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 norep inephrine-dobutamine in adult patients with septic shock. Specifically, we tested the hypothesis that norepinephrine in addition to dobutamine would i mprove cardiac index (CI) and stroke volume index (SVI) and increase left-v entricular afterload. Design: Prospective, descriptive, interventional study with no control grou p. Setting: Intensive care unit of a university hospital. Patients: Fourteen patients (group 1) were transferred to the intensive car e unit from other wards with septic shock not responsive to dobutamine infu sion, low blood pressure (systolic blood pressure of <90 mm Hg), clinical a nd laboratory signs of infection, clinical signs of poor organ perfusion, a nd blood lactate of >2.0 mmol/L. They were enrolled and treated by the addi tion of norepinephrine, while the dose of dobutamine remained constant. Thr ee 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 hig h CI (CI > 5/min/m(2), and other signs as outlined previously) who were tre ated 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 inc rements of 0.3 mu g/kg/min) until the correction of mean arterial blood pre ssure (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 d obutamine had similar MAPs but were significantly older and had significant ly lower CIs and SVIs and higher systemic vascular resistance than group 2 patients. In group 1 norepinephrine, in addition to dobutamine, significant ly increased MAP, CI, SVI, left ventricular stroke work index (LVSWI), and systemic vascular resistance (SVR). No change in heart rate or PCWP was obs erved. In group 2, norepinephrine used alone did not modify CI or SVI and i t significantly improved MAP, LVSWI, and SVR. No changes In heart rate or P CWP were observed. Blood lactate was significantly decreased in both groups . Comparing the two groups, in response to norepinephrine titrated to incre ase MAP to a similar concentration, patients with dobutamine-resistant sept ic shock had a statistically significantly greater increase in CI and SVI t han patients treated with norepinephrine alone. There were no other signifi cant differences in hemodynamic and metabolic responses to norepinephrine b etween groups 1 and 2. Conclusion: The addition of norepinephrine to treatment of patients with se ptic 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 norep inephrine in dobutamine-resistant septic shock may have some beneficial imp lications for the treatment of patients with inadequate myocardial performa nce associated with low SVR.