Abstract Objective To systematically evaluate the efficacy and safety of norepinephrine in the treatment of septic shock. Methods Literature retrieval of eligible randomized controlled trials (RCTs) on norepinephrine in the treatment of septic shock was performed in three English databases including PubMed, Web of Science, and Medline from database establishment to October 1, 2023. The Cochrane risk bias tool was used to evaluate the quality of the included literature. RevMan 5.3 software was used for meta-analysis. Results A total of 14 RCTs were included in this study, and the risk of bias was low. Our meta-analysis showed that the norepinephrine group had significantly better outcomes in reducing the 28-day mortality rate (RR = 0.92; 95% CI, 0.86 ~ 0.99; P = 0.03), the incidence of arrhythmia (RR = 0.54; 95% CI, 0.45 ~ 0.64; P < 0.0001), and the length of stay in intensive care unit (ICU) (MD = − 1.03; 95% CI, − 1.85 to approximately − 0.21; P = 0.01) than those of the control group. However, there were no statistically significant differences in in-hospital mortality rate (RR = 0.97; 95% CI, 0.90 ~ 1.04; P = 0.4), the 90-day mortality rate (RR = 1.07; 95% CI, 0.97 ~ 1.18; P = 0.15), length of hospital stay (MD = 0.03; 95% CI, − 1.13 ~ 1.18; P = 0.96), and the rate of achieving target MAP (RR = 1.27; 95% CI, 0.72 ~ 2.26; P = 0.41) between the norepinephrine group and the control group. Conclusion Norepinephrine has the advantages of improving 28-day mortality, shortening ICU hospitalization time, and reducing the incidence of arrhythmia. It is a more effective choice for the treatment of septic shock than other vasopressors, and the incidence of arrhythmia is low.
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