Cardiac Effects: Inhalational Agents Continued
Comparative pathophysiology: diastolic vs. systolic heart failure
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Inhalational Agent Effects on Diastolic Function
Halothane |
Halothane |
Enflurane |
Enflurane |
1Halothane and enflurane:
Myocardial compliance: Halothane effect on myocardial compliance remains unresolved.
Some studies suggest reduced ventricular compliance in early diastole as assessed by chamber-stiffness
Other studies have found halothane to be without effects on either chamber or myocardial stiffness.
Halothane, however does prolong the time constant of isovolumic relaxation (tau). In addition, coronary blood flow may be reduced.
Dose-dependent prolongation of tau is an apparent characteristic of all potent volatile agents.
Enflurane accordingly prolongs isovolumic relaxation; moreover, the agent may increase chamber stiffness.
Isoflurane |
Isoflurane |
Sevoflurane |
Sevoflurane |
Desflurane |
Desflurane |
1Isoflurane administration probably increases tau, but probably less than that caused by halothane or enflurane. These studies have typically utilized animal models. (This isoflurane effect has not been observed in every reported study)
1, 12Limited data is available from noninvasive studies in humans.
1, 12One approach utilized Doppler echocardiography for assessment of isoflurane effects on diastolic function. In that study no changes were seen in pulmonary flow and changes seen in transmitral flow was thought to be due to altered ventricular loading and atrial systolic function.
Desflurane and sevoflurane, similar to isoflurane, prolongs isovolumic relaxation (increased ) probably without affecting myocardial chamber stiffness.1,13 Desflurane and sevoflurane also impair initial diastolic filling, as estimated by maximum segment lengthing velocity (dL/dtmax). 1,13
1Inhalational agents and the Ischemic Myocardium:
Inhalational, volatile anesthetics, in vitro, depress normal myocardial function; however, they exert much greater depression overall in the globally damaged, dysfunctional myocardium.
In models of localized myocardial dysfunction (ischemic zones), halothane appeared well-tolerated.
In canine models which involved transient coronary artery occlusion to induce myocardial ischemia, halothane reduced ST-segment changes.
Using a different measure of ischemia, lactate production, in the isolated, ischemic canine model, enflurane reduced lactate production.
In a more complex model, in which regional myocardial ischemia was present, enflurane and isoflurane did not attenuate increases in contractility in regions of the myocardium far removed from the ischemic region. In this system, diastolic function as measured by tau and chamber stiffness in both ischemic and nonischemic domains improved in the presence of desflurane and isoflurane anesthesia, at least compared to the conscious state.
Myocardial stunning:
Myocardial stunning which is a post-ischemic myocardial dysfunction that is reversible is affected by volatile anesthetics.
The model involves ischemia followed by reperfusion.
In this setting volatile anesthetics appear cardioprotective; by contrast, nitrous oxide may be detrimental.
The mechanism by which volatile agents exhibit cardioprotection remains to be elucidated.
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1Inhalational Agents and Epinephrine-Induced Cardiac Arrhythmias
In the canine model, increasing doses of epinephrine produce the following cardiac rhythm anomalies: wandering atrial pacemaker, atrial ectopy, atrial ventricular dissociation, ventricular ectopy, ventricular bigeminy, and ultimately ventricular tachycardia.
Isoflurane and enflurane (halogenated ether agents) tend to be less sensitizing to epinephrine-induced arrhythmias compared to halothane.
In general the difficulty in assessing inter-relationships between volatile agents and epinephrine-induced arrhythmias is that different studies often use differing definitions of arrhythmias as well as different methods of epinephrine administration/dose.
For example if arrhythmias defined as 2 or more premature ventricular contractions in five minutes, epinephrine doses injected into the right atrial of dogs during halothane, isoflurane, andfluroxene anesthesia did not differ from those doses causing this arrhythmia in the absence of the anesthetic agent.
In another study in which arrhythmias were defined as 4 or more premature ventricular contractions in 15 seconds and epinephrine was infused (iv) during halothane or enflurane anesthesia (1.25 MAC), five times higher infusion rates and plasma levels of epinephrine were required to induce arrhythmias during enflurane anesthesia compared to halothane anesthesia.
This observation was extended to include sevoflurane and isoflurane.
In a swine model, this time defining arrhythmias as three or more premature ventricular contractions in one minute, results indicated that the arrhythmogenic effects of desflurane was comparable to that of isoflurane.
The order of arrhythmogenicity from more sensitizing to less sensitizing is probably halothane > enflurane > sevoflurane > isoflurane = desflurane.
The situation is somewhat different if thiopental has been used for induction.
The general effect is that the epinephrine dose required to induce an arrhythmia during subsequent volatile inhalational agent (halothane, enflurane, isoflurane andsevoflurane) anesthesia is reduced.
For example, with halothane anesthesia [canine model], thiopental decreases the epinephrine dose required for atrial ventricular dissociation, as well as for ventricular, but not atrial, arrhythmias.
Although thiopental has a limited anesthetic duration, this cardiovascular effect of thiopental lasts longer, 3-5 hours. The mechanism for the thiopental-sensitizing effect remains to be elucidated.
In a similar manner, the dose of epinephrine required to induce arrhythmias is also lowered following succinylcholine.
The dose of epinephrine required to induce arrhythmias under halothane anesthesia may, by contrast, be increased if induction was performed with ketamine or midazolam or with administration of amide-type local anesthetics with the epinephrine.
Prevention or treatment of epinephrine-induced arrhythmias in the context of inhalational anesthesia has been investigated.
Elevation of the epinephrine doses required to induce an arrhythmia results from administration of the adrenergic blockers propranolol or oxprenolol. In the canine model, during halothane anesthesia, the epinephrine dose required to induce arrhythmia was increased following esmolol infusion at doses up to 200 mcg/kg/min. Epinephrine-caused ventricular tachycardia may be immediately stopped by esmolol bolus dosing (1 mg/kg).
Other effective approaches include administration of the central 2-adrenergic agonist dexmedetomidine, calcium channel blocker diltiazem (bolus dose 0.1 mg/kg in man), and amiodarone.
1Park, KW, Haering, JM, Reiz, S, Lowenstein, E Effects of Inhalation Anesthetics on Systemic Hemodynamics and the Coronary Circulation in Cardiac Anesthesia, Fourth Edition (Kaplan, JA, ed; Reich, Dl and Konstadt, SN, Assoc eds) W.B. Saunders Co. A Division of Harcourt Brace and Company, Philadelphia, 1999. This chapter is the primary reference for all above material, except as noted.
2Suga, H, Sagawa, K, Shoukas, AA: Load independence of instantaneous pressure-volume ratio of the canine left ventricle and effects of epinephrine and heart rate on the ratio. Circ Res 32: 314, 1973. -second sourced from reference 1.
5Van Trigt, P, Christian, CC, Fagraeus, L, et al: "Myocardial depression by anesthetic agents [halothane, enflurane, and nitrous oxide]: Quantitation based on end-systolic pressure-dimension relations" Am J Cardiol 53: 243, 1984---second sourced from reference 1.
7Kemmotsu, O, Hashimota, Y, Shimosato, S: Inotropic effects of isoflurane on mechanism of contraction in isolated cat papillary muscles from normal and failing hearts. Anesthesiology 39: 470, 1973 --second sourced from reference 1.
8Pagel, PS, Kampine, JP, Schmeling, WT, Warltier, DC: Effects of nitrous oxide on myocardial contractility as evaluated by the preload recruitable stroke work relationship in chronically instrumented dogs. Anesthesiology 73: 1148, 1990. --second sourced from reference 1.
9Klein, AL, Taijik, AJ: Doppler assessment of pulmonary venous flow in healthy subjects and in patients with heart disease. J Am Soc Echocardiogr 4: 379-392, 1991--second sourced from reference 1.
10Kuecherer, HE, Muhiudeen IA, Kusumoto FM et al: Estimation of mean left atrial pressure from transesophageal pulsed Doppler echocardiography of pulmonary venous flow. Circulation 82: 127, 1990.--second sourced from reference 1.
11Rossvoll, O, Hatle, LK: Pulmonary venous flow velocity recorded by transthoracic Doppler ultrasound: Relation to left ventricular diastolic pressures JACC 21: 1687, 1993.--second sourced from reference 1.
12Oxorn D, Edelist, G, Harrington, E, et al: Echocardiographic assessment of left ventricular filling during isoflurane anesthesia Can J Anaesth 43: 569, 1996.--second sourced from reference 1.
13Pagel, PS, Hettrick DA< Lowe, D., et al: Desflurane and isoflurane exert modest beneficial actions on left ventricular diastolic function during myocardial ischemia in dogs. Anesthesiology 83:1021, 1995--second sourced from reference 1.
14Siker, D, Pagel PS, Pelc, LR, et al: Nitrous oxide impairs functional recovery of stunned myocardium in barbiturate-anesthetized, acutely instrumented dogs. Anesth Analg 75: 539-548, 1992.