia
- In soluble anesthestics: Duration of administration prolongs emergence
- Exhaled gases will be rebreathed unless fresh gas flow rate is increased
- rate of decrease in Pbr is relative to the decrease in PA
EEG Effects and Inhaled Anesthetics
MAC < 0.4 = same in all gases
Equal to 0.4 MAC = voltage shifts from posterior to anterior portions of the brain
Seizure Activity and Inhaled Anesthetics
- Enflurane has high voltages and frequencies (most similar to seizure)
- SUPPRESS convulsant Properties: Iso-, des-, sevo
- N2O: increased motor activity; withdrawal in animals may indicate acute dependence
Cerebral Blood Flow
Volatile anesthetics > 0.6 MAC produce cerebral vasodilation, decreased cerebral vascular resistance, dose-dependent increase
At 1.1 MAC: halothane > enflurane > isoflurane = Desflurane
N2O: increases
Increase occurs within minutes of administration of anesthetic
Cerebral Metabolic O2 Requirements
Dose dependent decrease
Isoflurane = desflurane = sevoflurane > halothane
Decreases metabolic requirement– decreased CO2 production -> vasoconstriction that decreases CBF
Cerebral Protection
Isoflurane shows protection from ischemia when used in carotid endarterectomy
Effects on MAP
Decrease: Sevo, Iso, Des, (Decrease SVR)
Decrease: Halo decreases contractility
NO change: Nitrous
Effects on HR
Increase: Des > Iso > Sevo (Sevo must be MAC > 1.5)
No change: Halothane
Des has highest increase
Effects on CO/SV
Left SV : decreases with ALL anesthetics
Slight increase: Nitrous
Decrease: Halothane (dose dependent)
No change: sevo, des, iso
Effects on SVR
Decrease: Iso > Des >Sevo
No change: Halothane, Nitrous
Iso has the most affect
Effects on Pulmonary Vascular Resistance
Volatile Anesthetics: little to no effect
Increases: Nitrous (exaggerated in Pulm HTN, neonates and congenital heart disease)
Cardiac Dysrhythmias
- Anesthesia decreases the dose of Epi needed to potentiate produce Ventricular dysrhythmias
- Effect is greatest with Halothane
Epi Dose: 6 mg/kg with Iso, Des, Sevo
Effects on Coronary Blood Flow
Volatile anesthetics cause coronary vasodilation
Ischemic Preconditioning (IPC)
- Brief episodes of myocardial ischemia that occur before a longer period of ischemia provide protection against myocardial dysfunction and necrosis
-protective mechanism against tissue injury
-Occurs after 5 minutes of ischemia; effect lasts for 1-2 hours, disappears and reoccurs at 24 hours
Second or late window may last as long as 3 day
airway resistance
Anesthetics produce decreased airway resistance after antigen induced bronchoconstriction
Halothane—direct relaxing effects on airway smooth muscle (decreases vagal nerve traffic from CNS)
Pattern of Breathing
- dose dependent increase in frequency of breathing
- tidal volume decreases with increased frequency—rapid and shallow breathing pattern
- decreased minute ventilation, increased PaCO2 -> respiratory acidosis
- isoflurane increases frequency of breathing at concentrations up to 1 MAC, then no further increase occurs
Pulmonary Vascular Resistance
Nitrous causes a modest increase in the normal pt.
Increases may be clinically significant in the pt with pre-existing Pulmonary HTN
Volatile Agents decrease
Des which increases at a MAC of 1.6
Hypoxic Pulmonary Vasoconstriction
- The ability of the pulmonary vasculature to constrict in response to regional hypoxemia.
- Mild by Volatile Anesthetics
- Nitrous inhibits this, so it is avoided in thoracic surgery
Hepatic Blood Flow
Iso @ 1.5%: dilates portal vein -> increased hepatic oxygenation
Halothane: vasoconstrictor
LFTs
- Transient increase with Des and enflurane
- surgical stimulation increases all
Fluoride-Induced Nephrotoxicity
Polyuria, hypernatremia, hyperosmolarity, serum creatinine, inability to concentrate urine
Vinyl Halide Nephrotoxicity
- CO2 absorbents (Baralyme, soda lime) react with sevoflurane and eliminate hydrogen fluoride from its isopropyl moiety to form breakdown products, including Compound A , a vinyl ether
- Compound A is a dose dependent nephrotoxin in rats
- Need to use at least 2L/minute fresh gas flow rate with sevoflurane to minimize concentration of Compound A that may accumulate in anesthesia breathing circuit
Neuromuscular junction
- Skeletal muscle relaxation with ether-derived fluorinated anesthetics
- N2O—no relaxation, maybe rigidity
- Ability to sustain contractions in response to continued stimulus is impaired with ether derivatives but not with halothane or N2O
- Ether derivatives can cause dose dependent enhancement of NM blockers
Malignant Hyperthermia
- genetic predisposition (tested by muscle biopsy)
- Halothane is highest trigger
- acute disorder developing during or after GA
- you have a constant leak of SR Ca++ through ryanodine receptor
- Caused by: Volatile Anesthetics or Succinylcholine
S/Sx of MH
Hypermetabolic state
Increased HR
Unexplained increase in End-Tidal Co2
-Respiratory and metabolic acidosis, rhabdomyolysis, arrhythmias, hyperkalemia and sudden cardiac arrest
Increased Temp is a LATE sign
Treatment of MH
- notify MD as soon as you suspect it
- Stop triggering agents (gas)
- Hyperventilate c 100% O2 (Use fresh tank instead of circuit)
- abort procedure
- Give IV dantrolene
- Bicarb
- Cooling
- Insulin for Hyperkalemia
- Monitor core temp
- Monitor UO to prevent shock
Nitrous Metabolism
Very little metabolism—mainly by anaerobic bacteria in GI tract
O2 concentration > 10% inhibits metabolism
Halothane Metabolism
- 15-20% metabolized by cytochrome P-450 enzymes
- Oxidation with ample O2, reduction when PaO2 decreased
- Oxidative metabolism produces trifluoroacetyl halide metabolite that may acetylate hepatic proteins resulting in formation of antibodies
- Reductive metabolism in hepatocyte hypoxia produces inorganic fluoride (below level to produce nephrotoxicity)
Enflurane Metabolism
- 3% metabolized by cytochrome P-450 enzymes
- Oxidative metabolism may produce fluoroacetylated hepatic protein-Ab complexes
- Chemical stability, low solubility in tissues; most exhaled unchanged
- Isoniazid increases nephrotoxic potential due to increased metabolism and defluorination
Isoflurane Metabolism
- 0.2% metabolized by cytochrome P-450 enzymes
- Oxidative metabolism to trifluoroacetic acid; possibility of production of acetylated hepatic protein-Ab complexes
- Chemical stability, low solubility; most exhaled unchanged
- Metabolism, concentration of inorganic fluoride produced is less than with enflurane
Desflurane Metabolism
- 0.02% metabolized by cytochrome P-450 enzymes
- Oxidative metabolism to trifluoroacetic acid; possibility of production of acetylated hepatic protein-Ab complexes
- Chemical stability, low solubility; most excreted unchanged
Metabolism of Sevoflurane
- 5% metabolized by cytochrome P-450 enzymes
- Oxidative metabolism—does not produce acetyl halides no possibility of hepatic protein-Ab complexes
- Degraded by CO2 absorbents to potentially nephrotoxic Compound A (Baralyme > soda lime); amount of Compound A produced is less than the toxic level
- Plasma fluoride concentration is higher after administration of sevoflurane than enflurane, but exposure of renal tubules to fluoride is limited because most elimination is through the lungs; hepatic production of fluoride may be less toxic than intrarenal production of fluoride
Carbon Monoxide Toxicity
- CO formation is a product of degradation of anesthetics with a CHF2 moiety by strong bases present in CO2 absorbents
-Desflurane > enflurane > isoflurane
-Halothane, sevoflurane have no vinyl group—no CO production
-Increases intraoperative carboxyhemoglobin concentration
-CO detection difficult because pulse oximetry can’t distinguish between carboxyhemoglobin and oxyhemoglobin
=Delayed neurophysiological sequelae—cognitive defects, personality changes, gait disturbances—can occur up to 3-21 days later
Factors that Increase the magnitude of Carbon Monoxide (CO) Production
- Dryness of CO2 absorbent—hydration prevents
- High temperature of absorbent—occurs during low fresh gas flows and/or increased metabolic production of CO2
- Prolonged high fresh gas flows—contributes to dryness of absorbent
- Type of absorbent (Baralyme > soda lime)
CO2 Absorber fires
- Sevoflurane reacts with desiccated CO2 absorbents to produce CO and flammable organic compounds (methanol, formaldehyde)
- Reaction produces heat, which increases chemical reaction speed so that sevoflurane breaks down rapidly
- Flammable metabolites can spontaneously combust at high temperatures
- Most often associated with Baralyme
Minimal Alveolar Concentration (MAC)
- A MAC (or 1 MAC) is the % of anesthetic agent (gas) which ceases movement in response to noxious stimuli in 50% of patients
- An increase to a MAC of 1.3 will prevent movement in ~95% of pts
- no change in gender
- increased in women with natural red hair presumably d/t mutations of melano-cortin-1 receptor gene and increased pheomelanin concentrations
Nitrous Oxide (N20)
- “laughing gas”
- Noninflammable, odorless,
- Low blood solubility -> rapid onset of action
- Fast induction and recovery time
- Low potency
- Combine with opioids or volatile anesthetics to produce general anesthesia
- Good analgesic effects (short lived; dissipates after ~ 20 min.), sedative effect persists after even after analgesic effect dissipates; minimal skeletal muscle relaxation
Nitrous Oxide Side Effects
- Post-operative—causes nausea and vomiting (controversial)
- Within closed body cavities, N2O can increase the volume -> pneumothorax or increased pressure e.g. in sinuses
- Inactivates Vit B12
Halothane
- Halogenated alkane
- Clear, nonflammable liquid with sweet non-pungent odor
- acceptable for inhalation induction
- Intermediate blood solubility (intermittent onset), high potency, rapid onset and recovery
- Stored in amber colored bottles; thymol added as preservative to prevent oxidative decomposition. Thymol can cause vaporizer to malfunction
- Possibility of hepatotoxicity
Enflurane
-Halogenated methyl ethyl ether
-Clear, nonflammable liquid; pungent odor
Intermediate blood solubility, high potency, intermediate onset and recovery
- Decreases threshold for seizures
- Oxidized in the liver to inorganic fluoride ions which can be nephrotoxic
-Used in cases where low seizure threshold is desirable such a electroconvulsive therapy
Isoflurane
- Halogenated methyl ethyl ether
- Clear, nonflammable liquid; pungent odor
Intermediate blood solubility, high potency, intermediate onset and recovery - Isomer of enflurane
-Extreme physical stability; no preservative required. No deterioration during 5 years of storage, carbon dioxide absorbents, or sunlight
Desflurane
- Fluorinated methyl ethyl ether (fluorine substituted for Cl in isoflurane)
- high vapor pressure, increased molecular stability, decreased potency
- would boil at room temperature; is converted to gas in vaporizer and mixed with diluent fresh gas flow
- Potency is 5-fold less than isoflurane
- Pungent odor causes airway irritation, salivation, breath-holding, coughing, or laryngospasm when >6% is used in the awake patient
Sevoflurane
- Fluorinated methyl isopropyl ether
- Vapor pressure resembles that of halothane and isoflurane permitting delivery of anesthetic with an unheated vaporizer
- Non-pungent, minimal odor; least irritating to airways—acceptable for inhalation induction
- blood:gas partition coefficient 0.69) prompt induction and recovery
Xenon
- Inert gas
MAC 63 - 74% in humans; more potent than N2O (MAC 104%) - MAC is gender dependent being less in females
Nonexplosive, non-pungent, odorless, unreactive, causes minimal cardiac depression - High cost: Needs more studies to prove morbidity and mortality with Xenon
-Has lowest blood:gas coefficient of 0.115
-Does have tendency of bubble expansion like nitrous
-does not contribute to MH
-Emergence is 2-3 times faster than nitrous or Sevo
-Potent hypnotic and analgesic resulting in suppression of hemodynamic and catecholamine responses to surgical stimulation
