Anesthesia Pharmacology:  General Anesthesia

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  • Neurocirculatory Responses:  Desflurane (Suprane)

    • Management of rapid increases in BP/heart rate resulting from changes in surgical stimulation intensity --

      • Desflurane (Suprane) effective due to solubility properties

    • Rapid changes in alveolar desflurane (Suprane;e.g., 4% to 12%) (or isoflurane (Forane)) concentrations induce increased sympathetic and renin-angiotensin system activity, increasing heart rate and arterial pressure

    • Sites mediating effect are localized in the upper airway and lungs

      • Not observed with sevoflurane (Sevorane, Ultane)

    • Reduction in cardiovascular responses to rapid changes in desflurane (Suprane) concentration:

      • Pre-treatment

        •  Fentanyl (Sublimaze) (IV five minutes before abrupt desflurane (Suprane) concentration increase)

        •  Esmolol (Brevibloc) (IV 1.5 minutes before desflurane (Suprane) concentration increased)

        •  Clonidine (Catapres) (PO 90 minutes before)

        •  Fentanyl (Sublimaze) pre-treatment -- most clinically useful because

          • Minimal cardiovascular depressive action

          • Little post-anesthetic sedation

  • Preexisting myocardial disease and inhaled anesthetic effects

    • Enhanced myocardial depression in patients with pre-existing impaired contractility

    • Myocardial depression following 40% nitrous oxide administration, occurs in patients with coronary vascular disease (not observed in patients without heart disease)

    • Anesthetic-induced circulatory effects and valvular heart disease

      • Isoflurane (Forane)-mediated peripheral vasodilation: undesirable in patients with aortic stenosis

      • Isoflurane (Forane)-mediated peripheral vasodilation: possibly beneficial in patients with mitral or aortic regurgitation

    • Arterial hypoxemia: enhancement of volatile anesthetic-mediated cardiac depression

    • Prior drug therapy -- sympathetic nervous system

      • Magnitude of  volatile agents effects influenced by the presence of  antihypertensive agents and beta-adrenergic blocking drugs

  • Ventilation Effects due to inhaled anesthetics: changes in breathing pattern, ventilatory response to CO2, ventilatory response to arterial hypoxemia and airway resistance

    • Breathing Pattern Effects:

      •  Dose-dependent increases in breathing frequency

        • Isoflurane (Forane) increases breathing frequency in a manner comparable to other agents up to a dose of 1 MAC (> 1 MAC, no further increase)

        • Nitrous oxide increases frequency to a greater extent than other agents at concentrations > 1 MAC

        • Mechanism: CNS stimulation

      • Reduced tidal volume associated with increases in breathing frequency

      • Decreases in tidal volume, despite increases in breathing frequency, causes a decrease in minute ventilation and an increase in PaCO2.

      •  Breathing pattern under anesthesia: regular and rhythmic (awake pattern: intermittent deep breaths separated by varying intervals of time(

  • Ventilatory Response to CO2

    • Volatile anesthetics:

      •  Dose-dependent ventilation depression

      •  Reduction in ventilatory response to CO2 and increases in PaCO2

    • Desflurane (Suprane) and sevoflurane (Sevorane, Ultane): causes apnea between 1.5-2 MAC

      •  Increase PaCO2

      •  Decrease ventilatory response to CO2

    •  COPD patients: increased volatile anesthetic-mediated PaCO2 elevation

    • Nitrous oxide does not increase PaCO2 (nitrous oxide use may permit reduction of volatile anesthetic causing less ventilation depression)

      •  Ventilation-depressants-sparing nitrous oxide effect: observed with all volatile anesthetics

  • Surgical Stimulation

    • Increases minute ventilation by about 40%, secondary to increasing tidal volume and breathing frequency.

    • PaCO2 decreases about 10%, despite increased minute ventilation -- mechanism: probably enhanced sympathetic nervous system activity caused by surgical stimulation.

      •  Increased sympathetic activity causes increased CO2 production

  • Mechanism of Anesthetic-induced ventilation depression

    •  Depression of medullary ventilatory center

    •  Possible reduction in intercostal muscle function, interfering with normal chest expansion

      •  This loss of chest wall stabilization interferes with normal diaphragmatic function

  • Ventilatory depression (volatile anesthetics): Management

    • Mechanical ventilation

  • Hypoxemia: Ventilatory response

    • Inhaled anesthetics: depress ventilatory response to hypoxemia ( response normally carotid body-mediated)

      •  0.1 MAC: 50%-70% depression

      •  1.1 MAC: 100% depression

  • Airway Resistance (volatile anesthetics)

    • Dose-dependent reduction in airway resistance is typically observed in the presence of underlying above-average bronchomotor tone (bronchoconstriction)

    • Halothane (Fluothane)-- reduction in airway resistance due to:

      •   Diminished vagal effect on airway smooth muscle

    • Sevoflurane (Sevorane, Ultane) and desflurane (Suprane): no evidence of promoting bronchospasm in patients with asthma

    • Halothane (Fluothane) and enflurane (Ethrane): reverse bronchoconstrictive effects of hypocapnia

      •  Prevents/reverses bronchoconstriction in patients with asthma

Stoelting, R.K., "Inhaled Anesthetics", in Pharmacology and Physiology in Anesthetic Practice, Lippincott-Raven Publishers, 1999, pp 36-76

Wray, D.L.,Rothstein, P., Thomas, S. J."Anesthesia for Cardiac Surgery", in Clincial Anesthesia, 3rd Edition, (Barash, P.G, Cullen, B. F. and Stoelting, R. K., eds) Lippincott-Raven Publishers, 1997, pp 835-867.

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