Anesthesia Pharmacology:  General Anesthesia

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Inhaled Anesthetics: Cardiovascular Effects

Manifestations of drug-mediated circulatory effects result from changes in

 Heart rate

 Stroke volume

 Peripheral vascular resistance

 Blood pressure

 Right atrial pressure

Cardiac rhythm

 Coronary blood flow

 Cardiac output

  •   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)  decrease 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) decreases systemic vascular resistance decrease by:

      •  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 β-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 β-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 β-adrenergic receptor blockers


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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