Effect of norepinephrine on the outcome of septic shock

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Abstract
Despite increasingly sophisticated critical care, the mortality of septic shock remains elevated. Accordingly, care remains supportive. Volume resuscitation combined with vasopressor support remains the standard of care as adjuvant therapy, and many consider dopamine to be the pressor of choice. Because of fear of excessive vasoconstriction, norepinephrine is considered to be deleterious. The present study was designed to identify factors associated with outcome in a cohort of septic shock patients. Special attention was paid to hemodynamic management and to the choice of vasopressor used, to determine whether the use of norepinephrine was associated with increased mortality. Prospective, observational, cohort study. Intensive care unit of a university hospital. Ninety-seven adult patients with septic shock. Data from these patients were examined to select variables independently and significantly associated with outcome during the hospital stay. Nineteen clinical, biological, and hemodynamic variables were collected at study entry or during the first 48–72 hrs and analyzed for each patient. A stepwise logistic regression analysis and a model building strategy were used to identify variables independently and significantly associated with outcome. The overall hospital mortality was 73% (71 patients). Five variables were significantly associated with outcome. One factor was strongly associated with a favorable outcome: the use of norepinephrine as part of the hemodynamic support of the patients. The 57 patients who were treated with norepinephrine had significantly lower hospital mortality (62% vs. 82%, p < .001; relative risk = 0.68; 95% confidence interval = 0.54–0.87) than the 40 patients treated with vasopressors other than norepinephrine (high-dose dopamine and/or epinephrine). Four variables were associated with a poor outcome and significantly higher hospital mortality: pneumonia as a cause of septic shock (82% vs. 61%, p < .03; relative risk = 1.47; 95% confidence interval = 1.07–1.77), organ system failure index ≤ 3 (92% vs. 60%, p < .001; relative risk = 1.47; 95% confidence interval = 1.17–1.82), low urine output at entry to the study (88% vs. 60%, p < .01; relative risk = 1.44; 95% confidence interval = 1.06–1.87), and admission blood lactate concentration > 4 mmol/L (91% vs. 63%, p < .01; relative risk = 1.60; 95% confidence interval = 1.27–1.84). Our results indicate that the use of norepinephrine as part of hemodynamic management may influence outcome favorably in septic shock patients. The data contradict the notion that norepinephrine potentiates end-organ hypoperfusion, thereby contributing to increased mortality. However, the present study suffers from some limitation because of its nonrandomized, open-label, observational design. Hence, a randomized clinical trial is needed to clearly establish that norepinephrine improves mortality of patients with septic shock, as compared with high-dose dopamine or epinephrine. Pneumonia as the cause of septic shock, high blood lactate concentration, and low urine output on admission are strong indicators of a poor prognosis. Multiple organ failure is confirmed as a reliable predictor of mortality in septic patients.