Inhalation Anesthetics

• General anesthetics can be administered via inhalation.

Objectives

• Characteristics of an ideal general anesthetic should be known.
• The concept of balanced anesthesia should be explained.
• The use of pre-anesthetic medications should be described.
• Induction and recovery times based on physical properties of general anesthetics should be explained.
• Factors controlling volatile anesthetic passage from machine to brain must be described.
• Understand what MAC means.
• Physiological indices for surgical anesthesia and anesthetic overdose should be described.
• Must be able to recognize malignant hyperthermia and know how to treat it.
• Physical, pharmacological, kinetic, toxicological properties, and uses of inhalation anesthetics should be compared and contrasted.
• An understanding of what an "incomplete anesthetic" is is crucial.

Goals of General Anesthesia

• Preserving patient life during the procedure is the primary goal.
• Providing an adequate surgical field for the surgeon is essential.
• Blocking pain during the procedure is critical.

Ideal General Anesthetic Characteristics

• Should provide a smooth and rapid induction of unconsciousness.
• Amnesia should occur.
• Inhibition of autonomic and sensory reflexes is expected.
• It should produce skeletal muscle relaxation.
• Analgesia should occur.
• Needs to allow a smooth and rapid emergence and recovery with no long-lasting adverse effects.

Balanced Anesthesia

• Ideal anesthetic agents should use a combination of drugs because no single agent is ideal.
• Drug combinations take advantage of the best properties of each drug and minimize undesirable side effects.
• Rapid induction involves IV anesthetics.
• Maintenance uses inhalation anesthetics.

Preanesthetic Medications

• They decrease anxiety without causing excessive drowsiness.
• They facilitate rapid, smooth induction without prolonging emergence.
• Amnesia is provided for the perioperative period.
• They relieve pre- and postoperative pain.
• Minimize side effects of anesthetics.

Types of Preanesthetic Medications

• Opioids like morphine and fentanyl lead to analgesia.
• Benzodiazepines like Diazepam reduce anxiety, sedate, and cause amnesia.
• Barbiturates like Phenobarbital and Secobarbital reduce anxiety, sedate, and induce rapid induction.
• Phenothiazines such as Promethazine sedate and prevent vomiting.
• Antimuscarinics like Atropine inhibit secretions and laryngospasms and act as an antiemetic.
• Antihistamines like hydroxyzine sedate, produce antimuscarinic effects, and prevent hypotension and bronchospasm caused by d-Tubocurarine-induced histamine release.

Inhaled Anesthetics

• Anesthetic gas includes nitrous oxide.
• Volatile liquids include Desflurane (Suprane), sevoflurane (Ultane), Isoflurane (Forane), Enflurane (Ethrane), and Methoxyflurane (Penthrane).

Mechanism of Anesthetic Action

• Inhibition of neuronal activity happens in many brain regions.
• Potency correlates with lipid/gas partition coefficient in the Meyer-Overton relationship.
• Nonspecific interactions occur with lipid membranes that modify ionic currents.
• Modification of ionic currents occurs via specific interactions with hydrophobic portions of proteins.
• GABAₐ Receptor is a major molecular target and enhances chloride influx even in the absence of GABA; it works in the transmembrane domain to alter gating.
• NMDA receptors are inhibited by ketamine.
• K+ channels include K2P, KV, and KATP channels.
• Nicotinic receptors are inhibited.

Potency

• Relative potency of anesthetic gases is expressed as MAC.
• A larger MAC means less potent.
• 1 MAC is the minimal alveolar concentration (% of total gas) that blocks movement in 50% of patients responding to incision (ED50 of quantal dose-response curve).
• Dosing measures MAC: 0.5-1.1 MAC.
• MAC values are additive; for example, 0.5 MAC of N2O + 0.5 MAC of isoflurane = 1 MAC and will anesthetize 50% of patients.
• Height, weight, and sex do not affect MAC values.
• Conditions that decrease MAC values require less anesthetic, these include: elderly, hypothermia, hypothyroidism and sedatives.
• MAC inversely correlates with the oil/gas partition coefficient.
• Anesthetics with large oil/gas partition coefficients are more potent and will reach surgical anesthesia at lower partial pressures.

Safety of Anesthetics

• Therapeutic indices for most general anesthetics is low (2 - 4).

Stages of General Anesthesia

• Stage I: Analgesia involves analgesia, amnesia, and euphoria, and depends on the agent.
• Stage II: Excitement (Blocks Inhibitory Neurons) causes excitement, delirium, and combative behavior.
• Stage III: Surgical Anesthesia (Depressed RAS) involves unconsciousness, regular respiration, and decreasing eye movement.
• Stage IV: Medullary Depression can cause respiratory arrest, cardiac depression, and arrest, and no eye movement.

Efficacy

• Efficacy of inhalation anesthetics relates to potency.
• Most anesthetics can produce all stages of anesthesia at low concentrations, which allows sufficient O2 to the patient (complete anesthetics).
• Nitrous oxide is an incomplete anesthetic because it cannot produce all stages of anesthesia without causing hypoxia (1 MAC = 100% of inhaled air). It does produce analgesia and amnesia.

Pharmacokinetics of Anesthetic Gases

• Depends on the rate of change of the partial pressure (concentration) of the anesthetic in the brain.
• Changes are determined by the partial pressure of the gas in arterial blood.
• The speed of induction is inversely correlated with the blood/gas partition coefficient.
• Inhalation anesthetics with smaller blood/gas partition coefficients, like nitrous oxide, saturate blood faster and therefore saturate the CNS faster.
• Increasing ventilation rate enhances the rate of loss of consciousness more for soluble gases than insoluble gases, this includes Opioid analgesics.
• Decreasing pulmonary blood flow (decreasing cardiac output) increases the induction rate of soluble gases, this includes hemorrhagic shock.
• Increasing the concentration of soluble gases in inspired air increases their induction rate.
• A high concentration of nitrous oxide increases the induction rate of more soluble anesthetics in the second gas effect.
• Rapid uptake of N₂O increases the partial pressure of the second gas in the lungs, causing the second gas to dissolve more rapidly.

Distribution of anesthetics: Blood to tissues

• Brain and Viscera have high perfusion, small partition coefficient, and rapid equilibration.
• Lean tissues have moderate perfusion, moderate partition coefficient, and moderately rapid equilibration.
• Fat has low perfusion, large partition coefficient, and slow equilibration.

Emergence (Recovery)

• Recovery mirrors the same factors operating in the reverse direction.
• Recovery particularly slows with more lipid-soluble anesthetics and longer durations of anesthesia.
• Diffusion Hypoxia occurs because of nitrous oxide.
• Rapid release of N₂O from blood to lungs requires that pure O₂ is given for a few minutes to counter this effect.

General Pharmacological effects on the CNS

• There is a dose-dependent depression of all portions of the CNS.
• The order of sensitivity (most to least) shows.
• Spinothalamic (analgesia) happens first, followed by the RAS and cortex (anesthesia), spinal reflexes (muscle relaxation), and then the medulla.
• There is an increase in intracranial pressure and an increase in cerebral blood flow by vasodilation of cerebral vasculature due to inhibition of sympathetic nerves.

Cardiovascular Effects

• Mean arterial pressure decreases from vasodilation caused by the inhibition of sympathetic nerves from Isoflurane, desflurane, and sevoflurane which causes reflex tachycardia.

Respiratory Effects

• There is a depression of the medullary respiratory center.
• The response to hypoxia is depressed (increased PCO2).
• Halothane and sevoflurane cause bronchodilation.
• Desflurane causes airway irritation and coughing.

Miscellaneous Effects

• Kidney function sees a decrease in renal blood flow.
• Liver function sees a decrease in hepatic blood flow.
• The uterine smooth muscle experiences relaxation via halogenated anesthetics, not N₂O, and an increased risk of abortion.

Properties of Specific Inhaled Anesthetics

• Nitrous Oxide:
• Oil gas ratio is 1.4
• MAC is >100%
• Blood-Gas Ratio 0.5
• Has a minimal effect on the CV
• There is no Muscular Relaxation
• Isn't metabolized
• It has the lowest potency but is often used in combo for rapid onset and recovery; has potential for abuse
• Enflurane oil gas ratio is 98.
• MAC is 1.7%
• Blood-gas ratio is 2.
• It decreases cardiac output.
• Induces medium muscle relaxation.
• Around 8% is metabolized.
• Can induce Tonic-clonic muscle spasms.
• Isoflurane oil gas ratio is 98.
• MAC is 1.3%
• Blood-gas ratio is 1.4
• It causes vasodilation and tachycardia.
• Induces medium muscle relaxation.
• Only a slight amount is metabolized.
• It can lead to bronchiolar secretions and spasms.
• Desflurane oil gas ratio is 19.
• MAC is 7%
• Blood-gas ratio is 0.4
• It causes vasodilation and tachycardia.
• Induces medium muscle relaxation.
• Almost none is metabolized.
• It has the Most rapid onset but can create airway irritation and coughing.
• Sevoflurane oil gas ratio is 51.
• MAC is 2.5%
• Blood-gas ratio is 0.7
• It causes vasodilation
• Induces medium muscle relaxation.
• Around 2-5% is metabolized into fluoride.
• It has a Rapid Onset and Recovery
• Methoxyflurane ratio is 0.2.
• Blood-gas ratio is 2
• 70% or more is metabolized into fluoride.
• It generally isn't used with a risk of nephrotoxicity.

Malignant Hyperthermia

• It is an autosomal dominant genetic disorder of skeletal muscle.
• It is characterized by Abnormal Ca²+ channels (ryanodine receptors).
• There is Exposure to potent inhalation anesthetics and depolarizing muscle relaxants like succinylcholine which cause abnormally large increase in Ca2+ within skeletal muscle.
• Rapid onset of severe muscle rigidity, hyperthermia, hyperkalemia, tachycardia, hypertension, and acid-base imbalance with acidosis
• It is a rare but important cause of anesthetic morbidity and mortality.
• Treated with Dantrolene which blocks calcium release channels in the sarcoplasmic reticulum.
• Requires Measures to control body temperature