Effects of norepinephrine plus dobutamine or norepinephrine alone on left ventricular performance of septic shock patients

Objective: To determine the hemodynamic effects of the combination of norepinephrine-dobutamine in adult patients with septic shock. Specifically, we tested the hypothesis that norepinephrine in addition to dobutamine would improve cardiac index (CI) and stroke volume index (SVI) and increase left-ventricular afterload. Design: Prospective, descriptive, interventional study with no control group. Setting: Intensive care unit of a university hospital. Patients: Fourteen patients (group 1) were transferred to the intensive care unit from other wards with septic shock not responsive to dobutamine infusion, low blood pressure (systolic blood pressure of <90 mm Hg), clinical and laboratory signs of infection, clinical signs of poor organ perfusion, and blood lactate of >2.0 mmol/L. They were enrolled and treated by the addition of norepinephrine, while the dose of dobutamine remained constant. Three of these patients required additional fluid loading to achieve adequate ventricular filling (pulmonary capillary wedge pressure [PCWP], 12-15 mm Hg). These patients were compared with 12 patients with septic shock with high CI (CI > 5/min/m(2), and other signs as outlined previously) who were treated with norepinephrine alone (group 2). Interventions: Patients in group 1 were maintained with the same dobutamine dose, and norepinephrine was added (initial dose, 0.5 mu g/kg/min, and increments of 0.3 mu g/kg/min) until the correction of mean arterial blood pressure (MAP greater than or equal to 75 mm Hg). Patients in group 2 received norepinephrine following the same protocol. Measurements and Main Results: At study entry, group 1 patients receiving dobutamine had similar MAPs but were significantly older and had significantly lower CIs and SVIs and higher systemic vascular resistance than group 2 patients. In group 1 norepinephrine, in addition to dobutamine, significantly increased MAP, CI, SVI, left ventricular stroke work index (LVSWI), and systemic vascular resistance (SVR). No change in heart rate or PCWP was observed. In group 2, norepinephrine used alone did not modify CI or SVI and it significantly improved MAP, LVSWI, and SVR. No changes In heart rate or PCWP were observed. Blood lactate was significantly decreased in both groups. Comparing the two groups, in response to norepinephrine titrated to increase MAP to a similar concentration, patients with dobutamine-resistant septic shock had a statistically significantly greater increase in CI and SVI than patients treated with norepinephrine alone. There were no other significant differences in hemodynamic and metabolic responses to norepinephrine between groups 1 and 2. Conclusion: The addition of norepinephrine to treatment of patients with septic shock unresponsive to dobutamine significantly improves MAP, CI, SVI, and LVSWI. A different pattern of evolution was observed if norepinephrine was used alone in younger patients with higher CI at study entry, increases in MAP and LVSWI, and no concomitant change in CI or SVI. The use of norepinephrine in dobutamine-resistant septic shock may have some beneficial implications for the treatment of patients with inadequate myocardial performance associated with low SVR.