February 1999

Comparative Myocardial Depression of Sevoflurane, Isoflurane, and Halothane in Cultured Neonatal Rat Ventricular Myocytes
Kanaya N; Kawana S; Tsuchida H; Miyamoto A; Ohshika H; Namiki A.
Anesth Analg 1998 Nov;87(5):1041-1047.
Commentary by Charles Coté,

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[ see abstract below ]

Kanaya et al, using cultured neonatal rat heart myocytes, compared the myocardial depression of sevoflurane, isoflurane, and halothane. This type of research is important because the major continuing source of morbidity and mortality in children, particularly infants, occurs during anesthetic induction. It is at this point in time that the infant is most vulnerable because of the rapidly changing concentration of inhalation agent, relative dehydration, and other factors such as hypoventilation or relative anesthetic overpressure resulting in a very rapid depression of myocardial function.

It is well known that all of the inhalation agents cause dose-dependent depression of cardiac function and that this is at least in part mediated through calcium channel blocking activity. Halothane is the most potent in terms of calcium channel blocking activity, and some pediatric anesthesiologists are suggesting that we should abandon halothane for the gaseous induction of anesthesia in children because of this potent cardiac depression. The implication is that sevoflurane is less likely to cause sudden cardiovascular collapse. There is, however, no clinical evidence that this is true and it is very unlikely that a randomized trial comparing adverse outcomes between halothane and sevoflurane will ever be attempted, especially since very large numbers of patients would be required. However, it is very important to separate out what we know and what is conjecture.

We do know that in older patients that there is slightly greater myocardial depression with equipotent concentrations of sevoflurane vs halothane (see AnesthesiaWeb, February 1997), but this effect may be different in the infant compared with the older child. [1,2] Early studies of sevoflurane demonstrated an increase in heart rate with sevoflurane but not halothane, suggesting that better cardiac function in older children may in part be mediated by the change in heart rate. However, infants and toddlers do not respond with an increase in heart rate, as do older children, and in fact many of the infants in the original MAC studies developed hypotension in response to sevoflurane. [3]

The current study has also demonstrated dose-related depression of myocyte function and greater depression with halothane compared with sevoflurane on a percent basis. However, when equi-MAC concentrations were used there was no difference between the drugs! Although there seems to be less myocardial depression with sevoflurane than with halothane, this effect appears to be related to other effects such as peripheral vascular resistance, changes in heart rate and perhaps other, as yet unknown, factors. More importantly, I believe that since we can turn a halothane vaporizer on to 5 percent (5.75 MAC), but a sevoflurane vaporizer only to 8 percent (2.5 MAC) [3], hypotension and cardiac arrests may likely reflect a systems issue rather than a drug issue-i.e., there is a limit as to how much sevoflurane can be delivered and we can push twice as much halothane as sevoflurane. Obviously much more research is required. But, being from the older generation that grew up with halothane, I am not yet prepared to discard this wonderful and cheap inhalation agent. I do use sevoflurane for induction because it is faster than halothane, but then I switch to halothane for maintenance.

References

1. Wodey E, Pladys P, Copin C, Lucas MM, Chaumont A, Carre P, et al. Comparative hemodynamic depression of sevoflurane versus halothane in infants: an echocardiographic study. Anesthesiology. 1997;87:795-800.

2. Holzman RS, van der Velde ME, Kaus SJ, Body SC, Colan SD, Sullivan LJ, et al. Sevoflurane depresses myocardial contractility less than halothane during induction of anesthesia in children. Anesthesiology. 1996;85:1260-1267.

3. Lerman J, Sikich N, Kleinman S, Yentis S. The pharmacology of sevoflurane in infants and children. Anesthesiology. 1994;80:814-824.

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