Exam 3 Inhalation Agents

Volatile Inhalation Agents and N2O

• Relative potency (MAC) of an anesthetic agent is measured by immobility, which is mediated by depressing AMPA and NMDA currents in the spinal cord.
• MAC amnesia is lower than MAC unconsciousness, which is lower than MAC immobility.
• Blood gas coefficient (BGC) affects the onset and emergence of an anesthetic; a lower BGC results in faster onset and emergence.

Determinants of Alveolar Partial Pressures

• PA (arterial pressure) and Pbr (partial pressure in brain) are determined by input (delivery) into the alveoli minus uptake (loss) of the drug from the alveoli into the pulmonary arterial blood.
• Input depends on PI, alveolar ventilation, and characteristics of the anesthetic breathing system.
• Uptake depends on solubility, cardiac output (CO), and alveolar-to-venous partial pressure difference (PA - Pv).

Second Gas Effect

• High-volume uptake of one gas (first gas) increases the concentration of other gases (second gas) in the alveoli, speeding up the uptake of the second gas.
• Nitrous oxide (N2O) can speed up the onset of inhalational anesthetic agents when used as a carrier gas.

Mechanism of Action

• Inhalation agents may influence K+ channels, protein binding, dissolvability in lipids (Meyer-Overton hypothesis), potentiate inhibitory glycine receptors, decrease neurotransmission at glutamate receptors, and block the effects of NMDA receptors.

Administration and Induction

• The primary objective of inhaled anesthesia is to achieve a constant and optimal brain partial pressure (Pbr) of the anesthetic.
• Factors influencing the rate of anesthetic induction include age, co-existing disease, and co-administration of other pharmacologic agents.
• Low cardiac output can lead to abrupt increases in alveolar pressure.

Metabolism and Elimination

• Absorption/Solubility: from vaporizer to alveoli to pulmonary capillary.
• Distribution: from capillary to site of action.
• Metabolism: liver or renal, depending on the agent's chemical structure, hepatic enzyme activity, genetic factors, and blood concentration.
• Elimination/Recovery: primarily through the lungs, with continued uptake/removal in other tissues depending on solubility and duration of exposure.

Factors Influencing MAC

• MAC is inversely affected by age.
• Decreased during pregnancy and returns to baseline in 12-72 hours.
• Red hair coupled with female gender increases MAC.
• MAC values for inhaled agents are additive.
• Opioids synergistically reduce inhaled anesthetic requirements.

Complications

• Cardiac dysrhythmia: halothane has a risk of cardiac depression and ventricular tachycardia (VT).
• Hepatic disease: halothane has a risk of postoperative hepatic dysfunction.
• Kidney injury: enflurane and sevoflurane can cause kidney damage due to nephrotoxic compounds produced during metabolism.
• Hypotension: decreases in MAP are due to decreases in SVR with isoflurane, desflurane, and sevoflurane.

Influence on Organ Systems

• Cardiovascular performance:
  • Cardiac output: halothane decreases CO, while isoflurane, desflurane, and sevoflurane increase HR.
  • Systemic vascular resistance: isoflurane, desflurane, and sevoflurane decrease SVR.
• Respiratory dynamics:
  • Rate and depth of ventilation: inhaled anesthetics increase RR and decrease Vt (except N2O).
  • Bronchiole smooth muscle tone/airways resistance: sevoflurane produces bronchodilation.
• Renal function: volatile anesthetics decrease renal blood flow and GFR in a dose-dependent fashion.
• Central nervous system effects:
  • Cerebral blood flow: inhalation agents produce dose-dependent increases in CBF, leading to increases in ICP.
  • EEG: at MAC, EEG changes are observed.

Volatile Inhalation Agents and N2O

• Relative potency (MAC) of an anesthetic agent is measured by immobility, which is mediated by depressing AMPA and NMDA currents in the spinal cord.
• MAC amnesia is lower than MAC unconsciousness, which is lower than MAC immobility.
• Blood gas coefficient (BGC) affects the onset and emergence of an anesthetic; a lower BGC results in faster onset and emergence.

Determinants of Alveolar Partial Pressures

• PA (arterial pressure) and Pbr (partial pressure in brain) are determined by input (delivery) into the alveoli minus uptake (loss) of the drug from the alveoli into the pulmonary arterial blood.
• Input depends on PI, alveolar ventilation, and characteristics of the anesthetic breathing system.
• Uptake depends on solubility, cardiac output (CO), and alveolar-to-venous partial pressure difference (PA - Pv).

Second Gas Effect

• High-volume uptake of one gas (first gas) increases the concentration of other gases (second gas) in the alveoli, speeding up the uptake of the second gas.
• Nitrous oxide (N2O) can speed up the onset of inhalational anesthetic agents when used as a carrier gas.

Mechanism of Action

• Inhalation agents may influence K+ channels, protein binding, dissolvability in lipids (Meyer-Overton hypothesis), potentiate inhibitory glycine receptors, decrease neurotransmission at glutamate receptors, and block the effects of NMDA receptors.

Administration and Induction

• The primary objective of inhaled anesthesia is to achieve a constant and optimal brain partial pressure (Pbr) of the anesthetic.
• Factors influencing the rate of anesthetic induction include age, co-existing disease, and co-administration of other pharmacologic agents.
• Low cardiac output can lead to abrupt increases in alveolar pressure.

Metabolism and Elimination

• Absorption/Solubility: from vaporizer to alveoli to pulmonary capillary.
• Distribution: from capillary to site of action.
• Metabolism: liver or renal, depending on the agent's chemical structure, hepatic enzyme activity, genetic factors, and blood concentration.
• Elimination/Recovery: primarily through the lungs, with continued uptake/removal in other tissues depending on solubility and duration of exposure.

Factors Influencing MAC

• MAC is inversely affected by age.
• Decreased during pregnancy and returns to baseline in 12-72 hours.
• Red hair coupled with female gender increases MAC.
• MAC values for inhaled agents are additive.
• Opioids synergistically reduce inhaled anesthetic requirements.

Complications

• Cardiac dysrhythmia: halothane has a risk of cardiac depression and ventricular tachycardia (VT).
• Hepatic disease: halothane has a risk of postoperative hepatic dysfunction.
• Kidney injury: enflurane and sevoflurane can cause kidney damage due to nephrotoxic compounds produced during metabolism.
• Hypotension: decreases in MAP are due to decreases in SVR with isoflurane, desflurane, and sevoflurane.

Influence on Organ Systems

• Cardiovascular performance:
  • Cardiac output: halothane decreases CO, while isoflurane, desflurane, and sevoflurane increase HR.
  • Systemic vascular resistance: isoflurane, desflurane, and sevoflurane decrease SVR.
• Respiratory dynamics:
  • Rate and depth of ventilation: inhaled anesthetics increase RR and decrease Vt (except N2O).
  • Bronchiole smooth muscle tone/airways resistance: sevoflurane produces bronchodilation.
• Renal function: volatile anesthetics decrease renal blood flow and GFR in a dose-dependent fashion.
• Central nervous system effects:
  • Cerebral blood flow: inhalation agents produce dose-dependent increases in CBF, leading to increases in ICP.
  • EEG: at MAC, EEG changes are observed.

Myocardial Ischemic Preconditioning

• Myocardial ischemic preconditioning occurs when the myocardium (heart muscle) is briefly exposed to an ischemic event, which triggers a protective mechanism.
• During this brief ischemic event, potassium channels in the myocardium tend to become hyperpolarized.
• As a result, when the myocardium is exposed to another ischemic event, the potassium channels do not react, protecting the heart from sustained ischemic or hypoxic insult.
• Volatile inhalation agents can mimic this protective effect, providing a similar safeguard against ischemic or hypoxic injury when used briefly.