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Do Alpha Agonists Increase Venous Return?

Butterworth, John M.D.

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To the Editor:—

I enjoyed reading the review by Gelman and Mushlin1 of catecholamine actions on the splanchnic vasculature. Nevertheless, I am confused by an unreferenced statement they made regarding the actions of α-agonists on venous return. They state, “Generally, α- agonists increase venous return under normovolemic conditions, but they decrease it when used at high doses or in the presence of severe hypovolemia.”
The animal data do not support the statement by Gelman and Mushlin. Yamazaki et al.2 studied dogs that had received spinal anesthesia and ganglionic blockers (surely analogous to hypovolemia) and found that methoxamine and clonidine increased venous return. Similarly, Supple et al.3 found that α2-agonists increased the venous return of dogs on constant-flow cardiopulmonary bypass. However, Imai et al.4 showed that α-agonists decrease venous return and β-agonists increase venous return. Similarly, we found that phenylephrine administered to dogs after spinal anesthesia decreased venous return, whereas isoproterenol and ephedrine increased venous return.5 Of note, in our study, the animals underwent splenectomy. The canine splenic capsule contracts with α-agonists, and the canine spleen contains a much larger fraction of total blood volume than the human spleen does.
The human data do not support the statement by Gelman and Mushlin. Bell et al.6 found that volunteers receiving a 20-min infusion of phenylephrine (20–120 μg/min—certainly not a “high” dose) showed an increase in splanchnic intravascular volume and a decrease in venous return. Leenen et al.7 infused epinephrine in healthy subjects with and without β-blockers. Using measured changes in left ventricular end-diastolic dimensions, these authors concluded that selective α-stimulation decreased venous return. Brooker et al.8 compared phenylephrine and epinephrine in patients with mild hypotension after spinal anesthesia. There was an increase in stroke volume and cardiac output with epinephrine, with no change or a decrease in cardiac output in those receiving phenylephrine. However, in a group of patients receiving a morphine-based anesthetic during constant-flow cardiopulmonary bypass, Müller-Ruchholtz et al.9 observed α-agonist–induced increase in venous reservoir volume.
In sum, animal and human studies do not provide convincing evidence that α-agonists generally increase venous return under any condition. Finally, the inappropriate use of α-agonists to increase venous return could have disastrous complications during resuscitation.
John Butterworth, M.D.
Wake Forest University School of Medicine, Winston-Salem, North Carolina. jbutter@wfubmc.edu
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References

1. Gelman S, Mushlin PS: Catecholamine-induced changes in the splanchnic circulation affecting systemic hemodynamics. Anesthesiology 2004; 100:434–9

2. Yamazaki R, Tsuchida K, Aihara H: Effect of alpha-adrenoceptor agonists on cardiac output and blood pressure in spinally anesthetized ganglion-blocked dogs. Arch Int Pharmacodyn Ther 1988; 295:80–93

3. Supple EW, Graham RM, Powell WJ Jr: Direct effects of α2-adrenergic receptor stimulation on intravascular systemic capacity in the dog. Hypertension 1988; 11:352–9

4. Imai Y, Satoh K, Taira N Role of the peripheral vasculature in changes in venous return caused by isoproterenol, norepinephrine, and methoxamine in anesthetized dogs. Circ Res 1978; 43:553–61

5. Butterworth JF IV, Piccione W Jr, Berrizbeitia LD, Dance G, Shemin RJ, Cohn LH: Augmentation of venous return by adrenergic agonists during spinal anesthesia. Anesth Analg 1986; 65:612–6

6. Bell L, Zaret BL, Rutlen DL: Influence of alpha-adrenergic receptor stimulation on splanchnic intravascular volume in conscious humans. Acta Physiol Scand 1991; 143:65–9

7. Leenen FH, Chan YK, Smith DL, Reeves RA: Epinephrine and left ventricular function in humans: Effects of beta-1 vs nonselective beta-blockade. Clin Pharmacol Ther 1988; 43:519–28

8. Brooker RF, Butterworth JF IV, Kitzman DW, Berman JM, Kashtan HI, McKinley AC: Treatment of hypotension after hyperbaric tetracaine spinal anesthesia: A randomized, double-blind, cross-over comparison of phenylephrine and epinephrine. Anesthesiology 1997; 86:797–805

9. Müller-Ruchholtz ER, Lösch H-M, Grund E, Lochner W: Effect of alpha adrenergic receptor stimulation on integrated systemic venous bed. Pflugers Arch 1977; 370:241–6

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