Vasopressor therapy for septic shock after adequate fluid resuscitation in the emergency department: a systematic review and meta-analysis

Authors

  • Mazi Mohammed Alanazi Saudi and Jordanian Board Emergency Medicine, Emergency Department, Head of Emergency Research Unit, First Health Cluster, Riyadh, Saudi Arabia Author
  • Rayan Ahmed Bahmaid Saudi board emergency Medicine Resident, Prince Sultan Military Medical City, Riyadh, Saudi Arabia Author
  • Reema Meshal Aldera Saudi board emergency Medicine Resident, Prince Sultan Military Medical City, Riyadh, Saudi Arabia Author

DOI:

https://doi.org/10.65759/ggs92j37

Keywords:

Septic shock, Norepinephrine, Vasopressors, Emergency department, Fluid resuscitation

Abstract

Background: Septic shock is a critical emergency, and vasopressor timing after initial fluid resuscitation is under debate. Data from emergency department, prehospital, and intensive care studies benefit from earlier norepinephrine initiation. Methods: We performed a systematic review and meta-analysis of studies evaluating vasopressor therapy, norepinephrine in septic shock after fluid resuscitation, with focus on timing of initiation. Nine studies were included in the qualitative analysis, while studies with extractable event counts were entered into the mortality meta-analysis. Pooled risk ratios (RRs) were calculated for short-term and 28-day mortality. Results: Earlier vasopressor initiation was associated with better hemodynamic and clinical outcomes in the included studies, including faster shock control, lower fluid exposure, and less organ failure progression. In the pooled short-term mortality analysis of four studies, early vasopressor initiation was associated with lower mortality (RR 0.72, 95% CI 0.56–0.92; I²=0%). In the stricter 28-day mortality analysis of three studies, early initiation also favored survival (RR 0.66, 95% CI 0.51–0.86; I²=0%). Conclusion: Early norepinephrine initiation improved short-term outcomes in septic shock. More high-quality emergency department studies are needed to define the best timing threshold and confirm the effect on mortality.

References

[1] Guarino M, Perna B, Cesaro AE, Maritati M, Spampinato MD, Contini C, et al. 2023 Update on Sepsis and Septic Shock in Adult Patients: Management in the Emergency Department. J Clin Med 2023;12. https://doi.org/10.3390/jcm12093188.

[2] Graham JD, Lanspa MJ, Peltan ID. Resuscitation Targets, Fluids, and Vasoactives in Septic Shock. Clin Chest Med 2025. https://doi.org/10.1016/j.ccm.2025.10.003.

[3] Ruslan MA, Baharuddin KA, Noor NM, Yazid MB, Noh AYM, Rahman A. Norepinephrine in septic shock: A systematic review and meta-analysis. Western Journal of Emergency Medicine 2021;22:196–203. https://doi.org/10.5811/WESTJEM.2020.10.47825.

[4] Xu QY, Jin YH, Fu L, Li YY. Application of norepinephrine in the treatment of septic shock: a meta-analysis. Ir J Med Sci 2025;194:361–9. https://doi.org/10.1007/s11845-024-03827-x.

[5] Black LP, Puskarich MA, Smotherman C, Miller T, Fernandez R, Guirgis FW. Time to vasopressor initiation and organ failure progression in early septic shock. JACEP Open 2020;1:222–30. https://doi.org/10.1002/emp2.12060.

[6] Messina A, Milani A, Morenghi E, Costantini E, Brusa S, Negri K, et al. Norepinephrine infusion in the emergency department in septic shock patients: A retrospective 2-years safety report and outcome analysis. Int J Environ Res Public Health 2021;18:1–9. https://doi.org/10.3390/ijerph18020824.

[7] Carlos Sanchez E, Pinsky MR, Sinha S, Mishra RC, Lopa AJ, Chatterjee R. Fluids and Early Vasopressors in the Management of Septic Shock: Do We Have the Right Answers Yet? J Crit Care Med 2023;9:138–47. https://doi.org/10.2478/jccm-2023-0022.

[8] Zhou F, Mao Z, Zeng X, Kang H, Liu H, Pan L, et al. Vasopressors in septic shock: A systematic review and network meta-analysis. Ther Clin Risk Manag 2015;11:1047–59. https://doi.org/10.2147/TCRM.S80060.

[9] Zhou H-X, Yang C-F, Wang H-Y, Teng Y, He H-Y. Should we initiate vasopressors earlier in patients with septic shock: A mini systemic review. World J Crit Care Med 2023;12:204–16. https://doi.org/10.5492/wjccm.v12.i4.204.

[10] Shi R, Braïk R, Monnet X, Gu WJ, Ospina-Tascon G, Permpikul C, et al. Early norepinephrine for patients with septic shock: an updated systematic review and meta-analysis with trial sequential analysis. Crit Care 2025;29. https://doi.org/10.1186/s13054-025-05400-z.

[11] Permpikul C, Tongyoo S, Viarasilpa T, Trainarongsakul T, Chakorn T, Udompanturak S. Early use of norepinephrine in septic shock resuscitation (CENSER) a randomized trial. Am J Respir Crit Care Med 2019;199:1097–105. https://doi.org/10.1164/rccm.201806-1034OC.

[12] Jouffroy R, Hajjar A, Gilbert B, Tourtier JP, Bloch-Laine E, Ecollan P, et al. Prehospital norepinephrine administration reduces 30-day mortality among septic shock patients. BMC Infect Dis 2022;22. https://doi.org/10.1186/s12879-022-07337-y.

[13] Bai X, Yu W, Ji W, Lin Z, Tan S, Duan K, et al. Early versus delayed administration of norepinephrine in patients with septic shock. Crit Care 2014;18. https://doi.org/10.1186/s13054-014-0532-y.

[14] Ospina-Tascón GA, Hernandez G, Alvarez I, Calderón-Tapia LE, Manzano-Nunez R, Sánchez-Ortiz AI, et al. Effects of very early start of norepinephrine in patients with septic shock: A propensity score-based analysis. Crit Care 2020;24. https://doi.org/10.1186/s13054-020-2756-3.

[15] Xu F, Zhong R, Shi S, Zeng Y, Tang Z. Early initiation of norepinephrine in patients with septic shock: A propensity score-based analysis. American Journal of Emergency Medicine 2022;54:287–96. https://doi.org/10.1016/j.ajem.2022.01.063.

[16] Abe T, Umemura Y, Ogura H, Kushimoto S, Fujishima S, Saitoh D, et al. Early versus delayed vasopressor administration in patients with septic shock. Acute Medicine & Surgery 2023;10. https://doi.org/10.1002/ams2.852.

[17] Gavelli F, Castello LM, Avanzi GC. Management of sepsis and septic shock in the emergency department. Intern Emerg Med 2021;16:1649–61. https://doi.org/10.1007/s11739-021-02735-7.

[18] Shi R, Hamzaoui O, De Vita N, Monnet X, Teboul J-L. Vasopressors in septic shock: which, when, and how much? Ann Transl Med 2020;8:794–794. https://doi.org/10.21037/atm.2020.04.24.

Downloads

Published

2026-03-31