TREATING SEPSIS

Norepinephrine

Norepinephrine (noradrenaline) is a complex and much misunderstood drug. Remember that this agent is the neurotransmitter at the majority of adrenergic post synaptic terminals in the body. Norepinephrine has pharmacologic effects on both alpha-1 and beta-1 adrenoceptors. In low dosage ranges, the beta effect is noticeable, and there is a mild increase in cardiac output. In most dosage ranges, vasoconstriction and increased mean arterial pressure are evident. Norepinephrine does not increase heart rate: its effects on MAP may actually reduce heart rate as a result of baroreceptor activation. The main beneficial effect of norepinephrine is to increase organ perfusion by increasing vascular tone. Studies that have compared norepinephrine to dopamine head to head have favored the former in terms of overall improvements in oxygen delivery, organ perfusion and oxygen consumption. Unlike epinephrine, norepinephrine reduces serum lactate levels (1). This data suggests a favorable influence on splanchnic perfusion. Norepinephrine is more effective at fulfilling targeted endpoints than dopamine (2), and is considerably less metabolically active than epinephrine.

The effects of norepinephrine on renal perfusion tend to be misunderstood. It appears that norepinephrine is as effective as dopamine at improving renal perfusion, as long as the patient is adequately resuscitated  (3).

Norepinephrine appears to be most effective at splanchnic resuscitation if used in combination with dobutamine. This combination improves oxygen delivery and consumption compared with dopamine (4).There is evidence of efficacy combining  dopamine and norepinephrine in healthy volunteers (5). In this circumstance, the main effect of low dose dopamine appears to be in increasing cardiac output and blood pressure.

The increase in splanchnic blood flow associated with dobutamine and norepinephrine appears to arise from beta adrenergic activity (4).

References

   (1)    Levy B, Bollaert PE, Charpentier C, Nace L, Audibert G, Bauer P et al. Comparison of norepinephrine and dobutamine to epinephrine for hemodynamics, lactate metabolism, and gastric tonometric variables in septic shock: a prospective, randomized study. Intensive Care Med 1997; 23(3):282-287.

   (2)    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.

   (3)    Martin C, Saux P, Eon B, Aknin P, Gouin F. Septic shock: a goal-directed therapy using volume loading, dobutamine and/or norepinephrine. Acta Anaesthesiol Scand 1990; 34(5):413-417.

   (4)    Hannemann L, Reinhart K, Grenzer O, Meier-Hellmann A, Bredle DL. Comparison of dopamine to dobutamine and norepinephrine for oxygen delivery and uptake in septic shock. Crit Care Med 1995; 23(12):1962-1970.

   (5)    Hoogenberg K, Smit AJ, Girbes AR. Effects of low-dose dopamine on renal and systemic hemodynamics during incremental norepinephrine infusion in healthy volunteers. Crit Care Med 1998; 26(2):260-265.

Copyright 2002 All rights reserved