In Reply:—

The overall tenor in the letter of Quintin and Ghignone in response to our article,1“Perioperative β-Adrenergic Receptor Blockade,” advocates the use of α2agonists as first-line drugs for cardioprotection in perioperative medicine. In this respect, we wish to stress some practical clinical points.

In contrast to the author’s recommendation, α2agonists should not be used to replace β-adrenergic antagonists in patients with high-degree heart blocks, simply because, in addition to their attenuation of catecholamine release, α2agonists induce bradycardia by vagomimetic effects.2,3 

Furthermore, α2agonists have controversial effects in congestive heart failure. As reviewed recently,4uncontrolled inhibition of sympathetic tone may have deleterious consequences.

There is often confusion regarding the cellular protective mechanisms underlying α2agonists and β-adrenergic antagonists. This is reflected by reference 8 cited by the authors in their letter. In principle, although both treatments decrease sympathetic outflow, β-adrenergic antagonists predominantly affect the end organ (reviewed in Zaugg et al.  2and Zaugg and Schaub4).

The usefulness of β-adrenergic antagonists in perioperative medicine relies on a limited number of studies with small sample sizes.1However, there is a substantive base of large clinical studies in the cardiology literature strongly supporting their use. This does not exist for α2agonists.

There is limited literature on the use of combinations of antiadrenergic therapies for cardioprotection (simultaneous treatment and not sequential). A useful discussion of this idea has recently been published in Zaugg et al.  2The combination of β-adrenergic antagonists with α2agonists may result in unexpected pharmacologic surprises, i.e. , clonidine plus sotalol may increase blood pressure. There is currently no evidence to combine antiadrenergic treatments except for regional anesthesia plus β-adrenergic antagonists or α2agonists (mostly intrathecally administered).

* Institute of Anesthesiology, University Hospital Zurich, and Institute of Pharmacology and Toxicology, University of Zurich, Zurich, Switzerland. michael.zaugg@ifa.usz.ch

References

1.
London JM, Zaugg M, Schaub MC, Spahn DR: Perioperative β-adrenergic receptor blockade. Anesthesiology 2004; 100:170–5
2.
Zaugg M, Schulz C, Wacker J, Schaub MC: Sympatho-modulatory therapies in perioperative medicine. Br J Anaesth 2004; 93:53–62
3.
Reid JL, Wing LM, Mathia CJ, Frankel HL, Neill E: The central hypotensive effects of clonidine: Studies in tetraplegic subjects. Clin Pharmacol Ther 1977; 21:375–81
4.
Zaugg M, Schaub MC: Cellular mechanisms in sympatho-modulation of the heat. Br J Anaesth 2004; 93:34–52