Inhalational Agents II Flashcards
Ether Day
October 16, 1846
Who successfully demonstrated how to use ether?
William T.G. Morton
Sevoflurane BP
57°
Sevo VP
159mmHg
Sevo Blood:Gas
0.65
Sevo Oil:Gas
47
Sevo MAC
2%
Isoflurane BP
49°
Iso VP
238mmHg
Iso Blood:Gas
1.46
Iso Oil:Gas
91
Iso MAC
1.2%
Desflurane BP
24°
Des VP
669mmHg
Des Blood:Gas
0.42
Des Oil:Gas
19
Des MAC
6%
Nitrous Oxide BP
-88°
N2O VP
38,770mmHg
N2O Blood:Gas
0.42
N2O Oil:Gas
1.4
N2O MAC
104%
What factors influence PK?
Absorption - uptake
Distribution - biotransformation
Excretion - elimination
Factors affecting FI
Fresh gas flow
Breathing system volume
Machine absorption
Factors affecting FA
Alveolar concentration
Agent blood solubility
Alveolar blood flow
Partial pressure b/w alveoli & venous blood
FA > ET
- Venous admixture
- Alveolar dead space
- Non-uniform distribution
Inhalational Agents MOA
??? NMDA receptors Tandem pore K+ channels VGNa+ Glycine receptors GABA Huff enough gas ya pass out
CNS Sites
Altered transmission in the cerebral cortex
Brain stem arousal centers - amnesia Central thalamus (pain relay center) - analgesia Spinal cord (skeletal muscle relaxation) - areflexia
Meyer Overton Theory
Lipophilicity = potency
Accepted dogma
BUT exceptions exist
CNS Effects
↓ CMRO2 ↑ CBF (dose dependent) Cerebral vascular responsiveness to CO2 - Vasodilate or constrict ICP concern → mild hyperventilation ↓ CO2 to compensate (vasoconstriction to prevent ↑ ICP)
EEG burst suppression
Evoked potentials ↓ amplitude ↑ latency
Spinal surgery w/ nerve monitoring consider TIVA
Uncoupling
Combined effects Increased w/ Sevoflurane ↓ CMRO2 ↑ CBF Exception: Nitrous oxide Mild hyperventilation helps attenuate ↑ CBF Cerebral vasculature responsive to CO2
Developmental Neurotoxicity
No evidence to support in human studies PANDA study, GAS trial, & population-based cohort study ↓ anesthetic agent usage Consider TIVA or regional w/ local Multimodal approaches Utilize short-acting medications
Post-operative Cognitive Dysfunction
Increased concern in elderly
No clinically significant association b/w major surgery & anesthesia w/ long-term cognitive dysfunction
Emergence Delirium
Pediatrics More common w/ Sevo & Des Potential to cause injury & delay discharge Preventative measures - Quiet, stress-free environment - Medication adjuncts
Cardiovascular Effects
All volatile inhalational agents ↓ CO
↓ MAP secondary to ↓ SVR (vasodilation)
Utilize N2O ↑SVR in combination to decrease
Heart rate changes via SA node antagonism, baroreflex activity modulation, & SNS activity
Reverse Robin Hood
Steal blood flow from ischemic areas and divert to well-perfused
Vasodilation ↓SVR in hypotensive patients
*Isoflurane (dilates coronary arteries)
Preconditioning
Exposure to mild intracellular events ↓HR ↓BP ↓CO that protect from ischemic injury & reperfusion insult
Pre-conditioned to respond to severe event
Develop “memory”
Sensitization
Volatile agents reduce catecholamines necessary to evoke arrhythmias
Less common in ASA I & II classifications
Safe epinephrine dosing
10mL 1:100,000 Epi
Halothane
Pulmonary Circulation
Nitrous oxide causes slight ↑ PVR
Worse in pulmonary hypertension patients (avoid N2O)
Volatile agents ↓ pulmonary artery pressure d/t vasodilation effects
Hypoxic pulmonary vasoconstriction mildly depressed
Isoflurane has greatest effect
Respiratory Effects
Shallow breaths ↓ TV ↑ RR (not sufficient to offset)
↓ CO2 responsiveness ↑ apneic threshold
Relaxes airway muscle & produces bronchodilation
Renal Effects
↓ renal SVR ↓ GFR ↓ UOP
Desflurane least impact on renal function
Sevoflurane associated w/ risk in renal compromise patients leading to haloalkene Compound A (nephrotoxic)
- Older absorbents CaOH or Lithium OH
- Do not exceed 2 MAC hours at flow < 2L/min (another dogma)
- Fresh gas flow < 1L/min not recommended
Hepatic Effects
Halothane hepatitis
Trifluoracetyl metabolites binding to proteins & forming anti-trifluoracetyl protein antibodies
Repeat exposure antibodies mediate massive hepatic necrosis
Potentially lethal
No longer use Halothane d/t metabolism & potential to impair hepatic function
Current volatile agents - significant liver damage extremely rare
Molecular structure fluorination resists hepatic degradation
No significant impact on hepatic flow
*Sevoflurane 5-8% metabolism
Neuromuscular Effects
All volatile agents produce dose-dependent skeletal muscle relaxation (areflexia)
Additive effect w/ NMBDs - potentiation
↓ 25-50% dose when compared to TIVA
Delay non-depolarizing NMBD recovery
The Ideal Anesthetic Agent
- Non-irritating
- Rapid induction & emergence
- Chemically stable (not flammable)
- Produce amnesia, analgesia, & areflexia
- Potent concentration
- No metabolism - excreted by respiratory tract
- Non-toxic & no allergic reactions
- Minimal systemic changes
- Uses standardized vaporizer
- Affordable
Inhalational Agent Physical Properties
Affect how agents work:
Vapor pressure
Boiling point
Partial pressure
Solubility
MAC Awake
Minimum alveolar concentration when 50% population opens eyes to command
Amnestic w/out analgesic or areflexic
MAC BAR
Block adrenergic response
Usually 1.3 MAC
Reduce w/ administering narcotic prior
Closer to ED95
MAC Unaffected by
Gender
Anesthesia duration
Comorbidities
Increase MAC
Hyperthermia Drug-induced ↑ CNS activity Hypernatremia Chronic alcohol abuse Red-haired females
Decrease MAC
Hypothermia Increasing age 6% decline each decade after 40yo Alpha 2 agonists Acute alcohol ingestion Pregnancy Hyponatremia
Vaporizers
Volatile agents delivery device
Facilitate anesthetic movement from machine to the patient through fresh gas flow, pressure, & temperature
Calibrated for specific agents
ISOFLURANE
Halogenated methyl ethyl ether
Most potent current volatile agents
Slower onset & recovery - most soluble blood:gas
Minimal cardiac depression & preserves carotid baroreceptors
Dilates coronary arteries - reverse Robin Hood concern
Pungent not used for inhalational induction
Tachypnea less pronounced
Most stable & consistent
DESFLURANE
Least potent volatile agent
Rapid induction & emergence
Boiling point close to room temperature
Overpressurizing not recommended d/t ↑HR ↑BP
Pungent - airway irritation, increased salivation, breath holding, coughing, laryngospasm, not used for inhalational induction
Avoid in patients w/ reactive airway disease
SEVOFLURANE
Fluorinated methyl isopropyl ether
Moderate potency - rapid induction & emergence
Prolong QT interval
CO less maintained than other volatile agents
No heart rate increase/compensation
Non-pungent preferred volatile for inhalational induction
Sevo Metabolism
CYP450 2E1
5-8% metabolism
Increased inorganic fluoride ions
Only volatile agent metabolized
Compound A
Sevoflurane absorbent soda lime potential to degrade into Compound A
Increased gas temperature, low flow anesthesia, high Sevo concentrations, & prolonged surgeries
Nephrotoxic?
Safety - utilize CaOh absorbent, flow 2L/min, avoid in patients w/ renal dysfunction
Dogma*
Nitrous Oxide (N2O)
Not volatile anesthetic Colorless & odorless Non-explosive & non-flammable NMDA receptor antagonist Lower chronic pain risk after surgery
N2O PD
Stimulates SNS Cardiovascular stability ↑ RR ↓ hypoxic drive ↑ CMRO2 ↑ CBF ↑ PONV risk
N2O Contraindications
Absolute:
Methionine synthase pathway deficiency
Gas-filled space expansion
Relative: PONV risk ↑ ICP 1st trimester (teratogenic effects) Pulmonary hypertension >6hr surgery
Xenon
Girl of the 21st century Ideal inhalational agent Nobel gas w/ known anesthetic properties Colorless & odorless Non-flammable Inert does not form chemical bonds MOA via NMDA & glycine receptor binding sites Minimal CV, hepatic, or renal effects Neuroprotective? No ozone layer effect Cost & limited availability
Malignant Hyperthermia
Pharmacogenetic disorder triggered by volatile anesthetics, succinylcholine, stress
Ryanodine receptor gene mutation (chromosome 19)
S/S: ↑CO2, muscle rigidity, tachycardia, tachypnea, metabolic acidosis, ↑temp (late sign)
Dantrolene Sodium
Muscle relaxant
1mg/kg up to 10mg/kg
20mg per vial
Admin until S/S subside
Ryanodex
New IV formulation to prevent & treat Fewer vials & less reconstitution Shorter half-life Mannitol supplementation 2.5mg/kg
