TREATING SEPSIS

Dopamine

Dopamine has predominantly beta adrenergic effects in low to moderate dose ranges (up to 10 mic/kg/min), although there is much inter-patient variability. This effect may be due to it’s conversion to norepinephrine in the myocardium, and activation of adrenergic receptors. In higher dose ranges, alpha adrenoceptor activation increase and causes vasoconstriction. The agent is thus a mixed inotrope and vasoconstrictor. At all dose ranges it is a potent chronotrope. There has been much controversy about the other metabolic functions of this agent. The so-called “renal protective” effect appears to be a misnomer (1). The logic behind this concept is the theory that, at low dosage (<5mic/kg/min) dopamine stimulates dopaminergic receptors in renal, mesenteric and coronary beds, resulting in vasodilatation. This causes an increase in urinary output, and is purported to protect the kidneys from ischemic insults. Most investigators have linked the apparent effects of dopamine to 1. An increase in cardiac output, due to inotropy, and thus renal perfusion pressure. 2. A direct diuretic action. Some would consider the concept of vasodilating vessels, which have constricted due to hypoxemia (acute renal “salvage”) as an unnecessary and potentially harmful interference in the body’s response to hypovolemia (2). Nonetheless, there is no evidence that dopamine, at low dose, protects or harms the kidneys.

The effects of dopamine elsewhere, though, may cause concern. Firstly, dopamine drives up heart rate, and may precipitate myocardial ischemia. Secondly, the effects of this agent on the splanchnic circulation appear complex: dopamine, whilst increasing overall mesenteric blood flow, may preferentially steal blood from the mucosa, and redistribute it to the larger vessels (3). Thirdly, the effects of exogenous administration of this drug at distal sites in the central nervous system and gut remain to be clarified: dopamine may interfere with pituitary (2;4)  and  thyroid function (2;5)  and have an immunosuppressive effect (6).

References

(1)   Bellomo R, Chapman M, Finfer S, Hickling K, Myburgh J. Low-dose dopamine in patients with early renal dysfunction: a placebo- controlled randomised trial. Australian and New Zealand Intensive Care Society (ANZICS) Clinical Trials Group. Lancet 2000; 356(9248):2139-2143.

(2)   Kellum JA, Bellomo R. Low-dose dopamine: what benefit? Crit Care Med 2000; 28(3):907-908.

(3)   Marik PE, Mohedin M. The contrasting effects of dopamine and norepinephrine on systemic and splanchnic oxygen utilization in hyperdynamic sepsis. JAMA 1994; 272(17):1354-1357.

(4)   Van den BG, de Zegher F. Anterior pituitary function during critical illness and dopamine treatment. Crit Care Med 1996; 24(9):1580-1590.

(5)   Van den BG, de Zegher F, Lauwers P. Dopamine and the sick euthyroid syndrome in critical illness. Clin Endocrinol (Oxf) 1994; 41(6):731-737.

(6)   Denton R, Slater R. Just how benign is renal dopamine? Eur J Anaesthesiol 1997; 14(4):347-349.

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