by Yuting Li, Hongxiang Li and Dong Zhang
Background
The 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.
Methods
We 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).
Results
Five 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%).
Conclusions
Early 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.
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