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Norepinephrine requirement is not an independent variable to predict outcome in severe septic shock patients


Although no ideal vasopressor agent is currently available, norepinephrine has been used to stabilize arterial pressure in euvolemic patients with septic shock. Few studies have suggested an association between norepinephrine dose and poor outcome.


To verify if norepinephrine dose requirement in severe septic shock is an independent variable to predict outcome.


We built a database, including demographic, hemodynamic and oxygen-derived variables, from 43 consecutive septic shock patients treated with norepinephrine, after fluid replacement, according to our institutional protocols. APACHE II at admission and daily LODS and SOFA scores were obtained to assess multiple organ dysfunctions. We chose standard prognostic variables including age, gender, mean arterial pressure (MAP), arterial pH, base excess, lactate levels and, norepinephrine dose requirements during 5 days after admission. We developed models to predict in-ICU mortality using univariate and multivariate analysis with stepwise regression. Consecutive variables were expressed as means ± SD. The best cut-off value was chosen using Youden's Index; P < 0.05 was considered significant. All statistical analyses were conducted using statistical software (SAS, Cary, NC, USA).


There were 29 males (67%) and 14 females (33%), with a mean age of 61 ± 2 years. Mean APACHE II score was 22.1 ± 1.1, with an overall mortality rate of 53.5%. ICU length of stay was 14.8 ± 1.2 days. Twelve variables were identified through univariate analysis, including age, SOFA (1st day), LODS (1st and 2nd days), arterial pH (1st and 2nd days), base excess (1st and 2nd days), norepinephrine dose (1st and 2nd days) and the highest norepinephrine dose in 5 days. Only two variables retained statistical significance following multivariate analysis with stepwise regression. They were LODS (2nd day) and arterial pH (2nd day). LODS (2nd day) ≥ 5 and arterial pH (second day) ≤ 7.33 were associated with a 29.6 and 19.9 times odds to death, respectively.


Although norepinephrine dose is associated with mortality by univariate analysis, it is not an independent variable in severe septic patients. The importance of the severity condition (LODS) is greater than the norepinephrine dose requirement.

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Silva, E., Machado, F., Sousa, E. et al. Norepinephrine requirement is not an independent variable to predict outcome in severe septic shock patients. Crit Care 6 (Suppl 1), P233 (2002).

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