TREATING SEPSIS

Other Vasoactive Drugs

Vasopressin

Vasopressin is emerging as an alternative vasoconstrictor in septic (and other forms of distributive) shock, in patients who have become resistant to catecholamines (1). In addition there appears to be a quantitative deficiency of this hormone in sepsis (2-5) . Experience and published data are limited, but we do know that pharmacological doses are much lower in vasodilated patients, as compared to normal (6). At present the most efficacious dose appears to be 0.04units/minute (7). Effects on splanchnic perfusion and the extremities are probably adverse (remember that vasopressin has traditionally been used to reduce splanchnic blood flow, in the treatment of bleeding esophageal varices), particularly as the dose escalates. Currently the principle use of this agent is as a physiologic replacement for depleted endogenous stores.

Dopexamine

Dopexamine was designed to combine the inodilatory effects of dobutamine and the dopaminergic effects of dopamine (it is a synthetic analogue of dopamine), thus improving cardiac output and splanchnic perfusion. To date, most of the studies utilizing this agent have been disappointing, and it is not in common usage.

Phenylephrine

Phenylephrine is an almost pure alpha-1 agonist, and is used predominantly in anesthesia practice to increase blood pressure without increasing heart rate in patients with vasoplegia, due to spinal-epidural anesthesia or to reverse the afterload reducing effects of propofol and volatile inhalation agents. Phenylephrine has traditionally been used in intensive care units as a vasoconstrictor to improve SVR (systemic vasccular resistance) in patients (in whom PA catheters had been inserted) in septic shock. This agent may be useful as an additional vasoconstrictor in fluid loaded patients where catecholamines are causing excessive tachycardia. The use of phenylephrine as a single agent is probably not wise, due to its tendency to reduce cardiac output. In a small study by Reinelt (8) patients in septic shock were treated initially with norepinephrine and subsequently crossed over to phenylephrine: a decrease in splanchnic blood flow, oxygen delivery and lactate uptake was observed. The most likely explanation for this phenomenon is reduced beta adrenergic stimulation.

Phosphodiesterase Inhibitors

There is little available data on the use of phosphodiesterase inhibitors in sepsis. These agents (milrinone/enoximone) are potent inotropes, but also cause vasodilatation and tachycardia, which limits their use in sepsis. Interestingly, these drugs have lusitropic properties – they relax the heart in diastole, compared to inoconstrictor type drugs, which appear to impair diastolic relaxation (9). These agents thus are of more value in cardiogenic shock.

References

(1)   Malay MB, Ashton RC, Jr., Landry DW, Townsend RN. Low-dose vasopressin in the treatment of vasodilatory septic shock. J Trauma 1999; 47(4):699-703.

(2)   Buijk SE, Bruining HA. Vasopressin deficiency contributes to the vasodilation of septic shock. Circulation 1998; 98(2):187.

(3)   Goldsmith SR. Vasopressin deficiency and vasodilation of septic shock. Circulation 1998; 97(3):292-293.

(4)   Landry DW, Levin HR, Gallant EM, Ashton RC, Jr., Seo S, D'Alessandro D et al. Vasopressin deficiency contributes to the vasodilation of septic shock. Circulation 1997; 95(5):1122-1125.

(5)   Reid IA. Role of vasopressin deficiency in the vasodilation of septic shock. Circulation 1997; 95(5):1108-1110.

(6)   Romand JA, Treggiari-Venzi M. Is vasopressin an ideal vasopressor to treat hypotension in septic shock? Intensive Care Med 1999; 25(7):763-764.

(7)   Tsuneyoshi I, Yamada H, Kakihana Y, Nakamura M, Nakano Y, Boyle WA, III. Hemodynamic and metabolic effects of low-dose vasopressin infusions in vasodilatory septic shock. Crit Care Med 2001; 29(3):487-493.

(8)   Reinelt H, Radermacher P, Kiefer P, Fischer G, Wachter U, Vogt J et al. Impact of exogenous beta-adrenergic receptor stimulation on hepatosplanchnic oxygen kinetics and metabolic activity in septic shock. Crit Care Med 1999; 27(2):325-331.

(9)   Jindal N, Hollenberg SM, Dellinger RP. Pharmacologic issues in the management of septic shock. Crit Care Clin 2000; 16(2):233-249.

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