COMPARISON OF NOREPINEPHRINE AND DOBUTAMINE TO EPINEPHRINE FOR HEMODYNAMICS, LACTATE METABOLISM, AND GASTRIC TONOMETRIC VARIABLES IN SEPTICSHOCK - A PROSPECTIVE, RANDOMIZED STUDY

Objectives: To compare the effects of norepinephrine and dobutamine to epinephrine on hemodynamics, lactate metabolism, and gastric tonometr ic variables in hyperdynamic dopamine-resistant septic shock. Design: A prospective, intervention, randomized clinical trial. Setting: Adult medical/surgical intensive care unit in a university hospital. Patien ts: 30 patients with a cardiac index (CI) > 3.51 . min(-1) . m(-2) and a mean arterial pressure (MAP) less than or equal to 60 mmHg after vo lume loading and dopamine 20 mu g/kg per min and either oliguria or hy perlactatemia. Interventions: Patients were randomized to receive an i nfusion of either norepinephrine-dobutamine or epinephrine titrated to obtain an MAP greater than 80 mmHg with a stable or increased CI. Mea surements and main results: Baseline measurements included: hemodynami c and tonometric parameters, arterial and mixed venous gases, and lact ate and pyruvate blood levels. These measurements were repeated after 1, 6, 12, and 24 h. All the patients fulfilled the therapeutic goals. No statistical difference was found between epinephrine and norepineph rine-dobutamine for systemic hemodynamic measurements. Considering met abolic and tonometric measurements and compared to baseline values, af ter 6 h, epinephrine infusion was associated with an increase in lacta te levels (from 3.1 +/- 1.5 to 5.9 +/- 1.0 mmol/l; p < 0.01), while la ctate levels decreased in the norepinephrine-dobutamine group (from 3. 1 +/- 1.5 to 2.7 +/- 1.0 mmol/l). The lactate/pyruvate ratio increased in the epinephrine group (from 15.5 +/- 5.4 to 21 +/- 5.8; p < 0.01) and did not change in the norepinephrine-dobutamine group (13.8 +/- 5 to 14 +/- 5.0). Gastric mucosal pH (pHi) decreased (from 7.29 +/- 0.11 to 7.16 +/- 0.07; p < 0.01) and the partial pressure of carbon dioxid e (PCO2) gap (tonometer PCO2 - arterial PCO2) increased (from 10 +/- 2 .7 to 14 +/- 2.7 mmHg; p < 0.01) in the epinephrine group. In the nore pinephrine-dobutamine group pHi (from 7.30 +/- 0.11 to 7.35 +/- 0.07) and the PCO2 gap (from 10 +/- 3.0 to 4 +/- 2.0 mmHg) were normalized w ithin 6 h (p, < 0.01). The decrease in pHi and the increase in the lac tate/pyruvate ratio in the epinephrine group was transient, since it r eturned to normal within 24 h. Conclusions: Considering the global hem odynamic effects, epinephrine is as effective as norepinephrine-dobuta mine. Nevertheless, gastric mucosal acidosis and global metabolic chan ges observed in epinephrine-treated patients are consistent with a mar kedly inadequate, although transient, splanchnic oxygen utilization. T he metabolic and splanchnic effects of the combination of norepinephri ne and dobutamine in hyperdynamic dopamine-resistant septic shock appe ared to be more predictable and more appropriate to the current goals of septic shock therapy than those of epinephrine alone.