IS IT TIME TO REPOSITION VASOPRESSORS AND INOTROPES IN SEPSIS

Objectives: To review the literature on the current use of vasopressor s and inotropes in patients with sepsis and sepsis syndrome with respe ct to the choice of agent, therapeutic end points, and safe and effect ive doses to be used. To examine the available evidence that supports or refutes goal-directed therapy toward supranormal oxygen transport i n optimizing the outcome of critically ill sepsis syndrome patients. D ata Sources: All pertinent English and French articles dealing with he modynamic support with selected vasopressors and inotropic agents in h uman sepsis and sepsis syndrome retrieved from a computerized MEDLINE search from 1985 to 1994. Study Selection: Clinical studies with norep inephrine, epinephrine, phenylephrine, dopamine, and dobutamine in sep sis syndrome were considered if goal-directed therapy with oxygen tran sport variables was utilized. Emphasis was placed on pro spective, ran domized, controlled comparative trials. However, open label, observati onal, and comparative studies, or case series, were also evaluated whe n limited data were available. Data Extraction: From the selected stud ies, information was obtained regarding patient population, dosing reg imen, type of therapeutic goals or end points (hemodynamic, or normal vs. supranormal oxygen transport variables) and outcome data (e.g., ac hievement of goals, resolution of the episode, mortality rate, and dev elopment of end-organ dysfunction). Data Synthesis: When used in large r than usual doses, epinephrine, norepinephrine, and phenylephrine uni formly increased hemodynamic values. Epinephrine may increase oxygen t ransport values more reliably than norepinephrine. Dobutamine doses in the range of 2.5 to 6 mu g/kg/min increase oxygen transport vari- abl es and hemodynamics to predetermined goals in only 30% to 70% of patie nts. Larger infusion rates offer no further benefits. Conclusions: Ins ufficient evidence exists to support goal-directed therapy with vasopr essors and inotropes in the treatment of sepsis syndrome. No definitiv e recommendations can be made about the superiority of a vasopressor o r inotropic agent due to the lack of data. However, it may be that eva luation of vasopressors earlier in sepsis syndrome will yield more pro mising results. Large, comparative, controlled trials assessing mortal ity rate and development of multiple organ system dysfunction are need ed.