International Journal of Medical and All Body Health Research  |  e-ISSN: 2582-8940  |  Double-Blind Peer Review  |  Open Access  |  CC BY-NC-SA 4.0

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     2026:7/4

International Journal of Medical and All Body Health Research

e-ISSN: 2582-8940 | Open Access

An Exploration of the role of Early Goal Directed Therapy in Sepsis

Dr. Nadia Islam

Coordinator and in charge of Dhaka Health Center, Bangladesh

Article Information

Volume / Issue6 / 2 (April-June 2025)
Pages119-130
AccessOpen Access

Publication Timeline

  • Received16 April 2025
  • Accepted17 May 2025

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Abstract

Sepsis is one of the most commonly encountered scenarios in critical care medicine. In spite of massive advances in critical care, the incidence and mortality burden of sepsis remains quite high. Resuscitation of septic patients is one of the most researched topic in modern day medicine. Sepsis resuscitation was initially influenced by observation of supra-normal survivor values generating the idea of goal directed therapy. Subsequent studies resuscitating septic patients to these supra-normal values revealed no benefit and possible harm in this strategy. In order to resolve this issue, early resuscitation of septic patients to fixed haemodynamic goals at the most proximal point of disease process was proposed in 2001 and was named ‘early goal directed therapy’. The study demonstrated a significant mortality benefit compared to usual care. This promising result led numerous trials to be conducted to test the hypothesis. Finally, after years of controversy, three large, multicentre trials were conducted in order to reach a conclusion and their results have recently been published. With the background of these recent changes, this review was conducted to describe the changes in ‘early goal directed therapy’ with time and to assess the available evidence guiding its use, specially focusing on the large new trials. This review also briefly outlines the pathophysiology of septic shock, describes the historical background of early goal directed therapy, and assesses the evidence regarding goal directed therapy in other physiological insults. To achieve these objectives, an extensive search in PubMed and general databases such as Google and Google scholar was carried out for published works. Studies were considered eligible for inclusion if they were randomised, controlled trials comparing early goal directed therapy to usual care in resuscitation of septic patients. After quality assessment of the selected studies, four studies were considered eligible to be included in the literature review. Analysis of these trials showed early goal directed therapy has no mortality benefit over patients receiving usual care. The analysis also revealed that the beneficial effects of early goal directed therapy in organ dysfunction could not be replicated in the newer three trials. Another important finding was that early goal directed therapy was not found to be cost effective. However, it should be taken into consideration that tremendous advance has occurred in critical care practice within the interval from the original trial to the publication of these newer trials and some components of the protocolised care may have been incorporated in routine care of septic patients. Contrary to these findings in patients with septic shock, goal-directed therapy has shown some promise when implemented in the peri-operative period. One large study along with meta-analysis revealed a lower incidence of morbidity and complications in patients treated with goal directed therapy compared to patients receiving usual care. However, no mortality benefit was demonstrated between the two groups. Overall, the publication of these new trials have made it evident that strict adherence to goal-oriented protocol is unlikely to be more beneficial and usual care based on good critical care practice should be the employed in sepsis resuscitation. 

Keywords

PhysiologicalFindingsUsual

References

  1. Rivers E, Nguyen B, Havstad S, Ressler J, Muzzin A, Knoblich B, et al. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J International Journal of Medical and All Body Health Research www.allmedicaljournal.com Med. 2001;345(19):1368 -77. DOI: 10.1056/NEJMoa010307. [Google Scholar][Crossref]
  2. The ProCESS Investigators, Yealy DM, Kellum JA, Huang DT, Barnato AE, Weissfeld LA, et al. A randomized trial of protocol-based care for early septic shock. N Engl J Med. 2014;370(18):1683 -93. DOI: 10.1056/NEJMoa1401602. [Google Scholar][Crossref]
  3. ARISE Investigators & ANZICS Clinical Trials Group, Peake SL, Delaney A, Bailey M, Bellomo R, Cameron PA, et al. Goal-directed resuscitation for patients with early septic shock. N Engl J Med. 2014;371(16):1496-506. DOI: 10.1056/NEJMoa1404380. [Google Scholar][Crossref]
  4. Mouncey PR, Osborn TM, Power GS, Harrison DA, Sadique MZ, Grieve RD, et al. Trial of early, goal-directed resuscitation for septic shock. N Engl J Med. 2015;372(14):1301-11. DOI: 10.1056/NEJMoa1500896. [Google Scholar][Crossref]
  5. Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, et al. The third international consensus definitions for sepsis and septic shock (Sepsis-3). JAMA. 2016;315(8):801 -10. DOI: 10.1001/jama.2016.0287. [Google Scholar][Crossref]
  6. Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, Opal SM, et al. Surviving Sepsis Campaign: International guidelines for management of severe sepsis and septic shock: 2012. Crit Care Med. 2013;41(2):580-637. DOI: 10.1097/CCM.0b013e31827e83af. [Google Scholar][Crossref]
  7. Bone RC, Balk RA, Cerra FB, Dellinger RP, Fein AM, Knaus WA, et al. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Chest. 1992;101(6):1644 -55. DOI: 10.1378/chest.101.6.1644. [Google Scholar][Crossref]
  8. Levy MM, Fink MP, Marshall JC, Abraham E, Angus D, Cook D, et al. 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Crit Care Med. 2003;31(4):1250 -6. DOI: 10.1097/01.CCM.0000050454.01978.3B. [Google Scholar][Crossref]
  9. Rhodes A, Evans LE, Alhazzani W, Levy MM, Antonelli M, Ferrer R, et al. Surviving Sepsis Campaign: International guidelines for management of sepsis and septic shock: 2016. Intensive Care Med. 2017;43(3):304-77. DOI: 10.1007/s00134-017-4683-6. [Google Scholar][Crossref]
  10. Evans LE, Rhodes A, Alhazzani W, Antonelli M, Coopersmith CM, French C, et al. Surviving Sepsis Campaign: International guidelines for management of sepsis and septic shock: 2021. Crit Care Med. 2021;49(11):e1063-e1143. DOI: 10.1097/CCM.0000000000005337. [Google Scholar][Crossref]
  11. de Jong E, van Oers JA, Beishuizen A, Vos P, Vermeijden WCW, Haas LE, et al. Efficacy and safety of procalcitonin guidance in reducing duration of antibiotic treatment in critically ill patients: a randomized clinical trial. JAMA Intern Med. 2016;176(8):1082-91. DOI: 10.1001/jamainternmed.2016.1212. [Google Scholar][Crossref]
  12. Bouadma L, Luyt CE, Tubach F, Cracco C, Alvarez A, Schwebel C, et al. Effect of procalcitonin-guided antibiotic treatment on clinical outcomes in intensive care unit patients with infection and sepsis: a patient-level meta-analysis of randomized trials. Crit Care. 2018;22(1):191. DOI: 10.1186/s13054-018-2125-7. [Google Scholar][Crossref]
  13. Schuetz P, Wirz Y, Sager R, Christ-Crain M, Stolz D, Tamm M, et al. Procalcitonin-guided antibiotic use vs standard care for lower respiratory tract infections in the emergency department: The ProACT randomized trial. N Engl J Med. 2017;377(6):510 -9. DOI: 10.1056/NEJMoa1706028. [Google Scholar][Crossref]
  14. Hernández G, Ospina-Tascón GA, Damiani LP, Estenssoro E, Dubin A, Hurtado J, et al. Effect of a resuscitation strategy targeting peripheral perfusion status vs serum lactate levels on 28-day mortality among patients with septic shock: The ANDROMEDA-SHOCK randomized clinical trial. JAMA. 2019;321(7):654-64. DOI: 10.1001/jama.2019.0551. [Google Scholar][Crossref]
  15. Hernández G, Castro R, Romero C, Chelly JE, Teboul JL. Perspectives on perfusion monitoring in septic shock after the ANDROMEDA-SHOCK study. Med Intensiva. 2020;44(2):109-15. DOI: 10.1016/j.medin.2019.07.008. [Google Scholar][Crossref]
  16. Jones AE, Troyer JL, Kline JA. Cost effectiveness of an emergency department-based early sepsis resuscitation protocol. Crit Care Med. 2011;39(6):1306-12. DOI: 10.1097/CCM.0b013e31820eb737. [Google Scholar][Crossref]
  17. Gu WJ, Zhang Z, Bakker J. Early lactate clearance– guided therapy in patients with sepsis: A meta-analysis with trial sequential analysis of randomized controlled trials. Intensive Care Med. 2015;41(10):1862-3. DOI: 10.1007/s00134-015-3955-2. [Google Scholar][Crossref]
  18. Pan J, Peng M, Liao C, Hu X, Wang A. Relative efficacy and safety of early lactate clearance–guided therapy in patients with sepsis: A meta-analysis. Medicine (Baltimore). 2019;98(8):e14453. DOI: 10.1097/MD.0000000000014453. [Google Scholar][Crossref]
  19. Peake SL, Higgins AM, Williams PJ, Harris AH. The cost-effectiveness of early goal-directed therapy: An economic evaluation alongside the ARISE trial. Crit Care Resusc. 2021;23(3):329 -36. DOI: 10.51893/2021.3.oa10. [Google Scholar][Crossref]
  20. Bhat SR, Swenson KE, Francis MW, Wira CR. Lactate clearance predicts survival among patients in the emergency department with severe sepsis or septic shock. West J Emerg Med. 2015;16(7):1118-26. DOI: 10.5811/westjem.2015.8.26135. [Google Scholar][Crossref]

How to Cite

Islam, N. (2025). An Exploration of the role of Early Goal Directed Therapy in Sepsis. International Journal of Medical and All Body Health Research, 6(2), 119-130.

Islam, Nadia. "An Exploration of the role of Early Goal Directed Therapy in Sepsis." International Journal of Medical and All Body Health Research, vol. 6, no. 2, 2025, pp. 119-130.

Islam, N. (2025) 'An Exploration of the role of Early Goal Directed Therapy in Sepsis', International Journal of Medical and All Body Health Research, 6(2), pp. 119-130.

Islam N. An Exploration of the role of Early Goal Directed Therapy in Sepsis. International Journal of Medical and All Body Health Research. 2025;6(2):119-130.

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