Is it time to reposition vasopressors and inotropes in sepsis?

Objectives: To review the literature on the current use of vasopressors and inotropes in patients with sepsis and sepsis syndrome with respect to the choice of agent, therapeutic end points, and safe and effective doses to be used. To examine the available evidence that supports or refutes goal-directed therapy toward supranormal oxygen transport in optimizing the outcome of critically ill sepsis syndrome patients. Data Sources: All pertinent English and French articles dealing with hemodynamic support with selected vasopressors and inotropic agents in human sepsis and sepsis syndrome retrieved from a computerized MEDLINE search from 1985 to 1994. Study Selection: Clinical studies with norepinephrine, epinephrine, phenylephrine, dopamine, and dobutamine in sepsis syndrome were considered if goal-directed therapy with oxygen transport variables was utilized. Emphasis was placed on pro spective, randomized, controlled comparative trials. However, open label, observational, and comparative studies, or case series, were also evaluated when limited data were available. Data Extraction: From the selected studies, information was obtained regarding patient population, dosing regimen, type of therapeutic goals or end points (hemodynamic, or normal vs. supranormal oxygen transport variables) and outcome data (e.g., achievement of goals, resolution of the episode, mortality rate, and development of end-organ dysfunction). Data Synthesis: When used in larger than usual doses, epinephrine, norepinephrine, and phenylephrine uniformly increased hemodynamic values. Epinephrine may increase oxygen transport values more reliably than norepinephrine. Dobutamine doses in the range of 2.5 to 6 mu g/kg/min increase oxygen transport vari- ables and hemodynamics to predetermined goals in only 30% to 70% of patients. Larger infusion rates offer no further benefits. Conclusions: Insufficient evidence exists to support goal-directed therapy with vasopressors and inotropes in the treatment of sepsis syndrome. No definitive recommendations can be made about the superiority of a vasopressor or inotropic agent due to the lack of data. However, it may be that evaluation of vasopressors earlier in sepsis syndrome will yield more promising results. Large, comparative, controlled trials assessing mortality rate and development of multiple organ system dysfunction are needed.