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Meta-Analysis
. 2021 Feb 16;22(2):196-203.
doi: 10.5811/westjem.2020.10.47825.

Norepinephrine in Septic Shock: A Systematic Review and Meta-analysis

Muhammad Azfar Ruslan  1   2 , Kamarul Aryffin Baharuddin  1   3 , Norhayati Mohd Noor  4 , Mohd Boniami Yazid  1   3 , Abu Yazid Md Noh  1   3 , Andey Rahman  1   3
Affiliations
Meta-Analysis

Norepinephrine in Septic Shock: A Systematic Review and Meta-analysis

Muhammad Azfar Ruslan et al. West J Emerg Med. .

Abstract

Introduction: Most experts recommend norepinephrine as the first-line agent in septic shock. Our objective was to determine the effectiveness and safety of norepinephrine in patients with septic shock.

Methods: We searched the Cochrane Central Register of Controlled Trials and Epistemonikos, as well as MEDLINE from 1966 till August 2019. Screening of full texts, evaluation for eligibility, and data extraction were done by four independent reviewers. We estimated risk ratios (RR) and mean differences (MD) using a random-effects model with 95% confidence intervals (CI). The primary outcomes included the number of participants who achieved the target mean arterial pressure (MAP), time to achieve the target MAP, and number of participants with all-cause 28-day mortality. The secondary outcomes included the length of stay in the intensive care unit, length of hospital stay, incidence of arrhythmia and myocardial infarction, vasopressor-free days, and number of participants with all-cause 90-day mortality.

Results: We identified 11 randomized controlled trials with a total of 4,803 participants. There was no difference in the number of participants who achieved the target MAP between those patients receiving norepinephrine and other vasopressors (RR 1.44; 95% CI, 0.32 to 6.54; P = 0.640; I2 = 94%; two trials, 116 participants). There was no significant difference in time to achieve the target MAP (MD -0.05; 95%, CI, -0.32 to 0.21; P = 0.690; I2 = 26%; two trials, 1763 participants) and all-cause 28-day mortality (RR 0.95; 95% CI, 0.89 to 1.02; P = 0.160; I2 = 0%; seven trials, 4,139 participants). Regarding the secondary outcome, norepinephrine may significantly reduce the incidence of arrhythmia as compared to other vasopressors (RR 0.64; 95% CI, 0.42 to 0.97; P = 0.030; I2 = 64%; six trials, 3974 participants). There was no difference in the incidence of myocardial infarction (RR 1.28; 95% CI, 0.79 to 2.09), vasopressor-free day (RR 0.46; 95% CI, -1.82 to 2.74) and all-cause 90-day mortality (RR 1.08; 95% CI, 0.96 to 1.21) between norepinephrine and vasopressors.

Conclusion: In minimizing the occurrence of an arrhythmia, norepinephrine is superior to other vasopressors, making it safe to be used in septic shock. However, there was insufficient evidence concerning mortality and achievement of the target MAP outcomes.

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Conflict of interest statement

Conflicts of Interest: By the WestJEM article submission agreement, all authors are required to disclose all affiliations, funding sources and financial or management relationships that could be perceived as potential sources of bias. No author has professional or financial relationships with any companies that are relevant to this study. There are no conflicts of interest or sources of funding to declare.

Figures

Figure 1
Figure 1
PRISMA flow chart of study selection for metanalysis of norepinephrine use in septic shock.
Figure 2
Figure 2
Comparison between norepinephrine and vasopressors for the outcome of the number of participants who achieved the target mean arterial pressure. M-H, Mantel-Haenszel method; CI, confidence interval.
Figure 3
Figure 3
Comparison between norepinephrine and vasopressors for the outcome of the number of participants with all-cause 28-day mortality. M-H, Mantel-Haenszel method; CI, confidence interval.
Figure 4
Figure 4
Comparison between norepinephrine and vasopressors for the outcome of the incidence of arrhythmia. M-H, Mantel-Haenszel method; CI, confidence interval.
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References

    1. Plevin R, Callcut R. Update in sepsis guidelines: What is really new? Trauma Surg Acute Care Open. 2017;2(1):e000088. - PMC - PubMed
    1. Rudd KE, Kissoon N, Limmathurotsakul D, et al. The global burden of sepsis: barriers and potential solutions. Crit Care. 2018;22(1):232. - PMC - PubMed
    1. Hajj J, Blaine N, Salavaci J, et al. The “centrality of sepsis”: a review on incidence, mortality, and cost of care. Healthcare (Basel) 2018;6(3):90. - PMC - PubMed
    1. Keeley A, Hine P, Nsutebu E. The recognition and management of sepsis and septic shock: a guide for non-intensivists. Postgrad Med J. 2017;93(1104):626–34. - PubMed
    1. Gül F, Arslantaş MK, Cinel İ, et al. Changing definitions of sepsis. Turk J Anaesthesiol Reanim. 2017;45(3):129–38. - PMC - PubMed