Timing of norepinephrine initiation in patients with septic shock: a systematic review and meta-analysis

Yuting Li,Dong Zhang,Hongxiang Li

doi:10.1186/s13054-020-03204-x

Yuting Li, Dong Zhang + Show 1 more

Open Access

https://doi.org/10.1186/s13054-020-03204-x

Copy DOI

Journal: Critical Care	Publication Date: Aug 6, 2020
Citations: 68	License type: open-access

Affiliation: First Hospital of Jilin University, Jilin University

Abstract

BackgroundThe effect of the timing of norepinephrine initiation on clinical outcomes in patients with septic shock is uncertain. A systematic review and meta-analysis was performed to evaluate the impact of early and late start of norepinephrine support on clinical outcomes in patients with septic shock.MethodsWe searched the PubMed, Cochrane, and Embase databases for randomized controlled trials (RCTs) and cohort studies from inception to the 1st of March 2020. We included studies involving adult patients (> 18 years) with septic shock. All authors reported our primary outcome of short-term mortality and clearly comparing early versus late norepinephrine initiation with clinically relevant secondary outcomes (ICU length of stay, time to achieved target mean arterial pressure (≥ 65 mmHg), and volume of intravenous fluids within 6 h). Results were expressed as odds ratio (OR) and mean difference (MD) with accompanying 95% confidence interval (CI).ResultsFive studies including 929 patients were included. The primary outcome of this meta-analysis showed that the short-term mortality of the early group was lower than that of the late group (odds ratio [OR] = 0.45; 95% CI, 0.34 to 0.61; P < 0.00001; χ2 = 3.74; I2 = 0%). Secondary outcomes demonstrated that the time to achieved target MAP of the early group was shorter than that of the late group (mean difference = − 1.39; 95% CI, − 1.81 to − 0.96; P < 0.00001; χ2 = 1.03; I2 = 0%). The volume of intravenous fluids within 6 h of the early group was less than that of the late group (mean difference = − 0.50; 95% CI, − 0.68 to − 0.32; P < 0.00001; χ2 = 33.76; I2 = 94%). There was no statistically significant difference in the ICU length of stay between the two groups (mean difference = − 0.11; 95% CI, − 1.27 to 1.05; P = 0.86; χ2 = 0.85; I2 = 0%).ConclusionsEarly initiation of norepinephrine in patients with septic shock was associated with decreased short-term mortality, shorter time to achieved target MAP, and less volume of intravenous fluids within 6 h. There was no significant difference in ICU length of stay between early and late groups. Further large-scale RCTs are still required to confirm these results.

Highlights

The effect of the timing of norepinephrine initiation on clinical outcomes in patients with septic shock is uncertain
Initiation of norepinephrine in patients with septic shock was associated with decreased shortterm mortality, shorter time to achieved target mean arterial pressure (MAP), and less volume of intravenous fluids within 6 h
There was no significant difference in intensive care unit (ICU) length of stay between early and late groups

Summary

Introduction

The effect of the timing of norepinephrine initiation on clinical outcomes in patients with septic shock is uncertain. Patients with septic shock can be identified with a clinical construct of sepsis with persisting hypotension requiring vasopressors to maintain mean arterial pressure (MAP) ≥ 65 mmHg and having a serum lactate level > 2 mmol/L (18 mg/dL) despite adequate volume resuscitation [4]. Besides relative and absolute hypovolemia, decreased vascular tone is one of the major characteristics of septic shock causing hypotension [10]. Norepinephrine is both an alpha1- and beta1-agonist and is able to increase vascular tone and contractility [11]. Recent guidelines recommend norepinephrine as the first-line vasopressor in septic shock [12]

Methods

Results

Discussion

Conclusion