Effect of norepinephrine dosage on mortality in patients with septic shock

Abstract

Background: Use of high-dose norepinephrine is thought to have an immunosuppressive action that increases mortality. This study aimed to evaluate the correlation between norepinephrine dosage and prognosis of patients with septic shock.

Methods: This study was a nested cohort of the DExmedetomidine for Sepsis in Intensive Care Unit Randomized Evaluation (DESIRE) trial. We evaluated 112 patients with septic shock and an initial Sequential Organ Failure Assessment Cardiovascular (SOFA-C) category score > 2 and initial lactate level > 2 mmol/L. We divided the patients into two groups according to the norepinephrine dosage administered over the initial 7 days: high dose (≥ 416 μg/kg/week) (H group, n = 56) and low dose (< 416 μg/kg/week) (L group, n = 56). The primary outcome of interest was 28-day mortality. Secondary outcomes were ventilator-free days, initial 24-h infusion volume, initial 24- to 48-h infusion volume, and the need for renal replacement therapy. For comparisons between the H group and L group, we used the chi-square test or Fisher's exact test for categorical variables and the t test or Wilcoxon rank sum test for continuous variables. For time-to-event outcomes, Cox proportional hazards models were used. Kaplan-Meier survival curves were created for graphical representation.

Results: Patient characteristics appeared to be similar between the two groups except for the SOFA-C score and fibrinogen degradation product level. The cumulative incidence of death at 28 days was 29.9% (16 patients) in the L group and 29.7% (15 patients) in the H group (p = 0.99). The median number of 28-day ventilator-free days was 20 (0, 25) in the L group and 16 (0, 22) in the H group (p < 0.05). Initial infusion volume at 0-24 h in the H group was significantly higher than that in the L group (p = 0.004). Infusion volume at 24-48 h in the H group was also significantly higher than that in the L group (p = 0.03).

Conclusions: No statistically significant difference was observed in 28-day mortality between patients with septic shock treated with high-dose norepinephrine compared with those treated with low-dose norepinephrine. However, the number of ventilator-free days in the L group was higher than that in the H group.

Trial registration: clinicaltrials.gov Identifier: NCT01760967 Date of trial registration: January 4, 2013.

Keywords: Norepinephrine; Septic shock; Ventilator-free days.

Conflict of interest statement

This study was approved by the institutional review boards of Wakayama Medical University and each participating institution. All patients provided necessary consent to participate in this study.No individual personal data are included in the study. All patients provided necessary consent to participate in this study.Dr. Yamamura reports receipt of lecture fees from Hospira Japan, Nipro, and Asahi Kasei and educational consulting fees from Toray Industries, CSL Behring, Teijin Pharma, and Nihon Pharmaceutical. Dr. Kawazoe reports receipt of lecture fees from Hospira Japan and Pfizer Japan and a scholarship from Hospira Japan. Dr. Miyamoto reports receipt of lecture fees from Becton Dickinson and Pfizer Japan. Dr. Morimoto reports receipt of lecture fees from AbbVie, AstraZeneca, Daiichi-Sankyo, Kowa, Kyorin, Mitsubishi-Tanabe, and Pfizer Japan and consulting fees from Asahi Kasei and Boston Scientific. Dr. Tomonori Yamamoto and Dr.Yoshinori Ohta, have no competing interests. The other authors declare no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1

Flow of participants in the norepinephrine dosage for septic shock study

Fig. 2

Twenty-eight-day mortality between the high-dose group and low-dose group

Fig. 3

Ventilator-free days between the high-dose group and low-dose group. p = 0.03; by Wilcoxon

Fig. 4

Dose of norepinephrine on each day. *p < 0.05 vs L group at each day