Advertisement

Intensive Care Medicine

, Volume 41, Issue 9, pp 1549–1560 | Cite as

A systematic review and meta-analysis of early goal-directed therapy for septic shock: the ARISE, ProCESS and ProMISe Investigators

  • D. C. Angus
  • A. E. Barnato
  • D. Bell
  • R. Bellomo
  • C.-R. Chong
  • T. J. Coats
  • A. Davies
  • A. Delaney
  • D. A. Harrison
  • A. Holdgate
  • B. Howe
  • D. T. Huang
  • T. Iwashyna
  • J. A. Kellum
  • S. L. PeakeEmail author
  • F. Pike
  • M. C. Reade
  • K. M. Rowan
  • M. Singer
  • S. A. R. Webb
  • L. A. Weissfeld
  • D. M. Yealy
  • J. D. Young
Seven-Day Profile Publication

Abstract

Purpose

To determine whether early goal-directed therapy (EGDT) reduces mortality compared with other resuscitation strategies for patients presenting to the emergency department (ED) with septic shock.

Methods

Using a search strategy of PubMed, EmBase and CENTRAL, we selected all relevant randomised clinical trials published from January 2000 to January 2015. We translated non-English papers and contacted authors as necessary. Our primary analysis generated a pooled odds ratio (OR) from a fixed-effect model. Sensitivity analyses explored the effect of including non-ED studies, adjusting for study quality, and conducting a random-effects model. Secondary outcomes included organ support and hospital and ICU length of stay.

Results

From 2395 initially eligible abstracts, five randomised clinical trials (n = 4735 patients) met all criteria and generally scored high for quality except for lack of blinding. There was no effect on the primary mortality outcome (EGDT: 23.2 % [495/2134] versus control: 22.4 % [582/2601]; pooled OR 1.01 [95 % CI 0.88–1.16], P = 0.9, with heterogeneity [I 2 = 57 %; P = 0.055]). The pooled estimate of 90-day mortality from the three recent multicentre studies (n = 4063) also showed no difference [pooled OR 0.99 (95 % CI 0.86–1.15), P = 0.93] with no heterogeneity (I 2 = 0.0 %; P = 0.97). EGDT increased vasopressor use (OR 1.25 [95 % CI 1.10–1.41]; P < 0.001) and ICU admission [OR 2.19 (95 % CI 1.82–2.65); P < 0.001]. Including six non-ED randomised trials increased heterogeneity (I 2 = 71 %; P < 0.001) but did not change overall results [pooled OR 0.94 (95 % CI 0.82 to 1.07); P = 0.33].

Conclusion

EGDT is not superior to usual care for ED patients with septic shock but is associated with increased utilisation of ICU resources.

Keywords

Early goal-directed therapy or EGDT Resuscitation Septic shock Central venous oxygen saturation Meta-analysis Systematic review Randomised clinical trials 

Notes

Conflicts of interest

The authors declare no conflict of interest.

Supplementary material

134_2015_3822_MOESM1_ESM.docx (114 kb)
Supplementary material 1 (DOCX 113 kb)

References

  1. 1.
    Rivers E, Nguyen B, Havstad S, Ressler J, Muzzin A, Knoblich B, Peterson E, Tomlanovich M, Early Goal-Directed Therapy Collaborative Group (2001) Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med 345:1368–1377CrossRefPubMedGoogle Scholar
  2. 2.
    Kortgen A, Niederprum P, Bauer M (2006) Implementation of an evidence-based standard operating procedure and outcome in septic shock. Crit Care Med 34:943–949CrossRefPubMedGoogle Scholar
  3. 3.
    Jones E, Focht A, Horton JM, Kline JA (2007) Prospective eternal validation of the clinical effectiveness of an emergency department-based early goal-directed therapy protocol for severe sepsis and septic shock. Chest 132:425–432PubMedCentralCrossRefPubMedGoogle Scholar
  4. 4.
    Levy MM, Rhodes A, Phillips GS, Townsend SR, Schorr CA, Beale R, Osborn T, Lemeshow S, Chiche JD, Artigas A, Dellinger RP (2014) Surviving sepsis campaign: association between performance metrics and outcomes in a 7.5 years study. Intensive Care Med 40:1623–1661CrossRefPubMedGoogle Scholar
  5. 5.
    Dellinger RP, Levy MM, Rhodes A et al (2013) Surviving Sepsis Campaign: guidelines for management of severe sepsis and septic shock. Intensive Care Med 39:165–228CrossRefPubMedGoogle Scholar
  6. 6.
    Peake S, Bailey M, Bellomo R, Cameron P, Cross A, Delaney A, Finfer S, Higgins A, Jones D, Myburgh J, Syres G, Webb S, the ARISE Investigators for the ANZICS CTG (2009) A multicentre, prospective, inception cohort study. Resuscitation 80:811–818CrossRefPubMedGoogle Scholar
  7. 7.
    Pike F, Yealy DM, Kellum JA, Huang DT, Barnato AE, Eaton TL, Angus DC, Weissfeld LA, I behalf of theProCESS Investigators (2013) Protocolized Care for Early Septic Shock (ProCESS) statistical analysis plan. Crit Care Resusc 15:301–310PubMedCentralPubMedGoogle Scholar
  8. 8.
    The ProCESS Investigators (2014) A randomised trial of protocol-based care for early septic shock. N Engl J Med 370:1683–1693PubMedCentralCrossRefGoogle Scholar
  9. 9.
    Delaney AP, Peake SL, Bellomo R, Cameron P, Holdgate A, Howe B, Higgins A, Presneill J, Webb D, For the ARISE Investigators (2013) The Australasian Resuscitation In Sepsis Evaluation (ARISE) trial statistical analysis plan. Crit Care Resusc 15:162–171PubMedGoogle Scholar
  10. 10.
    The ARISE Investigators and the ANZICS Clinical Trials Group (2014) Goal-directed resuscitation for patients with early septic shock. N Engl J Med 371:1496–1506CrossRefGoogle Scholar
  11. 11.
    Power GS, Harrison DA, Mouncey PR, Osborn TM, Harvey SE, Rowan KM (2013) The Protocolised Management in Sepsis (ProMISe) trial statistical analysis plan. Crit Care Resusc 15:311–317PubMedGoogle Scholar
  12. 12.
    Mouncey PR, Osborn TM, Power GS, Harrison DA, Sadique MZ, Grieve RG, Jahan R, Harvey SE, Bell D, Bion JF, Coats TJ, Singer M, Young JD, Rowan KM, ProMISe Trial Investigators (2015) Trial of early, goal-directed resuscitation for septic shock. N Engl J Med 372(14):1301–1311. doi: 10.1056/NEJMoa1500896 CrossRefPubMedGoogle Scholar
  13. 13.
    Higgins JPT, Green S (eds) (2011) Cochrane hand book for systematic reviews of interventions. The Cochrane Collaboration Version 5.1.0 [updated March 2011] http://handbook.cochrane.org. Accessed 29 Mar 2015
  14. 14.
    Moher D, Liberati A, Tetzlaff J, Altman DG, The PRISMA Group (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. BMJ 339:b2535. doi: 10.1136/bmj.b2535 PubMedCentralCrossRefPubMedGoogle Scholar
  15. 15.
    Gu W-J, Bakker J, Liu J-C (2014) The effect of goal-directed therapy on mortality in patients with sepsis—earlier is better: a meta-analysis of randomised controlled trials. Crit Care 18:570PubMedCentralCrossRefPubMedGoogle Scholar
  16. 16.
    Wira CR, Dodge K, Sather J, Dziura J (2014) Meta-analysis of protocolised goal-directed haemodynamic optimisation for the management of severe sepsis and septic shock in the emergency department. West J Emerg Med 15:51–59PubMedCentralCrossRefPubMedGoogle Scholar
  17. 17.
    Barochia AV, Cui X, Vitberg D, Suffredini AF, O’Grady NP, Banks SM, Minneci P, Kern SJ, Danner RL, Natanson C, Eichacker PG (2010) Bundled care for septic shock: analysis of clinical trials. Crit Care Med 38:668–678PubMedCentralCrossRefPubMedGoogle Scholar
  18. 18.
    Higgins JPT, Altman DG, Gotzche PC, Juni P, Moher D, Oxman AD, Savovic J Schulz KF, Weeks L, Sterne JAC, Cochrane Bias Methods Group, Cochrane Statistical Methods Group (2011) The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. BMJ 343:d5928. doi: 10.1136/bmj.d5928 PubMedCentralCrossRefPubMedGoogle Scholar
  19. 19.
    Jones AE, Shapiro NI, Trzeciak S, Arnold RC, Claremont HA, Kline JA, Emergency Medicine Shock Research Network (EMShockNet) Investigators (2010) Lactateclearance vs central venous oxygen saturation as goals of early sepsis therapy: a randomised clinical trial. JAMA 303:739–746PubMedCentralCrossRefPubMedGoogle Scholar
  20. 20.
    de Oliveira CF, de Oliveira DS, Gottschald AF, Moura JD, Costa GA, Ventura AC, Fernandes JC, Vaz FA, Carcillo JA, Rivers EP, Troster EJ (2008) ACCM/PALS haemodynamic support guidelines for paediatric septic shock: an outcomes comparison with and without monitoring central venous oxygen saturation. Intensive Care Med 34:1065–1075CrossRefPubMedGoogle Scholar
  21. 21.
    Wang X, Lu CJ, Gao FQ, Li XH, Yan WF, Ning FY (2006) Efficacy of goal-directed therapy in the treatment of septic shock. Zhongguo Wei Zhong Bing Ji Jiu Yi Xue 18:661–664PubMedGoogle Scholar
  22. 22.
    Early Goal-Directed Therapy Collaborative Group of Zhejiang Province (2010) The effect of early goal-directed therapy on treatment of critical patients with severe sepsis/septic shock: a multi-centre, prospective, randomised, controlled study. Zhongguo Wei Zhong Bing Ji Jiu Yi Xue 22:331–334Google Scholar
  23. 23.
    Tian HH, Han SS, Lv CJ, Wang T, Li Z, Hao D, Shang QM, Wang XZ (2012) The effect of early goal lactate clearance rate on the outcome of septic shock patients with severe pneumonia. Zhongguo Wei Zhong Bing Ji Jiu Yi Xue 24:42–45PubMedGoogle Scholar
  24. 24.
    Yu B, Tian HY, Hu ZJ, Zhao C, Liu LX, Zhang Y, Zhu GJ, Wang LT, Wu XH, Li J (2013) Comparison of the effect of fluid resuscitation as guided either by lactate clearance rate or by central venous oxygen saturation in patients with sepsis. Zhonghua Wei Zhong Bing Ji Jiu Yi Xue 25:578–583PubMedGoogle Scholar
  25. 25.
    Lu N, Zheng R, Lin H, Shao J, Yu J (2014) Clinical studies of surviving sepsis bundles according to PiCCO on septic shock patients. Zhonghua Wei Zhong Bing Ji Jiu Yi Xue 26:23–27PubMedGoogle Scholar
  26. 26.
    Guyatt GH, Oxman AD, Kunz R, Vist GE, Falck-Ytter Y, Schuneman HJ, For the GRADE Working Group (2008) GRADE: what is quality of evidence and why is it important to clinicians? BMJ 336:995–998PubMedCentralCrossRefPubMedGoogle Scholar
  27. 27.
    Wunsch H, Angus DC, Harrison DA, Collange O, Fowler R, Hoste EA, de Keizer NF, Kersten A, Linde-Zwirble WT, Sandiumenge A, Rowan KM (2008) Variation in critical care services across North America and Western Europe. Crit Care Med 36:2787–2793CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg and ESICM 2015

Authors and Affiliations

  • D. C. Angus
    • 1
  • A. E. Barnato
    • 3
  • D. Bell
    • 4
    • 5
  • R. Bellomo
    • 6
    • 7
  • C.-R. Chong
    • 8
    • 9
  • T. J. Coats
    • 10
  • A. Davies
    • 6
    • 11
  • A. Delaney
    • 6
    • 12
    • 26
  • D. A. Harrison
    • 13
    • 14
  • A. Holdgate
    • 15
  • B. Howe
    • 6
  • D. T. Huang
    • 1
  • T. Iwashyna
    • 6
    • 16
  • J. A. Kellum
    • 1
  • S. L. Peake
    • 6
    • 9
    • 25
    Email author
  • F. Pike
    • 1
  • M. C. Reade
    • 17
    • 18
  • K. M. Rowan
    • 13
    • 14
    • 19
    • 20
  • M. Singer
    • 21
  • S. A. R. Webb
    • 6
    • 22
  • L. A. Weissfeld
    • 23
  • D. M. Yealy
    • 2
  • J. D. Young
    • 24
  1. 1.Department of Critical Care MedicineUniversity of Pittsburgh School of MedicinePittsburghUSA
  2. 2.Department of Emergency MedicineUniversity of Pittsburgh School of MedicinePittsburghUSA
  3. 3.Department of MedicineUniversity of Pittsburgh School of MedicinePittsburghUSA
  4. 4.Faculty of MedicineImperial College LondonLondonUK
  5. 5.Department of Acute MedicineChelsea and Westminster Hospital NHS Foundation TrustLondonUK
  6. 6.Australian and New Zealand Intensive Care Research Centre, School of Public Health and Preventive MedicineMonash UniversityMelbourneAustralia
  7. 7.Austin HospitalMelbourneAustralia
  8. 8.Pharmacy DepartmentThe Queen Elizabeth HospitalAdelaideAustralia
  9. 9.School of MedicineUniversity of AdelaideAdelaideAustralia
  10. 10.Department of Cardiovascular SciencesUniversity of LeicesterLeicesterUK
  11. 11.Frankston HospitalFrankstonAustralia
  12. 12.Royal North Shore Hospital and University of SydneySydneyAustralia
  13. 13.Clinical Trials UnitIntensive Care National Audit and Research CentreLondonUk
  14. 14.London School of Hygiene and Tropical MedicineLondonUK
  15. 15.Liverpool Hospital and University of NSWSydneyAustralia
  16. 16.University of Michigan and VA Centre for Clinical Management ResearchAnn ArborUSA
  17. 17.Burns, trauma and critical care research centreUniversity of QueenslandBrisbaneAustralia
  18. 18.Joint Health CommandAustralian Defence ForceCanberraAustralia
  19. 19.Department of Health Services Research and PolicyLondon School of Hygiene and Tropical MedicineLondonUK
  20. 20.Division of Research StrategyUniversity College LondonLondonUK
  21. 21.Bloomsbury Institute of Intensive Care MedicineUniversity College LondonLondonUK
  22. 22.Royal Perth Hospital and University of Western AustraliaPerthAustralia
  23. 23.Statistics CollaborativeWashingtonUSA
  24. 24.Nuffield Division of AnaestheticsUniversity of OxfordOxfordUK
  25. 25.Department of Intensive Care MedicineThe Queen Elizabeth HospitalWoodvilleAustralia
  26. 26.Northern Clinical School, Sydney Medical SchoolUniversity of SydneySydneyAustralia

Personalised recommendations