Inhaled Anesthetics: Cardiovascular Effects

• Dose-dependent and drug-specific circulatory effects, e.g.:

  • Desflurane (Suprane) and sevoflurane (Sevorane, Ultane) -- similar to older inhaled anesthetics; 

  • Sevoflurane (Sevorane, Ultane): characteristics of both isoflurane (Forane) and halothane (Fluothane)

•   Inhalational anesthetic effects on circulation will be influenced by:

  • Controlled ventilation vs. spontaneous breathing

  • Existing heart disease

  • Presence of cardioactive drugs

•   Mechanisms by which inhalational agents influence the circulatory system:

  • Changing myocardial contractility

  • Affecting peripheral vascular smooth muscle tone

  • Altering autonomic nervous system activity

• Mean Arterial Pressure (MAP): inhalational agents

  • Halothane (Fluothane), and sevoflurane (Sevorane, Ultane), isoflurane (Forane), desflurane (Suprane): produce similar, dose-dependent decrease in MAP in healthy volunteers

    • Greater MAP decrease observed than with surgical stimulation

    • Reduction in MAP following volatile anesthetic administration may be due to the sum of:

      •  Reduced sympathetic activation caused by preoperative anxiety

      •  Direct pharmacological effects of volatile anesthetics

  • Nitrous oxide:

    • No change or slight increase in systemic blood-pressure

    • Substitution of nitrous oxide for some volatile anesthetic proportion reduces the BP magnitude decrease produced by the volatile anesthetic alone (equal MAC).

  • Halothane (Fluothane): mechanism of blood pressure reduction:

    •  Reduced myocardial contractility and reduced cardiac output

  •  Isoflurane (Forane), desflurane (Suprane), sevoflurane (Sevorane, Ultane): mechanism of blood pressure reduction:

    •  Reduced systemic vascular resistance

•  Heart rate: Inhalational agents

  • Increased rate in healthy individuals:

    • ­Isoflurane (Forane)

    • ­Desflurane (Suprane)

    • ­Sevoflurane (Sevorane, Ultane) (> 1.5 MAC)

• Heart rate in surgical patients: sensitive to a number of variables: e.g. --

  • Isoflurane (Forane)-mediated increase in heart rate prevented by preoperative morphine or fentanyl (Sublimaze) administered just before induction

  • Patients apprehension/anxiety (excessive sympathetic activity) increases preoperative heart rate and may reduce a further increase due to the volatile anesthetic

    • Excessive parasympathetic tone may predispose to a greater than anticipated increase in heart rate during anesthetic administration

  • Halothane (Fluothane):

    • Heart rate unchanged; BP decreased

      •  Mechanisms:

        •  Halothane (Fluothane)-mediated baroreceptor-reflex depression

        •  Reduced phase 4 depolarization (sinus node suppression by halothane (Fluothane))

      •   Halothane (Fluothane): -- generalized reduction in cardiac conduction velocity

  • Desflurane (Suprane) (0.5 MAC):

    • Reduced systemic blood-pressure (similar to isoflurane (Forane))

    • No increased heart rate compared to isoflurane (Forane) {at 0.5 MAC}

  • Isoflurane (Forane):

    • Neonates:

      •  Reduced blood pressure; no increase in heart rate

        •  Mechanism: - reduced carotid sinus reflex

    • Elderly patients: attenuated heart rate responses

    • Younger patients: increased heart rate {promoted by vagolytic drugs, e.g. atropine, pancuronium (Pavulon)}

• Cardiac Output/Stroke Volume

  • Halothane (Fluothane): dose-dependent decreased in cardiac output (normal volunteers)

  • Isoflurane (Forane), desflurane (Suprane), sevoflurane (Sevorane, Ultane): no effect on cardiac output in normal volunteers

  • Sevoflurane (Sevorane, Ultane):

    •  Decreased cardiac output at 1 and 1.5 MAC

    •  Minimal effect at 2 MAC

  • Generally: volatile anesthetics decrease left ventricular stroke volume by about 15% to 30% (calculated)

    • Cardiac output, in patients, maybe minimally affected since many volatile anesthetics increase heart rate ( compensating for a decrease in stroke volume)

  • Nitrous oxide: slightly increased cardiac output (nitrous oxide has a slight sympathomimetic effect)

  • Isoflurane (Forane):

    • Good maintenance of heart rate

    • Minimal cardiac output depression

    • Reduced impact of isoflurane (Forane) on myocardial contractility may be secondary to its higher anesthetic potency compared halothane (Fluothane) --i.e., the brain is depressed at a concentration less than that required to depress cardiac contractility

• Systemic Vascular Resistance:

  • Halothane (Fluothane): minimal effect on systemic vascular resistance in normal volunteers

    •  Some organ level vasodilation, i.e. cerebral vasodilation and significant cutaneous vessel vasodilation

    •  These effects offset by no change or vasoconstriction in other vascular beds

  • Isoflurane (Forane), desflurane (Suprane), sevoflurane (Sevorane, Ultane): decreased systemic vascular resistance in normal volunteers

  • All four agents reduce systemic blood-pressure -- only halothane (Fluothane) does so by primarily decreasing cardiac output {reduced myocardial contractility}

    •  The other agents do so by reducing vascular resistance.

  • Isoflurane (Forane) -- Mechanism of systemic vascular resistance decrease:

    •  Significant increase in skeletal muscle blood flow

    •  Increased cutaneous blood flow

      • Increased cutaneous flow is characteristic of all volatile anesthetics {in this condition peripheral venous blood provides an alternative to arterial blood sampling to evaluate pH and PaCO₂}

• Duration of Anesthetic Administration and Cardiac Effects:

  • Administration of a volatile anesthetic for longer than 5 hr results in the recovery from depressing effects -- i.e.:

    •  At constant MAC: cardiac output returns to normal after five hours

      • Heart rate may remain increased, systemic blood-pressure is unchanged {increase in cardiac output is balanced by decreases in systemic vascular resistance}

    • Recovery with time -- most apparent with halothane (Fluothane); least apparent with isoflurane (Forane) {note that isoflurane (Forane) does not significantly change cardiac output even at 1 hour}

    • Mechanism:

      • Probably a beta-adrenergic response, since propranolol (Inderal) pre-treatment prevents cardiovascular recovery with increased anesthetic administration time.

• Pulmonary Vascular Resistance

  • Inhalational agents: limited/not predictable effect on pulmonary vascular bed smooth muscle

  • Nitrous oxide: increased pulmonary vascular resistance in patient with pulmonary hypertension (preexisting)

  • Neonate: sensitive to nitrous oxide-mediated pulmonary vasculature vasoconstriction (independent of preexisting pulmonary hypertension)

  •  Congenital heart disease: nitrous oxide-mediated increasing pulmonary vascular resistance may cause increased right-to-left intracardiac blood shunting (May worsen arterial oxygenation)

•  Cardiac Arrhythmias:

  • Volatile anesthetics: range of myocardial sensitizing effects to epinephrine-induced arrhythmias

    •  Greatest sensitizing effect: halothane (Fluothane)

    •  Minimal/not apparent: isoflurane (Forane), desflurane (Suprane), sevoflurane (Sevorane, Ultane)

  • Lidocaine (Xylocaine) (0.5%) in submucosal-injected epinephrine reduces myocardial sensitivity to epinephrine

• Coronary Blood Flow:

  • Volatile anesthetics: cause coronary vasodilation

    •  target vessels: 20 microns - 200 microns in diameter

  • Isoflurane (Forane): preferential dilation of small coronary resistance vessels (relative to larger conductance vessels)

    •  Isoflurane (Forane): greater vasodilatory effects compared to halothane (Fluothane) or enflurane (Ethrane) (but less than adenosine

    • Preferential dilation of small coronary resistance vessels may cause blood redistribution from ischemic to relatively nonischemic areas, known as "coronary steal syndrome"

      •  "Coronary steal syndrome" more likely to be seen with potent coronary vasodilators, e.g. adenosine 

  • Evidence of intraoperative myocardial ischemia based upon ST segment ECG changes:

    •  Nitrous oxide-isoflurane (Forane) anesthesia

    •  Greater incidence of ischemia in patients undergoing CABG surgery when anesthetic included isoflurane (Forane) {relative to enflurane (Ethrane)}

  •  Factors predisposing to "coronary steal syndrome":

    • Total occlusion of the major artery with collateral flow distal also impeded by significant vessel stenosis (> 90%)

    • About 12% of patients may have requisite anatomy that predisposes to "coronary steal syndrome"

    • Ischemia incidence in patients with predisposing "coronary steal syndrome" anatomy is comparable in patients receiving isoflurane (Forane), halothane (Fluothane), enflurane (Ethrane), or sufentanil (Sufenta).

  • Generally, it is more likely that a patient {with or without coronary artery disease and without tachycardia or hypotension} will experience myocardial ischemia with isoflurane (Forane) compared to halothane (Fluothane).

  • Desflurane (Suprane) and sevoflurane (Sevorane, Ultane): no coronary vasodilation = no possibility of "coronary steal syndrome"

  • Nitrous oxide: no evidence for induction of myocardial ischemia in patients with coronary artery disease when nitrous oxide is an adjuvant to fentanyl (Sublimaze)

  • Significant factors predisposing to myocardial ischemia development:

    • Presence/absence of beta-adrenergic block

    • Changes in systemic blood-pressure

    • Changes in heart rate

  • Perioperative incidence of myocardial ischemia is usually a reflection of underlying coronary artery disease [as opposed to a consequence of a particular anesthetic used}

  • Avoiding perioperative myocardial ischemia:

    •  Inclusion of opioids in the anesthetic protocol

    •  Prior treatment with beta-adrenergic receptor blockers