INHALED ANESTHETICS


MAJOR FACTORS AFFECTING UPTAKE


Solubility


•  Partition coefficients express relative solubility of anesthetic gas at equilibrium


•  Lower partition coefficients imply ↓ solubility, faster equilibration of partial pressure (alveolus ↔ blood ↔ brain), rapid induction (e.g., desflurane)


•  Higher partition coefficients imply ↑ solubility, slower equilibration as more molecules are dissolved in blood, prolonged induction (e.g., halothane)


•  Tissue: Blood partition coefficient = time for equilibrium of tissue with arterial blood


Cardiac Output


•  Increased cardiac output results in faster uptake but ↓ alveolar concentration (Fa) and therefore slower induction (more blood passing through lungs = anesthetic is carried away faster).


•  Effect is less pronounced for insoluble agents


•  Note: Slower induction with R → L cardiac shunt due to no uptake of agent in shunted blood → dilution of arterial concentration despite faster ↑ in alveolar concentration (Fa); least soluble agents are affected most


Alveolar-Venous Concentration Gradient


•  Depends on uptake by desired (brain) and undesired (fat, muscle) tissues


•  Tissue uptake is determined by partition coefficients and regional blood flow


•  Less tissue uptake means blood returns to alveolus with higher partial pressure, thus alveolar concentration (Fa) can ↑ faster



OTHER FACTORS INFLUENCING UPTAKE


Concentration Effect: Increasing the inspired concentration of a gas results in a disproportionate ↑ in the alveolar concentration (Fa); most clinically significant with N2O, as can be used at ↑↑ inspired concentrations than volatile anesthetics


Second Gas Effect: Large-volume uptake of the first gas (classically N2O) causes ↓ total gas volume in alveolus, thereby ↑ alveolar concentration/accelerating uptake of second gas (volatile agent)



Factors that Speed Rate of Induction (↑ Fa/Fi)


•  Use of agents with ↓ solubility (low partition coefficients)


•  Low cardiac output with minimal R → L shunt and preserved cerebral blood flow


•  Increased alveolar minute ventilation, ↑ inspired concentration of agent, ↑ fresh gas flow rate (replaces anesthetic taken up in bloodstream)


•  Pediatric pts → faster induction due to ↑ alveolar ventilation, ↓ FRC, ↑ % of blood flow to brain


ELIMINATION/RECOVERY


•  Reduction of anesthetic in brain tissue is via exhalation >> biotransformation > transcutaneous loss


•  Biotransformation via P-450 enzymes more important for halothane (20%) than sevoflurane (5%), isoflurane (0.2%), or desflurane (<0.1%)


•  Recovery expedited by high fresh gas flows, elimination of rebreathing, low absorption by the circuit, decreased solubility, high cerebral blood flow and ↑ minute ventilation


•  Context-sensitive elimination time: Longer duration of anesthetic is associated with longer time to recovery; over longer time more anesthetic is deposited in undesired tissues and must be “washed out”; effect more pronounced with ↑ solubility of agent (see Fig. 2A-2)


Figure 2A-2. Solubility and duration of use affect rate of recovery from inhaled anesthetics.



DIFFUSION HYPOXIA


•  High concentrations of relatively insoluble gasses (N2O) diffuse out of the blood and enter the alveolus, displacing and reducing alveolar concentration of O2 and CO2


•  Dilution of alveolar O2 can lead to hypoxia, dilution of CO2 can ↓ ventilatory drive and worsen hypoxia


•  Administer high-flow 100% O2 for 5 to 10 min after discontinuation of N2O


MINIMUM ALVEOLAR CONCENTRATION (MAC)


•  Unitless value comparing potency of inhaled anesthetic agents


•  Reference point (1 MAC) = alveolar concentration at which 50% of patients will not move in response to a standardized surgical stimulus; analogous to ED50


•  MAC values are roughly additive (i.e., 0.5 MAC of N2O plus 0.5 MAC of sevoflurane ≈ 1.0 MAC)


•  MAC is greatest at 1 yr of age and reduced by 6% per decade of life


•  At MAC 1.3, 95% of patients will not move in response to surgical stimulus


•  MAC-BAR (1.5–2.0 MAC): Concentration which Blocks Adrenergic Response to nociceptive stimuli


•  MAC-Aware (estimated 0.4–0.5 MAC): Concentration at which 50% of patients will not be forming long-term memory


•  MAC-Awake (0.15–0.5 MAC): Concentration at which 50% of patients open eyes on command




CLINICAL CONSIDERATIONS OF INHALED ANESTHETICS


•  Volatile agents may trigger malignant hyperthermia (MH) (see Appendix C)


•  Agents in current use are nonflammable at clinical concentrations


•  All potentiate neuromuscular blockade, degree varies with combinations of drugs/agents; effect of volatiles > N2O


•  Carbon monoxide formed in reaction of volatile agents with desiccated CO2 absorbent, (desflurane > isoflurane >> halothane, sevoflurane); CO production ↑ with Baralyme, dry granules (classic example is Monday AM after O2 flows left on), ↑ temperature, ↑ concentration of agent


•  Exothermic degradation reaction of sevoflurane in the presence of desiccated Baralyme linked to rare absorbent canister fires


SYSTEMIC EFFECTS OF INHALED AGENTS


•  Cardiovascular:


• All volatile agents are dose-dependent CV depressants, though mechanism of ↓ BP differs (see Table, Differential Physiologic Effects of Inhaled Anesthetics)


• Heart rate effects vary with MAC and inspired concentration rate of change


•  Pulmonary:


• All agents cause ↑ RR with ↓ TV, overall volatile agents cause ↓ in minute ventilation and ↑ resting PaCO2


• All blunt ventilatory response to hypoxemia (even at 0.1 MAC), volatile agents ↓ response to hypercarbia


• Volatile agents are potent bronchodilators


• Minimal inhibition of hypoxic pulmonary vasoconstriction (HPV)


•  Neurologic:


• All agents ↑ cerebral blood flow causing ↑ ICP (especially halothane) and impair autoregulation of vascular tone (least with sevoflurane at <1 MAC)


• Volatile agents ↓ cerebral metabolic rate, N2O may ↑


• Desflurane and isoflurane at <1 MAC can suppress status epilepticus while ↑ sevoflurane concentrations associated with epileptiform EEG ∆


• All agents ↓ SSEP/MEP signals


•  Hepatic: Halothane causes both hepatic artery vasoconstriction and ↓ portal vein flow (potential for hypoxic hepatic injury, ↑ LFTs), others preserve vascular supply better with ↑ in hepatic artery flow compensating for ↓ portal vein flow


•  Renal: All cause ↓ renal blood flow, ↓ GFR, ↓ urine output without lasting dysfunction; untreated hypotension can cause acute kidney injury



INHALATIONAL ANESTHETICS, SPECIFIC COMMENTS


Nitrous Oxide (N2O)


•  Key features: MAC of 104% precludes use as solo agent for surgical anesthesia; used at 30–70% concentration as adjuvant to IV or potent inhaled anesthetics. Low solubility = rapid onset/offset of action. Nonpungent, has analgesic properties


•  Disadvantages: Rapidly diffuses into and expands air-containing cavities → avoid in air embolism, pneumothorax (75% N2O doubles size in 10 min), bowel obstruction, pneumocephalus, middle ear and retinal procedures; monitor ETT cuffs and PAC balloons for expansion


•  Prolonged exposure → inhibits B12-dependent enzymes responsible for myelin and nucleic acid synthesis; megaloblastic bone marrow possible with >12–24 hrs use; neurotoxicity with repeated exposures (abuse)


•  Increased homocystine levels possibly related to ↑ postoperative MI (ENIGMA trial; Anesth Analg. 2011 Feb;112(2):387–393)


•  Teratogenic in animal models, no evidence in humans at clinical doses


•  Not flammable, although does support combustion


•  May ↑ PONV risk


•  CV effects: Sympathomimetic, though direct myocardial depressant effect may prevail in hypovolemia, cardiac dx; ↑ PVR especially in patients with pre-existing pulmonary HTN


Isoflurane


•  Key features: Inexpensive; slower onset/offset of action, pungent. Versatile use


•  Disadvantages: Coronary vasodilator, potential for coronary “steal” effect (flow diverted away from vessels with fixed lesions) of uncertain clinical significance


Desflurane


•  Key features: Most rapid onset/offset of action among volatiles; very pungent


•  Disadvantages: High vapor pressure requires an electrically heated vaporizer (eliminates variation in delivery owing to in ambient temperature). Pungency may be irritant in patients prone to bronchospasm. Rapid increase or high MAC (>1.25) may cause transient but significant sympathetic stimulation


Sevoflurane


•  Key features: Least pungent (best choice for inhalational induction); fast onset/offset of action; causes ↓ tachycardia than desflurane or isoflurane; does not sensitize myocardium to catecholamines


•  Disadvantages: Controversial potential for nephrotoxicity due to metabolic production of fluoride ion and degradation to Compound A (nephrotoxic in animals). Compound A production ↑ with low flows, high concentrations of sevoflurane, desiccated barium lime absorbent; minimizing exposure recommended although studies have not shown nephrotoxicity in humans (if using flow rate of 1–2 L limit exposure to <2 MAC hrs; use >2 L for longer cases)


Halothane


•  Key features: Low pungency (ideal for gas induction), inexpensive, ↑ cerebral blood flow > other volatiles, especially potent bronchodilator


•  Disadvantages: Use ↓↓ due to rare but fulminant postoperative auto-immune hepatitis, CV depression and myocardial sensitization to catecholamines (↑ ventricular dysrhythmias)


Heliox (Helium–Oxygen Combination)


•  Non-anesthetic gas mixture, commonly 70–79% helium + 21–30% O2


•  Lower density of gasses (up to 2/3 ↓ than air + O2) promotes laminar flow, reduces turbulence in upper airway obstruction, asthma, COPD


•  Helps ↓ pressures needed to ventilate pts with small-diameter ETTs; ↓ work of spontaneous breathing


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Aug 28, 2016 | Posted by in ANESTHESIA | Comments Off on INHALED ANESTHETICS

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